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Sample records for rapidly metabolizes iaasp

  1. A rapid mitochondrial toxicity assay utilizing rapidly changing cell energy metabolism.

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    Sanuki, Yosuke; Araki, Tetsuro; Nakazono, Osamu; Tsurui, Kazuyuki

    2017-01-01

    Drug-induced liver injury is a major cause of safety-related drug-marketing withdrawals. Several drugs have been reported to disrupt mitochondrial function, resulting in hepatotoxicity. The development of a simple and effective in vitro assay to identify the potential for mitochondrial toxicity is thus desired to minimize the risk of causing hepatotoxicity and subsequent drug withdrawal. An in vitro test method called the "glucose-galactose" assay is often used in drug development but requires prior-culture of cells over several passages for mitochondrial adaptation, thereby restricting use of the assay. Here, we report a rapid version of this method with the same predictability as the original method. We found that replacing the glucose in the medium with galactose resulted in HepG2 cells immediately shifting their energy metabolism from glycolysis to oxidative phosphorylation due to drastic energy starvation; in addition, the intracellular concentration of ATP was reduced by mitotoxicants when glucose in the medium was replaced with galactose. Using our proposed rapid method, mitochondrial dysfunction in HepG2 cells can be evaluated by drug exposure for one hour without a pre-culture step. This rapid assay for mitochondrial toxicity may be more suitable for high-throughput screening than the original method at an early stage of drug development.

  2. Temperature-Sensitive Plant Cells with Shunted Indole-3-Acetic Acid Conjugation.

    Science.gov (United States)

    Oetiker, J. H.; Aeschbacher, G.

    1997-01-01

    Cells of henbane (Hyoscyamus muticus L.) grow indefinitely in culture without exogenous auxin. Cells of its temperature-sensitive variant XIIB2 grow like the wild type at 26[deg]C but die rapidly at 33[deg]C unless auxin is added to the medium. Despite this temperature-sensitive auxin auxotrophy, XIIB2 produces wild-type amounts of indole-3-acetic acid (IAA). IAA is the predominant auxin and is important for plant growth and development. Since the IAA production of the variant is functional, we investigated whether the synthesis or degradation of IAA metabolites, possibly active auxins themselves, is altered. The IAA metabolites were IAA-aspartate (IAAsp) and IAA-glucose. The wild type converted IAA mainly to IAAsp, whereas the variant produced mainly IAA-glucose. Exogenous auxin corrected the shunted IAA metabolism of the variant. The half-life of labeled IAAsp in the variant was reduced 21-fold, but in the presence of exogenous auxin it was not different from the wild type. The temperature sensitivity of XIIB2 was also corrected by supplying IAAsp. Pulse-chase experiments revealed that henbane rapidly metabolizes IAAsp to compounds not identical to IAA. The data show that the variant XIIB2 is a useful tool to study the function of IAA conjugates to challenge the popular hypothesis that IAA conjugates are merely slow-release storage forms of IAA. PMID:12223777

  3. The oncogene c-Myc coordinates regulation of metabolic networks to enable rapid cell cycle entry.

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    Morrish, Fionnuala; Neretti, Nicola; Sedivy, John M; Hockenbery, David M

    2008-04-15

    The c-myc proto-oncogene is rapidly activated by serum and regulates genes involved in metabolism and cell cycle progression. This gene is thereby uniquely poised to coordinate both the metabolic and cell cycle regulatory events required for cell cycle entry. However, this function of Myc has not been evaluated. Using a rat fibroblast model of isogenic cell lines, myc(-/-), myc(+/-), myc(+/+) and myc(-/-) cells with an inducible c-myc transgene (mycER), we show that the Myc protein programs cells to utilize both oxidative phosphorylation and glycolysis to drive cell cycle progression. We demonstrate this coordinate regulation of metabolic networks is essential, as specific inhibitors of these pathways block Myc-induced proliferation. Metabolic events temporally correlated with cell cycle entry include increased oxygen consumption, mitochondrial function, pyruvate and lactate production, and ATP generation. Treatment of normal cells with inhibitors of oxidative phosphorylation recapitulates the myc(-/-) phenotype, resulting in impaired cell cycle entry and reduced metabolism. Combined with a kinetic expression profiling analysis of genes linked to mitochondrial function, our study indicates that Myc's ability to coordinately regulate the mitochondrial metabolic network transcriptome is required for rapid cell cycle entry. This function of Myc may underlie the pervasive presence of Myc in many human cancers.

  4. Hyaluronic Acid-Serum Hydrogels Rapidly Restore Metabolism of Encapsulated Stem Cells and Promote Engraftment

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    Chan, Angel T.; Karakas, Mehmet F.; Vakrou, Styliani; Afzal, Junaid; Rittenbach, Andrew; Lin, Xiaoping; Wahl, Richard L.; Pomper, Martin G.; Steenbergen, Charles J.; Tsui, Benjamin M.W.; Elisseeff, Jennifer H.; Abraham, M. Roselle

    2015-01-01

    Background Cell death due to anoikis, necrosis and cell egress from transplantation sites limits functional benefits of cellular cardiomyoplasty. Cell dissociation and suspension, which are a pre-requisite for most cell transplantation studies, lead to depression of cellular metabolism and anoikis, which contribute to low engraftment. Objective We tissue engineered scaffolds with the goal of rapidly restoring metabolism, promoting viability, proliferation and engraftment of encapsulated stem cells. Methods The carboxyl groups of HA were functionalized with N-hydroxysuccinimide (NHS) to yield HA succinimidyl succinate (HA-NHS) groups that react with free amine groups to form amide bonds. HA-NHS was cross-linked by serum to generate HA:Serum (HA:Ser) hydrogels. Physical properties of HA:Ser hydrogels were measured. Effect of encapsulating cardiosphere-derived cells (CDCs) in HA:Ser hydrogels on viability, proliferation, glucose uptake and metabolism was assessed in vitro. In vivo acute intra-myocardial cell retention of 18FDG-labeled CDCs encapsulated in HA:Ser hydrogels was quantified. Effect of CDC encapsulation in HA:Ser hydrogels on in vivo metabolism and engraftment at 7 days was assessed by serial, dual isotope SPECT-CT and bioluminescence imaging of CDCs expressing the Na-iodide symporter and firefly luciferase genes respectively. Effect of HA:Ser hydrogels +/− CDCs on cardiac function was assessed at 7 days & 28 days post-infarct. Results HA:Ser hydrogels are highly bio-adhesive, biodegradable, promote rapid cell adhesion, glucose uptake and restore bioenergetics of encapsulated cells within 1 h of encapsulation, both in vitro and in vivo. These metabolic scaffolds can be applied epicardially as a patch to beating hearts or injected intramyocardially. HA:Ser hydrogels markedly increase acute intramyocardial retention (~6 fold), promote in vivo viability, proliferation, engraftment of encapsulated stem cells and angiogenesis. Conclusion HA:Ser hydrogels

  5. Gentamicin rapidly inhibits mitochondrial metabolism in high-frequency cochlear outer hair cells.

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    Heather C Jensen-Smith

    Full Text Available Aminoglycosides (AG, including gentamicin (GM, are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs preferentially succumb to multiple HL pathologies while inner hair cells (IHCs are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH fluorescence during acute (1 h GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies.

  6. Jacaric acid is rapidly metabolized to conjugated linoleic acid in rats.

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    Kijima, Ryo; Honma, Taro; Ito, Junya; Yamasaki, Masao; Ikezaki, Aya; Motonaga, Chihiro; Nishiyama, Kazuo; Tsuduki, Tsuyoshi

    2013-01-01

    We have shown previously that jacaric acid (JA; 8c,10t,12c-18:3), which has a conjugated triene system, has a strong anti-tumor effect. However, the characteristics of absorption and metabolism of JA have yet to be determined in vivo, and the details of absorption and metabolism of JA in the small intestine are particularly unclear. This information is required for effective use of JA in humans. Therefore, in this study we examined absorption and metabolism of JA using cannulation of the thoracic duct in rats. Emulsions of two test oils, jacaranda seed oil and tung oil, which contain JA and α-eleostearic acid (α-ESA; 9c,11t,13t-18:3), respectively, were administered to rats and lymph from the thoracic duct was collected over 24 h. We examined the rate of absorption of JA and possible conversion to a conjugated linoleic acid (CLA)containing a conjugated diene system. The positional isomerism of the CLA produced by JA metabolism was determined using gas chromatography-electron impact/mass spectrometry. The rate of absorption and percentage conversion of JA were compared with those of α-ESA. We found that JA is rapidly absorbed and converted to a CLA in rats and that the percentage conversion of JA was lower than that of α-ESA. This is the first report on the absorption and metabolism of JA and this information may be important for application of JA as a functional food.

  7. Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

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    Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

    2015-02-01

    Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

  8. Rapid countermeasure discovery against Francisella tularensis based on a metabolic network reconstruction.

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    Sidhartha Chaudhury

    Full Text Available In the future, we may be faced with the need to provide treatment for an emergent biological threat against which existing vaccines and drugs have limited efficacy or availability. To prepare for this eventuality, our objective was to use a metabolic network-based approach to rapidly identify potential drug targets and prospectively screen and validate novel small-molecule antimicrobials. Our target organism was the fully virulent Francisella tularensis subspecies tularensis Schu S4 strain, a highly infectious intracellular pathogen that is the causative agent of tularemia and is classified as a category A biological agent by the Centers for Disease Control and Prevention. We proceeded with a staggered computational and experimental workflow that used a strain-specific metabolic network model, homology modeling and X-ray crystallography of protein targets, and ligand- and structure-based drug design. Selected compounds were subsequently filtered based on physiological-based pharmacokinetic modeling, and we selected a final set of 40 compounds for experimental validation of antimicrobial activity. We began screening these compounds in whole bacterial cell-based assays in biosafety level 3 facilities in the 20th week of the study and completed the screens within 12 weeks. Six compounds showed significant growth inhibition of F. tularensis, and we determined their respective minimum inhibitory concentrations and mammalian cell cytotoxicities. The most promising compound had a low molecular weight, was non-toxic, and abolished bacterial growth at 13 µM, with putative activity against pantetheine-phosphate adenylyltransferase, an enzyme involved in the biosynthesis of coenzyme A, encoded by gene coaD. The novel antimicrobial compounds identified in this study serve as starting points for lead optimization, animal testing, and drug development against tularemia. Our integrated in silico/in vitro approach had an overall 15% success rate in terms of

  9. Rapid uptake, metabolism, and elimination of inhaled sulfuryl fluoride fumigant by rats.

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    Mendrala, A L; Markham, D A; Eisenbrandt, D L

    2005-08-01

    Sulfuryl fluoride (SO(2)F(2)) is a structural fumigant gas used to control drywood termites and wood-boring beetles. The pharmacokinetics and metabolism of inhaled SO(2)F(2) were evaluated in male Fischer-344 rats exposed to 30 or 300 ppm (35)S-labeled SO(2)F(2) for 4 h. Blood, urine and feces were collected during and after the exposures and analyzed for radioactivity, (35)S-labeled fluorosulfate and sulfate, and fluoride (urine and feces only). Selected tissues were collected 7 days post-exposure and analyzed for radioactivity. During and after unlabeled SO(2)F(2) exposures, blood, brain, and kidney were collected and analyzed for fluoride ion. SO(2)F(2) was rapidly absorbed, achieving maximum concentrations of radioactivity in both plasma and red blood cells (RBC) near the end of the 4-h exposure period. Radioactivity was rapidly excreted, mostly via the urine. Seven days post-exposure, small amounts of radioactivity were distributed among several tissues, with the highest concentration detected in respiratory tissues. Radioactivity associated with the RBC remained elevated 7 days post-exposure, and highly perfused tissues had higher levels of radioactivity than other non-respiratory tissues. Radioactivity cleared from plasma and RBC with initial half-lives of 2.5 h after 30 ppm and 1-2.5 h after 300 ppm exposures. The terminal half-life of radioactivity was 2.5-fold longer in RBC than plasma. Based on the radiochemical profiles, there was no evidence of parent (35)SO(2)F(2) in blood. Identification of fluorosulfate and sulfate in blood and urine suggests that SO(2)F(2) is hydrolyzed to fluorosulfate, with release of fluoride, followed by further hydrolysis to sulfate and release of the remaining fluoride.

  10. Invasive Aspergillus infection requiring lobectomy in a CYP2C19 rapid metabolizer with subtherapeutic voriconazole concentrations.

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    Hicks, J Kevin; Gonzalez, Blanca E; Zembillas, Anthony S; Kusick, Karissa; Murthy, Sudish; Raja, Siva; Gordon, Steven M; Hanna, Rabi

    2016-05-01

    Individuals who carry the CYP2C19*17 gain-of-function allele have lower voriconazole exposure and are therefore at risk of failing therapy. Utilizing CYP2C19 genotype to optimize voriconazole dosage may be a cost-effective method of improving treatment outcomes. However, there are limited data describing what initial voriconazole dosage should be used in those with increased CYP2C19 metabolic capacity. Herein, we present a case report of a pediatric CYP2C19 rapid metabolizer (i.e., CYP2C19*1/*17) requiring a voriconazole dosage of 14 mg/kg twice daily (usual pediatric dosage ranges from 7 to 9 mg/kg twice daily). This case report supports the clinical utility of using CYP2C19 genotype to guide voriconazole dosing, and provides data for establishing an initial voriconazole dose in pediatric CYP2C19 rapid metabolizers.

  11. Low Birthweight, Rapid Weight Gain and Metabolic Syndrome in Adolescence: An Illustrative Case Report

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    Onyiriuka Alphonsus N.

    2015-12-01

    Full Text Available A 16-year-old boy whose diabetes mellitus was diagnosed 3 months previously in a private hospital but was not placed on medication. The presenting complaints were fast breathing for 24 hours, weakness for 2 hours, and unresponsiveness to calls for 0.5 hours. His father was obese with type 2 diabetes mellitus and died 8 months earlier from cardiac arrest. His birthweight was low, 2.2kg. At first presentation, his weight, BMI and blood pressure were 60kg (25th-50th percentile, 19.4kg/m2 (25thpercentile and 110/70mmHg (systolic BP 50th percentile, diastolic BP 50th-90th percentile, respectively. He was managed for diabetic ketoacidosis and was discharged on subcutaneous premixed insulin, 1 Unit/kg/day. At point of discharge, weight and BP were 60.5 kg and 120/70 mmHg, respectively. The patient defaulted but presented again 6 months later at the age of 17 years. At second presentation, his weight, BMI and BP were 89 kg (95th percentile, 27.5 kg/m2 (90th-95th percentile and 180/80 mmHg (systolic 99th percentile; diastolic 90th percentile, respectively. His waist circumference was 98.7cm (> 90th percentile. We had no record of previous waist circumference. His lipid profile showed low HDL-cholesterol 0.7252 mmol/L [(28mg/dl; <5thpercentile]. His fasting blood glucose and HbA1C were 6.5 mmol/L (117mg/dl and 34 mol/mol (5.3%, respectively. A diagnosis of metabolic syndrome in a patient with ketosis-prone type 2 diabetes was made. He was referred to the pediatric cardiologist for management of his hypertension. He defaulted again and was lost to follow up. Conclusion: This report illustrates the association of low birth weight and rapid weight gain with metabolic syndrome in adolescence.

  12. Carboxylesterase 1A2 encoding gene with increased transcription and potential rapid drug metabolism in Asian populations

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Madsen, Majbritt Busk; Lyauk, Yassine Kamal

    2017-01-01

    The carboxylesterase 1 gene (CES1) encodes a hydrolase implicated in the metabolism of commonly used drugs. CES1A2, a hybrid of CES1 and a CES1-like pseudogene, has a promoter that is weak in most individuals. However, some individuals harbor a promoter haplotype of this gene with two overlapping...... Sp1 sites that confer significantly increased transcription potentially leading to rapid drug metabolism. This CES1A2 haplotype has previously been reported to be common among Asians. Using polymerase chain reaction followed by sequencing, the present study examined variation in the promoter and 5...

  13. Alterations in regional cerebral glucose metabolism across waking and non-rapid eye movement sleep in depression.

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    Nofzinger, Eric A; Buysse, Daniel J; Germain, Anne; Price, Julie C; Meltzer, Carolyn C; Miewald, Jean M; Kupfer, David J

    2005-04-01

    Depression is associated with sleep disturbances, including alterations in non-rapid eye movement (NREM) sleep. Non-rapid eye movement sleep is associated with decreases in frontal, parietal, and temporal cortex metabolic activity compared with wakefulness. To show that depressed patients would have less of a decrease than controls in frontal metabolism between waking and NREM sleep and to show that during NREM sleep, they would have increased activity in structures that promote arousal. Subjects completed electroencephalographic sleep and regional cerebral glucose metabolism assessments during both waking and NREM sleep using [(18)F]fluoro-2-deoxy-D-glucose positron emission tomography. General clinical research center. The study included 29 unmedicated patients who met the Structured Clinical Interview for DSM-IV criteria for current major depression and who had a score of 15 or greater on a 17-item Hamilton Rating Scale for Depression and 28 medically healthy subjects of comparable age and sex who were free of mental disorders. Electroencephalographic sleep and regional cerebral metabolism during waking and NREM sleep. Depressed patients showed smaller decreases than healthy subjects in relative metabolism in broad regions of the frontal, parietal, and temporal cortex from waking to NREM sleep. Depressed patients showed larger decreases than healthy subjects in relative metabolism in the left amygdala, anterior cingulate cortex, cerebellum, parahippocampal cortex, fusiform gyrus, and occipital cortex. However, in post hoc analyses, depressed patients showed hypermetabolism in these areas during both waking and NREM sleep. The smaller decrease in frontal metabolism from waking to NREM sleep in depressed patients is further evidence for a dynamic sleep-wake alteration in prefrontal cortex function in depression. Hypermetabolism in a ventral emotional neural system during waking in depressed patients persists into NREM sleep.

  14. Evidence of co-metabolic bentazone transformation by methanotrophic enrichment from a groundwater-fed rapid sand filter

    DEFF Research Database (Denmark)

    Hedegaard, Mathilde Jørgensen; Deliniere, Hélène; Prasse, Carsten

    2018-01-01

    and bentazone at concentrations below 2 mg/L showed methanotrophic co-metabolic bentazone transformation: The culture removed 53% of the bentazone in 21 days in presence of 5 mg/L of methane, while only 31% was removed in absence of methane. Addition of acetylene inhibited methane oxidation and stopped...... from 58 to 158, well within the range for methanotrophic co-metabolic degradation of trace contaminants calculated from the literature, with normalized substrate preferences varying from 3 to 400. High-resolution mass spectrometry revealed formation of the transformation products (TPs) 6-OH, 8-OH......, isopropyl-OH and di-OH-bentazone, with higher abundances of all TPs in the presence of methane. Overall, we found a suite of evidence all showing that bentazone was co-metabolically transformed to hydroxy-bentazone by a methanotrophic culture enriched from a rapid sand filter at a waterworks....

  15. Characterizing Urban Household Waste Generation and Metabolism Considering Community Stratification in a Rapid Urbanizing Area of China.

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    Lishan Xiao

    Full Text Available The relationship between social stratification and municipal solid waste generation remains uncertain under current rapid urbanization. Based on a multi-object spatial sampling technique, we selected 191 households in a rapidly urbanizing area of Xiamen, China. The selected communities were classified into three types: work-unit, transitional, and commercial communities in the context of housing policy reform in China. Field survey data were used to characterize household waste generation patterns considering community stratification. Our results revealed a disparity in waste generation profiles among different households. The three community types differed with respect to family income, living area, religious affiliation, and homeowner occupation. Income, family structure, and lifestyle caused significant differences in waste generation among work-unit, transitional, and commercial communities, respectively. Urban waste generation patterns are expected to evolve due to accelerating urbanization and associated community transition. A multi-scale integrated analysis of societal and ecosystem metabolism approach was applied to waste metabolism linking it to particular socioeconomic conditions that influence material flows and their evolution. Waste metabolism, both pace and density, was highest for family structure driven patterns, followed by lifestyle and income driven. The results will guide community-specific management policies in rapidly urbanizing areas.

  16. Characterizing Urban Household Waste Generation and Metabolism Considering Community Stratification in a Rapid Urbanizing Area of China.

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    Xiao, Lishan; Lin, Tao; Chen, Shaohua; Zhang, Guoqin; Ye, Zhilong; Yu, Zhaowu

    2015-01-01

    The relationship between social stratification and municipal solid waste generation remains uncertain under current rapid urbanization. Based on a multi-object spatial sampling technique, we selected 191 households in a rapidly urbanizing area of Xiamen, China. The selected communities were classified into three types: work-unit, transitional, and commercial communities in the context of housing policy reform in China. Field survey data were used to characterize household waste generation patterns considering community stratification. Our results revealed a disparity in waste generation profiles among different households. The three community types differed with respect to family income, living area, religious affiliation, and homeowner occupation. Income, family structure, and lifestyle caused significant differences in waste generation among work-unit, transitional, and commercial communities, respectively. Urban waste generation patterns are expected to evolve due to accelerating urbanization and associated community transition. A multi-scale integrated analysis of societal and ecosystem metabolism approach was applied to waste metabolism linking it to particular socioeconomic conditions that influence material flows and their evolution. Waste metabolism, both pace and density, was highest for family structure driven patterns, followed by lifestyle and income driven. The results will guide community-specific management policies in rapidly urbanizing areas.

  17. The Impact of Rapid Weight Loss on Oxidative Stress Markers and the Expression of the Metabolic Syndrome in Obese Individuals

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    Eva Tumova

    2013-01-01

    Full Text Available Objective. Obesity is linked with a state of increased oxidative stress, which plays an important role in the etiology of atherosclerosis and type 2 diabetes mellitus. The aim of our study was to evaluate the effect of rapid weight loss on oxidative stress markers in obese individuals with metabolic syndrome (MetS. Design and Methods. We measured oxidative stress markers in 40 obese subjects with metabolic syndrome (MetS+, 40 obese subjects without metabolic syndrome (MetS−, and 20 lean controls (LC at baseline and after three months of very low caloric diet. Results. Oxidized low density lipoprotein (ox-LDL levels decreased by 12% in MetS+ subjects, associated with a reduction in total cholesterol (TC, even after adjustment for age and sex. Lipoprotein associated phospholipase A2 (Lp-PLA2 activity decreased by 4.7% in MetS+ subjects, associated with a drop in LDL-cholesterol (LDL-C, TC, and insulin levels. Multivariate logistic regression analysis showed that a model including ox-LDL, LpPLA2 activity, and myeloperoxidase (MPO improved prediction of MetS status among obese individuals compared to each oxidative stress marker alone. Conclusions. Oxidative stress markers were predictive of MetS in obese subjects, suggesting a higher oxidative stress. Rapid weight loss resulted in a decline in oxidative stress markers, especially in MetS+ patients.

  18. "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

  19. Cerebral O2 metabolism and cerebral blood flow in humans during deep and rapid-eye-movement sleep

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    Madsen, P L; Schmidt, J F; Wildschiødtz, Gordon

    1991-01-01

    It could be expected that the various stages of sleep were reflected in variation of the overall level of cerebral activity and thereby in the magnitude of cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). The elusive nature of sleep imposes major methodological restrictions...... on examination of this question. We have now measured CBF and CMRO2 in young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness, deep sleep (stage 3/4), and rapid-eye-movement (REM) sleep as verified by standard polysomnography...

  20. Effects of Rapid Weight Loss on Systemic and Adipose Tissue Inflammation and Metabolism in Obese Postmenopausal Women.

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    Alemán, José O; Iyengar, Neil M; Walker, Jeanne M; Milne, Ginger L; Da Rosa, Joel Correa; Liang, Yupu; Giri, Dilip D; Zhou, Xi Kathy; Pollak, Michael N; Hudis, Clifford A; Breslow, Jan L; Holt, Peter R; Dannenberg, Andrew J

    2017-06-01

    Obesity is associated with subclinical white adipose tissue inflammation, as defined by the presence of crown-like structures (CLSs) consisting of dead or dying adipocytes encircled by macrophages. In humans, bariatric surgery-induced weight loss leads to a decrease in CLSs, but the effects of rapid diet-induced weight loss on CLSs and metabolism are unclear. To determine the effects of rapid very-low-calorie diet-induced weight loss on CLS density, systemic biomarkers of inflammation, and metabolism in obese postmenopausal women. Prospective cohort study. Rockefeller University Hospital, New York, NY. Ten obese, postmenopausal women with a mean age of 60.6 years (standard deviation, ±3.6 years). Effects on CLS density and gene expression in abdominal subcutaneous adipose tissue, cardiometabolic risk factors, white blood count, circulating metabolites, and oxidative stress (urinary isoprostane-M) were measured. Obese subjects lost approximately 10% body weight over a mean of 46 days. CLS density increased in subcutaneous adipose tissue without an associated increase in proinflammatory gene expression. Weight loss was accompanied by decreased fasting blood levels of high-sensitivity C-reactive protein, glucose, lactate, and kynurenine, and increased circulating levels of free fatty acids, glycerol, β-hydroxybutyrate, and 25 hydroxyvitamin D. Levels of urinary isoprostane-M declined. Rapid weight loss stimulated lipolysis and an increase in CLS density in subcutaneous adipose tissue in association with changes in levels of circulating metabolites, and improved systemic biomarkers of inflammation and insulin resistance. The observed change in levels of metabolites (i.e., lactate, β-hydroxybutyrate, 25 hydroxyvitamin D) may contribute to the anti-inflammatory effect of rapid weight loss.

  1. Development of a Rapid Microbore Metabolic Profiling Ultraperformance Liquid Chromatography-Mass Spectrometry Approach for High-Throughput Phenotyping Studies.

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    Gray, Nicola; Adesina-Georgiadis, Kyrillos; Chekmeneva, Elena; Plumb, Robert S; Wilson, Ian D; Nicholson, Jeremy K

    2016-06-07

    A rapid gradient microbore ultraperformance liquid chromatography-mass spectrometry (UPLC-MS) method has been developed to provide a high-throughput analytical platform for the metabolic phenotyping of urine from large sample cohorts. The rapid microbore metabolic profiling (RAMMP) approach was based on scaling a conventional reversed-phase UPLC-MS method for urinary profiling from 2.1 mm × 100 mm columns to 1 mm × 50 mm columns, increasing the linear velocity of the solvent, and decreasing the gradient time to provide an analysis time of 2.5 min/sample. Comparison showed that conventional UPLC-MS and rapid gradient approaches provided peak capacities of 150 and 50, respectively, with the conventional method detecting approximately 19 000 features compared to the ∼6 000 found using the rapid gradient method. Similar levels of repeatability were seen for both methods. Despite the reduced peak capacity and the reduction in ions detected, the RAMMP method was able to achieve similar levels of group discrimination as conventional UPLC-MS when applied to rat urine samples obtained from investigative studies on the effects of acute 2-bromophenol and chronic acetaminophen administration. When compared to a direct infusion MS method of similar analysis time the RAMMP method provided superior selectivity. The RAMMP approach provides a robust and sensitive method that is well suited to high-throughput metabonomic analysis of complex mixtures such as urine combined with a 5-fold reduction in analysis time compared with the conventional UPLC-MS method.

  2. Rapid transcriptional and metabolic regulation of the deacclimation process in cold acclimated Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Pagter, Majken; Alpers, Jessica; Erban, Alexander

    2017-01-01

    BACKGROUND: During low temperature exposure, temperate plant species increase their freezing tolerance in a process termed cold acclimation. This is accompanied by dampened oscillations of circadian clock genes and disrupted oscillations of output genes and metabolites. During deacclimation...... in response to warm temperatures, cold acclimated plants lose freezing tolerance and resume growth and development. While considerable effort has been directed toward understanding the molecular and metabolic basis of cold acclimation, much less information is available about the regulation of deacclimation....... RESULTS: We report metabolic (gas chromatography-mass spectrometry) and transcriptional (microarrays, quantitative RT-PCR) responses underlying deacclimation during the first 24 h after a shift of Arabidopsis thaliana (Columbia-0) plants cold acclimated at 4 °C back to warm temperature (20 °C). The data...

  3. Rapid Revival of a Patient after very Severe Metabolic Acidosis: A Case Report

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    Sajad Ahmadi

    2013-01-01

    Full Text Available Background: Metabolic acidosis is a fatal finding in trauma patients thatcomplicates the process of resuscitation.Case: The case was a 37-year-old man with open fracture in both legs and fracturein second lumbar vertebral (L2. The serial arterial blood gas (ABG test resultsshowed a pH value of 6.7 indicating a very severe and special case of metabolicacidosis. The rate of mortality for such a case was very high. The patient wastreated with sodium bicarbonate and successfully revived after four hours posttreatment and metabolic acidosis was resolved.Conclusion: This indicated that bicarbonate administration is useful for verysevere cases. The good condition of the patient after survival from the severeacademia allowed for extubation.

  4. Evidence of co-metabolic bentazone transformation by methanotrophic enrichment from a groundwater-fed rapid sand filter.

    Science.gov (United States)

    Hedegaard, Mathilde J; Deliniere, Hélène; Prasse, Carsten; Dechesne, Arnaud; Smets, Barth F; Albrechtsen, Hans-Jørgen

    2018-02-01

    The herbicide bentazone is recalcitrant in aquifers and is therefore frequently detected in wells used for drinking water production. However, bentazone degradation has been observed in filter sand from a rapid sand filter at a waterworks with methane-rich groundwater. Here, the association between methane oxidation and removal of bentazone was investigated with a methanotrophic enrichment culture derived from methane-fed column reactors inoculated with that filter sand. Several independent lines of evidence obtained from microcosm experiments with the methanotrophic enrichment culture, tap water and bentazone at concentrations below 2 mg/L showed methanotrophic co-metabolic bentazone transformation: The culture removed 53% of the bentazone in 21 days in presence of 5 mg/L of methane, while only 31% was removed in absence of methane. Addition of acetylene inhibited methane oxidation and stopped bentazone removal. The presence of bentazone partly inhibited methane oxidation since the methane consumption rate was significantly lower at high (1 mg/L) than at low (1 μg/L) bentazone concentrations. The transformation yield of methane relative to bentazone normalized by their concentration ratio ranged from 58 to 158, well within the range for methanotrophic co-metabolic degradation of trace contaminants calculated from the literature, with normalized substrate preferences varying from 3 to 400. High-resolution mass spectrometry revealed formation of the transformation products (TPs) 6-OH, 8-OH, isopropyl-OH and di-OH-bentazone, with higher abundances of all TPs in the presence of methane. Overall, we found a suite of evidence all showing that bentazone was co-metabolically transformed to hydroxy-bentazone by a methanotrophic culture enriched from a rapid sand filter at a waterworks. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Rapid Countermeasure Discovery against Francisella tularensis Based on a Metabolic Network Reconstruction

    Science.gov (United States)

    2013-05-21

    a given drug target. First, the selection of a subset of genes deemed to be essential for bacterial survival overlooks non-essential genes that may... Salmonella typhimurium during host-pathogen interaction. BMC Syst Biol 3: 38. 19. Shen Y, Liu J, Estiu G, Isin B, Ahn YY, et al. (2010) Blueprint for...and Medicine 48: 330–333. 69. Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival : application to proliferation and

  6. Potential of fermentation profiling via rapid measurement of amino acid metabolism by liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dalluge, Joseph J; Smith, Sean; Sanchez-Riera, Fernando; McGuire, Chris; Hobson, Russell

    2004-07-16

    Monitoring amino acid metabolism during fermentation has significant potential from the standpoint of strain selection, optimizing growth and production in host strains, and profiling microbial metabolism and growth state. A method has been developed based on rapid quantification of underivatized amino acids using liquid chromatography-electrospray tandem mass spectrometry (LC-MS-MS) to monitor the metabolism of 20 amino acids during microbial fermentation. The use of a teicoplanin-based chiral stationary phase coupled with electrospray tandem mass spectrometry allows complete amino acid analyses in less than 4 min. Quantification is accomplished using five isotopically labeled amino acids as internal standards. Because comprehensive chromatographic separation and derivatization are not required, analysis time is significantly less than traditional reversed- or normal-phase LC-based amino acid assays. Intra-sample precisions for amino acid measurements in fermentation supernatants using this method average 4.9% (R.S.D.). Inter-day (inter-fermentation) precisions for individual amino acid measurements range from 4.2 to 129% (R.S.D.). Calibration curves are linear over the range 0-300 microg/ml, and detection limits are estimated at 50-450 ng/ml. Data visualization techniques for constructing semi-quantitative fermentation profiles of nitrogen source utilization have also been developed and implemented, and demonstrate that amino acid profiles generally correlate with observed growth profiles. Further, cellular growth events, such as lag-time and cell lysis can be detected using this methodology. Correlation coefficients for the time profiles of each amino acid measured illustrate that while several amino acids are differentially metabolized in similar fermentations, a select group of amino acids display strong correlations in these samples, indicating a sub-population of analytes that may be most useful for fermentation profiling.

  7. Increases in myocardial workload induced by rapid atrial pacing trigger alterations in global metabolism.

    Directory of Open Access Journals (Sweden)

    Aslan T Turer

    Full Text Available To determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.There is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.Nineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS.Pacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006, ADP (+42%, p = 0.01, AMP (+79%, p = 0.004, GDP (+69%, p = 0.003, GMP (+58%, p = 0.01, IMP (+50%, p = 0.03, xanthine (+61%, p = 0.0006], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.Isolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

  8. The rapid internationalization of Annals of Pediatric Endocrinology & Metabolism as evidenced by journal metrics.

    Science.gov (United States)

    Huh, Sun

    2017-06-01

    Using journal metrics, this paper explores whether Annals of Pediatric Endocrinology & Metabolism has internationalized 4 years after changing its language to English only. From the journal's website and the Web of Science Core Collection, the following metrics were counted or calculated: Number of citable articles, countries of authors and editorial board members, total citations, impact factor, countries of citing authors, citing journal titles, and Hirsch index. From 2012 to 2017, 208 articles were citable. The authors had affiliations in 7 countries and the editorial board members in 14 countries. From 2014 to 2017, the total citations each year were 8, 81, 141, and 61; and the impact factors from 2014 to 2016 were calculated as 0.05, 0.987, and 1.165. The citing authors were from 60 countries, among which the United States, China, South Korea, Italy, and Germany were most common. The journal was cited by 215 journal titles. The Hirsch index was 7. These journal metrics showed that the journal achieved international status 4 years after changing the journals' language into English only. The journal's language policy successfully enabled the journal to rebrand as an international journal.

  9. Educational disparities in the metabolic syndrome in a rapidly changing society--the case of South Korea.

    Science.gov (United States)

    Kim, Myoung-Hee; Kim, Mi-Kyung; Choi, Bo Youl; Shin, Young-Jeon

    2005-12-01

    Most of the evidence about socioeconomic inequalities in the metabolic syndrome comes from Western industrialized societies. The aim of this study is to examine how the inequalities appear and what could explain them in Korea, a rapidly changing society. We analysed the nationwide survey data of 1998 and 2001 with a sample of 4630 men and 5896 women (> or = 25 years). The subjects were grouped into four birth cohorts based on the historical context: born before 1946, 1946-53, 1954-62, and since 1963. Socioeconomic position was defined by education level: high school graduation or above as the more educated group, and below that as the less educated one. The syndrome was defined according to ATP III criteria using abdominal obesity for Asians. The covariates included family history of diabetes, smoking, drinking, daily physical activity, regular exercise, suicidal ideation, weight change, and carbohydrates intake. The associations were examined by stratified logistic regression models across cohorts and gender. Less-educated women had higher prevalence with widening gaps across successive cohorts; the age-adjusted odds ratios of the less-educated group were 1.22 (0.86-1.71), 1.41 (1.01-1.97), 2.50 (1.87-3.35), and 2.64 (1.69-4.14). They hardly changed after covariate adjustment, and remained significant with considerable attenuation after controlling body mass index. However, educational disparities were not observed in men. We could observe the complex pattern of disparities in the metabolic syndrome across cohorts and gender. An equity-sensitive health promotion programme to prevent further spread of social inequalities may have beneficial effects on the metabolic syndrome and its components in Korea.

  10. The Role of Non-Rapid Eye Movement Slow-Wave Activity in Prefrontal Metabolism across Young and Middle Age Adults

    OpenAIRE

    Wilckens, K.A.; Aizenstein, H J; Nofzinger, E.A.; James, J. A.; Hasler, B.P.; Rosario-Rivera, B.L.; Franzen, P; Germain, A.; Hall, M. H.; Kupfer, D.J.; Price, J C.; Siegle, G.J.; Buysse, D. J.

    2016-01-01

    Electroencephalographic slow-wave activity (0.5���4 Hz) during non rapid-eye-movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow-wave activity during sleep may promote greater waking prefrontal metabolic rate, and in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow-wave activity was associated with higher prefrontal metabolism during wakefulness and whether this...

  11. The role of non-rapid eye movement slow-wave activity in prefrontal metabolism across young and middle-aged adults.

    Science.gov (United States)

    Wilckens, Kristine A; Aizenstein, Howard J; Nofzinger, Eric A; James, Jeffrey A; Hasler, Brant P; Rosario-Rivera, Bedda L; Franzen, Peter L; Germain, Anne; Hall, Martica H; Kupfer, David J; Price, Julie C; Siegle, Greg J; Buysse, Daniel J

    2016-06-01

    Electroencephalographic slow-wave activity (0.5-4 Hz) during non-rapid eye movement (NREM) sleep is a marker for cortical reorganization, particularly within the prefrontal cortex. Greater slow wave activity during sleep may promote greater waking prefrontal metabolic rate and, in turn, executive function. However, this process may be affected by age. Here we examined whether greater NREM slow wave activity was associated with higher prefrontal metabolism during wakefulness and whether this relationship interacted with age. Fifty-two participants aged 25-61 years were enrolled into studies that included polysomnography and a (18) [F]-fluoro-deoxy-glucose positron emission tomography scan during wakefulness. Absolute and relative measures of NREM slow wave activity were assessed. Semiquantitative and relative measures of cerebral metabolism were collected to assess whole brain and regional metabolism, focusing on two regions of interest: the dorsolateral prefrontal cortex and the orbitofrontal cortex. Greater relative slow wave activity was associated with greater dorsolateral prefrontal metabolism. Age and slow wave activity interacted significantly in predicting semiquantitative whole brain metabolism and outside regions of interest in the posterior cingulate, middle temporal gyrus and the medial frontal gyrus, such that greater slow-wave activity was associated with lower metabolism in the younger participants and greater metabolism in the older participants. These results suggest that slow-wave activity is associated with cerebral metabolism during wakefulness across the adult lifespan within regions important for executive function. © 2016 European Sleep Research Society.

  12. Rapid quantification of metabolic intermediates in blood by liquid chromatography-tandem mass spectrometry to investigate congenital lactic acidosis.

    Science.gov (United States)

    Peng, Minzhi; Cai, Yanna; Fang, Xiefan; Liu, Li

    2016-10-26

    A novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been established to quantify metabolic intermediates, including lactate (Lac), pyruvate (Pyr), acetoacetate (ACAC) and 3-hydroxybutyrate (3-HB) in blood. Samples were deproteinized with methanol-acetonitrile solution, and analytes were separated on an adamantyl group-bonded reverse phase column and detected in multiple reaction monitoring mode. Total analysis time was 4 min per sample. Method validation results displayed that limits of quantification were 10.0 μmol L(-1) for Lac and Pyr, and 5.0 μmol L(-1)for ACAC and 3-HB. The within- and between-run coefficients of variation were in the range of 1.2-6.4% for all analytes. The recoveries were ranged from 95.6 to 111.5%. The reference values of analytes were determined for the pediatric population. Duo to instability of Lac, Pyr and ACAC in vitro, a comprehensive stability assay was performed to determine optimal conditions for sample collection, pretreatment and storage. Results showed that precipitation of protein in blood at bedside combined with low storage temperature could effectively preserve the integrity of Lac, Pyr and 3-HB, but the precipitated protein accelerated degradation of ACAC. Isolation of supernatant fluid slowed degradation of ACAC. Supernatant samples could store at -20 °C for 10 days. The use of plasma or serum to determine these intermediates was not recommended. In this study, 450 samples from patients were analyzed, and 7 patients were diagnosed as congenital lactic acidosis. With the advantages of rapid, accurate and reliable, this method is very suitable for congenital lactic acidosis screening and researches related to energy metabolism. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Codeine Ultra-rapid Metabolizers: Age Appears to be a Key Factor in Adverse Effects of Codeine.

    Science.gov (United States)

    Heintze, K; Fuchs, W

    2015-12-01

    Codeine is widely used as an analgesic drug. Taking into account the high consumption of codeine, only few fatal adverse events have been published. A number of reports, where neonates and children showed serious or fatal adverse reactions, led to a restriction of the use of codeine in this patient group. Therefore, we reviewed the safety of codeine in adults. PubMed was systematically searched for clinical studies and case reports, with a special focus on CYP2D6, the enzyme that converts codeine to morphine and exhibits genetic polymorphism.181 cases were identified in adults in conjunction with serious or lethal effects of codeine. In the vast majority of cases, codeine was used in combination with other drugs by drug-dependent individuals or with a suicidal intent. Only 2 cases were found where ultra-rapid metabolizers experienced severe non-lethal adverse events. This is far less than would be predicted from the number of cases reported in children. The discrepancy may be explained by developmental changes in the disposition of codeine.The strategy of regulatory authorities to restrict access to codeine for infants and young children, the apparent highest risk group, has a factual and pharmacological rationale. By the same standards, there is no need for restrictions for adult use of codeine. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Physiological and metabolic adaptations of Potamogeton pectinatus L. tubers support rapid elongation of stem tissue in the absence of oxygen.

    Science.gov (United States)

    Dixon, M H; Hill, S A; Jackson, M B; Ratcliffe, R G; Sweetlove, L J

    2006-01-01

    Tubers of Potamogeton pectinatus L., an aquatic pondweed, over-winter in the anoxic sediments of rivers, lakes and marshes. Growth of the pre-formed shoot that emerges from the tuber is remarkably tolerant to anoxia, with elongation of the stem occurring faster when oxygen is absent. This response, which allows the shoot to reach oxygenated waters, occurs despite a 69-81% reduction in the rate of ATP production, and it is underpinned by several physiological and metabolic adaptations that contribute to efficient energy usage. First, extension of the pre-formed shoot is the result of cell expansion, without the accumulation of new cellular material. Secondly, after over-wintering, the tuber and pre-formed shoot have the enzymes necessary for a rapid fermentative response at the onset of growth under anoxia. Thirdly, the incorporation of [(35)S]methionine into protein is greatly reduced under anoxia. The majority of the anoxically synthesized proteins differ from those in aerobically grown tissue, implying an extensive redirection of protein synthesis under anoxia. Finally, anoxia-induced cytoplasmic acidosis is prevented to an unprecedented degree. The adaptations of this anoxia-tolerant plant tissue emphasize the importance of the mechanisms that balance ATP production and consumption in the absence of oxygen.

  15. Peripheral metabolic responses to prolonged weight reduction that promote rapid, efficient regain in obesity-prone rats.

    Science.gov (United States)

    MacLean, Paul S; Higgins, Janine A; Jackman, Matthew R; Johnson, Ginger C; Fleming-Elder, Brooke K; Wyatt, Holly R; Melanson, Edward L; Hill, James O

    2006-06-01

    Weight regain after weight loss is the most significant impediment to long-term weight reduction. We have developed a rodent paradigm that models the process of regain after weight loss, and we have employed both prospective and cross-sectional analyses to characterize the compensatory adaptations to weight reduction that may contribute to the propensity to regain lost weight. Obese rats were fed an energy-restricted (50-60% kcal) low-fat diet that reduced body weight by 14%. This reduced weight was maintained for up to 16 wk with limited provisions of the low-fat diet. Intake restriction was then removed, and the rats were followed for 56 days as they relapsed to the obese state. Prolonged weight reduction was accompanied by 1) a persistent energy gap resulting from an increased drive to eat and a reduced expenditure of energy, 2) a higher caloric efficiency of regain that may be linked with suppressed lipid utilization early in the relapse process, 3) preferential lipid accumulation in adipose tissue accompanied by adipocyte hyperplasia, and 4) humoral adiposity signals that underestimate the level of peripheral adiposity and likely influence the neural pathways controlling energy balance. Taken together, long-term weight reduction in this rodent paradigm is accompanied by a number of interrelated compensatory adjustments in the periphery that work together to promote rapid and efficient weight regain. These metabolic adjustments to weight reduction are discussed in the context of a homeostatic feedback system that controls body weight.

  16. TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Groh, K.R.

    1993-01-01

    This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglev MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.

  17. TransRapid TR-07 maglev-spectrum magnetic field effects on daily pineal indoleamine metabolic rhythms in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Groh, K.R.

    1993-06-01

    This study examined the effects on pineal function of magnetic field (MF) exposures (ac and dc components) similar to those produced by the TransRapid TR-07 and other electromagnetic maglev systems (EMS). Rats were entrained to a light-dark cycle and then exposed to a continuous, or to an inverted, intermittent (on = 45 s, off = 15 s, induced current = 267 G/s) simulated multifrequency ac and dc magnetic field (MF) at 1 or 7 times the TR-07 maglev vehicle MF intensity for 2 hr. Other groups of rats were exposed to only the ac or the dc-component of the maglev MF. For comparison, one group was exposed to an inverted, intermittent 60-Hz MF. Each group was compared to an unexposed group of rats for changes in pineal melatonin and serotonin-N-acetyltransferase (NAT). MF exposures at an intensity equivalent to that produced by the TR-07 vehicle had no effect on melatonin or NAT compared with sham-exposed animals under any of the conditions examined. However, 7X TR-07-level continuous 2-h MF exposures significantly depressed pineal NAT by 45%. Pineal melatonin was also depressed 33--43% by a continuous 7X TR-07 MF exposure and 28% by an intermittent 60-Hz 850-mG MF, but the results were not statically significant. This study demonstrates that intermittent, combined ac and dc MFs similar to those produced by the TR-07 EMS maglev vehicle alter the normal circadian rhythm of pineal indoleamine metabolism. The pineal regulatory enzyme NAT was more sensitive to MF exposure than melatonin and may be a more desirable measure of the biological effects of MF exposure.

  18. Beta-hydroxybutyrate and pyroglutamate can be included in a rapid GC-MS screening method for differential diagnosis of metabolic acidosis.

    Science.gov (United States)

    Føreid, Siri; Gadeholt, Gaut

    2017-04-01

    A rapid gas chromatographic mass spectrometric method for measuring anions associated with acute anion gap metabolic acidosis is described. The method is an extension of a previous method. The method quantifies glycolic acid, beta-hydroxybutyric acid with good linearity and pyroglutamic acid with a reproducible curvature relation between 1 and 20 mmol/L and can help the clinician distinguish effectively between ethylene glycol poisoning, alcoholic and diabetic ketoacidosis and cysteine deficiency so early that it will have clinical consequences.

  19. The protease inhibitors ritonavir and saquinavir influence lipid metabolism: a pig model for the rapid evaluation of new drugs

    DEFF Research Database (Denmark)

    Petersen, E.; Mu, Huiling; Porsgaard, Trine

    2010-01-01

    Background: Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Gottingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected t...

  20. Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial.

    Directory of Open Access Journals (Sweden)

    Matthew D Campbell

    Full Text Available To examine the metabolic, gluco-regulatory-hormonal and inflammatory cytokine responses to large reductions in rapid-acting insulin dose administered prandially before and after intensive running exercise in male type 1 diabetes patients.This was a single centre, randomised, controlled open label study. Following preliminary testing, 8 male patients (24±2 years, HbA1c 7.7±0.4%/61±4 mmol.l-1 treated with insulin's glargine and aspart, or lispro attended the laboratory on two mornings at ∼08:00 h and consumed a standardised breakfast carbohydrate bolus (1 g carbohydrate.kg-1BM; 380±10 kcal and self-administered a 75% reduced rapid-acting insulin dose 60 minutes before 45 minutes of intensive treadmill running at 73.1±0.9% VO2peak. At 60 minutes post-exercise, patients ingested a meal (1 g carbohydrate.kg-1BM; 660±21 kcal and administered either a Full or 50% reduced rapid-acting insulin dose. Blood glucose and lactate, serum insulin, cortisol, non-esterified-fatty-acids, β-Hydroxybutyrate, and plasma glucagon, adrenaline, noradrenaline, IL-6, and TNF-α concentrations were measured for 180 minutes post-meal.All participants were analysed. All glycaemic, metabolic, hormonal, and cytokine responses were similar between conditions up to 60 minutes following exercise. Following the post-exercise meal, serum insulin concentrations were lower under 50% (p<0.05 resulting in 75% of patients experiencing hyperglycaemia (blood glucose ≥8.0 mmol.l-1; 50% n = 6, Full n = 3. β-Hydroxybutyrate concentrations decreased similarly, such that at 180 minutes post-meal concentrations were lower than rest under Full and 50%. IL-6 and TNF-α concentrations remained similar to fasting levels under 50% but declined under Full. Under 50% IL-6 concentrations were inversely related with serum insulin concentrations (r = -0.484, p = 0.017.Heavily reducing rapid-acting insulin dose with a carbohydrate bolus before, and a meal after intensive

  1. Restriction of rapid eye movement sleep during adolescence increases energy gain and metabolic efficiency in young adult rats.

    Science.gov (United States)

    Ribeiro-Silva, Neila; Nejm, Mariana Bocca; da Silva, Sylvia Maria Affonso; Suchecki, Deborah; Luz, Jacqueline

    2016-02-01

    What is the central question of this study? Sleep curtailment in infancy and adolescence may lead to long-term risk for obesity, but the mechanisms involved have not yet been determined. This study examined the immediate and long-term metabolic effects produced by sleep restriction in young rats. What is the main finding and its importance? Prolonged sleep restriction reduced weight gain (body fat stores) in young animals. After prolonged recovery, sleep-restricted rats tended to save more energy and to store more fat, possibly owing to increased gross food efficiency. This could be the first step to understand this association. Sleep curtailment is associated with obesity and metabolic changes in adults and children. The aim of the present study was to evaluate the immediate and long-term metabolic alterations produced by sleep restriction in pubertal male rats. Male Wistar rats (28 days old) were allocated to a control (CTL) group or a sleep-restricted (SR) group. This was accomplished by the single platform technique for 18 h per day for 21 days. These groups were subdivided into the following four time points for assessment: sleep restriction and 1, 2 and 4 months of recovery. Body weight and food intake were monitored throughout the experiment. At the end of each time period, blood was collected for metabolic profiling, and the carcasses were processed for measurement of body composition and energy balance. During the period of sleep restriction, SR animals consumed less food in the home cages. This group also displayed lower body weight, body fat, triglycerides and glucose levels than CTL rats. At the end of the first month of recovery, despite eating as much as CTL rats, SR animals showed greater energy and body weight gain, increased gross food efficiency and decreased energy expenditure. At the end of the second and fourth months of recovery, the groups were no longer different, except for energy gain and gross food efficiency, which remained higher in SR

  2. Rapid metabolic profiling of Nicotiana tabacum defence responses against Phytophthora nicotianae using direct infrared laser desorption ionization mass spectrometry and principal component analysis.

    Science.gov (United States)

    Ibáñez, Alfredo J; Scharte, Judith; Bones, Philipp; Pirkl, Alexander; Meldau, Stefan; Baldwin, Ian T; Hillenkamp, Franz; Weis, Engelbert; Dreisewerd, Klaus

    2010-06-09

    Successful defence of tobacco plants against attack from the oomycete Phytophthora nicotianae includes a type of local programmed cell death called the hypersensitive response. Complex and not completely understood signaling processes are required to mediate the development of this defence in the infected tissue. Here, we demonstrate that different families of metabolites can be monitored in small pieces of infected, mechanically-stressed, and healthy tobacco leaves using direct infrared laser desorption ionization orthogonal time-of-flight mass spectrometry. The defence response was monitored for 1 - 9 hours post infection. Infrared laser desorption ionization orthogonal time-of-flight mass spectrometry allows rapid and simultaneous detection in both negative and positive ion mode of a wide range of naturally occurring primary and secondary metabolites. An unsupervised principal component analysis was employed to identify correlations between changes in metabolite expression (obtained at different times and sample treatment conditions) and the overall defence response.A one-dimensional projection of the principal components 1 and 2 obtained from positive ion mode spectra was used to generate a Biological Response Index (BRI). The BRI obtained for each sample treatment was compared with the number of dead cells found in the respective tissue. The high correlation between these two values suggested that the BRI provides a rapid assessment of the plant response against the pathogen infection. Evaluation of the loading plots of the principal components (1 and 2) reveals a correlation among three metabolic cascades and the defence response generated in infected leaves. Analysis of selected phytohormones by liquid chromatography electrospray ionization mass spectrometry verified our findings. The described methodology allows for rapid assessment of infection-specific changes in the plant metabolism, in particular of phenolics, alkaloids, oxylipins, and carbohydrates

  3. Rapid metabolic profiling of Nicotiana tabacum defence responses against Phytophthora nicotianae using direct infrared laser desorption ionization mass spectrometry and principal component analysis

    Directory of Open Access Journals (Sweden)

    Weis Engelbert

    2010-06-01

    Full Text Available Abstract Background Successful defence of tobacco plants against attack from the oomycete Phytophthora nicotianae includes a type of local programmed cell death called the hypersensitive response. Complex and not completely understood signaling processes are required to mediate the development of this defence in the infected tissue. Here, we demonstrate that different families of metabolites can be monitored in small pieces of infected, mechanically-stressed, and healthy tobacco leaves using direct infrared laser desorption ionization orthogonal time-of-flight mass spectrometry. The defence response was monitored for 1 - 9 hours post infection. Results Infrared laser desorption ionization orthogonal time-of-flight mass spectrometry allows rapid and simultaneous detection in both negative and positive ion mode of a wide range of naturally occurring primary and secondary metabolites. An unsupervised principal component analysis was employed to identify correlations between changes in metabolite expression (obtained at different times and sample treatment conditions and the overall defence response. A one-dimensional projection of the principal components 1 and 2 obtained from positive ion mode spectra was used to generate a Biological Response Index (BRI. The BRI obtained for each sample treatment was compared with the number of dead cells found in the respective tissue. The high correlation between these two values suggested that the BRI provides a rapid assessment of the plant response against the pathogen infection. Evaluation of the loading plots of the principal components (1 and 2 reveals a correlation among three metabolic cascades and the defence response generated in infected leaves. Analysis of selected phytohormones by liquid chromatography electrospray ionization mass spectrometry verified our findings. Conclusion The described methodology allows for rapid assessment of infection-specific changes in the plant metabolism, in particular

  4. Calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis: a rapid method to evaluate inhibitors of arachidonic acid metabolism in vivo

    Directory of Open Access Journals (Sweden)

    T. S. Rao

    1993-01-01

    Full Text Available The present investigation characterizes calcium ionophore (A-23187 induced peritoneal eicosanoid biosynthesis in the rat. Intraperitoneal injection of A-23187 (20 μg/rat stimulated marked biosynthesis of 6-keto-PGF1α (6-KPA, TxB2, LTC4 and LTB4, with no detectable changes on levels of PGE2. Levels of all eicosanoids decreased rapidly after a peak which was seen as early as 5 min. Enzyme markers of cellular contents of neutrophils and mononuclear cells, MPO and NAG respectively, decreased rapidly after ionophore injection; this was followed by increases after 60 min. Indomethacin, a selective cyclooxygenase inhibitor, and zileuton and ICI D-2138, two selective 5-lipoxygenase inhibitors attenuated prostaglandin and leukotriene pathways respectively. Oral administration of zileuton (20 mg/kg, p.o. inhibited LTB4 biosynthesis for up to 6 h suggesting a long duration of pharmacological activity in the rats consistent with its longer half-life. The rapid onset and the magnitude of increases in levels of eicosanoids render the ionophore induced peritoneal eicosanoid biosynthesis a useful model to evaluate pharmacological profiles of inhibitors of eicosanoid pathways in vivo.

  5. Rapid nanoparticle-mediated monitoring of bacterial metabolic activity and assessment of antimicrobial susceptibility in blood with magnetic relaxation.

    Directory of Open Access Journals (Sweden)

    Charalambos Kaittanis

    2008-09-01

    Full Text Available Considering the increased incidence of bacterial infections and the emergence of multidrug resistant bacteria at the global level, we designed superparamagnetic iron oxide nanoparticles as nanosensors for the assessment of antimicrobial susceptibility through magnetic relaxation. In this report, we demonstrate that iron oxide nanosensors, either dextran-coated supplemented with Con A or silica-coated conjugated directly to Con A, can be used for the fast (1 quantification of polysaccharides, (2 assessment of metabolic activity and (3 determination of antimicrobial susceptibility in blood. The use of these polysaccharide nanosensors in the determination of antimicrobial susceptibility in the clinic or the field, and the utilization of these nanoprobes in pharmaceutical R&D are anticipated.

  6. Rapid increase in fibroblast growth factor 21 in protein malnutrition and its impact on growth and lipid metabolism.

    Science.gov (United States)

    Ozaki, Yori; Saito, Kenji; Nakazawa, Kyoko; Konishi, Morichika; Itoh, Nobuyuki; Hakuno, Fumihiko; Takahashi, Shin-Ichiro; Kato, Hisanori; Takenaka, Asako

    2015-11-14

    Protein malnutrition promotes hepatic steatosis, decreases insulin-like growth factor (IGF)-I production and retards growth. To identify new molecules involved in such changes, we conducted DNA microarray analysis on liver samples from rats fed an isoenergetic low-protein diet for 8 h. We identified the fibroblast growth factor 21 gene (Fgf21) as one of the most strongly up-regulated genes under conditions of acute protein malnutrition (P<0·05, false-discovery rate<0·001). In addition, amino acid deprivation increased Fgf21 mRNA levels in rat liver-derived RL-34 cells (P<0·01). These results suggested that amino acid limitation directly increases Fgf21 expression. FGF21 is a polypeptide hormone that regulates glucose and lipid metabolism. FGF21 also promotes a growth hormone-resistance state and suppresses IGF-I in transgenic mice. Therefore, to determine further whether Fgf21 up-regulation causes hepatic steatosis and growth retardation after IGF-I decrease in protein malnutrition, we fed an isoenergetic low-protein diet to Fgf21-knockout (KO) mice. Fgf21-KO did not rescue growth retardation and reduced plasma IGF-I concentration in these mice. Fgf21-KO mice showed greater epididymal white adipose tissue weight and increased hepatic TAG and cholesterol levels under protein malnutrition conditions (P<0·05). Overall, the results showed that protein deprivation directly increased Fgf21 expression. However, growth retardation and decreased IGF-I were not mediated by increased FGF21 expression in protein malnutrition. Furthermore, FGF21 up-regulation rather appears to have a protective effect against obesity and hepatic steatosis in protein-malnourished animals.

  7. Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes.

    Directory of Open Access Journals (Sweden)

    Yi-Hung Liao

    Full Text Available Changes in an athlete's physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S, and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004, increased insulin/cortisol ratio (+59.9%, p = 0.004, reduced aerobic power (-2.43%, p = 0.043, increased body fat accumulation (body fat%: +21.3%, p < 0.001, decreased muscle mass (muscle mass%: -4.04%, p < 0.001, and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006. The neutrophil-to-lymphocyte ratio (NLR, a systemic inflammatory index, increased by 48.2% (p = 0.005. The change in aerobic capacity was correlated with the increased fat mass (r = -0.429, p = 0.049 but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044 and aerobic capacity (r = -0.439, p = 0.045. We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle loss

  8. The Relation of Rapid Changes in Obesity Measures to Lipid Profile - Insights from a Nationwide Metabolic Health Survey in 444 Polish Cities

    Science.gov (United States)

    Kaess, Bernhard M.; Jóźwiak, Jacek; Nelson, Christopher P.; Lukas, Witold; Mastej, Mirosław; Windak, Adam; Tomasik, Tomasz; Grzeszczak, Władysław; Tykarski, Andrzej; Gąsowski, Jerzy; Ślęzak-Prochazka, Izabella; Ślęzak, Andrzej; Charchar, Fadi J.; Sattar, Naveed; Thompson, John R.; Samani, Nilesh J.; Tomaszewski, Maciej

    2014-01-01

    Objective The impact of fast changes in obesity indices on other measures of metabolic health is poorly defined in the general population. Using the Polish accession to the European Union as a model of political and social transformation we examined how an expected rapid increase in body mass index (BMI) and waist circumference relates to changes in lipid profile, both at the population and personal level. Methods Through primary care centres in 444 Polish cities, two cross-sectional nationwide population-based surveys (LIPIDOGRAM 2004 and LIPIDOGRAM 2006) examined 15,404 and 15,453 adult individuals in 2004 and 2006, respectively. A separate prospective sample of 1,840 individuals recruited in 2004 had a follow-up in 2006 (LIPIDOGRAM PLUS). Results Two years after Polish accession to European Union, mean population BMI and waist circumference increased by 0.6% and 0.9%, respectively. This tracked with a 7.6% drop in HDL-cholesterol and a 2.1% increase in triglycerides (all prelation of BMI to the magnitude of change in both lipid fractions was comparable to that of waist circumference. Conclusions Moderate changes in obesity measures tracked with a significant deterioration in measures of pro-atherogenic dyslipidaemia at both personal and population level. These associations were predominantly driven by factors not measureable directly through either BMI or waist circumference. PMID:24497983

  9. Comparison of the effects of slowly and rapidly absorbed carbohydrates on postprandial glucose metabolism in type 2 diabetes mellitus patients: a randomized trial.

    Science.gov (United States)

    Ang, Meidjie; Linn, Thomas

    2014-10-01

    Isomaltulose attenuates postprandial glucose and insulin concentrations compared with sucrose in patients with type 2 diabetes mellitus (T2DM). However, the mechanism by which isomaltulose limits postprandial hyperglycemia has not been clarified. The objective was therefore to assess the effects of bolus administration of isomaltulose on glucose metabolism compared with sucrose in T2DM. In a randomized, double-blind, crossover design, 11 participants with T2DM initially underwent a 3-h euglycemic-hyperinsulinemic (0.8 mU · kg(-1) · min(-1)) clamp that was subsequently combined with 1 g/kg body wt of an oral (13)C-enriched isomaltulose or sucrose load. Hormonal responses and glucose kinetics were analyzed during a 4-h postprandial period. Compared with sucrose, absorption of isomaltulose was prolonged by ∼50 min (P = 0.004). Mean plasma concentrations of insulin, C-peptide, glucagon, and glucose-dependent insulinotropic peptide were ∼10-23% lower (P insulin-to-glucagon ratio (P Insulin action was enhanced after isomaltulose compared with sucrose (P = 0.013). Ingestion of slowly absorbed isomaltulose attenuates postprandial hyperglycemia by reducing oral glucose appearance, inhibiting endogenous glucose production (EGP), and increasing SGU compared with ingestion of rapidly absorbed sucrose in patients with T2DM. In addition, GLP-1 secretion contributes to a beneficial shift in the insulin-to-glucagon ratio, suppression of EGP, and enhancement of SGU after isomaltulose consumption. This trial was registered at clinicaltrials.gov as NCT01070238. © 2014 American Society for Nutrition.

  10. Serotonin mediates rapid changes of striatal glucose and lactate metabolism after systemic 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") administration in awake rats

    DEFF Research Database (Denmark)

    Gramsbergen, Jan Bert; Cumming, Paul

    2007-01-01

     The pathway for selective serotonergic toxicity of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") is poorly understood, but has been linked to hyperthermia and disturbed energy metabolism. We investigated the dose-dependency and time-course of MDMA-induced perturbations of cerebral glucose...

  11. Rapid development of systemic insulin resistance with overeating is not accompanied by robust changes in skeletal muscle glucose and lipid metabolism.

    Science.gov (United States)

    Cornford, Andrea S; Hinko, Alexander; Nelson, Rachael K; Barkan, Ariel L; Horowitz, Jeffrey F

    2013-05-01

    Prolonged overeating and the resultant weight gain are clearly linked with the development of insulin resistance and other cardiometabolic abnormalities, but adaptations that occur after relatively short periods of overeating are not completely understood. The purpose of this study was to characterize metabolic adaptations that may accompany the development of insulin resistance after 2 weeks of overeating. Healthy, nonobese subjects (n = 9) were admitted to the hospital for 2 weeks, during which time they ate ∼4000 kcals·day(-1) (70 kcal·kg(-1) fat free mass·day(-1)). Insulin sensitivity was estimated during a meal tolerance test, and a muscle biopsy was obtained to assess muscle lipid accumulation and protein markers associated with insulin resistance, inflammation, and the regulation of lipid metabolism. Whole-body insulin sensitivity declined markedly after 2 weeks of overeating (Matsuda composite index: 8.3 ± 1.3 vs. 4.6 ± 0.7, p insulin resistance and inflammation (i.e., phosphorylation of IRS-1-Ser(312), Akt-Ser(473), and c-Jun N-terminal kinase) were not altered by overeating. Intramyocellular lipids tended to increase after 2 weeks of overeating (triacylglyceride: 7.6 ± 1.6 vs. 10.0 ± 1.8 nmol·mg(-1) wet weight; diacylglyceride: 104 ± 10 vs. 142 ± 23 pmol·mg(-1) wet weight) but these changes did not reach statistical significance. Overeating induced a 2-fold increase in 24-h insulin response (area under the curve (AUC); p increase in muscle lipid accumulation. In summary, our findings suggest alterations in skeletal muscle metabolism may not contribute meaningfully to the marked whole-body insulin resistance observed after 2 weeks of overeating.

  12. Metabolic Imaging of Infection

    NARCIS (Netherlands)

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

    2017-01-01

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

  13. Genotypic Variation under Fe Deficiency Results in Rapid Changes in Protein Expressions and Genes Involved in Fe Metabolism and Antioxidant Mechanisms in Tomato Seedlings (Solanum lycopersicum L.)

    Science.gov (United States)

    Muneer, Sowbiya; Jeong, Byoung Ryong

    2015-01-01

    To investigate Fe deficiency tolerance in tomato cultivars, quantification of proteins and genes involved in Fe metabolism and antioxidant mechanisms were performed in “Roggusanmaru” and “Super Doterang”. Fe deficiency (Moderate, low and –Fe) significantly decreased the biomass, total, and apoplastic Fe concentration of “Roggusanmaru”, while a slight variation was observed in “Super Doterang” cultivar. The quantity of important photosynthetic pigments such as total chlorophyll and carotenoid contents significantly decreased in “Roggusanmaru” than “Super Doterang” cultivar. The total protein profile in leaves and roots determines that “Super Doterang” exhibited an optimal tolerance to Fe deficiency compared to “Roggusanmaru” cultivar. A reduction in expression of PSI (photosystem I), PSII (photosystem II) super-complexes and related thylakoid protein contents were detected in “Roggusanmaru” than “Super Doterang” cultivar. Moreover, the relative gene expression of SlPSI and SlPSII were well maintained in “Super Doterang” than “Roggusanmaru” cultivar. The relative expression of genes involved in Fe-transport (SlIRT1 and SlIRT2) and Fe(III) chelates reductase oxidase (SlFRO1) were relatively reduced in “Roggusanmaru”, while increased in “Super Doterang” cultivar under Fe deficient conditions. The H+-ATPase relative gene expression (SlAHA1) in roots were maintained in “Super Doterang” compared to “Roggusanmaru”. Furthermore, the gene expressions involved in antioxidant defense mechanisms (SlSOD, SlAPX and SlCAT) in leaves and roots showed that these genes were highly increased in “Super Doterang”, whereas decreased in “Roggusanmaru” cultivar under Fe deficiency. The present study suggested that “Super Doterang” is better tomato cultivar than “Roggusanmaru” for calcareous soils. PMID:26602920

  14. Metabolic Myopathies

    Science.gov (United States)

    ... Am A Patient / Caregiver Diseases & Conditions Metabolic Myopathies Metabolic Myopathies Fast Facts Metabolic myopathies are rare genetic ... no family history of the condition. What are metabolic myopathies? Metabolic myopathies are genetic defects that interfere ...

  15. Metabolic Panel

    Science.gov (United States)

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

  16. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys ... from the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known ...

  17. Metabolic neuropathies

    Science.gov (United States)

    Neuropathy - metabolic ... damage can be caused by many different things. Metabolic neuropathy may be caused by: A problem with ... is one of the most common causes of metabolic neuropathies. People who are at the highest risk ...

  18. Metabolic flexibility

    National Research Council Canada - National Science Library

    Storlien, Len; Oakes, Nick D; Kelley, David E

    2004-01-01

    ...). Such capacities characterize the healthy state and can be termed 'metabolic flexibility'. However, increasing evidence points to metabolic inflexibility as a key dysfunction of the cluster of disease states encompassed by the term 'metabolic syndrome...

  19. Rapid Prototyping

    Science.gov (United States)

    1999-01-01

    Javelin, a Lone Peak Engineering Inc. Company has introduced the SteamRoller(TM) System as a commercial product. The system was designed by Javelin during a Phase II NASA funded small commercial product. The purpose of the invention was to allow automated-feed of flexible ceramic tapes to the Laminated Object Manufacturing rapid prototyping equipment. The ceramic material that Javelin was working with during the Phase II project is silicon nitride. This engineered ceramic material is of interest for space-based component.

  20. Fluoroacetylcarnitine: metabolism and metabolic effects in mitochondria

    Energy Technology Data Exchange (ETDEWEB)

    Bremer, J.; Davis, E.J.

    1973-01-01

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

  1. Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus x Simmental cattle fed high-starch or low-starch diets

    National Research Council Canada - National Science Library

    Graugnard, Daniel E; Piantoni, Paola; Bionaz, Massimo; Berger, Larry L; Faulkner, Dan B; Loor, Juan J

    2009-01-01

    .... Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus...

  2. What is Nutrition & Metabolism?

    Directory of Open Access Journals (Sweden)

    Feinman Richard D

    2004-08-01

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

  3. Metabolic Disorders

    Science.gov (United States)

    ... as your liver, muscles, and body fat. A metabolic disorder occurs when abnormal chemical reactions in your ... that produce the energy. You can develop a metabolic disorder when some organs, such as your liver ...

  4. Metabolic Syndrome

    Science.gov (United States)

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

  5. Genome scale metabolic modeling of cancer

    DEFF Research Database (Denmark)

    Nilsson, Avlant; Nielsen, Jens

    2017-01-01

    Cancer cells reprogram metabolism to support rapid proliferation and survival. Energy metabolism is particularly important for growth and genes encoding enzymes involved in energy metabolism are frequently altered in cancer cells. A genome scale metabolic model (GEM) is a mathematical formalization...... of metabolism which allows simulation and hypotheses testing of metabolic strategies. It has successfully been applied to many microorganisms and is now used to study cancer metabolism. Generic models of human metabolism have been reconstructed based on the existence of metabolic genes in the human genome....... Cancer specific models of metabolism have also been generated by reducing the number of reactions in the generic model based on high throughput expression data, e.g. transcriptomics and proteomics. Targets for drugs and bio markers for diagnostics have been identified using these models. They have also...

  6. Nucleotide Metabolism

    DEFF Research Database (Denmark)

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

    2011-01-01

    Metabolic pathways are connected through their utilization of nucleotides as supplier of energy, allosteric effectors, and their role in activation of intermediates. Therefore, any attempt to exploit a given living organism in a biotechnological process will have an impact on nucleotide metabolism....... The aim of this article is to provide knowledge of nucleotide metabolism and its regulation to facilitate interpretation of data arising from genetics, proteomics, and transcriptomics in connection with biotechnological processes and beyond....

  7. Metabolic myopathies

    Science.gov (United States)

    Martin, A.; Haller, R. G.; Barohn, R.; Blomqvist, C. G. (Principal Investigator)

    1994-01-01

    Metabolic myopathies are disorders of muscle energy production that result in skeletal muscle dysfunction. Cardiac and systemic metabolic dysfunction may coexist. Symptoms are often intermittent and provoked by exercise or changes in supply of lipid and carbohydrate fuels. Specific disorders of lipid and carbohydrate metabolism in muscle are reviewed. Evaluation often requires provocative exercise testing. These tests may include ischemic forearm exercise, aerobic cycle exercise, and 31P magnetic resonance spectroscopy with exercise.

  8. Metabolic Syndrome

    Science.gov (United States)

    ... much saturated fat, and does not get enough physical activity may develop metabolic syndrome. Other causes include insulin resistance and a family ... you’re overweight. It also includes getting more physical activity and eating a ... syndrome treatment If you already have metabolic syndrome, making ...

  9. Drug Metabolism

    Indian Academy of Sciences (India)

    IAS Admin

    functional groups on which different reactions take place in the body. We have covered the detoxification pathways of drug metabolism; however, we still have to understand the toxic effects of drug metabolism via bioactivation process. 3.3 Bioactivation Reactions:Chemistry of Reactive Metabolites and Adverse Drug Effects.

  10. Metabolism of

    African Journals Online (AJOL)

    In many temperate woody species, short days (SDs) induced growth cessation has been shown to be prevented by the application of gibberellins (GAs). Evidence has also been forwarded for the influence of photoperiod on the metabolism of applied GAs. Continuing with this line of research, we studied the metabolism of ...

  11. [Metabolic acidosis].

    Science.gov (United States)

    Regolisti, Giuseppe; Fani, Filippo; Antoniotti, Riccardo; Castellano, Giuseppe; Cremaschi, Elena; Greco, Paolo; Parenti, Elisabetta; Morabito, Santo; Sabatino, Alice; Fiaccadori, Enrico

    2016-01-01

    Metabolic acidosis is frequently observed in clinical practice, especially among critically ill patients and/or in the course of renal failure. Complex mechanisms are involved, in most cases identifiable by medical history, pathophysiology-based diagnostic reasoning and measure of some key acid-base parameters that are easily available or calculable. On this basis the bedside differential diagnosis of metabolic acidosis should be started from the identification of the two main subtypes of metabolic acidosis: the high anion gap metabolic acidosis and the normal anion gap (or hyperchloremic) metabolic acidosis. Metabolic acidosis, especially in its acute forms with elevated anion gap such as is the case of lactic acidosis, diabetic and acute intoxications, may significantly affect metabolic body homeostasis and patients hemodynamic status, setting the stage for true medical emergencies. The therapeutic approach should be first aimed at early correction of concurrent clinical problems (e.g. fluids and hemodynamic optimization in case of shock, mechanical ventilation in case of concomitant respiratory failure, hemodialysis for acute intoxications etc.), in parallel to the formulation of a diagnosis. In case of severe acidosis, the administration of alkalizing agents should be carefully evaluated, taking into account the risk of side effects, as well as the potential need of renal replacement therapy.

  12. Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus x Simmental cattle fed high-starch or low-starch diets.

    Science.gov (United States)

    Graugnard, Daniel E; Piantoni, Paola; Bionaz, Massimo; Berger, Larry L; Faulkner, Dan B; Loor, Juan J

    2009-03-31

    Transcriptional networks coordinate adipocyte differentiation and energy metabolism in rodents. The level of fiber and starch in diets with adequate energy content fed to young cattle has the potential to alter intramuscular adipose tissue development in skeletal muscle. Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus muscle development across cattle types. Longissimus lumborum (LL) from Angus (n = 6) and Angus x Simmental (A x S; n = 6) steer calves (155 +/- 10 days age) fed isonitrogenous high-starch (HiS; 1.43 Mcal/kg diet dry matter; n = 6) or low-starch (LoS; 1.19 Mcal/kg diet dry matter; n = 6) diets was biopsied at 0, 56, and 112 days of feeding for transcript profiling of 31 genes associated with aspects of adipogenesis and energy metabolism. Intake of dietary energy (9.44 +/- 0.57 Mcal/d) across groups during the study did not differ but feed efficiency (weight gain/feed intake) during the first 56 days was greater for steers fed HiS. Expression of PPARG increased ca. 2-fold by day 56 primarily due to HiS in A x S steers. Several potential PPARG-target genes (e.g., ACACA, FASN, FABP4, SCD) increased 2.5-to-25-fold by day 56 across all groups, with responses (e.g., FASN, FABP4) being less pronounced in A x S steers fed LoS. This latter group of steers had markedly greater blood plasma glucose (0.99 vs. 0.79 g/L) and insulin (2.95 vs. 1.17 microg/L) by day 112, all of which were suggestive of insulin resistance. Interactions were observed for FABP4, FASN, GPAM, SCD, and DGAT2, such that feeding A x S steers high-starch and Angus steers low-starch resulted in greater fold-changes by day 56 or 112 (GPAM). Marked up-regulation of INSIG1 (4-to-8-fold) occurred throughout the study across all groups. SREBF1 expression, however, was only greater on day 112 namely due to LoS in A x S steers. The lipogenic

  13. Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus × Simmental cattle fed high-starch or low-starch diets

    Science.gov (United States)

    Graugnard, Daniel E; Piantoni, Paola; Bionaz, Massimo; Berger, Larry L; Faulkner, Dan B; Loor, Juan J

    2009-01-01

    Background Transcriptional networks coordinate adipocyte differentiation and energy metabolism in rodents. The level of fiber and starch in diets with adequate energy content fed to young cattle has the potential to alter intramuscular adipose tissue development in skeletal muscle. Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus muscle development across cattle types. Results Longissimus lumborum (LL) from Angus (n = 6) and Angus × Simmental (A × S; n = 6) steer calves (155 ± 10 days age) fed isonitrogenous high-starch (HiS; 1.43 Mcal/kg diet dry matter; n = 6) or low-starch (LoS; 1.19 Mcal/kg diet dry matter; n = 6) diets was biopsied at 0, 56, and 112 days of feeding for transcript profiling of 31 genes associated with aspects of adipogenesis and energy metabolism. Intake of dietary energy (9.44 ± 0.57 Mcal/d) across groups during the study did not differ but feed efficiency (weight gain/feed intake) during the first 56 days was greater for steers fed HiS. Expression of PPARG increased ca. 2-fold by day 56 primarily due to HiS in A × S steers. Several potential PPARG-target genes (e.g., ACACA, FASN, FABP4, SCD) increased 2.5-to-25-fold by day 56 across all groups, with responses (e.g., FASN, FABP4) being less pronounced in A × S steers fed LoS. This latter group of steers had markedly greater blood plasma glucose (0.99 vs. 0.79 g/L) and insulin (2.95 vs. 1.17 μg/L) by day 112, all of which were suggestive of insulin resistance. Interactions were observed for FABP4, FASN, GPAM, SCD, and DGAT2, such that feeding A × S steers high-starch and Angus steers low-starch resulted in greater fold-changes by day 56 or 112 (GPAM). Marked up-regulation of INSIG1 (4-to-8-fold) occurred throughout the study across all groups. SREBF1 expression, however, was only greater on day 112 namely due to LoS in A × S steers. The

  14. Adipogenic and energy metabolism gene networks in longissimus lumborum during rapid post-weaning growth in Angus and Angus × Simmental cattle fed high-starch or low-starch diets

    Directory of Open Access Journals (Sweden)

    Graugnard Daniel E

    2009-03-01

    Full Text Available Abstract Background Transcriptional networks coordinate adipocyte differentiation and energy metabolism in rodents. The level of fiber and starch in diets with adequate energy content fed to young cattle has the potential to alter intramuscular adipose tissue development in skeletal muscle. Post-weaning alterations in gene expression networks driving adipogenesis, lipid filling, and intracellular energy metabolism provide a means to evaluate long-term effects of nutrition on longissimus muscle development across cattle types. Results Longissimus lumborum (LL from Angus (n = 6 and Angus × Simmental (A × S; n = 6 steer calves (155 ± 10 days age fed isonitrogenous high-starch (HiS; 1.43 Mcal/kg diet dry matter; n = 6 or low-starch (LoS; 1.19 Mcal/kg diet dry matter; n = 6 diets was biopsied at 0, 56, and 112 days of feeding for transcript profiling of 31 genes associated with aspects of adipogenesis and energy metabolism. Intake of dietary energy (9.44 ± 0.57 Mcal/d across groups during the study did not differ but feed efficiency (weight gain/feed intake during the first 56 days was greater for steers fed HiS. Expression of PPARG increased ca. 2-fold by day 56 primarily due to HiS in A × S steers. Several potential PPARG-target genes (e.g., ACACA, FASN, FABP4, SCD increased 2.5-to-25-fold by day 56 across all groups, with responses (e.g., FASN, FABP4 being less pronounced in A × S steers fed LoS. This latter group of steers had markedly greater blood plasma glucose (0.99 vs. 0.79 g/L and insulin (2.95 vs. 1.17 μg/L by day 112, all of which were suggestive of insulin resistance. Interactions were observed for FABP4, FASN, GPAM, SCD, and DGAT2, such that feeding A × S steers high-starch and Angus steers low-starch resulted in greater fold-changes by day 56 or 112 (GPAM. Marked up-regulation of INSIG1 (4-to-8-fold occurred throughout the study across all groups. SREBF1 expression, however, was only greater on day 112 namely due to LoS in A

  15. Drug Metabolism

    Indian Academy of Sciences (India)

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

  16. METABOLIC SYNDROME

    OpenAIRE

    Dikanović, Marinko

    2015-01-01

    Metabolic syndrome is a cluster of disorders that include hyperlipidemia, inadequate insulin resistance, hypertension, and abdominal type obesity. Patients who suffer from this syndrome have an increased risk for heart disease and blood vessel disease, stroke and type II diabetes. The world's leading healthcare institutions also disagree on the exact definition of this organization poremećaja. NCEP (National Cholesterol Education Program) defines metabolic syndrome as a situation in which the...

  17. Metabolic Syndrome (For Parents)

    Science.gov (United States)

    ... Needs a Kidney Transplant Vision Facts and Myths Metabolic Syndrome KidsHealth > For Parents > Metabolic Syndrome Print A A ... this is a condition called metabolic syndrome . About Metabolic Syndrome Not to be confused with metabolic disease (which ...

  18. What is Metabolic Syndrome?

    Science.gov (United States)

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

  19. Metabolic consequences of sleep and circadian disorders

    Science.gov (United States)

    Depner, Christopher M.; Stothard, Ellen R.; Wright, Kenneth P.

    2014-01-01

    Sleep and circadian rhythms modulate or control daily physiological patterns with importance for normal metabolic health. Sleep deficiencies associated with insufficient sleep schedules, insomnia with short-sleep duration, sleep apnea, narcolepsy, circadian misalignment, shift work, night eating syndrome and sleep-related eating disorder may all contribute to metabolic dysregulation. Sleep deficiencies and circadian disruption associated with metabolic dysregulation may contribute to weight gain, obesity, and type 2 diabetes potentially by altering timing and amount of food intake, disrupting energy balance, inflammation, impairing glucose tolerance and insulin sensitivity. Given the rapidly increasing prevalence of metabolic diseases, it is important to recognize the role of sleep and circadian disruption in the development, progression, and morbidity of metabolic disease. Some findings indicate sleep treatments and countermeasures improve metabolic health, but future clinical research investigating prevention and treatment of chronic metabolic disorders through treatment of sleep and circadian disruption is needed. PMID:24816752

  20. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies.

    Science.gov (United States)

    O'Grady, John; Schwender, Jörg; Shachar-Hill, Yair; Morgan, John A

    2012-03-01

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (13)CO(2) dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  1. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies

    Energy Technology Data Exchange (ETDEWEB)

    O' Grady J.; Schwender J.; Shachar-Hill, Y.; Morgan, J. A.

    2012-03-01

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on {sup 13}CO{sub 2} dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  2. Metabolic cartography: experimental quantification of metabolic fluxes from isotopic labelling studies

    Energy Technology Data Exchange (ETDEWEB)

    O' Grady, J; Schwender, J; Shachar-Hill, Y; Morgan, JA

    2012-03-26

    For the past decade, flux maps have provided researchers with an in-depth perspective on plant metabolism. As a rapidly developing field, significant headway has been made recently in computation, experimentation, and overall understanding of metabolic flux analysis. These advances are particularly applicable to the study of plant metabolism. New dynamic computational methods such as non-stationary metabolic flux analysis are finding their place in the toolbox of metabolic engineering, allowing more organisms to be studied and decreasing the time necessary for experimentation, thereby opening new avenues by which to explore the vast diversity of plant metabolism. Also, improved methods of metabolite detection and measurement have been developed, enabling increasingly greater resolution of flux measurements and the analysis of a greater number of the multitude of plant metabolic pathways. Methods to deconvolute organelle-specific metabolism are employed with increasing effectiveness, elucidating the compartmental specificity inherent in plant metabolism. Advances in metabolite measurements have also enabled new types of experiments, such as the calculation of metabolic fluxes based on (CO2)-C-13 dynamic labelling data, and will continue to direct plant metabolic engineering. Newly calculated metabolic flux maps reveal surprising and useful information about plant metabolism, guiding future genetic engineering of crops to higher yields. Due to the significant level of complexity in plants, these methods in combination with other systems biology measurements are necessary to guide plant metabolic engineering in the future.

  3. T cell metabolism and the immune response.

    Science.gov (United States)

    Verbist, Katherine C; Wang, Ruoning; Green, Douglas R

    2012-12-01

    As T cells respond to pathogens, they must transition from a quiescent, naïve state, to a rapidly proliferating, active effector state, and back again to a quiescent state as they develop into memory cells. Such transitions place unique metabolic demands on the differentiating cells. T cells meet these demands by altering their metabolic profiles, which are, in turn, regulated by distinct signaling cascades and transcriptional programs. Here, we examine the metabolic profiles of T cells during an acute immune response and discuss the signal and transcriptional regulators of these metabolic changes. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. Metabolic Engineering

    Indian Academy of Sciences (India)

    IAS Admin

    processes such as generation of energy, production of fundamen- tal building blocks required for structural organization and syn- thesis of biomolecules having specialized functions. ... Symbiosis International. University, Pune. His research interests are in metabolic engineering of lactic acid bacteria for increasing their.

  5. Metabolic Analysis

    Science.gov (United States)

    Tolstikov, Vladimir V.

    Analysis of the metabolome with coverage of all of the possibly detectable components in the sample, rather than analysis of each individual metabolite at a given time, can be accomplished by metabolic analysis. Targeted and/or nontargeted approaches are applied as needed for particular experiments. Monitoring hundreds or more metabolites at a given time requires high-throughput and high-end techniques that enable screening for relative changes in, rather than absolute concentrations of, compounds within a wide dynamic range. Most of the analytical techniques useful for these purposes use GC or HPLC/UPLC separation modules coupled to a fast and accurate mass spectrometer. GC separations require chemical modification (derivatization) before analysis, and work efficiently for the small molecules. HPLC separations are better suited for the analysis of labile and nonvolatile polar and nonpolar compounds in their native form. Direct infusion and NMR-based techniques are mostly used for fingerprinting and snap phenotyping, where applicable. Discovery and validation of metabolic biomarkers are exciting and promising opportunities offered by metabolic analysis applied to biological and biomedical experiments. We have demonstrated that GC-TOF-MS, HPLC/UPLC-RP-MS and HILIC-LC-MS techniques used for metabolic analysis offer sufficient metabolome mapping providing researchers with confident data for subsequent multivariate analysis and data mining.

  6. Metabolic Surgery

    DEFF Research Database (Denmark)

    Pareek, Manan; Schauer, Philip R; Kaplan, Lee M

    2018-01-01

    The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown the superio......The alarming rise in the worldwide prevalence of obesity is paralleled by an increasing burden of type 2 diabetes mellitus. Metabolic surgery is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Randomized trials have recently shown...... the superiority of surgery over medical treatment alone in achieving improved glycemic control, as well as a reduction in cardiovascular risk factors. The mechanisms seem to extend beyond the magnitude of weight loss alone and include improvements in incretin profiles, insulin secretion, and insulin sensitivity...

  7. ER Stress and Lipid Metabolism in Adipocytes

    Directory of Open Access Journals (Sweden)

    Beth S. Zha

    2012-01-01

    Full Text Available The role of endoplasmic reticulum (ER stress is a rapidly emerging field of interest in the pathogenesis of metabolic diseases. Recent studies have shown that chronic activation of ER stress is closely linked to dysregulation of lipid metabolism in several metabolically important cells including hepatocytes, macrophages, β-cells, and adipocytes. Adipocytes are one of the major cell types involved in the pathogenesis of the metabolic syndrome. Recent advances in dissecting the cellular and molecular mechanisms involved in the regulation of adipogenesis and lipid metabolism indicate that activation of ER stress plays a central role in regulating adipocyte function. In this paper, we discuss the current understanding of the potential role of ER stress in lipid metabolism in adipocytes. In addition, we touch upon the interaction of ER stress and autophagy as well as inflammation. Inhibition of ER stress has the potential of decreasing the pathology in adipose tissue that is seen with energy overbalance.

  8. Rapid Prototyping Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The ARDEC Rapid Prototyping (RP) Laboratory was established in December 1992 to provide low cost RP capabilities to the ARDEC engineering community. The Stratasys,...

  9. Metabolic Constraints on the Eukaryotic Transition

    Science.gov (United States)

    Wallace, Rodrick

    2009-04-01

    Mutualism, obligate mutualism, symbiosis, and the eukaryotic ‘fusion’ of Serial Endosymbiosis Theory represent progressively more rapid and less distorted real-time communication between biological structures instantiating information sources. Such progression in accurate information transmission requires, in turn, progressively greater channel capacity that, through the homology between information source uncertainty and free energy density, requires ever more energetic metabolism. The eukaryotic transition, according to this model, may have been entrained by an ecosystem resilience shift from anaerobic to aerobic metabolism.

  10. Rapid Airplane Parametric Input Design (RAPID)

    Science.gov (United States)

    Smith, Robert E.

    1995-01-01

    RAPID is a methodology and software system to define a class of airplane configurations and directly evaluate surface grids, volume grids, and grid sensitivity on and about the configurations. A distinguishing characteristic which separates RAPID from other airplane surface modellers is that the output grids and grid sensitivity are directly applicable in CFD analysis. A small set of design parameters and grid control parameters govern the process which is incorporated into interactive software for 'real time' visual analysis and into batch software for the application of optimization technology. The computed surface grids and volume grids are suitable for a wide range of Computational Fluid Dynamics (CFD) simulation. The general airplane configuration has wing, fuselage, horizontal tail, and vertical tail components. The double-delta wing and tail components are manifested by solving a fourth order partial differential equation (PDE) subject to Dirichlet and Neumann boundary conditions. The design parameters are incorporated into the boundary conditions and therefore govern the shapes of the surfaces. The PDE solution yields a smooth transition between boundaries. Surface grids suitable for CFD calculation are created by establishing an H-type topology about the configuration and incorporating grid spacing functions in the PDE equation for the lifting components and the fuselage definition equations. User specified grid parameters govern the location and degree of grid concentration. A two-block volume grid about a configuration is calculated using the Control Point Form (CPF) technique. The interactive software, which runs on Silicon Graphics IRIS workstations, allows design parameters to be continuously varied and the resulting surface grid to be observed in real time. The batch software computes both the surface and volume grids and also computes the sensitivity of the output grid with respect to the input design parameters by applying the precompiler tool

  11. Rapid shallow breathing

    Science.gov (United States)

    ... the smallest air passages of the lungs in children ( bronchiolitis ) Pneumonia or other lung infection Transient tachypnea of the newborn Anxiety and panic Other serious lung disease Home Care Rapid, shallow breathing should not be treated at home. It is ...

  12. Rapid Strep Test

    Science.gov (United States)

    ... worse than normal. Your first thoughts turn to strep throat. A rapid strep test in your doctor’s office ... your suspicions.Viruses cause most sore throats. However, strep throat is an infection caused by the Group A ...

  13. RAPID3? Aptly named!

    Science.gov (United States)

    Berthelot, J-M

    2014-01-01

    The RAPID3 score is the sum of three 0-10 patient self-report scores: pain, functional impairment on MDHAQ, and patient global estimate. It requires 5 seconds for scoring and can be used in all rheumatologic conditions, although it has mostly been used in rheumatoid arthritis where cutoffs for low disease activity (12/30) have been set. A RAPID3 score of ≤ 3/30 with 1 or 0 swollen joints (RAPID3 ≤ 3 + ≤ SJ1) provides remission criteria comparable to Boolean, SDAI, CDAI, and DAS28 remission criteria, in far less time than a formal joint count. RAPID3 performs as well as the DAS28 in separating active drugs from placebos in clinical trials. RAPID3 also predicts subsequent structural disease progression. RAPID3 can be determined at short intervals at home, allowing the determination of the area under the curve of disease activity between two visits and flare detection. However, RAPID3 should not be seen as a substitute for DAS28 and face to face visits in routine care. Monitoring patient status with only self-report information without a rheumatologist's advice (including joints and physical examination, and consideration of imaging and laboratory tests) may indeed be as undesirable for most patients than joint examination without a patient questionnaire. Conversely, combining the RAPID3 and the DAS28 may consist in faster or more sensitive confirmation that a medication is effective. Similarly, better enquiring of most important concerns of patients (pain, functional status and overall opinion on their disorder) should reinforces patients' confidence in their rheumatologist and treatments.

  14. Dementia due to metabolic causes

    Science.gov (United States)

    Chronic brain - metabolic; Mild cognitive - metabolic; MCI - metabolic ... Possible metabolic causes of dementia include: Hormonal disorders, such as Addison disease , Cushing disease Heavy metal exposure, such as ...

  15. Comprehensive metabolic panel

    Science.gov (United States)

    Metabolic panel - comprehensive; Chem-20; SMA20; Sequential multi-channel analysis with computer-20; SMAC20; Metabolic panel 20 ... Chernecky CC, Berger BJ. Comprehensive metabolic panel (CMP) - ... Diagnostic Procedures . 6th ed. St Louis, MO: Elsevier Saunders; ...

  16. Carbohydrate Metabolism Disorders

    Science.gov (United States)

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

  17. The liver is a metabolic and immunologic organ: A reconsideration of metabolic decompensation due to infection in inborn errors of metabolism (IEM).

    Science.gov (United States)

    Tarasenko, Tatyana N; McGuire, Peter J

    2017-08-01

    Metabolic decompensation in inborn errors of metabolism (IEM) is characterized by a rapid deterioration in metabolic status leading to life-threatening biochemical perturbations (e.g. hypoglycemia, hyperammonemia, acidosis, organ failure). Infection is the major cause of metabolic decompensation in patients with IEM. We hypothesized that activation of the immune system during infection leads to further perturbations in end-organ metabolism resulting in increased morbidity. To address this, we established model systems of metabolic decompensation due to infection. Using these systems, we have described the pathologic mechanisms of metabolic decompensation as well as changes in hepatic metabolic reserve associated with infection. First and foremost, our studies have demonstrated that the liver experiences a significant local innate immune response during influenza infection that modulates hepatic metabolism. Based on these findings, we are the first to suggest that the role of the liver as a metabolic and immunologic organ is central in the pathophysiology of metabolic decompensation due to infection in IEM. The dual function of the liver as a major metabolic regulator and a lymphoid organ responsible for immunosurveillance places this organ at risk for hepatotoxicity. Mobilization of hepatic reserve and the regenerative capacity of a healthy liver compensates for this calculated risk. However, activation of the hepatic innate immune system may be deleterious in IEM. Based on this assertion, strategies aimed at modulating the innate immune response may be a viable target for intervention in the treatment of hepatic metabolic decompensation. Published by Elsevier Inc.

  18. Cancer stem cell metabolism

    National Research Council Canada - National Science Library

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

    2016-01-01

    .... Cancer stem cells also seem to adapt their metabolism to microenvironmental changes by conveniently shifting energy production from one pathway to another, or by acquiring intermediate metabolic phenotypes...

  19. Profiling metabolic networks to study cancer metabolism.

    Science.gov (United States)

    Hiller, Karsten; Metallo, Christian M

    2013-02-01

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

  20. 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

  1. Pharmacokinetics and metabolism of neurotensin in man

    DEFF Research Database (Denmark)

    Pedersen, J H; Andersen, H O; Olsen, P S

    1989-01-01

    was significantly higher in hepatic venous than in systemic plasma. In 6 patients with hepatic disease, systemic plasma intact NT levels were increased, but even more so in hepatic venous plasma. These results demonstrate that metabolism of intact NT is rapid, and a significant peripheral arterio-venous extraction...

  2. The impact of cellular metabolism on chromatin dynamics and epigenetics.

    Science.gov (United States)

    Reid, Michael A; Dai, Ziwei; Locasale, Jason W

    2017-11-01

    The substrates used to modify nucleic acids and chromatin are affected by nutrient availability and the activity of metabolic pathways. Thus, cellular metabolism constitutes a fundamental component of chromatin status and thereby of genome regulation. Here we describe the biochemical and genetic principles of how metabolism can influence chromatin biology and epigenetics, discuss the functional roles of this interplay in developmental and cancer biology, and present future directions in this rapidly emerging area.

  3. Rapid small lot manufacturing

    Energy Technology Data Exchange (ETDEWEB)

    Harrigan, R.W.

    1998-05-09

    The direct connection of information, captured in forms such as CAD databases, to the factory floor is enabling a revolution in manufacturing. Rapid response to very dynamic market conditions is becoming the norm rather than the exception. In order to provide economical rapid fabrication of small numbers of variable products, one must design with manufacturing constraints in mind. In addition, flexible manufacturing systems must be programmed automatically to reduce the time for product change over in the factory and eliminate human errors. Sensor based machine control is needed to adapt idealized, model based machine programs to uncontrolled variables such as the condition of raw materials and fabrication tolerances.

  4. Rat cardiac myocyte adenosine transport and metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Ford, D.A.; Rovetto, M.J.

    1987-01-01

    Based on the importance of myocardial adenosine and adenine nucleotide metabolism, the adenosine salvage pathway in ventricular myocytes was studied. Accurate estimates of transport rates, separate from metabolic fllux, were determined. Adenosine influx was constant between 3 and 60 s. Adenosine metabolism maintained intracellular adenosine concentrations < 10% of the extracellular adenosine concentrations and thus unidirectional influx could be measured. Myocytes transported adenosine via saturable and nonsaturable processes. A minimum estimate of the V/sub max/ of myocytic adenosine kinase indicated the saturable component of adenosine influx was independent of adenosine kinase activity. Saturable transport was inhibited by nitrobenzylthioinosine and verapamil. Extracellular adenosine taken up myocytes was rapidly phosphorylated to adenine taken up by myocytes was rapidly phosphorylated to adenine nucleotides. Not all extracellular adenosine, though, was phosphorylated on entering myocytes, since free, as opposed to protein-bound, intracellular adenosine was detected after digitonin extraction of cells in the presence of 1 mM ethylene-diaminetetraacetic acid.

  5. Rapid Cycling and Its Treatment

    Science.gov (United States)

    ... Announcements Public Service Announcements Partnering with DBSA Rapid Cycling and its Treatment What is bipolar disorder? Bipolar ... to Depression and Manic Depression . What is rapid cycling? Rapid cycling is defined as four or more ...

  6. Rapid manufacturing for microfluidics

    CSIR Research Space (South Africa)

    Land, K

    2012-10-01

    Full Text Available . Microfluidics is at the forefront of developing solutions for drug discovery, diagnostics (from glucose tests to malaria and TB testing) and environmental diagnostics (E-coli monitoring of drinking water). In order to quickly implement new designs, a rapid...

  7. Rapid Prototyping in PVS

    Science.gov (United States)

    Munoz, Cesar A.; Butler, Ricky (Technical Monitor)

    2003-01-01

    PVSio is a conservative extension to the PVS prelude library that provides basic input/output capabilities to the PVS ground evaluator. It supports rapid prototyping in PVS by enhancing the specification language with built-in constructs for string manipulation, floating point arithmetic, and input/output operations.

  8. Rapid Prototyping Reconsidered

    Science.gov (United States)

    Desrosier, James

    2011-01-01

    Continuing educators need additional strategies for developing new programming that can both reduce the time to market and lower the cost of development. Rapid prototyping, a time-compression technique adapted from the high technology industry, represents one such strategy that merits renewed evaluation. Although in higher education rapid…

  9. Inhibition of nitrification and carbon dioxide evolution as rapid tools ...

    African Journals Online (AJOL)

    Inhibition of nitrite formation and CO2 evolution displayed similar levels of sensitivities at 95% confidence levels. These results indicate that monitoring inhibition of metabolic processes rather than mortality was a more rapid and sensitive tool for ecotoxicological evaluation of chemicals employed in the petroleum industry in ...

  10. Rapid manufacturing facilitated customisation

    OpenAIRE

    Tuck, Christopher John; Hague, Richard; Ruffo, Massimiliano; Ransley, Michelle; Adams, Paul Russell

    2008-01-01

    Abstract This paper describes the production of body-fitting customised seat profiles utilising the following digital methods: three dimensional laser scanning, reverse engineering and Rapid Manufacturing (RM). The seat profiles have been manufactured in order to influence the comfort characteristics of an existing ejector seat manufactured by Martin Baker Aircraft Ltd. The seat, known as Navy Aircrew Common Ejection Seat (NACES), was originally designed with a generic profile. ...

  11. Rapid Detection of Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Perlin

    2005-08-14

    Pathogen identification is a crucial first defense against bioterrorism. A major emphasis of our national biodefense strategy is to establish fast, accurate and sensitive assays for diagnosis of infectious diseases agents. Such assays will ensure early and appropriate treatment of infected patients. Rapid diagnostics can also support infection control measures, which monitor and limit the spread of infectious diseases agents. Many select agents are highly transmissible in the early stages of disease, and it is critical to identify infected patients and limit the risk to the remainder of the population and to stem potential panic in the general population. Nucleic acid-based molecular approaches for identification overcome many of the deficiencies associated with conventional culture methods by exploiting both large- and small-scale genomic differences between organisms. PCR-based amplification of highly conserved ribosomal RNA (rRNA) genes, intergenic sequences, and specific toxin genes is currently the most reliable approach for bacterial, fungal and many viral pathogenic agents. When combined with fluorescence-based oligonucleotide detection systems, this approach provides real-time, quantitative, high fidelity analysis capable of single nucleotide allelic discrimination (4). These probe systems offer rapid turn around time (<2 h) and are suitable for high throughput, automated multiplex operations that are critical for clinical diagnostic laboratories. In this pilot program, we have used molecular beacon technology invented at the Public health Research Institute to develop a new generation of molecular probes to rapidly detect important agents of infectious diseases. We have also developed protocols to rapidly extract nucleic acids from a variety of clinical specimen including and blood and tissue to for detection in the molecular assays. This work represented a cooperative research development program between the Kramer-Tyagi/Perlin labs on probe development

  12. Metabolic syndrome and risk of restenosis in patients undergoing percutaneous coronary intervention

    NARCIS (Netherlands)

    Wouterjukema, J; Monraats, PS; Zwinderman, AH; De Maat, MPM; Kastelein, JJP; Doevendans, PAF; De Winter, RJ; Tio, RA; Frants, RR; Van der Laarse, A; Van der Wall, EE; Jukema, JW

    OBJECTIVE - Patients with metabolic syndrome have increased risk of cardiovascular events. The number of patients With Metabolic syndrome is rapidly increasing, and these patients Often need revascularization. However, only limited data are available on the effect of metabolic syndrome on restenosis

  13. A Modeling and Simulation Approach to the Study of Metabolic Control Analysis

    Science.gov (United States)

    Rodriguez-Caso, Carlos; Sanchez-Jimenez, Francisca; Medina, Miguel Angel

    2002-01-01

    Metabolic control analysis has contributed to the rapid advance in our understanding of metabolic regulation. However, up to now this topic has not been covered properly in biochemistry courses. This work reports the development and implementation of a practical lesson on metabolic control analysis (MCA) using modeling and simulation. The…

  14. Tiber Personal Rapid Transit

    Directory of Open Access Journals (Sweden)

    Diego Carlo D'agostino

    2011-02-01

    Full Text Available The project “Tiber Personal Rapid Transit” have been presented by the author at the Rome City Vision Competition1 2010, an ideas competition, which challenges architects, engineers, designers, students and creatives individuals to develop visionary urban proposals with the intention of stimulating and supporting the contemporary city, in this case Rome. The Tiber PRT proposal tries to answer the competition questions with the definition of a provocative idea: a Personal Rapid transit System on the Tiber river banks. The project is located in the central section of the Tiber river and aims at the renewal of the river banks with the insertion of a Personal Rapid Transit infrastructure. The project area include the riverbank of Tiber from Rome Transtevere RFI station to Piazza del Popolo, an area where main touristic and leisure attractions are located. The intervention area is actually no used by the city users and residents and constitute itself a strong barrier in the heart of the historic city.

  15. 'Sarcobesity': a metabolic conundrum.

    Science.gov (United States)

    Parr, Evelyn B; Coffey, Vernon G; Hawley, John A

    2013-02-01

    Two independent but inter-related conditions that have a growing impact on healthy life expectancy and health care costs in developed nations are an age-related loss of muscle mass (i.e., sarcopenia) and obesity. Sarcopenia is commonly exacerbated in overweight and obese individuals. Progression towards obesity promotes an increase in fat mass and a concomitant decrease in muscle mass, producing an unfavourable ratio of fat to muscle. The coexistence of diminished muscle mass and increased fat mass (so-called 'sarcobesity') is ultimately manifested by impaired mobility and/or development of life-style-related diseases. Accordingly, the critical health issue for a large proportion of adults in developed nations is how to lose fat mass while preserving muscle mass. Lifestyle interventions to prevent or treat sarcobesity include energy-restricted diets and exercise. The optimal energy deficit to reduce body mass is controversial. While energy restriction in isolation is an effective short-term strategy for rapid and substantial weight loss, it results in a reduction of both fat and muscle mass and therefore ultimately predisposes one to an unfavourable body composition. Aerobic exercise promotes beneficial changes in whole-body metabolism and reduces fat mass, while resistance exercise preserves lean (muscle) mass. Current evidence strongly supports the inclusion of resistance and aerobic exercise to complement mild energy-restricted high-protein diets for healthy weight loss as a primary intervention for sarcobesity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  16. Achieving diversity in the face of constraints: lessons from metabolism.

    Science.gov (United States)

    Milo, Ron; Last, Robert L

    2012-06-29

    Metabolic engineering of plants can reduce the cost and environmental impact of agriculture while providing for the needs of a growing population. Although our understanding of plant metabolism continues to increase at a rapid pace, relatively few plant metabolic engineering projects with commercial potential have emerged, in part because of a lack of principles for the rational manipulation of plant phenotype. One underexplored approach to identifying such design principles derives from analysis of the dominant constraints on plant fitness, and the evolutionary innovations in response to those constraints, that gave rise to the enormous diversity of natural plant metabolic pathways.

  17. [Porphyrin metabolism in women with metabolic syndrome].

    Science.gov (United States)

    Krivosheev, A B; Kuimov, A D; Kondratova, M A; Tuguleva, T A

    2014-01-01

    A total of 47 women with metabolic syndrome (MS) were examined with the fractional determination of porphyrins in urine (uroporphyrin and coproporphyrin) and feces (coproporphyrin and protoporphyrin) as well as their precursors (5-aminolevulinic acid and porphobilinogen). Disorders of porphyrin metabolism were documented in 29 (61.7%) women All patients had elevated levels of porphyrin precursors. Five women exhibited qualitative changes in the form of abnormal ratios of different porphyrin fractions(coproporphyrin/uroporphyrin porphyrin metabolism in the form of manifold increase of porphyrin levels in urine and/or feces and formation of biochemical syndromes of secondary coproporphyrinuiria, symptomatic rise in porphyrin content in feces, and chronic latent hepatic porfiria. Disorders of porphyrin metabolism were associated with insulin resistance. Changes of porphyrin metabolism in MS extend the spectrum of concomitant disturbances and can be regarded as an additional criterion.

  18. Rapidly variable relatvistic absorption

    Science.gov (United States)

    Parker, M.; Pinto, C.; Fabian, A.; Lohfink, A.; Buisson, D.; Alston, W.; Jiang, J.

    2017-10-01

    I will present results from the 1.5Ms XMM-Newton observing campaign on the most X-ray variable AGN, IRAS 13224-3809. We find a series of nine absorption lines with a velocity of 0.24c from an ultra-fast outflow. For the first time, we are able to see extremely rapid variability of the UFO features, and can link this to the X-ray variability from the inner accretion disk. We find a clear flux dependence of the outflow features, suggesting that the wind is ionized by increasing X-ray emission.

  19. Rapid prototype and test

    Energy Technology Data Exchange (ETDEWEB)

    Gregory, D.L.; Hansche, B.D.

    1996-06-01

    In order to support advanced manufacturing, Sandia has acquired the capability to produce plastic prototypes using stereolithography. Currently, these prototypes are used mainly to verify part geometry and ``fit and form`` checks. This project investigates methods for rapidly testing these plastic prototypes, and inferring from prototype test data actual metal part performance and behavior. Performances examined include static load/stress response, and structural dynamic (modal) and vibration behavior. The integration of advanced non-contacting measurement techniques including scanning laser velocimetry, laser holography, and thermoelasticity into testing of these prototypes is described. Photoelastic properties of the epoxy prototypes to reveal full field stress/strain fields are also explored.

  20. Right-Rapid-Rough

    Science.gov (United States)

    Lawrence, Craig

    2003-01-01

    IDEO (pronounced 'eye-dee-oh') is an international design, engineering, and innovation firm that has developed thousands of products and services for clients across a wide range of industries. Its process and culture attracted the attention of academics, businesses, and journalists around the world, and are the subject of a bestselling book, The Art of Innovation by Tom Kelley. One of the keys to IDEO's success is its use of prototyping as a tool for rapid innovation. This story covers some of IDEO's projects, and gives reasons for why they were successful.

  1. Inborn errors of metabolism

    Science.gov (United States)

    ... metabolism. A few of them are: Fructose intolerance Galactosemia Maple sugar urine disease (MSUD) Phenylketonuria (PKU) Newborn ... disorder. Alternative Names Metabolism - inborn errors of Images Galactosemia Phenylketonuria test References Bodamer OA. Approach to inborn ...

  2. BMP (Basic Metabolic Panel)

    Science.gov (United States)

    ... Links Patient Resources For Health Professionals Subscribe Search Basic Metabolic Panel (BMP) Send Us Your Feedback Choose ... Screen Chem 7 SMA 7 SMAC7 Formal Name Basic Metabolic Panel This article was last reviewed on ...

  3. Basic metabolic panel

    Science.gov (United States)

    ... Sequential multi-channel analysis with computer-7; SMA7; Metabolic panel 7; CHEM-7 ... Bope ET, Kellerman RD. Endocrine and metabolic disorders. In: Bope ET, ... PA: Elsevier; 2017:chap 5. Oh MS, Briefel G. Evaluation ...

  4. Metabolic networks of longevity

    NARCIS (Netherlands)

    Houtkooper, Riekelt H.; Williams, Robert W.; Auwerx, Johan

    2010-01-01

    Molecular and cellular networks implicated in aging depend on a multitude of proteins that collectively mount adaptive and contingent metabolic responses to environmental challenges. Here, we discuss the intimate links between metabolic regulation and longevity and outline new approaches for

  5. Cold-induced metabolism

    NARCIS (Netherlands)

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

    2003-01-01

    Cold-induced metabolism. van Marken Lichtenbelt WD, Daanen HA. Department of Human Biology, Maastricht University, Maastricht, The Netherlands. PURPOSE OF REVIEW: Cold response can be insulative (drop in peripheral temperature) or metabolic (increase in energy expenditure). Nonshivering

  6. Cold-induced metabolism

    NARCIS (Netherlands)

    Van Marken Lichtenbelt, Wouter D.; Daanen, Hein A M

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

  7. Cold-induced metabolism

    NARCIS (Netherlands)

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

    2003-01-01

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

  8. Metabolism and disease

    National Research Council Canada - National Science Library

    Grodzicker, Terri; Stewart, David J; Stillman, Bruce

    2011-01-01

    ...), cellular, organ system (cardiovascular, bone), and organismal (timing and life span) scales. Diseases impacted by metabolic imbalance or dysregulation that were covered in detail included diabetes, obesity, metabolic syndrome, and cancer...

  9. Lipid Metabolism Disorders

    Science.gov (United States)

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

  10. Ontogenetic scaling of metabolism, growth, and assimilation: testing metabolic scaling theory with Manduca sexta larvae.

    Science.gov (United States)

    Sears, Katie E; Kerkhoff, Andrew J; Messerman, Arianne; Itagaki, Haruhiko

    2012-01-01

    Metabolism, growth, and the assimilation of energy and materials are essential processes that are intricately related and depend heavily on animal size. However, models that relate the ontogenetic scaling of energy assimilation and metabolism to growth rely on assumptions that have yet to be rigorously tested. Based on detailed daily measurements of metabolism, growth, and assimilation in tobacco hornworms, Manduca sexta, we provide a first experimental test of the core assumptions of a metabolic scaling model of ontogenetic growth. Metabolic scaling parameters changed over development, in violation of the model assumptions. At the same time, the scaling of growth rate matches that of metabolic rate, with similar scaling exponents both across and within developmental instars. Rates of assimilation were much higher than expected during the first two instars and did not match the patterns of scaling of growth and metabolism, which suggests high costs of biosynthesis early in development. The rapid increase in size and discrete instars observed in larval insect development provide an ideal system for understanding how patterns of growth and metabolism emerge from fundamental cellular processes and the exchange of materials and energy between an organism and its environment.

  11. Rapid mineralocorticoid receptor trafficking.

    Science.gov (United States)

    Gekle, M; Bretschneider, M; Meinel, S; Ruhs, S; Grossmann, C

    2014-03-01

    The mineralocorticoid receptor (MR) is a ligand-dependent transcription factor that physiologically regulates water-electrolyte homeostasis and controls blood pressure. The MR can also elicit inflammatory and remodeling processes in the cardiovascular system and the kidneys, which require the presence of additional pathological factors like for example nitrosative stress. However, the underlying molecular mechanism(s) for pathophysiological MR effects remain(s) elusive. The inactive MR is located in the cytosol associated with chaperone molecules including HSP90. After ligand binding, the MR monomer rapidly translocates into the nucleus while still being associated to HSP90 and after dissociation from HSP90 binds to hormone-response-elements called glucocorticoid response elements (GREs) as a dimer. There are indications that rapid MR trafficking is modulated in the presence of high salt, oxidative or nitrosative stress, hypothetically by induction or posttranslational modifications. Additionally, glucocorticoids and the enzyme 11beta hydroxysteroid dehydrogenase may also influence MR activation. Because MR trafficking and its modulation by micro-milieu factors influence MR cellular localization, it is not only relevant for genomic but also for nongenomic MR effects. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. Rapid response manufacturing (RRM)

    Energy Technology Data Exchange (ETDEWEB)

    Cain, W.D. [Lockheed Martin Energy Systems, Inc., Oak Ridge, TN (United States); Waddell, W.L. [National Centers for Manufacturing Sciences, Ann Arbor, MI (United States)

    1997-02-18

    US industry is fighting to maintain its competitive edge in the global market place. Today markets fluctuate rapidly. Companies, to survive, have to be able to respond with quick-to-market, improved, high quality, cost efficient products. The way products are developed and brought to market can be improved and made more efficient through the proper incorporation of emerging technologies. The RRM project was established to leverage the expertise and resources of US private industries and federal agencies to develop, integrate, and deploy new technologies that meet critical needs for effective product realization. The RRM program addressed a needed change in the US Manufacturing infrastructure that will ensure US competitiveness in world market typified by mass customization. This project provided the effort needed to define, develop and establish a customizable infrastructure for rapid response product development design and manufacturing. A major project achievement was the development of a broad-based framework for automating and integrating the product and process design and manufacturing activities involved with machined parts. This was accomplished by coordinating and extending the application of feature-based product modeling, knowledge-based systems, integrated data management, and direct manufacturing technologies in a cooperative integrated computing environment. Key technological advancements include a product model that integrates product and process data in a consistent, minimally redundant manner, an advanced computer-aided engineering environment, knowledge-based software aids for design and process planning, and new production technologies to make products directly from design application software.

  13. Integrative metabolic engineering

    OpenAIRE

    George H McArthur IV; Pooja P Nanjannavar; Emily H Miller; Stephen S. Fong

    2015-01-01

    Recent advances in experimental and computational synthetic biology are extremely useful for achieving metabolic engineering objectives. The integration of synthetic biology and metabolic engineering within an iterative design-build-test framework will improve the practice of metabolic engineering by relying more on efficient design strategies. Computational tools that aid in the design and in silico simulation of metabolic pathways are especially useful. However, software helpful for constru...

  14. Metabolic Syndrome and Migraine

    OpenAIRE

    Amit eSachdev; Michael eMarmura

    2012-01-01

    Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, ...

  15. Pediatric Metabolic Syndrome: Pathophysiology and Laboratory Assessment.

    Science.gov (United States)

    Higgins, Victoria; Adeli, Khosrow

    2017-03-01

    Pediatric overweight and obesity is an emerging public health priority as rates have rapidly increased worldwide. Obesity is often clustered with other metabolic abnormalities including hypertension, dyslipidemia, and insulin resistance, leading to increased risk of cardiovascular disease. This cluster of risk factors, termed the metabolic syndrome, has traditionally been reported in adults. However, with the increased prevalence of pediatric obesity, the metabolic syndrome is now evident in children and adolescents. This complex cluster of risk factors is the result of the pathological interplay between several organs including adipose tissue, muscle, liver, and intestine with a common antecedent - insulin resistance. The association of the metabolic syndrome with several systemic alterations that involve numerous organs and tissues adds to the complexity and challenge of diagnosing the metabolic syndrome and identifying useful clinical indicators of the disease. The complex physiology of growing and developing children and adolescents further adds to the difficulties in standardizing laboratory assessment, diagnosis, and prognosis for the diverse pediatric population. However, establishing a consensus definition is critical to identifying and managing children and adolescents at high risk of developing the metabolic syndrome. As a result, the examination of novel metabolic syndrome biomarkers which can detect these metabolic abnormalities early with high specificity and sensitivity in the pediatric population has been of interest. Understanding this complex cluster of risk factors in the pediatric population is critical to ensure that this is not the first generation where children have a shorter life expectancy than their parents. This review will discuss the pathophysiology, consensus definitions and laboratory assessment of pediatric metabolic syndrome as well as potential novel biomarkers.

  16. Metabolic Engineering X Conference

    Energy Technology Data Exchange (ETDEWEB)

    Flach, Evan [American Institute of Chemical Engineers

    2015-05-07

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

  17. Synthetic metabolism: metabolic engineering meets enzyme design.

    Science.gov (United States)

    Erb, Tobias J; Jones, Patrik R; Bar-Even, Arren

    2017-04-01

    Metabolic engineering aims at modifying the endogenous metabolic network of an organism to harness it for a useful biotechnological task, for example, production of a value-added compound. Several levels of metabolic engineering can be defined and are the topic of this review. Basic 'copy, paste and fine-tuning' approaches are limited to the structure of naturally existing pathways. 'Mix and match' approaches freely recombine the repertoire of existing enzymes to create synthetic metabolic networks that are able to outcompete naturally evolved pathways or redirect flux toward non-natural products. The space of possible metabolic solution can be further increased through approaches including 'new enzyme reactions', which are engineered on the basis of known enzyme mechanisms. Finally, by considering completely 'novel enzyme chemistries' with de novo enzyme design, the limits of nature can be breached to derive the most advanced form of synthetic pathways. We discuss the challenges and promises associated with these different metabolic engineering approaches and illuminate how enzyme engineering is expected to take a prime role in synthetic metabolic engineering for biotechnology, chemical industry and agriculture of the future. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Rapid Refresh (RAP) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  19. Rapid Refresh (RAP) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Refresh (RAP) numerical weather model took the place of the Rapid Update Cycle (RUC) on May 1, 2012. Run by the National Centers for Environmental...

  20. Rapid chemical separations

    CERN Document Server

    Trautmann, N

    1976-01-01

    A survey is given on the progress of fast chemical separation procedures during the last few years. Fast, discontinuous separation techniques are illustrated by a procedure for niobium. The use of such techniques for the chemical characterization of the heaviest known elements is described. Other rapid separation methods from aqueous solutions are summarized. The application of the high speed liquid chromatography to the separation of chemically similar elements is outlined. The use of the gas jet recoil transport method for nuclear reaction products and its combination with a continuous solvent extraction technique and with a thermochromatographic separation is presented. Different separation methods in the gas phase are briefly discussed and the attachment of a thermochromatographic technique to an on-line mass separator is shown. (45 refs).

  1. Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

    Science.gov (United States)

    Allison, Katrina E; Coomber, Brenda L; Bridle, Byram W

    2017-10-01

    Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed. © 2017 John Wiley & Sons Ltd.

  2. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

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

  3. Metabolism of ethynyl estrogens.

    Science.gov (United States)

    Helton, E D; Goldzieher, J W

    1977-09-01

    The pharmacokinetics and metabolic conversion of the ethynylated estrogens are reviewed. Special emphasis is given to the comparative pharmacokinetics of ethynyl-estradiol in different populations of women. Similarly, the variability of ethynyl-estradiol and mestranol metabolism in humans resulting from presentation of radio-labeled steroid and purification of the metabolic products is presented and discussed. The concepts of estrogen hepatotoxicity are reviewed with respect to the known phenomenon of estrogen oxidative metabolism and covalent binding. Recent evidence for the metabolic removal of the 17alpha-ethynyl group is discussed, and its relationship to estrogen hepatoxicity is considered and related to the covalent binding phenomenon.

  4. Integrative metabolic engineering

    Directory of Open Access Journals (Sweden)

    George H McArthur IV

    2015-07-01

    Full Text Available Recent advances in experimental and computational synthetic biology are extremely useful for achieving metabolic engineering objectives. The integration of synthetic biology and metabolic engineering within an iterative design-build-test framework will improve the practice of metabolic engineering by relying more on efficient design strategies. Computational tools that aid in the design and in silico simulation of metabolic pathways are especially useful. However, software helpful for constructing, implementing, measuring and characterizing engineered pathways and networks should not be overlooked. In this review, we highlight computational synthetic biology tools relevant to metabolic engineering, organized in the context of the design-build-test cycle.

  5. Systems Biology of Metabolism.

    Science.gov (United States)

    Nielsen, Jens

    2017-06-20

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

  6. Engineering Cellular Metabolism

    DEFF Research Database (Denmark)

    Nielsen, Jens; Keasling, Jay

    2016-01-01

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

  7. Modularization of genetic elements promotes synthetic metabolic engineering.

    Science.gov (United States)

    Qi, Hao; Li, Bing-Zhi; Zhang, Wen-Qian; Liu, Duo; Yuan, Ying-Jin

    2015-11-15

    In the context of emerging synthetic biology, metabolic engineering is moving to the next stage powered by new technologies. Systematical modularization of genetic elements makes it more convenient to engineer biological systems for chemical production or other desired purposes. In the past few years, progresses were made in engineering metabolic pathway using synthetic biology tools. Here, we spotlighted the topic of implementation of modularized genetic elements in metabolic engineering. First, we overviewed the principle developed for modularizing genetic elements and then discussed how the genetic modules advanced metabolic engineering studies. Next, we picked up some milestones of engineered metabolic pathway achieved in the past few years. Last, we discussed the rapid raised synthetic biology field of "building a genome" and the potential in metabolic engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. T cell metabolic reprogramming and plasticity

    OpenAIRE

    Slack, Maria; Wang, Tingting; Wang, Ruoning

    2015-01-01

    Upon antigen stimulation, small and quiescent naïve T cells undergo an approximately 24hr growth phase followed by rapid proliferation. Depending on the nature of the antigen and cytokine milieu, these proliferating T cells differentiate into distinctive functional subgroups that are essential for appropriate immune defense and regulation. T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic and biosynthetic demands during the transition be...

  9. Building a rapid response team.

    Science.gov (United States)

    Halvorsen, Lisa; Garolis, Salomeja; Wallace-Scroggs, Allyson; Stenstrom, Judy; Maunder, Richard

    2007-01-01

    The use of rapid response teams is a relatively new approach for decreasing or eliminating codes in acute care hospitals. Based on the principles of a code team for cardiac and/or respiratory arrest in non-critical care units, the rapid response teams have specially trained nursing, respiratory, and medical personnel to respond to calls from general care units to assess and manage decompensating or rapidly changing patients before their conditions escalate to a full code situation. This article describes the processes used to develop a rapid response team, clinical indicators for triggering a rapid response team call, topics addressed in an educational program for the rapid response team members, and methods for evaluating effectiveness of the rapid response team.

  10. Metabolic Actions of Hypothalamic SIRT1

    Science.gov (United States)

    Coppari, Roberto

    2012-01-01

    The hypothalamus is a small structure located in the ventral diencephalon. Hypothalamic neurons sense changes in circulating metabolic cues (e.g.: leptin, insulin, glucose), and coordinate responses aimed at maintaining normal body weight and glucose homeostasis. Recent findings indicate that a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase (namely, SIRT1) expressed by hypothalamic neurons is crucial for mounting responses against diet-induced obesity and type 2 diabetes mellitus (T2DM). Here, the repercussions of these findings will be discussed and particular emphasis will be given to the potential exploitation of hypothalamic SIRT1 as a target for the treatment of the rapidly-spreading metabolic disorders of obesity and T2DM. The possible roles of hypothalamic SIRT1 on regulating metabolic ageing processes will also be addressed. PMID:22382036

  11. Metabolic effects of low glycaemic index diets

    Directory of Open Access Journals (Sweden)

    Rusu Emilia

    2009-01-01

    Full Text Available Abstract The persistence of an epidemic of obesity and type 2 diabetes suggests that new nutritional strategies are needed if the epidemic is to be overcome. A promising nutritional approach suggested by this thematic review is metabolic effect of low glycaemic-index diet. The currently available scientific literature shows that low glycaemic-index diets acutely induce a number of favorable effects, such as a rapid weight loss, decrease of fasting glucose and insulin levels, reduction of circulating triglyceride levels and improvement of blood pressure. The long-term effect of the combination of these changes is at present not known. Based on associations between these metabolic parameters and risk of cardiovascular disease, further controlled studies on low-GI diet and metabolic disease are needed.

  12. Problems of rapid growth.

    Science.gov (United States)

    Kim, T D

    1980-01-01

    South Korea's export-oriented development strategy has achieved a remarkable growth record, but it has also brought 2 different problems: 1) since the country's exports accounted for about 1% of total world export volume, the 1st world has become fearful about Korea's aggressive export drive; and 2) the fact that exports account for over 30% of its total gross national product (GNP) exposes the vulnerability of South Korea's economy itself. South Korea continues to be a poor nation, although it is rated as 1 of the most rapidly growing middle income economies. A World Bank 1978 report shows Korea to be 28th of 58 middle income countries in terms of per capita GNP in 1976. Of 11 newly industrializing countries (NIC), 5 in the European continent are more advanced than the others. A recent emphasis on the basic human needs approach has tended to downgrade the concept of GNP. Korea has only an abundant labor force and is without any natural resources. Consequently, Korea utilized an export-oriented development strategy. Oil requirements are met with imports, and almost all raw materials to be processed into exportable products must be imported. To pay import bills Korea must export and earn foreign exchange. It must be emphasized that foreign trade must always be 2-way traffic. In order to export more to middle income countries like Korea, the countries of the 1st world need to ease their protectionist measures against imports from developing countries.

  13. Rapid Polymer Sequencer

    Science.gov (United States)

    Stolc, Viktor (Inventor); Brock, Matthew W (Inventor)

    2013-01-01

    Method and system for rapid and accurate determination of each of a sequence of unknown polymer components, such as nucleic acid components. A self-assembling monolayer of a selected substance is optionally provided on an interior surface of a pipette tip, and the interior surface is immersed in a selected liquid. A selected electrical field is impressed in a longitudinal direction, or in a transverse direction, in the tip region, a polymer sequence is passed through the tip region, and a change in an electrical current signal is measured as each polymer component passes through the tip region. Each of the measured changes in electrical current signals is compared with a database of reference electrical change signals, with each reference signal corresponding to an identified polymer component, to identify the unknown polymer component with a reference polymer component. The nanopore preferably has a pore inner diameter of no more than about 40 nm and is prepared by heating and pulling a very small section of a glass tubing.

  14. Rapidly rotating red giants

    Science.gov (United States)

    Gehan, Charlotte; Mosser, Benoît; Michel, Eric

    2017-10-01

    Stellar oscillations give seismic information on the internal properties of stars. Red giants are targets of interest since they present mixed modes, wich behave as pressure modes in the convective envelope and as gravity modes in the radiative core. Mixed modes thus directly probe red giant cores, and allow in particular the study of their mean core rotation. The high-quality data obtained by CoRoT and Kepler satellites represent an unprecedented perspective to obtain thousands of measurements of red giant core rotation, in order to improve our understanding of stellar physics in deep stellar interiors. We developed an automated method to obtain such core rotation measurements and validated it for stars on the red giant branch. In this work, we particularly focus on the specific application of this method to red giants having a rapid core rotation. They show complex spectra where it is tricky to disentangle rotational splittings from mixed-mode period spacings. We demonstrate that the method based on the identification of mode crossings is precise and efficient. The determination of the mean core rotation directly derives from the precise measurement of the asymptotic period spacing ΔΠ1 and of the frequency at which the crossing of the rotational components is observed.

  15. Metabolic Regulation of Natural Killer Cell IFN-γ Production.

    Science.gov (United States)

    Mah, Annelise Y; Cooper, Megan A

    2016-01-01

    Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ). NK cells are innate immune lymphocytes that are poised for rapid activation during the early immune response. Although their basal metabolic rates do not change with short-term activation, they exhibit specific metabolic requirements for activation depending upon the stimulus received. These metabolic requirements for NK cell activation are altered by culturing NK cells with interleukin-15, which increases NK cell metabolic rates at baseline and shifts them toward aerobic glycolysis. We discuss the metabolic pathways important for NK cell production of IFN-γ protein and potential mechanisms whereby metabolism regulates NK cell function.

  16. Metabolic syndrome and migraine

    Directory of Open Access Journals (Sweden)

    Amit eSachdev

    2012-11-01

    Full Text Available Migraine and metabolic syndrome are highly prevaleirnt and costly conditions.The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogensis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.

  17. Migraine in metabolic syndrome.

    Science.gov (United States)

    Guldiken, Baburhan; Guldiken, Sibel; Taskiran, Bengur; Koc, Gonul; Turgut, Nilda; Kabayel, Levent; Tugrul, Armagan

    2009-03-01

    Recent studies suggest that insulin resistance is more common in patients with migraine. Insulin resistance underlies the pathogenesis of obesity, diabetes, and hypertension that are components of metabolic syndrome. As migraine is associated with an increased risk of vascular disorders, such as stroke, and migraine patients have higher diastolic blood pressure than healthy individuals, we aimed to investigate the 1-year prevalence of migraine in metabolic syndrome. Two hundred ten patients with metabolic syndrome were enrolled in the study. Migraine was diagnosed according to International Classification of Headache Disorders-II criteria. Migraine prevalence was estimated as 11.9% in men and 22.5% in women with metabolic syndrome. Of the metabolic syndrome components, diabetes, increased waist circumference, and body mass index were significantly more frequent in patients with migraine in contrast to those without migraine (Pmigraine prevalence in metabolic syndrome was higher than in the general population.

  18. Metabolic syndrome and migraine.

    Science.gov (United States)

    Sachdev, Amit; Marmura, Michael J

    2012-01-01

    Migraine and metabolic syndrome are highly prevalent and costly conditions. The two conditions coexist, but it is unclear what relationship may exist between the two processes. Metabolic syndrome involves a number of findings, including insulin resistance, systemic hypertension, obesity, a proinflammatory state, and a prothrombotic state. Only one study addresses migraine in metabolic syndrome, finding significant differences in the presentation of metabolic syndrome in migraineurs. However, controversy exists regarding the contribution of each individual risk factor to migraine pathogenesis and prevalence. It is unclear what treatment implications, if any, exist as a result of the concomitant diagnosis of migraine and metabolic syndrome. The cornerstone of migraine and metabolic syndrome treatments is prevention, relying heavily on diet modification, sleep hygiene, medication use, and exercise.

  19. [Menopause and metabolic syndrome].

    Science.gov (United States)

    Meirelles, Ricardo M R

    2014-03-01

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

  20. Rapid mixing kinetic techniques.

    Science.gov (United States)

    Martin, Stephen R; Schilstra, Maria J

    2013-01-01

    Almost all of the elementary steps in a biochemical reaction scheme are either unimolecular or bimolecular processes that frequently occur on sub-second, often sub-millisecond, time scales. The traditional approach in kinetic studies is to mix two or more reagents and monitor the changes in concentrations with time. Conventional spectrophotometers cannot generally be used to study reactions that are complete within less than about 20 s, as it takes that amount of time to manually mix the reagents and activate the instrument. Rapid mixing techniques, which generally achieve mixing in less than 2 ms, overcome this limitation. This chapter is concerned with the use of these techniques in the study of reactions which reach equilibrium; the application of these methods to the study of enzyme kinetics is described in several excellent texts (Cornish-Bowden, Fundamentals of enzyme kinetics. Portland Press, 1995; Gutfreund, Kinetics for the life sciences. Receptors, transmitters and catalysis. Cambridge University Press, 1995).There are various ways to monitor changes in concentration of reactants, intermediates and products after mixing, but the most common way is to use changes in optical signals (absorbance or fluorescence) which often accompany reactions. Although absorbance can sometimes be used, fluorescence is often preferred because of its greater sensitivity, particularly in monitoring conformational changes. Such methods are continuous with good time resolution but they seldom permit the direct determination of the concentrations of individual species. Alternatively, samples may be taken from the reaction volume, mixed with a chemical quenching agent to stop the reaction, and their contents assessed by techniques such as HPLC. These methods can directly determine the concentrations of different species, but are discontinuous and have a limited time resolution.

  1. Sleep Slow-Wave Activity Regulates Cerebral Glycolytic Metabolism

    OpenAIRE

    Wisor, Jonathan P; Rempe, Michael J; Schmidt, Michelle A.; Moore, Michele E.; Clegern, William C.

    2012-01-01

    Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1–4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cor...

  2. Impact of systems biology on metabolic engineering of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Nielsen, Jens; Jewett, Michael Christopher

    2008-01-01

    in the industrial application of this yeast. Developments in genomics and high-throughput systems biology tools are enhancing one's ability to rapidly characterize cellular behaviour, which is valuable in the field of metabolic engineering where strain characterization is often the bottleneck in strain development...... programmes. Here, the impact of systems biology on metabolic engineering is reviewed and perspectives on the role of systems biology in the design of cell factories are given....

  3. Transcriptional regulation of metabolism.

    Science.gov (United States)

    Desvergne, Béatrice; Michalik, Liliane; Wahli, Walter

    2006-04-01

    Our understanding of metabolism is undergoing a dramatic shift. Indeed, the efforts made towards elucidating the mechanisms controlling the major regulatory pathways are now being rewarded. At the molecular level, the crucial role of transcription factors is particularly well-illustrated by the link between alterations of their functions and the occurrence of major metabolic diseases. In addition, the possibility of manipulating the ligand-dependent activity of some of these transcription factors makes them attractive as therapeutic targets. The aim of this review is to summarize recent knowledge on the transcriptional control of metabolic homeostasis. We first review data on the transcriptional regulation of the intermediary metabolism, i.e., glucose, amino acid, lipid, and cholesterol metabolism. Then, we analyze how transcription factors integrate signals from various pathways to ensure homeostasis. One example of this coordination is the daily adaptation to the circadian fasting and feeding rhythm. This section also discusses the dysregulations causing the metabolic syndrome, which reveals the intricate nature of glucose and lipid metabolism and the role of the transcription factor PPARgamma in orchestrating this association. Finally, we discuss the molecular mechanisms underlying metabolic regulations, which provide new opportunities for treating complex metabolic disorders.

  4. Mathematical modelling of metabolism

    DEFF Research Database (Denmark)

    Gombert, Andreas Karoly; Nielsen, Jens

    2000-01-01

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

  5. Eicosanoids in Metabolic Syndrome

    Science.gov (United States)

    Hardwick, James P.; Eckman, Katie; Lee, Yoon Kwang; Abdelmegeed, Mohamed A.; Esterle, Andrew; Chilian, William M.; Chiang, John Y.; Song, Byoung-Joon

    2013-01-01

    Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism.The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS. PMID:23433458

  6. Two-Scale13C 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

  7. Rapid Active Sampling Package

    Science.gov (United States)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  8. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robotic designs. The software will support push-button validation...

  9. Rapid Robot Design Validation Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Energid Technologies will create a comprehensive software infrastructure for rapid validation of robot designs. The software will support push-button validation...

  10. Attractor metabolic networks.

    Science.gov (United States)

    De la Fuente, Ildefonso M; Cortes, Jesus M; Pelta, David A; Veguillas, Juan

    2013-01-01

    The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core) while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity. In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network. We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns, modify the efficiency in the connection between the multienzymatic complexes, and stably

  11. Attractor metabolic networks.

    Directory of Open Access Journals (Sweden)

    Ildefonso M De la Fuente

    Full Text Available BACKGROUND: The experimental observations and numerical studies with dissipative metabolic networks have shown that cellular enzymatic activity self-organizes spontaneously leading to the emergence of a Systemic Metabolic Structure in the cell, characterized by a set of different enzymatic reactions always locked into active states (metabolic core while the rest of the catalytic processes are only intermittently active. This global metabolic structure was verified for Escherichia coli, Helicobacter pylori and Saccharomyces cerevisiae, and it seems to be a common key feature to all cellular organisms. In concordance with these observations, the cell can be considered a complex metabolic network which mainly integrates a large ensemble of self-organized multienzymatic complexes interconnected by substrate fluxes and regulatory signals, where multiple autonomous oscillatory and quasi-stationary catalytic patterns simultaneously emerge. The network adjusts the internal metabolic activities to the external change by means of flux plasticity and structural plasticity. METHODOLOGY/PRINCIPAL FINDINGS: In order to research the systemic mechanisms involved in the regulation of the cellular enzymatic activity we have studied different catalytic activities of a dissipative metabolic network under different external stimuli. The emergent biochemical data have been analysed using statistical mechanic tools, studying some macroscopic properties such as the global information and the energy of the system. We have also obtained an equivalent Hopfield network using a Boltzmann machine. Our main result shows that the dissipative metabolic network can behave as an attractor metabolic network. CONCLUSIONS/SIGNIFICANCE: We have found that the systemic enzymatic activities are governed by attractors with capacity to store functional metabolic patterns which can be correctly recovered from specific input stimuli. The network attractors regulate the catalytic patterns

  12. The impact of music on metabolism.

    Science.gov (United States)

    Yamasaki, Alisa; Booker, Abigail; Kapur, Varun; Tilt, Alexandra; Niess, Hanno; Lillemoe, Keith D; Warshaw, Andrew L; Conrad, Claudius

    2012-01-01

    The study of music and medicine is a rapidly growing field that in the past, has been largely focused on the use of music as a complementary therapy. Increasing interest has been centered on understanding the physiologic mechanisms underlying the effects of music and, more recently, the suggested role of music in modulating metabolic responses. Research has established a role for music in the regulation of the hypothalamic-pituitary axis, the sympathetic nervous system, and the immune system, which have key functions in the regulation of metabolism and energy balance. More recent findings have shown a role for music in the metabolic recovery from stress, the regulation of gastric and intestinal motility, the moderation of cancer-related gastrointestinal symptoms, and the increase of lipid metabolism and lactic acid clearance during exercise and postexercise recovery. The purpose of this article is to summarize the most current understanding of the mechanisms by which music affects the metabolic responses in the context of potential applications. Copyright © 2012 Elsevier Inc. All rights reserved.

  13. T cell metabolic reprogramming and plasticity.

    Science.gov (United States)

    Slack, Maria; Wang, Tingting; Wang, Ruoning

    2015-12-01

    Upon antigen stimulation, small and quiescent naïve T cells undergo an approximately 24h growth phase followed by rapid proliferation. Depending on the nature of the antigen and cytokine milieu, these proliferating T cells differentiate into distinctive functional subgroups that are essential for appropriate immune defense and regulation. T cells undergo a characteristic metabolic rewiring that fulfills the dramatically increased bioenergetic and biosynthetic demands during the transition between resting, activation and differentiation. Beyond this, T cells are distributed throughout the body and are able to function in a wide range of physio-pathological environments, including some with a dramatic metabolic derangement. As such, T cells must quickly respond to and adapt to fluctuations in environmental nutrient levels. We consider such responsiveness and adaptation in terms of metabolic plasticity, that is, an evolutionarilly selected process which allows T cells to illicit robust immune functions in response to either a continuous or disrupted nutrient supply. In this review, we illustrate the relevant metabolic pathways in T cells and discuss the ability of T cells to change their metabolic substrates in response to changes in the environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Ultra-Rapid Vision in Birds.

    Directory of Open Access Journals (Sweden)

    Jannika E Boström

    Full Text Available Flying animals need to accurately detect, identify and track fast-moving objects and these behavioral requirements are likely to strongly select for abilities to resolve visual detail in time. However, evidence of highly elevated temporal acuity relative to non-flying animals has so far been confined to insects while it has been missing in birds. With behavioral experiments on three wild passerine species, blue tits, collared and pied flycatchers, we demonstrate temporal acuities of vision far exceeding predictions based on the sizes and metabolic rates of these birds. This implies a history of strong natural selection on temporal resolution. These birds can resolve alternating light-dark cycles at up to 145 Hz (average: 129, 127 and 137, respectively, which is ca. 50 Hz over the highest frequency shown in any other vertebrate. We argue that rapid vision should confer a selective advantage in many bird species that are ecologically similar to the three species examined in our study. Thus, rapid vision may be a more typical avian trait than the famously sharp vision found in birds of prey.

  15. Interdisciplinary Pathways for Urban Metabolism Research

    Science.gov (United States)

    Newell, J. P.

    2011-12-01

    With its rapid rise as a metaphor to express coupled natural-human systems in cities, the concept of urban metabolism is evolving into a series of relatively distinct research frameworks amongst various disciplines, with varying definitions, theories, models, and emphases. In industrial ecology, housed primarily within the disciplinary domain of engineering, urban metabolism research has focused on quantifying material and energy flows into, within, and out of cities, using methodologies such as material flow analysis and life cycle assessment. In the field of urban ecology, which is strongly influenced by ecology and urban planning, research focus has been placed on understanding and modeling the complex patterns and processes of human-ecological systems within urban areas. Finally, in political ecology, closely aligned with human geography and anthropology, scholars theorize about the interwoven knots of social and natural processes, material flows, and spatial structures that form the urban metabolism. This paper offers three potential interdisciplinary urban metabolism research tracks that might integrate elements of these three "ecologies," thereby bridging engineering and the social and physical sciences. First, it presents the idea of infrastructure ecology, which explores the complex, emergent interdependencies between gray (water and wastewater, transportation, etc) and green (e.g. parks, greenways) infrastructure systems, as nested within a broader socio-economic context. For cities to be sustainable and resilient over time-space, the theory follows, these is a need to understand and redesign these infrastructure linkages. Second, there is the concept of an urban-scale carbon metabolism model which integrates consumption-based material flow analysis (including goods, water, and materials), with the carbon sink and source dynamics of the built environment (e.g. buildings, etc) and urban ecosystems. Finally, there is the political ecology of the material

  16. Metabolic regulation of inflammation.

    Science.gov (United States)

    Gaber, Timo; Strehl, Cindy; Buttgereit, Frank

    2017-05-01

    Immune cells constantly patrol the body via the bloodstream and migrate into multiple tissues where they face variable and sometimes demanding environmental conditions. Nutrient and oxygen availability can vary during homeostasis, and especially during the course of an immune response, creating a demand for immune cells that are highly metabolically dynamic. As an evolutionary response, immune cells have developed different metabolic programmes to supply them with cellular energy and biomolecules, enabling them to cope with changing and challenging metabolic conditions. In the past 5 years, it has become clear that cellular metabolism affects immune cell function and differentiation, and that disease-specific metabolic configurations might provide an explanation for the dysfunctional immune responses seen in rheumatic diseases. This Review outlines the metabolic challenges faced by immune cells in states of homeostasis and inflammation, as well as the variety of metabolic configurations utilized by immune cells during differentiation and activation. Changes in cellular metabolism that contribute towards the dysfunctional immune responses seen in rheumatic diseases are also briefly discussed.

  17. Metabolic syndrome and menopause

    Directory of Open Access Journals (Sweden)

    Jouyandeh Zahra

    2013-01-01

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

  18. Non-metabolic functions of glycolytic enzymes in tumorigenesis.

    Science.gov (United States)

    Yu, X; Li, S

    2017-05-11

    Cancer cells reprogram their metabolism to meet the requirement for survival and rapid growth. One hallmark of cancer metabolism is elevated aerobic glycolysis and reduced oxidative phosphorylation. Emerging evidence showed that most glycolytic enzymes are deregulated in cancer cells and play important roles in tumorigenesis. Recent studies revealed that all essential glycolytic enzymes can be translocated into nucleus where they participate in tumor progression independent of their canonical metabolic roles. These noncanonical functions include anti-apoptosis, regulation of epigenetic modifications, modulation of transcription factors and co-factors, extracellular cytokine, protein kinase activity and mTORC1 signaling pathway, suggesting that these multifaceted glycolytic enzymes not only function in canonical metabolism but also directly link metabolism to epigenetic and transcription programs implicated in tumorigenesis. These findings underscore our understanding about how tumor cells adapt to nutrient and fuel availability in the environment and most importantly, provide insights into development of cancer therapy.

  19. Mycobacterium tuberculosis Metabolism

    Science.gov (United States)

    Warner, Digby F.

    2015-01-01

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

  20. Metabolic Engineering VII Conference

    Energy Technology Data Exchange (ETDEWEB)

    Kevin Korpics

    2012-12-04

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

  1. Glycogen metabolism in cancer.

    Science.gov (United States)

    Zois, Christos E; Favaro, Elena; Harris, Adrian L

    2014-11-01

    Since its identification more than 150 years ago, there has been an extensive characterisation of glycogen metabolism and its regulatory pathways in the two main glycogen storage organs of the body, i.e. liver and muscle. In recent years, glycogen metabolism has also been demonstrated to be upregulated in many tumour types, suggesting it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells. The various methods to detect glycogen in tumours in vivo are also reviewed. Finally, we discuss the targeting of glycogen metabolism as a strategy for cancer treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Metabolic imaging using PET

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, Takashi [University of Fukui, Biomedical Imaging Research Center, Eiheiji-cho, Fukui (Japan)

    2007-06-15

    There is growing evidence that myocardial metabolism plays a key role not only in ischaemic heart disease but also in a variety of diseases which involve myocardium globally, such as heart failure and diabetes mellitus. Understanding myocardial metabolism in such diseases helps to elucidate the pathophysiology and assists in making therapeutic decisions. As well as providing information on regional changes, PET can deliver quantitative information about both regional and global changes in metabolism. This capability of quantitative measurement is one of the major advantages of PET along with physiological positron tracers, especially relevant in evaluating diseases which involve the whole myocardium. This review discusses major PET tracers for metabolic imaging and their clinical applications and contributions to research regarding ischaemic heart disease and other diseases such as heart failure and diabetic heart disease. Future applications of positron metabolic tracers for the detection of vulnerable plaque are also highlighted briefly. (orig.)

  3. [Psychopharmacology and metabolic syndrome].

    Science.gov (United States)

    Telles-Correia, Diogo; Guerreiro, Diogo F; Coentre, Ricardo; Coentre, Rui; Góis, C; Figueira, Luísa

    2008-01-01

    Metabolic Syndrome consists in a group of metabolic changes, being the most important problem insulin resistence. Other important components of this syndrome are abdominal obesity, hypertension and hyperlipidemia /hypercholestrolemia. It was demonstrated that psychiatric patients have a greater risk to develop metabolic syndrome with a prevalence of 41%. Prevalence of this syndrome in psychiatric male patients is 138% higher than in general population and in female patients 251% higher. Some of the factors that can explain this increase of metabolic risk in psychiatric patients are psychiatric drugs. We preformed a systematic review of literature published until June, 2007, by means of MEDLINE. Studies reviewed include clinical cases, reviews, analytic and observational studies. We selected 72 articles. Authors pretend to understand the mechanisms, by which, different psychiatric drugs can influence metabolic syndrome, and strategies for prevention of this situation.

  4. Rapid prototyping in medical sciences

    Directory of Open Access Journals (Sweden)

    Ákos Márk Horváth

    2015-09-01

    Full Text Available Even if it sound a bit incredible rapid prototyping (RPT as production method has been used for decades in other professions. Nevertheless medical science just started discover the possibilities of this technology and use the offered benefits of 3D printing. In this paper authors have investigated the pharmaceutical usage of rapid prototyping.

  5. A workflow for mathematical modeling of subcellular metabolic pathways in leaf metabolism of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Thomas eNägele

    2013-12-01

    Full Text Available During the last decade genome sequencing has experienced a rapid technological development resulting in numerous sequencing projects and applications in life science. In plant molecular biology, the availability of sequence data on whole genomes has enabled the reconstruction of metabolic networks. Enzymatic reactions are predicted by the sequence information. Pathways arise due to the participation of chemical compounds as substrates and products in these reactions. Although several of these comprehensive networks have been reconstructed for the genetic model plant Arabidopsis thaliana, the integration of experimental data is still challenging. Particularly the analysis of subcellular organization of plant cells limits the understanding of regulatory instances in these metabolic networks in vivo. In this study, we develop an approach for the functional integration of experimental high-throughput data into such large-scale networks. We present a subcellular metabolic network model comprising 524 metabolic intermediates and 548 metabolic interactions derived from a total of 2769 reactions. We demonstrate how to link the metabolite covariance matrix of different Arabidopsis thaliana accessions with the subcellular metabolic network model for the inverse calculation of the biochemical Jacobian, finally resulting in the calculation of a matrix which satisfies a Lyaponov equation involving a covariance matrix. In this way, differential strategies of metabolite compartmentation and involved reactions were identified in the accessions when exposed to low temperature.

  6. Post exercise basil metabolic rate following a 6 minute high intensity interval workout

    National Research Council Canada - National Science Library

    Petrofsky, Jerrold; Laymon, Michael; Altenbernt, Lorna; Buffum, Alyx; Gonzales, Kristine; Guinto, Chez

    2011-01-01

    Recent evidence shows that a burst of rapid exercise with a duration of 10 minutes or less may be more effective in increasing body metabolism in the hours after exercise than is seen with low level aerobic exercise...

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

    Science.gov (United States)

    Moghe, Gaurav D.; Last, Robert L.

    2015-01-01

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

  8. Metabolic disorders in menopause

    Directory of Open Access Journals (Sweden)

    Grzegorz Stachowiak

    2015-04-01

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

  9. How Rapid is Rapid Prototyping? Analysis of ESPADON Programme Results

    Directory of Open Access Journals (Sweden)

    Ian D. Alston

    2003-05-01

    Full Text Available New methodologies, engineering processes, and support environments are beginning to emerge for embedded signal processing systems. The main objectives are to enable defence industry to field state-of-the-art products in less time and with lower costs, including retrofits and upgrades, based predominately on commercial off the shelf (COTS components and the model-year concept. One of the cornerstones of the new methodologies is the concept of rapid prototyping. This is the ability to rapidly and seamlessly move from functional design to the architectural design to the implementation, through automatic code generation tools, onto real-time COTS test beds. In this paper, we try to quantify the term “rapid” and provide results, the metrics, from two independent benchmarks, a radar and sonar beamforming application subset. The metrics show that the rapid prototyping process may be sixteen times faster than a conventional process.

  10. Personality and metabolic syndrome.

    Science.gov (United States)

    Sutin, Angelina R; Costa, Paul T; Uda, Manuela; Ferrucci, Luigi; Schlessinger, David; Terracciano, Antonio

    2010-12-01

    The prevalence of metabolic syndrome has paralleled the sharp increase in obesity. Given its tremendous physical, emotional, and financial burden, it is of critical importance to identify who is most at risk and the potential points of intervention. Psychological traits, in addition to physiological and social risk factors, may contribute to metabolic syndrome. The objective of the present research is to test whether personality traits are associated with metabolic syndrome in a large community sample. Participants (N = 5,662) from Sardinia, Italy, completed a comprehensive personality questionnaire, the NEO-PI-R, and were assessed on all components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose). Logistic regressions were used to predict metabolic syndrome from personality traits, controlling for age, sex, education, and current smoking status. Among adults over age 45 (n = 2,419), Neuroticism and low Agreeableness were associated with metabolic syndrome, whereas high Conscientiousness was protective. Individuals who scored in the top 10% on Conscientiousness were approximately 40% less likely to have metabolic syndrome (OR = 0.61, 95% CI = 0.41-0.92), whereas those who scored in the lowest 10% on Agreeableness were 50% more likely to have it (OR = 1.53, 95% CI = 1.09-2.16). At the facet level, traits related to impulsivity and hostility were the most strongly associated with metabolic syndrome. The present research indicates that those with fewer psychological resources are more vulnerable to metabolic syndrome and suggests a psychological component to other established risk factors.

  11. Microbial degradation of pesticides in rapid sand filters used for drinking water treatment

    DEFF Research Database (Denmark)

    Hedegaard, Mathilde Jørgensen

    in rapid sand filters was not associated with methane oxidation. Based on the present investigations and literature, it was suggested that phenoxy acid degradation in rapid sand filters is due to primary metabolism, and that degradation might be stimulated by enriching naturally occurring specific...... degraders in the sand filters upon exposure to phenoxy acid contaminated groundwater. A suite of evidence showed that the herbicide bentazone was co-metabolically transformed to hydroxy-bentazone by the methanotrophic enrichment culture. Subsequently, it was investigated whether bentazone degradation...... a sequential reactor system, where methanotrophs are grown in the aeration tanks and transported to the rapid sand filters where they can perform co-metabolic pesticide biodegradation. It was suggested that bentazone removal can be stimulated at waterworks, by stimulating growth of methanotrophs. Overall...

  12. Human Body Exergy Metabolism

    OpenAIRE

    Mady, Carlos

    2013-01-01

    The exergy analysis of the human body is a tool that can provide indicators of health and life quality. To perform the exergy balance it is necessary to calculate the metabolism on an exergy basis, or metabolic exergy, although there is not yet consensus in its calculation procedure. Hence, the aim of this work is to provide a general method to evaluate this physical quantity for human body based on indirect calorimetry data. To calculate the metabolism on an exergy basis it is necessary to d...

  13. A Metabolic Switch

    DEFF Research Database (Denmark)

    Hjorth, Poul G.

    Our muscles are metabolically flexible, i.e., they are capable of `switching' between two types of oxidation: (1) when fasting, a predominantly lipid oxidation with high rates of fatty acid uptake, and (2) when fed, suppression of lipid oxidation in favour of increased glucose uptake, oxidation...... and storage, in response to insulin. One of the many manifestations of obesity and Type 2 diabetes is an insulin resistance of the skeletal muscles, which suppresses this metabolic switch. This talk describes recent development of a low-dimensional system of ODEs that model the metabolic switch, displaying...

  14. Migraine and metabolism.

    Science.gov (United States)

    Casucci, G; Villani, V; Cologno, D; D'Onofrio, F

    2012-05-01

    Migraine is a chronic disorder with complex pathophysiology involving both neuronal and vascular mechanisms. Migraine is associated with an increased risk of vascular disorders, such as stroke and coronary heart disease. Obesity and diabetes are metabolic disorders with a complex association with migraine. Insulin resistance, which represents the main causal factor of diseases involved in metabolic syndrome, is more common in patients with migraine. A better understanding of the relationship between metabolic syndrome and migraine may be of great clinical interest for migraine management.

  15. Whole genome sequencing of Saccharomyces cerevisiae: from genotype to phenotype for improved metabolic engineering applications

    DEFF Research Database (Denmark)

    Otero, José Manuel; Vongsangnak, Wanwipa; Asadollahi, Mohammadali

    2010-01-01

    BACKGROUND: The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where s...... that provides clear and high-probability of success metabolic engineering targets. The genome sequence, annotation, and a SNP viewer of CEN.PK113-7D are deposited at http://www.sysbio.se/cenpk.......BACKGROUND: The need for rapid and efficient microbial cell factory design and construction are possible through the enabling technology, metabolic engineering, which is now being facilitated by systems biology approaches. Metabolic engineering is often complimented by directed evolution, where...... selective pressure is applied to a partially genetically engineered strain to confer a desirable phenotype. The exact genetic modification or resulting genotype that leads to the improved phenotype is often not identified or understood to enable further metabolic engineering. RESULTS: In this work we...

  16. Astrocytes take the stage in a tale of signaling-metabolism coupling

    DEFF Research Database (Denmark)

    Bak, Lasse K

    2017-01-01

    Astrocytes are crucial cells in the brain that are intimately coupled with neuronal metabolism. A new paper from San Martín et al. provides evidence that physiological levels of the gaseous signal molecule NO can rapidly and reversibly increase astrocyte metabolism of glucose and production...

  17. A sensitive mass spectrometry platform identifies metabolic changes of life history traits in C-elegans

    NARCIS (Netherlands)

    Gao, Arwen W.; Chatzispyrou, Iliana A.; Kamble, Rashmi; Liu, Yasmine J.; Herzog, Katharina; Smith, Reuben L.; van Lenthe, Henk; Vervaart, Martin A. T.; van Cruchten, Arno; Luyf, Angela C.; van Kampen, Antoine; Pras-Raves, Mia L.; Vaz, Frédéric M.; Houtkooper, Riekelt H.

    2017-01-01

    Abnormal nutrient metabolism is a hallmark of aging, and the underlying genetic and nutritional framework is rapidly being uncovered, particularly using C. elegans as a model. However, the direct metabolic consequences of perturbations in life history of C. elegans remain to be clarified. Based on

  18. Metabolic investigations prevent liver transplantation in two young children with citrullinemia type I

    NARCIS (Netherlands)

    de Groot, Martijn J.; Cuppen, Marcel; Eling, Marc; Verheijen, Frans W.; Rings, Edmond H. H. M.; Reijngoud, Dirk-Jan; de Vries, Maaike M. C.; van Spronsen, Francjan J.

    2010-01-01

    Acute liver failure may be caused by a variety of disorders including inborn errors of metabolism. In those cases, rapid metabolic investigations and adequate treatment may avoid the need for liver transplantation. We report two patients who presented with acute liver failure and were referred to

  19. A Rapid Coliform Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid genetic detector for spaceflight water systems to enable real-time detection of E-coli with minimal...

  20. Rapid Multiplex Microbial Detector Project

    Data.gov (United States)

    National Aeronautics and Space Administration — ORBITEC, in collaboration with Lucigen, proposes a rapid nucleic acid-based detector for spaceflight water systems to enable simultaneous quantification of multiple...

  1. Metabolism. Part III: Lipids.

    Science.gov (United States)

    Bodner, George M.

    1986-01-01

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

  2. Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... this process. One group of these disorders is amino acid metabolism disorders. They include phenylketonuria (PKU) and maple syrup urine disease. Amino acids are "building blocks" that join together to form ...

  3. Epigenetics and Cellular Metabolism

    Directory of Open Access Journals (Sweden)

    Wenyi Xu

    2016-01-01

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

  4. Engineering of metabolic control

    Science.gov (United States)

    Liao, James C.

    2004-03-16

    The invention features a method of producing heterologous molecules in cells under the regulatory control of a metabolite and metabolic flux. The method can enhance the synthesis of heterologous polypeptides and metabolites.

  5. The prevalence of metabolic syndrome and its components among ...

    African Journals Online (AJOL)

    Background: The incidence of metabolic syndrome (MetS), is rapidly increasing in developing countries. However, the epidemiology of MetS is not well reported in the pediatric and young adult population. We determined the prevalence of MetS and its components among overweight and obese Nigerian adolescents and ...

  6. The Prevalence of Metabolic Syndrome and Its Components among ...

    African Journals Online (AJOL)

    2016-09-30

    Sep 30, 2016 ... Background: The incidence of metabolic syndrome (MetS), is rapidly increasing in developing countries. However, the epidemiology of MetS is not well reported in the pediatric and young adult population. We determined the prevalence of. MetS and its components among overweight and obese Nigerian ...

  7. The Prevalence of Metabolic Syndrome and Its Components among ...

    African Journals Online (AJOL)

    2017-06-28

    Jun 28, 2017 ... Background: The incidence of metabolic syndrome (MetS), is rapidly increasing in developing countries. However, the epidemiology of MetS is not well reported in the pediatric and young adult population. We determined the prevalence of. MetS and its components among overweight and obese Nigerian ...

  8. Diphosphoinositol Polyphosphates: Metabolic Messengers?

    Science.gov (United States)

    Shears, Stephen B.

    2009-01-01

    The diphosphoinositol polyphosphates (“inositol pyrophosphates”) are a specialized subgroup of the inositol phosphate signaling family. This review proposes that many of the current data concerning the metabolic turnover and biological effects of the diphosphoinositol polyphosphates are linked by a common theme: these polyphosphates act as metabolic messengers. This review will also discuss the latest proposals concerning possible molecular mechanisms of action of this intriguing class of molecules. PMID:19439500

  9. Metabolic Theory: Energetic barriers

    OpenAIRE

    Locey, Kenneth

    2013-01-01

    This is an early talk I gave on a possible refinement to the metabolic theory of ecology (MTE). In short, the basic equation of MTE uses an Arrhenius-like formula (which in turn assumes a constant activation energy) to predict how metabolic related rates and species richness should vary with temperature. Here, I proposed that the simple Arrhenius relationship could be replaced with a more dynamical relationship where activation energy could be predicted to change, as is often observed in biol...

  10. Tobacco and metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Yatan Pal Singh Balhara

    2012-01-01

    Full Text Available Tobacco is a leading contributor to morbidity and mortality globally. Metabolic syndrome is a constellation of abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance (with and without glucose intolerance, pro-inflammatory state, and pro-thrombotic state. Tobacco use is associated with various core components of metabolic syndrome. It has been found to play a causal role in various pathways leading on to development this condition, the current article discusses various facets of this association.

  11. A review of parameters and heuristics for guiding metabolic pathfinding.

    Science.gov (United States)

    Kim, Sarah M; Peña, Matthew I; Moll, Mark; Bennett, George N; Kavraki, Lydia E

    2017-09-15

    Recent developments in metabolic engineering have led to the successful biosynthesis of valuable products, such as the precursor of the antimalarial compound, artemisinin, and opioid precursor, thebaine. Synthesizing these traditionally plant-derived compounds in genetically modified yeast cells introduces the possibility of significantly reducing the total time and resources required for their production, and in turn, allows these valuable compounds to become cheaper and more readily available. Most biosynthesis pathways used in metabolic engineering applications have been discovered manually, requiring a tedious search of existing literature and metabolic databases. However, the recent rapid development of available metabolic information has enabled the development of automated approaches for identifying novel pathways. Computer-assisted pathfinding has the potential to save biochemists time in the initial discovery steps of metabolic engineering. In this paper, we review the parameters and heuristics used to guide the search in recent pathfinding algorithms. These parameters and heuristics capture information on the metabolic network structure, compound structures, reaction features, and organism-specificity of pathways. No one metabolic pathfinding algorithm or search parameter stands out as the best to use broadly for solving the pathfinding problem, as each method and parameter has its own strengths and shortcomings. As assisted pathfinding approaches continue to become more sophisticated, the development of better methods for visualizing pathway results and integrating these results into existing metabolic engineering practices is also important for encouraging wider use of these pathfinding methods.

  12. Nutrient Acquisition and Metabolism by Campylobacter jejuni

    Directory of Open Access Journals (Sweden)

    Martin eStahl

    2012-02-01

    Full Text Available The gastrointestinal pathogen Campylobacter jejuni is able to colonize numerous different hosts and compete against the gut microbiota. To do this, it must be able to efficiently acquire sufficient nutrients from its environment to support its survival and rapid growth in the intestine. However, despite almost 50 years of research, many aspects as to how C. jejuni accomplishes this feat remain poorly understood. C. jejuni lacks many of the common metabolic pathways necessary for the use of glucose, galactose, or other carbohydrates upon which most other microbes thrive. It does however make efficient use of citric acid cycle intermediates and various amino acids. C. jejuni readily uses the amino acids aspartate, glutamate, serine, and proline, with certain strains also possessing additional pathways allowing for the use of glutamine and asparagine. More recent work has revealed that some C. jejuni strains can metabolize the sugar L-fucose. This finding has upset years of dogma that C. jejuni is an asaccharolytic organism. C. jejuni also possesses diverse mechanisms for the acquisition of various transition metals that are required for metabolic activities. In particular, iron acquisition is critical for the formation of iron-sulphur complexes. C. jejuni is also unique in possessing both molybdate and tungsten cofactored proteins and thus has an unusual regulatory scheme for these metals. Together these various metabolic and acquisition pathways help C. jejuni to compete and thrive in wide variety of hosts and environments.

  13. Metabolism of 6-nitrochrysene by intestinal microflora

    Energy Technology Data Exchange (ETDEWEB)

    Manning, B.W.; Campbell, W.L.; Franklin, W.; Delclos, B.; Cerniglia, C.E.

    1988-01-01

    Since bacterial nitroreduction may play a critical role in the activation of nitropolycyclic aromatic hydrocarbons, we have used batch and semicontinuous culture systems to determine the ability of intestinal microflora to metabolize the carcinogen 6-nitrochrysene (6-NC). 6-NC was metabolized by the intestinal microflora present in the semicontinuous culture system to 6-aminochrysene (6-AC), N-formyl-6-aminochrysene (6-FAC), and 6-nitrosochrysene (6-NOC). These metabolites were isolated and identified by high-performance liquid chromatography, mass spectrometry, and UV-visible spectrophotometry and compared with authentic compounds. Almost all of the 6-NC was metabolized after 10 days. Nitroreduction of 6-NC to 6-AC was rapid; the 6-AC concentration reached a maximum at 48 h. The ratio of the formation of 6-AC to 6-FAC to 6-NOC at 48 h was 93.4:6.3:0.3. Interestingly, compared with results in the semicontinuous culture system, the only metabolite detected in the batch studies was 6-AC. The rate of nitroreduction differed among human, rat, and mouse intestinal microflora, with human intestinal microflora metabolizing 6-NC to the greatest extent. Since 6-AC has been shown to be carcinogenic in mice and since nitroso derivatives of other nitropolycyclic aromatic hydrocarbons are biologically active, our results suggest that the intestinal microflora has the enzymatic capacity to generate genotoxic compounds and may play an important role in the carcinogenicity of 6-NC.

  14. Targeting glycogen metabolism in bladder cancer.

    Science.gov (United States)

    Ritterson Lew, Carolyn; Guin, Sunny; Theodorescu, Dan

    2015-07-01

    Metabolism has been a heavily investigated topic in cancer research for the past decade. Although the role of aerobic glycolysis (the Warburg effect) in cancer has been extensively studied, abnormalities in other metabolic pathways are only just being understood in cancer. One such pathway is glycogen metabolism; its involvement in cancer development, particularly in urothelial malignancies, and possible ways of exploiting aberrations in this process for treatment are currently being studied. New research shows that the glycogen debranching enzyme amylo-α-1,6-glucosidase, 4-α-glucanotransferase (AGL) is a novel tumour suppressor in bladder cancer. Loss of AGL leads to rapid proliferation of bladder cancer cells. Another enzyme involved in glycogen debranching, glycogen phosphorylase, has been shown to be a tumour promoter in cancer, including in prostate cancer. Studies demonstrate that bladder cancer cells in which AGL expression is lost are more metabolically active than cells with intact AGL expression, and these cells are more sensitive to inhibition of both glycolysis and glycine synthesis--two targetable pathways. As a tumour promoter and enzyme, glycogen phosphorylase can be directly targeted, and preclinical inhibitor studies are promising. However, few of these glycogen phosphorylase inhibitors have been tested for cancer treatment in the clinical setting. Several possible limitations to the targeting of AGL and glycogen phosphorylase might also exist.

  15. RAPYD--rapid annotation platform for yeast data.

    Science.gov (United States)

    Schneider, Jessica; Blom, Jochen; Jaenicke, Sebastian; Linke, Burkhard; Brinkrolf, Karina; Neuweger, Heiko; Tauch, Andreas; Goesmann, Alexander

    2011-08-20

    Lower eukaryotes of the kingdom Fungi include a variety of biotechnologically important yeast species that are in the focus of genome research for more than a decade. Due to the rapid progress in ultra-fast sequencing technologies, the amount of available yeast genome data increases steadily. Thus, an efficient bioinformatics platform is required that covers genome assembly, eukaryotic gene prediction, genome annotation, comparative yeast genomics, and metabolic pathway reconstruction. Here, we present a bioinformatics platform for yeast genomics named RAPYD addressing the key requirements of extensive yeast sequence data analysis. The first step is a comprehensive regional and functional annotation of a yeast genome. A region prediction pipeline was implemented to obtain reliable and high-quality predictions of coding sequences and further genome features. Functions of coding sequences are automatically determined using a configurable prediction pipeline. Based on the resulting functional annotations, a metabolic pathway reconstruction module can be utilized to rapidly generate an overview of organism-specific features and metabolic blueprints. In a final analysis step shared and divergent features of closely related yeast strains can be explored using the comparative genomics module. An in-depth application example of the yeast Meyerozyma guilliermondii illustrates the functionality of RAPYD. A user-friendly web interface is available at https://rapyd.cebitec.uni-bielefeld.de. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. DNA Tumor Viruses and Cell Metabolism.

    Science.gov (United States)

    Mushtaq, Muhammad; Darekar, Suhas; Kashuba, Elena

    2016-01-01

    Viruses play an important role in cancerogenesis. It is estimated that approximately 20% of all cancers are linked to infectious agents. The viral genes modulate the physiological machinery of infected cells that lead to cell transformation and development of cancer. One of the important adoptive responses by the cancer cells is their metabolic change to cope up with continuous requirement of cell survival and proliferation. In this review we will focus on how DNA viruses alter the glucose metabolism of transformed cells. Tumor DNA viruses enhance "aerobic" glycolysis upon virus-induced cell transformation, supporting rapid cell proliferation and showing the Warburg effect. Moreover, viral proteins enhance glucose uptake and controls tumor microenvironment, promoting metastasizing of the tumor cells.

  17. Thyroid hormone metabolism in poultry

    Directory of Open Access Journals (Sweden)

    Darras V.M.

    2000-01-01

    Full Text Available Thyroid hormone (TH receptors preferentially bind 3.5,3'-triiodothyronine (T3. Therefore the metabolism of thyroxine (T4 secreted by the thyroid gland in peripheral tissues, resulting in the production and degradation of receptor-active T3, plays a major role in thyroid function. The most important metabolic pathway for THs is deiodination. Another important pathway is sulfation, which is a reversible pathway that has been shown to interact with TH deiodination efficiency. The enzymes catalysing TH deiodination consist of three types. Type 1 deiodinase (D1 catalyses both outer ring (ORD and inner ring deiodinalion (IRD. Type II deiodinase (D2 only catalyses ORD while type III (D3 only catalyses IRD. The three chicken deiodinase cDNAs have been cloned recently. These enzymes all belong to the family of selenoproteins. Ontogenetic studies show that the availability of deiodinases is regulated in a tissue specific and developmental stage dependent way. Characteristic for the chicken is the presence of very high levels off, inactivating D3 enzyme in the embryonic liver. Hepatic D3 is subject to acute regulation in a number of situations. Both growth hormone and glucocorticoid injection rapidly decrease hepatic D3 levels, hereby increasing plasma T3 without affecting hepatic D1 levels. The inhibition of D3 seems to be regulated mainly at the level of D3 gene transcription. The effect of growth hormone on D3 expression persists throughout life, while glucocorticoids start to inhibit hepatic D1 expression in posthatch chickens. Food restriction in growing chickens increases hepatic D3 levels. This contributes to the decrease in plasma T3 necessary to reduce energy loss. Refeeding restores hepatic D3 and plasma T3 to control levels within a few hours. It can be concluded that the tissue and time dependent regulation of the balance between TH activating and inactivating enzymes plays an essential role in the control of local T3 availability and hence in

  18. 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...... 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...

  19. Apelin and energy metabolism

    Directory of Open Access Journals (Sweden)

    Chantal eBertrand

    2015-04-01

    Full Text Available A wide range of adipokines identified over the past years has allowed considering white adipose tissue as a secretory organ closely integrated into overall physiological and metabolic control. Apelin, an ubiquitous peptide was known to exert different physiological effects mainly on the cardiovascular system and the regulation of fluid homeostasis until its identification as an adipokine. This has increased its broad range of action and apelin now appears clearly as a new player in energy metabolism alongside leptin and adiponectin. Apelin has been shown to act on glucose and lipid metabolism but also to modulate insulin secretion. Moreover, different studies in both animals and humans have shown that plasma apelin concentrations are usually increased during obesity and type 2 diabetes. This mini-review will focus on the various systemic apelin effects on energy metabolism by addressing its mechanisms of action. The advances concerning the role of apelin in metabolic diseases in relation with the recent reports on apelin concentrations in obese and/or diabetic subjects will also be discussed.

  20. Metabolic surgery: quo vadis?

    Science.gov (United States)

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

    2014-01-01

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

  1. Dysregulated metabolic enzymes and metabolic reprogramming in cancer cells.

    Science.gov (United States)

    Sreedhar, Annapoorna; Zhao, Yunfeng

    2018-01-01

    Tumor cells carry various genetic and metabolic alterations, which directly contribute to their growth and malignancy. Links between metabolism and cancer are multifaceted. Metabolic reprogramming, such as enhanced aerobic glycolysis, mutations in the tricarboxylic acid (TCA) cycle metabolic enzymes, and dependence on lipid and glutamine metabolism are key characteristics of cancer cells. Understanding these metabolic alterations is crucial for development of novel anti-cancer therapeutic strategies. In the present review, the broad importance of metabolism in tumor biology is discussed, and the current knowledge on dysregulated metabolic enzymes involved in the vital regulatory steps of glycolysis, the TCA cycle, the pentose phosphate pathway, and lipid, amino acid, and mitochondrial metabolism pathways are reviewed.

  2. BioMet Toolbox: genome-wide analysis of metabolism

    DEFF Research Database (Denmark)

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

    2010-01-01

    rates, substrate uptake rates and metabolic production rates by detecting relevant fluxes, simulate single and double gene deletions or detect metabolites around which major transcriptional changes are concentrated. These tools can be used for high-throughput in silico screening and allows fully...... 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/.......The rapid progress of molecular biology tools for directed genetic modifications, accurate quantitative experimental approaches, high-throughput measurements, together with development of genome sequencing has made the foundation for a new area of metabolic engineering that is driven by metabolic...

  3. High incubation temperatures enhance mitochondrial energy metabolism in reptile embryos.

    Science.gov (United States)

    Sun, Bao-Jun; Li, Teng; Gao, Jing; Ma, Liang; Du, Wei-Guo

    2015-03-09

    Developmental rate increases exponentially with increasing temperature in ectothermic animals, but the biochemical basis underlying this thermal dependence is largely unexplored. We measured mitochondrial respiration and metabolic enzyme activities of turtle embryos (Pelodiscus sinensis) incubated at different temperatures to identify the metabolic basis of the rapid development occurring at high temperatures in reptile embryos. Developmental rate increased with increasing incubation temperatures in the embryos of P. sinensis. Correspondingly, in addition to the thermal dependence of mitochondrial respiration and metabolic enzyme activities, high-temperature incubation further enhanced mitochondrial respiration and COX activities in the embryos. This suggests that embryos may adjust mitochondrial respiration and metabolic enzyme activities in response to developmental temperature to achieve high developmental rates at high temperatures. Our study highlights the importance of biochemical investigations in understanding the proximate mechanisms by which temperature affects embryonic development.

  4. Recent advances in systems metabolic engineering tools and strategies.

    Science.gov (United States)

    Chae, Tong Un; Choi, So Young; Kim, Je Woong; Ko, Yoo-Sung; Lee, Sang Yup

    2017-10-01

    Metabolic engineering has been playing increasingly important roles in developing microbial cell factories for the production of various chemicals and materials to achieve sustainable chemical industry. Nowadays, many tools and strategies are available for performing systems metabolic engineering that allows systems-level metabolic engineering in more sophisticated and diverse ways by adopting rapidly advancing methodologies and tools of systems biology, synthetic biology and evolutionary engineering. As an outcome, development of more efficient microbial cell factories has become possible. Here, we review recent advances in systems metabolic engineering tools and strategies together with accompanying application examples. In addition, we describe how these tools and strategies work together in simultaneous and synergistic ways to develop novel microbial cell factories. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101).

    Science.gov (United States)

    McGraw, Joseph E; Waller, Donald P

    2006-05-26

    Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2',4',5,5') is a common, persistent non-coplanar PCB congener found in the ambient environment but information related to its metabolism in humans is lacking. Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP 2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in hamsters was also reported. To specifically identify the human CYP 450 isoforms responsible for PCB 101 metabolism, we compared human microsome metabolism to metabolism using several specific recombinant human CYP isoforms. These data characterized selective and extensive metabolism by human CYP 2A6. The product formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2',4',5,5') and was the only major metabolite observed in the recombinant and human microsome investigation. This is important information for predicting human specific toxicokinetics of PCBs.

  6. Perspectives on ruminant nutrition and metabolism. II. Metabolism in ruminant tissues.

    Science.gov (United States)

    Annison, E F; Bryden, W L

    1999-06-01

    The discovery of the dominance of short-chain fatty acids as energy sources in the 1940s and 1950s, as discussed in part I of this review (Annison & Bryden, 1998) led to uncertainties concerning the interrelationships of glucose and acetate in ruminant metabolism. These were resolved in the following decade largely by use of 14C-labelled substrates. Although only small amounts of glucose are absorbed in most dietary situations, glucose availability to ruminant tissues as measured by isotope dilution was shown to be substantial, indicating that gluconeogenesis is a major metabolic activity in both fed and fasted states. Studies with 14C-labelled glucose and acetate revealed that in contrast to non-ruminants, acetate and not glucose is the major precursor of long-chain fatty acids in ruminant tissues. Interest in the measurement of energy metabolism in livestock grew rapidly from the 1950s. Most laboratories adopted indirect calorimetry and precise measurements of the energy expenditure of ruminants contributed to the development of new feeding systems. More recently, alternative approaches to the measurement of energy expenditure have included the use of NMR spectroscopy, isotope dilution and the application of the Fick principle to measure O2 consumption in the whole animal and in defined tissues. The refinement of the classical arterio-venous difference procedure in the study of mammary gland metabolism in the 1960s, particularly when combined with isotope dilution, encouraged the use of these methods to generate quantitative data on the metabolism of a range of defined tissues. The recent introduction of new methods for the continuous monitoring of both blood flow and blood O2 content has greatly increased the precision and scope of arterio-venous difference measurements. The impact of data produced by these and other quantitative procedures on current knowledge of the metabolism of glucose, short-chain fatty acids and lipids, and on N metabolism, is outlined

  7. Composites by rapid prototyping technology

    CSIR Research Space (South Africa)

    Kumar, S

    2010-02-01

    Full Text Available powder is a fiber, problems of manufacturing occur. The method has also been used to make Metal Matrix Composite (MMC), e.g Fe and graphite [17], WC-Co [18,19], WC-Co and Cu [20,21], Fe, Ni and TiC [22] etc and Ceramic Matrix Composite (CMC) e.g. Si... of various materials used. Key words: : Rapid Prototyping (RP), Laser, Composites 1 Introduction Rapid Prototyping (RP) initially focussed on polymers. These were later re- placed/supplemented by ceramics, metals and composites. Composites are used in RP...

  8. Urea metabolism in plants.

    Science.gov (United States)

    Witte, Claus-Peter

    2011-03-01

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

  9. Nitrile Metabolizing Yeasts

    Science.gov (United States)

    Bhalla, Tek Chand; Sharma, Monica; Sharma, Nitya Nand

    Nitriles and amides are widely distributed in the biotic and abiotic components of our ecosystem. Nitrile form an important group of organic compounds which find their applications in the synthesis of a large number of compounds used as/in pharmaceutical, cosmetics, plastics, dyes, etc>. Nitriles are mainly hydro-lyzed to corresponding amide/acid in organic chemistry. Industrial and agricultural activities have also lead to release of nitriles and amides into the environment and some of them pose threat to human health. Biocatalysis and biotransformations are increasingly replacing chemical routes of synthesis in organic chemistry as a part of ‘green chemistry’. Nitrile metabolizing organisms or enzymes thus has assumed greater significance in all these years to convert nitriles to amides/ acids. The nitrile metabolizing enzymes are widely present in bacteria, fungi and yeasts. Yeasts metabolize nitriles through nitrilase and/or nitrile hydratase and amidase enzymes. Only few yeasts have been reported to possess aldoxime dehydratase. More than sixty nitrile metabolizing yeast strains have been hither to isolated from cyanide treatment bioreactor, fermented foods and soil. Most of the yeasts contain nitrile hydratase-amidase system for metabolizing nitriles. Transformations of nitriles to amides/acids have been carried out with free and immobilized yeast cells. The nitrilases of Torulopsis candida>and Exophiala oligosperma>R1 are enantioselec-tive and regiospecific respectively. Geotrichum>sp. JR1 grows in the presence of 2M acetonitrile and may have potential for application in bioremediation of nitrile contaminated soil/water. The nitrilase of E. oligosperma>R1 being active at low pH (3-6) has shown promise for the hydroxy acids. Immobilized yeast cells hydrolyze some additional nitriles in comparison to free cells. It is expected that more focus in future will be on purification, characterization, cloning, expression and immobilization of nitrile metabolizing

  10. Systems metabolic engineering in an industrial setting.

    Science.gov (United States)

    Sagt, Cees M J

    2013-03-01

    Systems metabolic engineering is based on systems biology, synthetic biology, and evolutionary engineering and is now also applied in industry. Industrial use of systems metabolic engineering focuses on strain and process optimization. Since ambitious yields, titers, productivities, and low costs are key in an industrial setting, the use of effective and robust methods in systems metabolic engineering is becoming very important. Major improvements in the field of proteomics and metabolomics have been crucial in the development of genome-wide approaches in strain and process development. This is accompanied by a rapid increase in DNA sequencing and synthesis capacity. These developments enable the use of systems metabolic engineering in an industrial setting. Industrial systems metabolic engineering can be defined as the combined use of genome-wide genomics, transcriptomics, proteomics, and metabolomics to modify strains or processes. This approach has become very common since the technology for generating large data sets of all levels of the cellular processes has developed quite fast into robust, reliable, and affordable methods. The main challenge and scope of this mini review is how to translate these large data sets in relevant biological leads which can be tested for strain or process improvements. Experimental setup, heterogeneity of the culture, and sample pretreatment are important issues which are easily underrated. In addition, the process of structuring, filtering, and visualization of data is important, but also, the availability of a genetic toolbox and equipment for medium/high-throughput fermentation is a key success factor. For an efficient bioprocess, all the different components in this process have to work together. Therefore, mutual tuning of these components is an important strategy.

  11. Synthetic Metabolic Pathways

    DEFF Research Database (Denmark)

    This volume outlines key steps associated with the design, building, and testing of synthetic metabolic pathways for optimal cell factory performance and robustness, and illustrates how data-driven learning from these steps can be used for rational cost-effective engineering of cell factories...... topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Synthetic Metabolic Pathways: Methods and Protocols aims to ensure successful results in the further study...

  12. Metabolic Instruction of Immunity.

    Science.gov (United States)

    Buck, Michael D; Sowell, Ryan T; Kaech, Susan M; Pearce, Erika L

    2017-05-04

    Choices have consequences. Immune cells survey and migrate throughout the body and sometimes take residence in niche environments with distinct communities of cells, extracellular matrix, and nutrients that may differ from those in which they matured. Imbedded in immune cell physiology are metabolic pathways and metabolites that not only provide energy and substrates for growth and survival, but also instruct effector functions, differentiation, and gene expression. This review of immunometabolism will reference the most recent literature to cover the choices that environments impose on the metabolism and function of immune cells and highlight their consequences during homeostasis and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Nutrient excess and autophagic deficiency: explaining metabolic diseases in obesity.

    Science.gov (United States)

    van Niekerk, Gustav; duToit, André; Loos, Ben; Engelbrecht, Anna-Mart

    2017-12-28

    Over-nutrition and a sedentary lifestyle are the driving forces behind the development of metabolic diseases. Conversely, caloric restriction and exercise have proven to be the most effective strategies in combating metabolic diseases. Interestingly, exercise and caloric restriction share a common feature: both represent a potent mechanism for upregulating autophagy. Autophagy is rapidly induced by nutrient deprivation, and conversely, inactivated by amino acids as well as growth factors (e.g. insulin). Here, we review evidence demonstrating that autophagy may indeed be attenuated in metabolic tissue such as liver, muscle, and adipose, in the context of obesity. We also highlight the mechanistic basis by which defective autophagy may contribute to the manifestation of metabolic diseases. This includes a compromised ability of the cell to perform quality control on the mitochondrial matrix, since autophagy plays a pivotal role in the degradation of defective mitochondria. Similarly, autophagy also plays an indispensable role in the clearance of protein aggregates and redundant large protein platforms such as inflammasomes. Autophagy might also play a key role in the metabolism of endotoxins, implicating the importance of autophagy in the pathogenesis of metabolic endotoxemia. These observations underpin an unprecedented role of autophagy in the manifestation of obesity-induced metabolic derangement. Copyright © 2017. Published by Elsevier Inc.

  14. Impact of the solvent capacity constraint on E. coli metabolism

    Directory of Open Access Journals (Sweden)

    Barabási Albert-László

    2008-01-01

    Full Text Available Abstract Background Obtaining quantitative predictions for cellular metabolic activities requires the identification and modeling of the physicochemical constraints that are relevant at physiological growth conditions. Molecular crowding in a cell's cytoplasm is one such potential constraint, as it limits the solvent capacity available to metabolic enzymes. Results Using a recently introduced flux balance modeling framework (FBAwMC here we demonstrate that this constraint determines a metabolic switch in E. coli cells when they are shifted from low to high growth rates. The switch is characterized by a change in effective optimization strategy, the excretion of acetate at high growth rates, and a global reorganization of E. coli metabolic fluxes, the latter being partially confirmed by flux measurements of central metabolic reactions. Conclusion These results implicate the solvent capacity as an important physiological constraint acting on E. coli cells operating at high metabolic rates and for the activation of a metabolic switch when they are shifted from low to high growth rates. The relevance of this constraint in the context of both the aerobic ethanol excretion seen in fast growing yeast cells (Crabtree effect and the aerobic glycolysis observed in rapidly dividing cancer cells (Warburg effect should be addressed in the future.

  15. Developmental evolution facilitates rapid adaptation.

    Science.gov (United States)

    Lin, Hui; Kazlauskas, Romas J; Travisano, Michael

    2017-11-21

    Developmental evolution has frequently been identified as a mode for rapid adaptation, but direct observations of the selective benefits and associated mechanisms of developmental evolution are necessarily challenging to obtain. Here we show rapid evolution of greatly increased rates of dispersal by developmental changes when populations experience stringent selection. Replicate populations of the filamentous fungus Trichoderma citrinoviride underwent 85 serial transfers, under conditions initially favoring growth but not dispersal. T. citrinoviride populations shifted away from multicellular growth toward increased dispersal by producing one thousand times more single-celled asexual conidial spores, three times sooner than the ancestral genotype. Conidia of selected lines also germinated fifty percent faster. Gene expression changed substantially between the ancestral and selected fungi, especially for spore production and growth, demonstrating rapid evolution of tight regulatory control for down-regulation of growth and up-regulation of conidia production between 18 and 24 hours of growth. These changes involved both developmentally fixed and plastic changes in gene expression, showing that complex developmental changes can serve as a mechanism for rapid adaptation.

  16. Multigrade Teaching Rapid Appraisal Procedure.

    Science.gov (United States)

    Nielsen, Dean

    Multigrade classes have been recognized as part of elementary education for many years, but their special needs have been largely ignored. This manual focuses on the survey research that should predate the design of instructional management strategies in multigrade classrooms. It describes rapid and reliable ways to collect information about the…

  17. Rapid thermal processing of semiconductors

    CERN Document Server

    Borisenko, Victor E

    1997-01-01

    Rapid thermal processing has contributed to the development of single wafer cluster processing tools and other innovations in integrated circuit manufacturing environments Borisenko and Hesketh review theoretical and experimental progress in the field, discussing a wide range of materials, processes, and conditions They thoroughly cover the work of international investigators in the field

  18. Furnace for rapid thermal processing

    NARCIS (Netherlands)

    Roozeboom, F.; Duine, P.A.; Sluis, P. van der

    2001-01-01

    A Method (1) for Rapid Thermal Processing of a wafer (7), wherein the wafer (7) is heated by lamps (9), and the heat radiation is reflected by an optical switching device (15,17) which is in the reflecting state during the heating stage. During the cooling stage of the wafer (7), the heat is

  19. Rapid Energy Modeling Workflow Demonstration

    Science.gov (United States)

    2013-10-31

    BIM Building Information Modeling BPA Building Performance Analysis BTU British Thermal Unit CBECS Commercial Building ...geometry, orientation, weather, and materials, generates 3D Building Information Models ( BIM ) guided by satellite views of building footprints and...Rapid Energy Modeling (REM) workflows that employed building information modeling ( BIM ) approaches and conceptual energy analysis.

  20. Portable Diagnostics and Rapid Germination

    Energy Technology Data Exchange (ETDEWEB)

    Dunn, Zachary Spencer [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

    2016-12-01

    In the Bioenergy and Defense Department of Sandia National Laboratories, characterization of the BaDx (Bacillus anthracis diagnostic cartridge) was performed and rapid germination chemistry was investigated. BaDx was tested with complex sample matrixes inoculated with Bacillus anthracis, and the trials proved that BaDx will detect Bacillus anthracis in a variety of the medium, such as dirt, serum, blood, milk, and horse fluids. The dimensions of the device were altered to accommodate an E. coli or Listeria lateral flow immunoassay, and using a laser printer, BaDx devices were manufactured to identify E. coli and Listeria. Initial testing with E. coli versions of BaDx indicate that the device will be viable as a portable diagnostic cartridge. The device would be more effective with faster bacteria germination; hence studies were performed the use of rapid germination chemistry. Trials with calcium dipicolinic acid displayed increased cell germination, as shown by control studies using a microplate reader. Upon lyophilization the rapid germination chemistry failed to change growth patterns, indicating that the calcium dipicolinic acid was not solubilized under the conditions tested. Although incompatible with the portable diagnostic device, the experiments proved that the rapid germination chemistry was effective in increasing cell germination.

  1. Metabolism at Evolutionary Optimal States

    Directory of Open Access Journals (Sweden)

    Iraes Rabbers

    2015-06-01

    Full Text Available Metabolism is generally required for cellular maintenance and for the generation of offspring under conditions that support growth. The rates, yields (efficiencies, adaptation time and robustness of metabolism are therefore key determinants of cellular fitness. For biotechnological applications and our understanding of the evolution of metabolism, it is necessary to figure out how the functional system properties of metabolism can be optimized, via adjustments of the kinetics and expression of enzymes, and by rewiring metabolism. The trade-offs that can occur during such optimizations then indicate fundamental limits to evolutionary innovations and bioengineering. In this paper, we review several theoretical and experimental findings about mechanisms for metabolic optimization.

  2. Sleep and Metabolism: An Overview

    Directory of Open Access Journals (Sweden)

    Sunil Sharma

    2010-01-01

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

  3. Macrophage Polarization in Metabolism and Metabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-08-01

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

  4. 1 H-NMR metabolomics: Profiling method for a rapid and efficient ...

    African Journals Online (AJOL)

    Principal component analysis was used to separate groups of samples and to relate known and unknown metabolites to transgenic events. The screening of 100 samples, from extraction to data mining, took 36 h. Thus, this procedure allows the rapid selection of metabolic phenotypes of interest among about 30 transgenic ...

  5. A rapid colorimetric assay for mold spore germination using XTT tetrazolium salt

    Science.gov (United States)

    Carol A. Clausen; Vina W. Yang

    2011-01-01

    Current laboratory test methods to measure efficacy of new mold inhibitors are time consuming, some require specialized test equipment and ratings are subjective. Rapid, simple quantitative assays to measure the efficacy of mold inhibitors are needed. A quantitative, colorimetric microassay was developed using XTT tetrazolium salt to metabolically assess mold spore...

  6. NMR analysis of budding yeast metabolomics: a rapid method for sample preparation.

    Science.gov (United States)

    Airoldi, C; Tripodi, F; Guzzi, C; Nicastro, R; Coccetti, P

    2015-02-01

    Here we propose the optimization of a rapid and reproducible protocol for intracellular metabolite extraction from yeast cells and their metabolic profiling by (1)H-NMR spectroscopy. The protocol reliability has been validated through comparison between the metabolome of cells in different phases of growth or with different genetic backgrounds.

  7. Metabolism of antiarrhythmics.

    Science.gov (United States)

    Ha, Huy Riem; Follath, Ferenc

    2004-12-01

    Antiarrhythmics are a group of drugs that manage the irregular electrical activity of the heart. Their use in the clinic is made difficult by their narrow therapeutic index. The disposition of antiarrhythmics is dependent on many factors, such as administration route, stereoselectivity in the first-pass effect, inhibition of enzymes, polymorphisms, etc. Consequently, the pharmacological activity of drugs may be interindividually variable. Experiments using organ homogenates or hepatic microsome fractions were used for simulating the biotransformation of the drug in vivo. The classical approaches, such as correlation analysis, specifically the inhibitory effect, or induction of chemicals, and immunoinhibition, may be combined with the use of recombinant enzymes for identifying the enzymes involved in the drug metabolism. The fate of the antiarrhythmics may also be investigated in live animals. A species-dependent metabolism was often observed. The pre-treatment with chemicals, which influences the change (inhibition or induction) in the drug disposition, may provide insights into the enzymes involved in vivo. However, published data indicated that the data obtained from animals should not be extrapolated directly to humans. Nevertheless, animal models are useful for investigating the mechanism of clinical observations. The clinical use of the antiarrhythmics becomes complex, when the drug metabolism is genetically/phenotypically dependent and active metabolites are formed. Furthermore, the stereoselectivity may also modify the disposition and the pharmacodynamic profile of a therapeutic agent. Only the knowledge of the drug metabolism and the status of each individual may allow the use of antiarrhythmics safely.

  8. Diversified glucosinolate metabolism

    DEFF Research Database (Denmark)

    Frisch, Tina; Motawie, Mohammed Saddik; Olsen, Carl Erik

    2015-01-01

    were biosynthesized from methionine. The biosynthesis of alliarinoside was shown not to bifurcate from sinigrin biosynthesis at the oxime level in contrast to the general scheme for hydroxynitrile glucoside biosynthesis. Instead, the aglucon of alliarinoside was formed from metabolism of sinigrin...

  9. Thyroid and lipid metabolism.

    Science.gov (United States)

    Pucci, E; Chiovato, L; Pinchera, A

    2000-06-01

    Thyroid hormones influence all major metabolic pathways. Their most obvious and well-known action is an increase in basal energy expenditure obtained acting on protein, carbohydrate and lipid metabolism. With specific regard to lipid metabolism, thyroid hormones affect synthesis, mobilization and degradation of lipids, although degradation is influenced more than synthesis. The main and best-known effects on lipid metabolism include: (a) enhanced utilization of lipid substrates; (b) increase in the synthesis and mobilization of triglycerides stored in adipose tissue; (c) increase in the concentration of non-esterified fatty acids (NEFA); and (d) increase of lipoprotein-lipase activity. While severe hypothyroidism is usually associated with an increased serum concentration of total cholesterol and atherogenic lipoproteins, the occurrence of acute myocardial infarction (AMI) in hypothyroid patients is not frequent. However, hypothyroid patients appear to have an increased incidence of residual myocardial ischemia following AMI. Even in subclinical hypothyroidism, which is characterized by raised serum TSH levels with normal serum thyroid hormone concentrations, mild hyperlipidemia is present and may contribute to an increased risk of atherogenesis. Prudent substitution therapy with L-thyroxine is indicated in patients with both overt and subclinical hypothyroidism, with or without angina, to counteract the cardiovascular risk resulting from hyper-dyslipidemia.

  10. Metabolic Diseases of Muscle

    Science.gov (United States)

    ... ing fuel, and no energy is produced for muscle function. 4 Metabolic Diseases of Muscle • ©2011 MDA A ... This slowly progressive disorder causes cardiac disease and muscle weakness in the hips, shoulders, and upper arms and legs. The neck and ...

  11. Ghrelin and Metabolic Surgery

    Directory of Open Access Journals (Sweden)

    Dimitrios J. Pournaras

    2010-01-01

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

  12. Neonatal nutrition and metabolism

    National Research Council Canada - National Science Library

    Thureen, Patti J; Hay, William W

    2006-01-01

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

  13. Metabolic Reprogramming in Glioma

    Science.gov (United States)

    Strickland, Marie; Stoll, Elizabeth A.

    2017-01-01

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

  14. The metabolic vascular syndrome - guide to an individualized treatment.

    Science.gov (United States)

    Hanefeld, Markolf; Pistrosch, Frank; Bornstein, Stefan R; Birkenfeld, Andreas L

    2016-03-01

    In ancient Greek medicine the concept of a distinct syndrome (going together) was used to label 'a group of signs and symptoms' that occur together and 'characterize a particular abnormality and condition'. The (dys)metabolic syndrome is a common cluster of five pre-morbid metabolic-vascular risk factors or diseases associated with increased cardiovascular morbidity, fatty liver disease and risk of cancer. The risk for major complications such as cardiovascular diseases, NASH and some cancers develops along a continuum of risk factors into clinical diseases. Therefore we still include hyperglycemia, visceral obesity, dyslipidemia and hypertension as diagnostic traits in the definition according to the term 'deadly quartet'. From the beginning elevated blood pressure and hyperglycemia were core traits of the metabolic syndrome associated with endothelial dysfunction and increased risk of cardiovascular disease. Thus metabolic and vascular abnormalities are in extricable linked. Therefore it seems reasonable to extend the term to metabolic-vascular syndrome (MVS) to signal the clinical relevance and related risk of multimorbidity. This has important implications for integrated diagnostics and therapeutic approach. According to the definition of a syndrome the rapid global rise in the prevalence of all traits and comorbidities of the MVS is mainly caused by rapid changes in life-style and sociocultural transition resp. with over- and malnutrition, low physical activity and social stress as a common soil.

  15. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

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

    2015-01-01

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

  16. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    A.M.S. Costa et al.

    2017-07-01

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

  17. Carglumic acid enhances rapid ammonia detoxification in classical organic acidurias with a favourable risk-benefit profile : a retrospective observational study

    NARCIS (Netherlands)

    Valayannopoulos, Vassili; Baruteau, Julien; Delgado, Maria Bueno; Cano, Aline; Couce, Maria L; Del Toro, Mireia; Donati, Maria Alice; Garcia-Cazorla, Angeles; Gil-Ortega, David; Gomez-de Quero, Pedro; Guffon, Nathalie; Hofstede, Floris C; Kalkan-Ucar, Sema; Coker, Mahmut; Lama-More, Rosa; Martinez-Pardo Casanova, Mercedes; Molina, Agustin; Pichard, Samia; Papadia, Francesco; Rosello, Patricia; Plisson, Celine; Le Mouhaer, Jeannie; Chakrapani, Anupam

    2016-01-01

    BACKGROUND: Isovaleric aciduria (IVA), propionic aciduria (PA) and methylmalonic aciduria (MMA) are inherited organic acidurias (OAs) in which impaired organic acid metabolism induces hyperammonaemia arising partly from secondary deficiency of N-acetylglutamate (NAG) synthase. Rapid reduction in

  18. SIRT1 and energy metabolism.

    Science.gov (United States)

    Li, Xiaoling

    2013-01-01

    Sirtuin 1 (SIRT1) is the most conserved mammalian NAD(+)-dependent protein deacetylase that has emerged as a key metabolic sensor in various metabolic tissues. In response to different environmental stimuli, SIRT1 directly links the cellular metabolic status to the chromatin structure and the regulation of gene expression, thereby modulating a variety of cellular processes such as energy metabolism and stress response. Recent studies have shown that SIRT1 controls both glucose and lipid metabolism in the liver, promotes fat mobilization and stimulates brown remodeling of the white fat in white adipose tissue, controls insulin secretion in the pancreas, senses nutrient availability in the hypothalamus, influences obesity-induced inflammation in macrophages, and modulates the activity of circadian clock in metabolic tissues. This review focuses on the role of SIRT1 in regulating energy metabolism at different metabolic tissues.

  19. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

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

  20. Can you boost your metabolism?

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000893.htm Can you boost your metabolism? To use the sharing ... boosting metabolism than tactics that work. Some myths can backfire. If you think you are burning more ...

  1. [The Idiopathic Parkinson's disease: A metabolic disease?].

    Science.gov (United States)

    Rieu, I; Boirie, Y; Morio, B; Derost, P; Ulla, M; Marques, A; Debilly, B; Bannier, S; Durif, F

    2010-10-01

    Parkinson's disease is a neurodegenerative disorder clinically characterized by motor impairments (tremor, bradykinesia, rigidity and postural instability) associated or not with non-motor complications (cognitive disorders, dysautonomia). Most of patients loose weight during evolution of their disease. Dysregulations of hypothalamus, which is considered as the regulatory center of satiety and energy metabolism, could play a major role in this phenomenon. Deep brain stimulation of the subthalamic nucleus (NST) is an effective method to treat patients with advanced Parkinson's disease providing marked improvement of motor impairments. This chirurgical procedure also induces a rapid and strong body weight gain and sometimes obesity. This post-operative weight gain, which exceeds largely weight lost recorded in non-operated patient, could be responsible of metabolic disorders (such as diabetes) and cardiovascular diseases. This review describes body weight variations generated by Parkinson' disease and deep brain stimulation of the NST, and focuses on metabolic disorders capable to explain them. Finally, this review emphasizes on the importance of an adequate nutritional follow up care for parkinsonian patient. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  2. Pharmacokinetics and metabolism of rosaramicin in humans.

    Science.gov (United States)

    Lin, C C; Chung, M; Gural, R; Schuessler, D; Kim, H K; Radwanski, E; Marco, A; DiGiore, C; Symchowicz, S

    1984-01-01

    The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t1/2S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (infinity) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces. PMID:6517543

  3. Comparative metabolism of 2-nitropropane in rats and chimpanzees

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, W.F.; Coulston, F.; Korte, F.

    1983-01-01

    To obtain more information about the metabolic fate of 2-nitropropane (2-NP) in rats and to study the relevance of the findings for man, the authors investigated the metabolism of 2-NP in rats and chimpanzees. The results of this study show that 2-NP is eliminated largely by exhalation, while excretion in urine and feces are only minor pathways. Carbon dioxide, acetone and isopropanol are the major metabolites. Preliminary chromatographic results suggest different conjugates formed by rats and chimpanzees. 2-NP has little potential for accumulation; the lipid tissues, which can absorb it to considerable concentrations, are rapidly depleted.

  4. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

    Directory of Open Access Journals (Sweden)

    Yilin Cao

    Full Text Available T lymphocytes (T cells undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

  5. Rapid scenarios and observed intensities

    OpenAIRE

    Franco Pettenati; Livio Sirovich

    2012-01-01

    After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS) and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology), which is reproduced for Figure 1. T...

  6. Rapid synthesis of beta zeolites

    Science.gov (United States)

    Fan, Wei; Chang, Chun -Chih; Dornath, Paul; Wang, Zhuopeng

    2015-08-18

    The invention provides methods for rapidly synthesizing heteroatom containing zeolites including Sn-Beta, Si-Beta, Ti-Beta, Zr-Beta and Fe-Beta. The methods for synthesizing heteroatom zeolites include using well-crystalline zeolite crystals as seeds and using a fluoride-free, caustic medium in a seeded dry-gel conversion method. The Beta zeolite catalysts made by the methods of the invention catalyze both isomerization and dehydration reactions.

  7. Sleep and Metabolism: An Overview

    OpenAIRE

    Sunil Sharma; Mani Kavuru

    2010-01-01

    Sleep and its disorders are increasingly becoming important in our sleep deprived society. Sleep is intricately connected to various hormonal and metabolic processes in the body and is important in maintaining metabolic homeostasis. Research shows that sleep deprivation and sleep disorders may have profound metabolic and cardiovascular implications. Sleep deprivation, sleep disordered breathing, and circadian misalignment are believed to cause metabolic dysregulation through myriad pathways i...

  8. Metabolic Syndrome, Androgens, and Hypertension

    OpenAIRE

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

    2011-01-01

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

  9. Rapid scenarios and observed intensities

    Directory of Open Access Journals (Sweden)

    Franco Pettenati

    2012-10-01

    Full Text Available After a destructive earthquake, national Governments need to know the approximate amount of damage, the number of casualties, and the financial losses as soon as possible. Rapid scenarios are also used to inform the general public; see the widely used Shakemap package [Wald et al. 1999, 2006] of the US Geological Survey (USGS and the one modified by the Istituto Nazionale di Geofisica e Vulcanologia (INGV; National Institute of Geophysics and Volcanology, which is reproduced for Figure 1. The general matter of the use of intensities in damage scenarios was discussed in a special session at the 2008 Annual Meeting of the Seismological Society of America (http://www.seismosoc.org/meetings/2008/specialsessions.html, and was also discussed in the NIS-1 session of the European Congress in Moscow, in August 2012 (http://www.esc2012-moscow.org/esc_thematicareas.html. The purposes of the present report are to: (i compare different types of intensities; (ii check two rapid scenarios of intensity; and (iii understand whether the KF formula [Sirovich 1996, Sirovich et al. 2009] can be used as a new 'attenuation' relationship to improve rapid scenarios. […

  10. Rapid diagnosis of mycobacterial infections

    Directory of Open Access Journals (Sweden)

    Michel Drancourt

    2015-01-01

    Full Text Available While pulmonary tuberculosis (PTB remains an important public health issue worldwide, there is an emerging interest in non-tuberculous mycobacteria (NTM which is responsible for opportunistic infections of the respiratory tract as well as other anatomical sites in both developed and developing countries. In this context the one goal of the clinical mycobacteriology laboratories is to provide physicians with an accurate identification of the mycobacterium as rapidly as possible. During the last ten years, several lines of laboratory tools have been developed in order to speed the isolation and identification of mycobacteria from clinical specimens. Chiefly, the composition of culture medium was renewed along with the protocol of incubation in order to recover Mycobacterium tuberculosis (MTB micro-colonies as soon as 48 h after the inoculation of the specimen. MALDI-TOF rapid identification is clearly the tool to be implemented in the laboratory for the rapid identification of the micro-colonies. Also, molecular tools and genomics are necessary in order to depict new mycobacteria species, including those of the Mycobacterium abscessus complex and the Mycobacterium avium complex. All these tools and their connections will be presented during this conference.

  11. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

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

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

    DEFF Research Database (Denmark)

    Patil, Kiran Raosaheb; Nielsen, Jens

    2005-01-01

    therefore developed an algorithm that is based on hypothesis-driven data analysis to uncover the transcriptional regulatory architecture of metabolic networks. By using information on the metabolic network topology from genome-scale metabolic reconstruction, we show that it is possible to reveal patterns...... or environmental perturbations. We find that cells respond to perturbations by changing the expression pattern of several genes involved in the specific part(s) of the metabolism in which a perturbation is introduced. These changes then are propagated through the metabolic network because of the highly connected......Cellular response to genetic and environmental perturbations is often reflected and/or mediated through changes in the metabolism, because the latter plays a key role in providing Gibbs free energy and precursors for biosynthesis. Such metabolic changes are often exerted through transcriptional...

  13. Assessing Cardiac Metabolism

    Science.gov (United States)

    Taegtmeyer, Heinrich; Young, Martin E.; Lopaschuk, Gary D.; Abel, E. Dale; Brunengraber, Henri; Darley-Usmar, Victor; Des Rosiers, Christine; Gerszten, Robert; Glatz, Jan F.; Griffin, Julian L.; Gropler, Robert J.; Holzhuetter, Hermann-Georg; Kizer, Jorge R.; Lewandowski, E. Douglas; Malloy, Craig R.; Neubauer, Stefan; Peterson, Linda R.; Portman, Michael A.; Recchia, Fabio A.; Van Eyk, Jennifer E.; Wang, Thomas J.

    2016-01-01

    In a complex system of interrelated reactions, the heart converts chemical energy to mechanical energy. Energy transfer is achieved through coordinated activation of enzymes, ion channels, and contractile elements, as well as structural and membrane proteins. The heart’s needs for energy are difficult to overestimate. At a time when the cardiovascular research community is discovering a plethora of new molecular methods to assess cardiac metabolism, the methods remain scattered in the literature. The present statement on “Assessing Cardiac Metabolism” seeks to provide a collective and curated resource on methods and models used to investigate established and emerging aspects of cardiac metabolism. Some of those methods are refinements of classic biochemical tools, whereas most others are recent additions from the powerful tools of molecular biology. The aim of this statement is to be useful to many and to do justice to a dynamic field of great complexity. PMID:27012580

  14. [Microbiota and metabolic syndrome].

    Science.gov (United States)

    Altuntaş, Yüksel; Batman, Adnan

    2017-04-01

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

  15. [Sleep and metabolic disorders].

    Science.gov (United States)

    Micić, Dragan D; Šumarac-Dumanović, Mirjana; Šušić, Veselinka; Pejković, Danica; Polovina, Snežana

    2011-01-01

    In the 20th century, the prevalence of obesity has been increasing worldwide at an alarming rate and it is followed by an increase in the diseases for which obesity is major risk factor, like metabolic syndrome, diabetes type 2 and hypertension. These facts has been resulting in explosion of investigation devoted to explanation of pathogenetic mechanisms of this serious social and medical problems with the main idea to find adequate way of prevention as well as of treatment. Together with the observed epidemy of obesity and Type 2 diabetes, it was found parallel tendency for sleep curtailment, that was confirmed in numerous epidemiological studies, that coincide with its beginning and progress with this two epidemies. This facts lead to investigations with the idea to try to explaine possible mechanisms of the association between sleep curtailment, obesity, type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. Having in mind that insulin resistance is one of the fundamental pathogenetic mechanism in these disorders, numerous studies were done with the aim to explain association between sleep curtailment and insulin resistance in obesity, Type 2 diabetes, metabolic syndrome and polycistic ovary syndrome. It was demonstrated that sleep curtailment may affect energy homeostasis of human organism with the effects on body weight increase through three different ways: appetite increase, prolongation of time for food intake and through decrease of energy expenditure. There are several postulated mechanism for the effect of sleep curtailment on development of insulin resistance as well as for predisposition for Type 2 diabetes. Among possible mechanism are included: increase of sympathetic neuronal acitvity, decreased cerebral utilisation of glucose, increase in evening cortisol values, growth hormone increase and disorder of neuroendocrine control of appetite which increases the risk for getting the body weight. Metabolic systems are of particular interest in

  16. Metabolic syndrome and anesthesia

    OpenAIRE

    Gómez-Alegría Claudio Jaime; Gómez-Camargo Doris; Palomino-Romero Roberto; Pomares-Estrada José

    2010-01-01

    Metabolic Syndrome (MS) represents a constellation of risk factors associated with an increased incidence of cardiovascular disease and progression to diabetes mellitus. Insulin resistance, a state of reduced biological response to physiological insulin concentrations, is a key component of this syndrome appears to result from a primary defect in skeletal muscle glucose transporter. The acute disease and the perioperative period are characterized by a state of insulin resistance that manifest...

  17. Scaling metabolic rate fluctuations

    OpenAIRE

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

    2007-01-01

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

  18. Paracetamol metabolism in man

    OpenAIRE

    Adriaenssens, P.I.

    1980-01-01

    The absorption, metabolism and elimination of paracetamol was investigated in healthy subjects after therapeutic doses and also in patients with paracetamol overdosage, some of whom developed liver damage. Paracetamol disposition was also studied in relation to treatment with N-acetylcysteine (NAG),cysteamine and methionine, which were used to prevent paracetamol hepatotoxicity. Sensitive, specific and reproducible analytical methods were developed for the estimation of para...

  19. Proton Transfer Reaction Mass Spectrometry detects rapid changes in volatile metabolite emission by Mycobacterium smegmatis after the addition of specific antimicrobial agents

    NARCIS (Netherlands)

    Crespo, E.; Cristescu, S. M.; de Ronde, H.; Kuijper, S.; Kolk, A.H.J.; Anthony, R.M.; Harren, F. J. M.

    2011-01-01

    The metabolic activity of plants, animals or microbes can be monitored by gas headspace analysis. This can be achieved using Proton Transfer Reaction Mass Spectrometry (PTR-MS), a highly sensitive detection method for trace gas analysis. PTR-MS is rapid and can detect metabolic responses on-line as

  20. Metabolic neuropathies and myopathies.

    Science.gov (United States)

    D'Amico, Adele; Bertini, Enrico

    2013-01-01

    Inborn errors of metabolism may impact on muscle and peripheral nerve. Abnormalities involve mitochondria and other subcellular organelles such as peroxisomes and lysosomes related to the turnover and recycling of cellular compartments. Treatable causes are β-oxidation defects producing progressive neuropathy; pyruvate dehydrogenase deficiency, porphyria, or vitamin B12 deficiency causing recurrent episodes of neuropathy or acute motor deficit mimicking Guillain-Barré syndrome. On the other hand, lysosomal (mucopolysaccharidosis, Gaucher and Fabry diseases), mitochondriopathic (mitochondrial or nuclear mutations or mDNA depletion), peroxisomal (adrenomyeloneuropathy, Refsum disease, sterol carrier protein-2 deficiency, cerebrotendinous xanthomatosis, α-methylacyl racemase deficiency) diseases are multisystemic disorders involving also the heart, liver, brain, retina, and kidney. Pathophysiology of most metabolic myopathies is related to the impairment of energy production or to abnormal production of reactive oxygen species (ROS). Main symptoms are exercise intolerance with myalgias, cramps and recurrent myoglobinuria or limb weakness associated with elevation of serum creatine kinase. Carnitine palmitoyl transferase deficiency, followed by acid maltase deficiency, and lipin deficiency, are the most common cause of isolated rhabdomyolysis. Metabolic myopathies are frequently associated to extra-neuromuscular disorders particularly involving the heart, liver, brain, retina, skin, and kidney. Copyright © 2013 Elsevier B.V. All rights reserved.

  1. Analytics for metabolic engineering

    Directory of Open Access Journals (Sweden)

    Christopher J Petzold

    2015-09-01

    Full Text Available Realizing the promise of metabolic engineering has been slowed by challenges related to moving beyond proof-of-concept examples to robust and economically viable systems. Key to advancing metabolic engineering beyond trial-and-error research is access to parts with well-defined performance metrics that can be readily applied in vastly different contexts with predictable effects. As the field now stands, research depends greatly on analytical tools that assay target molecules, transcripts, proteins, and metabolites across different hosts and pathways. Screening technologies yield specific information for many thousands of strain variants while deep omics analysis provide a systems-level view of the cell factory. Efforts focused on a combination of these analyses yield quantitative information of dynamic processes between parts and the host chassis that drive the next engineering steps. Overall, the data generated from these types of assays aid better decision-making at the design and strain construction stages to speed progress in metabolic engineering research.

  2. Blood Test: Comprehensive Metabolic Panel (CMP)

    Science.gov (United States)

    ... Voice in Health Care Decisions Blood Test: Comprehensive Metabolic Panel (CMP) KidsHealth > For Parents > Blood Test: Comprehensive Metabolic Panel ( ... or kidneys) is working. What Is a Comprehensive Metabolic Panel (CMP)? The comprehensive metabolic panel (CMP) is a ...

  3. Maternal cardiac metabolism in pregnancy

    Science.gov (United States)

    Liu, Laura X.; Arany, Zolt

    2014-01-01

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

  4. Different adipose tissue depots: Metabolic implications and effects of surgical removal.

    Science.gov (United States)

    Marcadenti, Aline; de Abreu-Silva, Erlon Oliveira

    2015-11-01

    Increased adiposity has been associated to worse metabolic profile, cardiovascular disease, and mortality. There are two main adipose tissue depots in the body, subcutaneous and visceral adipose tissue, which differ in anatomical location. A large body of evidence has shown the metabolic activity of adipose tissue; lipectomy and/or liposuction therefore appear to be alternatives for improving metabolic profile through rapid loss of adipose tissue. However, surgical removal of adipose tissue may be detrimental for metabolism, because subcutaneous adipose tissue has not been associated to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. In addition, animal studies have shown a compensatory growth of adipose tissue in response to lipectomy. This review summarizes the implications of obesity-induced metabolic dysfunction, its relationship with the different adipose tissue depots, and the effects of lipectomy on cardiometabolic risk factors. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  5. Metabolism of /sup 3/H-dopamine by human chorioamnion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Phillippe, M.; Niloff, J.M.

    1982-08-01

    Previous investigation has demonstrated biologically significant concentrations of catecholamines in amniotic fluid, which increase with gestation. The half life, metabolic clearance rate, and metabolic fate of these hormones in the amniotic compartment are yet to be established. This study was undertaken to demonstrate the ability of human chorioamnion to metabolize dopamine in vitro. Incubation experiments demonstrated that /sup 3/H-dopamine is rapidly metabolized to dihydroxyphenylacetic acid, 3-methoxy, 4-hydroxyphenylacetic acid, and 3-methoxy, 4-hydroxyphenylethanol-all products of monoamine oxidase. No significant 3-methoxytyramine, a catechol-o-methyltransferase product, was observed. Incubation experiments with pargyline, a monoamine oxidase inhibitor, resulted in significant reduction in /sup 3/H-dopamine metabolism. Catecholamines and their interaction with prostaglandin synthesis have been theorized to be a fetal signal for the initiation of parturition. The ability of chorioamnion to metabolize catecholamine could, therefore, provide another control mechanism by which fetal catecholamines are modulated.

  6. [Neuronal communication and synaptic metabolism in childhood epilepsy].

    Science.gov (United States)

    García-Cazorla, Àngels; Cortès-Saladelafont, Elisenda; Duarte, Sofia

    2015-03-01

    Basic neuroscience and neurometabolism are providing a rapidly increasing amount of knowledge on paediatric epilepsy and, more specifically, on the mechanisms involved in synaptic communication. There is, however, a mismatch between these advances and a vision that integrates them in a global way, in clinical and therapeutic practice. To offer an integrative view of the different molecular and metabolic mechanisms that are known and postulated in paediatric epilepsy, and to suggest concepts such as 'synaptic metabolism' and 'synaptic phenotypes' as useful tools for developing this approach. We also review the most notable studies that attempt to explain the essential characteristics of synaptic communication in the developing brain by means of different molecules, essentially synaptic proteins, ion channels (chlorine, sodium and potassium co-transporters), and pre- and post-synaptic compartmentalisation, as well as the main players in metabolism (neurotransmitters, energy metabolism, growth factors and lipids). This combination of biological mechanisms has led to examples of 'synaptic phenotypes' being suggested in two specific cases of genetic (SCN1A) and metabolic epilepsy (epilepsy with response to pyridoxine). A holistic perspective, which takes into account the diversity of elements that are related and which take place at certain times in neurodevelopment, can help to define phenotypes, channels for synaptic metabolism and brain connectivity, which facilitate not only the understanding of the pathophysiology, but also new therapeutic approaches in paediatric epilepsy.

  7. Metabolism of an Insecticide Fenitrothion by Cunninghamella elegans ATCC36112.

    Science.gov (United States)

    Zhu, Yong-Zhe; Fu, Min; Jeong, In-Hong; Kim, Jeong-Han; Zhang, Chuan-Jie

    2017-11-16

    In this study, the detailed metabolic pathways of fenitrothion (FNT), an organophosphorus insecticide by Cunninghamella elegans was investigated. Approximately 81% of FNT was degraded within 5 d after treatment with concomitant accumulation of four metabolites (M1-M4). The four metabolites were separated by HPLC and their structures were identified by MS and/or NMR. M3 is confirmed to be an initial precursor of others and identified as fenitrothion-oxon (FNTO). On the basis of their metabolic profiling, the possible metabolic pathways involved in phase I and II metabolism of FNT by C. elegans was proposed. We also found C. elegans was able to efficiently and rapidly degrade other organophosphorus pesticides (OPs). Thus, these results will provide an insight into understanding of the fungal degradation of FNT and the potential application for bioremediation of OPs. Furthermore, the ability of C. elegans to mimic mammalian metabolism would help us elucidate the metabolic fates of organic compounds occurring in mammalian liver cells and evaluate their toxicity and potential adverse effects.

  8. Metabolism of methoxychlor by Cunninghamella elegans ATCC36112.

    Science.gov (United States)

    Keum, Young Soo; Lee, Youn Hyung; Kim, Jeong-Han

    2009-09-09

    Methoxychlor is considered as pro-estrogen, while some of its metabolites are more potent endocrine disruptors than the parent insecticide. Major activation of methoxychlor is through cytochrome P450-catalyzed demethylation to bisphenol A-like metabolites. Cunninghamella elegans is a well-known fungal species with its strong resemblance of the xenobiotic metabolism of the mammalian system. In this study, the metabolism of methoxychlor was investigated with the corresponding organism. Methoxychlor was rapidly transformed to approximately 11 metabolites in phase I metabolism, including oxidation, hydroxylation, and dechlorination. Concentrations of phase I metabolites reached a maximum at 4-6 days and gradually decreased until the end of the experiments. Most metabolites from the phase I reaction were further transformed to sugar conjugates. Approximately 11 or more glucose conjugates were found in culture supernatants and gradually increased, while no glucuronides were observed throughout the experiments. Piperonyl butoxide and chlorpyrifos strongly inhibit the degradation of methoxychlor and concomitant accumulation of metabolites, indicating cytochrome P450 mediated metabolism. Little or no glycosides were detected in chlorpyrifos- and piperonyl butoxide-treated cultures. From the results, Cunninghamella elegans has shown strong similarities of the phase I metabolism of methoxychlor, while the conjugation reaction is different from those of animal metabolism.

  9. Disturbances of lipoprotein metabolism in metabolic syndro

    Directory of Open Access Journals (Sweden)

    Marta Czyżewska

    2010-01-01

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

  10. Tumor Metabolism of Malignant Gliomas

    Energy Technology Data Exchange (ETDEWEB)

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

    2013-11-08

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

  11. Sleep slow-wave activity regulates cerebral glycolytic metabolism.

    Science.gov (United States)

    Wisor, Jonathan P; Rempe, Michael J; Schmidt, Michelle A; Moore, Michele E; Clegern, William C

    2013-08-01

    Non-rapid eye movement sleep (NREMS) onset is characterized by a reduction in cerebral metabolism and an increase in slow waves, 1-4-Hz oscillations between relatively depolarized and hyperpolarized states in the cerebral cortex. The metabolic consequences of slow-wave activity (SWA) at the cellular level remain uncertain. We sought to determine whether SWA modulates the rate of glycolysis within the cerebral cortex. The real-time measurement of lactate concentration in the mouse cerebral cortex demonstrates that it increases during enforced wakefulness. In spontaneous sleep/wake cycles, lactate concentration builds during wakefulness and rapid eye movement sleep and declines during NREMS. The rate at which lactate concentration declines during NREMS is proportional to the magnitude of electroencephalographic (EEG) activity at frequencies of cerebral SWA promotes a decline in the rate of glycolysis in the cerebral cortex. These results demonstrate a cellular energetic function for sleep SWA, which may contribute to its restorative effects on brain function.

  12. Rapid synthesis of acetylcholine receptors at neuromuscular junctions.

    Science.gov (United States)

    Ramsay, D A; Drachman, D B; Pestronk, A

    1988-10-11

    The rate of acetylcholine receptor (AChR) degradation in mature, innervated mammalian neuromuscular junctions has recently been shown to be biphasic; up to 20% are rapidly turned over (RTOs; half life less than 1 day) whereas the remainder are lost more slowly ('stable' AChRs; half life 10-12 days). In order to maintain normal junctional receptor density, synthesis and insertion of AChRs should presumably be sufficiently rapid to replace both the RTOs and the stable receptors. We have tested this prediction by blocking pre-existing AChRs in the mouse sternomastoid muscle with alpha-bungarotoxin (alpha-BuTx), and monitoring the subsequent appearance of 'new' junctional AChRs at intervals of 3 h to 20 days by labeling them with 125I-alpha-BuTx. The results show that new receptors were initially inserted rapidly (16% at 24 h and 28% at 48 h). The rate of increase of 'new' 125I-alpha-BuTx binding sites gradually slowed down during the remainder of the time period studied. Control observations excluded possible artifacts of the experimental procedure including incomplete blockade of AChRs, dissociation of toxin-receptor complexes, or experimentally induced alteration of receptor synthesis. The present demonstration of rapid synthesis and incorporation of AChRs at innervated neuromuscular junctions provides support for the concept of a subpopulation of rapidly turned over AChRs. The RTOs may serve as precursors for the larger population of stable receptors and have an important role in the metabolism of the neuromuscular synapse.

  13. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Melcher, Cynthia P.

    2015-08-28

    The Wyoming Basin Rapid Ecoregional Assessment was conducted in partnership with the Bureau of Land Management (BLM). The overall goals of the BLM Rapid Ecoregional Assessments (REAs) are to identify important ecosystems and wildlife habitats at broad spatial scales; identify where these resources are at risk from Change Agents, including development, wildfire, invasive species, disease and climate change; quantify cumulative effects of anthropogenic stressors; and assess current levels of risk to ecological resources across a range of spatial scales and jurisdictional boundaries by assessing all lands within an ecoregion. There are several components of the REAs. Management Questions, developed by the BLM and stakeholders for the ecoregion, identify the regionally significant information needed for addressing land-management responsibilities. Conservation Elements represent regionally significant species and ecological communities that are of management concern. Change Agents that currently affect or are likely to affect the condition of species and communities in the future are identified and assessed. REAs also identify areas that have high conservation potential that are referred to as “large intact areas.” At the ecoregion level, the ecological value of large intact areas is based on the assumption that because these areas have not been greatly altered by human activities (such as development), they are more likely to contain a variety of plant and animal communities and to be resilient and resistant to changes resulting from natural disturbances such as fire, insect outbreaks, and disease.

  14. Rapid self-healing hydrogels

    Science.gov (United States)

    Phadke, Ameya; Zhang, Chao; Arman, Bedri; Hsu, Cheng-Chih; Mashelkar, Raghunath A.; Lele, Ashish K.; Tauber, Michael J.; Arya, Gaurav; Varghese, Shyni

    2012-01-01

    Synthetic materials that are capable of autonomous healing upon damage are being developed at a rapid pace because of their many potential applications. Despite these advancements, achieving self-healing in permanently cross-linked hydrogels has remained elusive because of the presence of water and irreversible cross-links. Here, we demonstrate that permanently cross-linked hydrogels can be engineered to exhibit self-healing in an aqueous environment. We achieve this feature by arming the hydrogel network with flexible-pendant side chains carrying an optimal balance of hydrophilic and hydrophobic moieties that allows the side chains to mediate hydrogen bonds across the hydrogel interfaces with minimal steric hindrance and hydrophobic collapse. The self-healing reported here is rapid, occurring within seconds of the insertion of a crack into the hydrogel or juxtaposition of two separate hydrogel pieces. The healing is reversible and can be switched on and off via changes in pH, allowing external control over the healing process. Moreover, the hydrogels can sustain multiple cycles of healing and separation without compromising their mechanical properties and healing kinetics. Beyond revealing how secondary interactions could be harnessed to introduce new functions to chemically cross-linked polymeric systems, we also demonstrate various potential applications of such easy-to-synthesize, smart, self-healing hydrogels. PMID:22392977

  15. Rapid generalization in phonotactic learning

    Directory of Open Access Journals (Sweden)

    Tal Linzen

    2017-10-01

    Full Text Available Speakers judge novel strings to be better potential words of their language if those strings consist of sound sequences that are attested in the language. These intuitions are often generalized to new sequences that share some properties with attested ones: Participants exposed to an artificial language where all words start with the voiced stops [b] and [d] will prefer words that start with other voiced stops (e.g., [g] to words that start with vowels or nasals. The current study tracks the evolution of generalization across sounds during the early stages of artificial language learning. In Experiments 1 and 2, participants received varying amounts of exposure to an artificial language. Learners rapidly generalized to new sounds: In fact, following short exposure to the language, attested patterns were not distinguished from unattested patterns that were similar in their phonological properties to the attested ones. Following additional exposure, participants showed an increasing preference for attested sounds, alongside sustained generalization to unattested ones. Finally, Experiment 3 tested whether participants can rapidly generalize to new sounds based on a single type of sound. We discuss the implications of our results for computational models of phonotactic learning.

  16. Rapid ISS Power Availability Simulator

    Science.gov (United States)

    Downing, Nicholas

    2011-01-01

    The ISS (International Space Station) Power Resource Officers (PROs) needed a tool to automate the calculation of thousands of ISS power availability simulations used to generate power constraint matrices. Each matrix contains 864 cells, and each cell represents a single power simulation that must be run. The tools available to the flight controllers were very operator intensive and not conducive to rapidly running the thousands of simulations necessary to generate the power constraint data. SOLAR is a Java-based tool that leverages commercial-off-the-shelf software (Satellite Toolkit) and an existing in-house ISS EPS model (SPEED) to rapidly perform thousands of power availability simulations. SOLAR has a very modular architecture and consists of a series of plug-ins that are loosely coupled. The modular architecture of the software allows for the easy replacement of the ISS power system model simulator, re-use of the Satellite Toolkit integration code, and separation of the user interface from the core logic. Satellite Toolkit (STK) is used to generate ISS eclipse and insulation times, solar beta angle, position of the solar arrays over time, and the amount of shadowing on the solar arrays, which is then provided to SPEED to calculate power generation forecasts. The power planning turn-around time is reduced from three months to two weeks (83-percent decrease) using SOLAR, and the amount of PRO power planning support effort is reduced by an estimated 30 percent.

  17. KEPLER RAPIDLY ROTATING GIANT STARS

    Energy Technology Data Exchange (ETDEWEB)

    Costa, A. D.; Martins, B. L. Canto; Bravo, J. P.; Paz-Chinchón, F.; Chagas, M. L. das; Leão, I. C.; Oliveira, G. Pereira de; Silva, R. Rodrigues da; Roque, S.; Oliveira, L. L. A. de; Silva, D. Freire da; De Medeiros, J. R., E-mail: renan@dfte.ufrn.br [Departamento de Física Teórica e Experimental, Universidade Federal do Rio Grande do Norte, Campus Universitário, Natal RN (Brazil)

    2015-07-10

    Rapidly rotating giant stars are relatively rare and may represent important stages of stellar evolution, resulting from stellar coalescence of close binary systems or accretion of substellar companions by their hosting stars. In the present Letter, we report 17 giant stars observed in the scope of the Kepler space mission exhibiting rapid rotation behavior. For the first time, the abnormal rotational behavior for this puzzling family of stars is revealed by direct measurements of rotation, namely from photometric rotation period, exhibiting a very short rotation period with values ranging from 13 to 55 days. This finding points to remarkable surface rotation rates, up to 18 times the rotation of the Sun. These giants are combined with six others recently listed in the literature for mid-infrared (IR) diagnostics based on Wide-field Infrared Survey Explorer information, from which a trend for an IR excess is revealed for at least one-half of the stars, but at a level far lower than the dust excess emission shown by planet-bearing main-sequence stars.

  18. Rapid starting methanol reactor system

    Science.gov (United States)

    Chludzinski, Paul J.; Dantowitz, Philip; McElroy, James F.

    1984-01-01

    The invention relates to a methanol-to-hydrogen cracking reactor for use with a fuel cell vehicular power plant. The system is particularly designed for rapid start-up of the catalytic methanol cracking reactor after an extended shut-down period, i.e., after the vehicular fuel cell power plant has been inoperative overnight. Rapid system start-up is accomplished by a combination of direct and indirect heating of the cracking catalyst. Initially, liquid methanol is burned with a stoichiometric or slightly lean air mixture in the combustion chamber of the reactor assembly. The hot combustion gas travels down a flue gas chamber in heat exchange relationship with the catalytic cracking chamber transferring heat across the catalyst chamber wall to heat the catalyst indirectly. The combustion gas is then diverted back through the catalyst bed to heat the catalyst pellets directly. When the cracking reactor temperature reaches operating temperature, methanol combustion is stopped and a hot gas valve is switched to route the flue gas overboard, with methanol being fed directly to the catalytic cracking reactor. Thereafter, the burner operates on excess hydrogen from the fuel cells.

  19. Rapidly Developing Toxic Epidermal Necrolysis

    Directory of Open Access Journals (Sweden)

    Viktoria Oline Barrios Poulsen

    2013-01-01

    Full Text Available Severe cutaneous reactions with potentially fatal outcomes can have many different causes. The Stevens-Johnson syndrome (SJS and toxic epidermal necrolysis (TEN are rare. They are characterized by a low incidence but high mortality, and drugs are most commonly implicated. Urgent active therapy is required. Prompt recognition and withdrawal of suspect drug and rapid intervention can result in favourable outcome. No further international guidelines for treatment exist, and much of the treatment relies on old or experimental concepts with no scientific evidence. We report on a 54-year-old man experiencing rapidly developing drug-induced severe TEN and presented multiorgan failure involving the respiratory and circulatory system, coagulopathy, and renal insufficiency. Detachment counted 30% of total body surface area (TBSA. SCORTEN = 5, indicating a mortality rate >90%. The patient was sedated and mechanically ventilated, supported with fluids and inotropes to maintain a stable circulation. Component therapy was guided by thromboelastography (TEG. The patient received plasmapheresis, and shock reversal treatment was initiated. He was transferred to a specialized intensive care burn unit within 24 hours from admittance. The initial care was continued, and hemodialysis was started. Pulmonary, circulatory, and renal sequelae resolved with intensive care, and re-epithelialization progressed slowly. The patient was discharged home on hospital day 19.

  20. Plasticity of specialized metabolism as mediated by dynamic metabolons

    DEFF Research Database (Denmark)

    Laursen, Tomas; Møller, Birger Lindberg; Bassard, Jean-Étienne André

    2015-01-01

    to organize in multienzyme clusters termed metabolons. Dynamic assembly and disassembly enable the plant to rapidly switch the product profile and thereby prioritize its resources. The lifetime of metabolons is largely unknown mainly due to technological limitations. This review focuses on the factors...... that facilitate and stimulate the dynamic assembly of metabolons, including microenvironments, noncatalytic proteins, and allosteric regulation. Understanding how plants organize carbon fluxes within their metabolic grids would enable targeted bioengineering of high-value specialized metabolites....

  1. Metabolic Signature of Antipsychotics used in the Treatment of Autism

    Science.gov (United States)

    2016-12-01

    human adipocytes. Methods Rat Model: Adult female Sprague-Dawley rats under normal diet were given cookie dough mixed with Olanzapine or... cookie dough mixed with vehicle, Olan or Zip at 4 mg/kg twice/day for 7 days. Fig 1 shows rapid increases in food intake and body weight, with Olan...peripheral fuel utilization to lipids, impairing metabolic flexibility in rodents. Schizophr.Bull. 38, 153-166 72. Minet-Ringuet,J. et al. (2007) Alterations

  2. Studies on growth, nitrogen and energy metabolism in rats

    DEFF Research Database (Denmark)

    Thorbek, G; Chwalibog, André; Eggum, B O

    1982-01-01

    Feed intake, growth, nitrogen retention and energy metabolism were measured in 12 male Wistar rats fed ad lib. for 14 weeks with non-purified diets. The feed intake increased rapidly in 4 weeks time from 16 g/d to 25 g/d, and then it was constant in the following 10 weeks. In relation to metabolic...... = 0.968. The nitrogen retention increased from 200 to 300 mg N/d in period III when the rats 60 days old, and then it decreased in the following 10 weeks to about 100 mg N/d. In relation to metabolic live weight nitrogen retention is assumed to be near maximum level, decreasing from 1100 to 200 mg N...

  3. Metabolic engineering of yeast for production of fuels and chemicals.

    Science.gov (United States)

    Nielsen, Jens; Larsson, Christer; van Maris, Antonius; Pronk, Jack

    2013-06-01

    Microbial production of fuels and chemicals from renewable carbohydrate feedstocks offers sustainable and economically attractive alternatives to their petroleum-based production. The yeast Saccharomyces cerevisiae offers many advantages as a platform cell factory for such applications. Already applied on a huge scale for bioethanol production, this yeast is easy to genetically engineer, its physiology, metabolism and genetics have been intensively studied and its robustness enables it to handle harsh industrial conditions. Introduction of novel pathways and optimization of its native cellular processes by metabolic engineering are rapidly expanding its range of cell-factory applications. Here we review recent scientific progress in metabolic engineering of S. cerevisiae for the production of bioethanol, advanced biofuels, and chemicals. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Dynamics of ammonia metabolism in man

    Energy Technology Data Exchange (ETDEWEB)

    Lockwood, J.S.; McDonald, J.M.; Reiman, R.E.; Gelbard, A.S.; Laughlin, J.S.; Duffy, T.E.; Plum, F.

    1977-01-01

    The cyclotron-produced radionuclide /sup 13/N, T/sub 1/2/ 10 min, was used to label NH/sub 3/ and study its metabolism in 5 normal subjects and 17 with liver disease, including 5 with portacaval shunts, and 11 with encephalopathy (HE). The arterial NH/sub 3/ levels were 100 +- 8 ..mu..M in the non-HE subjects and 149 +- 18 ..mu..M in those with HE, (P < 0.01). After an iv pulse of 10 mCi of carrier-free /sup 13/NH/sub 4/Cl, the rate of NH/sub 3/ clearance from the vascular compartment was a function of its arterial concentration: ..mu..mol/min = 4.71 (NH/sub 3/)/sub a/ + 3.76 (r = +0.85, P < 0.005). In all subjects, brain activity increased rapidly when the specific activity of arterial NH/sub 3/ was maximal, and plateaued at levels 5.1 times those due to an equivalent amount of blood, indicating rapid passage of NH/sub 3/ across the blood-brain barrier, followed by metabolic trapping. Quantitative body scans showed that 7.4 +- 0.3% of observed activity was trapped by the brain. The brain NH/sub 3/ utilization rate (BAUR), calculated from brain and blood activities, was a function of (NH/sub 3/)/sub a/: ..mu..mol/min = 0.32 (NH/sub 3/)/sub a/ + 1.8 (r = +0.93, P < 0.005). The BAUR was 34 +- 3 ..mu..mol/min in the non-HE subjects and 49 +- 6 in those with HE (P < 0.05). Assuming a normal cerebral blood flow and brain weight, 51 +- 4% of arterial NH/sub 3/ was extracted from the blood during a single pass through normal brains. Utilization was greatest in grey matter. Calculations show that NH/sub 3/ metabolism occurs in a compartment, perhaps in astrocytes, that contains less than 20% of all brain ammonia. Liver uptake (3 to 24%) was a function of its projected size on the scan. Skeletal muscle metabolized about 50% of the arterial NH/sub 3/ in normals, less in those with cachexia.

  5. Metabolic mechanisms in heart failure.

    Science.gov (United States)

    Ashrafian, Houman; Frenneaux, Michael P; Opie, Lionel H

    2007-07-24

    Although neurohumoral antagonism has successfully reduced heart failure morbidity and mortality, the residual disability and death rate remains unacceptably high. Though abnormalities of myocardial metabolism are associated with heart failure, recent data suggest that heart failure may itself promote metabolic changes such as insulin resistance, in part through neurohumoral activation. A detrimental self-perpetuating cycle (heart failure --> altered metabolism --> heart failure) that promotes the progression of heart failure may thus be postulated. Accordingly, we review the cellular mechanisms and pathophysiology of altered metabolism and insulin resistance in heart failure. It is hypothesized that the ensuing detrimental myocardial energetic perturbations result from neurohumoral activation, increased adverse free fatty acid metabolism, decreased protective glucose metabolism, and in some cases insulin resistance. The result is depletion of myocardial ATP, phosphocreatine, and creatine kinase with decreased efficiency of mechanical work. On the basis of the mechanisms outlined, appropriate therapies to mitigate aberrant metabolism include intense neurohumoral antagonism, limitation of diuretics, correction of hypokalemia, exercise, and diet. We also discuss more novel mechanistic-based therapies to ameliorate metabolism and insulin resistance in heart failure. For example, metabolic modulators may optimize myocardial substrate utilization to improve cardiac function and exercise performance beyond standard care. The ultimate success of metabolic-based therapy will be manifest by its capacity further to lessen the residual mortality in heart failure.

  6. Extranuclear Sirtuins and Metabolic Stress.

    Science.gov (United States)

    Elkhwanky, Mahmoud-Sobhy; Hakkola, Jukka

    2018-03-10

    Extranuclear sirtuins in cytosol (SIRT2) and mitochondria (SIRT3, SIRT4, and SIRT5) are key regulators of metabolic enzymes and the antioxidative defense mechanisms. They play an important role in the adjustment of metabolic pathways in alterations of the nutritional status. Recent Advances: Recent studies have shown that in addition to lysine deacetylation, sirtuins catalyze several different lysine deacylation reactions, removal of lipid modifications, and adenosine diphosphate-ribosylation. Large-scale studies have revealed hundreds of target proteins regulated by different sirtuin modifications. Sensing of the metabolic state and regulation of the sirtuin function and expression are critical components of the machinery, optimizing cellular functions in the switch from fed to fasting condition. Overfeeding, obesity, and metabolic diseases cause metabolic stress that dysregulates the sirtuins, which may play a role in the pathogenesis and complications of metabolic diseases such as type 2 diabetes, fatty liver disease, and cardiac diseases. In the current review, we will discuss the significance of the extranuclear sirtuins as metabolic regulators and in protection against the reactive oxygen species, and also how these sirtuins are regulated by metabolic status and their putative role in metabolic diseases. To efficiently utilize sirtuins as drug targets for treatment of the metabolic diseases, better understanding of the sirtuin functions, targets, regulation, and cross talk is needed. Furthermore, more studies in humans are needed to confirm the many observations mainly made in animal and cell models so far. Antioxid. Redox Signal. 28, 662-676.

  7. Polyamine metabolism revisited.

    Science.gov (United States)

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

    2001-09-01

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

  8. Inositol Metabolism in Plants

    Science.gov (United States)

    Kroh, M.; Miki-Hirosige, H.; Rosen, W.; Loewus, F.

    1970-01-01

    When detached flowers or isolated pistils of Lilium longiflorum are given myoinositol-U-14C or -2-3H as dilute solution through the severed pedicel, label is quickly distributed by the vascular system. In the case of pistils, a pattern of labeling in ovary, style, and stigma is obtained which indicates that products of myoinositol metabolism are utilized in the biosynthesis of exudate (secretion product) of the stigma and style as well as for components of pistil cell walls. Pollination had no discernible effect on labeling pattern. Images PMID:5436329

  9. [Obesity and bone metabolism].

    Science.gov (United States)

    Holecki, Michał; Zahorska-Markiewicz, Barbara; Wiecek, Andrzej; Nieszporek, Teresa; Zak-Gołab, Agnieszka

    2008-01-01

    Both bone and adipose tissue change their size, shape and distribution during the whole human being's life. Many factors, including genetic factors, hormones and activity of nervous system are responsible for these changes. It is generally accepted that obesity has a protective effect on bone tissue. On the other hand some authors present an opposite results--the lack of beneficial effect of obesity on development of osteoporosis fractures. The aim of this article was to present and discuss the relations between adipose tissue and bone metabolism.

  10. Crassulacean acid metabolism

    Directory of Open Access Journals (Sweden)

    Thomas David Geydan

    2005-07-01

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

  11. Rapid screening test for porphyria diagnosis using fluorescence spectroscopy

    Science.gov (United States)

    Lang, A.; Stepp, H.; Homann, C.; Hennig, G.; Brittenham, G. M.; Vogeser, M.

    2015-07-01

    Porphyrias are rare genetic metabolic disorders, which result from deficiencies of enzymes in the heme biosynthesis pathway. Depending on the enzyme defect, different types of porphyrins and heme precursors accumulate for the different porphyria diseases in erythrocytes, liver, blood plasma, urine and stool. Patients with acute hepatic porphyrias can suffer from acute neuropathic attacks, which can lead to death when undiagnosed, but show only unspecific clinical symptoms such as abdominal pain. Therefore, in addition to chromatographic methods, a rapid screening test is required to allow for immediate identification and treatment of these patients. In this study, fluorescence spectroscopic measurements were conducted on blood plasma and phantom material, mimicking the composition of blood plasma of porphyria patients. Hydrochloric acid was used to differentiate the occurring porphyrins (uroporphyrin-III and coproporphyrin-III) spectroscopically despite their initially overlapping excitation spectra. Plasma phantom mixtures were measured using dual wavelength excitation and the corresponding concentrations of uroporphyrin-III and coproporphyrin-III were determined. Additionally, three plasma samples of porphyria patients were examined and traces of coproporphyrin-III and uroporphyrin-III were identified. This study may therefore help to establish a rapid screening test method with spectroscopic differentiation of the occurring porphyrins, which consequently allows for the distinction of different porphyrias. This may be a valuable tool for clinical porphyria diagnosis and rapid or immediate treatment.

  12. Rapid and efficient galactose fermentation by engineered Saccharomyces cerevisiae.

    Science.gov (United States)

    Quarterman, Josh; Skerker, Jeffrey M; Feng, Xueyang; Liu, Ian Y; Zhao, Huimin; Arkin, Adam P; Jin, Yong-Su

    2016-07-10

    In the important industrial yeast Saccharomyces cerevisiae, galactose metabolism requires energy production by respiration; therefore, this yeast cannot metabolize galactose under strict anaerobic conditions. While the respiratory dependence of galactose metabolism provides benefits in terms of cell growth and population stability, it is not advantageous for producing fuels and chemicals since a substantial fraction of consumed galactose is converted to carbon dioxide. In order to force S. cerevisiae to use galactose without respiration, a subunit (COX9) of a respiratory enzyme was deleted, but the resulting deletion mutant (Δcox9) was impaired in terms of galactose assimilation. Interestingly, after serial sub-cultures on galactose, the mutant evolved rapidly and was able to use galactose via fermentation only. The evolved strain (JQ-G1) produced ethanol from galactose with a 94% increase in yield and 6.9-fold improvement in specific productivity as compared to the wild-type strain. (13)C-metabolic flux analysis demonstrated a three-fold reduction in carbon flux through the TCA cycle of the evolved mutant with redirection of flux toward the fermentation pathway. Genome sequencing of the JQ-G1 strain revealed a loss of function mutation in a master negative regulator of the Leloir pathway (Gal80p). The mutation (Glu348*) in Gal80p was found to act synergistically with deletion of COX9 for efficient galactose fermentation, and thus the double deletion mutant Δcox9Δgal80 produced ethanol 2.4 times faster and with 35% higher yield than a single knockout mutant with deletion of GAL80 alone. When we introduced a functional COX9 cassette back into the JQ-G1 strain, the JQ-G1-COX9 strain showed a 33% reduction in specific galactose uptake rate and a 49% reduction in specific ethanol production rate as compared to JQ-G1. The wild-type strain was also subjected to serial sub-cultures on galactose but we failed to isolate a mutant capable of utilizing galactose without

  13. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. (Univ. of California, Irvine (USA)); Gillin, J.C. (Univ. of California, San Diego (USA))

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.

  14. Rapid Adaptation in Digital Transformation

    DEFF Research Database (Denmark)

    Hansen, Anne Mette; Kræmmergaard, Pernille; Mathiassen, Lars

    2011-01-01

    the organization’s digitization approach. We demonstrate in detail how the leaders within these two organizations were engaged and offer recommendations for how other organizations can use the PPM to rapidly adapt their approaches to digital transformation through more effective IS leadership roles.......In today’s highly dynamic environments, organizational leaders need to quickly adapt existing approaches to digital transformation. However, without a shared mindset between IS and business leaders, it is difficult to adopt new approaches in response to changes in the competitive and technology...... landscape. In this article, we share insights gained from two public sector organizations in which IS and business leaders used the Participatory Process Model (PPM) designed by the authors to share their assumptions about IS leadership, challenge existing IT strategies and collaboration patterns and adapt...

  15. Moved by a Rapid Transit

    Science.gov (United States)

    Bueter, C.

    2013-04-01

    Enticing by virtue of its predictability, historical utility, and spectacle, the transit of Venus is a niche event among astronomical phenomena. Though the value of a transit for scientific purposes is now diminished, the brief appearance of Venus silhouetted against the background of the Sun in 2004 moved the artistic community to celebrate the rare alignment. Artists of all ages combined old traditions with fresh technology to create a 21st-century tapestry of music, sculpture, paintings, glasswork, quilts, sky shows, and digital imagery. A full catalog of transit-related art generated over the centuries would feature the sampling of entries presented here and at the Moved by a Rapid Transit website.

  16. [Rapid diagnostic test for malaria].

    Science.gov (United States)

    Houzé, S

    2017-02-01

    The rapid diagnostic tests (RDTs) whose main interest lies in their implementation without special equipment by unskilled personnel have grown significantly over the past fifteen years to diagnose malaria. They rely on the detection of specific Plasmodium proteins, PfHRP2, pLDH and aldolase. If the detection of PfHRP2 has very good sensitivity for the diagnosis of Plasmodium falciparum malaria, the detection of pLDH or aldolase is less efficient for other species, leaving its place to the reference microscopic diagnosis. RDT could not generally be used to monitor therapeutic efficacy because they can remain positive after clinical and parasitological cure. Furthermore, the development of the use of these tests has highlighted the need for quality assurance programs to monitor their production as their use.

  17. Rapid Solidification of Magnetic Oxides

    Science.gov (United States)

    Kalonji, G.; Deguire, M. R.

    1985-01-01

    The enhanced control over microstructural evolution inherent in rapid solidification processing techniques are exploited to create novel ceramic magnetic materials. The great sensitivity of magnetic properties to local structure provides a powerful probe both for the study of structure and of microscopic solidification mechanisms. The first system studied is the SrO-Fe2O3 binary, which contains the commercially important hard magnetic compound strontium hexaferrite. The products were analyzed by transmission electron microscopy, Mossbauer spectroscopy, magnetic measurements, and differential thermal analysis. As-quenched ribbons contain high concentrations of super-paramagnetic particles, 80 to 250 Angstroms in diameter, in a glassy matrix. This suggests the possibility of crystallizing monodomain strontium hexaferrite during subsequent heat treatment, with a resulting increase in coercivity over conventionally processed ferrite magnets. That magnetic properties can be controlled in solidification processing by varying the quench rate is demonstrated.

  18. Metabolic Reprogramming in Brain Tumors.

    Science.gov (United States)

    Venneti, Sriram; Thompson, Craig B

    2017-01-24

    Next-generation sequencing has substantially enhanced our understanding of the genetics of primary brain tumors by uncovering several novel driver genetic alterations. How many of these genetic modifications contribute to the pathogenesis of brain tumors is not well understood. An exciting paradigm emerging in cancer biology is that oncogenes actively reprogram cellular metabolism to enable tumors to survive and proliferate. We discuss how some of these genetic alterations in brain tumors rewire metabolism. Furthermore, metabolic alterations directly impact epigenetics well beyond classical mechanisms of tumor pathogenesis. Metabolic reprogramming in brain tumors is also influenced by the tumor microenvironment contributing to drug resistance and tumor recurrence. Altered cancer metabolism can be leveraged to noninvasively image brain tumors, which facilitates improved diagnosis and the evaluation of treatment effectiveness. Many of these aspects of altered metabolism provide novel therapeutic opportunities to effectively treat primary brain tumors.

  19. Metabolic syndrome, diet and exercise.

    Science.gov (United States)

    De Sousa, Sunita M C; Norman, Robert J

    2016-11-01

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

  20. Biochemical Hypermedia: Galactose Metabolism.

    Directory of Open Access Journals (Sweden)

    J.K. Sugai

    2013-05-01

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

  1. Metabolic Syndrome: Hyperlipidemia.

    Science.gov (United States)

    Bragg, Dee Ann Stults; Walling, Anne

    2015-08-01

    Metabolic syndrome is associated with an elevated risk of cardiovascular disease and premature mortality. When metabolic syndrome includes lipid abnormalities, management goals are weight loss and cardiovascular risk management through lifestyle modifications (eg, diet, exercise), and, when appropriate, lowering of lipid levels with pharmacotherapy. Healthy diets are recommended, particularly the Mediterranean diet. Patients also should set a goal of at least 30 minutes of moderate to vigorous exercise on most, preferably all, days of the week. Guidelines provide criteria for statin treatment based on overall cardiovascular risk. High-intensity statin treatment (eg, rosuvastatin 20 to 40 mg, atorvastatin 40 to 80 mg) typically is recommended unless the patient cannot tolerate therapy. Approximately 5% of patients experience statin-induced myalgia, in which case moderate-intensity treatment can be tried. Lipid levels should be reevaluated 4 to 12 weeks after initiating therapy; lipid levels can be measured without fasting. A lack of improvement often indicates nonadherence. Bile acid sequestrants, fibric acids, and niacin can be used if other drugs are not tolerated. The evidence to support use of integrative medicine is limited, but the strongest evidence of benefit is for garlic (Allium sativum). Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  2. [Sleep duration and metabolism].

    Science.gov (United States)

    Viot-Blanc, V

    2015-12-01

    Sleep duration has gradually diminished during the last decade while obesity and type 2 diabetes have become epidemics. Experimental sleep curtailment leads to increased appetite, hormonal disturbances and, especially, insulin resistance. Numerous epidemiological studies have therefore examined whether habitual short sleep is associated with obesity and type 2 diabetes. A large majority of cross-sectional studies have confirmed an association between short, and also long sleep duration and obesity in adults more than in the elderly. Short sleep is strongly associated to obesity in children and adolescents. Prospective studies, including studies in children, are not conclusive with regard to the effect of short sleep on the incidence of obesity. Both short and long sleep durations are associated with diabetes, but only short sleep duration seems predictive of future diabetes. Insomnia seems to be a strong contributor to short sleep duration but the association of insomnia with obesity is not clear. Insomnia is associated with type 2 diabetes and also predictive of a higher incidence. Other studies have shown that short sleep duration and insomnia are associated with, and sometime predictive of, other components of the metabolic syndrome, especially hypertension and the risk of coronary disease. The treatment of short sleep duration and insomnia with regard to their effects on the metabolic syndrome merits further study. Copyright © 2015 SPLF. Published by Elsevier Masson SAS. All rights reserved.

  3. Metabolic topography of Parkinsonism

    Energy Technology Data Exchange (ETDEWEB)

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

    2007-04-15

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

  4. Ceramic microfabrication by rapid prototyping process chains

    Indian Academy of Sciences (India)

    To avoid high tooling costs in product development, a rapid prototyping process chain has been established that enables rapid manufacturing of ceramic microcomponents from functional models to small lot series within a short time. This process chain combines the fast and inexpensive supply of master models by rapid ...

  5. Rapid Prototyping in Instructional Design: Creating Competencies

    Science.gov (United States)

    Fulton, Carolyn D.

    2010-01-01

    Instructional designers working in rapid prototyping environments currently do not have a list of competencies that help to identify the knowledge, skills, and attitudes (KSAs) required in these workplaces. This qualitative case study used multiple cases in an attempt to identify rapid prototyping competencies required in a rapid prototyping…

  6. Metabolic flexibility and insulin resistance

    OpenAIRE

    Galgani, Jose E.; Moro, Cedric; Ravussin, Eric

    2008-01-01

    Metabolic flexibility is the capacity for the organism to adapt fuel oxidation to fuel availability. The inability to modify fuel oxidation in response to changes in nutrient availability has been implicated in the accumulation of intramyocellular lipid and insulin resistance. The metabolic flexibility assessed by the ability to switch from fat to carbohydrate oxidation is usually impaired during a hyperinsulinemic clamp in insulin-resistant subjects; however, this “metabolic inflexibility” i...

  7. Parameters of metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy

    OpenAIRE

    Aditi Dhir; Suvasini Sharma; Puneet Jain; Bhakhri, Bhanu K.; Satinder Aneja

    2015-01-01

    Objectives: The prevalence of obesity is rapidly increasing among Indian children, who, in general, are more prone to develop metabolic complications at an early age. Valproate and phenytoin are commonly used antiepileptic drugs in children. This study aimed to assess the parameters of the metabolic syndrome in Indian children with epilepsy on valproate or phenytoin monotherapy. Methods: This cross-sectional study recruited children from the Pediatric Epilepsy Clinic, Department of Pediatrics...

  8. A key problem and challenge for hepatology: Obesity-related metabolic liver diseases.

    Science.gov (United States)

    Balaban, Yasemin Hatice

    2011-06-27

    With the arrival of the new millennium, gastroenterologists have been faced with the problem of metabolic liver diseases associated with obesity. The active role of the liver in metabolism and inflammation make it a key organ in the war against the rapidly-spreading world-wide epidemic of obesity. Many lives and much money could be saved if the work of hepatologists led to the development of effective diagnostic and therapeutic strategies against this growing leader of cirrhosis.

  9. Peculiarities of Teaching Problems of Metabolic Syndrome in Children to Interns

    OpenAIRE

    Bobrykovych, Olha

    2017-01-01

    Obesity has become one of the most urgent social problems worldwide. Continuous and rapid increase in obesity rates is considered by the World Health Organization as a global epidemic. Obesity affects children as well; the World Health Organization recognized childhood obesity as an acute public health crisis. Childhood obesity is often accompanied by arterial hypertension, hyperlipidemia and disorders of        carbohydrate metabolism resulting in symptom complex – metabolic syndrome. While ...

  10. Inhibition of Sphingolipid Metabolism Enhances Resveratrol Chemotherapy in Human Gastric Cancer Cells

    OpenAIRE

    Shin, Kyong-Oh; Park, Nam-Young; Seo, Cho-Hee; Hong, Seon-Pyo; Oh, Ki-Wan; Hong, Jin-Tae; Han, Sang-Kil; Lee, Yong-Moon

    2012-01-01

    Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol (100 ?M) for 24 hr induced...

  11. Rapid Tooling via Investment Casting and Rapid Prototype Patterns

    Energy Technology Data Exchange (ETDEWEB)

    Baldwin, Michael D.

    1999-06-01

    The objective of this work to develop the materials processing and design technologies required to reduce the die development time for metal mold processes from 12 months to 3 months, using die casting of Al and Mg as the example process. Sandia demonstrated that investment casting, using rapid prototype patterns produced from Stereo lithography or Selective laser Sintering, was a viable alternative/supplement to the current technology of machining form wrought stock. A demonstration die insert (ejector halt) was investment cast and subsequently tested in the die casting environment. The stationary half of the die insert was machined from wrought material to benchmark the cast half. The two inserts were run in a die casting machine for 3,100 shots of aluminum and at the end of the run no visible difference could be detected between the cast and machined inserts. Inspection concluded that the cast insert performed identically to the machined insert. Both inserts had no indications of heat checking or degradation.

  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. Clinical update on metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Juan Diego Hernández-Camacho

    2017-12-01

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

  14. Drug-Induced Metabolic Acidosis

    Science.gov (United States)

    Pham, Amy Quynh Trang; Xu, Li Hao Richie; Moe, Orson W.

    2015-01-01

    Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics. PMID:26918138

  15. Gut Microbiota and Metabolic Disorders

    Directory of Open Access Journals (Sweden)

    Kyu Yeon Hur

    2015-06-01

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

  16. Bilateral Diabetic Papillopathy and Metabolic Control

    DEFF Research Database (Denmark)

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

    2010-01-01

    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......-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...

  17. Cerebral blood flow and metabolism during sleep

    DEFF Research Database (Denmark)

    Madsen, Peter Lund; Vorstrup, S

    1991-01-01

    A review of the current literature regarding sleep-induced changes in cerebral blood flow (CBF) and cerebral metabolic rate (CMR) is presented. Early investigations have led to the notion that dreamless sleep was characterized by global values of CBF and CMR practically at the level of wakefulness......, while rapid eye movement (REM) sleep (dream sleep) was a state characterized by a dramatically increased level of CBF and possibly also of CMR. However, recent investigations firmly contradict this notion. Investigations on CBF and CMR performed during non-REM sleep, taking the effect of different...... levels of sleep into consideration, show that light sleep (stage II) is characterized by global levels of CBF and CMR only slightly reduced by 3-10% below the level associated with wakefulness, whereas CBF and CMR during deep sleep (stage III-IV) is dramatically reduced by 25-44%. Furthermore, recent...

  18. Genetic-Metabolic Coupling for Targeted Metabolic Engineering

    DEFF Research Database (Denmark)

    Cardinale, Stefano; Tueros Farfan, Felipe Gonzalo; Sommer, Morten Otto Alexander

    2017-01-01

    Production of chemicals in microbes often employs potent biosynthetic enzymes, which can interact with the microbial native metabolism to affect cell fitness and product yield. However, production optimization largely relies on data collected from wild-type strains in the absence of metabolic...

  19. Metabolic flux analysis: recent advances in carbon metabolism in plants.

    Science.gov (United States)

    Dieuaide-Noubhani, Martine; Alonso, Ana-Paula; Rolin, Dominique; Eisenreich, Wolfgang; Raymond, Philippe

    2007-01-01

    Isotopic tracers are used to both trace metabolic pathways and quantify fluxes through these pathways. The use of different labeling methods recently led to profound changes in our views of plant metabolism. Examples are taken from primary metabolism, with sugar interconversions, carbon partitioning between glycolysis and the pentose phosphate pathway, or metabolite inputs into the tricarboxylic acid (TCA) cycle, as well as from secondary metabolism with the relative contribution of the plastidial and cytosolic pathways to the biosynthesis of terpenoids. While labeling methods are often distinguished according to the instruments used for label detection, emphasis is put here on labeling duration. Short time labeling is adequate to study limited areas of the metabolic network. Long-term labeling, when designed to obtain metabolic and isotopic steady-state, allows to calculate various fluxes in large areas ofcentral metabolism. After longer labeling periods, large amounts of label accumulate in structural or storage compounds: their detailed study through the retrobiosynthetic method gives access to the biosynthetic pathways of otherwise undetectable precursors. This chapter presents the power and limits of the different methods, and illustrates how they can be associated with each other and with other methods of cell biology, to provide the information needed for a rational approach of metabolic engineering.

  20. Reconciling theories for metabolic scaling.

    Science.gov (United States)

    Maino, James L; Kearney, Michael R; Nisbet, Roger M; Kooijman, Sebastiaan A L M

    2014-01-01

    Metabolic theory specifies constraints on the metabolic organisation of individual organisms. These constraints have important implications for biological processes ranging from the scale of molecules all the way to the level of populations, communities and ecosystems, with their application to the latter emerging as the field of metabolic ecology. While ecologists continue to use individual metabolism to identify constraints in ecological processes, the topic of metabolic scaling remains controversial. Much of the current interest and controversy in metabolic theory relates to recent ideas about the role of supply networks in constraining energy supply to cells. We show that an alternative explanation for physicochemical constraints on individual metabolism, as formalised by dynamic energy budget (DEB) theory, can contribute to the theoretical underpinning of metabolic ecology, while increasing coherence between intra- and interspecific scaling relationships. In particular, we emphasise how the DEB theory considers constraints on the storage and use of assimilated nutrients and derive an equation for the scaling of metabolic rate for adult heterotrophs without relying on optimisation arguments or implying cellular nutrient supply limitation. Using realistic data on growth and reproduction from the literature, we parameterise the curve for respiration and compare the a priori prediction against a mammalian data set for respiration. Because the DEB theory mechanism for metabolic scaling is based on the universal process of acquiring and using pools of stored metabolites (a basal feature of life), it applies to all organisms irrespective of the nature of metabolic transport to cells. Although the DEB mechanism does not necessarily contradict insight from transport-based models, the mechanism offers an explanation for differences between the intra- and interspecific scaling of biological rates with mass, suggesting novel tests of the respective hypotheses. © 2013 The

  1. Structural Control of Metabolic Flux

    Science.gov (United States)

    Sajitz-Hermstein, Max; Nikoloski, Zoran

    2013-01-01

    Organisms have to continuously adapt to changing environmental conditions or undergo developmental transitions. To meet the accompanying change in metabolic demands, the molecular mechanisms of adaptation involve concerted interactions which ultimately induce a modification of the metabolic state, which is characterized by reaction fluxes and metabolite concentrations. These state transitions are the effect of simultaneously manipulating fluxes through several reactions. While metabolic control analysis has provided a powerful framework for elucidating the principles governing this orchestrated action to understand metabolic control, its applications are restricted by the limited availability of kinetic information. Here, we introduce structural metabolic control as a framework to examine individual reactions' potential to control metabolic functions, such as biomass production, based on structural modeling. The capability to carry out a metabolic function is determined using flux balance analysis (FBA). We examine structural metabolic control on the example of the central carbon metabolism of Escherichia coli by the recently introduced framework of functional centrality (FC). This framework is based on the Shapley value from cooperative game theory and FBA, and we demonstrate its superior ability to assign “share of control” to individual reactions with respect to metabolic functions and environmental conditions. A comparative analysis of various scenarios illustrates the usefulness of FC and its relations to other structural approaches pertaining to metabolic control. We propose a Monte Carlo algorithm to estimate FCs for large networks, based on the enumeration of elementary flux modes. We further give detailed biological interpretation of FCs for production of lactate and ATP under various respiratory conditions. PMID:24367246

  2. Metabolic therapy: a new paradigm for managing malignant brain cancer.

    Science.gov (United States)

    Seyfried, Thomas N; Flores, Roberto; Poff, Angela M; D'Agostino, Dominic P; Mukherjee, Purna

    2015-01-28

    Little progress has been made in the long-term management of glioblastoma multiforme (GBM), considered among the most lethal of brain cancers. Cytotoxic chemotherapy, steroids, and high-dose radiation are generally used as the standard of care for GBM. These procedures can create a tumor microenvironment rich in glucose and glutamine. Glucose and glutamine are suggested to facilitate tumor progression. Recent evidence suggests that many GBMs are infected with cytomegalovirus, which could further enhance glucose and glutamine metabolism in the tumor cells. Emerging evidence also suggests that neoplastic macrophages/microglia, arising through possible fusion hybridization, can comprise an invasive cell subpopulation within GBM. Glucose and glutamine are major fuels for myeloid cells, as well as for the more rapidly proliferating cancer stem cells. Therapies that increase inflammation and energy metabolites in the GBM microenvironment can enhance tumor progression. In contrast to current GBM therapies, metabolic therapy is designed to target the metabolic malady common to all tumor cells (aerobic fermentation), while enhancing the health and vitality of normal brain cells and the entire body. The calorie restricted ketogenic diet (KD-R) is an anti-angiogenic, anti-inflammatory and pro-apoptotic metabolic therapy that also reduces fermentable fuels in the tumor microenvironment. Metabolic therapy, as an alternative to the standard of care, has the potential to improve outcome for patients with GBM and other malignant brain cancers. Copyright © 2014. Published by Elsevier Ireland Ltd.

  3. Nutritional lipidomics: molecular metabolism, analytics, and diagnostics.

    Science.gov (United States)

    Smilowitz, Jennifer T; Zivkovic, Angela M; Wan, Yu-Jui Yvonne; Watkins, Steve M; Nording, Malin L; Hammock, Bruce D; German, J Bruce

    2013-08-01

    The field of lipidomics is providing nutritional science a more comprehensive view of lipid intermediates. Lipidomics research takes advantage of the increase in accuracy and sensitivity of mass detection of MS with new bioinformatics toolsets to characterize the structures and abundances of complex lipids. Yet, translating lipidomics to practice via nutritional interventions is still in its infancy. No single instrumentation platform is able to solve the varying analytical challenges of the different molecular lipid species. Biochemical pathways of lipid metabolism remain incomplete and the tools to map lipid compositional data to pathways are still being assembled. Biology itself is dauntingly complex and simply separating biological structures remains a key challenge to lipidomics. Nonetheless, the strategy of combining tandem analytical methods to perform the sensitive, high-throughput, quantitative, and comprehensive analysis of lipid metabolites of very large numbers of molecules is poised to drive the field forward rapidly. Among the next steps for nutrition to understand the changes in structures, compositions, and function of lipid biomolecules in response to diet is to describe their distribution within discrete functional compartments lipoproteins. Additionally, lipidomics must tackle the task of assigning the functions of lipids as signaling molecules, nutrient sensors, and intermediates of metabolic pathways. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Metabolic engineering to enhance bacterial hydrogen production

    Science.gov (United States)

    Maeda, Toshinari; Sanchez‐Torres, Viviana; Wood, Thomas K.

    2008-01-01

    Summary Hydrogen fuel is renewable, efficient and clean, and fermentative bacteria hold great promise for its generation. Here we use the isogenic Escherichia coli K‐12 KEIO library to rapidly construct multiple, precise deletions in the E. coli genome to direct the metabolic flux towards hydrogen production. Escherichia coli has three active hydrogenases, and the genes involved in the regulation of the formate hydrogen lyase (FHL) system for synthesizing hydrogen from formate via hydrogenase 3 were also manipulated to enhance hydrogen production. Specifically, we altered regulation of FHL by controlling the regulators HycA and FhlA, removed hydrogen consumption by hydrogenases 1 and 2 via the hyaB and hybC mutations, and re‐directed formate metabolism using the fdnG, fdoG, narG, focA, fnr and focB mutations. The result was a 141‐fold increase in hydrogen production from formate to create a bacterium (BW25113 hyaB hybC hycA fdoG/pCA24N‐FhlA) that produces the largest amount of hydrogen to date and one that achieves the theoretical yield for hydrogen from formate. In addition, the hydrogen yield from glucose was increased by 50%, and there was threefold higher hydrogen production from glucose with this strain. PMID:21261819

  5. Metabolic Profiling of Alpine and Ecuadorian Lichens

    Directory of Open Access Journals (Sweden)

    Verena K. Mittermeier

    2015-10-01

    Full Text Available Non-targeted 1H-NMR methods were used to determine metabolite profiles from crude extracts of Alpine and Ecuadorian lichens collected from their natural habitats. In control experiments, the robustness of metabolite detection and quantification was estimated using replicate measurements of Stereocaulon alpinum extracts. The deviations in the overall metabolite fingerprints were low when analyzing S. alpinum collections from different locations or during different annual and seasonal periods. In contrast, metabolite profiles observed from extracts of different Alpine and Ecuadorian lichens clearly revealed genus- and species-specific profiles. The discriminating functions determining cluster formation in principle component analysis (PCA were due to differences in the amounts of genus-specific compounds such as sticticin from the Sticta species, but also in the amounts of ubiquitous metabolites, such as sugar alcohols or trehalose. However, varying concentrations of these metabolites from the same lichen species e.g., due to different environmental conditions appeared of minor relevance for the overall cluster formation in PCA. The metabolic clusters matched phylogenetic analyses using nuclear ribosomal DNA (nrDNA internal transcribed spacer (ITS sequences of lichen mycobionts, as exemplified for the genus Sticta. It can be concluded that NMR-based non-targeted metabolic profiling is a useful tool in the chemo-taxonomy of lichens. The same approach could also facilitate the discovery of novel lichen metabolites on a rapid and systematical basis.

  6. The metabolic syndrome.

    Science.gov (United States)

    Harris, Mark F

    2013-08-01

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

  7. A Metabolic Race

    Directory of Open Access Journals (Sweden)

    Amanda Mendonça da Silva Costa

    2017-10-01

    Full Text Available It is common among medical students and other courses in biomedical area, to raise questions about the applicability of certain biochemical concepts. Since such contents will be present throughout their professional lifes, it is essential to emphasize the relevance of the basic cycle, stage of the medical training in which biochemistry teaching is inserted. With the aim of bring together theory and future clinical practice, a board game was developed based on a biochemical approach of Metabolic Syndrome (MS clinical cases. The game reproduces the environment and routine experienced by students of Federal Fluminense University, in which players are divided into “patients and doctors” and move on a simplified map of Niterói city. Questions and challenge cards are used to test students' biochemical knowledge and a scoring system based on three of the five criteria to diagnose MS, is used to provide proportional diagnoses to the each player’s performance.

  8. Regulation of Terpene Metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Rodney Croteau

    2004-03-14

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

  9. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1989-11-09

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

  10. Aldosterone in Metabolic Alkalosis*

    Science.gov (United States)

    Kassirer, Jerome P.; Appleton, Frederick M.; Chazan, Joseph A.; Schwartz, William B.

    1967-01-01

    Studies have been carried out in human volunteer subjects to evaluate the role of aldosterone in the development, maintenance, and correction of metabolic alkalosis induced by selective depletion of hydrochloric acid. During the first phase of our study the rate of aldosterone secretion was measured before the induction of alkalosis (while the subjects were on a low salt diet) and again after a steady state of metabolic alkalosis had been established. The data demonstrate a fall in aldosterone secretion from a value of approximately 500 μg/day to a value of approximately 200 μg/day. Thus, it appears that an increased rate of aldosterone secretion is not a prerequisite to the elevation of the renal bicarbonate threshold. During the second phase of our study, aldosterone was administered to the alkalotic subjects in doses of 1000 μg/day (or deoxycorticosterone acetate in doses of 40 mg/day) in order to determine the effects of a persistent steroid excess on the ability of sodium chloride to correct the acid-base disturbance. The data demonstrate that despite the administration of steroid, the ingestion of sodium chloride led to a reduction in plasma bicarbonate concentration from 39 to 29 mEq/liter, accompanied by a suppression of renal acid excretion. This reduction in plasma bicarbonate concentration occurred without a concomitant retention of potassium, a deficit of as much as 400-500 mEq of potassium persisting during repair of the acid-base disturbance. Our findings suggest that “saline-resistant” alkalosis, when it occurs in the absence of primary hyperadrenalism, cannot be attributed to aldosterone excess and/or potassium depletion of the magnitude seen in our study. We also suggest the need for a reappraisal of the way in which aldosterone excess contributes to the genesis and maintenance of alkalosis in primary aldosteronism. PMID:6061733

  11. Metabolism of endocannabinoids

    Directory of Open Access Journals (Sweden)

    Michał Biernacki

    2016-08-01

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

  12. Rapid response oxygen-sensing nanofibers

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Ruipeng [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States); Behera, Prajna; Viapiano, Mariano S. [Department of Neurosurgery, Brigham and Women' s Hospital, Harvard Medical School, Boston, MA 02115 (United States); Lannutti, John J., E-mail: lannutti.1@osu.edu [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States)

    2013-08-01

    Molecular oxygen has profound effects on cell and tissue viability. Relevant sensor forms that can rapidly determine dissolved oxygen levels under biologically relevant conditions provide critical metabolic information. Using 0.5 μm diameter electrospun polycaprolactone (PCL) fiber containing an oxygen-sensitive probe, tris (4,7-diphenyl-1,10-phenanthroline) ruthenium(II) dichloride, we observed a response time of 0.9 ± 0.12 s while the t{sub 95} for the corresponding film was more than two orders of magnitude greater. Interestingly, the response and recovery times of slightly larger diameter PCL fibers were 1.79 ± 0.23 s and 2.29 ± 0.13 s, respectively, while the recovery time was not statistically different likely due to the more limited interactions of nitrogen with the polymer matrix. A more than 10-fold increase in PCL fiber diameter reduces oxygen sensitivity while having minor effects on response time; conversely, decreases in fiber diameter to less than 0.5 μm would likely decrease response times even further. In addition, a 50 °C heat treatment of the electrospun fiber resulted in both increased Stern–Volmer slope and linearity likely due to secondary recrystallization that further homogenized the probe microenvironment. At exposure times up to 3600 s in length, photobleaching was observed but was largely eliminated by the use of either polyethersulfone (PES) or a PES–PCL core–shell composition. However, this resulted in 2- and 3-fold slower response times. Finally, even the non-core shell compositions containing the Ru oxygen probe result in no apparent cytotoxicity in representative glioblastoma cell populations. Highlights: • Nanofiber-based structures can self-report localized oxygen concentrations. • Ideal for tissue engineering as they allow close interaction of cells. • Nanofiber-incorporated oxygen-sensitive probes provide a perfectly linear response. • Photobleaching is largely eliminated by the use of PES–PCL core

  13. Wyoming Basin Rapid Ecoregional Assessment

    Science.gov (United States)

    Carr, Natasha B.; Means, Robert E.

    2013-01-01

    The overall goal of the Wyoming Basin Rapid Ecoregional Assessment (REA) is to provide information that supports regional planning and analysis for the management of ecological resources. The REA provides an assessment of baseline ecological conditions, an evaluation of current risks from drivers of ecosystem change (including energy development, fire, and invasive species), and a predictive capacity for evaluating future risks (including climate change). Additionally, the REA may be used for identifying priority areas for conservation or restoration and for assessing cumulative effects of multiple land uses. The Wyoming Basin REA will address Management Questions developed by the Bureau of Land Management and other agency partners for 8 major biomes and 19 species or species assemblages. The maps developed for addressing Management Questions will be integrated into overall maps of landscape-level ecological values and risks. The maps can be used to address the goals of the REA at a number of levels: for individual species, species assemblages, aquatic and terrestrial systems, and for the entire ecoregion. This allows flexibility in how the products of the REA are compiled to inform planning and management actions across a broad range of spatial scales.

  14. Rapid purification of recombinant histones.

    Directory of Open Access Journals (Sweden)

    Henrike Klinker

    Full Text Available The development of methods to assemble nucleosomes from recombinant histones decades ago has transformed chromatin research. Nevertheless, nucleosome reconstitution remains time consuming to this day, not least because the four individual histones must be purified first. Here, we present a streamlined purification protocol of recombinant histones from bacteria. We termed this method "rapid histone purification" (RHP as it circumvents isolation of inclusion bodies and thereby cuts out the most time-consuming step of traditional purification protocols. Instead of inclusion body isolation, whole cell extracts are prepared under strongly denaturing conditions that directly solubilize inclusion bodies. By ion exchange chromatography, the histones are purified from the extracts. The protocol has been successfully applied to all four canonical Drosophila and human histones. RHP histones and histones that were purified from isolated inclusion bodies had similar purities. The different purification strategies also did not impact the quality of octamers reconstituted from these histones. We expect that the RHP protocol can be readily applied to the purification of canonical histones from other species as well as the numerous histone variants.

  15. Rapid typing of Coxiella burnetii.

    Directory of Open Access Journals (Sweden)

    Heidie M Hornstra

    Full Text Available Coxiella burnetii has the potential to cause serious disease and is highly prevalent in the environment. Despite this, epidemiological data are sparse and isolate collections are typically small, rare, and difficult to share among laboratories as this pathogen is governed by select agent rules and fastidious to culture. With the advent of whole genome sequencing, some of this knowledge gap has been overcome by the development of genotyping schemes, however many of these methods are cumbersome and not readily transferable between institutions. As comparisons of the few existing collections can dramatically increase our knowledge of the evolution and phylogeography of the species, we aimed to facilitate such comparisons by extracting SNP signatures from past genotyping efforts and then incorporated these signatures into assays that quickly and easily define genotypes and phylogenetic groups. We found 91 polymorphisms (SNPs and indels among multispacer sequence typing (MST loci and designed 14 SNP-based assays that could be used to type samples based on previously established phylogenetic groups. These assays are rapid, inexpensive, real-time PCR assays whose results are unambiguous. Data from these assays allowed us to assign 43 previously untyped isolates to established genotypes and genomic groups. Furthermore, genotyping results based on assays from the signatures provided here are easily transferred between institutions, readily interpreted phylogenetically and simple to adapt to new genotyping technologies.

  16. Rapid Response Flood Water Mapping

    Science.gov (United States)

    Policelli, Fritz; Brakenridge, G. R.; Coplin, A.; Bunnell, M.; Wu, L.; Habib, Shahid; Farah, H.

    2010-01-01

    Since the beginning of operation of the MODIS instrument on the NASA Terra satellite at the end of 1999, an exceptionally useful sensor and public data stream have been available for many applications including the rapid and precise characterization of terrestrial surface water changes. One practical application of such capability is the near-real time mapping of river flood inundation. We have developed a surface water mapping methodology based on using only bands 1 (620-672 nm) and 2 (841-890 nm). These are the two bands at 250 m, and the use of only these bands maximizes the resulting map detail. In this regard, most water bodies are strong absorbers of incoming solar radiation at the band 2 wavelength: it could be used alone, via a thresholding procedure, to separate water (dark, low radiance or reflectance pixels) from land (much brighter pixels) (1, 2). Some previous water mapping procedures have in fact used such single band data from this and other sensors that include similar wavelength channels. Adding the second channel of data (band 1), however, allows a band ratio approach which permits sediment-laden water, often relatively light at band 2 wavelengths, to still be discriminated, and, as well, provides some removal of error by reducing the number of cloud shadow pixels that would otherwise be misclassified as water.

  17. MetAssimulo: simulation of realistic NMR metabolic profiles.

    Science.gov (United States)

    Muncey, Harriet J; Jones, Rebecca; De Iorio, Maria; Ebbels, Timothy M D

    2010-10-06

    Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics), the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control') specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with which to develop and test new data analysis techniques

  18. Evolutionary programming as a platform for in silico metabolic engineering

    Directory of Open Access Journals (Sweden)

    Förster Jochen

    2005-12-01

    Full Text Available Abstract Background Through genetic engineering it is possible to introduce targeted genetic changes and hereby engineer the metabolism of microbial cells with the objective to obtain desirable phenotypes. However, owing to the complexity of metabolic networks, both in terms of structure and regulation, it is often difficult to predict the effects of genetic modifications on the resulting phenotype. Recently genome-scale metabolic models have been compiled for several different microorganisms where structural and stoichiometric complexity is inherently accounted for. New algorithms are being developed by using genome-scale metabolic models that enable identification of gene knockout strategies for obtaining improved phenotypes. However, the problem of finding optimal gene deletion strategy is combinatorial and consequently the computational time increases exponentially with the size of the problem, and it is therefore interesting to develop new faster algorithms. Results In this study we report an evolutionary programming based method to rapidly identify gene deletion strategies for optimization of a desired phenotypic objective function. We illustrate the proposed method for two important design parameters in industrial fermentations, one linear and other non-linear, by using a genome-scale model of the yeast Saccharomyces cerevisiae. Potential metabolic engineering targets for improved production of succinic acid, glycerol and vanillin are identified and underlying flux changes for the predicted mutants are discussed. Conclusion We show that evolutionary programming enables solving large gene knockout problems in relatively short computational time. The proposed algorithm also allows the optimization of non-linear objective functions or incorporation of non-linear constraints and additionally provides a family of close to optimal solutions. The identified metabolic engineering strategies suggest that non-intuitive genetic modifications span

  19. MetAssimulo:Simulation of Realistic NMR Metabolic Profiles

    Directory of Open Access Journals (Sweden)

    De Iorio Maria

    2010-10-01

    Full Text Available Abstract Background Probing the complex fusion of genetic and environmental interactions, metabolic profiling (or metabolomics/metabonomics, the study of small molecules involved in metabolic reactions, is a rapidly expanding 'omics' field. A major technique for capturing metabolite data is 1H-NMR spectroscopy and this yields highly complex profiles that require sophisticated statistical analysis methods. However, experimental data is difficult to control and expensive to obtain. Thus data simulation is a productive route to aid algorithm development. Results MetAssimulo is a MATLAB-based package that has been developed to simulate 1H-NMR spectra of complex mixtures such as metabolic profiles. Drawing data from a metabolite standard spectral database in conjunction with concentration information input by the user or constructed automatically from the Human Metabolome Database, MetAssimulo is able to create realistic metabolic profiles containing large numbers of metabolites with a range of user-defined properties. Current features include the simulation of two groups ('case' and 'control' specified by means and standard deviations of concentrations for each metabolite. The software enables addition of spectral noise with a realistic autocorrelation structure at user controllable levels. A crucial feature of the algorithm is its ability to simulate both intra- and inter-metabolite correlations, the analysis of which is fundamental to many techniques in the field. Further, MetAssimulo is able to simulate shifts in NMR peak positions that result from matrix effects such as pH differences which are often observed in metabolic NMR spectra and pose serious challenges for statistical algorithms. Conclusions No other software is currently able to simulate NMR metabolic profiles with such complexity and flexibility. This paper describes the algorithm behind MetAssimulo and demonstrates how it can be used to simulate realistic NMR metabolic profiles with

  20. Metabolic Flux Analysis of Mammalian Cells

    NARCIS (Netherlands)

    Martens, D.E.

    2006-01-01

    Metabolic flux analysis has become a standard tool for analyzing metabolism and optimizing bioprocesses. Metabolic flux analysis makes use of a metabolic reaction network in combination with extra-cellular measurements and mass balancing to calculate flux distributions in metabolism. It is a useful

  1. Sex steroids and lipoprotein metabolism

    NARCIS (Netherlands)

    Gevers Leuven, J.A.

    1994-01-01

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

  2. Metabolic syndrome-associated osteoarthritis.

    Science.gov (United States)

    Courties, Alice; Sellam, Jérémie; Berenbaum, Francis

    2017-03-01

    Interest in the metabolic syndrome-associated osteoarthritis phenotype is increasing. Here, we summarize recently published significant findings. Meta-analyses confirmed an association between type 2 diabetes and osteoarthritis and between cardiovascular diseases and osteoarthritis. Recent advances in the study of metabolic syndrome-associated osteoarthritis have focused on a better understanding of the role of metabolic diseases in inducing or aggravating joint damage. In-vivo models of obesity, diabetes, or dyslipidemia have helped to better decipher this association. They give emerging evidence that, beyond the role of common pathogenic mechanisms for metabolic diseases and osteoarthritis (i.e., low-grade inflammation and oxidative stress), metabolic diseases have a direct systemic effect on joints. In addition to the impact of weight, obesity-associated inflammation is associated with osteoarthritis severity and may modulate osteoarthritis progression in mouse models. As well, osteoarthritis synovium from type 2 diabetic patients shows insulin-resistant features, which may participate in joint catabolism. Finally, exciting data are emerging on the association of gut microbiota and circadian rhythm and metabolic syndrome-associated osteoarthritis. The systemic role of metabolic syndrome in osteoarthritis pathophysiology is now better understood, but new avenues of research are being pursued to better decipher the metabolic syndrome-associated osteoarthritis phenotype.

  3. Selected Metabolic Responses to Skateboarding

    Science.gov (United States)

    Hetzler, Ronald K.; Hunt, Ian; Stickley, Christopher D.; Kimura, Iris F.

    2011-01-01

    Despite the popularity of skateboarding worldwide, the authors believe that no previous studies have investigated the metabolic demands associated with recreational participation in the sport. Although metabolic equivalents (METs) for skateboarding were published in textbooks, the source of these values is unclear. Therefore, the rise in…

  4. Metabolic syndrome and acute pancreatitis.

    Science.gov (United States)

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

    2016-07-01

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

  5. Cancer Metabolism: A Modeling Perspective

    DEFF Research Database (Denmark)

    Ghaffari, Pouyan; Mardinoglu, Adil; Nielsen, Jens

    2015-01-01

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

  6. Strategies for reversing the effects of metabolic disorders induced as a consequence of developmental programming

    Directory of Open Access Journals (Sweden)

    Mark H Vickers

    2012-07-01

    Full Text Available Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioural influences, rather than genetic causes, are fuelling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment.

  7. De novo biosynthesis of secondary metabolism enzymes in homogeneous cultures of Penicillium urticae.

    OpenAIRE

    Grootwassink, J W; Gaucher, G M

    1980-01-01

    The initiation of patulin biosynthesis in submerged batch cultures of Penicillium urticae NRRL 2159A was investigated at the enzyme level. In contrast to earlier studies, this study achieved a clear temporal separation of growing cells devoid of secondary metabolism-specific enzymes from nongrowing cells, which rapidly produce these enzymes. A spore inoculum, silicone-treated flasks, and two new media which supported a rapid, pellet-free, filamentous type of growth were used. In yeast extract...

  8. Metabolic management of heart disease

    Directory of Open Access Journals (Sweden)

    Akshyaya K Pradhan

    2016-01-01

    Full Text Available Alterations of cardiac metabolism occur with ischemia and heart failure (HF. This results in increased utilization of noncarbohydrate substrates for energy production and depletion of myocardial adenosine triphosphate, phosphocreatine, and creatine kinase with decreased efficiency of mechanical work. A direct approach to manipulate cardiac energy metabolism consists in modifying substrate utilization by the failing heart. The results of research suggest that shifting the energy substrate preference away from fatty acid metabolism and toward glucose metabolism could be an effective adjunctive treatment in patients with HF, in terms of left ventricular function and glucose metabolism improvement. In this paper, some of these concepts will be discussed, and the role of drugs such as trimetazidine will be discussed.

  9. Metabolic effects of renal denervation.

    Science.gov (United States)

    Thomopoulos, Costas; Spanoudi, Filio; Kyriazis, Ioannis; Anastasopoulos, Ioannis; Ioannidis, Ioannis

    2013-08-01

    In the present review article we address the issue of the potential effect of renal sympathetic denervation (RSD) on metabolic states associated with resistant hypertension. So far, there is an established pathophysiological background denoting that abnormalities in glucose metabolism especially in obese patients and in those with sleep apnea are constantly accompanied by increased sympathetic firing, as assessed by markers of sympathetic activity. Since resistant hypertension is also characterized by enhanced sympathetic activity, it seems logical and biologically plausible, that RSD might favorably influence impaired glucose metabolism, sleep disorders and increased body adiposity beyond BP lowering. Despite the limited evidence from clinical trials, there are promising data suggesting that RSD indeed ameliorates glucose metabolism-related measures in resistant hypertension. Well-designed randomized trials recruiting a larger number of patients with hypertension, and focused on metabolic parameters, may refine the role of RSD as a potential intervention to treat dysmetabolic states associated with hypertension.

  10. Retinoid Metabolism and Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Eun-Jung Rhee

    2012-06-01

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

  11. Vasomotor symptoms and metabolic syndrome.

    Science.gov (United States)

    Tuomikoski, Pauliina; Savolainen-Peltonen, Hanna

    2017-03-01

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

  12. The metabolic switch of cancer

    Directory of Open Access Journals (Sweden)

    Yuting Ma

    2017-03-01

    Full Text Available Although remarkable progress has been made in oncology research, cancer is still a leading cause of death worldwide. It is well recognized that cancer is a genetic disease, yet metabolic alterations or reprogramming are the major phenotypes associated with the (epi-genetic modifications of cancer cells. Thus, understanding the metabolic changes of tumor cells will facilitate the diagnosis of cancer, alleviate drug resistance and provide novel druggable targets that can lead to cures for cancer. The first Sino-US Symposium on Cancer Metabolism was held in Chongqing on October 10th and 11th, with the theme of “cancer metabolism and precision cancer therapy”. The symposium brought about a dozen keynote speakers each from the US and mainland China, as well as one hundred delegates with an interest in cancer metabolism. This short article will briefly summarize the advances reported during this meeting.

  13. [Hypovitaminosis D and metabolic syndrome].

    Science.gov (United States)

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

    2014-12-23

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

  14. Osmotic Challenge Drives Rapid and Reversible Chromatin Condensation in Chondrocytes

    Science.gov (United States)

    Irianto, Jerome; Swift, Joe; Martins, Rui P.; McPhail, Graham D.; Knight, Martin M.; Discher, Dennis E.; Lee, David A.

    2013-01-01

    Changes in extracellular osmolality have been shown to alter gene expression patterns and metabolic activity of various cell types, including chondrocytes. However, mechanisms by which physiological or pathological changes in osmolality impact chondrocyte function remain unclear. Here we use quantitative image analysis, electron microscopy, and a DNase I assay to show that hyperosmotic conditions (>400 mOsm/kg) induce chromatin condensation, while hypoosmotic conditions (100 mOsm/kg) cause decondensation. Large density changes (p condensation and decondensation during a daily loading cycle. The effect of changes in osmolality on nuclear morphology (p condensation (p condensation and osmolality was accurately modeled by a polymer gel model which, along with the rapid nature of the chromatin condensation (<20 s), reveals the basic physicochemical nature of the process. Alterations in chromatin structure are expected to influence gene expression and thereby regulate chondrocyte activity in response to osmotic changes. PMID:23442954

  15. Combining Targeted Metabolomic Data with a Model of Glucose Metabolism: Toward Progress in Chondrocyte Mechanotransduction.

    Science.gov (United States)

    Salinas, Daniel; Minor, Cody A; Carlson, Ross P; McCutchen, Carley N; Mumey, Brendan M; June, Ronald K

    2017-01-01

    Osteoarthritis is a debilitating disease likely involving altered metabolism of the chondrocytes in articular cartilage. Chondrocytes can respond metabolically to mechanical loads via cellular mechanotransduction, and metabolic changes are significant because they produce the precursors to the tissue matrix necessary for cartilage health. However, a comprehensive understanding of how energy metabolism changes with loading remains elusive. To improve our understanding of chondrocyte mechanotransduction, we developed a computational model to calculate the rate of reactions (i.e. flux) across multiple components of central energy metabolism based on experimental data. We calculated average reaction flux profiles of central metabolism for SW1353 human chondrocytes subjected to dynamic compression for 30 minutes. The profiles were obtained solving a bounded variable linear least squares problem, representing the stoichiometry of human central energy metabolism. Compression synchronized chondrocyte energy metabolism. These data are consistent with dynamic compression inducing early time changes in central energy metabolism geared towards more active protein synthesis. Furthermore, this analysis demonstrates the utility of combining targeted metabolomic data with a computational model to enable rapid analysis of cellular energy utilization.

  16. Is Metabolic Syndrome On the Radar? Improving Real-Time Detection of Metabolic Syndrome and Physician Response by Computerized Scan of the Electronic Medical Record

    Science.gov (United States)

    Lui, Kingwai; Randhawa, Gagandeep; Totten, Vicken; Smith, Adam E.; Raese, Joachim

    2016-01-01

    Objective: Metabolic syndrome is a common underdiagnosed condition among psychiatric patients exacerbated by second-generation antipsychotics, with the exception of aripiprazole and ziprasidone. This study evaluated the prescribing and treating behavior with regard to antipsychotics and metabolic syndrome of psychiatrists before and after implementation of a mandatory admission order set and electronic notification of results. Method: Baseline data from 9,100 consecutive psychiatric admissions to a mental health hospital (July 2013–July 2014) were compared to postintervention data (July 2014–January 2015), which included 1,499 consecutive patient records. The intervention initiated standardized admission testing with electronic notification to psychiatrists when patients met metabolic syndrome criteria (according to Axis III of the DSM-IV). Charts were examined for inclusion of this diagnosis at discharge and for treatment changes. Results: At baseline, only 2.4% of patients (n = 214) were evaluated for metabolic syndrome. Of these, 34.5% (0.8% of the total sample) met metabolic syndrome criteria. Only 15 patients (0.16%) were comprehensively treated. No chart listed metabolic syndrome under Axis III of the DSM-IV. After the intervention, the diagnosis of patients meeting the criteria for metabolic syndrome increased from 0% to 29.3%. Less than 3% of patients were switched to drugs with a more benign metabolic profile. All patients who continued on second-generation antipsychotics had metabolic retesting. Thirty-eight experienced a significant and rapid increase in triglyceride levels after only 3 to 17 days. Conclusions: Mandatory intake testing increases the number of patients evaluated for metabolic syndrome. Electronic alerts increase the inclusion of metabolic syndrome among discharge diagnoses but rarely affect prescribing practices. PMID:27247842

  17. Metabolic memory: Evolving concepts.

    Science.gov (United States)

    Misra, Anoop; Bloomgarden, Zachary

    2018-03-01

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

  18. Metabolic Surgery Profoundly Influences Gut Microbial-Host Metabolic Crosstalk

    Science.gov (United States)

    Li, Jia V.; Ashrafian, Hutan; Bueter, Marco; Kinross, James; Sands, Caroline; le Roux, Carel W; Bloom, Stephen R.; Darzi, Ara; Athanasiou, Thanos; Marchesi, Julian R.; Nicholson, Jeremy K.; Holmes, Elaine

    2013-01-01

    Background and Aims Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes. Methods We apply a parallel and statistically integrated metagenomic and metabonomic approach to characterize Roux-en-Y gastric bypass (RYGB) effects in a rat model. Results We show substantial shifts of the main gut phyla towards higher levels of Proteobacteria (52-fold) specifically Enterobacter hormaechei. We also find low levels of Firmicutes (4.5-fold) and Bacteroidetes (2-fold) in comparison to sham-operated rats. Faecal extraction studies reveal a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diamnoethane. We find decreased urinary amines and cresols and demonstrate indices of modulated energy metabolism post-RYGB including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which associates with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically-induced effect on the gut-brain-liver metabolic axis is inferred by increased neurotropic compounds; faecal γ-aminobutyric acid (GABA) and glutamate. Conclusion This profound co-dependence of mammalian and microbial metabolism, which is systematically altered following RYGB surgery, suggests that RYGB exerts local and global metabolic activities. The effect of RYGB surgery on the host metabolic-microbial crosstalk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases. PMID:21572120

  19. Hepatic metabolism of carcinogenic β-asarone.

    Science.gov (United States)

    Cartus, Alexander T; Stegmüller, Simone; Simson, Nadine; Wahl, Andrea; Neef, Sylvia; Kelm, Harald; Schrenk, Dieter

    2015-09-21

    compounds (E)- and (Z)-3'-oxoasarone (5, 7). 1'-Oxoasarone (3) was probably also formed in incubations with 1 but was not detectable, possibly due to its rapid reaction with nucleophiles. Eventually, three mono-O-demethylated metabolites of 1 were detected in minor concentrations. The time course of metabolite formation and determined kinetic parameters show little species-specific differences in the microsomal metabolism of 1. Furthermore, the kinetic parameters imply a very low dependence of the pattern of metabolite formation from substrate concentration. In human liver microsomes, 71-75% of 1 will be metabolized via epoxidation, 21-15% via hydroxylation (and further oxidation), and 8-10% via demethylation at lower as well as higher concentrations of 1, respectively (relative values). On the basis of our results, we hypothesize that the genotoxic epoxides of 1 are the ultimate carcinogens formed from 1.

  20. [Electrolyte metabolism and emergency].

    Science.gov (United States)

    Nakao, I; Ito, T; Kasai, N

    1983-02-01

    In outlining the pathology of various electrolyte metabolism abnormalities in cancer patients we considered the main clinical points between pathologies and emergency treatment. In regard to sodium (Na+) metabolism, one pathologic state that requires our attention is hypernatremia. Hypernatremia is accompanied with dehydration and is due to water loss, vomiting, diarrhea and renal insufficiency. One of the major causes of this condition is lack of the antidiuretic hormone due to intracranial metastasis of the tumor. When hypernatremia becomes severe, it is accompanied with circulatory failure, muscular asthenia, disorientation, convulsions, coma and other cerebral symptoms. Treatment consists of replenishing the water content by infusion of electrolyte solutions which should be carefully conducted after complete diagnose of the severity of the patient's pathological condition. Hyponatremia, like sick cell syndrome, is observed relatively frequently in cancer patients. When the serum Na level falls markedly, it induces cerebral edema and causes disorders of consciousness. The major treatment consists of providing both water and sodium supplements. Hyperkalemia is observed at the time of renal insufficiency, tissue lesions, vomiting, and diarrhea. When serum potassium level rises, it causes bradycardia, ventricular fibrillation, or cardiac arrest. It is important to diagnostically apprehend the severity of this condition using EKG and determining the serum K1+ level. For emergency treatment injection of calcium gluconate is very effective. Hypokalemia is often manifested by the loss of intestinal fluids due to diarrhea or during administration of diuretic agents. Clinical symptoms include neural paralysis but emergencies occur relatively infrequently. K C1 injections are used in treating this condition. Hypercalcemia is manifested in cancer patients during hyperparathyroidism. Its clinical symptoms include lassitude, tachycardia, nausea, vomiting, and renal dys

  1. Microbial metabolism of tholin

    Science.gov (United States)

    Stoker, C. R.; Boston, P. J.; Mancinelli, R. L.; Segal, W.; Khare, B. N.; Sagan, C.

    1990-05-01

    In this paper, we show that a wide variety of common soil bacteria are able to obtain their carbon and energy needs from tholin (a class of complex organic heteropolymers thought to be widely distributed through the solar system; in this case tholin was produced by passage of electrical discharge through a mixture of methane, ammonia, and water vapor). We have isolated aerobic, anaerobic, and facultatively anaerobic bacteria which are able to use tholin as a sole carbon source. Organisms which metabolize tholin represent a variety of bacterial genera including Clostridium, Pseudomonas, Bacillus, Acinetobacter, Paracoccus, Alcaligenes, Micrococcus, Cornebacterium, Aerobacter, Arthrobacter, Flavobacterium,and Actinomyces. Aerobic tholin-using bacteria were firrst isolated from soils containing unusual or sparse carbon sources. Some of these organisms were found to be facultatively anaerobic. Strictly anaerobic tholin-using bacteria were isolated from both carbon-rich and carbon-poor anaerobic lake muds. In addition, both aerobic and anaerobic tholin-using bacteria were isolated from common soil collected outside the laboratory building. Some, but not all, of the strains that were able to obtain carbon from tholin were also able to obtain their nitrogen requirements from tholin. Bacteria isolated from common soils were tested for their ability to obtain carbon from the water-soluble fraction, the ethanol-soluble fraction, and the water/ethanol-insoluble fraction of the tholin. Of the 3.5 × 10 7 bacteria isolated per gram of common soils, 1.7 0.5, and 0.2%, respectively, were able to obtaib their carbon requirements from the water-soluble fraction, the ethanol-soluble fraction and the water/ethanol-insoluble fraction of the tholin. The palatability of tholins to modern microbes may have implications for the early evolution of microbial life on Earth. Tholins may have formed the base of the food chain for an early heterotrophic biosphere before the evolution of

  2. Rapid flow-induced responses in endothelial cells

    Science.gov (United States)

    Stamatas, G. N.; McIntire, L. V.

    2001-01-01

    Endothelial cells alter their morphology, growth rate, and metabolism in response to fluid shear stress. To study rapid flow-induced responses in the 3D endothelial cell morphology and calcium distribution, coupled fluorescence microscopy with optical sectioning, digital imaging, and numerical deconvolution techniques have been utilized. Results demonstrate that within the first minutes of flow application nuclear calcium is increasing. In the same time frame whole cell height and nuclear height are reduced by about 1 microm. Whole cell height changes may facilitate reduction of shear stress gradients on the luminal surface, whereas nuclear structural changes may be important for modulating endothelial growth rate and metabolism. To study the role of the cytoskeleton in these responses, endothelial cells have been treated with specific disrupters (acrylamide, cytochalasin D, and colchicine) of each of the cytoskeleton elements (intermediate filaments, microfilaments, and microtubules, respectively). None of these compounds had any effect on the shear-induced calcium response. Cytochalasin D and acrylamide did not affect the shear-induced nuclear morphology changes. Colchicine, however, completely abrogated the response, indicating that microtubules may be implicated in force transmission from the plasma membrane to the nucleus. A pedagogical model based on tensegrity theory principles is presented that is consistent with the results on the 3D endothelial morphology.

  3. Drosophila provides rapid modeling of renal development, function, and disease

    Science.gov (United States)

    Romero, Michael F.

    2010-01-01

    The evolution of specialized excretory cells is a cornerstone of the metazoan radiation, and the basic tasks performed by Drosophila and human renal systems are similar. The development of the Drosophila renal (Malpighian) tubule is a classic example of branched tubular morphogenesis, allowing study of mesenchymal-to-epithelial transitions, stem cell-mediated regeneration, and the evolution of a glomerular kidney. Tubule function employs conserved transport proteins, such as the Na+, K+-ATPase and V-ATPase, aquaporins, inward rectifier K+ channels, and organic solute transporters, regulated by cAMP, cGMP, nitric oxide, and calcium. In addition to generation and selective reabsorption of primary urine, the tubule plays roles in metabolism and excretion of xenobiotics, and in innate immunity. The gene expression resource FlyAtlas.org shows that the tubule is an ideal tissue for the modeling of renal diseases, such as nephrolithiasis and Bartter syndrome, or for inborn errors of metabolism. Studies are assisted by uniquely powerful genetic and transgenic resources, the widespread availability of mutant stocks, and low-cost, rapid deployment of new transgenics to allow manipulation of renal function in an organotypic context. PMID:20926630

  4. Treatment of Amino Acid Metabolism Disorders

    Science.gov (United States)

    ... amino acid metabolism disorders Treatment of amino acid metabolism disorders E-mail to a friend Please fill ... It's been added to your dashboard . Amino acid metabolism disorders are rare health conditions that affect a ...

  5. The Application Trends of Rapid Prototyping Manufacturing

    Directory of Open Access Journals (Sweden)

    Qiu Xiao Lin

    2016-01-01

    characteristics of laser stero lithography (LSL selective laser sintering (SLS, three-dimensional printing (DP, fused deposition modeling (FDM, computer numerical control (CNC and other rapid prototyping technologies. After discussed these five rapid prototyping technology materials, we presented the hotspot and direction of rapid prototyping technology and look forward to the development of its technique, the expansion of its field and the progress of its academic ideology.

  6. Xenobiotic Metabolism and Gut Microbiomes.

    Directory of Open Access Journals (Sweden)

    Anubhav Das

    Full Text Available Humans are exposed to numerous xenobiotics, a majority of which are in the form of pharmaceuticals. Apart from human enzymes, recent studies have indicated the role of the gut bacterial community (microbiome in metabolizing xenobiotics. However, little is known about the contribution of the plethora of gut microbiome in xenobiotic metabolism. The present study reports the results of analyses on xenobiotic metabolizing enzymes in various human gut microbiomes. A total of 397 available gut metagenomes from individuals of varying age groups from 8 nationalities were analyzed. Based on the diversities and abundances of the xenobiotic metabolizing enzymes, various bacterial taxa were classified into three groups, namely, least versatile, intermediately versatile and highly versatile xenobiotic metabolizers. Most interestingly, specific relationships were observed between the overall drug consumption profile and the abundance and diversity of the xenobiotic metabolizing repertoire in various geographies. The obtained differential abundance patterns of xenobiotic metabolizing enzymes and bacterial genera harboring them, suggest their links to pharmacokinetic variations among individuals. Additional analyses of a few well studied classes of drug modifying enzymes (DMEs also indicate geographic as well as age specific trends.

  7. Metabolic syndrome in androgenic alopecia.

    Science.gov (United States)

    Gopinath, Hima; Upadya, Gatha M

    2016-01-01

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

  8. Cancer metabolism: a modeling perspective

    Directory of Open Access Journals (Sweden)

    Pouyan eGhaffari Nouran

    2015-12-01

    Full Text Available Tumor cells alter their metabolism to maintain unregulated cellular proliferation and survival, but this transformation leaves them reliant on constant supply of nutrients and energy. In addition to the widely studied dysregulated glucose metabolism to fuel tumor cell growth, accumulating evidences suggest that utilization of amino acids and lipids contributes significantly to cancer cell metabolism. Also recent progresses in our understanding of carcinogenesis have revealed that cancer is a complex disease and cannot be understood through simple investigation of genetic mutations of cancerous cells. Cancer cells present in complex tumor tissues communicate with the surrounding microenvironment and develop traits which promote their growth, survival and metastasis. Decoding the full scope and targeting dysregulated metabolic pathways that support neoplastic transformations and their preservation requires both the advancement of experimental technologies for more comprehensive measurement of omics as well as the advancement of robust computational methods for accurate analysis of the generated data. Here, we review cancer-associated reprogramming of metabolism and highlight the capability of genome-scale metabolic modeling approaches in perceiving a system-level perspective of cancer metabolism and in detecting novel selective drug targets

  9. Rapid Automated Mission Planning System Project

    Data.gov (United States)

    National Aeronautics and Space Administration — The proposed innovation is an automated UAS mission planning system that will rapidly identify emergency (contingency) landing sites, manage contingency routing, and...

  10. WIST: toolkit for rapid, customized LIMS development

    National Research Council Canada - National Science Library

    Huang, Y Wayne; Arkin, Adam P; Chandonia, John-Marc

    2011-01-01

    Workflow Information Storage Toolkit (WIST) is a set of application programming interfaces and web applications that allow for the rapid development of customized laboratory information management systems (LIMS...

  11. JIEDDO Experience Provides Rapid Acquisition Insights

    National Research Council Canada - National Science Library

    James P Craft

    2015-01-01

    .... JIDA's rapid acquisition capabilities were preserved by transitioning the expedient organization that received supplemental funding into the Defense Department's newest combat support agency (CSA...

  12. Physics of metabolic organization

    Science.gov (United States)

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology.

  13. Physics of metabolic organization.

    Science.gov (United States)

    Jusup, Marko; Sousa, Tânia; Domingos, Tiago; Labinac, Velimir; Marn, Nina; Wang, Zhen; Klanjšček, Tin

    2017-03-01

    We review the most comprehensive metabolic theory of life existing to date. A special focus is given to the thermodynamic roots of this theory and to implications that the laws of physics-such as the conservation of mass and energy-have on all life. Both the theoretical foundations and biological applications are covered. Hitherto, the foundations were more accessible to physicists or mathematicians, and the applications to biologists, causing a dichotomy in what always should have been a single body of work. To bridge the gap between the two aspects of the same theory, we (i) adhere to the theoretical formalism, (ii) try to minimize the amount of information that a reader needs to process, but also (iii) invoke examples from biology to motivate the introduction of new concepts and to justify the assumptions made, and (iv) show how the careful formalism of the general theory enables modular, self-consistent extensions that capture important features of the species and the problem in question. Perhaps the most difficult among the introduced concepts, the utilization (or mobilization) energy flow, is given particular attention in the form of an original and considerably simplified derivation. Specific examples illustrate a range of possible applications-from energy budgets of individual organisms, to population dynamics, to ecotoxicology. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. [Regulation of terpene metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Croteau, R.

    1991-01-01

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

  15. [Metabolic safety of antidepressant medicines].

    Science.gov (United States)

    Łężak, Wojciech; Mokros, Łukasz; Karbownik, Michał Seweryn; Witusik, Andrzej; Kosmalski, Marcin; Kowalczyk, Edward; Pietras, Tadeusz

    2017-05-23

    Metabolic syndrome is a very serious health issue, not only from internal medicine's point of view. Patients suffering from overweight, arterial hypertension, lipids and carbohydrates metabolism disorders are also in the circle of interest of other areas of medicine, including psychiatry. Currently, one of key problems of pharmacotherapy is a comorbidity of metabolic syndrome and mental disorder. Depression is more common than schizophrenia. Despite the fact that in everyday clinical practice there are more patients with depression than schizophrenia, there is a bigger interest among scientists for metabolic syndrome after antipsychotic drugs than as an effect of use of antidepressant agents. The aim of an analysis was to review literature committed to influence of depression pharmacotherapy on development of metabolic syndrome. 169 results were provided, including 18 original publications. Final analysis consists of 9 that investigate correlation between antidepressive medicines use and metabolic syndrome development (but not its each individual component). In general, antidepressant pharmacotherapy is associated not only with increased risk of metabolic syndrome occurrence but also their worsening. However, it needs to be emphasized that there is a difference between antidepressants groups - tricyclic antidepressive medicines are the most commonly associated with risk of developing metabolic disorders, but also SNRIs and SSRIs are mentioned as significant contributors. Mechanisms of aforementioned changes are still unclear. However, their influence on histamine and serotonin pathways, which take part in regulation of i.e. food intake, is suggested. The search for mechanisms that are precisely responsible for metabolic changes continues, in hope of finding a way to avoid adverse effects of antidepressant medicines use.

  16. Cardiac metabolism in myocardial ischemia.

    Science.gov (United States)

    Rosano, Giuseppe M C; Fini, Massimo; Caminiti, Giuseppe; Barbaro, Giuseppe

    2008-01-01

    Myocardial ischemia occurs for a mismatch between blood flow and metabolic requirements, when the rate of oxygen and metabolic substrates delivery to the myocardium is insufficient to meet the myocardial energy requirements for a given myocardial workload. During ischemia, substantial changes occur in cardiac energy metabolism, as a consequence of the reduced oxygen availability. Some of these metabolic changes are beneficial and may help the heart adapt to the ischemic condition. However, most of the changes are maladaptive and contribute to the severity of the ischemic injury leading stunned or hibernating myocardium, cell death and ultimately to contractile disfunction. Dramatic changes in cardiac metabolism and contractile function, also occur during myocardial reperfusion as a consequence of the generation of oxygen free radicals, loss of cation homeostasis, depletion of energy stores, and changes in subcellular activities. The reperfusion injury may cause in the death of cardiac myocytes that were still viable immediately before myocardial reperfusion. This form of myocardial injury, by itself can induce cardiomyocyte death and increase infarct size. During acute ischemia the relative substrate concentration is the prime factor defining preference and utilization rate. Allosteric enzyme regulation and protein phosphorylation cascades, partially controlled by hormones such as insulin, modulate the concentration effect; together they provide short-term adjustments of cardiac energy metabolism. The expression of metabolic genes is also dynamically regulated in response to developmental and (patho)physiological conditions, leading to long-term adjustments. Specific nuclear receptor transcription factors and co-activators regulate the expression of these genes. Understanding the functional role of these changes is critical for developing the concept of metabolic intervention for heart disease. The paper will review the alterations in energy metabolism that occur

  17. MicroRNAs in Metabolism and Metabolic Disorders

    Science.gov (United States)

    Rottiers, Veerle; Näär, Anders M.

    2014-01-01

    MicroRNAs (miRNAs) have recently emerged as key regulators of metabolism. For example, miR-33a and b play a crucial role in controlling cholesterol and lipid metabolism in concert with their host genes, the SREBP transcription factors. Metabolic miRNAs such as miR-103 and miR-107 regulate insulin and glucose homeostasis, while others, such as miR-34a, may be key regulators of hepatic lipid homeostasis. The discovery of circulating miRNAs has highlighted their potential as both endocrine signalling molecules and disease markers. Dysregulation of miRNAs may contribute to metabolic abnormalities, suggesting that miRNAs may potentially serve as therapeutic targets to ameliorate cardiometabolic disorders. PMID:22436747

  18. Metabolic interrelationships software application: Interactive learning tool for intermediary metabolism*.

    Science.gov (United States)

    Verhoeven, Adrie J M; Doets, Mathijs; Lamers, Jos M J; Koster, Johan F

    2005-11-01

    We developed and implemented the software application titled Metabolic Interrelationships as a self-learning and -teaching tool for intermediary metabolism. It is used by undergraduate medical students in an integrated organ systems-based and disease-oriented core curriculum, which started in our medical faculty in 2001. The computer program provides an interactive environment in which students learn to integrate the major metabolic pathways as well as their hormonal control mechanisms as far as they depend on nutritional status. Students can explore the time- and tissue-dependent changes in mammalian intermediary metabolism during a feeding-fasting cycle. Starting from a whole-body view of interorgan nutrient fluxes, the student can make excursions to individual organs and, from there, to increasing levels of molecular detail and to explanatory animations. The application is well received by students and staff. Copyright © 2005 International Union of Biochemistry and Molecular Biology, Inc.

  19. Metabolic Programming in the Immediate Postnatal Life

    National Research Council Canada - National Science Library

    Patel, Mulchand S; Srinivasan, Malathi

    2011-01-01

    The metabolic programming effects of nutritional modifications in the immediate postnatal life are increasingly recognized to independently contribute to the development of metabolic syndrome in later life...

  20. Ocular associations of metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Rupali Chopra

    2012-01-01

    Full Text Available Metabolic syndrome is a cluster of diseases including central obesity, dyslipidemia, hyperglycemia, and high blood pressure. People with metabolic syndrome have been shown to be at an increased risk of developing cardiovascular disease, beyond the risk associated with individual components of the syndrome. The association of diabetes and hypertension with retinopathy, cataract, and raised intraocular pressure is well known. This review highlights the association of metabolic syndrome, including all its components, with various ocular conditions such as retinopathy, central retinal artery occlusion, cataracts, and raised intraocular pressure.

  1. Interrogating Metabolism in Brain Cancer.

    Science.gov (United States)

    Salzillo, Travis C; Hu, Jingzhe; Nguyen, Linda; Whiting, Nicholas; Lee, Jaehyuk; Weygand, Joseph; Dutta, Prasanta; Pudakalakatti, Shivanand; Millward, Niki Zacharias; Gammon, Seth T; Lang, Frederick F; Heimberger, Amy B; Bhattacharya, Pratip K

    2016-11-01

    This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Analysis of metabolic flux using dynamic labeling and metabolic modeling

    OpenAIRE

    Fernie, A.; Morgan, J.

    2013-01-01

    Metabolic fluxes and the capacity to modulate them are a crucial component of the ability of the plant cell to react to environmental perturbations. Our ability to quantify them and to attain information concerning the regulatory mechanisms which control them is therefore essential to understand and influence metabolic networks. For all but the simplest of flux measurements labelling methods have proven to be the most informative. Both steady-state and dynamic labelling approaches having been...

  3. Rapid measurement of meat spoilage using fluorescence spectroscopy

    Science.gov (United States)

    Wu, Binlin; Dahlberg, Kevin; Gao, Xin; Smith, Jason; Bailin, Jacob

    2017-02-01

    Food spoilage is mainly caused by microorganisms, such as bacteria. In this study, we measure the autofluorescence in meat samples longitudinally over a week in an attempt to develop a method to rapidly detect meat spoilage using fluorescence spectroscopy. Meat food is a biological tissue, which contains intrinsic fluorophores, such as tryptophan, collagen, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) etc. As meat spoils, it undergoes various morphological and chemical changes. The concentrations of the native fluorophores present in a sample may change. In particular, the changes in NADH and FAD are associated with microbial metabolism, which is the most important process of the bacteria in food spoilage. Such changes may be revealed by fluorescence spectroscopy and used to indicate the status of meat spoilage. Therefore, such native fluorophores may be unique, reliable and nonsubjective indicators for detection of spoiled meat. The results of the study show that the relative concentrations of all above fluorophores change as the meat samples kept in room temperature ( 19° C) spoil. The changes become more rapidly after about two days. For the meat samples kept in a freezer ( -12° C), the changes are much less or even unnoticeable over a-week-long storage.

  4. Rapid neutrophil adhesion to activated endothelium mediated by GMP-140.

    Science.gov (United States)

    Geng, J G; Bevilacqua, M P; Moore, K L; McIntyre, T M; Prescott, S M; Kim, J M; Bliss, G A; Zimmerman, G A; McEver, R P

    1990-02-22

    Granule membrane protein-140 (GMP-140), a membrane glycoprotein of platelet and endothelial cell secretory granules, is rapidly redistributed to the plasma membrane during cellular activation and degranulation. Also known as PADGEM protein, GMP-140 is structurally related to two molecules involved in leukocyte adhesion to vascular endothelium: ELAM-1, a cytokine-inducible endothelial cell receptor for neutrophils, and the MEL-14 lymphocyte homing receptor. These three proteins define a new gene family, termed selectins, each of which contains an N-terminal lectin domain, followed by an epidermal growth factor-like module, a variable number of repeating units related to those in complement-binding proteins, a transmembrane domain, and a short cytoplasmic tail. Here we demonstrate that GMP-140 can mediate leukocyte adhesion, thus establishing a functional similarity with the other selectins. Human neutrophils and promyelocytic HL-60 cells bind specifically to COS cells transfected with GMP-140 complementary DNA and to microtitre wells coated with purified GMP-140. Cell binding does not require active neutrophil metabolism but is dependent on extracellular Ca2+. Within minutes after stimulation with phorbol esters or histamine, human endothelial cells become adhesive for neutrophils; this interaction is inhibited by antibodies to GMP-140. Thus, GMP-140 expressed by activated endothelium might promote rapid neutrophil targeting to sites of acute inflammation.

  5. Diet rapidly and reproducibly alters the human gut microbiome

    Science.gov (United States)

    David, Lawrence A.; Maurice, Corinne F.; Carmody, Rachel N.; Gootenberg, David B.; Button, Julie E.; Wolfe, Benjamin E.; Ling, Alisha V.; Devlin, A. Sloan; Varma, Yug; Fischbach, Michael A.; Biddinger, Sudha B.; Dutton, Rachel J.; Turnbaugh, Peter J.

    2013-01-01

    Long-term diet influences the structure and activity of the trillions of microorganisms residing in the human gut1–5, but it remains unclear how rapidly and reproducibly the human gut microbiome responds to short-term macronutrient change. Here, we show that the short-term consumption of diets composed entirely of animal or plant products alters microbial community structure and overwhelms inter-individual differences in microbial gene expression. The animal-based diet increased the abundance of bile-tolerant microorganisms (Alistipes, Bilophila, and Bacteroides) and decreased the levels of Firmicutes that metabolize dietary plant polysaccharides (Roseburia, Eubacterium rectale, and Ruminococcus bromii). Microbial activity mirrored differences between herbivorous and carnivorous mammals2, reflecting trade-offs between carbohydrate and protein fermentation. Foodborne microbes from both diets transiently colonized the gut, including bacteria, fungi, and even viruses. Finally, increases in the abundance and activity of Bilophila wadsworthia on the animal-based diet support a link between dietary fat, bile acids, and the outgrowth of microorganisms capable of triggering inflammatory bowel disease6. In concert, these results demonstrate that the gut microbiome can rapidly respond to altered diet, potentially facilitating the diversity of human dietary lifestyles. PMID:24336217

  6. Adult-onset phenylketonuria with rapidly progressive dementia and parkinsonism.

    Science.gov (United States)

    Tufekcioglu, Zeynep; Cakar, Arman; Bilgic, Basar; Hanagasi, Hasmet; Gurvit, Hakan; Emre, Murat

    2016-06-01

    Phenylketonuria (PKU) is an autosomal recessive metabolic disorder due to mutations in the phenylalanine hydroxylase (PAH) gene, which converts phenylalanine (PHE) to tyrosine. Although it is principally a childhood disorder, in rare cases, the first signs of PKU may develop in late adulthood resembling common neurological diseases. Here we report a 59-year-old, previously normal functioning man who was admitted with blurred vision, cognitive problems, and gait difficulty that began 8 months before. He had brisk reflexes and left side dominant parkinsonism. His Mini-Mental State Examination (MMSE) score was 25/30, and neuropsychological evaluation revealed a dysexecutive syndrome with simultanagnosia and constructional apraxia. His Clinical Dementia Rating score (CDR) was 1. Cranial MRI revealed bilateral diffuse hyperintense lesions in parietal and occipital white matter in T2, fluid-attenuated inversion recovery, and diffusion weighted images. Diagnostic workup for rapidly progressive dementias was all normal except PHE level which was found to be highly elevated (1075 μmol/L, normal 39-240 μmol/L) with normal tyrosine level (61.20 μmol/L, normal 35-100 μmol/L). Three months after PHE-restricted diet, his cognitive impairment and signs of parkinsonism significantly improved, with MRI scan unchanged. This case demonstrates that late-onset PKU is a rare, treatable cause of rapidly progressive dementia and parkinsonism with certain constellations such as consanguinity and white matter abnormalities (WMAs) in imaging.

  7. Metabolic network visualization eliminating node redundance and preserving metabolic pathways

    Directory of Open Access Journals (Sweden)

    Sagot Marie-France

    2007-07-01

    Full Text Available Abstract Background The tools that are available to draw and to manipulate the representations of metabolism are usually restricted to metabolic pathways. This limitation becomes problematic when studying processes that span several pathways. The various attempts that have been made to draw genome-scale metabolic networks are confronted with two shortcomings: 1- they do not use contextual information which leads to dense, hard to interpret drawings, 2- they impose to fit to very constrained standards, which implies, in particular, duplicating nodes making topological analysis considerably more difficult. Results We propose a method, called MetaViz, which enables to draw a genome-scale metabolic network and that also takes into account its structuration into pathways. This method consists in two steps: a clustering step which addresses the pathway overlapping problem and a drawing step which consists in drawing the clustered graph and each cluster. Conclusion The method we propose is original and addresses new drawing issues arising from the no-duplication constraint. We do not propose a single drawing but rather several alternative ways of presenting metabolism depending on the pathway on which one wishes to focus. We believe that this provides a valuable tool to explore the pathway structure of metabolism.

  8. Plant Metabolic Modeling: Achieving New Insight into Metabolism and Metabolic Engineering

    Science.gov (United States)

    Baghalian, Kambiz; Hajirezaei, Mohammad-Reza; Schreiber, Falk

    2014-01-01

    Models are used to represent aspects of the real world for specific purposes, and mathematical models have opened up new approaches in studying the behavior and complexity of biological systems. However, modeling is often time-consuming and requires significant computational resources for data development, data analysis, and simulation. Computational modeling has been successfully applied as an aid for metabolic engineering in microorganisms. But such model-based approaches have only recently been extended to plant metabolic engineering, mainly due to greater pathway complexity in plants and their highly compartmentalized cellular structure. Recent progress in plant systems biology and bioinformatics has begun to disentangle this complexity and facilitate the creation of efficient plant metabolic models. This review highlights several aspects of plant metabolic modeling in the context of understanding, predicting and modifying complex plant metabolism. We discuss opportunities for engineering photosynthetic carbon metabolism, sucrose synthesis, and the tricarboxylic acid cycle in leaves and oil synthesis in seeds and the application of metabolic modeling to the study of plant acclimation to the environment. The aim of the review is to offer a current perspective for plant biologists without requiring specialized knowledge of bioinformatics or systems biology. PMID:25344492

  9. Redesigned Human Metabolic Simulator

    Science.gov (United States)

    Duffield, Bruce; Jeng, Frank; Lange, Kevin

    2008-01-01

    A design has been formulated for a proposed improved version of an apparatus that simulates atmospheric effects of human respiration by introducing controlled amounts of carbon dioxide, water vapor, and heat into the air. Denoted a human metabolic simulator (HMS), the apparatus is used for testing life-support equipment when human test subjects are not available. The prior version of the HMS, to be replaced, was designed to simulate the respiratory effects of as many as four persons. It exploits the catalytic combustion of methyl acetate, for which the respiratory quotient (the molar ratio of carbon dioxide produced to oxygen consumed) is very close to the human respiratory quotient of about 0.86. The design of the improved HMS provides for simulation of the respiratory effects of as many as eight persons at various levels of activity. The design would also increase safety by eliminating the use of combustion. The improved HMS (see figure) would include a computer that would exert overall control. The computer would calculate the required amounts of oxygen removal, carbon dioxide addition, water addition, and heat addition by use of empirical equations for metabolic profiles of respiration and heat. A blower would circulate air between the HMS and a chamber containing a life-support system to be tested. With the help of feedback from a mass flowmeter, the blower speed would be adjusted to regulate the rate of flow according to the number of persons to be simulated and to a temperature-regulation requirement (the air temperature would indirectly depend on the rate of flow, among other parameters). Oxygen would be removed from the circulating air by means of a commercially available molecular sieve configured as an oxygen concentrator. Oxygen, argon, and trace amounts of nitrogen would pass through a bed in the molecular sieve while carbon dioxide, the majority of nitrogen, and other trace gases would be trapped by the bed and subsequently returned to the chamber. If

  10. Metabolic Syndrome in Nurses

    Directory of Open Access Journals (Sweden)

    María Escasany

    2014-01-01

    Full Text Available Objectives: To estimate the prevalence of metabolic syndrome (MS in female nurses in the Hospital Juan A. Fernandez (HJAF, Buenos Aires, Argentina, and to determine whether work, rest, diet, and health, are predictive of it.Materials and methods: For the first objective, a descriptive, observational and cross-sectional study was conducted, and for the second, a multivariate cross-sectional observational multivariate analysis was made comparing independent samples. A total of 192 nurses were studied between October 2008 and March 2009. They completed a questionnaire that include indicators that could be predictors of MS. Anthropometric measurements, including blood pressure were taken, was well as a blood sample to analyze fasting glucose, HDL-C and plasma triglycerides.Results: It was found that 35% and 41% of nurses were overweight and obese, respectively. A total of 92% had centro-abdominal obesity. The prevalence of MS found was 33.3% (95%CI, 26.7 to 40.5. Those who had this disease were between 53±9 years. Statistically significant differences were found in the bivariate analysis between MS and the variables, age, length of service, time worked during night shift, and academic studies.Conclusions: The prevalence of MS was 64/192 in HJAF nurses (33.3% I 95%CI, 26.7-40.5. There were no statistically significant differences with the indicators of, age, “time worked during night shift”, and “studies”. These results suggest that age is the most important variable in predicting the onset of MS in the population of nurses.

  11. Serum uric acid levels and metabolic syndrome.

    Science.gov (United States)

    Ciarla, Sara; Struglia, Manuela; Giorgini, Paolo; Striuli, Rinaldo; Necozione, Stefano; Properzi, Giuliana; Ferri, Claudio

    2014-07-01

    To investigate the relationship among serum uric acid levels and metabolic syndrome. Anthropometric parameters, serum uric acid and metabolic parameters were evaluated in 139 subjects. Serum uric acid levels were significantly higher in subjects with than without metabolic syndrome (p metabolic syndrome components (p for trend uric acid significantly correlated with various anthropometric and serum metabolic parameters. Serum uric acid levels were higher in individuals with rather than without metabolic syndrome and raised gradually as the number of metabolic syndrome components increased. The relationship between serum uric acid levels and various metabolic parameters suggests that uric acid might be considered as a component of metabolic syndrome. Hyperuricemia is a common finding in patients with the metabolic syndrome. Recent studies indicated that hyperuricemia may be also a predictor of metabolic syndrome development.

  12. [In vitro metabolism of forscolin isolated from Coleus forskohlii].

    Science.gov (United States)

    Zhang, Man; Meng, Zhi-Yun; Zhu, Xiao-Xia; Dou, Gui-Fang

    2013-03-01

    This paper is to report the study of the metabolism of forscolin in plasma and liver microsomes for guiding clinical therapy. Forscolin was quantified by HPLC-MS/MS. The metabolic stability of forscolin in rat, Beagle dog, monkey and human plasma and liver microsomes, mediated enzymes of forscolin and its inhibition on cytochrome P450 isoforms in human liver microsomes were studied. Results showed that forscolin was not metabolized in plasma of the four species but metabolized in liver microsomes of the four species. The t1/2 of forscolin in rat, Beagle dog, monkey and human liver microsomes were (52.0 +/- 15.0), (51.2 +/- 5.9), (6.0 +/- 0.2) and (11.9 +/- 1.8) min; CL(int) were (75.6 +/- 18.7), (60.9 +/- 6.8), (513.8 +/- 14.3) and (176.2 +/- 25.6) mL x min(-1) x kg(-1); CL were (34.8 +/- 4.5), (23.3 +/- 1.0), (40.3 +/- 0.5) and (17.9 +/- 0.3) mL x min(-1) x kg(-1), respectively. Forscolin was metabolized by CYP3A4 in human liver microsomes. There was definite inhibition on CYP3A4 at the concentrations of forscolin between 0.1 ng x mL(-1) and 5 microg x mL(-1). Therefore, forscolin is rapidly excreted from liver microsomes. Attention should be paid to the drug interaction when forscolin was used along with other drugs metabolized by CYP3A4 in clinics.

  13. Human drug metabolism: an introduction

    National Research Council Canada - National Science Library

    Coleman, Michael D

    2010-01-01

    Human Drug Metabolism, An Introduction, Second Edition provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences...

  14. Identification of Metabolic Pathway Systems

    National Research Council Canada - National Science Library

    Dolatshahi, Sepideh; Voit, Eberhard O

    2016-01-01

    .... Under ideal conditions, the first phase of DFE yields numerical representations of all fluxes within a metabolic pathway system, either as values at each time point or as plots against their substrates and modulators...

  15. Context-dependent metabolic networks

    CERN Document Server

    Beguerisse-Díaz, Mariano; Oyarzún, Diego; Picó, Jesús; Barahona, Mauricio

    2016-01-01

    Cells adapt their metabolism to survive changes in their environment. We present a framework for the construction and analysis of metabolic reaction networks that can be tailored to reflect different environmental conditions. Using context-dependent flux distributions from Flux Balance Analysis (FBA), we produce directed networks with weighted links representing the amount of metabolite flowing from a source reaction to a target reaction per unit time. Such networks are analyzed with tools from network theory to reveal salient features of metabolite flows in each biological context. We illustrate our approach with the directed network of the central carbon metabolism of Escherichia coli, and study its properties in four relevant biological scenarios. Our results show that both flow and network structure depend drastically on the environment: networks produced from the same metabolic model in different contexts have different edges, components, and flow communities, capturing the biological re-routing of metab...

  16. Metabolic-hydaulic model Data

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — The data contained in this workbook were compiled to investigate the relationship between hydrology of the Colorado River and ecosystem metabolism parameters (i.e.,...

  17. Metabolic Acidosis: Diagnostics and Treatment

    Directory of Open Access Journals (Sweden)

    R. F. Tepaev

    2016-01-01

    Full Text Available Metabolic acidosis is the most common child acid-base balance disorder. This condition accompanies a variety of diseases, and the degree of its severity correlates with the patients’ survival: although not a separate disease in itself, metabolic acidosis, however, can worsen the disease course and even lead to death. The pathology causes are various (in connection with life-threatening changes in various organs and systems — lungs, heart and blood vessels, kidneys, and also due to a violation of lipid metabolism, in case of diabetes, poisoning, etc., which determines the fact that a wide range of specialists are interested in the issue. Approaches to the diagnosis simplify the search for the etiology of metabolic acidosis. This study presents data on the physiological basis of acid-base balance regulation, and its etiology and pathophysiology; the principles of therapy are observed.

  18. Macrophages, immunity, and metabolic disease

    National Research Council Canada - National Science Library

    McNelis, Joanne C; Olefsky, Jerrold M

    2014-01-01

    .... It is well recognized that the immune system and metabolism are highly integrated, and macrophages, in particular, have been identified as critical effector cells in the initiation of inflammation...

  19. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  20. Metabolic Resistance in Bed Bugs

    Directory of Open Access Journals (Sweden)

    Omprakash Mittapalli

    2011-03-01

    Full Text Available Blood-feeding insects have evolved resistance to various insecticides (organochlorines, pyrethroids, carbamates, etc. through gene mutations and increased metabolism. Bed bugs (Cimex lectularius are hematophagous ectoparasites that are poised to become one of the major pests in households throughout the United States. Currently, C. lectularius has attained a high global impact status due to its sudden and rampant resurgence. Resistance to pesticides is one factor implicated in this phenomenon. Although much emphasis has been placed on target sensitivity, little to no knowledge is available on the role of key metabolic players (e.g., cytochrome P450s and glutathione S-transferases towards pesticide resistance in C. lectularius. In this review, we discuss different modes of resistance (target sensitivity, penetration resistance, behavioral resistance, and metabolic resistance with more emphasis on metabolic resistance.

  1. Metabolic syndrome and periodontal disease

    Directory of Open Access Journals (Sweden)

    Bharti Vipin

    2009-01-01

    Full Text Available It is important for a dentist to be well informed and updated on the latest research on the association of oral and systemic health. Of late, the metabolic syndrome has gained importance in dental literature, and metabolic syndrome and periodontal disease have been linked. Metabolic syndrome (MeS is a group of three or more (up to five interrelated metabolic abnormalities, which increases the risk of cardiovascular morbidity and mortality. Also, both MeS and periodontal disease may be linked through a common pathophysiological pathway. Some studies have been conducted to show such an association and additional studies are required to establish this association. A dental surgeon can play a major role in evaluating patients with MeS and thus prevent the development of overt cardiovascular disease.

  2. Histone variants and lipid metabolism

    NARCIS (Netherlands)

    Borghesan, Michela; Mazzoccoli, Gianluigi; Sheedfar, Fareeba; Oben, Jude; Pazienza, Valerio; Vinciguerra, Manlio

    2014-01-01

    Within nucleosomes, canonical histones package the genome, but they can be opportunely replaced with histone variants. The incorporation of histone variants into the nucleosome is a chief cellular strategy to regulate transcription and cellular metabolism. In pathological terms, cellular steatosis

  3. Complex systems in metabolic engineering.

    Science.gov (United States)

    Winkler, James D; Erickson, Keesha; Choudhury, Alaksh; Halweg-Edwards, Andrea L; Gill, Ryan T

    2015-12-01

    Metabolic engineers manipulate intricate biological networks to build efficient biological machines. The inherent complexity of this task, derived from the extensive and often unknown interconnectivity between and within these networks, often prevents researchers from achieving desired performance. Other fields have developed methods to tackle the issue of complexity for their unique subset of engineering problems, but to date, there has not been extensive and comprehensive examination of how metabolic engineers use existing tools to ameliorate this effect on their own research projects. In this review, we examine how complexity affects engineering at the protein, pathway, and genome levels within an organism, and the tools for handling these issues to achieve high-performing strain designs. Quantitative complexity metrics and their applications to metabolic engineering versus traditional engineering fields are also discussed. We conclude by predicting how metabolic engineering practices may advance in light of an explicit consideration of design complexity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. Test plan for the Rapid Geophysical Surveyor

    Energy Technology Data Exchange (ETDEWEB)

    Roybal, L.G.

    1993-06-01

    This document describes the test plant for demonstrating and testing a set of optically pumped cesium-based total field magnetometers using the Rapid Geophysical Surveyor platform. The proposed testing will be used to assess the function of these magnetometers as deployed on the Rapid Geophysical Surveyor and evaluate the practical utility of high resolution magnetic data for supporting waste retrieval efforts.

  5. Rapid eye movement sleep behavior disorder

    DEFF Research Database (Denmark)

    Schenck, C H; Montplaisir, J Y; Frauscher, B

    2013-01-01

    We aimed to provide a consensus statement by the International Rapid Eye Movement Sleep Behavior Disorder Study Group (IRBD-SG) on devising controlled active treatment studies in rapid eye movement sleep behavior disorder (RBD) and devising studies of neuroprotection against Parkinson disease (PD...

  6. Rapid Prototyping of Mobile Learning Games

    Science.gov (United States)

    Federley, Maija; Sorsa, Timo; Paavilainen, Janne; Boissonnier, Kimo; Seisto, Anu

    2014-01-01

    This position paper presents the first results of an on-going project, in which we explore rapid prototyping method to efficiently produce digital learning solutions that are commercially viable. In this first phase, rapid game prototyping and an iterative approach was tested as a quick and efficient way to create learning games and to evaluate…

  7. Rapid methods for detection of bacteria

    DEFF Research Database (Denmark)

    Corfitzen, Charlotte B.; Andersen, B.Ø.; Miller, M.

    2006-01-01

    Traditional methods for detection of bacteria in drinking water e.g. Heterotrophic Plate Counts (HPC) or Most Probable Number (MNP) take 48-72 hours to give the result. New rapid methods for detection of bacteria are needed to protect the consumers against contaminations. Two rapid methods...

  8. Cryopreservation of precision-cut tissue slices for application in drug metabolism research

    NARCIS (Netherlands)

    de Graaf, I.A.M.; Koster, H

    Cryopreservation of tissue slices greatly facilitates their use in drug metabolism research, leading to efficient use of human organ material and a decrease of laboratory animal use. In the present review, various mechanisms of cryopreservation such as equilibrium slow freezing, rapid freezing and

  9. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    . They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  10. Microelements and inherited metabolic diseases.

    Science.gov (United States)

    Marklová, Eliska

    2002-01-01

    In addition to the main groups of inherited metabolic diseases, including mitochondrial, peroxisomal and lysosomal defects, organic acidurias, porphyrias, defects of amino acids, saccharides and fatty acids metabolism, disorders of transport and utilisation of microelements have also been recognized. Recent findings concerning hereditary hemochromatosis (iron), Wilson and Menkes diseases (copper), molybdenum cofactor deficiency (molybdenum), defects of cobalamine synthesis (cobalt) and acrodermatitis enteropathica (zinc) are reviewed.

  11. Dietary Fats and Metabolic Syndrome

    OpenAIRE

    Danijela Ristic-Medic

    2013-01-01

    The quantity and quality of fats consumed in the diet can have important effects on prevention and/or improvement clustering metabolic abnormalities of the metabolic syndrome. Fatty acids as food ingredients regulate cholesterol homeostasis and concentrations of blood lipoproteins, and affect the levels of other cardiometabolic risk factors, such as blood pressure, haemostasis, and body weight, through various mechanisms. There is convincing evidence that exchanging dietary saturated fat with...

  12. Metabolic studies in thyroid disease

    OpenAIRE

    McCulloch, Alan Jackson

    1983-01-01

    The effects of thyroid hormones on intermediary metabolism have been investigated in hyperthyroid and hypothyroid man and in experimentally induced thyroid disease in the rat. Glucose metabolism was investigated by measurement of blood glucose, fasting and in 3 14 response to meals and by using both H-3-glucose and C-l-glucose as tracers in kinetic studies. Analysis of glycerol clearance from blood following bulk infusions of glycerol permitted evaluation of gluconeoge...

  13. Metabolic syndrome and cardiovascular risk

    Directory of Open Access Journals (Sweden)

    Abdullah M Alshehri

    2010-11-01

    Full Text Available The constellation of dyslipidemia (hypertriglyceridemia and low levels of high-density lipoprotein cholesterol, elevated blood pressure, impaired glucose tolerance, and central obesity is now classified as metabolic syndrome, also called syndrome X. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria for use in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general, they include a combination of multiple and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics, commonly manifest a prothrombotic state as well as and a proinflammatory state. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB, increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C. The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of atherosclerotic cardiovascular disease (ASCVD risk factors, that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to the components of the syndrome present as well as the other, non-metabolic syndrome risk factors in a particular person.

  14. Metabolic surgery and nutritional deficiencies.

    Science.gov (United States)

    Stroh, Christine; Manger, Thomas; Benedix, Frank

    2017-10-01

    The increasing prevalence of morbid obesity in Germany is associated with an increasing number of metabolic surgical interventions. Short-term surgical and long-term metabolic complications such as nutrient deficiencies can be considered as the main risks of metabolic surgery with its malabsorptive but also restrictive procedures. The aim of this review was to characterize the most relevant metabolic complications specific for the various bariatric procedures, which, subsequently, require a permanent surveillance and supplementation, respectively. Furthermore, we aimed to identify if there are diagnostic and therapeutic measures that can prevent those complications. Restrictive bariatric surgery such as "gastric banding" and "sleeve gastrectomy" can be associated with deficiencies related to B-vitamins whereas iron, folate, vitamin B1, B12 and D deficiencies are associated with the malabsorptive procedure such as "biliopancreatic diversion," "duodenal switch" and "Roux-en-Y gastric bypass". Due to possible metabolic and surgical complications after bariatric surgery, patients need to undergo life-long medical and dietetic surveillance. The recently published guidelines of the "American Association of Bariatric and Metabolic Surgery" are the basis for recommendations on supplementation and treatment following weight loss surgery.

  15. Sleep apnoea and metabolic dysfunction

    Directory of Open Access Journals (Sweden)

    Maria R. Bonsignore

    2013-09-01

    Full Text Available Obstructive sleep apnoea (OSA is a highly prevalent condition often associated with central obesity. In the past few years, several studies have analysed the potential independent contribution of OSA to the pathogenesis of metabolic abnormalities, including type 2 diabetes, the metabolic syndrome and non-alcoholic fatty liver disease. New perspectives in OSA patient care have been opened by the promotion of lifestyle interventions, such as diet and exercise programmes that could improve both OSA and the metabolic profile. The rich clinical literature on this subject, together with the growing amount of data on pathophysiological mechanisms provided by animal studies using the chronic intermittent hypoxia model, urged the organising Committee of the Sleep and Breathing meeting to organise a session on sleep apnoea and metabolic dysfunction, in collaboration with the European Association for the Study of Diabetes. This review summarises the state-of-the-art lectures presented in the session, more specifically the relationship between OSA and diabetes, the role of OSA in the metabolic consequences of obesity, and the effects of lifestyle interventions on nocturnal respiratory disturbances and the metabolic profile in OSA patients.

  16. The challenges of in silico contributions to drug metabolism in lead optimization.

    Science.gov (United States)

    Vaz, Roy J; Zamora, Ismael; Li, Yi; Reiling, Stephan; Shen, Jian; Cruciani, Gabriele

    2010-07-01

    The site of metabolism (SOM) predictions by CYP 3A4 are extremely important during the drug discovery process especially during the lead discovery or library design phases. With the ability to rapidly characterize metabolites from these enzymes, the challenges facing in silico contribution change during the drug optimization phase. Some of the challenges are addressed in this article. Some aspects of the SOM prediction software and methodology are discussed in this opinion article and examples of software utility in overcoming metabolic instability in drug optimization are shown. SOM prediction by various approaches is discussed. Two ways of overcoming metabolic instability, blocking the metabolic softspots and rational modification of the instable molecule to avoid interaction with the CYP pocket, are discussed. The contribution plot in MetaSite and its use are discussed. The reader will gain an understanding of possible approaches to either blocking the metabolic softspot or rationally modifying the molecule using MetaSite software or docking approaches. Blocking metabolism using fluorination has risks especially introducing multifluorinated benzene rings in the molecule. During the lead optimization phase of drug discovery, when metabolic instability is an issue in a series, in silico approaches can be used to modify the molecule in order to decrease clearance due to metabolism, even that due to CYP3A4.

  17. Effect of novel dietary supplement on metabolism in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Roger A. Vaughan

    2017-01-01

    Full Text Available Obesity is an increasingly prevalent and preventable morbidity with multiple behavioral, surgical and pharmacological interventions currently available. Commercial dietary supplements are often advertised to stimulate metabolism and cause rapid weight and/or fat loss, although few well-controlled studies have demonstrated such effects. We describe a commercially available dietary supplement (purportedly containing caffeine, catechins, and other metabolic stimulators on resting metabolic rate in humans, and on metabolism, mitochondrial content, and related gene expression in vitro. Human males ingested either a placebo or commercially available supplement (RF in a randomized double-blind placebo-controlled cross-over fashion. Metabolic rate, respiratory exchange ratio, and blood pressure were measured hourly for 3 h post-ingestion. To investigate molecular effects, human rhabdomyosarcoma cells (RD and mouse myocytes (C2C12 were treated with various doses of RF for various durations. RF enhanced energy expenditure and systolic blood pressure in human males without altering substrate utilization. In myocytes, RF enhanced metabolism, metabolic gene expression, and mitochondrial content suggesting RF may target common energetic pathways which control mitochondrial biogenesis. RF appears to increase metabolism immediately following ingestion, although it is unclear if RF provides benefits beyond those provided by caffeine alone. Additional research is needed to examine safety and efficacy for human weight loss.

  18. Bisphenol A and Metabolic Diseases: Challenges for Occupational Medicine

    Science.gov (United States)

    Caporossi, Lidia; Papaleo, Bruno

    2017-01-01

    The prevalence of metabolic diseases has markedly increased worldwide during the last few decades. Lifestyle factors (physical activity, energy-dense diets), together with a genetic predisposition, are well known factors in the pathophysiology of health problems. Bisphenol A (BPA) is a chemical compound used for polycarbonate plastics, food containers, epoxy resins coating metallic cans for food and beverage conservation. The ability of BPA to act as an endocrine disruptor—xenoestrogen in particular—is largely documented in literature, with numerous publications of in vivo and in vitro studies as well as epidemiological data on humans. Recently, different researchers studied the involvement of BPA in the development of insulin resistance; evidences in this way showed a potential role in etiology of metabolic disease, both for children and for adults. We review the epidemiological literature in the relation between BPA exposure and the risk of metabolic diseases in adults, with a focus on occupational exposure. Considering published data and the role of occupational physicians in promoting Workers’ Health, specific situations of exposure to BPA in workplace are described, and proposals for action to be taken are suggested. The comparison of the studies showed that exposure levels were higher in workers than in the general population, even if, sometimes, the measurement units used did not permit rapid comprehension. Nevertheless, occupational medicine focus on reproductive effects and not metabolic ones. PMID:28841159

  19. Nitrogen metabolism in Lignifying Pinus taeda cell cultures

    Science.gov (United States)

    van Heerden, P. S.; Towers, G. H.; Lewis, N. G.

    1996-01-01

    The primary metabolic fate of phyenylalanine, following its deamination in plants, is conscription of its carbon skeleton for lignin, suberin, flavonoid, and related metabolite formation. Since this accounts for approximately 30-40% of all organic carbon, an effective means of recycling the liberated ammonium ion must be operative. In order to establish how this occurs, the uptake and metabolism of various 15N-labeled precursors (15N-Phe, 15NH4Cl, 15N-Gln, and 15N-Glu) in lignifying Pinus taeda cell cultures was investigated, using a combination of high performance liquid chromatography, 15N NMR, and gas chromatograph-mass spectrometry analyses. It was found that the ammonium ion released during active phenylpropanoid metabolism was not made available for general amino acid/protein synthesis. Rather it was rapidly recycled back to regenerate phenylalanine, thereby providing an effective means of maintaining active phenylpropanoid metabolism with no additional nitrogen requirement. These results strongly suggest that, in lignifying cells, ammonium ion reassimilation is tightly compartmentalized.

  20. STAT3 Activities and Energy Metabolism: Dangerous Liaisons

    Energy Technology Data Exchange (ETDEWEB)

    Camporeale, Annalisa, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Demaria, Marco [Buck Institute for Research on Aging, 8001 Redwood Blvd, Novato, CA 94945 (United States); Monteleone, Emanuele [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy); Giorgi, Carlotta [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Wieckowski, Mariusz R. [Nencki Institute of Experimental Biology, Department of Biochemistry, Pasteur Str. 3, Warsaw 02-093 (Poland); Pinton, Paolo [Department of Experimental and Diagnostic Medicine, Section of General Pathology, Laboratory for Technologies of Advances Therapies (LTTA), University of Ferrara, Via Fossato di Mortara 70, Ferrara 44121 (Italy); Poli, Valeria, E-mail: annalisa.camporeale@unito.it [Molecular Biotechnology Center and Department of Molecular Biotechnology and Life Sciences, University of Turin, Via Nizza 52, Turin 10126 (Italy)

    2014-07-31

    STAT3 mediates cytokine and growth factor receptor signalling, becoming transcriptionally active upon tyrosine 705 phosphorylation (Y-P). Constitutively Y-P STAT3 is observed in many tumors that become addicted to its activity, and STAT3 transcriptional activation is required for tumor transformation downstream of several oncogenes. We have recently demonstrated that constitutively active STAT3 drives a metabolic switch towards aerobic glycolysis through the transcriptional induction of Hif-1α and the down-regulation of mitochondrial activity, in both MEF cells expressing constitutively active STAT3 (Stat3{sup C/C}) and STAT3-addicted tumor cells. This novel metabolic function is likely involved in mediating pre-oncogenic features in the primary Stat3{sup C/C} MEFs such as resistance to apoptosis and senescence and rapid proliferation. Moreover, it strongly contributes to the ability of primary Stat3{sup C/C} MEFs to undergo malignant transformation upon spontaneous immortalization, a feature that may explain the well known causative link between STAT3 constitutive activity and tumor transformation under chronic inflammatory conditions. Taken together with the recently uncovered role of STAT3 in regulating energy metabolism from within the mitochondrion when phosphorylated on Ser 727, these data place STAT3 at the center of a hub regulating energy metabolism under different conditions, in most cases promoting cell survival, proliferation and malignant transformation even though with distinct mechanisms.

  1. Extreme phenotypic plasticity in metabolic physiology of Antarctic Demosponges

    Directory of Open Access Journals (Sweden)

    Simon Anthony Morley

    2016-01-01

    Full Text Available Seasonal measurements of the metabolic physiology of four Antarctic demosponges and their associated assemblages, maintained in a flow through aquarium facility, demonstrated one of the largest differences in seasonal strategies between species and their associated sponge communities. The sponge oxygen consumption measured here exhibited both the lowest and highest seasonal changes for any Antarctic species; metabolic rates varied from a 25% decrease to a 5.8 fold increase from winter to summer, a range which was greater than all 17 Antarctic marine species (encompassing 8 phyla previously investigated and amongst the highest recorded for any marine environment. The differences in nitrogen excretion, metabolic substrate utilisation and tissue composition between species were, overall, greater than seasonal changes. The largest seasonal difference in tissue composition was an increase in CHN (Carbon, Hydrogen and Nitrogen content in Homaxinella balfourensis, a pioneer species in ice-scour regions, which changed growth form to a twig-like morph in winter. The considerable flexibility in seasonal and metabolic physiology across the Demospongiae likely enables these species to respond to rapid environmental change such as ice-scour, reductions in sea ice cover and ice-shelf collapse in the Polar Regions, shifting the paradigm that polar sponges always live life in the slow lane. Great phenotypic plasticity in physiology has been linked to differences in symbiotic community composition, and this is likely to be a key factor in the global success of sponges in all marine environments and their dominant role in many climax communities.

  2. Temporal Coordination of Carbohydrate Metabolism during Mosquito Reproduction.

    Directory of Open Access Journals (Sweden)

    Yuan Hou

    2015-07-01

    Full Text Available Hematophagous mosquitoes serve as vectors of multiple devastating human diseases, and many unique physiological features contribute to the incredible evolutionary success of these insects. These functions place high-energy demands on a reproducing female mosquito, and carbohydrate metabolism (CM must be synchronized with these needs. Functional analysis of metabolic gene profiling showed that major CM pathways, including glycolysis, glycogen and sugar metabolism, and citrate cycle, are dramatically repressed at post eclosion (PE stage in mosquito fat body followed by a sharply increase at post-blood meal (PBM stage, which were also verified by Real-time RT-PCR. Consistent to the change of transcript and protein level of CM genes, the level of glycogen, glucose and trehalose and other secondary metabolites are also periodically accumulated and degraded during the reproductive cycle respectively. Levels of triacylglycerols (TAG, which represent another important energy storage form in the mosquito fat body, followed a similar tendency. On the other hand, ATP, which is generated by catabolism of these secondary metabolites, showed an opposite trend. Additionally, we used RNA interference studies for the juvenile hormone and ecdysone receptors, Met and EcR, coupled with transcriptomics and metabolomics analyses to show that these hormone receptors function as major regulatory switches coordinating CM with the differing energy requirements of the female mosquito throughout its reproductive cycle. Our study demonstrates how, by metabolic reprogramming, a multicellular organism adapts to drastic and rapid functional changes.

  3. Temporal Coordination of Carbohydrate Metabolism during Mosquito Reproduction.

    Science.gov (United States)

    Hou, Yuan; Wang, Xue-Li; Saha, Tusar T; Roy, Sourav; Zhao, Bo; Raikhel, Alexander S; Zou, Zhen

    2015-07-01

    Hematophagous mosquitoes serve as vectors of multiple devastating human diseases, and many unique physiological features contribute to the incredible evolutionary success of these insects. These functions place high-energy demands on a reproducing female mosquito, and carbohydrate metabolism (CM) must be synchronized with these needs. Functional analysis of metabolic gene profiling showed that major CM pathways, including glycolysis, glycogen and sugar metabolism, and citrate cycle, are dramatically repressed at post eclosion (PE) stage in mosquito fat body followed by a sharply increase at post-blood meal (PBM) stage, which were also verified by Real-time RT-PCR. Consistent to the change of transcript and protein level of CM genes, the level of glycogen, glucose and trehalose and other secondary metabolites are also periodically accumulated and degraded during the reproductive cycle respectively. Levels of triacylglycerols (TAG), which represent another important energy storage form in the mosquito fat body, followed a similar tendency. On the other hand, ATP, which is generated by catabolism of these secondary metabolites, showed an opposite trend. Additionally, we used RNA interference studies for the juvenile hormone and ecdysone receptors, Met and EcR, coupled with transcriptomics and metabolomics analyses to show that these hormone receptors function as major regulatory switches coordinating CM with the differing energy requirements of the female mosquito throughout its reproductive cycle. Our study demonstrates how, by metabolic reprogramming, a multicellular organism adapts to drastic and rapid functional changes.

  4. Real-Time monitoring of intracellular wax ester metabolism

    Directory of Open Access Journals (Sweden)

    Karp Matti

    2011-09-01

    Full Text Available Abstract Background Wax esters are industrially relevant molecules exploited in several applications of oleochemistry and food industry. At the moment, the production processes mostly rely on chemical synthesis from rather expensive starting materials, and therefore solutions are sought from biotechnology. Bacterial wax esters are attractive alternatives, and especially the wax ester metabolism of Acinetobacter sp. has been extensively studied. However, the lack of suitable tools for rapid and simple monitoring of wax ester metabolism in vivo has partly restricted the screening and analyses of potential hosts and optimal conditions. Results Based on sensitive and specific detection of intracellular long-chain aldehydes, specific intermediates of wax ester synthesis, bacterial luciferase (LuxAB was exploited in studying the wax ester metabolism in Acinetobacter baylyi ADP1. Luminescence was detected in the cultivation of the strain producing wax esters, and the changes in signal levels could be linked to corresponding cell growth and wax ester synthesis phases. Conclusions The monitoring system showed correlation between wax ester synthesis pattern and luminescent signal. The system shows potential for real-time screening purposes and studies on bacterial wax esters, revealing new aspects to dynamics and role of wax ester metabolism in bacteria.

  5. Autophagy inhibition in cancer therapy: metabolic considerations for antitumor immunity.

    Science.gov (United States)

    Townsend, Katelin N; Hughson, Luke R K; Schlie, Katrin; Poon, Vincent I; Westerback, Ashley; Lum, Julian J

    2012-09-01

    Tumors and the immune system are intertwined in a competition where tilting the fine balance between tumor-specific immunity and tolerance can ultimately decide the fate of the host. Defensive and suppressive immunological responses to cancer are exquisitely sensitive to metabolic features of rapidly growing tumors, such as hypoxia, low nutrient availability, and aberrant growth factor signaling. As a result, clinical therapies impacting these properties change the in situ antitumor immune response by virtue of disrupting the tumor environment. To compensate for disruptions in cellular metabolism, cells activate autophagy to promote survival. On the basis of this notion, strategies designed to block autophagy in tumor cells are currently being tested in several human clinical trials. However, therapies that impair tumor metabolism must also take into account their effect on lymphocytes activated in the immune response to cancer. Given that a strong antitumor immune response is a positive prognostic factor in overall patient survival, identifying ways to block essential processes in tumor cells and suppressive immune cells while promoting those that are important for a robust immune response are of critical importance. Herein, we review the effects of anti-cancer agents that impact metabolism administered concurrently with autophagy inhibitors on immune cells and consider the implications for patient response to therapy. © 2012 John Wiley & Sons A/S.

  6. Rapid spheroid clearing on a microfluidic chip.

    Science.gov (United States)

    Silva Santisteban, Tomas; Rabajania, Omid; Kalinina, Iana; Robinson, Stephen; Meier, Matthias

    2017-12-19

    Spheroids are three-dimensional (3D) cell cultures that aim to bridge the gap between the use of whole animals and cellular monolayers. Microfluidics is regarded as an enabling technology to actively control the chemical environment of 3D cell cultures. Although a wide variety of platforms have been developed to handle spheroid cultures, the development of analytical systems for spheroids remains a major challenge. In this study, we engineered a microfluidic large-scale integration (mLSI) chip platform for tissue-clearing and imaging. To enable handling and culturing of spheroids on mLSI chips, with diameters within hundreds of microns, we first developed a general rapid prototyping procedure, which allows scaling up of the size of pneumatic membrane valves (PMV). The presented prototyping method makes use of milled poly(methylmethacrylate) (PMMA) molds for obtaining semi-circular microchannels with heights up to 750 μm. Semi-circular channel profiles are required for the functioning of the commonly used PMVs in normally open configuration. Height limits to tens of microns for this channel profile on photolithographic molds have hampered the application of 3D tissue models on mLSI chips. The prototyping technique was applied to produce an mLSI chip for miniaturization, automation, and integration of the steps involved in the tissue clearing method CLARITY, including spheroid fixation, acrylamide hydrogel infiltration, temperature-initiated hydrogel polymerization, lipid extraction, and immuno-fluorescence staining of the mitochondrial protein COX-IV, and metabolic enzyme GAPDH. Precise fluidic control over the liquids in the spheroid culturing chambers allowed implementation of a local hydrogel polymerization reaction, exclusively within the spheroid tissue. Hydrogel-embedded spheroids undergo swelling and shrinkage depending on the pH of the surrounding buffer solution. A pH-jump from 8.5 to 5.5 shrinks the hydrogel-embedded spheroid volume by 108% with a rate

  7. Glutamate metabolism in the brain focusing on astrocytes

    DEFF Research Database (Denmark)

    Schousboe, Arne; Scafidi, Susanna; Bak, Lasse Kristoffer

    2014-01-01

    Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both the anaplero......Metabolism of glutamate, the main excitatory neurotransmitter and precursor of GABA, is exceedingly complex and highly compartmentalized in brain. Maintenance of these neurotransmitter pools is strictly dependent on the de novo synthesis of glutamine in astrocytes which requires both......, as well as in nitrogen trafficking and ammonia homeostasis in brain. The anatomical specialization of astrocytic endfeet enables these cells to rapidly and efficiently remove neurotransmitters from the synaptic cleft to maintain homeostasis, and to provide glutamine to replenish neurotransmitter pools...... summarizes the evidence that astrocytes are essential and dynamic partners in both glutamatergic and GABAergic neurotransmission in brain....

  8. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-09-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCA and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.

  9. Oxidative Stress and the Homeodynamics of Iron Metabolism

    Science.gov (United States)

    Bresgen, Nikolaus; Eckl, Peter M.

    2015-01-01

    Iron and oxygen share a delicate partnership since both are indispensable for survival, but if the partnership becomes inadequate, this may rapidly terminate life. Virtually all cell components are directly or indirectly affected by cellular iron metabolism, which represents a complex, redox-based machinery that is controlled by, and essential to, metabolic requirements. Under conditions of increased oxidative stress—i.e., enhanced formation of reactive oxygen species (ROS)—however, this machinery may turn into a potential threat, the continued requirement for iron promoting adverse reactions such as the iron/H2O2-based formation of hydroxyl radicals, which exacerbate the initial pro-oxidant condition. This review will discuss the multifaceted homeodynamics of cellular iron management under normal conditions as well as in the context of oxidative stress. PMID:25970586

  10. Relevance of the Human Genome Project to inherited metabolic disease.

    Science.gov (United States)

    Burn, J

    1994-01-01

    The Human Genome Project is an international effort to identify the complete structure of the human genome. HUGO, the Human Genome Organization, facilitates international cooperation and exchange of information while the Genome Data Base will act as the on-line information retrieval and storage system for the huge amount of information being accumulated. The clinical register MIM (Mendelian Inheritance in Man) established by Victor McKusick is now an on-line resource that will allow biochemists working with inborn errors of metabolism to access the rapidly expanding body of knowledge. Biochemical and molecular genetics are complementary and should draw together to find solutions to the academic and clinical problems posed by inborn errors of metabolism.

  11. Protein and metabolic engineering for the production of organic acids.

    Science.gov (United States)

    Liu, Jingjing; Li, Jianghua; Shin, Hyun-Dong; Liu, Long; Du, Guocheng; Chen, Jian

    2017-09-01

    Organic acids are natural metabolites of living organisms. They have been widely applied in the food, pharmaceutical, and bio-based materials industries. In recent years, biotechnological routes to organic acids production from renewable raw materials have been regarded as very promising approaches. In this review, we provide an overview of current developments in the production of organic acids using protein and metabolic engineering strategies. The organic acids include propionic acid, pyruvate, itaconic acid, succinic acid, fumaric acid, malic acid and citric acid. We also expect that rapid developments in the fields of systems biology and synthetic biology will accelerate protein and metabolic engineering for microbial organic acid production in the future. Copyright © 2017. Published by Elsevier Ltd.

  12. Fenofibrate and metabolic syndrome.

    Science.gov (United States)

    Kraja, Aldi T; Province, Michael A; Straka, Robert J; Ordovas, Jose M; Borecki, Ingrid B; Arnett, Donna K

    2010-06-01

    The fibric acid derivative, fenofibrate (FF) has been used in the US since 1998 to manage patients with dyslipidemia. Typical changes in serum lipids as result a of FF treatment include clinically important mean reductions of serum triglycerides (TG) by a mean change of -93.7 mg/dL (-39.3%), increases of high density lipoprotein cholesterol (HDLC) by +5.5 mg/dL (+12.4%), and reductions in low density lipoprotein cholesterol (LDLC) by -17.9 mg/dL (-12.3%). The greatest reductions in serum TG are usually observed in subjects with elevated baseline TGs including those with the metabolic syndrome (MetS). Although statins remain the mainstay of therapy for most dyslipidemic patients, their combined use with FF would be expected to address residual risk resulting from less than optimal TG and HDLC levels in such patients. Clinical trials examining the cardiovascular benefits of FF alone or combined with statins have produced mixed results. These observations underscore our lack of understanding of which patients may benefit from FF therapy and which do not. Although FF's basic mechanism of action is known to involve PPAR-alpha agonist activity resulting in altered transcription of several genes, the actual genetic bases for variability in lipid response is poorly understood. Studies, such as our GOLDN study and others designed to better understand the genetic determinants of variability in the response to FF treatment and lipid levels. As a result several important genetic determinants of lipid levels have been identified. For example, in the GOLDN study SNPs from different genes were significantly associated with baseline lipid levels before treatment (APOA5- rs662799, rs3135506; APOC3- rs5128, rs2854117, rs4520); APOA4- rs5104; PPARA- rs9626730, rs135543, rs11703495; LPL- rs1801177), after treatment PPARA- rs11708495; LPL- rs1801177, and appeared to modulate overall response to FF treatment (NOS3- rs1799983). In this article, we will review the literature leading up to

  13. Regulation of drug metabolism in man by environmental chemicals and diet

    Energy Technology Data Exchange (ETDEWEB)

    Conney, A.H. (Hoffmann-LaRoche Inc., Nutley, NJ); Pantuck, E.J.; Hsiao, K.C.; Kuntzman, R.; Alvares, A.P.; Kappas, A.

    1977-04-01

    Studies in animals have shown that many environmental pollutants induce the synthesis or inhibit the activity of microsomal mixed-function oxygenases that metabolize drugs, carcinogens and normal body constituents such as steroid hormones. These effects on microsomal enzyme activity alter the duration and intensity of action of foreign and endogenous chemicals in animals, and such effects on metabolism may influence the carcinogenicity of some pollutants in man. Studies on the effects of environmental chemicals on drug metabolism in man are sparse. Exposure of humans to DDT or lindane in a pesticide factory results in an enhanced rate of metabolism of antipyrine and phenylbutazone and an increased urinary excretion of 6-..beta..-hydroxycortisol. Polycyclic aromatic hydrocarbons present in cigarette smoke, in charcoal-broiled meats, and in polluted city air are potent inducers of drug-metabolizing enzymes in animals. In humans, cigarette smoking stimulates the activity of placental enzymes that metabolize several drugs and carcinogens. In addition, cigarette smokers metabolize phenacetin, theophylline, and other drugs more rapidly in vivo than nonsmokers. Dietary factors are important in the regulation of drug metabolism in animals and man. Feeding rats brussels sprouts or cabbage stimulates the intestinal and hepatic metabolism of drugs in animals. This effect is caused, at least in part, by certain indoles normally present in these vegetables. The feeding of a charcoal-broiled beef diet to rats stimulates the metabolism of phenacetin in vitro, and a similar diet stimulates the in vivo metabolism of phenacetin in man. It is likely that polycyclic aromatic hydrocarbons are the major inducers in charcoal-broiled beef.

  14. Rapid sensing of l-leucine by human and murine hypothalamic neurons: Neurochemical and mechanistic insights.

    Science.gov (United States)

    Heeley, Nicholas; Kirwan, Peter; Darwish, Tamana; Arnaud, Marion; Evans, Mark L; Merkle, Florian T; Reimann, Frank; Gribble, Fiona M; Blouet, Clemence

    2018-02-07

    Dietary proteins are sensed by hypothalamic neurons and strongly influence multiple aspects of metabolic health, including appetite, weight gain, and adiposity. However, little is known about the mechanisms by which hypothalamic neural circuits controlling behavior and metabolism sense protein availability. The aim of this study is to characterize how neurons from the mediobasal hypothalamus respond to a signal of protein availability: the amino acid l-leucine. We used primary cultures of post-weaning murine mediobasal hypothalamic neurons, hypothalamic neurons derived from human induced pluripotent stem cells, and calcium imaging to characterize rapid neuronal responses to physiological changes in extracellular l-Leucine concentration. A neurochemically diverse subset of both mouse and human hypothalamic neurons responded rapidly to l-leucine. Consistent with l-leucine's anorexigenic role, we found that 25% of mouse MBH POMC neurons were activated by l-leucine. 10% of MBH NPY neurons were inhibited by l-leucine, and leucine rapidly reduced AGRP secretion, providing a mechanism for the rapid leucine-induced inhibition of foraging behavior in rodents. Surprisingly, none of the candidate mechanisms previously implicated in hypothalamic leucine sensing (K ATP channels, mTORC1 signaling, amino-acid decarboxylation) were involved in the acute activity changes produced by l-leucine. Instead, our data indicate that leucine-induced neuronal activation involves a plasma membrane Ca 2+ channel, whereas leucine-induced neuronal inhibition is mediated by inhibition of a store-operated Ca 2+ current. A subset of neurons in the mediobasal hypothalamus rapidly respond to physiological changes in extracellular leucine concentration. Leucine can produce both increases and decreases in neuronal Ca 2+ concentrations in a neurochemically-diverse group of neurons, including some POMC and NPY/AGRP neurons. Our data reveal that leucine can signal through novel mechanisms to rapidly

  15. Symptoms and Diagnosis of Metabolic Syndrome

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More Symptoms and Diagnosis of Metabolic Syndrome Updated:Apr 13,2017 What are the symptoms ... Syndrome? This content was last reviewed August 2016. Metabolic Syndrome • Home • About Metabolic Syndrome • Why Metabolic Syndrome Matters • ...

  16. Inferring ancient metabolism using ancestral core metabolic models of enterobacteria.

    Science.gov (United States)

    Baumler, David J; Ma, Bing; Reed, Jennifer L; Perna, Nicole T

    2013-06-11

    Enterobacteriaceae diversified from an ancestral lineage ~300-500 million years ago (mya) into a wide variety of free-living and host-associated lifestyles. Nutrient availability varies across niches, and evolution of metabolic networks likely played a key role in adaptation. Here we use a paleo systems biology approach to reconstruct and model metabolic networks of ancestral nodes of the enterobacteria phylogeny to investigate metabolism of ancient microorganisms and evolution of the networks. Specifically, we identified orthologous genes across genomes of 72 free-living enterobacteria (16 genera), and constructed core metabolic networks capturing conserved components for ancestral lineages leading to E. coli/Shigella (~10 mya), E. coli/Shigella/Salmonella (~100 mya), and all enterobacteria (~300-500 mya). Using these models we analyzed the capacity for carbon, nitrogen, phosphorous, sulfur, and iron utilization in aerobic and anaerobic conditions, identified conserved and differentiating catabolic phenotypes, and validated predictions by comparison to experimental data from extant organisms. This is a novel approach using quantitative ancestral models to study metabolic network evolution and may be useful for identification of new targets to control infectious diseases caused by enterobacteria.

  17. Analysis of metabolic flux using dynamic labelling and metabolic modelling.

    Science.gov (United States)

    Fernie, A R; Morgan, J A

    2013-09-01

    Metabolic fluxes and the capacity to modulate them are a crucial component of the ability of the plant cell to react to environmental perturbations. Our ability to quantify them and to attain information concerning the regulatory mechanisms that control them is therefore essential to understand and influence metabolic networks. For all but the simplest of flux measurements labelling methods have proven to be the most informative. Both steady-state and dynamic labelling approaches have been adopted in the study of plant metabolism. Here the conceptual basis of these complementary approaches, as well as their historical application in microbial, mammalian and plant sciences, is reviewed, and an update on technical developments in label distribution analyses is provided. This is supported by illustrative cases studies involving the kinetic modelling of secondary metabolism. One issue that is particularly complex in the analysis of plant fluxes is the extensive compartmentation of the plant cell. This problem is discussed from both theoretical and experimental perspectives, and the current approaches used to address it are assessed. Finally, current limitations and future perspectives of kinetic modelling of plant metabolism are discussed. © 2013 John Wiley & Sons Ltd.

  18. A new method for rapid Canine retraction

    Directory of Open Access Journals (Sweden)

    "Khavari A

    2001-06-01

    Full Text Available Distraction osteogenesis method (Do in bone lengthening and rapid midpalatal expansion have shown the great ability of osteognic tissues for rapid bone formation under distraction force and special protocol with optimum rate of one millimeter per day. Periodontal membrane of teeth (PDM is the extension of periostium in the alveolar socked. Orthodontic force distracts PDM fibers in the tension side and then bone formation will begin.Objects: Rapid retraction of canine tooth into extraction space of first premolar by DO protocol in order to show the ability of the PDM in rapid bone formation. The other objective was reducing total orthodontic treatment time of extraction cases.Patients and Methods: Tweleve maxillary canines in six patients were retracted rapidly in three weeks by a custom-made tooth-born appliance. Radiographic records were taken to evaluate the effects of heavy applied force on canine and anchorage teeth.Results: Average retraction was 7.05 mm in three weeks (2.35 mm/week. Canines rotated distal- in by mean 3.5 degrees.Anchorage loss was from 0 to 0.8 mm with average of 0.3 mm.Root resorption of canines was negligible, and was not significant clinically. Periodontium was normal after rapid retraction. No hazard for pulp vitality was observed.Discussion: PDM responded well to heavy distraction force by Do protocol. Rapid canine retraction seems to be a safe method and can considerabely reduce orthodontic time.

  19. Risks and Benefits of Rapid Clozapine Titration.

    Science.gov (United States)

    Lochhead, Jeannie D; Nelson, Michele A; Schneider, Alan L

    2016-05-18

    Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS) during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  20. Risks and benefits of rapid clozapine titration

    Directory of Open Access Journals (Sweden)

    Jeannie D. Lochhead

    2016-05-01

    Full Text Available Clozapine is often considered the gold standard for the treatment of schizophrenia. Clinical guidelines suggest a gradual titration over 2 weeks to reduce the risks of adverse events such as seizures, hypotension, agranulocytosis, and myocarditis. The slow titration often delays time to therapeutic response. This raises the question of whether, in some patients, it may be safe to use a more rapid clozapine titration. The following case illustrates the potential risks associated with the use of multiple antipsychotics and rapid clozapine titration. We present the case of a young man with schizophrenia who developed life threatening neuroleptic malignant syndrome (NMS during rapid clozapine titration and treatment with multiple antipsychotics. We were unable to find another case in the literature of NMS associated with rapid clozapine titration. This case is meant to urge clinicians to carefully evaluate the risks and benefits of rapid clozapine titration, and to encourage researchers to further evaluate the safety of rapid clozapine titration. Rapid clozapine titration has implications for decreasing health care costs associated with prolonged hospitalizations, and decreasing the emotional suffering associated with uncontrolled symptoms of psychosis. Clozapine is considered the most effective antipsychotic available thus efforts should focus on developing strategies that would allow for safest and most efficient use of clozapine to encourage its utilization for treatment resistance schizophrenia.

  1. Quantification of intracellular metabolite dynamics for experimental studies of microbial metabolism; Quantifizierung intrazellulaerer Metabolitdynamiken zur Untersuchung mikrobieller Stoffwechselnetzwerke

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, A.K.

    2002-02-01

    The rational improvement of the productivity of cellular systems is one of the main goals of modern biotechnology and may be accomplished in two ways. One approach is the optimization of the production process ('bioprocess engineering'). Another possibility is the improvement of the cellular system itself by manipulating the metabolic pathways ('metabolic engineering'). A precise manipulation of microbial metabolism, and thereby a rational strain development, is possible today by using the tools of molecular biology. However, a prerequisite of this manipulation is a detailed and quantitative knowledge of the dynamics and regulation of metabolic fluxes in microbial metabolism. In this work a dynamic method is used for the quantification of microbial metabolism. The microorganism is cultivated in a substrate limited steady state and then rapidly shifted away from this metabolic equilibrium by application of a substrate pulse ('pulse experiment'). Samples are taken using a rapid sampling and quenching technique, which was developed in earlier works. The metabolites are then extracted and analyzed to determine the metabolic response of the microorganism. Using a novel system for injecting substrate pulses, a number of dynamic pulse experiments were performed. Intracellular metabolite dynamics were quantified using newly developed analytical techniques based on HPLC-MS, UV-HPLC, CE and enzymatic assays. (orig.)

  2. Changing urban phosphorus metabolism: Evidence from Longyan City, China.

    Science.gov (United States)

    Cui, Shenghui; Xu, Su; Huang, Wei; Bai, Xuemei; Huang, Yunfeng; Li, Guilin

    2015-12-01

    Rapid worldwide urbanization calls for a better understanding of phosphorus (P) metabolism and the interaction of the physical, ecological and social drivers of P cycling in urban systems. We quantified the P metabolism in Longyan, a city with a major agricultural economy, and analyzed its long-term trends over the rapid urbanization period of 1985-2010. Both input P (from 4811 t P to 14,296 t P) and output P (from 4565 t P to 13,509 t P) increased significantly. The agricultural subsystem contributed most to the P metabolism, accounting for 85% of total P input. The share of P input lost to the environment, i.e. discharge to water, accumulation in the soil and landfill, increased from 66% to 72%, while food production efficiency decreased from 48% to 29%. Per capita P input showed linear relationships with the Human Development Index (HDI), S-curve relationship with the urbanization rate, and logistic curve relationship with per capita disposable income. A more meat-based diet shift both in Longyan and surrounding cities greatly affected Longyan's food production structure. Our results demonstrate that P metabolic quantity, configuration, and efficiency in production systems can change drastically in response to changes in consumer and producer behavior as well as in socioeconomic structure. A larger regional scale should be considered in urban P management, when trying to mitigate the increase in P use. The results also imply that sustainable urban P management will require a system-wide, cross-sector and cross-boundary approach. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. The metabolic fate of nectar nicotine in worker honey bees.

    Science.gov (United States)

    du Rand, Esther E; Pirk, Christian W W; Nicolson, Susan W; Apostolides, Zeno

    2017-04-01

    Honey bees (Apis mellifera) are generalist pollinators that forage for nectar and pollen of a very large variety of plant species, exposing them to a diverse range of secondary metabolites produced as chemical defences against herbivory. Honey bees can tolerate high levels of many of these toxic compounds, including the alkaloid nicotine, in their diet without incurring apparent fitness costs. Very little is known about the underlying detoxification processes mediating this tolerance. We examined the metabolic fate of nicotine in newly emerged worker bees using radiolabeled nicotine and LC-MS/MS analysis to determine the kinetic distribution profile of nicotine as well as the absence or presence and identity of any nicotine-derived metabolites. Nicotine metabolism was extensive; virtually no unmetabolised nicotine were recovered from the rectum. The major metabolite found was 4-hydroxy-4-(3-pyridyl) butanoic acid, the end product of 2'C-oxidation of nicotine. It is the first time that 4-hydroxy-4-(3-pyridyl) butanoic acid has been identified in an insect as a catabolite of nicotine. Lower levels of cotinine, cotinine N-oxide, 3'hydroxy-cotinine, nicotine N-oxide and norcotinine were also detected. Our results demonstrated that formation of 4-hydroxy-4-(3-pyridyl) butanoic acid is quantitatively the most significant pathway of nicotine metabolism in honey bees and that the rapid excretion of unmetabolised nicotine does not contribute significantly to nicotine tolerance in honey bees. In nicotine-tolerant insects that do not rely on the rapid excretion of nicotine like the Lepidoptera, it is possible that the 2'C-oxidation of nicotine is the conserved metabolic pathway instead of the generally assumed 5'C-oxidation pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Analog regulation of metabolic demand

    Directory of Open Access Journals (Sweden)

    Muskhelishvili Georgi

    2011-03-01

    Full Text Available Abstract Background The 3D structure of the chromosome of the model organism Escherichia coli is one key component of its gene regulatory machinery. This type of regulation mediated by topological transitions of the chromosomal DNA can be thought of as an analog control, complementing the digital control, i.e. the network of regulation mediated by dedicated transcription factors. It is known that alterations in the superhelical density of chromosomal DNA lead to a rich pattern of differential expressed genes. Using a network approach, we analyze these expression changes for wild type E. coli and mutants lacking nucleoid associated proteins (NAPs from a metabolic and transcriptional regulatory network perspective. Results We find a significantly higher correspondence between gene expression and metabolism for the wild type expression changes compared to mutants in NAPs, indicating that supercoiling induces meaningful metabolic adjustments. As soon as the underlying regulatory machinery is impeded (as for the NAP mutants, this coherence between expression changes and the metabolic network is substantially reduced. This effect is even more pronounced, when we compute a wild type metabolic flux distribution using flux balance analysis and restrict our analysis to active reactions. Furthermore, we are able to show that the regulatory control exhibited by DNA supercoiling is not mediated by the transcriptional regulatory network (TRN, as the consistency of the expression changes with the TRN logic of activation and suppression is strongly reduced in the wild type in comparison to the mutants. Conclusions So far, the rich patterns of gene expression changes induced by alterations of the superhelical density of chromosomal DNA have been difficult to interpret. Here we characterize the effective networks formed by supercoiling-induced gene expression changes mapped onto reconstructions of E. coli's metabolic and transcriptional regulatory network. Our

  5. A scoping review of rapid review methods.

    Science.gov (United States)

    Tricco, Andrea C; Antony, Jesmin; Zarin, Wasifa; Strifler, Lisa; Ghassemi, Marco; Ivory, John; Perrier, Laure; Hutton, Brian; Moher, David; Straus, Sharon E

    2015-09-16

    Rapid reviews are a form of knowledge synthesis in which components of the systematic review process are simplified or omitted to produce information in a timely manner. Although numerous centers are conducting rapid reviews internationally, few studies have examined the methodological characteristics of rapid reviews. We aimed to examine articles, books, and reports that evaluated, compared, used or described rapid reviews or methods through a scoping review. MEDLINE, EMBASE, the Cochrane Library, internet websites of rapid review producers, and reference lists were searched to identify articles for inclusion. Two reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted. We included 100 articles plus one companion report that were published between 1997 and 2013. The studies were categorized as 84 application papers, seven development papers, six impact papers, and four comparison papers (one was included in two categories). The rapid reviews were conducted between 1 and 12 months, predominantly in Europe (58 %) and North America (20 %). The included studies failed to report 6 % to 73 % of the specific systematic review steps examined. Fifty unique rapid review methods were identified; 16 methods occurred more than once. Streamlined methods that were used in the 82 rapid reviews included limiting the literature search to published literature (24 %) or one database (2 %), limiting inclusion criteria by date (68 %) or language (49 %), having one person screen and another verify or screen excluded studies (6 %), having one person abstract data and another verify (23 %), not conducting risk of bias/quality appraisal (7 %) or having only one reviewer conduct the quality appraisal (7 %), and presenting results as a narrative summary (78 %). Four case studies were identified that compared the results of rapid reviews to systematic reviews. Three studies found that the conclusions between

  6. New developments in rapidly solidified magnesium alloys

    Energy Technology Data Exchange (ETDEWEB)

    Das, S.K. [Allied-Signal, Inc., Morristown, NJ (United States); Chang, C.F. [Allied-Signal, Inc., Morristown, NJ (United States); Raybould, D. [Allied-Signal, Inc., Morristown, NJ (United States); King, J.F. [Magnesium Elektron Ltd., Manchester (United Kingdom); Thistlethwaite, S. [Magnesium Elektron Ltd., Manchester (United Kingdom)

    1992-12-31

    In the present paper, we will examine the new developments in the rapidly solidified Mg-Al-Zn-Nd (EA55RS) alloy. We shall first briefly review the process scale-up currently employed for producing rapidly solidified magnesium alloys in large quantities, and then discuss the effect of billet size and processing parameters on the mechanical properties of various mill product forms such as extrusions and sheets. The superplastic behavior of EA55RS extrusions and rolled sheets are also discussed. Finally, some results on magnesium metal-matrix composites using rapidly solidified EA55RS matrix powders and SiC particulates are presented. (orig.)

  7. An effect of phenobarbitone on griseofulvin metabolism in the rat

    Science.gov (United States)

    Busfield, Dorothy; Child, K. J.; Tomich, E. G.

    1964-01-01

    Prior administration of phenobarbitone to male and female rats dosed orally or intravenously with griseofulvin caused a fall in blood levels of the antibiotic. The effect of a single oral dose of phenobarbitone was significant after 12 hr and maximal between 12 and 48 hr, and it lasted for at least 96 hr; it was more pronounced when the barbiturate was administered repeatedly. Liver slices from animals dosed with phenobarbitone metabolized griseofulvin more rapidly than did those from undosed animals. The possible relevance of these findings to the clinical use of griseofulvin is discussed. PMID:14126043

  8. [Lead compound optimization strategy (1)--changing metabolic pathways and optimizing metabolism stability].

    Science.gov (United States)

    Wang, Jiang; Liu, Hong

    2013-10-01

    Lead compound optimization plays an important role in new drug discovery and development. The strategies for changing metabolic pathways can modulate pharmacokinetic properties, prolong the half life, improve metabolism stability and bioavailability of lead compounds. The strategies for changing metabolic pathways and improving metabolism stability are reviewed. These methods include blocking metabolic site, reduing lipophilicity, changing ring size, bioisosterism, and prodrug.

  9. Response to trauma and metabolic changes: posttraumatic metabolism.

    Science.gov (United States)

    Şimşek, Turgay; Şimşek, Hayal Uzelli; Cantürk, Nuh Zafer

    2014-01-01

    Stress response caused by events such as surgical trauma includes endocrine, metabolic and immunological changes. Stress hormones and cytokines play a role in these reactions. More reactions are induced by greater stress, ultimately leading to greater catabolic effects. Cuthbertson reported the characteristic response that occurs in trauma patients: protein and fat consumption and protection of body fluids and electrolytes because of hypermetabolism in the early period. The oxygen and energy requirement increases in proportion to the severity of trauma. The awareness of alterations in amino acid, lipid, and carbohydrate metabolism changes in surgical patients is important in determining metabolic and nutritional support. The main metabolic change in response to injury that leads to a series of reactions is the reduction of the normal anabolic effect of insulin, i.e. the development of insulin resistance. Free fatty acids are primary sources of energy after trauma. Triglycerides meet 50 to 80 % of the consumed energy after trauma and in critical illness. Surgical stress and trauma result in a reduction in protein synthesis and moderate protein degradation. Severe trauma, burns and sepsis result in increased protein degradation. The aim of glucose administration to surgical patients during fasting is to reduce proteolysis and to prevent loss of muscle mass. In major stress such as sepsis and trauma, it is important both to reduce the catabolic response that is the key to faster healing after surgery and to obtain a balanced metabolism in the shortest possible time with minimum loss. For these reasons, the details of metabolic response to trauma should be known in managing these situations and patients should be treated accordingly.

  10. Metabolic triggered inflammation in osteoarthritis.

    Science.gov (United States)

    Wang, X; Hunter, D; Xu, J; Ding, C

    2015-01-01

    Osteoarthritis (OA) is a common chronic joint disorder with a multifactorial etiology including genetic and environmental factors. Metabolic triggered inflammation, induced by nutrient overload and metabolic surplus, consists of components such as obesity, pro-inflammatory cytokines and adipokines, abnormal metabolites, acute phase proteins, vitamin D deficiency, and deregulated microRNAs that may play a role in OA pathophysiology. Obesity-related metabolic factors, especially adipokines, contribute to OA development by inducing pro-inflammatory cytokines and degradative enzymes, leading to cartilage matrix impairment and subchondral bone remodeling. Ectopic metabolite deposition and low-grade systemic inflammation can contribute to a toxic internal environment that exacerbates OA. Complement components highly expressed in osteoarthritic joints have also been proposed as causative factors. Vitamin D deficiency has been associated with obesity and is implicated to be associated with cartilage loss in OA. Metabolic microRNAs may explain the inflammatory link between obesity and OA. Therapies targeting metabolic-triggered inflammation and its components are anticipated to have potential for the treatment of OA. Copyright © 2014 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  11. Metabolic Cost of Experimental Exercises

    Science.gov (United States)

    Webb, James T.; Gernhardt, Michael L.

    2009-01-01

    Although the type and duration of activity during decompression was well documented, the metabolic cost of 1665 subject-exposures with 8 activity profiles from 17 altitude decompression sickness (DCS) protocols at Brooks City-Base, TX from 1983-2005 was not determined. Female and male human volunteers (30 planned, 4 completed) performed activity profiles matching those 8 activity profiles at ground level with continuous monitoring of metabolic cost. A Cosmed K4b2 Cardio Pulmonary Exercise Testing device was used to measure oxygen uptake (VO2) during the profiles. The results show levels of metabolic cost to the females for the profiles tested varied from 4.3 to 25.5 ml/kg/min and from 3.0 to 12.0 ml/kg/min to the males. The increase in VO2 from seated rest to the most strenuous of the 8 activity profiles was 3.6-fold for the females and 2.8-fold for the males. These preliminary data on 4 subjects indicate close agreement of oxygen uptake for activity performed during many subject-exposures as published earlier. The relatively low average oxygen uptake required to perform the most strenuous activity may imply the need for adjustment of modeling efforts using metabolic cost as a risk factor. Better definition of metabolic cost during exposure to altitude, a critical factor in DCS risk, may allow refinement of DCS prediction models.

  12. Metabolic acceleration in Mediterranean Perciformes

    Science.gov (United States)

    Lika, Konstadia; Kooijman, Sebastiaan A. L. M.; Papandroulakis, Nikos

    2014-11-01

    Larval stages are considered the most critical of fish development. During a very short period of time (2 to 3 months), larvae undergo major morphoanatomical and functional changes in order to transform into juveniles while remaining functioning (developing, eating, surviving). Depending on species and environmental conditions, patterns in larval development may vary. We study the patterns of larval development for nine fish species of Perciformes reared under aquaculture conditions and compare them in terms of species-specific parameters derived from DEB theory. We extended the standard DEB model to include metabolic acceleration during the larval period, where maximum specific assimilation and energy conductance increase with length between birth and metabolic metamorphosis. Metabolic acceleration has as a consequence that larvae initially grow slower than juveniles and adults. Our results indicate that the species with higher acceleration have lower growth rates at birth and they also suggest that metabolic acceleration is related to spawning season. High metabolic acceleration of demersal species is associated with summer-autumn spawning in the Mediterranean, where temperature is high and food availability is low.

  13. Thermodynamic Constraints Improve Metabolic Networks.

    Science.gov (United States)

    Krumholz, Elias W; Libourel, Igor G L

    2017-08-08

    In pursuit of establishing a realistic metabolic phenotypic space, the reversibility of reactions is thermodynamically constrained in modern metabolic networks. The reversibility constraints follow from heuristic thermodynamic poise approximations that take anticipated cellular metabolite concentration ranges into account. Because constraints reduce the feasible space, draft metabolic network reconstructions may need more extensive reconciliation, and a larger number of genes may become essential. Notwithstanding ubiquitous application, the effect of reversibility constraints on the predictive capabilities of metabolic networks has not been investigated in detail. Instead, work has focused on the implementation and validation of the thermodynamic poise calculation itself. With the advance of fast linear programming-based network reconciliation, the effects of reversibility constraints on network reconciliation and gene essentiality predictions have become feasible and are the subject of this study. Networks with thermodynamically informed reversibility constraints outperformed gene essentiality predictions compared to networks that were constrained with randomly shuffled constraints. Unconstrained networks predicted gene essentiality as accurately as thermodynamically constrained networks, but predicted substantially fewer essential genes. Networks that were reconciled with sequence similarity data and strongly enforced reversibility constraints outperformed all other networks. We conclude that metabolic network analysis confirmed the validity of the thermodynamic constraints, and that thermodynamic poise information is actionable during network reconciliation. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  14. Transgenerational inheritance of metabolic disease.

    Science.gov (United States)

    Stegemann, Rachel; Buchner, David A

    2015-07-01

    Metabolic disease encompasses several disorders including obesity, type 2 diabetes, and dyslipidemia. Recently, the incidence of metabolic disease has drastically increased, driven primarily by a worldwide obesity epidemic. Transgenerational inheritance remains controversial, but has been proposed to contribute to human metabolic disease risk based on a growing number of proof-of-principle studies in model organisms ranging from Caenorhabditis elegans to Mus musculus to Sus scrofa. Collectively, these studies demonstrate that heritable risk is epigenetically transmitted from parent to offspring over multiple generations in the absence of a continued exposure to the triggering stimuli. A diverse assortment of initial triggers can induce transgenerational inheritance including high-fat or high-sugar diets, low-protein diets, various toxins, and ancestral genetic variants. Although the mechanistic basis underlying the transgenerational inheritance of disease risk remains largely unknown, putative molecules mediating transmission include small RNAs, histone modifications, and DNA methylation. Due to the considerable impact of metabolic disease on human health, it is critical to better understand the role of transgenerational inheritance of metabolic disease risk to open new avenues for therapeutic intervention and improve upon the current methods for clinical diagnoses and treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Calcium metabolism & hypercalcemia in adults.

    Science.gov (United States)

    Lumachi, F; Motta, R; Cecchin, D; Ave, S; Camozzi, V; Basso, S M M; Luisetto, G

    2011-01-01

    Calcium is essential for many metabolic process, including nerve function, muscle contraction, and blood clotting. The metabolic pathways that contribute to maintain serum calcium levels are bone remodeling processes, intestinal absorption and secretion, and renal handling, but hypercalcemia occurs when at least 2 of these 3 metabolic pathways are altered. Calcium metabolism mainly depends on the activity of parathyroid hormone (PTH). Its secretion is strictly controlled by the ionized serum calcium levels through a negative feed-back, which is achieved by the activation of calcium-sensing receptors (CaSRs) mainly expressed on the surface of the parathyroid cells. The PTH receptor in bone and kidney is now referred as PTHR1. The balance of PTH, calcitonin, and vitamin D has long been considered the main regulator of calcium metabolism, but the function of other actors, such as fibroblast growth factor-23 (FGF-23), Klotho, and TPRV5 should be considered. Primary hyperparathyroidism and malignancy are the most common causes of hypercalcemia, accounting for more than 90% of cases. Uncontrolled hypercalcemia may cause renal impairment, both temporary (alteration of renal tubular function) and progressive (relapsing nephrolithiasis), leading to a progressive loss of renal function, as well as severe bone diseases, and heart damages. Advances in the understanding of all actors of calcium homeostasis will be crucial, having several practical consequences in the treatment and prevention of hypercalcemia. This would allow to move from a support therapy, sometimes ineffective, to a specific and addressed therapy, especially in patients with chronic hypercalcemic conditions unsuitable for surgery.

  16. Metabolic studies of oxyguno in horses

    Energy Technology Data Exchange (ETDEWEB)

    Wong, April S.Y., E-mail: april.sy.wong-rl@hkjc.org.hk [Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong (China); Ho, Emmie N.M. [Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong (China); Wan, Terence S.M., E-mail: terence.sm.wan@hkjc.org.hk [Racing Laboratory, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T., Hong Kong (China); Lam, Kenneth K.H.; Stewart, Brian D. [Veterinary Regulation & International Liaison, The Hong Kong Jockey Club, Sha Tin Racecourse, Sha Tin, N.T, Hong Kong (China)

    2015-09-03

    group at C4 and the keto group at C3. M5 was resulted from hydroxylation at C20 and two reductions at either the olefin group at C4, the keto group at C3, or the keto group at C11. M6 was assigned as the 17-epimer of oxyguno. The major biotransformation pathways of oxyguno identified were reduction, hydroxylation and epimerisation. The structures of all metabolites were tentatively assigned by mass spectral interpretation. The longest detection time observed in urine was up to 10 h for the in vivo metabolite M4. Urinary and plasma oxyguno decreased rapidly and was no longer detectable at respectively 7 and 12 h post-administration. The above studies have provided useful information for the monitoring of oxyguno administration in racehorses. - Highlights: • Oxyguno is a synthetic oral anabolic androgenic steroid commercially available. • Oxyguno is prohibited in equine sports due to its anabolic enhancement effect. • This is the first paper describing its metabolic studies in racehorses. • It reports the most appropriate target metabolites to detect oxyguno administration.

  17. Implementation of rapid diagnostics with antimicrobial stewardship.

    Science.gov (United States)

    Minejima, Emi; Wong-Beringer, Annie

    2016-11-01

    Antimicrobial stewardship (ASP) is an intervention-based program to improve patient outcomes to infection while limiting spread of resistance and unintended consequences. Many rapid diagnostic tools are now FDA cleared for clinical use, with three evaluated across multiple settings: Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry, Verigene, and FilmArray. Areas covered: This review will focus on studies published that evaluated ASP intervention with rapid diagnostic implementation on outcomes of infection. A description of the key ASP personnel, rapid diagnostic notification methods, hours of notification, and scope of ASP intervention is summarized. Expert commentary: It is critical that ASPs continually re-evaluate and evolve with technological advances. Rapid diagnostic tools are powerful in their ability to identify organisms quickly. A trained clinician is needed to evaluate the results and interact with the providers to educate them on result interpretation and optimal antimicrobial selection to maximize treatment success.

  18. Rapid Update Cycle (RUC) [20 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  19. Rapid Update Cycle (RUC) [13 km

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The Rapid Update Cycle (RUC) weather forecast model was developed by the National Centers for Environmental Prediction (NCEP). On May 1, 2012, the RUC was replaced...

  20. Rapid Chemical Exposure and Dose Research

    Science.gov (United States)

    EPA evaluates the potential risks of the manufacture and use of thousands of chemicals. To assist with this evaluation, EPA scientists developed a rapid, automated model using off the shelf technology that predicts exposures for thousands of chemicals.

  1. Innovative rapid construction/reconstruction methods.

    Science.gov (United States)

    2005-07-01

    Innovative construction and reconstruction methods provide the opportunity to significantly reduce the time of roadway projects while maintaining the necessary quality of workmanship. The need for these rapid methods stems from the increase in ...

  2. Colorado Plateau Rapid Ecoregion Assessment Data Catalog

    Data.gov (United States)

    Bureau of Land Management, Department of the Interior — Datasets used in the analysis of the Colorado Plateau (COP) Rapid Ecoregion Assessment (REA).They can be downloaded via a layer package (lpk, similar to a zip file...

  3. Development of a Rapid Thermoplastic Impregnation Device

    NARCIS (Netherlands)

    Weustink, A.P.D.

    2007-01-01

    A melt impregnation device for rapid thermoplastic impregnation of fiber bundles has been developed through modeling and experiments. The basic principles behind the thermoplastic impregnation process are investigated and the properties needed for a successful thermoplastic impregnation device are

  4. Practical implications of rapid development methodologies

    CSIR Research Space (South Africa)

    Gerber, A

    2007-11-01

    Full Text Available Rapid development methodologies are popular approaches for the development of modern software systems. The goals of these methodologies are the inclusion of the client into the analysis, design and implementation activities, as well...

  5. The Rapid Perceptual Impact of Emotional Distractors.

    Directory of Open Access Journals (Sweden)

    Briana L Kennedy

    Full Text Available The brief presentation of an emotional distractor can temporarily impair perception of a subsequent, rapidly presented target, an effect known as emotion-induced blindness (EIB. How rapidly does this impairment unfold? To probe this question, we examined EIB for targets that immediately succeeded ("lag-1" emotional distractors in a rapid stream of items relative to EIB for targets at later serial positions. Experiments 1 and 2 suggested that emotional distractors interfere with items presented very soon after them, with impaired target perception emerging as early as lag-1. Experiment 3 included an exploratory examination of individual differences, which suggested that EIB onsets more rapidly among participants scoring high in measures linked to negative affect.

  6. Breast Cancer Metabolism and Mitochondrial Activity: The Possibility of Chemoprevention with Metformin

    Directory of Open Access Journals (Sweden)

    Massimiliano Cazzaniga

    2015-01-01

    Full Text Available Metabolic reprogramming refers to the ability of cancer cells to alter their metabolism in order to support the increased energy request due to continuous growth, rapid proliferation, and other characteristics typical of neoplastic cells. It has long been believed that the increase of metabolic request was independent of the mitochondrial action but recently we know that mitochondrial activity together with metabolism plays a pivotal role in the regulation of the energy needed for tumor cell growth and proliferation. For these reasons the mitochondria pathways could be a new target for therapeutic and chemopreventive intervention. Metformin in particular is actually considered a promising agent against mitochondrial activity thanks to its ability to inhibit the mitochondrial complex I.

  7. Carbohydrate-Restriction with High-Intensity Interval Training: An Optimal Combination for Treating Metabolic Diseases?

    Directory of Open Access Journals (Sweden)

    Monique E. Francois

    2017-10-01

    Full Text Available Lifestyle interventions incorporating both diet and exercise strategies remain cornerstone therapies for treating metabolic disease. Carbohydrate-restriction and high-intensity interval training (HIIT have independently been shown to improve cardiovascular and metabolic health. Carbohydrate-restriction reduces postprandial hyperglycemia, thereby limiting potential deleterious metabolic and cardiovascular consequences of excessive glucose excursions. Additionally, carbohydrate-restriction has been shown to improve body composition and blood lipids. The benefits of exercise for improving insulin sensitivity are well known. In this regard, HIIT has been shown to rapidly improve glucose control, endothelial function, and cardiorespiratory fitness. Here, we report the available evidence for each strategy and speculate that the combination of carbohydrate-restriction and HIIT will synergistically maximize the benefits of both approaches. We hypothesize that this lifestyle strategy represents an optimal intervention to treat metabolic disease; however, further research is warranted in order to harness the potential benefits of carbohydrate-restriction and HIIT for improving cardiometabolic health.

  8. Adverse Metabolic Risk Profiles in Greenlandic Inuit Children Compared to Danish Children

    DEFF Research Database (Denmark)

    Munch-Andersen, T.; Sorensen, K.; Andersen, L. B.

    2013-01-01

    Objective During recent decades, the prevalence of metabolic morbidity has increased rapidly in adult Greenlandic Inuit. To what extent this is also reflected in the juvenile Inuit population is unknown. The objective was, therefore, in the comparison with Danish children, to evaluate metabolic...... BMI, body fat %, HbA1c, and significantly lower aerobic fitness and ApoA1 levels than northern living Inuit children. Conclusions Greenlandic Inuit children had adverse metabolic health profile compared to the Danish children, the differences where more pronounced in Inuit children living in Nuuk....... The tendencies toward higher prevalence of diabetes and metabolic morbidity in the adult Greenlandic Inuit population may also be present in the Inuit children population....

  9. Peculiarities of Teaching Problems of Metabolic Syndrome in Children to Interns

    Directory of Open Access Journals (Sweden)

    Olha Bobrykovych

    2017-10-01

    Full Text Available Obesity has become one of the most urgent social problems worldwide. Continuous and rapid increase in obesity rates is considered by the World Health Organization as a global epidemic. Obesity affects children as well; the World Health Organization recognized childhood obesity as an acute public health crisis. Childhood obesity is often accompanied by arterial hypertension, hyperlipidemia and disorders of        carbohydrate metabolism resulting in symptom complex – metabolic syndrome. While teaching the problems of metabolic syndrome in children to interns, a significant attention is paid to risk factors, diagnosis, treatment and prevention of syndrome. Such approach will allow future pediatricians to diagnose and prevent the development of early complications of metabolic syndrome in children timely.

  10. Intersections of post-transcriptional gene regulatory mechanisms with intermediary metabolism.

    Science.gov (United States)

    Arif, Waqar; Datar, Gandhar; Kalsotra, Auinash

    2017-03-01

    Intermediary metabolism studies have typically concentrated on four major regulatory mechanisms-substrate availability, allosteric enzyme regulation, post-translational enzyme modification, and regulated enzyme synthesis. Although transcriptional control has been a big focus, it is becoming increasingly evident that many post-transcriptional events are deeply embedded within the core regulatory circuits of enzyme synthesis/breakdown that maintain metabolic homeostasis. The prominent post-transcriptional mechanisms affecting intermediary metabolism include alternative pre-mRNA processing, mRNA stability and translation control, and the more recently discovered regulation by noncoding RNAs. In this review, we discuss the latest advances in our understanding of these diverse mechanisms at the cell-, tissue- and organismal-level. We also highlight the dynamics, complexity and non-linear nature of their regulatory roles in metabolic decision making, and deliberate some of the outstanding questions and challenges in this rapidly expanding field. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension

    Directory of Open Access Journals (Sweden)

    Zeid Khitan

    2013-01-01

    Full Text Available Diabetes mellitus and the metabolic syndrome are becoming leading causes of death in the world. Identifying the etiology of diabetes is key to prevention. Despite the similarity in their structures, fructose and glucose are metabolized in different ways. Uric acid, a byproduct of uncontrolled fructose metabolism is known risk factor for hypertension. In the liver, fructose bypasses the two highly regulated steps in glycolysis, glucokinase and phosphofructokinase, both of which are inhibited by increasing concentrations of their byproducts. Fructose is metabolized by fructokinase (KHK. KHK has no negative feedback system, and ATP is used for phosphorylation. This results in intracellular phosphate depletion and the rapid generation of uric acid due to activation of AMP deaminase. Uric acid, a byproduct of this reaction, has been linked to endothelial dysfunction, insulin resistance, and hypertension. We present possible mechanisms by which fructose causes insulin resistance and suggest actions based on this association that have therapeutic implications.

  12. Rapidly curable electrically conductive clear coatings

    Energy Technology Data Exchange (ETDEWEB)

    Bowman, Mark P.; Anderson, Lawrence G.; Post, Gordon L.

    2018-01-16

    Rapidly curable electrically conductive clear coatings are applied to substrates. The electrically conductive clear coating includes to clear layer having a resinous binder with ultrafine non-stoichiometric tungsten oxide particles dispersed therein. The clear coating may be rapidly cured by subjecting the coating to infrared radiation that heats the tungsten oxide particles and surrounding resinous binder. Localized heating increases the temperature of the coating to thereby thermally cure the coating, while avoiding unwanted heating of the underlying substrate.

  13. Rapidly separating microneedles for transdermal drug delivery.

    Science.gov (United States)

    Zhu, Dan Dan; Wang, Qi Lei; Liu, Xu Bo; Guo, Xin Dong

    2016-09-01

    The applications of polymer microneedles (MNs) into human skin emerged as an alternative of the conventional hypodermic needles. However, dissolving MNs require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin, which may lead to the low drug delivery efficiency. To address these issues, we introduce rapidly separating MNs that can rapidly deliver drugs into the skin in a minimally invasive way. For the rapidly separating MNs, drug loaded dissolving MNs are mounted on the top of solid MNs, which are made of biodegradable polylactic acid which eliminate the biohazardous waste. These MNs have sufficient mechanical strength to be inserted into the skin with the drug loaded tips fully embedded for subsequent dissolution. Compared with the traditional MNs, rapidly separating MNs achieve over 90% of drug delivery efficiency in 30s while the traditional MNs needs 2min to achieve the same efficiency. With the in vivo test in mice, the micro-holes caused by rapidly separating MNs can heal in 1h, indicating that the rapidly separating MNs are safe for future applications. These results indicate that the design of rapidly separating dissolvable MNs can offer a quick, high efficient, convenient, safe and potentially self-administered method of drug delivery. Polymer microneedles offer an attractive, painless and minimally invasive approach for transdermal drug delivery. However, dissolving microneedles require many minutes to be dissolved in the skin and typically have difficulty being fully inserted into the skin due to the skin deformation, which may lead to the low drug delivery efficiency. In this work we proposed rapidly separating microneedles which can deliver over 90% of drug into the skin in 30s. The in vitro and in vivo results indicate that the new design of these microneedles can offer a quick, high efficient, convenient and safe method for transdermal drug delivery. Copyright © 2016 Acta Materialia Inc

  14. Exploring data with RapidMiner

    CERN Document Server

    Chisholm, Andrew

    2013-01-01

    A step-by-step tutorial style using examples so that users of different levels will benefit from the facilities offered by RapidMiner.If you are a computer scientist or an engineer who has real data from which you want to extract value, this book is ideal for you. You will need to have at least a basic awareness of data mining techniques and some exposure to RapidMiner.

  15. Metabolic traits of pathogenic streptococci.

    Science.gov (United States)

    Willenborg, Jörg; Goethe, Ralph

    2016-11-01

    Invasive and noninvasive diseases caused by facultative pathogenic streptococci depend on their equipment with virulence factors and on their ability to sense and adapt to changing nutrients in different host environments. The knowledge of the principal metabolic mechanisms which allow these bacteria to recognize and utilize nutrients in host habitats is a prerequisite for our understanding of streptococcal pathogenicity and the development of novel control strategies. This review aims to summarize and compare the central carbohydrate metabolic and amino acid biosynthetic pathways of a selected group of streptococcal species, all belonging to the naso-oropharyngeal microbiome in humans and/or animals. We also discuss the urgent need of comprehensive metabolomics approaches for a better understanding of the streptococcal metabolism during host-pathogen interaction. © 2016 Federation of European Biochemical Societies.

  16. Opioid metabolism and clinical aspects.

    Science.gov (United States)

    Mercadante, Sebastiano

    2015-12-15

    Opioids are are commonly used for the management of acute and chronic pain. Opioids have different physicochemical and pharmacokinetic characteristics, which explain the profound changes in the clinical effect in several clinical conditions. Pharmacokinetics influences the opioid response affecting bioavailability, production of metabolites with residual clinical activity, and elimination. Generality of opioid metabolism and clinical implications for specific opioids in different clinical conditions were reviewed to bridge the gap between pharmacokinetics and clinical response. The knowledge of opioid metabolism is essential, particularly for older and complicated patients who receive multiple medications and may have impaired of renal and hepatic function. The recognition of possible metabolic problems and the consideration of adverse drug-drug interactions are fundamental to optimize the use of opioids in clinical practice. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Novel genes in LDL metabolism

    DEFF Research Database (Denmark)

    Christoffersen, Mette; Tybjærg-Hansen, Anne

    2015-01-01

    PURPOSE OF REVIEW: To summarize recent findings from genome-wide association studies (GWAS), whole-exome sequencing of patients with familial hypercholesterolemia and 'exome chip' studies pointing to novel genes in LDL metabolism. RECENT FINDINGS: The genetic loci for ATP-binding cassette......-exome sequencing and 'exome chip' studies have additionally suggested several novel genes in LDL metabolism including insulin-induced gene 2, signal transducing adaptor family member 1, lysosomal acid lipase A, patatin-like phospholipase domain-containing protein 5 and transmembrane 6 superfamily member 2. Most...... of these findings still require independent replications and/or functional studies to confirm the exact role in LDL metabolism and the clinical implications for human health. SUMMARY: GWAS, exome sequencing studies, and recently 'exome chip' studies have suggested several novel genes with effects on LDL cholesterol...

  18. Enzymes of inorganic polyphosphate metabolism.

    Science.gov (United States)

    Kulakovskaya, Tatyana; Kulaev, Igor

    2013-01-01

    Inorganic polyphosphate (PolyP) is a linear polymer containing a few to several hundred orthophosphate residues linked by energy-rich phosphoanhydride bonds. Investigation of PolyP-metabolizing enzymes is important for medicine, because PolyPs perform numerous functions in the cells. In human organism, PolyPs are involved in the regulation of Ca(2+) uptake in mitochondria, bone tissue development, and blood coagulation. The essentiality of polyphosphate kinases in the virulence of pathogenic bacteria is a basis for the discovery of new antibiotics. The properties of the major enzymes of PolyP metabolism, first of all polyphosphate kinases and exopolyphosphatases, are described in the review. The main differences between the enzymes of PolyP biosynthesis and utilization of prokaryotic and eukaryotic cells, as well as the multiple functions of some enzymes of PolyP metabolism, are considered.

  19. Exercise training in metabolic myopathies

    DEFF Research Database (Denmark)

    Vissing, J

    2016-01-01

    Metabolic myopathies encompass muscle glycogenoses (GSD) and disorders of muscle fat oxidation (FAOD). FAODs and GSDs can be divided into two main clinical phenotypes; those with static symptoms related to fixed muscle weakness and atrophy, and those with dynamic, exercise-related symptoms...... that are brought about by a deficient supply of ATP. Together with mitochondrial myopathies, metabolic myopathies are unique among muscle diseases, as the limitation in exercise performance is not solely caused by structural damage of muscle, but also or exclusively related to energy deficiency. ATP consumption...... can increase 50-100-fold in contracting, healthy muscle from rest to exercise, and testing patients with exercise is therefore an appropriate approach to disclose limitations in work capacity and endurance in metabolic myopathies. Muscles rely almost exclusively on muscle glycogen in the initial...

  20. Fat sensing and metabolic syndrome.

    Science.gov (United States)

    Youn, Jang H

    2014-12-01

    Overconsumption of dietary fat contributes to the development of obesity and metabolic syndrome. Recent evidence suggests that high dietary fat may promote these metabolic states not only by providing calories but also by inducing impaired control of energy balance. In normal metabolic states, fat interacts with various organs or receptors to generate signals for the regulation of energy balance. Many of these interactions are impaired by high-fat diets or in obesity, contributing to the development or maintenance of obesity. These impairments may arise largely from fundamental alterations in the hypothalamus where all peripheral signals are integrated to regulate energy balance. This review focuses on various mechanisms by which fat is sensed at different stages of ingestion, circulation, storage, and utilization to regulate food intake, and how these individual mechanisms are altered by high-fat diets or in obesity.