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Sample records for acid cycle activity

  1. Structure-activity relationship between carboxylic acids and T cell cycle blockade.

    PubMed

    Gilbert, Kathleen M; DeLoose, Annick; Valentine, Jimmie L; Fifer, E Kim

    2006-04-01

    This study was designed to examine the potential structure-activity relationship between carboxylic acids, histone acetylation and T cell cycle blockade. Toward this goal a series of structural homologues of the short-chain carboxylic acid n-butyrate were studied for their ability to block the IL-2-stimulated proliferation of cloned CD4+ T cells. The carboxylic acids were also tested for their ability to inhibit histone deacetylation. In addition, Western blotting was used to examine the relative capacity of the carboxlic acids to upregulate the cyclin kinase-dependent inhibitor p21cip1 in T cells. As shown earlier n-butyrate effectively inhibited histone deacetylation. The increased acetylation induced by n-butyrate was associated with the upregulation of the cyclin-dependent kinase inhibitor p21cip1 and the cell cycle blockade of CD4+ T cells. Of the other carboxylic acids studied, the short chain acids, C3-C5, without branching were the best inhibitors of histone deacetylase. This inhibition correlated with increased expression of the cell cycle blocker p21cip1, and the associated suppression of CD4+ T cell proliferation. The branched-chain carboxylic acids tested were ineffective in all the assays. These results underline the relationship between the ability of a carboxylic acid to inhibit histone deacetylation, and their ability to block T cell proliferation, and suggests that branching inhibits these effects.

  2. Activities of Tricarboxylic Acid Cycle Enzymes, Glyoxylate Cycle Enzymes, and Fructose Diphosphatase in Bakers' Yeast During Adaptation to Acetate Oxidation

    PubMed Central

    Gosling, J. P.; Duggan, P. F.

    1971-01-01

    Bakers' yeast oxidizes acetate at a high rate only after an adaptation period during which the capacity of the glyoxylate cycle is found to increase. There was apparently no necessity for the activity of acetyl-coenzyme A synthetase, the capacity of the tricarboxylic acid cycle, or the concentrations of the cytochromes to increase for this adaptation to occur. Elevation of fructose 1,6 diphosphatase occurred only when acetate oxidation was nearly maximal. Cycloheximide almost completely inhibited adaptation as well as increases in the activities of isocitrate lyase and aconitate hydratase, the only enzymes assayed. p-Fluorophenylalanine was partially effective and chloramphenicol did not inhibit at all. The presence of ammonium, which considerably delayed adaptation of the yeast to acetate oxidation, inhibited the increases in the activities of the glyoxylate cycle enzymes to different degrees, demonstrating noncoordinate control of these enzymes. Under the various conditions, the only enzyme activity increase consistently related to the rising oxygen uptake rate was that of isocitrate lyase which apparently limited the activity of the cycle. PMID:5557595

  3. Sex-dependent activity of the spinal excitatory amino acid transporter: Role of estrous cycle.

    PubMed

    Sajjad, Jahangir; Felice, Valeria D; Golubeva, Anna V; Cryan, John F; O'Mahony, Siobhain M

    2016-10-01

    Females are more likely to experience visceral pain than males, yet mechanisms underlying this sex bias are not fully elucidated. Moreover, pain sensitivity can change throughout the menstrual cycle. Alterations in the glutamatergic system have been implicated in several pain-disorders; however, whether these are sex-dependent is unclear. Thus, we aimed to investigate sex differences in the spinal cord glutamate uptake and how it varies across the estrous cycle. The activity of the glutamate transporters, excitatory amino acid transporters (EAATs) was assessed using an ex vivo aspartate radioactive uptake assay in the lumbosacral spinal cord in Sprague-Dawley male and female rats. The gene expression of EAATs, glutamate receptor subunits NR1 and NR2B and the estrogen receptors ERα & ERβ in the spinal cord were also analyzed. EAAT activity was lower in females, particularly during the estrus phase, and this was the only cycle stage that was responsive to the pharmacological effects of the EAATs activator riluzole. Interestingly, EAAT1 mRNA expression was lower in high-estrogen and high-ERα states compared to diestrus in females. We conclude that the Spinal EAAT activity in females is different to that in males, and varies across the estrous cycle. Furthermore, the expression levels of estrogen receptors also showed a cycle-dependent pattern that may affect EAATs function and expression. PMID:27471194

  4. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.

    PubMed

    Patterson, Rainey E; Kalavalapalli, Srilaxmi; Williams, Caroline M; Nautiyal, Manisha; Mathew, Justin T; Martinez, Janie; Reinhard, Mary K; McDougall, Danielle J; Rocca, James R; Yost, Richard A; Cusi, Kenneth; Garrett, Timothy J; Sunny, Nishanth E

    2016-04-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH.

  5. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.

    PubMed

    Patterson, Rainey E; Kalavalapalli, Srilaxmi; Williams, Caroline M; Nautiyal, Manisha; Mathew, Justin T; Martinez, Janie; Reinhard, Mary K; McDougall, Danielle J; Rocca, James R; Yost, Richard A; Cusi, Kenneth; Garrett, Timothy J; Sunny, Nishanth E

    2016-04-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH. PMID:26814015

  6. L-Malate dehydrogenase activity in the reductive arm of the incomplete citric acid cycle of Nitrosomonas europaea.

    PubMed

    Deutch, Charles E

    2013-11-01

    The autotrophic nitrifying bacterium Nitrosomonas europaea does not synthesize 2-oxoglutarate (α-ketoglutarate) dehydrogenase under aerobic conditions and so has an incomplete citric acid cycle. L-malate (S-malate) dehydrogenase (MDH) from N. europaea was predicted to show similarity to the NADP(+)-dependent enzymes from chloroplasts and was separated from the NAD(+)-dependent proteins from most other bacteria or mitochondria. MDH activity in a soluble fraction from N. europaea ATCC 19718 was measured spectrophotometrically and exhibited simple Michaelis-Menten kinetics. In the reductive direction, activity with NADH increased from pH 6.0 to 8.5 but activity with NADPH was consistently lower and decreased with pH. At pH 7.0, the K m for oxaloacetate was 20 μM; the K m for NADH was 22 μM but that for NADPH was at least 10 times higher. In the oxidative direction, activity with NAD(+) increased with pH but there was very little activity with NADP(+). At pH 7.0, the K m for L-malate was 5 mM and the K m for NAD(+) was 24 μM. The reductive activity was quite insensitive to inhibition by L-malate but the oxidative activity was very sensitive to oxaloacetate. MDH activity was not strongly activated or inhibited by glycolytic or citric acid cycle metabolites, adenine nucleotides, NaCl concentrations, or most metal ions, but increased with temperature up to about 55 °C. The reductive activity was consistently 10-20 times higher than the oxidative activity. These results indicate that the L-malate dehydrogenase in N. europaea is similar to other NAD(+)-dependent MDHs (EC 1.1.1.37) but physiologically adapted for its role in a reductive biosynthetic sequence.

  7. Solar activity secular cycles

    NASA Astrophysics Data System (ADS)

    Kramynin, A. P.; Mordvinov, A. V.

    2013-12-01

    Long-term variations in solar activity secular cycles have been studied using a method for the expansion of reconstructed sunspot number series Sn( t) for 11400 years in terms of natural orthogonal functions. It has been established that three expansion components describe more than 98% of all Sn( t) variations. In this case, the contribution of the first expansion component is about 92%. The averaged form of the 88year secular cycle has been determined based on the form of the first expansion coordinate function. The quasi-periodicities modulating the secular cycle have been revealed based on the time function conjugate to the first function. The quasi-periodicities modulating the secular cycle coincide with those observed in the Sn( t) series spectrum. A change in the secular cycle form and the time variations in this form are described by the second and third expansion components, the contributions of which are about 4 and 2%, respectively. The variations in the steepness of the secular cycle branches are more pronounced in the 200-year cycle, and the secular cycle amplitude varies more evidently in the 2300-year cycle.

  8. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders. PMID:26476839

  9. Acute Carnosine Administration Increases Respiratory Chain Complexes and Citric Acid Cycle Enzyme Activities in Cerebral Cortex of Young Rats.

    PubMed

    Macedo, Levy W; Cararo, José H; Maravai, Soliany G; Gonçalves, Cinara L; Oliveira, Giovanna M T; Kist, Luiza W; Guerra Martinez, Camila; Kurtenbach, Eleonora; Bogo, Maurício R; Hipkiss, Alan R; Streck, Emilio L; Schuck, Patrícia F; Ferreira, Gustavo C

    2016-10-01

    Carnosine (β-alanyl-L-histidine) is an imidazole dipeptide synthesized in excitable tissues of many animals, whose biochemical properties include carbonyl scavenger, anti-oxidant, bivalent metal ion chelator, proton buffer, and immunomodulating agent, although its precise physiological role(s) in skeletal muscle and brain tissues in vivo remain unclear. The aim of the present study was to investigate the in vivo effects of acute carnosine administration on various aspects of brain bioenergetics of young Wistar rats. The activity of mitochondrial enzymes in cerebral cortex was assessed using a spectrophotometer, and it was found that there was an increase in the activities of complexes I-III and II-III and succinate dehydrogenase in carnosine-treated rats, as compared to vehicle-treated animals. However, quantitative real-time RT-PCR (RT-qPCR) data on mRNA levels of mitochondrial biogenesis-related proteins (nuclear respiratory factor 1 (Nrf1), peroxisome proliferator-activated receptor-γ coactivator 1-α (Ppargc1α), and mitochondrial transcription factor A (Tfam)) were not altered significantly and therefore suggest that short-term carnosine administration does not affect mitochondrial biogenesis. It was in agreement with the finding that immunocontent of respiratory chain complexes was not altered in animals receiving carnosine. These observations indicate that acute carnosine administration increases the respiratory chain and citric acid cycle enzyme activities in cerebral cortex of young rats, substantiating, at least in part, a neuroprotector effect assigned to carnosine against oxidative-driven disorders.

  10. Activation and repression of Epstein-Barr Virus and Kaposi's sarcoma-associated herpesvirus lytic cycles by short- and medium-chain fatty acids.

    PubMed

    Gorres, Kelly L; Daigle, Derek; Mohanram, Sudharshan; Miller, George

    2014-07-01

    The lytic cycles of Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are induced in cell culture by sodium butyrate (NaB), a short-chain fatty acid (SCFA) histone deacetylase (HDAC) inhibitor. Valproic acid (VPA), another SCFA and an HDAC inhibitor, induces the lytic cycle of KSHV but blocks EBV lytic reactivation. To explore the hypothesis that structural differences between NaB and VPA account for their functional effects on the two related viruses, we investigated the capacity of 16 structurally related short- and medium-chain fatty acids to promote or prevent lytic cycle reactivation. SCFAs differentially affected EBV and KSHV reactivation. KSHV was reactivated by all SCFAs that are HDAC inhibitors, including phenylbutyrate. However, several fatty acid HDAC inhibitors, such as isobutyrate and phenylbutyrate, did not reactivate EBV. Reactivation of KSHV lytic transcripts could not be blocked completely by any fatty acid tested. In contrast, several medium-chain fatty acids inhibited lytic activation of EBV. Fatty acids that blocked EBV reactivation were more lipophilic than those that activated EBV. VPA blocked activation of the BZLF1 promoter by NaB but did not block the transcriptional function of ZEBRA. VPA also blocked activation of the DNA damage response that accompanies EBV lytic cycle activation. Properties of SCFAs in addition to their effects on chromatin are likely to explain activation or repression of EBV. We concluded that fatty acids stimulate the two related human gammaherpesviruses to enter the lytic cycle through different pathways. Importance: Lytic reactivation of EBV and KSHV is needed for persistence of these viruses and plays a role in carcinogenesis. Our direct comparison highlights the mechanistic differences in lytic reactivation between related human oncogenic gammaherpesviruses. Our findings have therapeutic implications, as fatty acids are found in the diet and produced by the human microbiota. Small

  11. In vitro evidence that D-serine disturbs the citric acid cycle through inhibition of citrate synthase activity in rat cerebral cortex.

    PubMed

    Zanatta, Angela; Schuck, Patrícia Fernanda; Viegas, Carolina Maso; Knebel, Lisiane Aurélio; Busanello, Estela Natacha Brandt; Moura, Alana Pimentel; Wajner, Moacir

    2009-11-17

    The present work investigated the in vitro effects of D-serine (D-Ser) on important parameters of energy metabolism in cerebral cortex of young rats. The parameters analyzed were CO(2) generation from glucose and acetate, glucose uptake and the activities of the respiratory chain complexes I-IV, of the citric acid cycle enzymes citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, fumarase and malate dehydrogenase and of creatine kinase and Na(+),K(+)-ATPase. Our results show that D-Ser significantly reduced CO(2) production from acetate, but not from glucose, reflecting an impairment of the citric acid cycle function. Furthermore, D-Ser did not affect glucose uptake. We also observed that the activity of the mitochondrial enzyme citrate synthase from mitochondrial preparations and purified citrate synthase was significantly inhibited by D-Ser, whereas the other activities of the citric acid cycle as well as the activities of complexes I-III, II-III, II and IV of the respiratory chain, creatine kinase and Na(+),K(+)-ATPase were not affected by this D-amino acid. We also found that L-serine did not affect citrate synthase activity from mitochondrial preparations and purified enzyme. The data indicate that D-Ser impairs the citric acid cycle activity via citrate synthase inhibition, therefore compromising energy metabolism production in cerebral cortex of young rats. Therefore, it is presumed that this mechanism may be involved at least in part in the neurological damage found in patients affected by disorders in which D-Ser metabolism is impaired, with altered cerebral concentrations of this D-amino acid.

  12. Activation of lytic cycle of Epstein-Barr virus by suberoylanilide hydroxamic acid leads to apoptosis and tumor growth suppression of nasopharyngeal carcinoma.

    PubMed

    Hui, K F; Ho, Dona N; Tsang, C M; Middeldorp, Jaap M; Tsao, George S W; Chiang, Alan K S

    2012-10-15

    Nasopharyngeal carcinoma (NPC) is strongly associated with Epstein-Barr virus (EBV). We reported that suberoylanilide hydroxamic acid (SAHA) induced EBV lytic cycle in EBV-positive gastric carcinoma cells and mediated enhanced cell death. However, expression of EBV lytic proteins was thought to exert antiapoptotic effect in EBV-infected cells. Here, we examined the in vitro and in vivo effects of SAHA on EBV lytic cycle induction in NPC cells and investigated the cellular consequences. Micromolar concentrations of SAHA significantly induced EBV lytic cycle in EBV-positive NPC cells. Increased apoptosis and proteolytic cleavage of poly(ADP-ribose) polymerase and caspase-3, -7 and -9 in EBV-positive versus EBV-negative NPC cells were observed. More than 85% of NPC cells expressing immediate-early (Zta), early (BMRF1) or late (gp350/220) lytic proteins coexpressed cleaved caspase-3. Tracking of expression of EBV lytic proteins and cleaved caspase-3 over time demonstrated that NPC cells proceeded to apoptosis following EBV lytic cycle induction. Inhibition of EBV DNA replication and late lytic protein expression by phosphonoformic acid did not impact on SAHA's induced cell death in NPC, indicating that early rather than late phase of EBV lytic cycle contributed to the apoptotic effect. In vivo effects of SAHA on EBV lytic cycle induction and tumor growth suppression were also observed in NPC xenografts in nude mice. Taken together, our data indicated that activation of lytic cycle from latent cycle of EBV by SAHA leads to apoptosis and tumor growth suppression of NPC thereby providing experimental evidence for virus-targeted therapy against EBV-positive cancer.

  13. Palladium alpha-lipoic acid complex formulation enhances activities of Krebs cycle dehydrogenases and respiratory complexes I-IV in the heart of aged rats.

    PubMed

    Sudheesh, N P; Ajith, T A; Janardhanan, K K; Krishnan, C V

    2009-08-01

    Age-related decline in the capacity to withstand stress, such as ischemia and reperfusion, results in congestive heart failure. Though the mechanisms underlying cardiac decay are not clear, age dependent somatic damages to mitochondrial DNA (mtDNA), loss of mitochondrial function, and a resultant increase in oxidative stress in heart muscle cells may be responsible for the increased risk for cardiovascular diseases. The effect of a safe nutritional supplement, POLY-MVA, containing the active ingredient palladium alpha-lipoic acid complex, was evaluated on the activities of the Krebs cycle enzymes such as isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, and malate dehydrogenase as well as mitochondrial complexes I, II, III, and IV in heart mitochondria of aged male albino rats of Wistar strain. Administration of 0.05 ml/kg of POLY-MVA (which is equivalent to 0.38 mg complexed alpha-lipoic acid/kg, p.o), once daily for 30 days, was significantly (p<0.05) effective to enhance the Krebs cycle dehydrogenases, and mitochondrial electron transport chain complexes. The unique electronic and redox properties of palladium alpha-lipoic acid complex appear to be a key to this physiological effectiveness. The results strongly suggest that this formulation might be effective to protect the aging associated risk of cardiovascular and neurodegenerative diseases.

  14. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    PubMed

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis. PMID:26306846

  15. Changes in urinary amino acids excretion in relationship with muscle activity markers over a professional cycling stage race: in search of fatigue markers.

    PubMed

    Corsetti, Roberto; Barassi, Alessandra; Perego, Silvia; Sansoni, Veronica; Rossi, Alessandra; Damele, Clara Anna Linda; Melzi D'Eril, Gianlodovico; Banfi, Giuseppe; Lombardi, Giovanni

    2016-01-01

    The aim of this study was to identify the relationship between metabolic effort, muscular damage/activity indices, and urinary amino acids profile over the course of a strenuous prolonged endurance activity, as a cycling stage race is, in order to identify possible fatigue markers. Nine professional cyclists belonging to a single team, competing in the Giro d'Italia cycling stage race, were anthropometrically characterized and sampled for blood and urine the day before the race started, and on days 12 and 23 of the race. Diet was kept the same over the race, and power output and energy expenditure were recorded. Sera were assayed for muscle markers (lactate dehydrogenase, aspartate aminotransferase, and creatine kinase activities, and blood urea nitrogen), and creatinine, all corrected for plasma volume changes. Urines were profiled for amino acid concentrations, normalized on creatinine excretion. Renal function, in terms of glomerular filtration rate, was monitored by MDRD equation corrected on body surface area. Creatine kinase activity and blood urea were increased during the race as did serum creatinine while kidney function remained stable. Among the amino acids, taurine, glycine, cysteine, leucine, carnosine, 1-methyl histidine, and 3-methyl histidine showed a net decreased, while homocysteine was increased. Taurine and the dipeptide carnosine (β-alanyl-L-histidine) were significantly correlated with the muscle activity markers and the indices of effort. In conclusion, the metabolic profile is modified strikingly due to the effort. Urinary taurine and carnosine seem useful tools to evaluate the muscle damage and possibly the fatigue status on a long-term basis.

  16. Tropospheric cycle of nitrous acid

    NASA Astrophysics Data System (ADS)

    Harrison, Roy M.; Peak, John D.; Collins, Gareth M.

    1996-06-01

    Measurements of the land surface exchange of nitrous acid over grass and sugar beet surfaces reveal both upward and downward fluxes with flux reversal occurring at an ambient concentration of nitrogen dioxide of about 10 ppb. This confirms earlier preliminary findings and strengthens the hypothesis that substantial production of nitrous acid can occur on land surfaces from reaction of nitrogen dioxide and water vapor. Detailed measurements of nitrous acid have been made in central urban, suburban, and rural environments. These measurements, in conjunction with a simple box model, indicate that the atmospheric concentrations of nitrous acid are explicable in terms of a small number of basic processes in which the most important are the surface production of nitrous acid from nitrogen dioxide, atmospheric production from the NO-OH reaction and loss of nitrous acid by photolysis and dry deposition. In the suburban atmosphere, concentrations of nitrous acid are strongly correlated with nitrogen dioxide. In the rural atmosphere a different behavior is seen, with much higher nitrous acid to nitrogen dioxide ratios occurring in more polluted air with nitrogen dioxide concentrations in excess of 10 ppb. At lower nitrogen dioxide concentrations, net deposition of nitrous acid at the ground leads to very low concentrations in advected air. The model study indicates that during daytime in the suburban atmosphere, production of HONO from the NO-OH reaction can compete with photolysis giving a HONO concentration of a few tenths of a part per billion. At the highest observed daytime concentrations of HONO, production of OH radical from its photolysis can proceed at a rate more than 10 times faster than from photolysis of ozone.

  17. New betulinic acid derivatives induce potent and selective antiproliferative activity through cell cycle arrest at the S phase and caspase dependent apoptosis in human cancer cells.

    PubMed

    Santos, Rita C; Salvador, Jorge A R; Cortés, Roldán; Pachón, Gisela; Marín, Silvia; Cascante, Marta

    2011-06-01

    New semisynthetic derivatives of betulinic acid (BA) RS01, RS02 and RS03 with 18-45 times improved cytotoxic activity against HepG2 cells, were tested for their ability to induce apoptosis and cell cycle arrest in HepG2, HeLa and Jurkat cells. All the compounds induced significant increase in the population at the S phase more effectively than BA. RS01, RS02 and RS03 were also found to be potent inducers of apoptosis with RS01 being markedly more potent than BA, suggesting that the introduction of the imidazolyl moiety is crucial for enhancing the induction of apoptosis and the cell cycle arrest. The mechanism of apoptosis induction has been studied in HepG2 cells and found to be mediated by activation of the postmitochondrial caspases-9 and -3 cascade and possibly by mitochondrial amplification loop involving caspase-8. These facts were corroborated by detection of mitochondrial cytochrome c release and DNA fragmentation. Because RS01, RS02 and RS03 exhibited significant improved antitumor activity with respect to BA, they may be promising new agents for the treatment of cancer. In particular, RS01 is the most promising compound with an IC(50) value 45 times lower than BA on HepG2 cells and 61 times lower than the one found for the non-tumoral Chang liver cells.

  18. Docosohaexanoic acid-supplemented PACA44 cell lines and over-activation of Krebs cycle: an integrated proteomic, metabolomic and interactomic overview.

    PubMed

    D'Alessandro, Angelo; D'Amici, Gian Maria; Timperio, Anna Maria; Merendino, Nicolò; Zolla, Lello

    2011-09-01

    Recent investigations have pointed out the ability of fatty acids, in particular of docosohaexanoic acid (DHA), to induce growth inhibition and apoptosis in the human PaCa-44 pancreatic cancer cell line through a series of mechanisms which has been hypothesized to mimic apoptosis. While preliminary evidences indicated the involvement of lipid-targeting oxidative stress in DHA-induced apoptotic processes, mainly through the alteration of the glutathione (GSH) homeostasis and oxidized-glutathione (GSSG) turn-over through their extra-cellular extrusion, no further molecular data have been hitherto accumulated. To this end, we hereby propose simultaneous protein-targeting and metabolite-oriented analyses, which have been integrated through the auxilium of in silico elaboration of those protein-protein interaction pathways and enrichment of biological/molecular functions. To determine the most suitable time window for the early onset of the DHA-triggered apoptosis phenomena we performed flow cytometry-based apoptotic assessment at 24, 48 and 72 h. Results indicated that the focus of apoptosis onset ranged from 48 to 72 h. From these analyses it emerges that the metabolism of control human PaCa-44 pancreatic cancer cell line mainly leans on glycolytic pathways, while it is promptly switched to Kreb's cycle activation (overexpression of Kreb's cycle enzymes in DHA-treated cells against controls) and modulation of the GSH homeostasis through an increased production of GSSG-reducing NADPH coenzyme via the shift of the glycolytic energy flux towards the pentose phosphate pathway. Interestingly, it also emerges a role for structural protein alteration in DHA-treated cells, which might be linked to cytoskeletal alterations occurring during apoptosis.

  19. Tricarboxylic-acid-cycle intermediates and cycle endurance capacity.

    PubMed

    Brown, Amy C; Macrae, Holden S H; Turner, Nathan S

    2004-12-01

    The purpose of this study was to determine whether ingestion of a multinutrient supplement containing 3 tricarboxylic-acid-cycle intermediates (TCAIs; pyridoxine-alpha-ketoglutarate, malate, and succinate) and other substances potentially supporting the TCA cycle (such as aspartate and glutamate) would improve cyclists' time to exhaustion during a submaximal endurance-exercise test (approximately 70 % to 75 % VO2peak) and rate of recovery. Seven well-trained male cyclists (VO2max 67.4 2.1 mL x kg(-1) x in(-1), 28.6 +/- 2.4 y) participated in a randomized, double-blind crossover study for 7 wk. Each took either the treatment or a placebo 30 min before and after their normal training sessions for 3 wk and before submaximal exercise tests. There were no significant differences between the TCAI group (KI) and placebo group (P) in time to exhaustion during cycling (KI = 105 +/- 18, P = 113 +/- 11 min); respiratory-exchange ratio at 20-min intervals; blood lactate and plasma glucose before, after, and at 30-min intervals during exercise; perceived exertion at 20-min intervals during exercise; or time to fatigue after the 30-min recovery (KI = 16.1 +/- 3.2, P = 15 +/- 2 min). Taking a dietary sport supplement containing several TCAIs and supporting substances for 3 wk does not improve cycling performance at 75 % VO2peak or speed recovery from previously fatiguing exercise.

  20. Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators, tricarboxylic acid cycle activity and exacerbates recognition memory deficit in rat model of Alzheimer's disease.

    PubMed

    Shaerzadeh, Fatemeh; Motamedi, Fereshteh; Khodagholi, Fariba

    2014-11-01

    3-Methyladenine (3-MA), as a PI3K inhibitor, is widely used for inhibition of autophagy. Inhibition of PI3K class I leads to inhibition of Akt phosphorylation, a central molecule involved in diverse arrays of intracellular cascades in nervous system. Accordingly, in the present study, we aimed to determine the alterations of specific mitochondrial biogenesis markers and mitochondrial function in 3-MA-injected rats following amyloid beta (Aβ) insult. Our data revealed that inhibition of Akt phosphorylation downregulates master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Our data also showed that decrease in PGC-1α level presumably is due to decrease in the phosphorylation of cAMP-response element binding and AMP-activated kinase, two upstream activators of PGC-1α. As a consequence, the level of some mitochondrial biogenesis factors including nuclear respiratory factor-1, mitochondrial transcription factor A, and Cytochrome c decreased significantly. Also, activities of tricarboxylic acid cycle (TCA) enzymes such as Aconitase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reduced in the presence of 3-MA with or without Aβ insult. Decrease in mitochondrial biogenesis factors and TCA enzyme activity in the rats receiving 3-MA and Aβ were more compared to the rats that received either alone; indicating the additive destructive effects of these two agents. In agreement with our molecular results, data obtained from behavioral test (using novel objective recognition test) indicated that inhibition of Akt phosphorylation with or without Aβ injection impaired novel recognition (non-spatial) memory. Our results suggest that 3-MA amplified deleterious effects of Aβ by targeting central molecule Akt.

  1. Stellar activity cycles and asteroseismology

    NASA Astrophysics Data System (ADS)

    Salabert, D.

    2011-12-01

    The success of helioseismology is due to its capability to accurately measure the p-mode parameters of the solar eigenmode spectrum, which allow us to infer unique information about the internal structure and dynamics of the Sun from its surface all the way down to the core. It has contributed greatly to a clearer understanding of the Sun and provided insights into the complex solar magnetism, by means for instance of the variability of the characteristics of the p-mode spectrum. Indeed, variations in the mean strength of the solar magnetic field lead to significant shifts in the frequencies of even the lowest-degree p modes with high levels of correlation with solar surface activity proxies. These frequency shifts are explained to arise from structural changes in the outer layers of the Sun during the 11-year activity cycle, which is understood to be driven by a dynamo process. However, clear differences between p-mode frequencies and solar surface activity during the unusually extended minimum of cycle 23 were observed. The origin of the p-mode variability is thus far from being properly understood and a better comprehension of its relationship with solar and stellar activity cycles will help us in our understanding of the dynamo processes. Spectroscopic measurements of Ca H and K emission lines revealed magnetic activity variations in a large sample of solar-type stars with timescales ranging from 2.5 and 25 years. This broad range of cycle periods is thought to reflect differences in the rotational properties and the depths of the surface convection zones with various masses and ages. However, spectroscopic measurements are only good proxies of surface magnetic fields. The recent discovery of variations with magnetic activity in the p-mode oscillation frequencies of the solar-like star HD 49933 observed by CoRoT, with a frequency dependence comparable in shape to the one observed in the Sun, opens a new era in the study of the physical phenomena involved in the

  2. Sulfuric acid-sulfur heat storage cycle

    DOEpatents

    Norman, John H.

    1983-12-20

    A method of storing heat is provided utilizing a chemical cycle which interconverts sulfuric acid and sulfur. The method can be used to levelize the energy obtained from intermittent heat sources, such as solar collectors. Dilute sulfuric acid is concentrated by evaporation of water, and the concentrated sulfuric acid is boiled and decomposed using intense heat from the heat source, forming sulfur dioxide and oxygen. The sulfur dioxide is reacted with water in a disproportionation reaction yielding dilute sulfuric acid, which is recycled, and elemental sulfur. The sulfur has substantial potential chemical energy and represents the storage of a significant portion of the energy obtained from the heat source. The sulfur is burned whenever required to release the stored energy. A particularly advantageous use of the heat storage method is in conjunction with a solar-powered facility which uses the Bunsen reaction in a water-splitting process. The energy storage method is used to levelize the availability of solar energy while some of the sulfur dioxide produced in the heat storage reactions is converted to sulfuric acid in the Bunsen reaction.

  3. Citric acid cycle intermediates in cardioprotection.

    PubMed

    Czibik, Gabor; Steeples, Violetta; Yavari, Arash; Ashrafian, Houman

    2014-10-01

    Over the last decade, there has been a concerted clinical effort to deliver on the laboratory promise that a variety of maneuvers can profoundly increase cardiac tolerance to ischemia and/or reduce additional damage consequent upon reperfusion. Here we will review the proximity of the metabolic approach to clinical practice. Specifically, we will focus on how the citric acid cycle is involved in cardioprotection. Inspired by cross-fertilization between fundamental cancer biology and cardiovascular medicine, a set of metabolic observations have identified novel metabolic pathways, easily manipulable in man, which can harness metabolism to robustly combat ischemia-reperfusion injury.

  4. The Pyruvate-Tricarboxylic Acid Cycle Node

    PubMed Central

    Bücker, René; Heroven, Ann Kathrin; Becker, Judith; Dersch, Petra; Wittmann, Christoph

    2014-01-01

    Despite our increasing knowledge of the specific pathogenicity factors in bacteria, the contribution of metabolic processes to virulence is largely unknown. Here, we elucidate a tight connection between pathogenicity and core metabolism in the enteric pathogen Yersinia pseudotuberculosis by integrated transcriptome and [13C]fluxome analysis of the wild type and virulence-regulator mutants. During aerobic growth on glucose, Y. pseudotuberculosis reveals an unusual flux distribution with a high level of secreted pyruvate. The absence of the transcriptional and post-transcriptional regulators RovA, CsrA, and Crp strongly perturbs the fluxes of carbon core metabolism at the level of pyruvate metabolism and the tricarboxylic acid (TCA) cycle, and these perturbations are accompanied by transcriptional changes in the corresponding enzymes. Knock-outs of regulators of this metabolic branch point and of its central enzyme, pyruvate kinase (ΔpykF), result in mutants with significantly reduced virulence in an oral mouse infection model. In summary, our work identifies the pyruvate-TCA cycle node as a focal point for controlling the host colonization and virulence of Yersinia. PMID:25164818

  5. Characterization of lead (Ⅱ)-containing activated carbon and its excellent performance of extending lead-acid battery cycle life for high-rate partial-state-of-charge operation

    NASA Astrophysics Data System (ADS)

    Tong, Pengyang; Zhao, Ruirui; Zhang, Rongbo; Yi, Fenyun; Shi, Guang; Li, Aiju; Chen, Hongyu

    2015-07-01

    In this work, lead (Ⅱ)-containing activated carbon (Pb@C) is prepared as the additive of negative active mass (NAM), aiming to enhance the electrochemical characteristics of the lead-acid battery. The characters of the Pb@C materials and their electrochemical properties are characterized by XRD, SEM, back-scattering electron image (BESI) and electrochemical methods. The lead (Ⅱ) ions disperse well in the carbon bulk of the obtained Pb@C materials as observed, and these materials exhibit remarkable higher specific capacitance and higher hydrogen evolution over-potential compared with original carbons. Many 2 V lead-acid batteries are assembled manually in our lab, and then the batteries are disassembled after formation and high-rate-partial-state-of-charge (HRPSoC) cycling. Results manifest that the Pb@C additives exhibit high affinity to lead and act as a porous-skeleton in the formation process as well as under HRPSoC cycling conditions, leading to the small and fine formation of PbSO4 particles and accordingly higher active material utilization rate more than 50%, better cycling performance and charging acceptance. Besides, excellent cycle performances of these batteries have great relationship with the dazzling hydrogen evolution performance of Pb@C materials. A possible working mechanism is also proposed based on the testing data in this paper.

  6. Fatty acid biosynthesis during the life cycle of Debaryomyces etchellsii.

    PubMed

    Arous, Fatma; Mechichi, Tahar; Nasri, Moncef; Aggelis, George

    2016-07-01

    Fatty acid biosynthesis during the life cycle of the ascomycetous yeast Debaryomyces etchellsii cultivated on a non-fermentable substrate, i.e. glycerol, in nitrogen rich media (NRM) and nitrogen limited media (NLM) has been studied. Although considerable activities of key lipogenic enzymes, such as ATP citrate lyase (ACL) and malic enzyme (ME), were detected in vegetative cells during asexual proliferation (which occurred in the first growth stages in both NRM and NLM), lipid accumulation was restricted due to the high activities of NAD+-isocitrate dehydrogenase (NAD+-ICDH). A similar enzymatic profile has been found in ascii and free ascospores produced in NRM; thus lipid accumulation was low. On the contrary, very high activities of both ACL and ME and low activities of NAD+-ICDH were detected in ascii and free ascospores produced in NLM resulting in lipid accumulation. Neutral lipids (NL) were the predominant fraction of cellular lipids produced in vegetative cells and ascospores in both NRM and NLM. On the other hand, phospholipids (P) were the major polar lipids while glycolipids (G) were synthesized in low proportions. During transition from asexual to sexual phase, the percentage of NL increased with a significant decrease of P and, to a lesser extent, of G. High quantities of linoleic acid were found esterified in polar lipids, especially in P, during the vegetative stage of growth, while, with a few exceptions, during transition from asexual to sexual stage, linoleic acid concentration decreased markedly, mainly in P, while oleic acid concentration increased. PMID:27129978

  7. Cell cycle nucleic acids, polypeptides and uses thereof

    DOEpatents

    Gordon-Kamm, William J.; Lowe, Keith S.; Larkins, Brian A.; Dilkes, Brian R.; Sun, Yuejin

    2007-08-14

    The invention provides isolated nucleic acids and their encoded proteins that are involved in cell cycle regulation. The invention further provides recombinant expression cassettes, host cells, transgenic plants, and antibody compositions. The present invention provides methods and compositions relating to altering cell cycle protein content, cell cycle progression, cell number and/or composition of plants.

  8. Citric acid cycle and role of its intermediates in metabolism.

    PubMed

    Akram, Muhammad

    2014-04-01

    The citric acid cycle is the final common oxidative pathway for carbohydrates, fats and amino acids. It is the most important metabolic pathway for the energy supply to the body. TCA is the most important central pathway connecting almost all the individual metabolic pathways. In this review article, introduction, regulation and energetics of TCA cycle have been discussed. The present study was carried out to review literature on TCA cycle.

  9. Microbial Iron Cycling in Acidic Geothermal Springs of Yellowstone National Park: Integrating Molecular Surveys, Geochemical Processes, and Isolation of Novel Fe-Active Microorganisms

    PubMed Central

    Kozubal, Mark A.; Macur, Richard E.; Jay, Zackary J.; Beam, Jacob P.; Malfatti, Stephanie A.; Tringe, Susannah G.; Kocar, Benjamin D.; Borch, Thomas; Inskeep, William P.

    2012-01-01

    Geochemical, molecular, and physiological analyses of microbial isolates were combined to study the geomicrobiology of acidic iron oxide mats in Yellowstone National Park. Nineteen sampling locations from 11 geothermal springs were studied ranging in temperature from 53 to 88°C and pH 2.4 to 3.6. All iron oxide mats exhibited high diversity of crenarchaeal sequences from the Sulfolobales, Thermoproteales, and Desulfurococcales. The predominant Sulfolobales sequences were highly similar to Metallosphaera yellowstonensis str. MK1, previously isolated from one of these sites. Other groups of archaea were consistently associated with different types of iron oxide mats, including undescribed members of the phyla Thaumarchaeota and Euryarchaeota. Bacterial sequences were dominated by relatives of Hydrogenobaculum spp. above 65–70°C, but increased in diversity below 60°C. Cultivation of relevant iron-oxidizing and iron-reducing microbial isolates included Sulfolobus str. MK3, Sulfobacillus str. MK2, Acidicaldus str. MK6, and a new candidate genus in the Sulfolobales referred to as Sulfolobales str. MK5. Strains MK3 and MK5 are capable of oxidizing ferrous iron autotrophically, while strain MK2 oxidizes iron mixotrophically. Similar rates of iron oxidation were measured for M. yellowstonensis str. MK1 and Sulfolobales str. MK5. Biomineralized phases of ferric iron varied among cultures and field sites, and included ferric oxyhydroxides, K-jarosite, goethite, hematite, and scorodite depending on geochemical conditions. Strains MK5 and MK6 are capable of reducing ferric iron under anaerobic conditions with complex carbon sources. The combination of geochemical and molecular data as well as physiological observations of isolates suggests that the community structure of acidic Fe mats is linked with Fe cycling across temperatures ranging from 53 to 88°C. PMID:22470372

  10. Microbial iron cycling in acidic geothermal springs of yellowstone national park: integrating molecular surveys, geochemical processes, and isolation of novel fe-active microorganisms.

    PubMed

    Kozubal, Mark A; Macur, Richard E; Jay, Zackary J; Beam, Jacob P; Malfatti, Stephanie A; Tringe, Susannah G; Kocar, Benjamin D; Borch, Thomas; Inskeep, William P

    2012-01-01

    Geochemical, molecular, and physiological analyses of microbial isolates were combined to study the geomicrobiology of acidic iron oxide mats in Yellowstone National Park. Nineteen sampling locations from 11 geothermal springs were studied ranging in temperature from 53 to 88°C and pH 2.4 to 3.6. All iron oxide mats exhibited high diversity of crenarchaeal sequences from the Sulfolobales, Thermoproteales, and Desulfurococcales. The predominant Sulfolobales sequences were highly similar to Metallosphaera yellowstonensis str. MK1, previously isolated from one of these sites. Other groups of archaea were consistently associated with different types of iron oxide mats, including undescribed members of the phyla Thaumarchaeota and Euryarchaeota. Bacterial sequences were dominated by relatives of Hydrogenobaculum spp. above 65-70°C, but increased in diversity below 60°C. Cultivation of relevant iron-oxidizing and iron-reducing microbial isolates included Sulfolobus str. MK3, Sulfobacillus str. MK2, Acidicaldus str. MK6, and a new candidate genus in the Sulfolobales referred to as Sulfolobales str. MK5. Strains MK3 and MK5 are capable of oxidizing ferrous iron autotrophically, while strain MK2 oxidizes iron mixotrophically. Similar rates of iron oxidation were measured for M. yellowstonensis str. MK1 and Sulfolobales str. MK5. Biomineralized phases of ferric iron varied among cultures and field sites, and included ferric oxyhydroxides, K-jarosite, goethite, hematite, and scorodite depending on geochemical conditions. Strains MK5 and MK6 are capable of reducing ferric iron under anaerobic conditions with complex carbon sources. The combination of geochemical and molecular data as well as physiological observations of isolates suggests that the community structure of acidic Fe mats is linked with Fe cycling across temperatures ranging from 53 to 88°C.

  11. Titer of trastuzumab produced by a Chinese hamster ovary cell line is associated with tricarboxylic acid cycle activity rather than lactate metabolism.

    PubMed

    Ishii, Yoichi; Imamoto, Yasufumi; Yamamoto, Rie; Tsukahara, Masayoshi; Wakamatsu, Kaori

    2015-04-01

    Achieving high productivity and quality is the final goal of therapeutic antibody development, but the productivity and quality of antibodies are known to be substantially dependent on the nature of the cell lines expressing the antibodies. We characterized two contrasting cell lines that produce trastuzumab, namely cell line A with a high titer and a low aggregate content and cell line B with a low titer and a high aggregate content to identify the causes of the differences. We observed the following differences: cell growth (A > B), proportion of defucosylated oligosaccharides on antibodies (A < B), and proportion of covalent antibody aggregates (A > B). Our results suggest that the high monoclonal antibody (mAb) titers in cell line A is associated with the high proliferation and is not caused by the lactate metabolism shift (switching from lactate production to net lactate consumption). Rather, these differences can be accounted for by the following: levels of tricarboxylic acid cycle intermediates (A > B), ammonium ion levels (A ≤ B), and oxidative stress (A > B). PMID:25449760

  12. Tricarboxylic Acid Cycle-Dependent Attenuation of Staphylococcus aureus In Vivo Virulence by Selective Inhibition of Amino Acid Transport▿

    PubMed Central

    Zhu, Yefei; Xiong, Yan Q.; Sadykov, Marat R.; Fey, Paul D.; Lei, Mei G.; Lee, Chia Y.; Bayer, Arnold S.; Somerville, Greg A.

    2009-01-01

    Staphylococci are the leading causes of endovascular infections worldwide. Commonly, these infections involve the formation of biofilms on the surface of biomaterials. Biofilms are a complex aggregation of bacteria commonly encapsulated by an adhesive exopolysaccharide matrix. In staphylococci, this exopolysaccharide matrix is composed of polysaccharide intercellular adhesin (PIA). PIA is synthesized when the tricarboxylic acid (TCA) cycle is repressed. The inverse correlation between PIA synthesis and TCA cycle activity led us to hypothesize that increasing TCA cycle activity would decrease PIA synthesis and biofilm formation and reduce virulence in a rabbit catheter-induced model of biofilm infection. TCA cycle activity can be induced by preventing staphylococci from exogenously acquiring a TCA cycle-derived amino acid necessary for growth. To determine if TCA cycle induction would decrease PIA synthesis in Staphylococcus aureus, the glutamine permease gene (glnP) was inactivated and TCA cycle activity, PIA accumulation, biofilm forming ability, and virulence in an experimental catheter-induced endovascular biofilm (endocarditis) model were determined. Inactivation of this major glutamine transporter increased TCA cycle activity, transiently decreased PIA synthesis, and significantly reduced in vivo virulence in the endocarditis model in terms of achievable bacterial densities in biofilm-associated cardiac vegetations, kidneys, and spleen. These data confirm the close linkage of TCA cycle activity and virulence factor production and establish that this metabolic linkage can be manipulated to alter infectious outcomes. PMID:19667045

  13. The Hydrologic Cycle Distributed Active Archive Center

    NASA Technical Reports Server (NTRS)

    Hardin, Danny M.; Goodman, H. Michael

    1995-01-01

    The Marshall Space Flight Center Distributed Active Archive Center in Huntsville, Alabama supports the acquisition, production, archival and dissemination of data relevant to the study of the global hydrologic cycle. This paper describes the Hydrologic Cycle DAAC, surveys its principle data holdings, addresses future growth, and gives information for accessing the data sets.

  14. Metabolism: Part II. The Tricarboxylic Acid (TCA), Citric Acid, or Krebs Cycle.

    ERIC Educational Resources Information Center

    Bodner, George M.

    1986-01-01

    Differentiates the tricarboxylic acid (TCA) cycle (or Krebs cycle) from glycolysis, and describes the bridge between the two as being the conversion of pyruvate into acetyl coenzyme A. Discusses the eight steps in the TCA cycle, the results of isotopic labeling experiments, and the net effects of the TCA cycle. (TW)

  15. Phosphorus constrains accelerated nitrogen cycling in limed acidic forests

    NASA Astrophysics Data System (ADS)

    Deforest, J. L.; Shaw, A. N.; Kluber, L. A.; Burke, D. J.; Carrino-Kyker, S. R.; Smemo, K. A.

    2011-12-01

    Anthropogenic deposition can increase phosphorus (P) limitation by abiotic and biotic means. Soil acidification can remove P from available pools and nitrogen (N) deposition can increase the demand for P. We reason that chronic acidic deposition is promoting P limitation in acidic hardwood forests and thereby altering N cycling. The objectives of this study were to investigate the interactive influence of P availability and soil pH on N and P cycling and availability to determine if the response varies between two physiographic regions experiencing similar chronic acidic deposition. We addressed these objectives by experimentally manipulating soil pH, P, or both in strongly acidic glaciated and unglaciated hardwood forests in eastern Ohio, USA. Our results suggest complex interactions between P, soil pH, and the N cycle. Glaciated soils were found to be more N-saturated with nitrification rates 18 times greater than in unglaciated soils. Elevating pH, with or without added P, doubled nitrification rates in glaciated soils. For unglaciated soils, raising pH increased nitrification 10-fold, but increased nitrification only 5-fold in combination with P. This result suggests raising soil pH lowered the demand of soil N, or directly stimulated nitrifying activity, and that increasing P availability could limit N availability. To various degrees, readily available P was geochemically or biologically immobilized in all treatments, suggesting chronic P deficiency in these ecosystems. Phosphorus immobilization decreased as soil pH was elevated, but elevated P either had no effect (glaciated) or doubled P immobilization rates (unglaciated). These results suggest that raising soil pH reduces microbial P limitation for phosphate, whereas adding P appears to make phosphate scarcer. We suggest that P plays an important role in N transformations and cycling, but appears more important in unglaciated soils than in glaciated soils. Chronic soil acidification may have a greater

  16. Sulfuric acid on Europa and the radiolytic sulfur cycle

    NASA Technical Reports Server (NTRS)

    Carlson, R. W.; Johnson, R. E.; Anderson, M. S.

    1999-01-01

    A comparison of laboratory spectra with Galileo data indicates that hydrated sulfuric acid is present and is a major component of Europa's surface. In addition, this moon's visually dark surface material, which spatially correlates with the sulfuric acid concentration, is identified as radiolytically altered sulfur polymers. Radiolysis of the surface by magnetospheric plasma bombardment continuously cycles sulfur between three forms: sulfuric acid, sulfur dioxide, and sulfur polymers, with sulfuric acid being about 50 times as abundant as the other forms. Enhanced sulfuric acid concentrations are found in Europa's geologically young terrains, suggesting that low-temperature, liquid sulfuric acid may influence geological processes.

  17. Effects of intermediate metabolite carboxylic acids of TCA cycle on Microcystis with overproduction of phycocyanin.

    PubMed

    Bai, Shijie; Dai, Jingcheng; Xia, Ming; Ruan, Jing; Wei, Hehong; Yu, Dianzhen; Li, Ronghui; Jing, Hongmei; Tian, Chunyuan; Song, Lirong; Qiu, Dongru

    2015-04-01

    Toxic Microcystis species are the main bloom-forming cyanobacteria in freshwaters. It is imperative to develop efficient techniques to control these notorious harmful algal blooms (HABs). Here, we present a simple, efficient, and environmentally safe algicidal way to control Microcystis blooms, by using intermediate carboxylic acids from the tricarboxylic acid (TCA) cycle. The citric acid, alpha-ketoglutaric acid, succinic acid, fumaric acid, and malic acid all exhibited strong algicidal effects, and particularly succinic acid could cause the rapid lysis of Microcystis in a few hours. It is revealed that the Microcystis-lysing activity of succinic acid and other carboxylic acids was due to their strong acidic activity. Interestingly, the acid-lysed Microcystis cells released large amounts of phycocyanin, about 27-fold higher than those of the control. On the other hand, the transcription of mcyA and mcyD of the microcystin biosynthesis operon was not upregulated by addition of alpha-ketoglutaric acid and other carboxylic acids. Consider the environmental safety of intermediate carboxylic acids. We propose that administration of TCA cycle organic acids may not only provide an algicidal method with high efficiency and environmental safety but also serve as an applicable way to produce and extract phycocyanin from cyanobacterial biomass.

  18. Redox cycling of a copper complex with benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone contributes to its enhanced antitumor activity, but no change in the mechanism of action occurs after chelation.

    PubMed

    Yang, Yinli; Li, Cuiping; Fu, Yun; Liu, Youxun; Zhang, Yu; Zhang, Yanfang; Zhou, Pingxin; Yuan, Yanbin; Zhou, Sufeng; Li, Shaoshan; Li, Changzheng

    2016-03-01

    Many anticancer drugs used in the clinical have potent metal chelating ability. The formed metal complex(es) may exhibit improved (or antagonistic) antitumor activity. However, the underlying mechanism has received limited attention. Therefore, investigation of the mechanism involved in the change upon chelation is required to extend our understanding of the effects of various drugs. In the present study, the proliferation inhibition effect of benzaldehyde nitrogen mustard-2-pyridine carboxylic acid hydrazone (BNMPH) and its copper complex on tumor cell lines was investigated. The copper chelate exhibited almost a 10-fold increase in antitumor activity (with IC50 <5 µM). The results showed that both BNMPH and its copper complex induced reactive oxygen species (ROS) generation, and caused upregulation of caspase 8 and Bax as well as the downregulation of Bcl-2, indicating that apoptosis was involved in the cytotoxic effects. DNA fragmentation noted in the comet assay further supported ROS involvement. The present study indicated that BNMPH and its copper complex effectively induced S phase arrest and the cell cycle arrest was associated with the downregulation of cyclin D1. The formation of acidic vesicular organelles (AVOs) and an increase in cleaved LC3-II demonstrated that autophagy occurred in the HepG2 cells treated with the agents. Taken together, BNMPH and its copper complex exhibited proliferation inhibition via apoptosis, cell cycle arrest and autophagy, which was dependent on ROS. The enhanced antitumor activity of the copper complex was due to its redox-cycling ability, but the mechanism was not altered compared to BNMPH. Our findings may significantly contribute to the understanding of the anti-proliferative effect of BNMPH and its copper complex.

  19. Patterns of diversity of citric acid cycle enzymes.

    PubMed

    Weitzman, P D

    1987-01-01

    The citric acid cycle performs a dual role in cell metabolism, acting as a source of both 'energy' and biosynthetic starting materials. The widespread occurrence of the cycle throughout Nature is an excellent example of the unity of biochemistry, but closer examination reveals that there is considerable diversity in the citric acid cycle of different organisms with respect to metabolic role, molecular enzymology and mode of regulation. Two enzymes of the cycle--citrate synthase and succinate thiokinase--have been found to exhibit particularly striking patterns of diversity in structure and catalytic and regulatory function. Some of these patterns show a correlation with the taxonomic groupings of the organisms and with their physiological characteristics. Comparative enzyme studies have a contribution to make to an ultimate understanding of the cycle and its cellular operation, and there are substantial benefits to be gained from interactive studies on both prokaryotic and eukaryotic systems.

  20. A possible activity cycle in Proxima Centauri

    NASA Astrophysics Data System (ADS)

    Cincunegui, C.; Díaz, R. F.; Mauas, P. J. D.

    2007-01-01

    Context: Several late-type stars present activity cycles resembling the Solar one. This fact has been observed mostly in stars ranging from F to K, i.e., in stars with a radiative core and an outer convective layer. Aims: This work aims at studying whether an activity cycle can be detected in the dM5.5e star Proxima Centauri, which is supposed to be completely convective. Methods: We present periodical medium-resolution echelle observations covering the complete visual range, which were taken at the CASLEO Argentinean Observatory. These observations are distributed over 7 years. We discarded the spectra that present flare activity, and analyze the remaining activity levels using four different statistical techniques to look for a period of activity. Results: We find strong evidence of a cyclic activity, with a period of ~442 days. We also estimate that the Ca ~II S index varies around 130% due to activity variations outside of flares.

  1. Discrimination in the dark. Resolving the interplay between metabolic and physical constraints to phosphoenolpyruvate carboxylase activity during the crassulacean acid metabolism cycle.

    PubMed

    Griffiths, Howard; Cousins, Asaph B; Badger, Murray R; von Caemmerer, Susanne

    2007-02-01

    A model defining carbon isotope discrimination (delta13C) for crassulacean acid metabolism (CAM) plants was experimentally validated using Kalanchoe daigremontiana. Simultaneous measurements of gas exchange and instantaneous CO2 discrimination (for 13C and 18O) were made from late photoperiod (phase IV of CAM), throughout the dark period (phase I), and into the light (phase II). Measurements of CO2 response curves throughout the dark period revealed changing phosphoenolpyruvate carboxylase (PEPC) capacity. These systematic changes in PEPC capacity were tracked by net CO2 uptake, stomatal conductance, and online delta13C signal; all declined at the start of the dark period, then increased to a maximum 2 h before dawn. Measurements of delta13C were higher than predicted from the ratio of intercellular to external CO2 (p(i)/p(a)) and fractionation associated with CO2 hydration and PEPC carboxylations alone, such that the dark period mesophyll conductance, g(i), was 0.044 mol m(-2) s(-1) bar(-1). A higher estimate of g(i) (0.085 mol m(-2) s(-1) bar(-1)) was needed to account for the modeled and measured delta18O discrimination throughout the dark period. The differences in estimates of g(i) from the two isotope measurements, and an offset of -5.5 per thousand between the 18O content of source and transpired water, suggest spatial variations in either CO2 diffusion path length and/or carbonic anhydrase activity, either within individual cells or across a succulent leaf. Our measurements support the model predictions to show that internal CO2 diffusion limitations within CAM leaves increase delta13C discrimination during nighttime CO2 fixation while reducing delta13C during phase IV. When evaluating the phylogenetic distribution of CAM, carbon isotope composition will reflect these diffusive limitations as well as relative contributions from C3 and C4 biochemistry.

  2. A possible activity cycle in Proxima Centauri

    NASA Astrophysics Data System (ADS)

    Cincunegui, C.; Díaz, R. F.; Mauas, P. J. D.

    Several late-type stars (stars with a radiative core and an outer convective layer) present activity cycles resembling the Solar one. This work aims at studying whether an activity cycle can be detected in the dM5.5e star Proxima Centauri, which is supposed to be completely convective. We present periodical medium-resolution echelle observations covering the complete visual range, which were taken at the CASLEO Argentinean Observatory. These observations are distributed along 7 years. We analize the activity levels to look for a period of activity. We find strong evidence of a cyclic activity, with a period of ˜442 days. We also estimated that the Ca II S index varies around 130% due to activity variations outside of flares.

  3. Combined cycle phosphoric acid fuel cell electric power system

    SciTech Connect

    Mollot, D.J.; Micheli, P.L.

    1995-12-31

    By arranging two or more electric power generation cycles in series, combined cycle systems are able to produce electric power more efficiently than conventional single cycle plants. The high fuel to electricity conversion efficiency results in lower plant operating costs, better environmental performance, and in some cases even lower capital costs. Despite these advantages, combined cycle systems for the 1 - 10 megawatt (MW) industrial market are rare. This paper presents a low noise, low (oxides of nitrogen) NOx, combined cycle alternative for the small industrial user. By combining a commercially available phosphoric acid fuel cell (PAFC) with a low-temperature Rankine cycle (similar to those used in geothermal applications), electric conversion efficiencies between 45 and 47 percent are predicted. While the simple cycle PAFC is competitive on a cost of energy basis with gas turbines and diesel generators in the 1 to 2 MW market, the combined cycle PAFC is competitive, on a cost of energy basis, with simple cycle diesel generators in the 4 to 25 MW market. In addition, the efficiency and low-temperature operation of the combined cycle PAFC results in a significant reduction in carbon dioxide emissions with NO{sub x} concentration on the order of 1 parts per million (per weight) (ppmw).

  4. Forecasting the solar activity cycle: new insights

    NASA Astrophysics Data System (ADS)

    Nandy, Dibyendu; Karak, Bidya Binay

    2013-07-01

    Having advance knowledge of solar activity is important because the Sun's magnetic output governs space weather and impacts technologies reliant on space. However, the irregular nature of the solar cycle makes solar activity predictions a challenging task. This is best achieved through appropriately constrained solar dynamo simulations and as such the first step towards predictions is to understand the underlying physics of the solar dynamo mechanism. In Babcock-Leighton type dynamo models, the poloidal field is generated near the solar surface whereas the toroidal field is generated in the solar interior. Therefore a finite time is necessary for the coupling of the spatially segregated source layers of the dynamo. This time delay introduces a memory in the dynamo mechanism which allows forecasting of future solar activity. Here we discuss how this forecasting ability of the solar cycle is affected by downward turbulent pumping of magnetic flux. With significant turbulent pumping the memory of the dynamo is severely degraded and thus long term prediction of the solar cycle is not possible; only a short term prediction of the next cycle peak may be possible based on observational data assimilation at the previous cycle minimum.

  5. Citric acid cycle and the origin of MARS.

    PubMed

    Eswarappa, Sandeepa M; Fox, Paul L

    2013-05-01

    The vertebrate multiaminoacyl tRNA synthetase complex (MARS) is an assemblage of nine aminoacyl tRNA synthetases (ARSs) and three non-synthetase scaffold proteins, aminoacyl tRNA synthetase complex-interacting multifunctional protein (AIMP)1, AIMP2, and AIMP3. The evolutionary origin of the MARS is unclear, as is the significance of the inclusion of only nine of 20 tRNA synthetases. Eight of the nine amino acids corresponding to ARSs of the MARS are derived from two citric acid cycle intermediates, α-ketoglutatrate and oxaloacetate. We propose that the metabolic link with the citric acid cycle, the appearance of scaffolding proteins AIMP2 and AIMP3, and the subsequent disappearance of the glyoxylate cycle, together facilitated the origin of the MARS in a common ancestor of metazoans and choanoflagellates.

  6. A Functional Tricarboxylic Acid Cycle Operates during Growth of Bordetella pertussis on Amino Acid Mixtures as Sole Carbon Substrates.

    PubMed

    Izac, Marie; Garnier, Dominique; Speck, Denis; Lindley, Nic D

    2015-01-01

    It has been claimed that citrate synthase, aconitase and isocitrate dehydrogenase activities are non-functional in Bordetella pertussis and that this might explain why this bacterium's growth is sometimes associated with accumulation of polyhydroxybutyrate (PHB) and/or free fatty acids. However, the sequenced genome includes the entire citric acid pathway genes. Furthermore, these genes were expressed and the corresponding enzyme activities detected at high levels for the pathway when grown on a defined medium imitating the amino acid content of complex media often used for growth of this pathogenic microorganism. In addition, no significant PHB or fatty acids could be detected. Analysis of the carbon balance and stoichiometric flux analysis based on specific rates of amino acid consumption, and estimated biomass requirements coherent with the observed growth rate, clearly indicate that a fully functional tricarboxylic acid cycle operates in contrast to previous reports.

  7. A Functional Tricarboxylic Acid Cycle Operates during Growth of Bordetella pertussis on Amino Acid Mixtures as Sole Carbon Substrates

    PubMed Central

    Garnier, Dominique; Speck, Denis

    2015-01-01

    It has been claimed that citrate synthase, aconitase and isocitrate dehydrogenase activities are non-functional in Bordetella pertussis and that this might explain why this bacterium’s growth is sometimes associated with accumulation of polyhydroxybutyrate (PHB) and/or free fatty acids. However, the sequenced genome includes the entire citric acid pathway genes. Furthermore, these genes were expressed and the corresponding enzyme activities detected at high levels for the pathway when grown on a defined medium imitating the amino acid content of complex media often used for growth of this pathogenic microorganism. In addition, no significant PHB or fatty acids could be detected. Analysis of the carbon balance and stoichiometric flux analysis based on specific rates of amino acid consumption, and estimated biomass requirements coherent with the observed growth rate, clearly indicate that a fully functional tricarboxylic acid cycle operates in contrast to previous reports. PMID:26684737

  8. POSSIBLE CHROMOSPHERIC ACTIVITY CYCLES IN AD LEO

    SciTech Connect

    Buccino, Andrea P.; Petrucci, Romina; Mauas, Pablo J. D.; Jofré, Emiliano

    2014-01-20

    AD Leo (GJ 388) is an active dM3 flare star that has been extensively observed both in the quiescent and flaring states. Since this active star is near the fully convective boundary, studying its long-term chromospheric activity in detail could be an appreciable contribution to dynamo theory. Here, using the Lomb-Scargle periodogram, we analyze the Ca II K line-core fluxes derived from CASLEO spectra obtained between 2001 and 2013 and the V magnitude from the ASAS database between 2004 and 2010. From both of these totally independent time series, we obtain a possible activity cycle with a period of approximately seven years and a less significant shorter cycle of approximately two years. A tentative interpretation is that a dynamo operating near the surface could be generating the longer cycle, while a second dynamo operating in the deep convection zone could be responsible for the shorter one. Based on the long duration of our observing program at CASLEO and the fact that we observe different spectral features simultaneously, we also analyze the relation between simultaneous measurements of the Na I index (R{sub D}{sup ′}), Hα, and Ca II K fluxes at different activity levels of AD Leo, including flares.

  9. [Influence of chosen metals on the citric acid cycle].

    PubMed

    Rojczyk-Gołebiewska, Ewa; Kucharzewski, Marek

    2013-03-01

    Industrial activity growth influenced not only technological progress, but also had negative effects on human natural environment. It results among others in increased human exposition to heavy metals. In case of detoxication mechanisms disturbance in organism, heavy metals cumulate in tissues causing mutations and disrupting metabolism, including Krebs cycle. Recent studies have revealed that iron, zinc and manganese have especially strong influence on Krebs cycle. These elements act as cofactors or inhibitors regulating activity of particular enzymes of this cycle, which has a reflection in cellular energy production disturbances.

  10. [Effects of polyunsaturated fatty acids on Krebs cycle in the rat kidney in chronic phosphorus intoxication].

    PubMed

    Kulkybaev, G A; Merkusheva, N V

    1992-01-01

    The investigation of Krebs cycle state in kidney homogenates of August rats subjected to oral intoxication with oil solution of yellow phosphorus in a dose of 0.3 mg/kg, has shown that under conditions of balanced nutrition the activity of NAD-dependent isocitrate dehydrogenase, succinate dehydrogenase and accumulation of the substrate fund of the cycle decreased 3.5-fold as compared to the control. The addition of polyunsaturated fatty acids to the ration produced a positive effect on Krebs cycle state: dehydrogenase activity was not significantly changed, accumulation of Krebs cycle substrate was two-fold lower. However, this ration did not completely abolish the toxic action of yellow phosphorus on Krebs cycle.

  11. Stochastic cycle selection in active flow networks.

    PubMed

    Woodhouse, Francis G; Forrow, Aden; Fawcett, Joanna B; Dunkel, Jörn

    2016-07-19

    Active biological flow networks pervade nature and span a wide range of scales, from arterial blood vessels and bronchial mucus transport in humans to bacterial flow through porous media or plasmodial shuttle streaming in slime molds. Despite their ubiquity, little is known about the self-organization principles that govern flow statistics in such nonequilibrium networks. Here we connect concepts from lattice field theory, graph theory, and transition rate theory to understand how topology controls dynamics in a generic model for actively driven flow on a network. Our combined theoretical and numerical analysis identifies symmetry-based rules that make it possible to classify and predict the selection statistics of complex flow cycles from the network topology. The conceptual framework developed here is applicable to a broad class of biological and nonbiological far-from-equilibrium networks, including actively controlled information flows, and establishes a correspondence between active flow networks and generalized ice-type models. PMID:27382186

  12. Commercial Alloys for Sulfuric Acid Vaporization in Thermochemical Hydrogen Cycles

    SciTech Connect

    Thomas M. Lillo; Karen M. Delezene-Briggs

    2005-10-01

    Most thermochemical cycles being considered for producing hydrogen include a processing stream in which dilute sulfuric acid is concentrated, vaporized and then decomposed over a catalyst. The sulfuric acid vaporizer is exposed to highly aggressive conditions. Liquid sulfuric acid will be present at a concentration of >96 wt% (>90 mol %) H2SO4 and temperatures exceeding 400oC [Brown, et. al, 2003]. The system will also be pressurized, 0.7-3.5 MPa, to keep the sulfuric acid in the liquid state at this temperature and acid concentration. These conditions far exceed those found in the commercial sulfuric acid generation, regeneration and handling industries. Exotic materials, e.g. ceramics, precious metals, clad materials, etc., have been proposed for this application [Wong, et. al., 2005]. However, development time, costs, reliability, safety concerns and/or certification issues plague such solutions and should be considered as relatively long-term, optimum solutions. A more cost-effective (and relatively near-term) solution would be to use commercially-available metallic alloys to demonstrate the cycle and study process variables. However, the corrosion behavior of commercial alloys in sulfuric acid is rarely characterized above the natural boiling point of concentrated sulfuric acid (~250oC at 1 atm). Therefore a screening study was undertaken to evaluate the suitability of various commercial alloys for concentration and vaporization of high-temperature sulfuric acid. Initially alloys were subjected to static corrosion tests in concentrated sulfuric acid (~95-97% H2SO4) at temperatures and exposure times up to 200oC and 480 hours, respectively. Alloys with a corrosion rate of less than 5 mm/year were then subjected to static corrosion tests at a pressure of 1.4 MPa and temperatures up to 375oC. Exposure times were shorter due to safety concerns and ranged from as short as 5 hours up to 144 hours. The materials evaluated included nickel-, iron- and cobalt

  13. Sporulation of Tricarboxylic Acid Cycle Mutants of Bacillus subtilis

    PubMed Central

    Yousten, Allan A.; Hanson, Richard S.

    1972-01-01

    A mutant of Bacillus subtilis 168 lacking aconitase (EC 4.2.1.3) was found to be blocked at stage 0 or I of sporulation. Although adenosine triphosphate levels, which normally decrease in tricarboxylic acid cycle mutants at the completion of exponential growth, could be maintained at higher levels by feeding metabolizable carbon sources, this did not permit the cells to progress further into the sporulation sequence. When post-exponential-phase cells of mutants blocked in the first half of the tricarboxylic acid cycle were resuspended with an energy source in culture fluid from post-exponential-phase wild-type B. subtilis or Escherichia coli, good sporulation occurred. The spores produced retained the mutant genotype and were heat stable but lost refractility and heat stability several hours after their production. Images PMID:4110146

  14. Glyoxylate cycle and metabolism of organic acids in the scutellum of barley seeds during germination.

    PubMed

    Ma, Zhenguo; Marsolais, Frédéric; Bernards, Mark A; Sumarah, Mark W; Bykova, Natalia V; Igamberdiev, Abir U

    2016-07-01

    During the developmental processes from dry seeds to seedling establishment, the glyoxylate cycle becomes active in the mobilization of stored oils in the scutellum of barley (Hordeum vulgare L.) seeds, as indicated by the activities of isocitrate lyase and malate synthase. The succinate produced is converted to carbohydrates via phosphoenolpyruvate carboxykinase and to amino acids via aminotransferases, while free organic acids may participate in acidifying the endosperm tissue, releasing stored starch into metabolism. The abundant organic acid in the scutellum was citrate, while malate concentration declined during the first three days of germination, and succinate concentration was low both in scutellum and endosperm. Malate was more abundant in endosperm tissue during the first three days of germination; before citrate became predominant, indicating that malate may be the main acid acidifying the endosperm. The operation of the glyoxylate cycle coincided with an increase in the ATP/ADP ratio, a buildup of H2O2 and changes in the redox state of ascorbate and glutathione. It is concluded that operation of the glyoxylate cycle in the scutellum of cereals may be important not only for conversion of fatty acids to carbohydrates, but also for the acidification of endosperm and amino acid synthesis. PMID:27181945

  15. Effects of oxolinic acid on the sleep-wakefulness cycle of the rat

    PubMed Central

    D'Angelo, L.; Monti, J.M.

    1981-01-01

    1 A study was carried out in rats (prepared for chronic sleep recording) of the effects of oxolinic acid on the sleep-wakefulness cycle. 2 In addition, the actions of oxolinic acid on the sleep-wake cycle were assessed after pretreatment with drugs interfering with central catecholamine mechanisms or facilitating central γ-aminobutyric acid (GABA) activity. 3 Oxolinic acid (8-32 mg/kg) induced a significant and dose-related increase of waking EEG, while slow wave and REM sleep were decreased. 4 The effects of oxolinic acid on waking, slow wave and REM sleep were antagonized by α-methyl-p-tyrosine (50-100 mg/kg) which interferes with the synthesis of catecholamines. 5 FLA-63 (25 mg/kg) which is a specific inhibitor of noradrenaline synthesis, was effective in blocking oxolinic acid-related increase of waking and decrease of slow wave sleep. 6 Haloperidol (0.4-0.6 mg/kg) which blocks central dopamine and noradrenaline receptors, reversed oxolinic acid-induced actions on waking and slow wave sleep. Spiroperidol (2-4 mg/kg) which interferes with dopamine and 5-hydroxytryptamine mechanisms, only antagonized the effect of oxolinic acid on light slow wave sleep. REM sleep was further decreased by both neuroleptic agents. 7 γ-Hydroxybutyrate (25-50 mg/kg), which acts as a GABA agonist and amino-oxyacetic acid (20 mg/kg), which considerably increases central GABA levels, were ineffective in blocking oxolinic acid-related disruption of the sleep-wake cycle. 8 Our results suggest that the catecholamines are involved in the arousing effect of oxolinic acid. PMID:7317689

  16. Bioluminescence regenerative cycle (BRC) system for nucleic acid quantification assays

    NASA Astrophysics Data System (ADS)

    Hassibi, Arjang; Lee, Thomas H.; Davis, Ronald W.; Pourmand, Nader

    2003-07-01

    A new label-free methodology for nucleic acid quantification has been developed where the number of pyrophosphate molecules (PPi) released during polymerization of the target nucleic acid is counted and correlated to DNA copy number. The technique uses the enzymatic complex of ATP-sulfurylase and firefly luciferase to generate photons from PPi. An enzymatic unity gain positive feedback is also implemented to regenerate the photon generation process and compensate any decay in light intensity by self regulation. Due to this positive feedback, the total number of photons generated by the bioluminescence regenerative cycle (BRC) can potentially be orders of magnitude higher than typical chemiluminescent processes. A system level kinetic model that incorporates the effects of contaminations and detector noise was used to show that the photon generation process is in fact steady and also proportional to the nucleic acid quantity. Here we show that BRC is capable of detecting quantities of DNA as low as 1 amol (10-18 mole) in 40μlit aqueous solutions, and this enzymatic assay has a controllable dynamic range of 5 orders of magnitude. The sensitivity of this technology, due to the excess number of photons generated by the regenerative cycle, is not constrained by detector performance, but rather by possible PPi or ATP (adenosine triphosphate) contamination, or background bioluminescence of the enzymatic complex.

  17. Maintenance Carbon Cycle in Crassulacean Acid Metabolism Plant Leaves 1

    PubMed Central

    Kenyon, William H.; Severson, Ray F.; Black, Clanton C.

    1985-01-01

    The reciprocal relationship between diurnal changes in organic acid and storage carbohydrate was examined in the leaves of three Crassulacean acid metabolism plants. It was found that depletion of leaf hexoses at night was sufficient to account quantitatively for increase in malate in Ananas comosus but not in Sedum telephium or Kalanchoë daigremontiana. Fructose and to a lesser extent glucose underwent the largest changes. Glucose levels in S. telephium leaves oscillated diurnally but were not reciprocally related to malate fluctuations. Analysis of isolated protoplasts and vacuoles from leaves of A. comosus and S. telephium revealed that vacuoles contain a large percentage (>50%) of the protoplast glucose, fructose and malate, citrate, isocitrate, ascorbate and succinate. Sucrose, a major constituent of intact leaves, was not detectable or was at extremely low levels in protoplasts and vacuoles from both plants. In isolated vacuoles from both A. comosus and S. telephium, hexose levels decreased at night at the same time malate increased. Only in A. comosus, however, could hexose metabolism account for a significant amount of the nocturnal increase in malate. We conclude that, in A. comosus, soluble sugars are part of the daily maintenance carbon cycle and that the vacuole plays a dynamic role in the diurnal carbon assimilation cycle of this Crassulacean acid metabolism plant. PMID:16664005

  18. Suppression of tricarboxylic acid cycle in Escherichia coli exposed to sub-MICs of aminoglycosides.

    PubMed Central

    Cavallero, A; Eftimiadi, C; Radin, L; Schito, G C

    1990-01-01

    The metabolic activity of Escherichia coli ATCC 25922 challenged with sub-MICs of aminoglycosides was analyzed with a batch calorimeter. High-performance and gas-liquid chromatographic techniques were utilized to evaluate the concentrations of metabolic reactants, intermediates, and end products. The data reported indicate that aminoglycosides inhibit or delay bacterial catabolism of carboxylic acids, with the following relative degrees of activity: amikacin greater than gentamicin greater than sisomicin greater than netilmicin greater than kanamycin. The decrease in total biomass production was proportional to the degree of tricarboxylic acid cycle inhibition. PMID:2183717

  19. Effect of alternative pathway therapy on branched chain amino acid metabolism in urea cycle disorder patients.

    PubMed

    Scaglia, Fernando; Carter, Susan; O'Brien, William E; Lee, Brendan

    2004-04-01

    Urea cycle disorders (UCDs) are a group of inborn errors of hepatic metabolism caused by the loss of enzymatic activities that mediate the transfer of nitrogen from ammonia to urea. These disorders often result in life-threatening hyperammonemia and hyperglutaminemia. A combination of sodium phenylbutyrate and sodium phenylacetate/benzoate is used in the clinical management of children with urea cycle defects as a glutamine trap, diverting nitrogen from urea synthesis to alternatives routes of excretion. We have observed that patients treated with these compounds have selective branched chain amino acid (BCAA) deficiency despite adequate dietary protein intake. However, the direct effect of alternative therapy on the steady state levels of plasma branched chain amino acids has not been well characterized. We have measured steady state plasma branched chain and other essential non-branched chain amino acids in control subjects, untreated ornithine transcarbamylase deficiency females and treated null activity urea cycle disorder patients in the fed steady state during the course of stable isotope studies. Steady-state leucine levels were noted to be significantly lower in treated urea cycle disorder patients when compared to either untreated ornithine transcarbamylase deficiency females or control subjects (P<0.0001). This effect was reproduced in control subjects who had depressed leucine levels when treated with sodium phenylacetate/benzoate (P<0.0001). Our studies suggest that this therapeutic modality has a substantial impact on the metabolism of branched chain amino acids in urea cycle disorder patients. These findings suggest that better titration of protein restriction could be achieved with branched chain amino acid supplementation in patients with UCDs who are on alternative route therapy.

  20. Permanent active longitudes and activity cycles on RS CVn stars

    NASA Astrophysics Data System (ADS)

    Berdyugina, Svetlana V.; Tuominen, Ilkka

    1998-08-01

    A new analysis of the published long-term photometric observations has revealed permanent active-longitude structures in four RS CVn stars: EI Eri, II Peg, sigma Gem, and HR 7275. Two active longitudes separated by half of the period are found to dominate on the surface during all available seasons. The positions of the longitudes on three stars (EI Eri, II Peg, HR 7275) are migrating in the orbital reference frame, and there is no preferred orientation with respect to the line of centres in the binaries. The rate of migration is approximately constant. In case of sigma Gem the active longitude migration is synchronized with the orbital motion in the direction of the line of centres in the binary. The active region lifetimes can be longer than the time span of the observations (>=15 yr). The periods of the active longitude rotation are determined: for EI Eri 1fd 9510, for II Peg 6fd 7066, for sigma Gem 19fd 604, for HR 7275 28fd 263. Long-term activity cycles of the stars are discovered from the analysis of the relative contribution of the two longitudes to the photometric variability. One longitude is found to be usually more active than the other at a given moment, and the change of the activity level between the longitudes is cyclic with periods of years. The switch of the activity takes a much shorter time, about a few months, similar to the ``flip-flop'' phenomenon found for FK Com stars. Moments of switching are regarded as new tracers of the activity, and total cycles, which return activity to the same longitude, are found to be for EI Eri 9.0 yr, for II Peg 9.3 yr, for sigma Gem 14.9 yr, for HR 7275 17.5 yr.

  1. Acetaminophen toxicity and 5-oxoproline (pyroglutamic acid): a tale of two cycles, one an ATP-depleting futile cycle and the other a useful cycle.

    PubMed

    Emmett, Michael

    2014-01-01

    The acquired form of 5-oxoproline (pyroglutamic acid) metabolic acidosis was first described in 1989 and its relationship to chronic acetaminophen ingestion was proposed the next year. Since then, this cause of chronic anion gap metabolic acidosis has been increasingly recognized. Many cases go unrecognized because an assay for 5-oxoproline is not widely available. Most cases occur in malnourished, chronically ill women with a history of chronic acetaminophen ingestion. Acetaminophen levels are very rarely in the toxic range; rather, they are usually therapeutic or low. The disorder generally resolves with cessation of acetaminophen and administration of intravenous fluids. Methionine or N-acetyl cysteine may accelerate resolution and methionine is protective in a rodent model. The disorder has been attributed to glutathione depletion and activation of a key enzyme in the γ-glutamyl cycle. However, the specific metabolic derangements that cause the 5-oxoproline accumulation remain unclear. An ATP-depleting futile 5-oxoproline cycle can explain the accumulation of 5-oxoproline after chronic acetaminophen ingestion. This cycle is activated by the depletion of both glutathione and cysteine. This explanation contributes to our understanding of acetaminophen-induced 5-oxoproline metabolic acidosis and the beneficial role of N-acetyl cysteine therapy. The ATP-depleting futile 5-oxoproline cycle may also play a role in the energy depletions that occur in other acetaminophen-related toxic syndromes.

  2. Metabolic effects of intestinal absorption and enterohepatic cycling of bile acids

    PubMed Central

    Ferrebee, Courtney B.; Dawson, Paul A.

    2015-01-01

    The classical functions of bile acids include acting as detergents to facilitate the digestion and absorption of nutrients in the gut. In addition, bile acids also act as signaling molecules to regulate glucose homeostasis, lipid metabolism and energy expenditure. The signaling potential of bile acids in compartments such as the systemic circulation is regulated in part by an efficient enterohepatic circulation that functions to conserve and channel the pool of bile acids within the intestinal and hepatobiliary compartments. Changes in hepatobiliary and intestinal bile acid transport can alter the composition, size, and distribution of the bile acid pool. These alterations in turn can have significant effects on bile acid signaling and their downstream metabolic targets. This review discusses recent advances in our understanding of the inter-relationship between the enterohepatic cycling of bile acids and the metabolic consequences of signaling via bile acid-activated receptors, such as farnesoid X nuclear receptor (FXR) and the G-protein-coupled bile acid receptor (TGR5). PMID:26579438

  3. Regulation of leukocyte tricarboxylic acid cycle in drug-naïve Bipolar Disorder.

    PubMed

    de Sousa, Rafael T; Streck, Emilio L; Forlenza, Orestes V; Brunoni, Andre R; Zanetti, Marcus V; Ferreira, Gabriela K; Diniz, Breno S; Portela, Luis V; Carvalho, André F; Zarate, Carlos A; Gattaz, Wagner F; Machado-Vieira, Rodrigo

    2015-09-25

    Several lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naïve BD patients in a major depressive episode (n=18) and compared to 24 age-matched healthy controls. Drug-naïve BD patients did not show differences in activities of citrate synthase (p=0.79), malate dehydrogenase (p=0.17), and succinate dehydrogenase (p=0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD. PMID:26297865

  4. Regulation of leukocyte tricarboxylic acid cycle in drug-naïve Bipolar Disorder.

    PubMed

    de Sousa, Rafael T; Streck, Emilio L; Forlenza, Orestes V; Brunoni, Andre R; Zanetti, Marcus V; Ferreira, Gabriela K; Diniz, Breno S; Portela, Luis V; Carvalho, André F; Zarate, Carlos A; Gattaz, Wagner F; Machado-Vieira, Rodrigo

    2015-09-25

    Several lines of evidence suggest a role for mitochondrial dysfunction in the pathophysiology of bipolar disorder (BD). The tricarboxylic acid cycle (TCA cycle) is fundamental for mitochondrial energy production and produces substrates used in oxidative phosphorylation by the mitochondrial electron transport chain. The activity of the key TCA cycle enzymes citrate synthase, malate dehydrogenase, and succinate dehydrogenase has never been evaluated in BD. In the present study, these enzymes were assayed from leukocytes of drug-naïve BD patients in a major depressive episode (n=18) and compared to 24 age-matched healthy controls. Drug-naïve BD patients did not show differences in activities of citrate synthase (p=0.79), malate dehydrogenase (p=0.17), and succinate dehydrogenase (p=0.35) compared with healthy controls. No correlation between any TCA cycle enzyme activity and severity of depressive symptoms was observed. Overall, these data suggest that the activities of the TCA cycle enzymes are not altered in major depressive episodes of recent-onset BD, which may support the concept of illness staging and neuroprogression in BD.

  5. Endolysosomes Are the Principal Intracellular Sites of Acid Hydrolase Activity.

    PubMed

    Bright, Nicholas A; Davis, Luther J; Luzio, J Paul

    2016-09-12

    The endocytic delivery of macromolecules from the mammalian cell surface for degradation by lysosomal acid hydrolases requires traffic through early endosomes to late endosomes followed by transient (kissing) or complete fusions between late endosomes and lysosomes. Transient or complete fusion results in the formation of endolysosomes, which are hybrid organelles from which lysosomes are re-formed. We have used synthetic membrane-permeable cathepsin substrates, which liberate fluorescent reporters upon proteolytic cleavage, as well as acid phosphatase cytochemistry to identify which endocytic compartments are acid hydrolase active. We found that endolysosomes are the principal organelles in which acid hydrolase substrates are cleaved. Endolysosomes also accumulated acidotropic probes and could be distinguished from terminal storage lysosomes, which were acid hydrolase inactive and did not accumulate acidotropic probes. Using live-cell microscopy, we have demonstrated that fusion events, which form endolysosomes, precede the onset of acid hydrolase activity. By means of sucrose and invertase uptake experiments, we have also shown that acid-hydrolase-active endolysosomes and acid-hydrolase-inactive, terminal storage lysosomes exist in dynamic equilibrium. We conclude that the terminal endocytic compartment is composed of acid-hydrolase-active, acidic endolysosomes and acid hydrolase-inactive, non-acidic, terminal storage lysosomes, which are linked and function in a lysosome regeneration cycle. PMID:27498570

  6. Coronal activity cycles in solar analog stars

    NASA Astrophysics Data System (ADS)

    Favata, Fabio

    2013-10-01

    We propose continuation into AO13 of the ongoing long-term program for the monitoring of coronal cycles in a sample of five solar-type stars in three stellar systems. The targets have been monitored continuously since AO1, yielding the first unambiguous evidence of cyclic behavior in the X-ray emission from the coronae of cool stars. Thanks to the long-term monitoring our program is starting to show evidence of the complex behavior of stellar cycles, with significant cycle-to-cycle variability becoming apparent. The observations requested in AO-13 will allow us to capitalize on our long-term investment of XMM-Newton observing time and to continue assembling a unique long-term data set that is likely to remain unmatched for a long time.

  7. Meridional Flow Variations in Cycles 23 and 24: Active Latitude Control of Sunspot Cycle Amplitudes

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Upton, Lisa

    2013-01-01

    We have measured the meridional motions of magnetic elements observed in the photosphere over sunspot cycles 23 and 24 using magnetograms from SOHO/MDI and SDO/HMI. Our measurements confirm the finding of Komm, Howard, and Harvey (1993) that the poleward meridional flow weakens at cycle maxima. Our high spatial and temporal resolution analyses show that this variation is in the form of a superimposed inflow toward the active latitudes. This inflow is weaker in cycle 24 when compared to the inflow in 23, the stronger cycle. This systematic modulation of the meridional flow can modulate the amplitude of the following sunspot cycle through its influence on the Sun's polar fields.

  8. Hypertonic stress regulates amino acid transport and cell cycle proteins in chick embryo hepatocytes.

    PubMed

    Bruscalupi, Giovannella; Massimi, Mara; Spagnuolo, Silvana; Fiore, Anna Maria; Leoni, Silvia

    2012-02-01

    Hyperosmotic stress affects cell growth, decreasing cell volume and increasing the uptake of organic osmolytes. However, the sensitivity of embryonic cells to osmotic treatment remains to be established. We have analysed some aspects of cell-cycle control and amino-acid transport in hypertonic conditions during prenatal life. The effects of hyperosmotic stress on amino-acid uptake mediated by system A, (3)H-thymidine incorporation, and regulation of cell-cycle proteins were analysed in chick embryo hepatocytes. Hypertonic stress increased system A activity and caused cell-cycle delay. Effects on amino-acid transport involved p38 kinase activation and new carrier synthesis. Cyclin D1, cdk4 (cyclin-dependent kinase 4) and PCNA (proliferating-cell nuclear antigen) levels decreased, whereas cyclin E, p21 and p53 levels were unchanged. Incorporation of (3)H-leucine indicated decreased synthesis of cyclin D1. In contrast, analysis of mRNA by qRT-PCR (quantitative real-time PCR) showed a net increase of cyclin D1 transcripts, suggesting post-transcriptional regulation. The data show that chick embryo hepatocytes respond to hyperosmotic conditions by arresting cell growth to prevent DNA damage and increasing osmolyte uptake to regulate cell volume, indicating that the adaptive response to environmental stress exists during prenatal life.

  9. Pull-in urea cycle for the production of fumaric acid in Escherichia coli.

    PubMed

    Zhang, Ting; Wang, Zening; Deng, Li; Tan, Tianwei; Wang, Fang; Yan, Yajun

    2015-06-01

    Fumaric acid (FA) is an important raw material in the chemical and pharmaceutical industries. In this work, Escherichia coli was metabolically engineered for the production of FA. The fumA, fumB, fumC, and frdABCD genes were deleted to cut off the downstream pathway of FA. In addition, the iclR and arcA genes were also deleted to activate the glyoxylate shunt and to reinforce the oxidative Krebs cycle. To increase the FA yield, this base strain was further engineered to be pulled in the urea cycle by overexpressing the native carAB, argI, and heterologous rocF genes. The metabolites and the proteins of the Krebs cycle and the urea cycle were analyzed to confirm that the induced urea cycle improved the FA accumulation. With the induced urea cycle, the resulting strain ABCDIA-RAC was able to produce 11.38 mmol/L of FA from 83.33 mmol/L of glucose in a flask culture during 24 h of incubation.

  10. Metabolic engineering in the biotechnological production of organic acids in the tricarboxylic acid cycle of microorganisms: Advances and prospects.

    PubMed

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

    2015-11-01

    Organic acids, which are chemically synthesized, are also natural intermediates in the metabolic pathways of microorganisms, among which the tricarboxylic acid (TCA) cycle is the most crucial route existing in almost all living organisms. Organic acids in the TCA cycle include citric acid, α-ketoglutaric acid, succinic acid, fumaric acid, l-malic acid, and oxaloacetate, which are building-block chemicals with wide applications and huge markets. In this review, we summarize the synthesis pathways of these organic acids and review recent advances in metabolic engineering strategies that enhance organic acid production. We also propose further improvements for the production of organic acids with systems and synthetic biology-guided metabolic engineering strategies.

  11. Rest-Activity Cycles in Childhood and Adolescent Depression.

    ERIC Educational Resources Information Center

    Armitage, Roseanne; Hoffmann, Robert; Emslie, Graham; Rintelman, Jeanne; Moore, Jarrette; Lewis, Kelly

    2004-01-01

    Objective: To quantify circadian rhythms in rest-activity cycles in depressed children and adolescents. Method: Restactivity cycles were evaluated by actigraphy over five consecutive 24-hour periods in 100 children and adolescents, including 59 outpatients with major depressive disorder (MDD) and 41 healthy normal controls. Total activity, total…

  12. Materials study supporting thermochemical hydrogen cycle sulfuric acid decomposer design

    NASA Astrophysics Data System (ADS)

    Peck, Michael S.

    Increasing global climate change has been driven by greenhouse gases emissions originating from the combustion of fossil fuels. Clean burning hydrogen has the potential to replace much of the fossil fuels used today reducing the amount of greenhouse gases released into the atmosphere. The sulfur iodine and hybrid sulfur thermochemical cycles coupled with high temperature heat from advanced nuclear reactors have shown promise for economical large-scale hydrogen fuel stock production. Both of these cycles employ a step to decompose sulfuric acid to sulfur dioxide. This decomposition step occurs at high temperatures in the range of 825°C to 926°C dependent on the catalysis used. Successful commercial implementation of these technologies is dependent upon the development of suitable materials for use in the highly corrosive environments created by the decomposition products. Boron treated diamond film was a potential candidate for use in decomposer process equipment based on earlier studies concluding good oxidation resistance at elevated temperatures. However, little information was available relating the interactions of diamond and diamond films with sulfuric acid at temperatures greater than 350°C. A laboratory scale sulfuric acid decomposer simulator was constructed at the Nuclear Science and Engineering Institute at the University of Missouri-Columbia. The simulator was capable of producing the temperatures and corrosive environments that process equipment would be exposed to for industrialization of the sulfur iodide or hybrid sulfur thermochemical cycles. A series of boron treated synthetic diamonds were tested in the simulator to determine corrosion resistances and suitability for use in thermochemical process equipment. These studies were performed at twenty four hour durations at temperatures between 600°C to 926°C. Other materials, including natural diamond, synthetic diamond treated with titanium, silicon carbide, quartz, aluminum nitride, and Inconel

  13. An ATP and Oxalate Generating Variant Tricarboxylic Acid Cycle Counters Aluminum Toxicity in Pseudomonas fluorescens

    PubMed Central

    Singh, Ranji; Lemire, Joseph; Mailloux, Ryan J.; Chénier, Daniel; Hamel, Robert; Appanna, Vasu D.

    2009-01-01

    Although the tricarboxylic acid (TCA) cycle is essential in almost all aerobic organisms, its precise modulation and integration in global cellular metabolism is not fully understood. Here, we report on an alternative TCA cycle uniquely aimed at generating ATP and oxalate, two metabolites critical for the survival of Pseudomonas fluorescens. The upregulation of isocitrate lyase (ICL) and acylating glyoxylate dehydrogenase (AGODH) led to the enhanced synthesis of oxalate, a dicarboxylic acid involved in the immobilization of aluminum (Al). The increased activity of succinyl-CoA synthetase (SCS) and oxalate CoA-transferase (OCT) in the Al-stressed cells afforded an effective route to ATP synthesis from oxalyl-CoA via substrate level phosphorylation. This modified TCA cycle with diminished efficacy in NADH production and decreased CO2-evolving capacity, orchestrates the synthesis of oxalate, NADPH, and ATP, ingredients pivotal to the survival of P. fluorescens in an Al environment. The channeling of succinyl-CoA towards ATP formation may be an important function of the TCA cycle during anaerobiosis, Fe starvation and O2-limited conditions. PMID:19809498

  14. Crassulacean acid metabolism-cycling in Euphorbia milii

    PubMed Central

    Herrera, Ana

    2013-01-01

    Crassulacean acid metabolism (CAM) occurs in many Euphorbiaceae, particularly Euphorbia, a genus with C3 and C4 species as well. With the aim of contributing to our knowledge of the evolution of CAM in this genus, this study examined the possible occurrence of CAM in Euphorbia milii, a species with leaf succulence and drought tolerance suggestive of this carbon fixation pathway. Leaf anatomy consisted of a palisade parenchyma, a spongy parenchyma and a bundle sheath with chloroplasts, which indicates the possible functioning of C2 photosynthesis. No evidence of nocturnal CO2 fixation was found in plants of E. milii either watered or under drought; watered plants had a low nocturnal respiration rate (R). After 12 days without watering, the photosynthetic rate (PN) decreased 85 % and nocturnal R was nearly zero. Nocturnal H+ accumulation (ΔH+) in watered plants was 18 ± 2 (corresponding to malate) and 18 ± 4 (citrate) μmol H+ (g fresh mass)−1. Respiratory CO2 recycling through acid synthesis contributed to a night-time water saving of 2 and 86 % in watered plants and plants under drought, respectively. Carbon isotopic composition (δ13C) was −25.2 ± 0.7 ‰ in leaves and −24.7 ± 0.1 ‰ in stems. Evidence was found for the operation of weak CAM in E. milii, with statistically significant ΔH+, no nocturnal CO2 uptake and values of δ13C intermediate between C3 and constitutive CAM plants; ΔH+ was apparently attributable to both malate and citrate. The results suggest that daily malate accumulation results from recycling of part of the nocturnal respiratory CO2, which helps explain the occurrence of an intermediate value of leaf δ13C. Euphorbia milii can be considered as a CAM-cycling species. The significance of the operation of CAM-cycling in E. milii lies in water conservation, rather than carbon acquisition. The possible occurrence of C2 photosynthesis merits research. PMID:23596548

  15. Staphylococcus epidermidis Polysaccharide Intercellular Adhesin Production Significantly Increases during Tricarboxylic Acid Cycle Stress

    PubMed Central

    Vuong, Cuong; Kidder, Joshua B.; Jacobson, Erik R.; Otto, Michael; Proctor, Richard A.; Somerville, Greg A.

    2005-01-01

    Staphylococcal polysaccharide intercellular adhesin (PIA) is important for the development of a mature biofilm. PIA production is increased during growth in a nutrient-replete or iron-limited medium and under conditions of low oxygen availability. Additionally, stress-inducing stimuli such as heat, ethanol, and high concentrations of salt increase the production of PIA. These same environmental conditions are known to repress tricarboxylic acid (TCA) cycle activity, leading us to hypothesize that altering TCA cycle activity would affect PIA production. Culturing Staphylococcus epidermidis with a low concentration of the TCA cycle inhibitor fluorocitrate dramatically increased PIA production without impairing glucose catabolism, the growth rate, or the growth yields. These data lead us to speculate that one mechanism by which staphylococci perceive external environmental change is through alterations in TCA cycle activity leading to changes in the intracellular levels of biosynthetic intermediates, ATP, or the redox status of the cell. These changes in the metabolic status of the bacteria result in the attenuation or augmentation of PIA production. PMID:15838022

  16. Inferences on Stellar Activity and Stellar Cycles from Asteroseismology

    NASA Astrophysics Data System (ADS)

    Chaplin, William J.; Basu, Sarbani

    2014-12-01

    The solar activity cycle can be studied using many different types of observations, such as counting sunspots, measuring emission in the Ca II H&K lines, magnetograms, radio emissions, etc. One of the more recent ways of studying solar activity is to use the changing properties of solar oscillations. Stellar activity cycles are generally studied using the Ca II lines, or sometimes using photometry. Asteroseismology is potentially an exciting means of studying these cycles. In this article we examine whether or not asteroseismic data can be used for this purpose, and what the asteroseismic signatures of stellar activity are. We also examine how asteroseismology may help in more indirect ways.

  17. New low-antimony alloy for straps and cycling service in lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Prengaman, R. David

    Lead-antimony alloys used for the positive grids in lead-acid batteries for cycling service have generally used antimony contents of 4.5 wt.% and above. Tubular batteries for cycling service that impart high compression of the active material to the grid surface via gauntlet use alloys with antimony contents as low as 1.5 wt.%. These batteries are generally employed in less-severe cycling service. Value-regulated lead-acid (VRLA) batteries can give good cycling service without lead-antimony in the positive grid, but require a high tin content and high compression. The change in automotive battery positive grid alloys to lead-calcium-tin and the tin contents of VRLA positive grids and straps have dramatically increased the tin content of the recycled grid and strap lead in the USA, Europe, and Australia. The higher tin contents can contaminate the lead used for lead-antimony battery grids and generally must be removed to low levels to meet the specifications. This study describes a low-antimony alloy that contains a substantial amount of tin. The high tin content reduces the rate of corrosion of low-antimony positive grid alloys, improves conductivity, increases the bond between the grid and the active material, and cycles as well as the traditional 5-6 wt.% antimony alloys employed in conventional flat-plate batteries. The alloy is also used as a corrosion-resistant cast-on strap alloy for automotive batteries for high temperature service, as well as for posts, bushings, and connectors for all wet batteries.

  18. Forecasting the Peak of the Present Solar Activity Cycle

    NASA Astrophysics Data System (ADS)

    Hamid, Rabab; Marzouk, Beshir

    2016-07-01

    Solar forecasting of the level of sun Activity is very important subject for all space programs. Most predictions are based on the physical conditions prevailing at or before the solar cycle minimum preceding the maximum in question. Our aim is to predict the maximum peak of cycle 24 using precursor techniques in particular those using spotless event, geomagnetic aa min. index and solar flux F10.7. Also prediction of exact date of the maximum (Tr) is taken in consideration. A study of variation over previous spotless event for cycles 7-23 and that for even cycles (8-22) are carried out for the prediction. Linear correlation between RM and spotless event around the preceding minimum gives RM24t = 101.9with rise time Tr = 4.5 Y. For the even cycles RM24e = 108.3 with rise time Tr = 3.9 Y. Based on the average aa min. index for the year of sunspot minimum cycles (13 - 23), we estimate the expected amplitude for cycle 24 to be RMaa = 116.5 for both the total and even cycles. Application of the data of solar flux F10.7 which cover only cycles (19-23) was taken in consideration and gives predicted maximum amplitude R24 10.7 = 146, which are over estimation. Our result indicating a somewhat weaker cycle 24 as compared to cycles 21-23.

  19. Abnormalities in the tricarboxylic Acid cycle in Huntington disease and in a Huntington disease mouse model.

    PubMed

    Naseri, Nima N; Xu, Hui; Bonica, Joseph; Vonsattel, Jean Paul G; Cortes, Etty P; Park, Larry C; Arjomand, Jamshid; Gibson, Gary E

    2015-06-01

    Glucose metabolism is reduced in the brains of patients with Huntington disease (HD). The mechanisms underlying this deficit, its link to the pathology of the disease, and the vulnerability of the striatum in HD remain unknown. Abnormalities in some of the key mitochondrial enzymes involved in glucose metabolism, including the pyruvate dehydrogenase complex (PDHC) and the tricarboxylic acid (TCA) cycle, may contribute to these deficits. Here, activities for these enzymes and select protein levels were measured in human postmortem cortex and in striatum and cortex of an HD mouse model (Q175); mRNA levels encoding for these enzymes were also measured in the Q175 mouse cortex. The activities of PDHC and nearly all of the TCA cycle enzymes were dramatically lower (-50% to 90%) in humans than in mice. The activity of succinate dehydrogenase increased with HD in human (35%) and mouse (23%) cortex. No other changes were detected in the human HD cortex or mouse striatum. In Q175 cortex, there were increased activities of PDHC (+12%) and aconitase (+32%). Increased mRNA levels for succinyl thiokinase (+88%) and isocitrate dehydrogenase (+64%) suggested an upregulation of the TCA cycle. These patterns of change differ from those reported in other diseases, which may offer unique metabolic therapeutic opportunities for HD patients.

  20. Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria.

    PubMed

    Daloso, Danilo M; Müller, Karolin; Obata, Toshihiro; Florian, Alexandra; Tohge, Takayuki; Bottcher, Alexandra; Riondet, Christophe; Bariat, Laetitia; Carrari, Fernando; Nunes-Nesi, Adriano; Buchanan, Bob B; Reichheld, Jean-Philippe; Araújo, Wagner L; Fernie, Alisdair R

    2015-03-17

    Plant mitochondria have a fully operational tricarboxylic acid (TCA) cycle that plays a central role in generating ATP and providing carbon skeletons for a range of biosynthetic processes in both heterotrophic and photosynthetic tissues. The cycle enzyme-encoding genes have been well characterized in terms of transcriptional and effector-mediated regulation and have also been subjected to reverse genetic analysis. However, despite this wealth of attention, a central question remains unanswered: "What regulates flux through this pathway in vivo?" Previous proteomic experiments with Arabidopsis discussed below have revealed that a number of mitochondrial enzymes, including members of the TCA cycle and affiliated pathways, harbor thioredoxin (TRX)-binding sites and are potentially redox-regulated. We have followed up on this possibility and found TRX to be a redox-sensitive mediator of TCA cycle flux. In this investigation, we first characterized, at the enzyme and metabolite levels, mutants of the mitochondrial TRX pathway in Arabidopsis: the NADP-TRX reductase a and b double mutant (ntra ntrb) and the mitochondrially located thioredoxin o1 (trxo1) mutant. These studies were followed by a comparative evaluation of the redistribution of isotopes when (13)C-glucose, (13)C-malate, or (13)C-pyruvate was provided as a substrate to leaves of mutant or WT plants. In a complementary approach, we evaluated the in vitro activities of a range of TCA cycle and associated enzymes under varying redox states. The combined dataset suggests that TRX may deactivate both mitochondrial succinate dehydrogenase and fumarase and activate the cytosolic ATP-citrate lyase in vivo, acting as a direct regulator of carbon flow through the TCA cycle and providing a mechanism for the coordination of cellular function.

  1. Thioredoxin, a master regulator of the tricarboxylic acid cycle in plant mitochondria

    PubMed Central

    Daloso, Danilo M.; Müller, Karolin; Obata, Toshihiro; Florian, Alexandra; Tohge, Takayuki; Bottcher, Alexandra; Riondet, Christophe; Bariat, Laetitia; Carrari, Fernando; Nunes-Nesi, Adriano; Buchanan, Bob B.; Reichheld, Jean-Philippe; Araújo, Wagner L.; Fernie, Alisdair R.

    2015-01-01

    Plant mitochondria have a fully operational tricarboxylic acid (TCA) cycle that plays a central role in generating ATP and providing carbon skeletons for a range of biosynthetic processes in both heterotrophic and photosynthetic tissues. The cycle enzyme-encoding genes have been well characterized in terms of transcriptional and effector-mediated regulation and have also been subjected to reverse genetic analysis. However, despite this wealth of attention, a central question remains unanswered: “What regulates flux through this pathway in vivo?” Previous proteomic experiments with Arabidopsis discussed below have revealed that a number of mitochondrial enzymes, including members of the TCA cycle and affiliated pathways, harbor thioredoxin (TRX)-binding sites and are potentially redox-regulated. We have followed up on this possibility and found TRX to be a redox-sensitive mediator of TCA cycle flux. In this investigation, we first characterized, at the enzyme and metabolite levels, mutants of the mitochondrial TRX pathway in Arabidopsis: the NADP-TRX reductase a and b double mutant (ntra ntrb) and the mitochondrially located thioredoxin o1 (trxo1) mutant. These studies were followed by a comparative evaluation of the redistribution of isotopes when 13C-glucose, 13C-malate, or 13C-pyruvate was provided as a substrate to leaves of mutant or WT plants. In a complementary approach, we evaluated the in vitro activities of a range of TCA cycle and associated enzymes under varying redox states. The combined dataset suggests that TRX may deactivate both mitochondrial succinate dehydrogenase and fumarase and activate the cytosolic ATP-citrate lyase in vivo, acting as a direct regulator of carbon flow through the TCA cycle and providing a mechanism for the coordination of cellular function. PMID:25646482

  2. Response of Solar Oscillations to Magnetic Activity in Cycle 24

    NASA Astrophysics Data System (ADS)

    Jain, K.; Tripathy, S. C.; Hill, F.

    2015-12-01

    Acoustic mode parameters are generally used to study the variability of the solar interior in response to changing magnetic activity. While oscillation frequencies do vary in phase with the solar activity, the mode amplitudes are anti-correlated. Now, continuous measurements from ground and space allow us study the origin of such variability in detail. Here we use intermediate-dgree mode frequencies computed from a ground-based 6-site network ( GONG), covering almost two solar cycles from the minimum of cycle 23 to the declining phase of cycle 24, to investigate the effect of remarkably low solar activity on the solar oscillations in current cycle and the preceding minimum; is the response of acoustic oscillations to magnetic activity in cycle 24 similar to cycle 23 or there are differences between cycles 23 and 24? In this paper, we analyze results for both solar cycles, and try to understand the origin of similarities/differences between them. We will also compare our findings with the contemporaneous observations from space (SOHO/MDI and SDO/HMI).

  3. The connection between stellar activity cycles and magnetic field topology

    NASA Astrophysics Data System (ADS)

    See, V.; Jardine, M.; Vidotto, A. A.; Donati, J.-F.; Boro Saikia, S.; Bouvier, J.; Fares, R.; Folsom, C. P.; Gregory, S. G.; Hussain, G.; Jeffers, S. V.; Marsden, S. C.; Morin, J.; Moutou, C.; do Nascimento, J. D.; Petit, P.; Waite, I. A.

    2016-08-01

    Zeeman Doppler imaging has successfully mapped the large-scale magnetic fields of stars over a large range of spectral types, rotation periods and ages. When observed over multiple epochs, some stars show polarity reversals in their global magnetic fields. On the Sun, polarity reversals are a feature of its activity cycle. In this paper, we examine the magnetic properties of stars with existing chromospherically determined cycle periods. Previous authors have suggested that cycle periods lie on multiple branches, either in the cycle period-Rossby number plane or the cycle period-rotation period plane. We find some evidence that stars along the active branch show significant average toroidal fields that exhibit large temporal variations while stars exclusively on the inactive branch remain dominantly poloidal throughout their entire cycle. This lends credence to the idea that different shear layers are in operation along each branch. There is also evidence that the short magnetic polarity switches observed on some stars are characteristic of the inactive branch while the longer chromospherically determined periods are characteristic of the active branch. This may explain the discrepancy between the magnetic and chromospheric cycle periods found on some stars. These results represent a first attempt at linking global magnetic field properties obtained form ZDI and activity cycles.

  4. A solar cycle timing predictor - The latitude of active regions

    NASA Technical Reports Server (NTRS)

    Schatten, Kenneth H.

    1990-01-01

    A 'Spoerer butterfly' method is used to examine solar cycle 22. It is shown from the latitude of active regions that the cycle can now be expected to peak near November 1989 + or - 8 months, basically near the latter half of 1989.

  5. The connection between stellar activity cycles and magnetic field topology

    NASA Astrophysics Data System (ADS)

    See, V.; Jardine, M.; Vidotto, A. A.; Donati, J.-F.; Boro Saikia, S.; Bouvier, J.; Fares, R.; Folsom, C. P.; Gregory, S. G.; Hussain, G.; Jeffers, S. V.; Marsden, S. C.; Morin, J.; Moutou, C.; do Nascimento, J. D.; Petit, P.; Waite, I. A.

    2016-11-01

    Zeeman-Doppler imaging (ZDI) has successfully mapped the large-scale magnetic fields of stars over a large range of spectral types, rotation periods and ages. When observed over multiple epochs, some stars show polarity reversals in their global magnetic fields. On the Sun, polarity reversals are a feature of its activity cycle. In this paper, we examine the magnetic properties of stars with existing chromospherically determined cycle periods. Previous authors have suggested that cycle periods lie on multiple branches, either in the cycle period-Rossby number plane or the cycle period-rotation period plane. We find some evidence that stars along the active branch show significant average toroidal fields that exhibit large temporal variations while stars exclusively on the inactive branch remain dominantly poloidal throughout their entire cycle. This lends credence to the idea that different shear layers are in operation along each branch. There is also evidence that the short magnetic polarity switches observed on some stars are characteristic of the inactive branch while the longer chromospherically determined periods are characteristic of the active branch. This may explain the discrepancy between the magnetic and chromospheric cycle periods found on some stars. These results represent a first attempt at linking global magnetic field properties obtained from ZDI and activity cycles.

  6. Acid Rain: Activities for Science Teachers.

    ERIC Educational Resources Information Center

    Johnson, Eric; And Others

    1983-01-01

    Seven complete secondary/college level acid rain activities are provided. Activities include overview; background information and societal implications; major concepts; student objectives; vocabulary/material lists; procedures; instructional strategies; and questions/discussion and extension suggestions. Activities consider effects of acid rain on…

  7. Stability of Supported Platinum Sulfuric Acid Decomposition Catalysts for use in Thermochemical Water Splitting Cycles

    SciTech Connect

    Daniel M. Ginosar; Lucia M. Petkovic; Anne W. Glenn; Kyle C. Burch

    2007-03-01

    The activity and stability of several metal oxide supported platinum catalysts were explored for the sulfuric acid decomposition reaction. The acid decomposition reaction is common to several sulfur based thermochemical water splitting cycles. Reactions were carried out using a feed of concentrated liquid sulfuric acid (96 wt%) at atmospheric pressure at temperatures between 800 and 850 °C and a weight hour space velocity of 52 g acid/g catalyst/hr. Reactions were run at these high space velocities such that variations in kinetics were not masked by surplus catalyst. The influence of exposure to reaction conditions was explored for three catalysts; 0.1-0.2 wt% Pt supported on alumina, zirconia and titania. The higher surface area Pt/Al2O3 and Pt/ZrO2 catalysts were found to have the highest activity but deactivated rapidly. A low surface area Pt/TiO2 catalyst was found to have good stability in short term tests, but slowly lost activity for over 200 hours of continuous operation.

  8. Acid-Tolerant Sulfate-Reducing Bacteria Play a Major Role in Iron Cycling in Acidic Iron Rich Sediments

    NASA Astrophysics Data System (ADS)

    Enright, K. A.; Moreau, J. W.

    2008-12-01

    Climate change drives drying and acidification of many rivers and lakes. Abundant sedimentary iron in these systems oxidizes chemically and biologically to form iron-ox(yhydrox)ide crusts and "hardpans". Given generally high sulfate concentrations, the mobilization and cycling of iron in these environments can be strongly influenced by bacterial sulfate reduction. Sulfate-reducing bacteria (SRB) induce reductive dissolution of oxidized iron phases by producing the reductant bisulfide as a metabolic product. These environmentally ubiquitous microbes also recycle much of the fixed carbon in sediment-hosted microbial mat communities. With prevalent drying, the buffering capacity for protons liberated from iron oxidation is exceeded, and the activity of sulfate-reducers is restricted to those species capable of tolerating low pH (and generally highly saline, i.e. sulfate-rich) conditions. These species will sustain the recycling of iron from more crystalline phases to more bioavailable species, as well as act as the only source of bisulfide for photosynthesizing microbial communities. The phylogeny and physiology of acid-tolerant SRB is therefore important to Fe, S and C cycling in iron-rich sedimentary environments, particularly those on a geochemical trajectory towards acidification. Previous studies have shown that these SRB species tend to be highly novel. We studied two distinct environments along a geochemical continuum towards acidification. In both settings, iron redox transformations exert a major, if not controlling, influence on reduction potential. An acidified, iron- rich tidal marsh receiving acid-mine drainage (San Francisco Bay, CA, USA) contained abundant textural evidence for reductive dissolution of Fe(III) in sediments with pH values varying from 2.4 - 3.8. From these sediments, full-length novel dsrAB gene sequences from acid-tolerant SRB were recovered, and sulfur isotope profiles reflected biological fractionation of sulfur under even the most

  9. The effect of propionic acid and valeric acid on the cell cycle in root meristems of Pisum sativum

    SciTech Connect

    Tramontano, W.A.; Yang, Shauyu; Delillo, A.R. )

    1990-01-01

    Propionic acid and valeric acid at 1mM reduced the mitotic index of root meristem cells of Pisum sativum to < 1% after 12 hr in aerated White's medium. This effect varied with different acid concentrations. After a 12 hr exposure to either acid, seedlings transferred to fresh medium without either acid, resumed their normal mitotic index after 12 hr, with a burst of mitosis 8 hr post-transfer. Exposure of root meristem cells to either acid also inhibited ({sup 3}H)-TdR incorporation. Neither acid significantly altered the distribution of meristematic cells in G1 and G2 after 12 hr. The incorporation of ({sup 3}H) - uridine was also unaltered by the addition of either acid. This information suggests that propionic acid and valeric acid, limit progression through the cell cycle by inhibiting DNA synthesis and arresting cells in G1 and G2. These results were consistent with previous data which utilized butyric acid.

  10. Butterfly Diagram and Activity Cycles in HR 1099

    NASA Astrophysics Data System (ADS)

    Berdyugina, Svetlana V.; Henry, Gregory W.

    2007-04-01

    We analyze photometric data of the active RS CVn-type star HR 1099 for the years 1975-2006 with an inversion technique and reveal the nature of two activity cycles of 15-16 yr and 5.3+/-0.1 yr duration. The 16 yr cycle is related to variations of the total spot area and is coupled with the differential rotation, while the 5.3 yr cycle is caused by the symmetric redistribution of the spotted area between the opposite stellar hemispheres (flip-flop cycle). We recover long-lived active regions comprising two active longitudes that migrate in the orbital reference frame with a variable rate because of the differential rotation along with changes in the mean spot latitudes. The migration pattern is periodic with the 16 yr cycle. Combining the longitudinal migration of the active regions with a previously measured differential rotation law, we recover the first stellar butterfly diagram without an assumption about spot shapes. We find that mean latitudes of active regions at opposite longitudes change antisymmetrically in the course of the 16 yr cycle: while one active region migrates to the pole, the other approaches the equator. This suggests a precession of the global magnetic field with respect to the stellar rotational axis.

  11. Meridional Flow Variations in Cycles 23 and 24: Active Latitude Control of Sunspot Cycle Amplitudes

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.; Upton, Lisa

    2013-01-01

    We have measured the meridional motions of magnetic elements observed in the photosphere over sunspot cycles 23 and 24 using magnetograms from SOHO/MDI and SDO/HMI. Our measurements confirm the finding of Komm, Howard, and Harvey (1993) that the poleward meridional flow weakens at cycle maxima. Our high spatial and temporal resolution analyses show that this variation is in the form of a superimposed inflow toward the active latitudes. This inflow is weaker in cycle 24 when compared to the inflow in 23, the stronger cycle. This systematic modulation of the meridional flow should also modulate the amplitude of the following sunspot cycle through its influence on the Sun's polar fields. The observational evidence and the theoretical consequences (similar to those of Cameron and Schussler (2012)) will be described.

  12. Meridional Flow Variations in Cycles 23 and 24: Active Latitude Control of Sunspot Cycle Amplitudes

    NASA Astrophysics Data System (ADS)

    Hathaway, David H.; Upton, L.

    2013-07-01

    We have measured the meridional motions of magnetic elements observed in the photosphere over sunspot cycles 23 and 24 using magnetograms from SOHO/MDI and SDO/HMI. Our measurements confirm the finding of Komm, Howard, and Harvey (1993) that the poleward meridional flow weakens at cycle maxima. Our high spatial and temporal resolution analyses show that this variation is in the form of a superimposed inflow toward the active latitudes. This inflow is weaker in cycle 24 when compared to the inflow in 23, the stronger cycle. This systematic modulation of the meridional flow should also modulate the amplitude of the following sunspot cycle through its influence on the Sun’s polar fields. The observational evidence and the theoretical consequences (similar to those of Cameron and Schussler (2012)) will be described. Komm, Howard, and Harvey (1993) Solar Phys. 147, 207. Cameron and Schussler (2012) Astron. Astrophys. 548, A57.

  13. Salicylic acid antagonizes abscisic acid inhibition of shoot growth and cell cycle progression in rice

    NASA Astrophysics Data System (ADS)

    Meguro, Ayano; Sato, Yutaka

    2014-04-01

    We analysed effects of abscisic acid (ABA, a negative regulatory hormone), alone and in combination with positive or neutral hormones, including salicylic acid (SA), on rice growth and expression of cell cycle-related genes. ABA significantly inhibited shoot growth and induced expression of OsKRP4, OsKRP5, and OsKRP6. A yeast two-hybrid assay showed that OsKRP4, OsKRP5, and OsKRP6 interacted with OsCDKA;1 and/or OsCDKA;2. When SA was simultaneously supplied with ABA, the antagonistic effect of SA completely blocked ABA inhibition. SA also blocked ABA inhibition of DNA replication and thymidine incorporation in the shoot apical meristem. These results suggest that ABA arrests cell cycle progression by inducing expression of OsKRP4, OsKRP5, and OsKRP6, which inhibit the G1/S transition, and that SA antagonizes ABA by blocking expression of OsKRP genes.

  14. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington's Disease Patients.

    PubMed

    Naseri, Nima N; Bonica, Joseph; Xu, Hui; Park, Larry C; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington's disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  15. Extending food deprivation reverses the short-term lipolytic response to fasting: role of the triacylglycerol/fatty acid cycle.

    PubMed

    Weber, Jean-Michel; Reidy, Shannon P

    2012-05-01

    The effects of short-term food deprivation on lipid metabolism are well documented, but little is known about prolonged fasting. This study monitored the kinetics of glycerol (rate of appearance, R(a) glycerol) and non-esterified fatty acids (R(a) NEFA) in fasting rabbits. Our goals were to determine whether lipolysis is stimulated beyond values seen for short-term fasting, and to characterize the roles of primary (intracellular) and secondary (with transit through the circulation) triacylglycerol/fatty acid cycling (TAG/FA cycling) in regulating fatty acid allocation to oxidation or re-esterification. R(a) glycerol (9.62±0.72 to 15.29±0.96 μmol kg(-1) min(-1)) and R(a) NEFA (18.05±2.55 to 31.25±1.93 μmol kg(-1) min(-1)) were stimulated during the first 2 days of fasting, but returned to baseline after 4 days. An initial increase in TAG/FA cycling was followed by a reduction below baseline after 6 days without food, with primary and secondary cycling contributing to these responses. We conclude that the classic activation of lipolysis caused by short-term fasting is abolished when food deprivation is prolonged. High rates of re-esterification may become impossible to sustain, and TAG/FA cycling could decrease to reduce its cost to 3% of total energy expenditure. Throughout prolonged fasting, fatty acid metabolism gradually shifts towards increased oxidation and reduced re-esterification. Survival is achieved by pressing fuel selection towards the fatty acid dominance of energy metabolism and by slowing substrate cycles to assist metabolic suppression. However, TAG/FA cycling remains active even after prolonged fasting, suggesting that re-esterification is a crucial mechanism that cannot be stopped without harmful consequences.

  16. Activation of carboxylic acids in asymmetric organocatalysis.

    PubMed

    Monaco, Mattia Riccardo; Poladura, Belén; Diaz de Los Bernardos, Miriam; Leutzsch, Markus; Goddard, Richard; List, Benjamin

    2014-07-01

    Organocatalysis, catalysis using small organic molecules, has recently evolved into a general approach for asymmetric synthesis, complementing both metal catalysis and biocatalysis. Its success relies to a large extent upon the introduction of novel and generic activation modes. Remarkably though, while carboxylic acids have been used as catalyst directing groups in supramolecular transition-metal catalysis, a general and well-defined activation mode for this useful and abundant substance class is still lacking. Herein we propose the heterodimeric association of carboxylic acids with chiral phosphoric acid catalysts as a new activation principle for organocatalysis. This self-assembly increases both the acidity of the phosphoric acid catalyst and the reactivity of the carboxylic acid. To illustrate this principle, we apply our concept in a general and highly enantioselective catalytic aziridine-opening reaction with carboxylic acids as nucleophiles.

  17. Photochemical synthesis of citric acid cycle intermediates based on titanium dioxide.

    PubMed

    Saladino, Raffaele; Brucato, John Robert; De Sio, Antonio; Botta, Giorgia; Pace, Emanuele; Gambicorti, Lisa

    2011-10-01

    The emergence of the citric acid cycle is one of the most remarkable occurrences with regard to understanding the origin and evolution of metabolic pathways. Although the chemical steps of the cycle are preserved intact throughout nature, diverse organisms make wide use of its chemistry, and in some cases organisms use only a selected portion of the cycle. However, the origins of this cycle would have arisen in the more primitive anaerobic organism or even back in the proto-metabolism, which likely arose spontaneously under favorable prebiotic chemical conditions. In this context, we report that UV irradiation of formamide in the presence of titanium dioxide afforded 6 of the 11 carboxylic acid intermediates of the reductive version of the citric acid cycle. Since this cycle is the central metabolic pathway of contemporary biology, this report highlights the role of photochemical processes in the origin of the metabolic apparatus.

  18. Geothermal activity helps life survive glacial cycles.

    PubMed

    Fraser, Ceridwen I; Terauds, Aleks; Smellie, John; Convey, Peter; Chown, Steven L

    2014-04-15

    Climate change has played a critical role in the evolution and structure of Earth's biodiversity. Geothermal activity, which can maintain ice-free terrain in glaciated regions, provides a tantalizing solution to the question of how diverse life can survive glaciations. No comprehensive assessment of this "geothermal glacial refugia" hypothesis has yet been undertaken, but Antarctica provides a unique setting for doing so. The continent has experienced repeated glaciations that most models indicate blanketed the continent in ice, yet many Antarctic species appear to have evolved in almost total isolation for millions of years, and hence must have persisted in situ throughout. How could terrestrial species have survived extreme glaciation events on the continent? Under a hypothesis of geothermal glacial refugia and subsequent recolonization of nongeothermal regions, we would expect to find greater contemporary diversity close to geothermal sites than in nongeothermal regions, and significant nestedness by distance of this diversity. We used spatial modeling approaches and the most comprehensive, validated terrestrial biodiversity dataset yet created for Antarctica to assess spatial patterns of diversity on the continent. Models clearly support our hypothesis, indicating that geothermally active regions have played a key role in structuring biodiversity patterns in Antarctica. These results provide critical insights into the evolutionary importance of geothermal refugia and the history of Antarctic species.

  19. Geothermal activity helps life survive glacial cycles

    PubMed Central

    Fraser, Ceridwen I.; Terauds, Aleks; Smellie, John; Convey, Peter; Chown, Steven L.

    2014-01-01

    Climate change has played a critical role in the evolution and structure of Earth’s biodiversity. Geothermal activity, which can maintain ice-free terrain in glaciated regions, provides a tantalizing solution to the question of how diverse life can survive glaciations. No comprehensive assessment of this “geothermal glacial refugia” hypothesis has yet been undertaken, but Antarctica provides a unique setting for doing so. The continent has experienced repeated glaciations that most models indicate blanketed the continent in ice, yet many Antarctic species appear to have evolved in almost total isolation for millions of years, and hence must have persisted in situ throughout. How could terrestrial species have survived extreme glaciation events on the continent? Under a hypothesis of geothermal glacial refugia and subsequent recolonization of nongeothermal regions, we would expect to find greater contemporary diversity close to geothermal sites than in nongeothermal regions, and significant nestedness by distance of this diversity. We used spatial modeling approaches and the most comprehensive, validated terrestrial biodiversity dataset yet created for Antarctica to assess spatial patterns of diversity on the continent. Models clearly support our hypothesis, indicating that geothermally active regions have played a key role in structuring biodiversity patterns in Antarctica. These results provide critical insights into the evolutionary importance of geothermal refugia and the history of Antarctic species. PMID:24616489

  20. Geothermal activity helps life survive glacial cycles.

    PubMed

    Fraser, Ceridwen I; Terauds, Aleks; Smellie, John; Convey, Peter; Chown, Steven L

    2014-04-15

    Climate change has played a critical role in the evolution and structure of Earth's biodiversity. Geothermal activity, which can maintain ice-free terrain in glaciated regions, provides a tantalizing solution to the question of how diverse life can survive glaciations. No comprehensive assessment of this "geothermal glacial refugia" hypothesis has yet been undertaken, but Antarctica provides a unique setting for doing so. The continent has experienced repeated glaciations that most models indicate blanketed the continent in ice, yet many Antarctic species appear to have evolved in almost total isolation for millions of years, and hence must have persisted in situ throughout. How could terrestrial species have survived extreme glaciation events on the continent? Under a hypothesis of geothermal glacial refugia and subsequent recolonization of nongeothermal regions, we would expect to find greater contemporary diversity close to geothermal sites than in nongeothermal regions, and significant nestedness by distance of this diversity. We used spatial modeling approaches and the most comprehensive, validated terrestrial biodiversity dataset yet created for Antarctica to assess spatial patterns of diversity on the continent. Models clearly support our hypothesis, indicating that geothermally active regions have played a key role in structuring biodiversity patterns in Antarctica. These results provide critical insights into the evolutionary importance of geothermal refugia and the history of Antarctic species. PMID:24616489

  1. Closed cycle ion exchange method for regenerating acids, bases and salts

    DOEpatents

    Dreyfuss, Robert M.

    1976-01-01

    A method for conducting a chemical reaction in acidic, basic, or neutral solution as required and then regenerating the acid, base, or salt by means of ion exchange in a closed cycle reaction sequence which comprises contacting the spent acid, base, or salt with an ion exchanger, preferably a synthetic organic ion-exchange resin, so selected that the counter ions thereof are ions also produced as a by-product in the closed reaction cycle, and then regenerating the spent ion exchanger by contact with the by-product counter ions. The method is particularly applicable to closed cycle processes for the thermochemical production of hydrogen.

  2. Methylcitrate cycle defines the bactericidal essentiality of isocitrate lyase for survival of Mycobacterium tuberculosis on fatty acids

    PubMed Central

    Eoh, Hyungjin; Rhee, Kyu Y.

    2014-01-01

    Few mutations attenuate Mycobacterium tuberculosis (Mtb) more profoundly than deletion of its isocitrate lyases (ICLs). However, the basis for this attenuation remains incompletely defined. Mtb’s ICLs are catalytically bifunctional isocitrate and methylisocitrate lyases required for growth on even and odd chain fatty acids. Here, we report that Mtb’s ICLs are essential for survival on both acetate and propionate because of its methylisocitrate lyase (MCL) activity. Lack of MCL activity converts Mtb’s methylcitrate cycle into a “dead end” pathway that sequesters tricarboxylic acid (TCA) cycle intermediates into methylcitrate cycle intermediates, depletes gluconeogenic precursors, and results in defects of membrane potential and intrabacterial pH. Activation of an alternative vitamin B12-dependent pathway of propionate metabolism led to selective corrections of TCA cycle activity, membrane potential, and intrabacterial pH that specifically restored survival, but not growth, of ICL-deficient Mtb metabolizing acetate or propionate. These results thus resolve the biochemical basis of essentiality for Mtb’s ICLs and survival on fatty acids. PMID:24639517

  3. Correlation between citric acid and nitrate metabolisms during CAM cycle in the atmospheric bromeliad Tillandsia pohliana.

    PubMed

    Freschi, Luciano; Rodrigues, Maria Aurineide; Tiné, Marco Aurélio Silva; Mercier, Helenice

    2010-12-15

    Crassulacean acid metabolism (CAM) confers crucial adaptations for plants living under frequent environmental stresses. A wide metabolic plasticity can be found among CAM species regarding the type of storage carbohydrate, organic acid accumulated at night and decarboxylating system. Consequently, many aspects of the CAM pathway control are still elusive while the impact of this photosynthetic adaptation on nitrogen metabolism has remained largely unexplored. In this study, we investigated a possible link between the CAM cycle and the nitrogen assimilation in the atmospheric bromeliad Tillandsia pohliana by simultaneously characterizing the diel changes in key enzyme activities and metabolite levels of both organic acid and nitrate metabolisms. The results revealed that T. pohliana performed a typical CAM cycle in which phosphoenolpyruvate carboxylase and phosphoenolpyruvate carboxykinase phosphorylation seemed to play a crucial role to avoid futile cycles of carboxylation and decarboxylation. Unlike all other bromeliads previously investigated, almost equimolar concentrations of malate and citrate were accumulated at night. Moreover, a marked nocturnal depletion in the starch reservoirs and an atypical pattern of nitrate reduction restricted to the nighttime were also observed. Since reduction and assimilation of nitrate requires a massive supply of reducing power and energy and considering that T. pohliana lives overexposed to the sunlight, we hypothesize that citrate decarboxylation might be an accessory mechanism to increase internal CO₂ concentration during the day while its biosynthesis could provide NADH and ATP for nocturnal assimilation of nitrate. Therefore, besides delivering photoprotection during the day, citrate might represent a key component connecting both CAM pathway and nitrogen metabolism in T. pohliana; a scenario that certainly deserves further study not only in this species but also in other CAM plants that nocturnally accumulate citrate.

  4. Data Assimilation Approach for Forecast of Solar Activity Cycles

    NASA Astrophysics Data System (ADS)

    Kitiashvili, Irina N.

    2016-11-01

    Numerous attempts to predict future solar cycles are mostly based on empirical relations derived from observations of previous cycles, and they yield a wide range of predicted strengths and durations of the cycles. Results obtained with current dynamo models also deviate strongly from each other, thus raising questions about criteria to quantify the reliability of such predictions. The primary difficulties in modeling future solar activity are shortcomings of both the dynamo models and observations that do not allow us to determine the current and past states of the global solar magnetic structure and its dynamics. Data assimilation is a relatively new approach to develop physics-based predictions and estimate their uncertainties in situations where the physical properties of a system are not well-known. This paper presents an application of the ensemble Kalman filter method for modeling and prediction of solar cycles through use of a low-order nonlinear dynamo model that includes the essential physics and can describe general properties of the sunspot cycles. Despite the simplicity of this model, the data assimilation approach provides reasonable estimates for the strengths of future solar cycles. In particular, the prediction of Cycle 24 calculated and published in 2008 is so far holding up quite well. In this paper, I will present my first attempt to predict Cycle 25 using the data assimilation approach, and discuss the uncertainties of that prediction.

  5. Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle.

    PubMed

    Bowtell, Joanna L; Marwood, Simon; Bruce, Mark; Constantin-Teodosiu, Dumitru; Greenhaff, Paul L

    2007-01-01

    The tricarboxylic acid (TCA) cycle is the major final common pathway for oxidation of carbohydrates, lipids and some amino acids, which produces reducing equivalents in the form of nicotinamide adenine dinucleotide and flavin adenine dinucleotide that result in production of large amounts of adenosine triphosphate (ATP) via oxidative phosphorylation. Although regulated primarily by the products of ATP hydrolysis, in particular adenosine diphosphate, the rate of delivery of reducing equivalents to the electron transport chain is also a potential regulatory step of oxidative phosphorylation. The TCA cycle is responsible for the generation of approximately 67% of all reducing equivalents per molecule of glucose, hence factors that influence TCA cycle flux will be of critical importance for oxidative phosphorylation. TCA cycle flux is dependent upon the supply of acetyl units, activation of the three non-equilibrium reactions within the TCA cycle, and it has been suggested that an increase in the total concentration of the TCA cycle intermediates (TCAi) is also necessary to augment and maintain TCA cycle flux during exercise. This article reviews the evidence of the functional importance of the TCAi pool size for oxidative metabolism in exercising human skeletal muscle. In parallel with increased oxidative metabolism and TCA cycle flux during exercise, there is an exercise intensity-dependent 4- to 5-fold increase in the concentration of the TCAi. TCAi concentration reaches a peak after 10-15 minutes of exercise, and thereafter tends to decline. This seems to support the suggestion that the concentration of TCAi may be of functional importance for oxidative phosphorylation. However, researchers have been able to induce dissociations between TCAi pool size and oxidative energy provision using a variety of nutritional, pharmacological and exercise interventions. Brief periods of endurance training (5 days or 7 weeks) have been found to result in reduced TCAi pool

  6. Tricarboxylic acid cycle intermediate pool size: functional importance for oxidative metabolism in exercising human skeletal muscle.

    PubMed

    Bowtell, Joanna L; Marwood, Simon; Bruce, Mark; Constantin-Teodosiu, Dumitru; Greenhaff, Paul L

    2007-01-01

    The tricarboxylic acid (TCA) cycle is the major final common pathway for oxidation of carbohydrates, lipids and some amino acids, which produces reducing equivalents in the form of nicotinamide adenine dinucleotide and flavin adenine dinucleotide that result in production of large amounts of adenosine triphosphate (ATP) via oxidative phosphorylation. Although regulated primarily by the products of ATP hydrolysis, in particular adenosine diphosphate, the rate of delivery of reducing equivalents to the electron transport chain is also a potential regulatory step of oxidative phosphorylation. The TCA cycle is responsible for the generation of approximately 67% of all reducing equivalents per molecule of glucose, hence factors that influence TCA cycle flux will be of critical importance for oxidative phosphorylation. TCA cycle flux is dependent upon the supply of acetyl units, activation of the three non-equilibrium reactions within the TCA cycle, and it has been suggested that an increase in the total concentration of the TCA cycle intermediates (TCAi) is also necessary to augment and maintain TCA cycle flux during exercise. This article reviews the evidence of the functional importance of the TCAi pool size for oxidative metabolism in exercising human skeletal muscle. In parallel with increased oxidative metabolism and TCA cycle flux during exercise, there is an exercise intensity-dependent 4- to 5-fold increase in the concentration of the TCAi. TCAi concentration reaches a peak after 10-15 minutes of exercise, and thereafter tends to decline. This seems to support the suggestion that the concentration of TCAi may be of functional importance for oxidative phosphorylation. However, researchers have been able to induce dissociations between TCAi pool size and oxidative energy provision using a variety of nutritional, pharmacological and exercise interventions. Brief periods of endurance training (5 days or 7 weeks) have been found to result in reduced TCAi pool

  7. Stoichiometry of Reducing Equivalents and Splitting of Water in the Citric Acid Cycle.

    ERIC Educational Resources Information Center

    Madeira, Vitor M. C.

    1988-01-01

    Presents a solution to the problem of finding the source of extra reducing equivalents, and accomplishing the stoichiometry of glucose oxidation reactions. Discusses the citric acid cycle and glycolysis. (CW)

  8. Hydrogen Storage in the Carbon Dioxide - Formic Acid Cycle.

    PubMed

    Fink, Cornel; Montandon-Clerc, Mickael; Laurenczy, Gabor

    2015-01-01

    This year Mankind will release about 39 Gt carbon dioxide into the earth's atmosphere, where it acts as a greenhouse gas. The chemical transformation of carbon dioxide into useful products becomes increasingly important, as the CO(2) concentration in the atmosphere has reached 400 ppm. One approach to contribute to the decrease of this hazardous emission is to recycle CO(2), for example reducing it to formic acid. The hydrogenation of CO(2) can be achieved with a series of catalysts under basic and acidic conditions, in wide variety of solvents. To realize a hydrogen-based charge-discharge device ('hydrogen battery'), one also needs efficient catalysts for the reverse reaction, the dehydrogenation of formic acid. Despite of the fact that the overwhelming majority of these reactions are carried out using precious metals-based catalysts (mainly Ru), we review here developments for catalytic hydrogen evolution from formic acid with iron-based complexes. PMID:26842324

  9. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle

    NASA Astrophysics Data System (ADS)

    Zubarev, Dmitry Yu; Rappoport, Dmitrij; Aspuru-Guzik, Alán

    2015-01-01

    We consider the hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach to quantify the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for investigations of the origin of the common metabolic core should be significantly extended.

  10. Building biologically active nucleic acid nanocomplexes.

    PubMed

    Smith, C I Edvard; Lundin, Karin E; Simonson, Oscar E; Moreno, Pedro M D; Svahn, Mathias G; Wenska, Malgorzata; Strömberg, Roger

    2008-01-01

    The Bioplex technology allows the hybridization of functional entities to various forms of nucleic acids by the use of synthetic nucleic acid analogs. Such supramolecular assemblies can be made in a predetermined fashion and can confer new properties. The Zorro technology is based on a novel construct generated to simultaneously bind to both DNA strands. Such compounds may have gene silencing activity.

  11. Plans and Activities for NASA's Global Water Cycle Research

    NASA Astrophysics Data System (ADS)

    Schlosser, C. A.

    2002-05-01

    Strictly speaking, the water (or hydrologic) cycle is by definition a global phenomenon. To observe, analyze, characterize, understand, and predict its structure and variations requires a coordinated, global effort of observations as well as global prediction systems which can assimilate and predict key fluxes and quantities. The National Aeronautics and Space Administration (NASA) has the unique capability of space-based experimental and research measurements that observe the Earth's system as well as core modelling activities to exploit these space-based observations for assimilation in diagnostic studies and initialization in weather and climate predictions. A summary of NASA's current water-cycle activities and implementation plans will be presented. Currently, NASA's Global Water and Energy Cycle and Terrestrial Hydrology (formally known as the Land Surface Hydrology) Programs are the key funding sources which support relevant scientific research. These programs not only fund individual scientists, but also support large-scale field missions (for example the Cold Land Processes Experiment, CLPX, and the Soil Moisture Experiment, SMEx) which are critical for calibration/validation of space instruments and retrievals as well as gaining fundamental understanding of local-scale processes which comprise the global system. In addition, a new initiative for Water and Energy cycle Research (WatER) is being formulated which responds to the recent charge of USGCRP and NRC scientific panels calling for focused and prioritized research plans that serve to make significant strides in our understanding and prediction of the global water cycle. Following NASA's unique vocation, the WatER initative sets priorities for science/research support for key observable quantities of the water cycle (precipitation and surface wetness) whose instrument technology is tactable and scientfic end-returns not only benefit water-cycle predictions, but also serve to benefit other critical

  12. Lead acid battery performance and cycle life increased through addition of discrete carbon nanotubes to both electrodes

    NASA Astrophysics Data System (ADS)

    Sugumaran, Nanjan; Everill, Paul; Swogger, Steven W.; Dubey, D. P.

    2015-04-01

    Contemporary applications are changing the failure mechanisms of lead acid batteries. Sulfation at the negative electrode, acid stratification, and dendrite formation now precede positive electrode failures such as grid corrosion and active material shedding. To attenuate these failures, carbon has been explored as a negative electrode additive to increase charge acceptance, eliminate sulfation, and extend cycle life. Frequently, however, carbon incorporation decreases paste density and hinders manufacturability. Discrete carbon nanotubes (dCNT), also known as Molecular Rebar®, are lead acid battery additives which can be stably incorporated into either electrode to increase charge acceptance and cycle life with no change to paste density and without impeding the manufacturing process. Here, full-scale automotive batteries containing dCNT in the negative electrode or both negative and positive electrodes are compared to control batteries. dCNT batteries show little change to Reserve Capacity, improved Cold Cranking, increased charge acceptance, and enhanced overall system efficiency. Life cycle tests show >60% increases when dCNT are incorporated into the negative electrode (HRPSoC/SBA) and up to 500% when incorporated into both electrodes (SBA), with water loss per cycle reduced >20%. Failure modes of cycled batteries are discussed and a hypothesis of dCNT action is introduced: the dCNT/Had Overcharge Reaction Mechanism.

  13. The onset of the solar active cycle 22

    NASA Technical Reports Server (NTRS)

    Ahluwalia, H. S.

    1989-01-01

    There is a great deal of interest in being able to predict the main characteristics of a solar activity cycle (SAC). One would like to know, for instance, how large the amplitude (R sub m) of a cycle is likely to be, i.e., the annual mean of the sunspot numbers at the maximum of SAC. Also, how long a cycle is likely to last, i.e., its period. It would also be interesting to be able to predict the details, like how steep the ascending phase of a cycle is likely to be. Questions like these are of practical importance to NASA in planning the launch schedule for the low altitude, expensive spacecrafts like the Hubble Space Telescope, the Space Station, etc. Also, one has to choose a proper orbit, so that once launched the threat of an atmospheric drag on the spacecraft is properly taken into account. Cosmic ray data seem to indicate that solar activity cycle 22 will surpass SAC 21 in activity. The value of R sub m for SAC 22 may approach that of SAC 19. It would be interesting to see whether this prediction is borne out. Researchers are greatly encouraged to proceed with the development of a comprehensive prediction model which includes information provided by cosmic ray data.

  14. Amino Acid Pools and Metabolism During the Cell Division Cycle of Arginine-Grown Candida utilis

    PubMed Central

    Nurse, P.; Wiemken, A.

    1974-01-01

    Synchronous cultures obtained by isopycnic density gradient centrifugation are used to investigate amino acid metabolism during the cell division cycle of the food yeast Candida utilis. Isotopic labeling experiments demonstrate that the rates of uptake and catabolism of arginine, the sole source of nitrogen, double abruptly during the first half of the cycle, while the cells undergo bud expansion. This is accompanied by a doubling in rate of amino acid biosynthesis, and an accumulation of amino acids. The accumulation probably occurs within the storage pools of the vacuoles. Amino acids derived from protein degradation contribute little to this accumulation. For the remainder of the cell cycle, during cell separation and until the next bud initiation, the rates of uptake and catabolism of arginine and amino acid biosynthesis remain constant. Despite the abrupt doubling in the rate of formation of amino acid pools, their rate of utilization for macromolecular synthesis increases steadily throughout the cycle. The significance of this temporal organization of nitrogen source uptake and amino acid metabolism during the cell division cycle is discussed. Images PMID:4591945

  15. New insights in nutritional management and amino acid supplementation in urea cycle disorders.

    PubMed

    Scaglia, Fernando

    2010-01-01

    Sodium phenylbutyrate is used in the pharmacological treatment of urea cycle disorders to create alternative pathways for nitrogen excretion. The primary metabolite, phenylacetate, conjugates glutamine in the liver and kidney to form phenylacetylglutamine that is readily excreted in the urine. Patients with urea cycle disorders taking sodium phenylbutyrate have a selective reduction in the plasma concentrations of branched chain amino acids despite adequate dietary protein intake. Moreover, this depletion is usually the harbinger of a metabolic crisis. Plasma branched chain amino acids and other essential amino acids were measured in control subjects, untreated ornithine transcarbamylase deficiency females, and treated patients with urea cycle disorders (ornithine transcarbamylase deficiency and argininosuccinate synthetase deficiency) in the absorptive state during the course of stable isotope studies. Branched chain amino acid levels were significantly lower in treated patients with urea cycle disorders when compared to untreated ornithine transcarbamylase deficiency females or control subjects. These results were replicated in control subjects who had low steady-state branched chain amino acid levels when treated with sodium phenylbutyrate. These studies suggested that alternative pathway therapy with sodium phenylbutyrate causes a substantial impact on the metabolism of branched chain amino acids in patients with urea cycle disorders, implying that better titration of protein restriction can be achieved with branched chain amino acid supplementation in these patients who are on alternative pathway therapy.

  16. MAGNETIC ACTIVITY CYCLES IN THE EXOPLANET HOST STAR {epsilon} ERIDANI

    SciTech Connect

    Metcalfe, T. S.; Mathur, S.; Buccino, A. P.; Mauas, P. J. D.; Petrucci, R.; Brown, B. P.; Soderblom, D. R.; Henry, T. J.; Hall, J. C.; Basu, S.

    2013-02-01

    The active K2 dwarf {epsilon} Eri has been extensively characterized both as a young solar analog and more recently as an exoplanet host star. As one of the nearest and brightest stars in the sky, it provides an unparalleled opportunity to constrain stellar dynamo theory beyond the Sun. We confirm and document the 3-year magnetic activity cycle in {epsilon} Eri originally reported by Hatzes and coworkers, and we examine the archival data from previous observations spanning 45 years. The data show coexisting 3-year and 13-year periods leading into a broad activity minimum that resembles a Maunder minimum-like state, followed by the resurgence of a coherent 3-year cycle. The nearly continuous activity record suggests the simultaneous operation of two stellar dynamos with cycle periods of 2.95 {+-} 0.03 years and 12.7 {+-} 0.3 years, which, by analogy with the solar case, suggests a revised identification of the dynamo mechanisms that are responsible for the so-called 'active' and 'inactive' sequences as proposed by Boehm-Vitense. Finally, based on the observed properties of {epsilon} Eri, we argue that the rotational history of the Sun is what makes it an outlier in the context of magnetic cycles observed in other stars (as also suggested by its Li depletion), and that a Jovian-mass companion cannot be the universal explanation for the solar peculiarities.

  17. Zymographic detection of cinnamic acid decarboxylase activity.

    PubMed

    Prim, Núria; Pastor, F I Javier; Diaz, Pilar

    2002-11-01

    The manuscript includes a concise description of a new, fast and simple method for detection of cinnamic acid decarboxylase activity. The method is based on a color shift caused a by pH change and may be an excellent procedure for large screenings of samples from natural sources, as it involves no complex sample processing or purification. The method developed can be used in preliminary approaches to biotransformation processes involving detection of hydroxycinnamic acid decarboxylase activity.

  18. Focusing pharmacoeconomic activities: reimbursement or the drug life cycle?

    PubMed

    Langley, Paul C

    2004-01-01

    The purpose of this paper is to consider the role of pharmacoeconomic activities in the drug life cycle and not just as activities to support reimbursement applications and market entry. These activities are important in establishing the value case for a drug product to both internal and external audiences. Unless these activities are fully integrated into establishing the business case for a product from the pre-phase I period of drug discovery, manufacturers run the risk of establishing a unit price for the product and claims for cost-effectiveness which are inconsistent with achieving reimbursement. Importantly, manufacturers need to consider at an early stage the evidentiary and analytical needs for product evaluation under formulary submission guidelines (AMCP; NICE) and the integration of pharmacoeconomic activities over the life cycle. These activities include justifying assumptions for business opportunity assessments and an early commitment to developing a mock reimbursement submission at post-phase II. The integration of pharmacoeconomic activities in the drug cycle is not only an antidote to excessive clinical optimism but also provides the basis for an effective assessment of the likely performance of new products in the health-care market place at a price and formulary position acceptable both to the manufacturer and the reimburser.

  19. Periods of activity cycles in late-type stars

    NASA Technical Reports Server (NTRS)

    Kliorin, N. I.; Ruzmaykin, A. A.; Sokolov, D. D.

    1983-01-01

    The mean magnetic field dynamo theory is utilized to obtain the qualitative dependence of the period of activity on the angular velocity of rotation for stars with sufficiently extensive convective shells. The dependence of the cycle period on the spectral class is also discussed.

  20. FOC/48 Monthly Activation (camera Section - Cycle 4

    NASA Astrophysics Data System (ADS)

    Miebach, Manfred

    1994-01-01

    This is an FOC engineering program needed to RE-ACTIVATE the FOC/48 detector according to CARD item 3.4.2.1 every 30 days. In order to avoid HV-ON cycles on the Intensifier HV Power Supplies the Camera Section is turned ON ONLY.

  1. Spots, activity cycles, and differential rotation on cool stars

    NASA Astrophysics Data System (ADS)

    Alekseev, I. Yu.

    2005-01-01

    The first results are reported from a search for activity cycles in stars similar to the sun based on modelling their spotting with an algorithm developed at the Crimean Astrophysical Observatory. Of the more than thirty program stars, 10 manifested a cyclical variation in their central latitudes and total starspot area. The observed cycles have durations of 4-15 years, i.e., analogous to the 11 year Schwabe sunspot cycle. Most of the stars have a rough analog of the solar butterfly pattern, with a reduction in the average latitude of the spots as their area increases. A flip-flop effect during the epoch of the maximum average latitude is noted in a number of these objects (e.g., the analog LQ Hya of the young sun or the RS CVn-type variable V711 Tau), as well as a reduction in the photometric rotation period of a star as the spots drift toward the equator, an analog of the differential rotation effect in the sun. Unlike in the sun, the observed spot formation cycles do not correlate uniquely with other indicators of activity— chromospheric emission in the CaII HK lines (Be Cet, EK Dra, Dx Leo), H line emission (LQ Hya, VY Ari, EV Lac), or cyclical flare activity (EV Lac). In V833 Tau, BY Dra, EK Dra, and VY Ari short Schwabe cycles coexist with long cycles that are analogous to the Gleissberg solar cycle, in which the spotted area can approach half the entire area of the star.

  2. A cycling workstation to facilitate physical activity in office settings.

    PubMed

    Elmer, Steven J; Martin, James C

    2014-07-01

    Facilitating physical activity during the workday may help desk-bound workers reduce risks associated with sedentary behavior. We 1) evaluated the efficacy of a cycling workstation to increase energy expenditure while performing a typing task and 2) fabricated a power measurement system to determine the accuracy and reliability of an exercise cycle. Ten individuals performed 10 min trials of sitting while typing (SIT type) and pedaling while typing (PED type). Expired gases were recorded and typing performance was assessed. Metabolic cost during PED type was ∼ 2.5 × greater compared to SIT type (255 ± 14 vs. 100 ± 11 kcal h(-1), P < 0.01). Typing time and number of typing errors did not differ between PED type and SIT type (7.7 ± 1.5 vs. 7.6 ± 1.6 min, P = 0.51, 3.3 ± 4.6 vs. 3.8 ± 2.7 errors, P = 0.80). The exercise cycle overestimated power by 14-138% compared to actual power but actual power was reliable (r = 0.998, P < 0.01). A cycling workstation can facilitate physical activity without compromising typing performance. The exercise cycle's inaccuracy could be misleading to users. PMID:24681071

  3. Electrochemical gating of tricarboxylic acid cycle in electricity-producing bacterial cells of Shewanella.

    PubMed

    Matsuda, Shoichi; Liu, Huan; Kouzuma, Atsushi; Watanabe, Kazuya; Hashimoto, Kazuhito; Nakanishi, Shuji

    2013-01-01

    Energy-conversion systems mediated by bacterial metabolism have recently attracted much attention, and therefore, demands for tuning of bacterial metabolism are increasing. It is widely recognized that intracellular redox atmosphere which is generally tuned by dissolved oxygen concentration or by appropriate selection of an electron acceptor for respiration is one of the important factors determining the bacterial metabolism. In general, electrochemical approaches are valuable for regulation of redox-active objects. However, the intracellular redox conditions are extremely difficult to control electrochemically because of the presence of insulative phospholipid bilayer membranes. In the present work, the limitation can be overcome by use of the bacterial genus Shewanella, which consists of species that are able to respire via cytochromes abundantly expressed in their outer-membrane with solid-state electron acceptors, including anodes. The electrochemical characterization and the gene expression analysis revealed that the activity of tricarboxylic acid (TCA) cycle in Shewanella cells can be reversibly gated simply by changing the anode potential. Importantly, our present results for Shewanella cells cultured in an electrochemical system under poised potential conditions showed the opposite relationship between the current and electron acceptor energy level, and indicate that this unique behavior originates from deactivation of the TCA cycle in the (over-)oxidative region. Our result obtained in this study is the first demonstration of the electrochemical gating of TCA cycle of living cells. And we believe that our findings will contribute to a deeper understanding of redox-dependent regulation systems in living cells, in which the intracellular redox atmosphere is a critical factor determining the regulation of various metabolic and genetic processes.

  4. The active RS Canum Venaticorum binary II Pegasi. IV. The SPOT activity cycle

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Berdyugin, A. V.; Ilyin, I.; Tuominen, I.

    1999-10-01

    A total of 6 new surface images of II Peg obtained for the years 1997 and 1998 confirms the recently revealed permanent active longitude structure. The lower limit of the active longitudes' lifetime is now extended up to 25 years. A new ``flip-flop'' phenomenon, redefined as a switch of the activity between the active longitudes, has started in summer of 1998. It coincides reasonably well with the moment predicted from the activity cycle of the star. This confirms definitely the cyclic behaviour of the activity of II Peg we recently discovered. Therefore, we assign numbers to the cycles of 4.65 yr since the earliest photoelectric observations of II Peg and define the active longitudes as ``odd'' and ``even'' corresponding to odd and even numbers of cycles. With such a definition, in late 1998 the 7th cycle began and the ``odd'' active longitude became more active. From the analysis of the spot area evolution within the active longitudes we conclude that the activity cycle is developed as a rearrangement of the nearly constant amount of the spot area between the active longitudes. We discuss the ``flip-flop'' phenomenon as a tracer of stellar activity and the role of the unseen secondary in establishing the cycle. Based on observations collected at the Nordic Optical Telescope (NOT), La Palma, Spain; the 1.25m telescope of the Crimean Astrophysical Observatory, Ukraine; the Phoenix 10 robotic telescope, APT Observatory, Arizona, USA.}

  5. A Geomagnetic Precursor Technique for Predicting the Solar Activity Cycle

    NASA Astrophysics Data System (ADS)

    Sobel, E. I.; Rabin, D. M.

    2015-12-01

    The Western hemisphere has been recording sunspot numbers since Galileo discovered sunspots in the early 17th century, and the roughly 11-year solar cycle has been recognized since the 19th century. However, predicting the strength of any particular cycle remains a relatively imprecise task. This project's aim was to update and improve a forecasting technique based on geomagnetic precursors of future solar activity The model is a refinement of R. J. Thompson's 1993 paper that relates the number of geomagnetically disturbed days, as defined by the aa and Ap indices, to the sum of the sunspot number in the current and the previous cycle, Rn + Rn-1.[1] The method exploits the fact that two cycles coexist for some period on the Sun near solar minimum and therefore that the number of sunspots and disturbed days during the declining phase of one cycle gives an indication of the following cycle's strength. We wrote and updated IDL software procedures to define disturbed days with varying threshold values and graphed Rn + Rn-1 against them. The aa threshold was derived from the Ap threshold. After comparing the graphs for Ap values from 20 to 50, an Ap threshold of 30 and the corresponding aa threshold of 44 were chosen as yielding the best correlation. Confidence regions were computed to provide a quantitative uncertainty on future predictions. The 80% confidence region gives a range of ±40 in sunspot number. [1] Thompson, R. J. (1993). A technique for predicting the amplitude of the solar cycle. Solar Physics, 148, 2, 383-388.

  6. SOLAR ROTATION RATE DURING THE CYCLE 24 MINIMUM IN ACTIVITY

    SciTech Connect

    Antia, H. M.; Basu, Sarbani E-mail: sarbani.basu@yale.ed

    2010-09-01

    The minimum of solar cycle 24 is significantly different from most other minima in terms of its duration as well as its abnormally low levels of activity. Using available helioseismic data that cover epochs from the minimum of cycle 23 to now, we study the differences in the nature of the solar rotation between the minima of cycles 23 and 24. We find that there are significant differences between the rotation rates during the two minima. There are differences in the zonal-flow pattern too. We find that the band of fast rotating region close to the equator bifurcated around 2005 and recombined by 2008. This behavior is different from that during the cycle 23 minimum. By autocorrelating the zonal-flow pattern with a time shift, we find that in terms of solar dynamics, solar cycle 23 lasted for a period of 11.7 years, consistent with the result of Howe et al. (2009). The autocorrelation coefficient also confirms that the zonal-flow pattern penetrates through the convection zone.

  7. Photoreduction fuels biogeochemical cycling of iron in Spain's acid rivers

    USGS Publications Warehouse

    Gammons, C.H.; Nimick, D.A.; Parker, S.R.; Snyder, D.M.; McCleskey, R.B.; Amils, R.; Poulson, S.R.

    2008-01-01

    A number of investigations have shown that photoreduction of Fe(III) causes midday accumulations of dissolved Fe(II) in rivers and lakes, leading to large diel (24-h) fluctuations in the concentration and speciation of total dissolved iron. Less well appreciated is the importance of photoreduction in providing chemical energy for bacteria to thrive in low pH waters. Diel variations in water chemistry from the highly acidic (pH 2.3 to 3.1) Ri??o Tinto, Ri??o Odiel, and Ri??o Agrio of southwestern Spain (Iberian Pyrite Belt) resulted in daytime increases in Fe(II) concentration of 15 to 66????M at four diel sampling locations. Dissolved Fe(II) concentrations increased with solar radiation, and one of the stream sites showed an antithetic relationship between dissolved Fe(II) and Fe(III) concentrations; both results are consistent with photoreduction. The diel data were used to estimate rates of microbially catalyzed Fe(II) oxidation (1 to 3??nmol L- 1 s- 1) and maximum rates of Fe(III) photoreduction (1.7 to 4.3??nmol L- 1 s- 1). Bioenergetic calculations indicate that the latter rates are sufficient to build up a population of Fe-oxidizing bacteria to the levels observed in the Ri??o Tinto in about 30??days. We conclude that photoreduction plays an important role in the bioenergetics of the bacterial communities of these acidic rivers, which have previously been shown to be dominated by autotrophic Fe(II)-oxidizers such as Acidithiobacillus ferrooxidans and Leptospirillum ferrooxidans. Given the possibility of the previous existence of acidic, Fe(III)-rich water on Mars, photoreduction may be an important process on other planets, a fact that could have implications to astrobiological research. ?? 2008 Elsevier B.V. All rights reserved.

  8. An alternative mechanism for guanidinoacetic acid to affect methylation cycle.

    PubMed

    Ostojic, Sergej M

    2014-12-01

    Guanidinoacetic acid (also known as glycocyamine; GAA) is an endogenous substance which occurs in humans and plays a central role in the biosynthesis of creatine. The formation of creatine from GAA consumes methyl groups, and increases production of homocysteine. GAA may have the potential to stimulate insulin secretion. Insulin reduces plasma homocysteine and raises methyl group supply. It is possible that the ability of GAA to trigger the insulin secretion modulates methyl group metabolism, and comparatively counterbalance for the direct effect of GAA on increased methylation demand. Possible insulinotropic effect of GAA may contribute to total in vivo methylation demand during biotransformation. PMID:25468046

  9. Activity Scratchpad Prototype: Simplifying the Rover Activity Planning Cycle

    NASA Technical Reports Server (NTRS)

    Abramyan, Lucy

    2005-01-01

    The Mars Exploration Rover mission depends on the Science Activity Planner as its primary interface to the Spirit and Opportunity Rovers. Scientists alternate between a series of mouse clicks and keyboard inputs to create a set of instructions for the rovers. To accelerate planning by minimizing mouse usage, a rover planning editor should receive the majority of inputted commands from the keyboard. Thorough investigation of the Eclipse platform's Java editor has provided the understanding of the base model for the Activity Scratchpad. Desirable Eclipse features can be mapped to specific rover planning commands, such as auto-completion for activity titles and content assist for target names. A custom editor imitating the Java editor's features was created with an XML parser for experimenting purposes. The prototype editor minimized effort for redundant tasks and significantly improved the visual representation of XML syntax by highlighting keywords, coloring rules, folding projections, and providing hover assist, templates and an outline view of the code.

  10. p21 induction plays a dual role in anti-cancer activity of ursolic acid

    PubMed Central

    Zhang, Xudong; Song, Xinhua; Yin, Shutao; Zhao, Chong; Fan, Lihong

    2015-01-01

    Previous studies have shown that induction of G1 arrest and apoptosis by ursolic acid is associated with up-regulation of cyclin-dependent kinase inhibitor (CDKI) protein p21 in multiple types of cancer cells. However, the functional role of p21 induction in G1 cell cycle arrest and apoptosis, and the mechanisms of p21 induction by ursolic acid have not been critically addressed. In the current study, we demonstrated that p21 played a mediator role in G1 cell cycle arrest by ursolic acid, whereas p21-mediated up-regulation of Mcl-1 compromised apoptotic effect of ursolic acid. These results suggest that p21 induction plays a dual role in the anti-cancer activity of ursolic acid in terms of cell cycle and apoptosis regulation. p21 induction by ursolic acid was attributed to p53 transcriptional activation. Moreover, we found that ursolic acid was able to inhibit murine double minute-2 protein (MDM2) and T-LAK cell-originated protein kinase (TOPK), the two negative regulator of p53, which in turn contributed to ursolic acid-induced p53 activation. Our findings provided novel insights into understanding of the mechanisms involved in cell cycle arrest and apoptosis induction in response to ursolic acid exposure. PMID:26582056

  11. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    PubMed

    Morrish, F; Isern, N; Sadilek, M; Jeffrey, M; Hockenbery, D M

    2009-07-01

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell-cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell-cycle entry is unknown. Here, we report the metabolic fates of [U-(13)C] glucose in serum-stimulated myc(-/-) and myc(+/+) fibroblasts by (13)C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased (13)C labeling of ribose sugars, purines and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked N-acetylglucosamine protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing function for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its function in directing metabolic networks required for cell proliferation.

  12. c-Myc activates multiple metabolic networks to generate substrates for cell-cycle entry.

    SciTech Connect

    Morrish, Fionnuala M.; Isern, Nancy; Sadilek, Martin; Jeffrey, Mark; Hockenbery, David M.

    2009-05-18

    Cell proliferation requires the coordinated activity of cytosolic and mitochondrial metabolic pathways to provide ATP and building blocks for DNA, RNA, and protein synthesis. Many metabolic pathway genes are targets of the c-myc oncogene and cell cycle regulator. However, the contribution of c-Myc to the activation of cytosolic and mitochondrial metabolic networks during cell cycle entry is unknown. Here, we report the metabolic fates of [U-13C] glucose in serum-stimulated myc-/- and myc+/+ fibroblasts by 13C isotopomer NMR analysis. We demonstrate that endogenous c-myc increased 13C-labeling of ribose sugars, purines, and amino acids, indicating partitioning of glucose carbons into C1/folate and pentose phosphate pathways, and increased tricarboxylic acid cycle turnover at the expense of anaplerotic flux. Myc expression also increased global O-linked GlcNAc protein modification, and inhibition of hexosamine biosynthesis selectively reduced growth of Myc-expressing cells, suggesting its importance in Myc-induced proliferation. These data reveal a central organizing role for the Myc oncogene in the metabolism of cycling cells. The pervasive deregulation of this oncogene in human cancers may be explained by its role in directing metabolic networks required for cell proliferation.

  13. Halogenated methanesulfonic acids: A new class of organic micropollutants in the water cycle.

    PubMed

    Zahn, Daniel; Frömel, Tobias; Knepper, Thomas P

    2016-09-15

    Mobile and persistent organic micropollutants may impact raw and drinking waters and are thus of concern for human health. To identify such possible substances of concern nineteen water samples from five European countries (France, Switzerland, The Netherlands, Spain and Germany) and different compartments of the water cycle (urban effluent, surface water, ground water and drinking water) were enriched with mixed-mode solid phase extraction. Hydrophilic interaction liquid chromatography - high resolution mass spectrometry non-target screening of these samples led to the detection and structural elucidation of seven novel organic micropollutants. One structure could already be confirmed by a reference standard (trifluoromethanesulfonic acid) and six were tentatively identified based on experimental evidence (chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethanesulfonic acid, bromomethanesulfonic acid, dibromomethanesulfonic acid and bromochloromethanesulfonic acid). Approximated concentrations for these substances show that trifluoromethanesulfonic acid, a chemical registered under the European Union regulation REACH with a production volume of more than 100 t/a, is able to spread along the water cycle and may be present in concentrations up to the μg/L range. Chlorinated and brominated methanesulfonic acids were predominantly detected together which indicates a common source and first experimental evidence points towards water disinfection as a potential origin. Halogenated methanesulfonic acids were detected in drinking waters and thus may be new substances of concern. PMID:27267477

  14. Halogenated methanesulfonic acids: A new class of organic micropollutants in the water cycle.

    PubMed

    Zahn, Daniel; Frömel, Tobias; Knepper, Thomas P

    2016-09-15

    Mobile and persistent organic micropollutants may impact raw and drinking waters and are thus of concern for human health. To identify such possible substances of concern nineteen water samples from five European countries (France, Switzerland, The Netherlands, Spain and Germany) and different compartments of the water cycle (urban effluent, surface water, ground water and drinking water) were enriched with mixed-mode solid phase extraction. Hydrophilic interaction liquid chromatography - high resolution mass spectrometry non-target screening of these samples led to the detection and structural elucidation of seven novel organic micropollutants. One structure could already be confirmed by a reference standard (trifluoromethanesulfonic acid) and six were tentatively identified based on experimental evidence (chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethanesulfonic acid, bromomethanesulfonic acid, dibromomethanesulfonic acid and bromochloromethanesulfonic acid). Approximated concentrations for these substances show that trifluoromethanesulfonic acid, a chemical registered under the European Union regulation REACH with a production volume of more than 100 t/a, is able to spread along the water cycle and may be present in concentrations up to the μg/L range. Chlorinated and brominated methanesulfonic acids were predominantly detected together which indicates a common source and first experimental evidence points towards water disinfection as a potential origin. Halogenated methanesulfonic acids were detected in drinking waters and thus may be new substances of concern.

  15. Pt/TiO2 (Rutile) Catalysts for Sulfuric Acid Decomposition in Sulfur-Based Thermochemical Water-Splitting Cycles

    SciTech Connect

    L. M. Petkovic; D. M. Ginosar; H. W. Rollins; K. C. Burch; P. J. Pinhero; H. H. Farrell

    2008-04-01

    Thermochemical cycles consist of a series of chemical reactions to produce hydrogen from water at lower temperatures than by direct thermal decomposition. All the sulfur-based cycles for water splitting employ the sulfuric acid decomposition reaction. This work reports the studies performed on platinum supported on titania (rutile) catalysts to investigate the causes of catalyst deactivation under sulfuric acid decomposition reaction conditions. Samples of 1 wt% Pt/TiO2 (rutile) catalysts were submitted to flowing concentrated sulfuric acid at 1123 K and atmospheric pressure for different times on stream (TOS) between 0 and 548 h. Post-operation analyses of the spent catalyst samples showed that Pt oxidation and sintering occurred under reaction conditions and some Pt was lost by volatilization. Pt loss rate was higher at initial times but total loss appeared to be independent of the gaseous environment. Catalyst activity showed an initial decrease that lasted for about 66 h, followed by a slight recovery of activity between 66 and 102 h TOS, and a period of slower deactivation after 102 h TOS. Catalyst sulfation did not seem to be detrimental to catalyst activity and the activity profile suggested that a complex dynamical situation involving platinum sintering, volatilization, and oxidation, along with TiO2 morphological changes affected catalyst activity in a non-monotonic way.

  16. The effects of climate change on the nitrogen cycle and acid deposition

    SciTech Connect

    Penner, J.E.; Walton, J.J. ); Graboske, B.C. )

    1990-09-01

    Increases in greenhouse gases are expected to lead to a number of changes to the atmosphere which may impact regional and global chemical cycles. With the increasing awareness of climate change and the possibility of global chemical changes to the atmosphere, it becomes important to ask whether these changes to global climate and chemical cycles might benefit or hinder control programs aimed at reducing acid deposition. In the following, we review several possible changes to climate that may be expected to impact the global cycle of reactive nitrogen. We then use our global model of the reactive nitrogen cycle to estimate the effects of several of the more important changes on the continental-scale deposition of nitric acid. 7 refs., 1 tab.

  17. Magnetic activity in the young solar analog LQ Hydrae. I. Active longitudes and cycles

    NASA Astrophysics Data System (ADS)

    Berdyugina, S. V.; Pelt, J.; Tuominen, I.

    2002-11-01

    We present the first evidence that a single active dwarf of solar type can show a long-lived, nonaxisymmetric spot distribution - active longitudes on opposite hemispheres, similar to evolved, rapidly rotating RS CVn-type binary stars. We analyse new as well as published photometric observations of the young active dwarf LQ Hya, spanning almost 20 years. We find that activity of the star has three activity cycles: a 5.2-yr ``flip-flop'' cycle, a 7.7-yr period in the amplitude modulation of the brightness and an approximately 15-yr period in variations of the mean brightness. The two shorter cycles are related to the alternating active longitudes and are similar to cycles observed in RS CVn-type stars. The 15-yr cycle reflects periodic changes of the mean spottedness of the star and resembles the solar 11-year cycle. The spot rotation period (about 1.6 days) changes during the 15-yr cycle, indicating the presence of small differential rotation. The lengths of the three cycles are related as 3:2:1, with the repetition of the spot configuration after 15 years. We discuss the possibility that the observed spot cycles represent two different magnetic dynamo modes operating in LQ Hya: an axisymmetric mode, as in the Sun, and a nonaxisymmetric higher order mode with two cycles in spot patterns. Our results suggest that young stars exhibit their cycles in spot distribution, as seen in LQ Hya. This is in contrast to the conclusion based on the analysis of Ca Ii H&K emission from plages. The results suggest also that the Vaughan-Preston gap represents a transition from a multiple-mode dynamo to a single-mode dynamo. Table 2 is only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.128.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A/394/505

  18. Glutamate Utilization Couples Oxidative Stress Defense and the Tricarboxylic Acid Cycle in Francisella Phagosomal Escape

    PubMed Central

    Ramond, Elodie; Gesbert, Gael; Rigard, Mélanie; Dairou, Julien; Dupuis, Marion; Dubail, Iharilalao; Meibom, Karin; Henry, Thomas; Barel, Monique; Charbit, Alain

    2014-01-01

    Intracellular bacterial pathogens have developed a variety of strategies to avoid degradation by the host innate immune defense mechanisms triggered upon phagocytocis. Upon infection of mammalian host cells, the intracellular pathogen Francisella replicates exclusively in the cytosolic compartment. Hence, its ability to escape rapidly from the phagosomal compartment is critical for its pathogenicity. Here, we show for the first time that a glutamate transporter of Francisella (here designated GadC) is critical for oxidative stress defense in the phagosome, thus impairing intra-macrophage multiplication and virulence in the mouse model. The gadC mutant failed to efficiently neutralize the production of reactive oxygen species. Remarkably, virulence of the gadC mutant was partially restored in mice defective in NADPH oxidase activity. The data presented highlight links between glutamate uptake, oxidative stress defense, the tricarboxylic acid cycle and phagosomal escape. This is the first report establishing the role of an amino acid transporter in the early stage of the Francisella intracellular lifecycle. PMID:24453979

  19. Impact of activation process on fog life cycle

    NASA Astrophysics Data System (ADS)

    Mazoyer, Marie; Burnet, Frédéric; Lac, Christine; Roberts, Greg; Dupont, Jean-Charles; Haeffelin, Martial; Elias, Thierry

    2015-04-01

    Fogs are complex meteorological system dealing with fine scale processes. Subtle interaction between radiative, dynamic, turbulent and microphysic processes can lead to different fog life cycle, which make prediction difficult. The droplets that composed fogs are formed trough the activation of aerosol particles called CCN (cloud condensation nuclei) described by the Köhler theory (Köhler, 1936). The number and distribution of the droplets activated during fog formation is determined by the aerosols particles properties and number and the ambient vapor supersaturation of the atmosphere. In the frame of the PreViBOSS project, an in-situ measurement platform of fog properties at ground level was deployed at SIRTA (Instrumented Site for Atmospheric Remote Sensing Research) during winter 2010 to 2013. Microphysics data supply a detailed characterization of number size spectrum from dry to wet aerosols particles and inform on the abilities of the aerosols particles to act as a CCN. 48 fog events have been studied. Supersaturation critical values and concentrations of CCN have been determined and linked to aerosols properties. The main impact of aerosols size distribution on activation have been pointed out. The study of droplets spectra evolution reveals the major physical processes into fogs and suggests that even if thermodynamic dominates the fog life cycle, activation process seems to have a significant effect. Large eddy simulation of fog run with Meso-NH model allow to explore precisely the interaction between fog physical processes and to quantify activation impact. Supersaturation modelling is a key point, a new pseudo-prognostic scheme (Thouron et al., 2012) is used. Confrontation between a detailed experimental study and three-dimensional fine scale simulation in LES provides an accurate investigation of the impact of activation process on fog life cycle.

  20. Chopper-controlled discharge life cycling studies on lead-acid batteries

    NASA Technical Reports Server (NTRS)

    Kraml, J. J.; Ames, E. P.

    1982-01-01

    State-of-the-art 6 volt lead-acid golf car batteries were tested. A daily charge/discharge cycling to failure points under various chopper controlled pulsed dc and continuous current load conditions was undertaken. The cycle life and failure modes were investigated for depth of discharge, average current chopper frequency, and chopper duty cycle. It is shown that battery life is primarily and inversely related to depth of discharge and discharge current. Failure mode is characterized by a gradual capacity loss with consistent evidence of cell element aging.

  1. Results of chopper-controlled discharge life cycling studies on lead acid batteries

    NASA Technical Reports Server (NTRS)

    Ewashinka, J. G.; Sidik, S. M.

    1982-01-01

    A group of 108 state of the art nominally 6 volt lead acid batteries were tested in a program of one charge/discharge cycle per day for over two years or to ultimate battery failure. The primary objective was to determine battery cycle life as a function of depth of discharge (25 to 75 percent), chopper frequency (100 to 1000 Hz), duty cycle (25 to 87.5 percent), and average discharge current (20 to 260 A). The secondary objective was to determine the types of battery failure modes, if any, were due to the above parameters. The four parameters above were incorporated in a statistically designed test program.

  2. Uncertainty of Prebiotic Scenarios: The Case of the Non-Enzymatic Reverse Tricarboxylic Acid Cycle

    NASA Astrophysics Data System (ADS)

    Zubarev, Dmitry; Rappoport, Dmitrij; Aspuru-Guzik, Alan

    2015-03-01

    We consider the much discussed hypothesis of the primordial nature of the non-enzymatic reverse tricarboxylic acid (rTCA) cycle and describe a modeling approach that quantifies the uncertainty of this hypothesis due to the combinatorial aspect of the constituent chemical transformations. Our results suggest that a) rTCA cycle belongs to a degenerate optimum of auto-catalytic cycles, and b) the set of targets for the investigations of the origin of the common metabolic core should be significantly extended. This work was supported by a grant from the Simons Foundation (SCOL 291937, Dmitry Zubarev).

  3. The activity of Krebs cycle enzymes in the visual analyzer of rats in the norm and under stress.

    PubMed

    Lutsenko, N S; Yakushev, V S

    1993-01-01

    Higher activity of the NAD-dependent dehydrogenases of the tricarboxylic acid cycle (TAC) is observed in the optic retina, and of FAD-dependent dehydrogenases in the occipital lobes of the brain, in the visual analyzer of intact rats. The influence of stress using Desiderato's method induces a compensatory increase in the activity of succinate dehydrogenase. Acute stress induces a change in the regulation of the activity of the TAC dehydrogenases, assessed on the basis of the reaction to functional load. The animals' remaining in the dark following stress promotes the restoration of the activity of the TAC cycle to the normal level. PMID:8413911

  4. NHI-Acid Concentration Membranes -- Membrane Recommendations for the S-I Cycle

    SciTech Connect

    Frederick F Stewart

    2007-03-01

    Scope: The purpose of this draft report is to make recommendations concerning the applicability of specific membrane materials for acid concentration processes to the Sulfur-Iodine (S-I) thermochemical cycle integrated laboratory scale (ILS) demonstration. Introduction Acid concentration membrane processes have been studied for possible inclusion in the Sulfur-Iodine integrated laboratory scale (S-I ILS) demonstration. The need for this technology is driven by the chemical processes required for economical water splitting using the S-I cycle. Of the chemical processes inherent to the S-I cycle that have been identified as targets for deployment of membrane technology, three have been studied during the past three fiscal years as a part of the DOE Nuclear Hydrogen Initiative. First, the ability to concentrate hydriodic acid (HI) and iodine mixtures was sought as a method for aiding in the isolation of HI away from water and iodine. Isolated HI would then be delivered to the HI decomposition process for liberation of product hydrogen. Second, an extension of this technology to sulfuric acid was proposed to benefit sulfuric acid decomposition recycle. Third, decomposition of HI to form hydrogen is equilibrium limited. Removal of hydrogen, utilizing Le Chatelier’s principle, will increase to overall conversion and thus increasing the efficiency of the S-I cycle.

  5. Inhibition of Pyruvate Dehydrogenase Kinase 2 Protects Against Hepatic Steatosis Through Modulation of Tricarboxylic Acid Cycle Anaplerosis and Ketogenesis.

    PubMed

    Go, Younghoon; Jeong, Ji Yun; Jeoung, Nam Ho; Jeon, Jae-Han; Park, Bo-Yoon; Kang, Hyeon-Ji; Ha, Chae-Myeong; Choi, Young-Keun; Lee, Sun Joo; Ham, Hye Jin; Kim, Byung-Gyu; Park, Keun-Gyu; Park, So Young; Lee, Chul-Ho; Choi, Cheol Soo; Park, Tae-Sik; Lee, W N Paul; Harris, Robert A; Lee, In-Kyu

    2016-10-01

    Hepatic steatosis is associated with increased insulin resistance and tricarboxylic acid (TCA) cycle flux, but decreased ketogenesis and pyruvate dehydrogenase complex (PDC) flux. This study examined whether hepatic PDC activation by inhibition of pyruvate dehydrogenase kinase 2 (PDK2) ameliorates these metabolic abnormalities. Wild-type mice fed a high-fat diet exhibited hepatic steatosis, insulin resistance, and increased levels of pyruvate, TCA cycle intermediates, and malonyl-CoA but reduced ketogenesis and PDC activity due to PDK2 induction. Hepatic PDC activation by PDK2 inhibition attenuated hepatic steatosis, improved hepatic insulin sensitivity, reduced hepatic glucose production, increased capacity for β-oxidation and ketogenesis, and decreased the capacity for lipogenesis. These results were attributed to altered enzymatic capacities and a reduction in TCA anaplerosis that limited the availability of oxaloacetate for the TCA cycle, which promoted ketogenesis. The current study reports that increasing hepatic PDC activity by inhibition of PDK2 ameliorates hepatic steatosis and insulin sensitivity by regulating TCA cycle anaplerosis and ketogenesis. The findings suggest PDK2 is a potential therapeutic target for nonalcoholic fatty liver disease.

  6. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    PubMed

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-01

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated.

  7. Contribution of the tricarboxylic acid (TCA) cycle and the glyoxylate shunt in Saccharomyces cerevisiae to succinic acid production during dough fermentation.

    PubMed

    Rezaei, Mohammad N; Aslankoohi, Elham; Verstrepen, Kevin J; Courtin, Christophe M

    2015-07-01

    Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated. PMID:25828707

  8. The Cell Cycle: An Activity Using Paper Plates to Represent Time Spent in Phases of the Cell Cycle

    ERIC Educational Resources Information Center

    Scherer, Yvette D.

    2014-01-01

    In this activity, students are given the opportunity to combine skills in math and geometry for a biology lesson in the cell cycle. Students utilize the data they collect and analyze from an online onion-root-tip activity to create a paper-plate time clock representing a 24-hour cell cycle. By dividing the paper plate into appropriate phases of…

  9. Thermochemical cycles

    NASA Technical Reports Server (NTRS)

    Funk, J. E.; Soliman, M. A.; Carty, R. H.; Conger, W. L.; Cox, K. E.; Lawson, D.

    1975-01-01

    The thermochemical production of hydrogen is described along with the HYDRGN computer program which attempts to rate the various thermochemical cycles. Specific thermochemical cycles discussed include: iron sulfur cycle; iron chloride cycle; and hybrid sulfuric acid cycle.

  10. Short-period Stellar Activity Cycles with Kepler Photometry

    NASA Astrophysics Data System (ADS)

    Arkhypov, Oleksiy V.; Khodachenko, Maxim L.; Lammer, Helmut; Güdel, Manuel; Lüftinger, Theresa; Johnstone, Colin P.

    2015-07-01

    We study the short-periodic component of stellar activity with a cycle period of {P}{cyc}\\lt {10}3 days using the Kepler mission photometry of fast-rotating (1\\lt P\\lt 4 days) stars with spectra of M4V to F3V. Applying the originally developed two non-spectral methods, we measured the effective period of stellar cycles in 462 objects. The obtained results are in accordance with previous measurements by Vida et al. and do not seem to result from a beating effect. The performed measurements of Pcyc cluster in a specific branch that covers the previously unstudied region in the Saar & Brandenburg diagram and connects the branch of inactive stars with the area populated by super-active objects. It is shown that the formation of the discovered branch is due to the α-quenching effect, which saturates the magnetic dynamo and decreases the cycle periods with the increase of the inverted Rossby number. This finding is important in the context of the discussion on catastrophic quenching and other heuristic approximations of the nonlinear α-effect.

  11. Interplay between cell cycle and autophagy induced by boswellic acid analog

    PubMed Central

    Pathania, Anup S.; Guru, Santosh K.; Kumar, Suresh; Kumar, Ashok; Ahmad, Masroor; Bhushan, Shashi; Sharma, Parduman R.; Mahajan, Priya; Shah, Bhahwal A.; Sharma, Simmi; Nargotra, Amit; Vishwakarma, Ram; Korkaya, Hasan; Malik, Fayaz

    2016-01-01

    In this study, we investigated the role of autophagy induced by boswellic acid analog BA145 on cell cycle progression in pancreatic cancer cells. BA145 induced robust autophagy in pancreatic cancer cell line PANC-1 and exhibited cell proliferation inhibition by inducing cells to undergo G2/M arrest. Inhibition of G2/M progression was associated with decreased expression of cyclin A, cyclin B, cyclin E, cdc2, cdc25c and CDK-1. Pre-treatment of cells with autophagy inhibitors or silencing the expression of key autophagy genes abrogated BA145 induced G2/M arrest and downregulation of cell cycle regulatory proteins. It was further observed that BA145 induced autophagy by targeting mTOR kinase (IC50 1 μM), leading to reduced expression of p-mTOR, p-p70S6K (T389), p-4EBP (T37/46) and p-S6 (S240/244). Notably, inhibition of mTOR signalling by BA145 was followed by attendant activation of AKT and its membrane translocation. Inhibition of Akt through pharmacological inhibitors or siRNAs enhanced BA145 mediated autophagy, G2/M arrest and reduced expression of G2/M regulators. Further studies revealed that BA145 arbitrated inhibition of mTOR led to the activation of Akt through IGFR/PI3k/Akt feedback loop. Intervention in IGFR/PI3k/Akt loop further depreciated Akt phosphorylation and its membrane translocation that culminates in augmented autophagy with concomitant G2/M arrest and cell death. PMID:27680387

  12. The variations of prominence activities during solar cycle

    NASA Astrophysics Data System (ADS)

    Shimojo, Masumi

    The prominence activities (prominence eruption/disappearance) in the solar atmosphere closely relate with the CMEs that cause great influences on heliosphere and magnetosphere. Gopal-swarmy et al. (2003) reported that 72 The Nobeyama Radioheliograph (NoRH) is observing Sun in microwave (17 GHz) since 1992. At a flare, the main component of the microwave from Sun is emitted from non-thermal electrons that are accelerated by flare. On the other hand, the main component of the microwave is thermal emission when Sun is quiet, and a prominence is clearly observed in microwave because there is the prominence on the limb. We developed the automatic prominence activity detection program based on 17 GHz images observed by NoRH, and investigated the variation of the properties of the prominence activities that oc-curred from 1992 to the end of 2009. We found the following results. 1. The variation in the number of prominence activities is similar to that of sunspots during one solar cycle but there are differences between the peak times of prominence activities and sunspots. 2. The frequency distribution as a function of the magnitude of the prominence activities the size of activated prominences at each phase shows a power-law distribution. The power-law index of the distribution does not change except around the solar minimum. 3. The number of promi-nence activities has a dependence on the latitude On the other hand the average magnitude is independent of the latitude. In the paper, we will also discuss the relationship the other properties of prominence eruptions, solar cycle and the photospheric magnetic field.

  13. Ethanol Metabolism Activates Cell Cycle Checkpoint Kinase, Chk2

    PubMed Central

    Clemens, Dahn L.; Mahan Schneider, Katrina J.; Nuss, Robert F.

    2011-01-01

    Chronic ethanol abuse results in hepatocyte injury and impairs hepatocyte replication. We have previously shown that ethanol metabolism results in cell cycle arrest at the G2/M transition, which is partially mediated by inhibitory phosphorylation of the cyclin-dependent kinase, Cdc2. To further delineate the mechanisms by which ethanol metabolism mediates this G2/M arrest, we investigated the involvement of upstream regulators of Cdc2 activity. Cdc2 is activated by the phosphatase Cdc25C. The activity of Cdc25C can, in turn, be regulated by the checkpoint kinase, Chk2, which is regulated by the kinase ataxia telangiectasia mutated (ATM). To investigate the involvement of these regulators of Cdc2 activity, VA-13 cells, which are Hep G2 cells modified to efficiently express alcohol dehydrogenase, were cultured in the presence or absence of 25 mM ethanol. Immunoblots were performed to determine the effects of ethanol metabolism on the activation of Cdc25C, Chk2, and ATM. Ethanol metabolism increased the active forms of ATM, and Chk2, as well as the phosphorylated form of Cdc25C. Additionally, inhibition of ATM resulted in approximately 50% of the cells being rescued from the G2/M cell cycle arrest, and ameliorated the inhibitory phosphorylation of Cdc2. Our findings demonstrate that ethanol metabolism activates ATM. ATM can activate the checkpoint kinase Chk2, resulting in phosphorylation of Cdc25C, and ultimately in the accumulation of inactive Cdc2. This may, in part, explain the ethanol metabolism-mediated impairment in hepatocyte replication, which may be important in the initiation and progression of alcoholic liver injury. PMID:21924579

  14. Numerical Analysis of an Active Magnetic Regenerator (AMR) Refrigeration Cycle

    NASA Astrophysics Data System (ADS)

    Dikeos, J.; Rowe, A.; Tura, A.

    2006-04-01

    An alternative cycle proposed for refrigeration and gas liquefaction is active magnetic regenerator (AMR) refrigeration. This technology relies on solid materials exhibiting the magnetocaloric effect (MCE), a nearly reversible temperature change induced by a magnetic field change. This work focuses on numerical simulations of the AMR refrigeration cycle. A transient one-dimensional finite element model developed in FEMLAB™ incorporates energy equations for the refrigerant and the heat transfer fluid. The results of the model are validated by comparison to room temperature experiments with Gd. Predictions are then made for the performance of DyAl2 AMR beds near 70 K. Numerical results for simulations significantly above the Curie temperature are found to be dependent upon the initial conditions.

  15. Kinetics of salicylic acid adsorption on activated carbon.

    PubMed

    Polakovic, Milan; Gorner, Tatiana; Villiéras, Frédéric; de Donato, Philippe; Bersillon, Jean Luc

    2005-03-29

    The adsorption and desorption of salicylic acid from water solutions was investigated in HPLC microcolumns packed with activated carbon. The adsorption isotherm was obtained by the step-up frontal analysis method in a concentration range of 0-400 mg/L and was well fitted with the Langmuir equation. The investigation of rate aspects of salicylic acid adsorption was based on adsorption/desorption column experiments where different inlet concentrations of salicylic acid were applied in the adsorption phase and desorption was conducted with pure water. The concentration profiles of individual adsorption/desorption cycles data were fitted using several single-parameter models of the fixed-bed adsorption to assess the influence of different phenomena on the column behavior. It was found that the effects of axial dispersion and extraparticle mass transfer were negligible. A rate-determining factor of fixed-bed column dynamics was the kinetics of pore surface adsorption. A bimodal kinetic model reflecting the heterogeneous character of adsorbent pores was verified by a simultaneous fit of the column outlet concentration in four adsorption/desorption cycles. The fitted parameters were the fraction of mesopores and the adsorption rate constants in micropores and mesopores, respectively. It was shown that the former rate constant was an intrinsic one whereas the latter one was an apparent value due to the effects of pore blocking and diffusional hindrances in the micropores. PMID:15779975

  16. EEG activity during estral cycle in the rat.

    PubMed

    Corsi-Cabrera, M; Juárez, J; Ponce-de-León, M; Ramos, J; Velázquez, P N

    1992-10-01

    EEG activity was recorded from right and left parietal cortex in adult female rats daily during 6 days. Immediately after EEG recording vaginal smears were taken and were microscopically analyzed to determine the estral stage. Absolute and relative powers and interhemispheric correlation of EEG activity were calculated and compared between estral stages. Interhemispheric correlation was significantly lower during diestrous as compared to proestrous and estrous. Absolute and relative powers did not show significant differences between estral stages. Absolute powers of alpha1, alpha2, beta1 and beta2 bands were significantly higher at the right parietal cortex. Comparisons of the same EEG records with estral stages randomly grouped showed no significant differences for any of the EEG parameters. EEG activity is a sensitive tool to study functional changes related to the estral cycle.

  17. Sunspot Activity Near Cycle Minimum and What it Might Suggest for Cycle 24, the Next Sunspot Cycle

    NASA Technical Reports Server (NTRS)

    Wilson, Robert M.; Hathaway, David H.

    2009-01-01

    In late 2008, 12-month moving averages of sunspot number, number of spotless days, number of groups, area of sunspots, and area per group were reflective of sunspot cycle minimum conditions for cycle 24, these values being of or near record value. The first spotless day occurred in January 2004 and the first new-cycle, high-latitude spot was reported in January 2008, although old-cycle, low-latitude spots have continued to be seen through April 2009, yielding an overlap of old and new cycle spots of at least 16 mo. New-cycle spots first became dominant over old-cycle spots in September 2008. The minimum value of the weighted mean latitude of sunspots occurred in May 2007, measuring 6.6 deg, and the minimum value of the highest-latitude spot followed in June 2007, measuring 11.7 deg. A cycle length of at least 150 mo is inferred for cycle 23, making it the longest cycle of the modern era. Based on both the maximum-minimum and amplitude-period relationships, cycle 24 is expected to be only of average to below-average size, peaking probably in late 2012 to early 2013, unless it proves to be a statistical outlier.

  18. Prebiotic Metabolism: Production by Mineral Photoelectrochemistry of α-Ketocarboxylic Acids in the Reductive Tricarboxylic Acid Cycle

    NASA Astrophysics Data System (ADS)

    Guzman, Marcelo I.; Martin, Scot T.

    2009-11-01

    A reductive tricarboxylic acid (rTCA) cycle could have fixed carbon dioxide as bio chemically useful energy-storage molecules on early Earth. Nonenzymatic chemical pathways for some steps of the rTCA cycle, however, such as the production of the α-ketocarboxylic acids pyruvate and α-ketoglutarate, remain a challenging problem for the viability of the proposed prebiotic cycle. As a class of compounds, α-ketocarboxylic acids have high free energies of formation that disfavor their production. We report herein the production of pyruvate from lactate and of α-ketoglutarate from pyruvate in the millimolar concentration range as promoted by ZnS mineral photoelectrochemistry. Pyruvate is produced from the photooxidation of lactate with 70% yield and a quantum efficiency of 0.009 at 15°C across the wavelength range of 200-400 nm. The produced pyruvate undergoes photoreductive back reaction to lactate at a 30% yield and with a quantum efficiency of 0.0024. Pyruvate alternatively continues in photooxidative forward reaction to α-ketoglutarate with a 50% yield and a quantum efficiency of 0.0036. The remaining 20% of the carbon follows side reactions that produce isocitrate, glutarate, and succinate. Small amounts of acetate are also produced. The results of this study suggest that α-ketocarboxylic acids produced by mineral photoelectrochemistry could have participated in a viable enzyme-free cycle for carbon fixation in an environment where light, sulfide minerals, carbon dioxide, and other organic compounds interacted on prebiotic Earth.

  19. Sources of solar wind over the solar activity cycle

    PubMed Central

    Poletto, Giannina

    2012-01-01

    Fast solar wind has been recognized, about 40 years ago, to originate in polar coronal holes (CHs), that, since then, have been identified with sources of recurrent high speed wind streams. As of today, however, there is no general consensus about whether there are, within CHs, preferential locations where the solar wind is accelerated. Knowledge of slow wind sources is far from complete as well. Slow wind observed in situ can be traced back to its solar source by backward extrapolation of magnetic fields whose field lines are streamlines of the outflowing plasma. However, this technique often has not the necessary precision for an indisputable identification of the region where wind originates. As the Sun progresses through its activity cycle, different wind sources prevail and contribute to filling the heliosphere. Our present knowledge of different wind sources is here summarized. Also, a Section addresses the problem of wind acceleration in the low corona, as inferred from an analysis of UV data, and illustrates changes between fast and slow wind profiles and possible signatures of changes along the solar cycle. A brief reference to recent work about the deep roots of solar wind and their changes over different solar cycles concludes the review. PMID:25685421

  20. Sources of solar wind over the solar activity cycle.

    PubMed

    Poletto, Giannina

    2013-05-01

    Fast solar wind has been recognized, about 40 years ago, to originate in polar coronal holes (CHs), that, since then, have been identified with sources of recurrent high speed wind streams. As of today, however, there is no general consensus about whether there are, within CHs, preferential locations where the solar wind is accelerated. Knowledge of slow wind sources is far from complete as well. Slow wind observed in situ can be traced back to its solar source by backward extrapolation of magnetic fields whose field lines are streamlines of the outflowing plasma. However, this technique often has not the necessary precision for an indisputable identification of the region where wind originates. As the Sun progresses through its activity cycle, different wind sources prevail and contribute to filling the heliosphere. Our present knowledge of different wind sources is here summarized. Also, a Section addresses the problem of wind acceleration in the low corona, as inferred from an analysis of UV data, and illustrates changes between fast and slow wind profiles and possible signatures of changes along the solar cycle. A brief reference to recent work about the deep roots of solar wind and their changes over different solar cycles concludes the review.

  1. Unsuspected task for an old team: succinate, fumarate and other Krebs cycle acids in metabolic remodeling.

    PubMed

    Bénit, Paule; Letouzé, Eric; Rak, Malgorzata; Aubry, Laetitia; Burnichon, Nelly; Favier, Judith; Gimenez-Roqueplo, Anne-Paule; Rustin, Pierre

    2014-08-01

    Seventy years from the formalization of the Krebs cycle as the central metabolic turntable sustaining the cell respiratory process, key functions of several of its intermediates, especially succinate and fumarate, have been recently uncovered. The presumably immutable organization of the cycle has been challenged by a number of observations, and the variable subcellular location of a number of its constitutive protein components is now well recognized, although yet unexplained. Nonetheless, the most striking observations have been made in the recent period while investigating human diseases, especially a set of specific cancers, revealing the crucial role of Krebs cycle intermediates as factors affecting genes methylation and thus cell remodeling. We review here the recent advances and persisting incognita about the role of Krebs cycle acids in diverse aspects of cellular life and human pathology.

  2. Thiram and dimethyldithiocarbamic acid interconversion in Saccharomyces cerevisiae: a possible metabolic pathway under the control of the glutathione redox cycle.

    PubMed

    Elskens, M T; Penninckx, M J

    1997-07-01

    A rapid decrease of intracellular glutathione (GSH) was observed when exponentially growing cells of Saccharomyces cerevisiae were treated with sublethal concentrations of either dimethyldithiocarbamic acid or thiram [bis(dimethylthiocarbamoyl) disulfide]. The underlying mechanism of this effect possibly involves the intracellular oxidation of dimethyldithiocarbamate anions to thiram, which in turn oxidizes GSH. Overall, a linear relationship was found between thiram concentrations up to 21 microM and production of oxidized GSH (GSSG). Cytochrome c can serve as the final electron acceptor for dimethyldithiocarbamate reoxidation, and it was demonstrated in vitro that NADPH handles the final electron transfer from GSSG to the fungicide by glutathione reductase. These cycling reactions induce transient alterations in the intracellular redox state of several electron carriers and interfere with the respiration of the yeast. Thiram and dimethyldithiocarbamic acid also inactivate yeast glutathione reductase when the fungicide is present within the cells as the disulfide. Hence, whenever the GSH regeneration rate falls below its oxidation rate, the GSH:GSSG molar ratio drops from 45 to 1. Inhibition of glutathione reductase may be responsible for the saturation kinetics observed in rates of thiram elimination and uptake by the yeast. The data suggest also a leading role for the GSH redox cycle in the control of thiram and dimethyldithiocarbamic acid fungitoxicity. Possible pathways for the handling of thiram and dimethyldithiocarbamic acid by yeast are considered with respect to the physiological status, the GSH content, and the activity of glutathione reductase of the cells.

  3. Thiram and dimethyldithiocarbamic acid interconversion in Saccharomyces cerevisiae: a possible metabolic pathway under the control of the glutathione redox cycle.

    PubMed Central

    Elskens, M T; Penninckx, M J

    1997-01-01

    A rapid decrease of intracellular glutathione (GSH) was observed when exponentially growing cells of Saccharomyces cerevisiae were treated with sublethal concentrations of either dimethyldithiocarbamic acid or thiram [bis(dimethylthiocarbamoyl) disulfide]. The underlying mechanism of this effect possibly involves the intracellular oxidation of dimethyldithiocarbamate anions to thiram, which in turn oxidizes GSH. Overall, a linear relationship was found between thiram concentrations up to 21 microM and production of oxidized GSH (GSSG). Cytochrome c can serve as the final electron acceptor for dimethyldithiocarbamate reoxidation, and it was demonstrated in vitro that NADPH handles the final electron transfer from GSSG to the fungicide by glutathione reductase. These cycling reactions induce transient alterations in the intracellular redox state of several electron carriers and interfere with the respiration of the yeast. Thiram and dimethyldithiocarbamic acid also inactivate yeast glutathione reductase when the fungicide is present within the cells as the disulfide. Hence, whenever the GSH regeneration rate falls below its oxidation rate, the GSH:GSSG molar ratio drops from 45 to 1. Inhibition of glutathione reductase may be responsible for the saturation kinetics observed in rates of thiram elimination and uptake by the yeast. The data suggest also a leading role for the GSH redox cycle in the control of thiram and dimethyldithiocarbamic acid fungitoxicity. Possible pathways for the handling of thiram and dimethyldithiocarbamic acid by yeast are considered with respect to the physiological status, the GSH content, and the activity of glutathione reductase of the cells. PMID:9212433

  4. Evolution and functional implications of the tricarboxylic acid cycle as revealed by phylogenetic analysis.

    PubMed

    Cavalcanti, João Henrique Frota; Esteves-Ferreira, Alberto A; Quinhones, Carla G S; Pereira-Lima, Italo A; Nunes-Nesi, Adriano; Fernie, Alisdair R; Araújo, Wagner L

    2014-10-01

    The tricarboxylic acid (TCA) cycle, a crucial component of respiratory metabolism, is composed of a set of eight enzymes present in the mitochondrial matrix. However, most of the TCA cycle enzymes are encoded in the nucleus in higher eukaryotes. In addition, evidence has accumulated demonstrating that nuclear genes were acquired from the mitochondrial genome during the course of evolution. For this reason, we here analyzed the evolutionary history of all TCA cycle enzymes in attempt to better understand the origin of these nuclear-encoded proteins. Our results indicate that prior to endosymbiotic events the TCA cycle seemed to operate only as isolated steps in both the host (eubacterial cell) and mitochondria (alphaproteobacteria). The origin of isoforms present in different cell compartments might be associated either with gene-transfer events which did not result in proper targeting of the protein to mitochondrion or with duplication events. Further in silico analyses allow us to suggest new insights into the possible roles of TCA cycle enzymes in different tissues. Finally, we performed coexpression analysis using mitochondrial TCA cycle genes revealing close connections among these genes most likely related to the higher efficiency of oxidative phosphorylation in this specialized organelle. Moreover, these analyses allowed us to identify further candidate genes which might be used for metabolic engineering purposes given the importance of the TCA cycle during development and/or stress situations.

  5. Evolution and Functional Implications of the Tricarboxylic Acid Cycle as Revealed by Phylogenetic Analysis

    PubMed Central

    Cavalcanti, João Henrique Frota; Esteves-Ferreira, Alberto A.; Quinhones, Carla G.S.; Pereira-Lima, Italo A.; Nunes-Nesi, Adriano; Fernie, Alisdair R.; Araújo, Wagner L.

    2014-01-01

    The tricarboxylic acid (TCA) cycle, a crucial component of respiratory metabolism, is composed of a set of eight enzymes present in the mitochondrial matrix. However, most of the TCA cycle enzymes are encoded in the nucleus in higher eukaryotes. In addition, evidence has accumulated demonstrating that nuclear genes were acquired from the mitochondrial genome during the course of evolution. For this reason, we here analyzed the evolutionary history of all TCA cycle enzymes in attempt to better understand the origin of these nuclear-encoded proteins. Our results indicate that prior to endosymbiotic events the TCA cycle seemed to operate only as isolated steps in both the host (eubacterial cell) and mitochondria (alphaproteobacteria). The origin of isoforms present in different cell compartments might be associated either with gene-transfer events which did not result in proper targeting of the protein to mitochondrion or with duplication events. Further in silico analyses allow us to suggest new insights into the possible roles of TCA cycle enzymes in different tissues. Finally, we performed coexpression analysis using mitochondrial TCA cycle genes revealing close connections among these genes most likely related to the higher efficiency of oxidative phosphorylation in this specialized organelle. Moreover, these analyses allowed us to identify further candidate genes which might be used for metabolic engineering purposes given the importance of the TCA cycle during development and/or stress situations. PMID:25274566

  6. Gas-aerosol cycling of ammonia and nitric acid in The Netherlands

    NASA Astrophysics Data System (ADS)

    Roelofs, Geert-Jan; Derksen, Jeroen

    2010-05-01

    Atmospheric ammonia and nitric acid are present over NW Europe in large abundance. Observations made during the IMPACT measurement campaign (May 2008, Cabauw, The Netherlands) show a pronounced diurnal cycle of aerosol ammonium and nitrate on relatively dry days. Simultaneously, AERONET data show a distinct diurnal cycle in aerosol optical thickness (AOT). We used a global aerosol-climate model (ECHAM5-HAM) and a detailed aerosol-cloud column model to help analyse the observations from this period. The study shows that the diurnal cycle in AOT is partly associated with particle number concentration, with distinct peaks in the morning and evening. More important is relative humidity (RH). RH maximizes in the night and early morning, decreases during the morning and increases again in the evening. The particle wet radius, and therefore AOT, changes accordingly. In addition, the RH variability also influences chemistry associated with ammonia and nitric acid (formation of ammonium nitrate, dissolution in aerosol water), resulting in the observed diurnal cycle of aerosol ammonium and nitrate. The additional aerosol matter increases the hygroscopicity of the particles, and this leads to further swelling by water vapor condensation and a further increase of AOT. During the day, as RH decreases and the particles shrink, aerosol ammonium and nitrate are again partly expelled to the gas phase. This behaviour contributes significantly to the observed diurnal cycle in AOT, and it illustrates the complexity of using AOT as a proxy for aerosol concentrations in aerosol climate studies in the case of heavily polluted areas.

  7. Temperature effects on sealed lead acid batteries and charging techniques to prolong cycle life.

    SciTech Connect

    Hutchinson, Ronda

    2004-06-01

    Sealed lead acid cells are used in many projects in Sandia National Laboratories Department 2660 Telemetry and Instrumentation systems. The importance of these cells in battery packs for powering electronics to remotely conduct tests is significant. Since many tests are carried out in flight or launched, temperature is a major factor. It is also important that the battery packs are properly charged so that the test is completed before the pack cannot supply sufficient power. Department 2665 conducted research and studies to determine the effects of temperature on cycle time as well as charging techniques to maximize cycle life and cycle times on sealed lead acid cells. The studies proved that both temperature and charging techniques are very important for battery life to support successful field testing and expensive flight and launched tests. This report demonstrates the effects of temperature on cycle time for SLA cells as well as proper charging techniques to get the most life and cycle time out of SLA cells in battery packs.

  8. High temperature abatement of acid gases from waste incineration. Part II: Comparative life cycle assessment study.

    PubMed

    Biganzoli, Laura; Racanella, Gaia; Marras, Roberto; Rigamonti, Lucia

    2015-01-01

    The performances of a new dolomitic sorbent, named Depurcal®MG, to be directly injected at high temperature in the combustion chamber of Waste-To-Energy (WTE) plants as a preliminary stage of deacidification, were experimentally tested during full-scale commercial operation. Results of the experimentations were promising, and have been extensively described in Biganzoli et al. (2014). This paper reports the Life Cycle Assessment (LCA) study performed to compare the traditional operation of the plants, based on the sole sodium bicarbonate feeding at low temperature, with the new one, where the dolomitic sorbent is injected at high temperature. In the latter the sodium bicarbonate is still used, but at lower rate because of the decreased load of acid gases entering the flue gas treatment line. The major goal of the LCA was to make sure that a burden shifting was not taking place somewhere in the life cycle stages, as it might be the case when a new material is used in substitution of another one. According to the comparative approach, only the processes which differ between the two operational modes were included in the system boundaries. They are the production of the two reactants and the treatment of the corresponding solid residues arising from the neutralisation of acid gases. The additional CO2 emission at the stack of the WTE plant due to the activation of the sodium bicarbonate was also included in the calculation. Data used in the modelling of the foreground system are primary, derived from the experimental tests described in Biganzoli et al. (2014) and from the dolomitic sorbent production plant. The results of the LCA show minor changes in the potential impacts between the two operational modes of the plants. These differences are for 8 impact categories in favour of the new operational mode based on the addition of the dolomitic sorbent, and for 7 impact categories in favour of the traditional operation. A final evaluation was conducted on the potential

  9. High temperature abatement of acid gases from waste incineration. Part II: Comparative life cycle assessment study.

    PubMed

    Biganzoli, Laura; Racanella, Gaia; Marras, Roberto; Rigamonti, Lucia

    2015-01-01

    The performances of a new dolomitic sorbent, named Depurcal®MG, to be directly injected at high temperature in the combustion chamber of Waste-To-Energy (WTE) plants as a preliminary stage of deacidification, were experimentally tested during full-scale commercial operation. Results of the experimentations were promising, and have been extensively described in Biganzoli et al. (2014). This paper reports the Life Cycle Assessment (LCA) study performed to compare the traditional operation of the plants, based on the sole sodium bicarbonate feeding at low temperature, with the new one, where the dolomitic sorbent is injected at high temperature. In the latter the sodium bicarbonate is still used, but at lower rate because of the decreased load of acid gases entering the flue gas treatment line. The major goal of the LCA was to make sure that a burden shifting was not taking place somewhere in the life cycle stages, as it might be the case when a new material is used in substitution of another one. According to the comparative approach, only the processes which differ between the two operational modes were included in the system boundaries. They are the production of the two reactants and the treatment of the corresponding solid residues arising from the neutralisation of acid gases. The additional CO2 emission at the stack of the WTE plant due to the activation of the sodium bicarbonate was also included in the calculation. Data used in the modelling of the foreground system are primary, derived from the experimental tests described in Biganzoli et al. (2014) and from the dolomitic sorbent production plant. The results of the LCA show minor changes in the potential impacts between the two operational modes of the plants. These differences are for 8 impact categories in favour of the new operational mode based on the addition of the dolomitic sorbent, and for 7 impact categories in favour of the traditional operation. A final evaluation was conducted on the potential

  10. C-Myc induced compensated cardiac hypertrophy increases free fatty acid utilization for the citric acid cycle.

    PubMed

    Olson, Aaron K; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly Priddy, Colleen; Isern, Nancy; Portman, Michael A

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam) injections. Isolated working hearts and (13)Carbon ((13)C)-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing (13)C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (Cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was assessed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contributions in NTG. Substrate utilization was not significantly altered in 3dMyc versus Cont. The free fatty acid FC was significantly greater in 7dMyc versus Cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to Cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes for the citric acid cycle did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the

  11. Genipin as a novel chemical activator of EBV lytic cycle.

    PubMed

    Son, Myoungki; Lee, Minjung; Ryu, Eunhyun; Moon, Aree; Jeong, Choon-Sik; Jung, Yong Woo; Park, Gyu Hwan; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

    2015-02-01

    Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC. PMID:25626372

  12. Effects of Low Activity Solar Cycle on Orbital Debris Lifetime

    NASA Technical Reports Server (NTRS)

    Cable, Samual B.; Sutton, Eric K.; Lin, chin S.; Liou, J.-C.

    2011-01-01

    Long duration of low solar activity in the last solar minimum has an undesirable consequence of extending the lifetime of orbital debris. The AFRL TacSat-2 satellite decommissioned in 2008 has finally re-entered into the atmosphere on February 5th after more than one year overdue. Concerning its demise we have monitored its orbital decay and monthly forecasted Tacsat-2 re-entry since September 2010 by using the Orbital Element Prediction (OEP) model developed by the AFRL Orbital Drag Environment program. The model combines estimates of future solar activity with neutral density models, drag coefficient models, and an orbit propagator to predict satellite lifetime. We run the OEP model with solar indices forecast by the NASA Marshall Solar Activity Future Estimation model, and neutral density forecast by the MSIS-00 neutral density model. Based on the two line elements in 2010 up to mid September, we estimated at a 50% confidence level TacSat-2's re-entry time to be in early February 2011, which turned out to be in good agreement with Tacsat-2's actual re-entry date. The potential space weather effects of the coming low activity solar cycle on satellite lifetime and orbital debris population are examined. The NASA long-term orbital debris evolutionary model, LEGEND, is used to quantify the effects of solar flux on the orbital debris population in the 200-600 km altitude environment. The results are discussed for developing satellite orbital drag application product.

  13. Genipin as a novel chemical activator of EBV lytic cycle.

    PubMed

    Son, Myoungki; Lee, Minjung; Ryu, Eunhyun; Moon, Aree; Jeong, Choon-Sik; Jung, Yong Woo; Park, Gyu Hwan; Sung, Gi-Ho; Cho, Hyosun; Kang, Hyojeung

    2015-02-01

    Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that causes acute infection and establishes life-long latency. EBV causes several human cancers, including Burkitt's lymphoma, nasopharyngeal and gastric carcinoma. Antiviral agents can be categorized as virucides, antiviral chemotherapeutic agents, and immunomodulators. Most antiviral agents affect actively replicating viruses, but not their latent forms. Novel antiviral agents must be active on both the replicating and the latent forms of the virus. Gardenia jasminoides is an evergreen flowering plant belonging to the Rubiaceae family and is most commonly found growing wild in Vietnam, Southern China, Taiwan, Japan, Myanmar, and India. Genipin is an aglycone derived from an iridoid glycoside called geniposide, which is present in large quantities in the fruit of G. jasminoides. In this study, genipin was evaluated for its role as an antitumor and antiviral agent that produces inhibitory effects against EBV and EBV associated gastric carcinoma (EBVaGC). In SNU719 cells, one of EBVaGCs, genipin caused significant cytotoxicity (70 μM), induced methylation on EBV C promoter and tumor suppressor gene BCL7A, arrested cell-cycle progress (S phases), upregulated EBV latent/lytic genes in a dose-dependent manner, stimulated EBV progeny production, activated EBV F promoter for EBV lytic activation, and suppressed EBV infection. These results indicated that genipin could be a promising candidate for antiviral and antitumor agents against EBV and EBVaGC.

  14. Novel flowering and fatty acid characters in rapid cycling Brassica napus L. resynthesized by protoplast fusion.

    PubMed

    Hansen, L N; Earle, E D

    1994-12-01

    Novel rapid cycling Brassica napus lines have been produced by protoplast fusion between rapid cycling B. oleracea and rapid cycling B. rapa. Fusion products were selected based on iodoacetate inactivation and regeneration ability. A total of 36 plants was recovered from 3 regenerating calli. All were confirmed as somatic hybrids by morphological features, flow cytometric estimation of nuclear DNA content, RAPD analysis and/or DNA hybridization. Plants from two of the calli contained chloroplasts from B. rapa, and plants from the third contained B. oleracea chloroplasts. Some plants flowered in vitro, but on average flowering was initiated 22 days after transfer to soil. Although seed set was fairly low after self pollination, more seeds were obtained from pollination of open flowers than from pollination of buds. Seeds of the somatic hybrid B. napus showed novel fatty acid compositions, different from the mean of the two parental lines. Flowering was monitored in plants grown from seeds of the somatic hybrids, rapid cycling B. napus (CrGC 5-1) and the two diploid parental genotypes. Progeny of the somatic hybrids flowered faster and were more vigorous than rapid cycling B. napus (CrGC 5-1). The improved lines contain chloroplasts from B. rapa, unlike rapid cycling B. napus (CrGC 5-1), which has B. oleracea chloroplasts. The somatic hybrid lines produced may be useful for genetic studies or further in vitro manipulations.

  15. Novel Metabolic Abnormalities in the Tricarboxylic Acid Cycle in Peripheral Cells From Huntington’s Disease Patients

    PubMed Central

    Naseri, Nima N.; Bonica, Joseph; Xu, Hui; Park, Larry C.; Arjomand, Jamshid; Chen, Zhengming; Gibson, Gary E.

    2016-01-01

    Metabolic dysfunction is well-documented in Huntington’s disease (HD). However, the link between the mutant huntingtin (mHTT) gene and the pathology is unknown. The tricarboxylic acid (TCA) cycle is the main metabolic pathway for the production of NADH for conversion to ATP via the electron transport chain (ETC). The objective of this study was to test for differences in enzyme activities, mRNAs and protein levels related to the TCA cycle between lymphoblasts from healthy subjects and from patients with HD. The experiments utilize the advantages of lymphoblasts to reveal new insights about HD. The large quantity of homogeneous cell populations permits multiple dynamic measures to be made on exactly comparable tissues. The activities of nine enzymes related to the TCA cycle and the expression of twenty-nine mRNAs encoding for these enzymes and enzyme complexes were measured. Cells were studied under baseline conditions and during metabolic stress. The results support our recent findings that the activities of the pyruvate dehydrogenase complex (PDHC) and succinate dehydrogenase (SDH) are elevated in HD. The data also show a large unexpected depression in MDH activities. Furthermore, message levels for isocitrate dehydrogenase 1 (IDH1) were markedly increased in in HD lymphoblasts and were responsive to treatments. The use of lymphoblasts allowed us to clarify that the reported decrease in aconitase activity in HD autopsy brains is likely due to secondary hypoxic effects. These results demonstrate the mRNA and enzymes of the TCA cycle are critical therapeutic targets that have been understudied in HD. PMID:27611087

  16. Pseudolaric Acid B Induced Cell Cycle Arrest, Autophagy and Senescence in Murine Fibrosarcoma L929 Cell

    PubMed Central

    hua Yu, Jing; yu Liu, Chun; bin Zheng, Gui; Zhang, Li Ying; hui Yan, Ming; yan Zhang, Wen; ying Meng, Xian; fang Yu, Xiao

    2013-01-01

    Objective: PAB induced various cancer cell apoptosis, cell cycle arrest and senescence. But in cell line murine fibrosarcoma L929, PAB did not induce apoptosis, but autophagy, therefore it was thought by us as a good model to research the relationship of cell cycle arrest, autophagy and senescence bypass apoptosis. Methods: Inhibitory ratio was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Phase contrast microscopy visualized cell morphology. Hoechst 33258 staining for nuclear change, propidium iodode (PI) staining for cell cycle, monodansylcadaverine (MDC) staining for autophagy, and rodanmine 123 staining for mitochondrial membrane potential (MMP) were measured by fluorescence microscopy or flowcytometry. Apoptosis was determined by DNA ladder test. Protein kinase C (PKC) activity was detected by PKC assay kit. SA-β-galactosidase assay was used to detect senescence. Protein expression was examined by western blot. Results: PAB inhibited L929 cell growth in time-and dose-dependent manner. At 12 h, 80 μmol/L PAB induced obvious mitotic arrest; at 24 h, PAB began to induce autophagy; at 36 h, cell-treated with PAB slip into G1 cell cycle; and 3 d PAB induced senescence. In time sequence PAB induced firstly cell cycle arrest, then autophagy, then slippage into G1 phase, lastly senescence. Senescent cells had high level of autophagy, inhibiting autophagy led to apoptosis, and no senescence. PAB activated PKC activity to induce cell cycle arrest, autophagy and senescence, inhibiting PKC activity suppressed cell cycle arrest, autophagy and senescence. Conclusion: PAB induced cell cycle arrest, autophagy and senescence in murine fibrosarcoma L929 cell through PKC. PMID:23630435

  17. Solar wind and coronal rotation during an activity cycle

    NASA Astrophysics Data System (ADS)

    Pinto, Rui; Brun, Allan Sacha

    The properties of the solar wind flow are strongly affected by the time-varying strength and geometry of the global background magnetic field. The wind velocity and mass flux depend directly on the size and position of the wind sources at the surface, and on the geometry of the magnetic flux-tubes along which the wind flows. We address these problems by performing numerical simulations coupling a kinematic dynamo code (STELEM) evolve in a 2.5D axisymmetric coronal MHD code (DIP) covering an 11 yr activity cycle. The latitudinal distribution of the calculated wind velocities agrees with in-situ (ULYSSES, HELIO) and radio measurements (IPS). The transition from fast to slow wind flows can be explained in terms of the high overall flux-tube superradial expansion factors in the vicinities of coronal streamer boundaries. We found that the Alfvén radii and the global Sun's mass loss rate vary considerably throughout the cycle (by a factor 4.5 and 1.6, respectively), leading to strong temporal modulations of the global angular momentum flux and magnetic braking torque. The slowly varying magnetic topology introduces strong non-uniformities in the coronal rotation rate in the first few solar radii. Finally, we point out directions to assess the effects of surface transient phenomena on the global properties of the solar wind.

  18. Global changes in biogeochemical cycles in response to human activities

    NASA Technical Reports Server (NTRS)

    Moore, Berrien, III; Melillo, Jerry

    1994-01-01

    The main objective of our research was to characterize biogeochemical cycles at continental and global scales in both terrestrial and aquatic ecosystems. This characterization applied to both natural ecosystems and those disturbed by human activity. The primary elements of interest were carbon and nitrogen and the analysis sought to quantify standing stocks and dynamic cycling processes. The translocation of major nutrients from the terrestrial landscape to the atmosphere (via trace gases) and to fluvial systems (via leaching, erosional losses, and point source pollution) were of particular importance to this study. Our aim was to develop the first generation of Earth System Models. Our research was organized around the construction and testing of component biogeochemical models which treated terrestrial ecosystem processes, aquatic nutrient transport through drainage basins, and trace gas exchanges at the continental and global scale. A suite of three complementary models were defined within this construct. The models were organized to operate at a 1/2 degree latitude by longitude level of spatial resolution and to execute at a monthly time step. This discretization afforded us the opportunity to understand the dynamics of the biosphere down to subregional scales, while simultaneously placing these dynamics into a global context.

  19. Intertwined arbovirus transmission activity: reassessing the transmission cycle paradigm

    PubMed Central

    Diaz, Luis A.; Flores, Fernando S.; Quaglia, Agustín; Contigiani, Marta S.

    2013-01-01

    Arboviruses are emerging/reemerging infectious agents worldwide. The factors within this scenario include vector and host population fluctuations, climatic changes, anthropogenic activities that disturb ecosystems, an increase in international flights, human mobility, and genetic mutations that allow spill-over phenomenon. Arboviruses are maintained by biologic transmission among vectors and hosts. Sometimes this biological transmission is specific and includes one vector and host species such as Chikungunya (CHIKV), Dengue (DENV), and urban Yellow Fever (YFV). However, most of the arboviruses are generalist and they use many vectors and hosts species. From this perspective, arboviruses are maintained through a transmission network rather than a transmission cycle. This allows us to understand the complexity and dynamics of the transmission and maintenance of arboviruses in the ecosystems. The old perspective that arboviruses are maintained in close and stable transmission cycles should be modified by a new more integrative and dynamic idea, representing the real scenario where biological interactions have a much broader representation, indicating the constant adaptability of the biological entities. PMID:23335900

  20. Photoinduced biochemical activity of fullerene carboxylic acid

    SciTech Connect

    Tokuyama, Hidetoshi; Yamago, Shigeru; Nakamura, Eiichi; Shiraki, Takashi; Sugiura, Yukio

    1993-08-25

    Here we report the preparation of a water-miscible fullerene carboxylic acid (2) and its biological activity-cytotoxicity and G-selective DNA cleaving ability. What is truly remarkable is that the biological activity of C{sub 60} was observed only under irradiation with visible light and not in the dark, suggesting that fullerenes may serve as useful photosensitive biochemical probes. We have found, for the first time, that even low-energy visible light is surfficient to induce biological activity in fullerene derivatives. Among the numerous implications of the present findings, the most exciting prospect includes the use of fullerene derivatives for photodynamic therapy. 18 refs., 2 figs., 1 tab.

  1. On a hypothetical generational relationship between HCN and constituents of the reductive citric acid cycle.

    PubMed

    Eschenmoser, Albert

    2007-04-01

    Encouraged by observations made on the course of reactions the HCN-tetramer can undergo with acetaldehyde, I delineate a constitutional and potentially generational relationship between HCN and those constituents of the reductive citric acid cycle that are direct precursors of amino acids in contemporary metabolism. In this context, the robustness postulate of classical prebiotic chemistry is questioned, and, by an analysis of the (hypothetical) reaction-tree of a stepwise hydrolysis of the HCN-tetramer, it is shown how such a non-robust chemical reaction platform could harbor the potential for the emergence of autocatalytic cycles. It is concluded that the chemistry of HCN should be revisited by focussing on its non-robust parts in order to demonstrate its full potential as one of the possible roots of prebiotic self-organizing chemical processes.

  2. Effect on combined cycle efficiency of stack gas temperature constraints to avoid acid corrosion

    NASA Technical Reports Server (NTRS)

    Nainiger, J. J.

    1980-01-01

    To avoid condensation of sulfuric acid in the gas turbine exhaust when burning fuel oils contaning sulfur, the exhaust stack temperature and cold-end heat exchanger surfaces must be kept above the condensation temperature. Raising the exhaust stack temperature, however, results in lower combined cycle efficiency compared to that achievable by a combined cycle burning a sulfur-free fuel. The maximum difference in efficiency between the use of sulfur-free and fuels containing 0.8 percent sulfur is found to be less than one percentage point. The effect of using a ceramic thermal barrier coating (TBC) and a fuel containing sulfur is also evaluated. The combined-cycle efficiency gain using a TBC with a fuel containing sulfur compared to a sulfur-free fuel without TBC is 0.6 to 1.0 percentage points with air-cooled gas turbines and 1.6 to 1.8 percentage points with water-cooled gas turbines.

  3. Viral activities and life cycles in deep subseafloor sediments.

    PubMed

    Engelhardt, Tim; Orsi, William D; Jørgensen, Bo Barker

    2015-12-01

    Viruses are highly abundant in marine subsurface sediments and can even exceed the number of prokaryotes. However, their activity and quantitative impact on microbial populations are still poorly understood. Here, we use gene expression data from published continental margin subseafloor metatranscriptomes to qualitatively assess viral diversity and activity in sediments up to 159 metres below seafloor (mbsf). Mining of the metatranscriptomic data revealed 4651 representative viral homologues (RVHs), representing 2.2% of all metatranscriptome sequence reads, which have close translated homology (average 77%, range 60-97% amino acid identity) to viral proteins. Archaea-infecting RVHs are exclusively detected in the upper 30 mbsf, whereas RVHs for filamentous inoviruses predominate in the deepest sediment layers. RVHs indicative of lysogenic phage-host interactions and lytic activity, notably cell lysis, are detected at all analysed depths and suggest a dynamic virus-host association in the marine deep biosphere studied here. Ongoing lytic viral activity is further indicated by the expression of clustered, regularly interspaced, short palindromic repeat-associated cascade genes involved in cellular defence against viral attacks. The data indicate the activity of viruses in subsurface sediment of the Peruvian margin and suggest that viruses indeed cause cell mortality and may play an important role in the turnover of subseafloor microbial biomass. PMID:26109514

  4. Viral activities and life cycles in deep subseafloor sediments.

    PubMed

    Engelhardt, Tim; Orsi, William D; Jørgensen, Bo Barker

    2015-12-01

    Viruses are highly abundant in marine subsurface sediments and can even exceed the number of prokaryotes. However, their activity and quantitative impact on microbial populations are still poorly understood. Here, we use gene expression data from published continental margin subseafloor metatranscriptomes to qualitatively assess viral diversity and activity in sediments up to 159 metres below seafloor (mbsf). Mining of the metatranscriptomic data revealed 4651 representative viral homologues (RVHs), representing 2.2% of all metatranscriptome sequence reads, which have close translated homology (average 77%, range 60-97% amino acid identity) to viral proteins. Archaea-infecting RVHs are exclusively detected in the upper 30 mbsf, whereas RVHs for filamentous inoviruses predominate in the deepest sediment layers. RVHs indicative of lysogenic phage-host interactions and lytic activity, notably cell lysis, are detected at all analysed depths and suggest a dynamic virus-host association in the marine deep biosphere studied here. Ongoing lytic viral activity is further indicated by the expression of clustered, regularly interspaced, short palindromic repeat-associated cascade genes involved in cellular defence against viral attacks. The data indicate the activity of viruses in subsurface sediment of the Peruvian margin and suggest that viruses indeed cause cell mortality and may play an important role in the turnover of subseafloor microbial biomass.

  5. A New Simple Dynamo Model for Stellar Activity Cycle

    NASA Astrophysics Data System (ADS)

    Yokoi, N.; Schmitt, D.; Pipin, V.; Hamba, F.

    2016-06-01

    A new simple dynamo model for stellar activity cycle is proposed. By considering an inhomogeneous flow effect on turbulence, it is shown that turbulent cross helicity (velocity-magnetic-field correlation) enters the expression of turbulent electromotive force as the coupling coefficient for the mean absolute vorticity. This makes the present model different from the current α-Ω-type models in two main ways. First, in addition to the usual helicity (α) and turbulent magnetic diffusivity (β) effects, we consider the cross-helicity effect as a key ingredient of the dynamo process. Second, the spatiotemporal evolution of cross helicity is solved simultaneously with the mean magnetic fields. The basic scenario is as follows. In the presence of turbulent cross helicity, the toroidal field is induced by the toroidal rotation. Then, as in usual models, the α effect generates the poloidal field from the toroidal one. This induced poloidal field produces a turbulent cross helicity whose sign is opposite to the original one (negative production). With this cross helicity of the reversed sign, a reversal in field configuration starts. Eigenvalue analyses of the simplest possible model give a butterfly diagram, which confirms the above scenario and the equatorward migrations, the phase relationship between the cross helicity and magnetic fields. These results suggest that the oscillation of the turbulent cross helicity is a key for the activity cycle. The reversal of the cross helicity is not the result of the magnetic-field reversal, but the cause of the latter. This new model is expected to open up the possibility of the mean-field or turbulence closure dynamo approaches.

  6. A New Simple Dynamo Model for Stellar Activity Cycle

    NASA Astrophysics Data System (ADS)

    Yokoi, N.; Schmitt, D.; Pipin, V.; Hamba, F.

    2016-06-01

    A new simple dynamo model for stellar activity cycle is proposed. By considering an inhomogeneous flow effect on turbulence, it is shown that turbulent cross helicity (velocity–magnetic-field correlation) enters the expression of turbulent electromotive force as the coupling coefficient for the mean absolute vorticity. This makes the present model different from the current α–Ω-type models in two main ways. First, in addition to the usual helicity (α) and turbulent magnetic diffusivity (β) effects, we consider the cross-helicity effect as a key ingredient of the dynamo process. Second, the spatiotemporal evolution of cross helicity is solved simultaneously with the mean magnetic fields. The basic scenario is as follows. In the presence of turbulent cross helicity, the toroidal field is induced by the toroidal rotation. Then, as in usual models, the α effect generates the poloidal field from the toroidal one. This induced poloidal field produces a turbulent cross helicity whose sign is opposite to the original one (negative production). With this cross helicity of the reversed sign, a reversal in field configuration starts. Eigenvalue analyses of the simplest possible model give a butterfly diagram, which confirms the above scenario and the equatorward migrations, the phase relationship between the cross helicity and magnetic fields. These results suggest that the oscillation of the turbulent cross helicity is a key for the activity cycle. The reversal of the cross helicity is not the result of the magnetic-field reversal, but the cause of the latter. This new model is expected to open up the possibility of the mean-field or turbulence closure dynamo approaches.

  7. [Suppression of cycling activity in sheep using parenteral progestagen treatment].

    PubMed

    Janett, F; Camponovo, L; Lanker, U; Hässig, M; Thun, R

    2004-03-01

    The objective of this study was to evaluate the effect of two synthetic progestagen preparations Chlormadinone acetate (CAP, Chronosyn, Veterinaria AG Zürich) and Medroxyprogesterone acetate (MPA, Nadigest, G Streuli & Co. Uznach) on cycling activity and fertility in sheep. A flock of 28 non pregnant white alpine sheep was randomly divided into three groups, A (n = 10), B (n = 9) and C (n = 9). During a period of 4 weeks the cycling activity was confirmed by blood progesterone analysis. Thereafter, the animals of group A were treated with 50 mg CAP, those of group B with 140 mg MPA and those of group C with physiological saline solution. All injections were given intramuscularly. Suppression of endogenous progesterone secretion lasted from 28 to 49 days (mean = 39 days) in group A and from 42 to 70 days (mean = 50 days) in group B. The synchronization effect of both preparations was unsatisfactory as the occurrence of first estrus was distributed over a period of 3 weeks in group A and 4 weeks in group B. These findings could also be confirmed by the lambing period which lasted 52 days in group A and 36 days in group B. Control animals lambed within 9 days due to the synchronizing effect of the ram. The first fertile estrus was observed 36 days (group A) and 45 days (group B) after the treatment. In group A all 10 animals and in groups B and C 8 of 9 ewes each became pregnant. Parenteral progestagen application with CAP and MPA is a simple, safe and reversible method of estrus suppression in the sheep. The minimal suppressive duration of 4 (CAP) and 5 weeks (MPA) is not sufficient when a period of 3 months (alpine pasture period) is desired.

  8. Discovery of HDAC Inhibitors with Potent Activity Against Multiple Malaria Parasite Life Cycle Stages

    PubMed Central

    Hansen, Finn K.; Sumanadasa, Subathdrage D. M.; Stenzel, Katharina; Duffy, Sandra; Meister, Stephan; Marek, Linda; Schmetter, Rebekka; Kuna, Krystina; Hamacher, Alexandra; Mordmüller, Benjamin; Kassack, Matthias U.; Winzeler, Elizabeth A.; Avery, Vicky M.; Andrews, Katherine T.; Kurz, Thomas

    2015-01-01

    In this work we investigated the antiplasmodial activity of a series of HDAC inhibitors containing an alkoxyamide connecting-unit linker region. HDAC inhibitor 1a (LMK235), previously shown to be a novel and specific inhibitor of human HDAC4 and 5, was used as a starting point to rapidly construct a mini-library of HDAC inhibitors using a straightforward solid-phase supported synthesis. Several of these novel HDAC inhibitors were found to have potent in vitro activity against asexual stage P. falciparum malaria parasites. Representative compounds were shown to hyperacetylate P. falciparum histones and to inhibit deacetylase activity of recombinant PfHDAC1 and P. falciparum nuclear extracts. All compounds were also screened in vitro for activity against P. berghei exo-erythrocytic stages and selected compounds were further tested against late stage (IV and V) P. falciparum gametocytes. Of note, some compounds showed nanomolar activity against all three life cycle stages tested (asexual, exo-erythrocytic and gametocyte stages) and several compounds displayed significantly increased parasite selectivity compared to the reference HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). These data suggest that it may be possible to develop HDAC inhibitors that target multiple malaria parasite life cycle stages. PMID:24904967

  9. The role of the cell cycle in the cellular uptake of folate-modified poly(l-amino acid) micelles in a cell population

    NASA Astrophysics Data System (ADS)

    Tang, Jihui; Liu, Ziwei; Ji, Fenqi; Li, Yao; Liu, Junjie; Song, Jian; Li, Jun; Zhou, Jianping

    2015-12-01

    Nanoparticles are widely recognized as a vehicle for tumor-targeted therapies. There are many factors that can influence the uptake of nanoparticles, such as the size of the nanoparticles, and/or their shape, elasticity, surface charge and even the cell cycle phase. However, the influence of the cell cycle on the active targeting of a drug delivery system has been unknown until now. In this study, we initially investigated the folate receptor α (FR-α) expression in different phases of HeLa cells by flow cytometric and immunocytochemical methods. The results obtained showed that FR-α expression was cell cycle-dependent, i.e. the S cells' folate receptor expression was the highest as the cell progressed through its cycle. Then, we used folate modified poly(l-amino acid) micelles (FA-PM) as an example to investigate the influence of the cell cycle on the active targeting drug delivery system. The results obtained indicated that the uptake of FA-PM by cells was influenced by the cell cycle phase, and the S cells took up the greatest number of folate conjugated nanoparticles. Our findings suggest that future studies on ligand-mediated active targeting preparations should consider the cell cycle, especially when this system is used for a cell cycle-specific drug.

  10. rre37 Overexpression Alters Gene Expression Related to the Tricarboxylic Acid Cycle and Pyruvate Metabolism in Synechocystis sp. PCC 6803

    PubMed Central

    Iijima, Hiroko; Watanabe, Atsuko; Takanobu, Junko; Hirai, Masami Yokota; Osanai, Takashi

    2014-01-01

    The tricarboxylic acid (TCA) cycle and pyruvate metabolism of cyanobacteria are unique and important from the perspectives of biology and biotechnology research. Rre37, a response regulator induced by nitrogen depletion, activates gene expression related to sugar catabolism. Our previous microarray analysis has suggested that Rre37 controls the transcription of genes involved in sugar catabolism, pyruvate metabolism, and the TCA cycle. In this study, quantitative real-time PCR was used to measure the transcript levels of 12 TCA cycle genes and 13 pyruvate metabolism genes. The transcripts of 6 genes (acnB, icd, ppc, pyk1, me, and pta) increased after 4 h of nitrogen depletion in the wild-type GT strain but the induction was abolished by rre37 overexpression. The repression of gene expression of fumC, ddh, and ackA caused by nitrogen depletion was abolished by rre37 overexpression. The expression of me was differently affected by rre37 overexpression, compared to the other 24 genes. These results indicate that Rre37 differently controls the genes of the TCA cycle and pyruvate metabolism, implying the key reaction of the primary in this unicellular cyanobacterium. PMID:25614900

  11. Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum.

    PubMed

    Amador-Noguez, Daniel; Feng, Xiao-Jiang; Fan, Jing; Roquet, Nathaniel; Rabitz, Herschel; Rabinowitz, Joshua D

    2010-09-01

    Obligatory anaerobic bacteria are major contributors to the overall metabolism of soil and the human gut. The metabolic pathways of these bacteria remain, however, poorly understood. Using isotope tracers, mass spectrometry, and quantitative flux modeling, here we directly map the metabolic pathways of Clostridium acetobutylicum, a soil bacterium whose major fermentation products include the biofuels butanol and hydrogen. While genome annotation suggests the absence of most tricarboxylic acid (TCA) cycle enzymes, our results demonstrate that this bacterium has a complete, albeit bifurcated, TCA cycle; oxaloacetate flows to succinate both through citrate/alpha-ketoglutarate and via malate/fumarate. Our investigations also yielded insights into the pathways utilized for glucose catabolism and amino acid biosynthesis and revealed that the organism's one-carbon metabolism is distinct from that of model microbes, involving reversible pyruvate decarboxylation and the use of pyruvate as the one-carbon donor for biosynthetic reactions. This study represents the first in vivo characterization of the TCA cycle and central metabolism of C. acetobutylicum. Our results establish a role for the full TCA cycle in an obligatory anaerobic organism and demonstrate the importance of complementing genome annotation with isotope tracer studies for determining the metabolic pathways of diverse microbes.

  12. Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells.

    PubMed

    So, Wai Wing; Liu, Wai Nam; Leung, Kwok Nam

    2015-08-18

    Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G0/G1 cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-XL protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity.

  13. Identification of novel Saccharomyces cerevisiae proteins with nuclear export activity: cell cycle-regulated transcription factor ace2p shows cell cycle-independent nucleocytoplasmic shuttling.

    PubMed

    Jensen, T H; Neville, M; Rain, J C; McCarthy, T; Legrain, P; Rosbash, M

    2000-11-01

    Nuclear export of proteins containing leucine-rich nuclear export signals (NESs) is mediated by the NES receptor CRM1/Crm1p. We have carried out a yeast two-hybrid screen with Crm1p as a bait. The Crm1p-interacting clones were subscreened for nuclear export activity in a visual assay utilizing the Crm1p-inhibitor leptomycin B (LMB). This approach identified three Saccharomyces cerevisiae proteins not previously known to have nuclear export activity. These proteins are the 5' RNA triphosphatase Ctl1p, the cell cycle-regulated transcription factor Ace2p, and a protein encoded by the previously uncharacterized open reading frame YDR499W. Mutagenesis analysis show that YDR499Wp contains an NES that conforms to the consensus sequence for leucine-rich NESs. Mutagenesis of Ctl1p and Ace2p were unable to identify specific NES residues. However, a 29-amino-acid region of Ace2p, rich in hydrophobic residues, contains nuclear export activity. Ace2p accumulates in the nucleus at the end of mitosis and activates early-G(1)-specific genes. We now provide evidence that Ace2p is nuclear not only in late M-early G(1) but also during other stages of the cell cycle. This feature of Ace2p localization explains its ability to activate genes such as CUP1, which are not expressed in a cell cycle-dependent manner.

  14. The sequence of learning cycle activities in high school chemistry

    NASA Astrophysics Data System (ADS)

    Abraham, Michael R.; Renner, John W.

    The sequence of the three phases of two high school learning cycles in chemistry was altered in order to: (I ) give insights into the factors which account for the success of the learning cycle, (2) serve as an indirect test of the association between Piaget's theory and the learning cycle, and (3) to compare the learning cycle with traditional instruction. Each of the six sequences (one n o d and five altered) was studied with content and atritudc measures. The outcomes of the study supported the contention that the normal learning cycle sequence is the optimum sequence for achievement of content knowledge.

  15. High temperature abatement of acid gases from waste incineration. Part II: Comparative life cycle assessment study

    SciTech Connect

    Biganzoli, Laura; Racanella, Gaia; Marras, Roberto; Rigamonti, Lucia

    2015-01-15

    Highlights: • Two scenarios of acid gases removal in WTE plants were compared in an LCA study. • A detailed inventory based on primary data has been reported for the production of the new dolomitic sorbent. • Results show that the comparison between the two scenarios does not show systematic differences. • The potential impacts are reduced only if there is an increase in the energy efficiency of the WTE plant. - Abstract: The performances of a new dolomitic sorbent, named Depurcal®MG, to be directly injected at high temperature in the combustion chamber of Waste-To-Energy (WTE) plants as a preliminary stage of deacidification, were experimentally tested during full-scale commercial operation. Results of the experimentations were promising, and have been extensively described in Biganzoli et al. (2014). This paper reports the Life Cycle Assessment (LCA) study performed to compare the traditional operation of the plants, based on the sole sodium bicarbonate feeding at low temperature, with the new one, where the dolomitic sorbent is injected at high temperature. In the latter the sodium bicarbonate is still used, but at lower rate because of the decreased load of acid gases entering the flue gas treatment line. The major goal of the LCA was to make sure that a burden shifting was not taking place somewhere in the life cycle stages, as it might be the case when a new material is used in substitution of another one. According to the comparative approach, only the processes which differ between the two operational modes were included in the system boundaries. They are the production of the two reactants and the treatment of the corresponding solid residues arising from the neutralisation of acid gases. The additional CO{sub 2} emission at the stack of the WTE plant due to the activation of the sodium bicarbonate was also included in the calculation. Data used in the modelling of the foreground system are primary, derived from the experimental tests described in

  16. Cell cycle-dependent activity of the volume- and Ca2+-activated anion currents in Ehrlich lettre ascites cells.

    PubMed

    Klausen, Thomas Kjaer; Bergdahl, Andreas; Hougaard, Charlotte; Christophersen, Palle; Pedersen, Stine F; Hoffmann, Else K

    2007-03-01

    Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current decreased in G1 and increased in early S phase, compared to that in G0. The isotonic steady-state current, which seems to be predominantly VRAC, also decreased in G1, and increased again in early S phase, to a level similar to that in G0. In contrast, the maximal CaCC current (500 nM free Ca2+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle-dependent changes in the capacity for conductive Cl- transport. It is suggested that in ELA cells, entrance into the S phase requires an increase in VRAC activity and/or an increased potential for regulatory volume decrease (RVD), and at the same time a decrease in CaCC magnitude. PMID:17111356

  17. Exercise, physical activity, and exertion over the business cycle.

    PubMed

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes.

  18. Exercise, physical activity, and exertion over the business cycle.

    PubMed

    Colman, Gregory; Dave, Dhaval

    2013-09-01

    Shifts in time and income constraints over economic expansions and contractions would be expected to affect individuals' behaviors. We explore the impact of the business cycle on individuals' exercise, time use, and total physical exertion, utilizing information on 112,000 individual records from the 2003-2010 American Time Use Surveys. In doing so, we test a key causal link that has been hypothesized in the relation between unemployment and health, but not heretofore assessed. Using more precise measures of exercise (and other activities) than previous studies, we find that as work-time decreases during a recession, recreational exercise, TV-watching, sleeping, childcare, and housework increase. This, however, does not compensate for the decrease in work-related exertion due to job-loss, and total physical exertion declines. These effects are strongest among low-educated men, which is validating given that employment in the Great Recession has declined most within manufacturing, mining, and construction. We also find evidence of intra-household spillover effects, wherein individuals respond to shifts in spousal employment conditional on their own labor supply. The decrease in total physical activity during recessions is especially problematic for vulnerable populations concentrated in boom-and-bust industries, and may have longer-term effects on obesity and related health outcomes. PMID:23906116

  19. ENZYME ACTIVITIES DURING THE ASEXUAL CYCLE OF NEUROSPORA CRASSA

    PubMed Central

    Stine, G. J.

    1968-01-01

    Three enzymes, (a) nicotinamide adenine diphosphate-dependent glutamic dehydrogenase (NAD enzyme), (b) nictoinamide adenine triphosphate-dependent glutamic dehydrogenase (NADP enzyme), and (c) nicotinamide-adenine dinucleotidase (NADase), were measured in separate extracts of Neurospora crassa grown in Vogel's medium N and medium N + glutamate. Specific activities and total units per culture of each enzyme were determined at nine separate intervals phased throughout the asexual cycle. The separate dehydrogenases were lowest in the conidia, increased slowly during germination, and increased rapidly during logarithmic mycelial growth. The amounts of these enzymes present during germination were small when compared with those found later during the production of the conidiophores. The NAD enzyme may be necessary for pregermination synthesis. The NADP-enzyme synthesis was associated with the appearance of the germ tube. Although higher levels of the dehydrogenases in the conidiophores resulted in more enzyme being found in the differentiated conidia, the rate of germination was uneffected. The greatest activity for the NADase enzyme was associated with the conidia, early phases of germination, and later production of new conidia. NADase decreased significantly with the onset of logarithmic growth, remained low during the differentiation of conidiophores, and increased considerably as the conidiophores aged. PMID:4384627

  20. High pressure sulfuric acid decomposition experiments for the sulfur-iodine thermochemical cycle.

    SciTech Connect

    Velasquez, Carlos E; Reay, Andrew R.; Andazola, James C.; Naranjo, Gerald E.; Gelbard, Fred

    2005-09-01

    A series of three pressurized sulfuric acid decomposition tests were performed to (1) obtain data on the fraction of sulfuric acid catalytically converted to sulfur dioxide, oxygen, and water as a function of temperature and pressure, (2) demonstrate real-time measurements of acid conversion for use as process control, (3) obtain multiple measurements of conversion as a function of temperature within a single experiment, and (4) assess rapid quenching to minimize corrosion of metallic components by undecomposed acid. All four of these objectives were successfully accomplished. This report documents the completion of the NHI milestone on high pressure H{sub 2}SO{sub 4} decomposition tests for the Sulfur-Iodine (SI) thermochemical cycle project. All heated sections of the apparatus, (i.e. the boiler, decomposer, and condenser) were fabricated from Hastelloy C276. A ceramic acid injection tube and a ceramic-sheathed thermocouple were used to minimize corrosion of hot liquid acid on the boiler surfaces. Negligible fracturing of the platinum on zirconia catalyst was observed in the high temperature decomposer. Temperature measurements at the exit of the decomposer and at the entry of the condenser indicated that the hot acid vapors were rapidly quenched from about 400 C to less than 20 C within a 14 cm length of the flow path. Real-time gas flow rate measurements of the decomposition products provided a direct measurement of acid conversion. Pressure in the apparatus was preset by a pressure-relief valve that worked well at controlling the system pressure. However, these valves sometimes underwent abrupt transitions that resulted in rapidly varying gas flow rates with concomitant variations in the acid conversion fraction.

  1. Lead-acid battery with improved cycle life and increased efficiency for lead leveling application and electric road vehicles

    NASA Astrophysics Data System (ADS)

    Winsel, A.; Schulz, J.; Guetlich, K. F.

    1983-11-01

    Lifetime and efficiency of lead acid batteries are discussed. A gas lift pump was used to prevent acid stratification and to reduce the charging factor (down to 1.03 to 1.05). A re-expansion method was applied and an expander depot and a compound separation were built in. Cycle life is increased from 700 cycles to 1690 cycles. Efficiency is increased by energy and time saving due to the reduced charging factor and by the use of a recombination stopper and a charge indicator with remote control. It is suggested that the lead acid system is still one of the best possibilities for electric road vehicle applications.

  2. Modulation of fatty acid metabolism and tricarboxylic acid cycle to enhance the lipstatin production through medium engineering in Streptomyces toxytricini.

    PubMed

    Kumar, Punit; Dubey, Kashyap Kumar

    2016-08-01

    This work investigated the potential of medium engineering to obtain maximum biomass, non-conventional carbon sources for lipstatin production and modulation of tricarboxylic acid (TCA) cycle to promote lipstatin synthesis. It was found that 2:3 carbon and nitrogen ratio, produced maximum biomass of 7.9g/L in growth medium and 6.6g/L in pre-seed medium. Among the studied non-conventional carbon sources i.e., soya flour 40g/L and sesame oil 30mL/L were found producing 1109.37mg/L (1.24-fold of control) and 1196.75mg/L (1.34-fold of control) lipstatin respectively. Supplementation of TCA cycle intermediates revealed that NADH and succinic acid showed lipstatin production to 1132.99mg/L and 1171.10mg/L respectively. Experimental outcome was validated in 7L bioreactor and produced 2242.63mg/L lipstatin which was ∼14% higher than shake flask. PMID:26897471

  3. Long-Range Solar Activity Predictions: A Reprieve from Cycle #24's Activity

    NASA Technical Reports Server (NTRS)

    Richon, K.; Schatten, K.

    2003-01-01

    We discuss the field of long-range solar activity predictions and provide an outlook into future solar activity. Orbital predictions for satellites in Low Earth Orbit (LEO) depend strongly on exospheric densities. Solar activity forecasting is important in this regard, as the solar ultra-violet (UV) and extreme ultraviolet (EUV) radiations inflate the upper atmospheric layers of the Earth, forming the exosphere in which satellites orbit. Rather than concentrate on statistical, or numerical methods, we utilize a class of techniques (precursor methods) which is founded in physical theory. The geomagnetic precursor method was originally developed by the Russian geophysicist, Ohl, using geomagnetic observations to predict future solar activity. It was later extended to solar observations, and placed within the context of physical theory, namely the workings of the Sun s Babcock dynamo. We later expanded the prediction methods with a SOlar Dynamo Amplitude (SODA) index. The SODA index is a measure of the buried solar magnetic flux, using toroidal and poloidal field components. It allows one to predict future solar activity during any phase of the solar cycle, whereas previously, one was restricted to making predictions only at solar minimum. We are encouraged that solar cycle #23's behavior fell closely along our predicted curve, peaking near 192, comparable to the Schatten, Myers and Sofia (1996) forecast of 182+/-30. Cycle #23 extends from 1996 through approximately 2006 or 2007, with cycle #24 starting thereafter. We discuss the current forecast of solar cycle #24, (2006-2016), with a predicted smoothed F10.7 radio flux of 142+/-28 (1-sigma errors). This, we believe, represents a reprieve, in terms of reduced fuel costs, etc., for new satellites to be launched or old satellites (requiring reboosting) which have been placed in LEO. By monitoring the Sun s most deeply rooted magnetic fields; long-range solar activity can be predicted. Although a degree of uncertainty

  4. C-Myc Induced Compensated Cardiac Hypertrophy Increases Free Fatty Acid Utilization for the Citric Acid Cycle

    SciTech Connect

    Olson, Aaron; Ledee, Dolena; Iwamoto, Kate; Kajimoto, Masaki; O'Kelly-Priddy, Colleen M.; Isern, Nancy G.; Portman, Michael A.

    2013-02-01

    The protooncogene C-Myc (Myc) regulates cardiac hypertrophy. Myc promotes compensated cardiac function, suggesting that the operative mechanisms differ from those leading to heart failure. Myc regulation of substrate metabolism is a reasonable target, as Myc alters metabolism in other tissues. We hypothesize that Myc-induced shifts in substrate utilization signal and promote compensated hypertrophy. We used cardiac specific Myc-inducible C57/BL6 male mice between 4-6 months old that develop hypertrophy with tamoxifen (tam). Isolated working hearts and 13Carbon (13C )-NMR were used to measure function and fractional contributions (Fc) to the citric acid cycle by using perfusate containing 13C-labeled free fatty acids, acetoacetate, lactate, unlabeled glucose and insulin. Studies were performed at pre-hypertrophy (3-days tam, 3dMyc), established hypertrophy (7-days tam, 7dMyc) or vehicle control (cont). Non-transgenic siblings (NTG) received 7-days tam or vehicle to assess drug effect. Hypertrophy was confirmed by echocardiograms and heart weights. Western blots were performed on key metabolic enzymes. Hypertrophy occurred in 7dMyc only. Cardiac function did not differ between groups. Tam alone did not affect substrate contribution in NTG. Substrate utilization was not significantly altered in 3dMyc versus cont. The free fatty acid FC was significantly greater in 7dMyc vs cont with decreased unlabeled Fc, which is predominately exogenous glucose. Free fatty acid flux to the citric acid cycle increased while lactate flux was diminished in 7dMyc compared to cont. Total protein levels of a panel of key metabolic enzymes were unchanged; however total protein O-GlcNAcylation was increased in 7dMyc. Substrate utilization changes did not precede hypertrophy; therefore they are not the primary signal for cardiac growth in this model. Free fatty acid utilization and oxidation increase at established hypertrophy. Understanding the mechanisms whereby this change maintained

  5. A Krebs Cycle Component Limits Caspase Activation Rate through Mitochondrial Surface Restriction of CRL Activation.

    PubMed

    Aram, Lior; Braun, Tslil; Braverman, Carmel; Kaplan, Yosef; Ravid, Liat; Levin-Zaidman, Smadar; Arama, Eli

    2016-04-01

    How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids. In vitro and in vivo evidence suggests that this interaction occurs on the mitochondrial surface, thereby limiting the source of CRL3 complex activation to the vicinity of this organelle and reducing the potential rate of caspase activation by at least 60%. Domain swapping between A-Sβ and the GTP-specific SCSβ (G-Sβ), which functions redundantly in the Krebs cycle, show that the metabolic and structural roles of A-Sβ in spermatids can be uncoupled, highlighting a moonlighting function of this Krebs cycle component in CRL activation.

  6. A Krebs Cycle Component Limits Caspase Activation Rate through Mitochondrial Surface Restriction of CRL Activation.

    PubMed

    Aram, Lior; Braun, Tslil; Braverman, Carmel; Kaplan, Yosef; Ravid, Liat; Levin-Zaidman, Smadar; Arama, Eli

    2016-04-01

    How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids. In vitro and in vivo evidence suggests that this interaction occurs on the mitochondrial surface, thereby limiting the source of CRL3 complex activation to the vicinity of this organelle and reducing the potential rate of caspase activation by at least 60%. Domain swapping between A-Sβ and the GTP-specific SCSβ (G-Sβ), which functions redundantly in the Krebs cycle, show that the metabolic and structural roles of A-Sβ in spermatids can be uncoupled, highlighting a moonlighting function of this Krebs cycle component in CRL activation. PMID:27052834

  7. Commercial Activated Carbon for the Catalytic Production of Hydrogen via the Sulfur-Iodine Thermochemical Water Splitting Cycle

    SciTech Connect

    Daniel M. Ginosar; Lucia M. Petkovic; Kyle C. Burch

    2011-07-01

    Eight activated carbon catalysts were examined for their catalytic activity to decompose hydroiodic acid (HI) to produce hydrogen; a key reaction in the sulfur-iodine (S-I) thermochemical water splitting cycle. Activity was examined under a temperature ramp from 473 to 773 K. No statistically significant correlation was found between catalyst sample properties and catalytic activity. Four of the eight samples were examined for one week of continuous operation at 723 K. All samples appeared to be stable over the period of examination.

  8. Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.

    PubMed

    Burrage, Lindsay C; Jain, Mahim; Gandolfo, Laura; Lee, Brendan H; Nagamani, Sandesh C S

    2014-01-01

    Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. PMID:25042691

  9. Genetic and biochemical interactions involving tricarboxylic acid cycle (TCA) function using a collection of mutants defective in all TCA cycle genes.

    PubMed

    Przybyla-Zawislak, B; Gadde, D M; Ducharme, K; McCammon, M T

    1999-05-01

    The eight enzymes of the tricarboxylic acid (TCA) cycle are encoded by at least 15 different nuclear genes in Saccharomyces cerevisiae. We have constructed a set of yeast strains defective in these genes as part of a comprehensive analysis of the interactions among the TCA cycle proteins. The 15 major TCA cycle genes can be sorted into five phenotypic categories on the basis of their growth on nonfermentable carbon sources. We have previously reported a novel phenotype associated with mutants defective in the IDH2 gene encoding the Idh2p subunit of the NAD+-dependent isocitrate dehydrogenase (NAD-IDH). Null and nonsense idh2 mutants grow poorly on glycerol, but growth can be enhanced by extragenic mutations, termed glycerol suppressors, in the CIT1 gene encoding the TCA cycle citrate synthase and in other genes of oxidative metabolism. The TCA cycle mutant collection was utilized to search for other genes that can suppress idh2 mutants and to identify TCA cycle genes that display a similar suppressible growth phenotype on glycerol. Mutations in 7 TCA cycle genes were capable of functioning as suppressors for growth of idh2 mutants on glycerol. The only other TCA cycle gene to display the glycerol-suppressor-accumulation phenotype was IDH1, which encodes the companion Idh1p subunit of NAD-IDH. These results provide genetic evidence that NAD-IDH plays a unique role in TCA cycle function.

  10. Citric acid induces cell-cycle arrest and apoptosis of human immortalized keratinocyte cell line (HaCaT) via caspase- and mitochondrial-dependent signaling pathways.

    PubMed

    Ying, Tsung-Ho; Chen, Chia-Wei; Hsiao, Yu-Ping; Hung, Sung-Jen; Chung, Jing-Gung; Yang, Jen-Hung

    2013-10-01

    Citric acid is an alpha-hydroxyacid (AHA) widely used in cosmetic dermatology and skincare products. However, there is concern regarding its safety for the skin. In this study, we investigated the cytotoxic effects of citric acid on the human keratinocyte cell line HaCaT. HaCaT cells were treated with citric acid at 2.5-12.5 mM for different time periods. Cell-cycle arrest and apoptosis were investigated by 4,6-diamidino-2-phenylindole dihydrochloride (DAPI) staining, flow cytometry, western blot and confocal microscopy. Citric acid not only inhibited proliferation of HaCaT cells in a dose-dependent manner, but also induced apoptosis and cell cycle-arrest at the G2/M phase (before 24 h) and S phase (after 24 h). Citric acid increased the level of Bcl-2-associated X protein (BAX) and reduced the levels of B-cell lymphoma-2 (BCL-2), B-cell lymphoma-extra large (BCL-XL) and activated caspase-9 and caspase-3, which subsequently induced apoptosis via caspase-dependent and caspase-independent pathways. Citric acid also activated death receptors and increased the levels of caspase-8, activated BH3 interacting-domain death agonist (BID) protein, Apoptosis-inducing factor (AIF), and Endonuclease G (EndoG). Therefore, citric acid induces apoptosis through the mitochondrial pathway in the human keratinocyte cell line HaCaT. The study results suggest that citric acid is cytotoxic to HaCaT cells via induction of apoptosis and cell-cycle arrest in vitro.

  11. A Summary of Closed Brayton Cycle Development Activities at NASA

    NASA Technical Reports Server (NTRS)

    Mason, Lee S.

    2009-01-01

    NASA has been involved in the development of Closed Brayton Cycle (CBC) power conversion technology since the 1960's. CBC systems can be coupled to reactor, isotope, or solar heat sources and offer the potential for high efficiency, long life, and scalability to high power. In the 1960's and 1970's, NASA and industry developed the 10 kW Brayton Rotating Unit (BRU) and the 2 kW mini-BRU demonstrating technical feasibility and performance, In the 1980's, a 25 kW CBC Solar Dynamic (SD) power system option was developed for Space Station Freedom and the technology was demonstrated in the 1990's as part of the 2 kW SO Ground Test Demonstration (GTD). Since the early 2000's, NASA has been pursuing CBC technology for space reactor applications. Before it was cancelled, the Jupiter Icy Moons Orbiter (HMO) mission was considering a 100 kWclass CBC system coupled to a gas-cooled fission reactor. Currently, CBC technology is being explored for Fission Surface Power (FSP) systems to provide base power on the moon and Mars. These recent activities have resulted in several CBC-related technology development projects including a 50 kW Alternator Test Unit, a 20 kW Dual Brayton Test Loop, a 2 kW Direct Drive Gas Brayton Test Loop, and a 12 kW FSP Power Conversion Unit design.

  12. Quantifying promoter activity during the developmental cycle of Chlamydia trachomatis

    PubMed Central

    Cong, Yanguang; Gao, Leiqiong; Zhang, Yan; Xian, Yuqi; Hua, Ziyu; Elaasar, Hiba; Shen, Li

    2016-01-01

    Chlamydia trachomatis is an important human pathogen that undergoes a characteristic development cycle correlating with stage-specific gene expression profiles. Taking advantage of recent developments in the genetic transformation in C. trachomatis, we constructed a versatile green fluorescent protein (GFP) reporter system to study the development-dependent function of C. trachomatis promoters in an attempt to elucidate the mechanism that controls C. trachomatis adaptability. We validated the use of the GFP reporter system by visualizing the activity of an early euo gene promoter. Additionally, we uncovered a new ompA promoter, which we named P3, utilizing the GFP reporter system combined with 5′ rapid amplification of cDNA ends (RACE), in vitro transcription assays, real-time quantitative RT-PCR (RT-qPCR), and flow cytometry. Mutagenesis of the P3 region verifies that P3 is a new class of C. trachomatis σ66-dependent promoter, which requires an extended −10 TGn motif for transcription. These results corroborate complex developmentally controlled ompA expression in C. trachomatis. The exploitation of genetically labeled C. trachomatis organisms with P3-driven GFP allows for the observation of changes in ompA expression in response to developmental signals. The results of this study could be used to complement previous findings and to advance understanding of C. trachomatis genetic expression. PMID:27263495

  13. A Solar Cycle Dependence of Nonlinearity in Magnetospheric Activity

    SciTech Connect

    Johnson, Jay R; Wing, Simon

    2005-03-08

    The nonlinear dependencies inherent to the historical K(sub)p data stream (1932-2003) are examined using mutual information and cumulant based cost as discriminating statistics. The discriminating statistics are compared with surrogate data streams that are constructed using the corrected amplitude adjustment Fourier transform (CAAFT) method and capture the linear properties of the original K(sub)p data. Differences are regularly seen in the discriminating statistics a few years prior to solar minima, while no differences are apparent at the time of solar maximum. These results suggest that the dynamics of the magnetosphere tend to be more linear at solar maximum than at solar minimum. The strong nonlinear dependencies tend to peak on a timescale around 40-50 hours and are statistically significant up to one week. Because the solar wind driver variables, VB(sub)s and dynamical pressure exhibit a much shorter decorrelation time for nonlinearities, the results seem to indicate that the nonlinearity is related to internal magnetospheric dynamics. Moreover, the timescales for the nonlinearity seem to be on the same order as that for storm/ring current relaxation. We suggest that the strong solar wind driving that occurs around solar maximum dominates the magnetospheric dynamics suppressing the internal magnetospheric nonlinearity. On the other hand, in the descending phase of the solar cycle just prior to solar minimum, when magnetospheric activity is weaker, the dynamics exhibit a significant nonlinear internal magnetospheric response that may be related to increased solar wind speed.

  14. Synthesis of cellulose by Acetobacter xylinum. VI. Growth on citric acid-cycle intermediates.

    PubMed

    GROMET-ELHANAN, Z; HESTRIN, S

    1963-02-01

    Gromet-Elhanan, Zippora (The Hebrew University, Jerusalem, Israel) and Shlomo Hestrin. Synthesis of cellulose by Acetobacter xylinum. VI. Growth on citric acid-cycle intermediates. J. Bacteriol. 85:284-292. 1963.-Acetobacter xylinum could be made to grow on ethanol, acetate, succinate, or l-malate. The growth was accompanied by formation of opaque leathery pellicles on the surface of the growth medium. These pellicles were identified as cellulose on the basis of their chemical properties, solubility behavior, and infrared absorption spectra. Washed-cell suspensions prepared from cultures grown on ethanol or the organic acids, in contrast to washed sugar-grown cells, were able to transform citric-cycle intermediates into cellulose. The variations in the substrate spectrum of cellulose synthesis between sugar-grown cells and organic acids-grown cells were found to be correlated with differences in the oxidative capacity of the cells. The significance of the findings that A. xylinum could be made to grow on ethanol on complex as well as synthetic media is discussed from the viewpoint of the whole pattern of Acetobacter classification.

  15. Cinnamic acid derivatives induce cell cycle arrest in carcinoma cell lines.

    PubMed

    Sova, Matej; Žižak, Željko; Stanković, Jelena A Antic; Prijatelj, Matevž; Turk, Samo; Juranić, Zorica D; Mlinarič-Raščan, Irena; Gobec, Stanislav

    2013-08-01

    Cinnamic acid derivatives can be found in plant material, and they possess a remarkable variety of biological effects. In the present study, we have investigated the cytotoxic effects of representative cinnamic acid esters and amides. The cytotoxicity was determined by MTT test on human cervix adenocarcinoma (HeLa), myelogenous leukemia (K562), malignant melanoma (Fem-x), and estrogen-receptor-positive breast cancer (MCF-7) cells, versus peripheral blood mononuclear cells (PBMCs) without or with the addition of the plant lectin phytohemaglutinin (PHA). The compounds tested showed significant cytotoxicity (IC50s between 42 and 166 µM) and furthermore selectivity of these cytotoxic effects on the malignant cell lines versus the PBMCs was also seen, especially when electron-withdrawing groups, such as a cyano group (compound 5), were present on the aromatic rings of the alcohol or amine parts of the cinnamic acid derivatives. The additional study on cell cycle phase distribution indicated that novel cinnamic acid derivatives inhibit cell growth by induction of cell death. Thus, cinnamic acids derivatives represent important lead compounds for further development of antineoplastic agents.

  16. An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis.

    PubMed

    Castro-Garza, Jorge; González-Salazar, Francisco; Quinn, Frederick D; Karls, Russell K; De La Garza-Salinas, Laura Hermila; Guzmán-de la Garza, Francisco J; Vargas-Villarreal, Javier

    2016-01-01

    Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease. PMID:26948102

  17. An acidic sphingomyelinase Type C activity from Mycobacterium tuberculosis.

    PubMed

    Castro-Garza, Jorge; González-Salazar, Francisco; Quinn, Frederick D; Karls, Russell K; De La Garza-Salinas, Laura Hermila; Guzmán-de la Garza, Francisco J; Vargas-Villarreal, Javier

    2016-01-01

    Sphingomyelinases (SMases) catalyze the hydrolysis of sphingomyelin to ceramide and phosphorylcholine. Sphingolipids are recognized as diverse and dynamic regulators of a multitude of cellular processes mediating cell cycle control, differentiation, stress response, cell migration, adhesion, and apoptosis. Bacterial SMases are virulence factors for several species of pathogens. Whole cell extracts of Mycobacterium tuberculosis strains H37Rv and CDC1551 were assayed using [N-methyl-(14)C]-sphingomyelin as substrate. Acidic Zn(2+)-dependent SMase activity was identified in both strains. Peak SMase activity was observed at pH 5.5. Interestingly, overall SMase activity levels from CDC1551 extracts are approximately 1/3 of those of H37Rv. The presence of exogenous SMase produced by M. tuberculosis during infection may interfere with the normal host inflammatory response thus allowing the establishment of infection and disease development. This Type C activity is different from previously identified M. tuberculosis SMases. Defining the biochemical characteristics of M. tuberculosis SMases helps to elucidate the roles that these enzymes play during infection and disease.

  18. "JCE" Classroom Activity #109: My Acid Can Beat Up Your Acid!

    ERIC Educational Resources Information Center

    Putti, Alice

    2011-01-01

    In this guided-inquiry activity, students investigate the ionization of strong and weak acids. Bead models are used to study acid ionization on a particulate level. Students analyze seven strong and weak acid models and make generalizations about the relationship between acid strength and dissociation. (Contains 1 table and 2 figures.)

  19. Gluconeogenesis is associated with high rates of tricarboxylic acid and pyruvate cycling in fasting northern elephant seals.

    PubMed

    Champagne, Cory D; Houser, Dorian S; Fowler, Melinda A; Costa, Daniel P; Crocker, Daniel E

    2012-08-01

    Animals that endure prolonged periods of food deprivation preserve vital organ function by sparing protein from catabolism. Much of this protein sparing is achieved by reducing metabolic rate and suppressing gluconeogenesis while fasting. Northern elephant seals (Mirounga angustirostris) endure prolonged fasts of up to 3 mo at multiple life stages. During these fasts, elephant seals maintain high levels of activity and energy expenditure associated with breeding, reproduction, lactation, and development while maintaining rates of glucose production typical of a postabsorptive mammal. Therefore, we investigated how fasting elephant seals meet the requirements of glucose-dependent tissues while suppressing protein catabolism by measuring the contribution of glycogenolysis, glycerol, and phosphoenolpyruvate (PEP) to endogenous glucose production (EGP) during their natural 2-mo postweaning fast. Additionally, pathway flux rates associated with the tricarboxylic acid (TCA) cycle were measured specifically, flux through phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate cycling. The rate of glucose production decreased during the fast (F(1,13) = 5.7, P = 0.04) but remained similar to that of postabsorptive mammals. The fractional contributions of glycogen, glycerol, and PEP did not change with fasting; PEP was the primary gluconeogenic precursor and accounted for ∼95% of EGP. This large contribution of PEP to glucose production occurred without substantial protein loss. Fluxes through the TCA cycle, PEPCK, and pyruvate cycling were higher than reported in other species and were the most energetically costly component of hepatic carbohydrate metabolism. The active pyruvate recycling fluxes detected in elephant seals may serve to rectify gluconeogeneic PEP production during restricted anaplerotic inflow in these fasting-adapted animals.

  20. Transport and cycling of iron and hydrogen peroxide in a freshwater stream: Influence of organic acids

    USGS Publications Warehouse

    Scott, D.T.; Runkel, R.L.; McKnight, Diane M.; Voelker, B.M.; Kimball, B.A.; Carraway, E.R.

    2003-01-01

    An in-stream injection of two dissolved organic acids (phthalic and aspartic acids) was performed in an acidic mountain stream to assess the effects of organic acids on Fe photoreduction and H2O2 cycling. Results indicate that the fate of Fe is dependent on a net balance of oxidative and reductive processes, which can vary over a distance of several meters due to changes in incident light and other factors. Solution phase photoreduction rates were high in sunlit reaches and were enhanced by the organic acid addition but were also limited by the amount of ferric iron present in the water column. Fe oxide photoreduction from the streambed and colloids within the water column resulted in an increase in the diurnal load of total filterable Fe within the experimental reach, which also responded to increases in light and organic acids. Our results also suggest that Fe(II) oxidation increased in response to the organic acids, with the result of offsetting the increase in Fe(II) from photoreductive processes. Fe(II) was rapidly oxidized to Fe(III) after sunset and during the day within a well-shaded reach, presumably through microbial oxidation. H2O 2, a product of dissolved organic matter photolysis, increased downstream to maximum concentrations of 0.25 ??M midday. Kinetic calculations show that the buildup of H2O2 is controlled by reaction with Fe(III), but this has only a small effect on Fe(II) because of the small formation rates of H2O2 compared to those of Fe(II). The results demonstrate the importance of incorporating the effects of light and dissolved organic carbon into Fe reactive transport models to further our understanding of the fate of Fe in streams and lakes.

  1. Polymorphisms in Genes of Tricarboxylic Acid Cycle Key Enzymes Are Associated with Early Recurrence of Hepatocellular Carcinoma.

    PubMed

    Wan, Shaogui; Wu, Yousheng; Zhou, Xingchun; Chen, Yibing; An, Jiaze; Yu, Xiaohe; Zhang, Huiqing; Yang, Hushan; Xing, Jinliang

    2015-01-01

    Alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes have been indicated in several malignancies, including hepatocellular carcinoma (HCC). They play an important role in the progression of cancer. However, the impact of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes on the recurrence of HCC has not been investigated. In this study, we genotyped 17 SNPs in genes encoding TCA cycle key enzymes and analyzed their association with recurrence-free survival (RFS) in a cohort of 492 Chinese HCC patients by Cox proportional hazard model and survival tree analysis. We identified 7 SNPs in SDHC, SDHD, FH, and IDH2 genes to be significantly associated with the RFS of HCC patients. Moreover, all these SNPs were associated with the early recurrence (within 2 years after surgery) risk of diseases. Cumulative effect analysis showed that these SNPs exhibited a dose-dependent effect on the overall and early recurrence. Further stratified analysis suggested that number of risk genotypes modified the protective effect on HCC recurrence conferred by transcatheter arterial chemoembolization treatment. Finally, the survival tree analysis revealed that SNP rs10789859 in SDHD gene was the primary factor contributing to HCC recurrence in our population. To the best of our knowledge, we for the first time observed the association between SNPs in genes encoding TCA cycle key enzymes and HCC recurrence risk. Further observational and functional studies are needed to validate our findings and generalize its clinical usage. PMID:25894340

  2. Antioxidant and antimicrobial activities of cinnamic acid derivatives.

    PubMed

    Sova, M

    2012-07-01

    Cinnamic acid is an organic acid occurring naturally in plants that has low toxicity and a broad spectrum of biological activities. In the search for novel pharmacologically active compounds, cinnamic acid derivatives are important and promising compounds with high potential for development into drugs. Many cinnamic acid derivatives, especially those with the phenolic hydroxyl group, are well-known antioxidants and are supposed to have several health benefits due to their strong free radical scavenging properties. It is also well known that cinnamic acid has antimicrobial activity. Cinnamic acid derivatives, both isolated from plant material and synthesized, have been reported to have antibacterial, antiviral and antifungal properties. Acids, esters, amides, hydrazides and related derivatives of cinnamic acid with such activities are here reviewed.

  3. Analysis of the citric acid cycle intermediates using gas chromatography-mass spectrometry.

    PubMed

    Kombu, Rajan S; Brunengraber, Henri; Puchowicz, Michelle A

    2011-01-01

    Researchers view analysis of the citric acid cycle (CAC) intermediates as a metabolomic approach to identifying unexpected correlations between apparently related and unrelated pathways of metabolism. Relationships of the CAC intermediates, as measured by their concentrations and relative ratios, offer useful information to understanding interrelationships between the CAC and metabolic pathways under various physiological and pathological conditions. This chapter presents a relatively simple method that is sensitive for simultaneously measuring concentrations of CAC intermediates (relative and absolute) and other related intermediates of energy metabolism using gas chromatography-mass spectrometry.

  4. Corrosive Resistant Diamond Coatings for the Acid Based Thermo-Chemical Hydrogen Cycles

    SciTech Connect

    Mark A. Prelas

    2009-06-25

    This project was designed to test diamond, diamond-like and related materials in environments that are expected in thermochemical cycles. Our goals were to build a High Temperature Corrosion Resistance (HTCR) test stand and begin testing the corrosive properties of barious materials in a high temperature acidic environment in the first year. Overall, we planned to test 54 samples each of diamond and diamond-like films (of 1 cm x 1 cm area). In addition we use a corrosion acceleration method by treating the samples at a temperature much larger than the expected operating temperature. Half of the samples will be treated with boron using the FEDOA process.

  5. Mathematical modelling of the citric acid cycle for the analysis of glutamine isotopomers from cerebellar astrocytes incubated with [1(-13)C]glucose.

    PubMed

    Merle, M; Martin, M; Villégier, A; Canioni, P

    1996-08-01

    A mathematical model of the citric acid cycle devoted to the analysis of 13C-NMR data was developed for determining the relative flux of molecules through the anaplerotic versus oxidative pathways and the relative pyruvate carboxylase versus pyruvate dehydrogenase activities. Different variants of the model were considered depending on the reversibility of the conversion of fumarate into malate and oxaloacetate. The model also included the possibility of orientation-conserved transfer of the four-carbon citric acid cycle intermediates, leading to conversion of succinyl-CoA C1 into either malate C1 or C4. It was used to analyse NMR data from glutamine isotopomers produced by cerebellar astrocytes incubated with [1-13C]glucose. Partial cycling (39%) between oxaloacetate and fumarate was evident from the analysis. Application of the model to glutamate isotopomers from granule cells incubated with [1-13C]glucose [Martin, M.. Portais, J.C.. Labouesse. J., Canioni. P, & Merle, M. (1993) Eur. J. Biochem. 217, 617-625] indicated that total cycling of oxaloacetate into fumarate was, in this case, required to get the best fit. The results emphasized some important differences in carbon metabolism between cerebellar astrocytes and granule cells concerning the sources of carbon fuelling the citric acid cycle and the carbon fluxes on different pathways.

  6. Acid phosphatase and protease activities in immobilized rat skeletal muscles

    NASA Technical Reports Server (NTRS)

    Witzmann, F. A.; Troup, J. P.; Fitts, R. H.

    1982-01-01

    The effect of hind-limb immobilization on selected Iysosomal enzyme activities was studied in rat hing-limb muscles composed primarily of type 1. 2A, or 2B fibers. Following immobilization, acid protease and acid phosphatase both exhibited signifcant increases in their activity per unit weight in all three fiber types. Acid phosphatase activity increased at day 14 of immobilization in the three muscles and returned to control levels by day 21. Acid protease activity also changed biphasically, displaying a higher and earlier rise than acid phosphatase. The pattern of change in acid protease, but not acid phosphatase, closely parallels observed muscle wasting. The present data therefore demonstrate enhanced proteolytic capacity of all three fiber types early during muscular atrophy. In addition, the data suggest a dependence of basal hydrolytic and proteolytic activities and their adaptive response to immobilization on muscle fiber composition.

  7. Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae.

    PubMed

    van Rossum, Harmen M; Kozak, Barbara U; Niemeijer, Matthijs S; Duine, Hendrik J; Luttik, Marijke A H; Boer, Viktor M; Kötter, Peter; Daran, Jean-Marc G; van Maris, Antonius J A; Pronk, Jack T

    2016-05-01

    Pyruvate and acetyl-coenzyme A, located at the interface between glycolysis and TCA cycle, are important intermediates in yeast metabolism and key precursors for industrially relevant products. Rational engineering of their supply requires knowledge of compensatory reactions that replace predominant pathways when these are inactivated. This study investigates effects of individual and combined mutations that inactivate the mitochondrial pyruvate-dehydrogenase (PDH) complex, extramitochondrial citrate synthase (Cit2) and mitochondrial CoA-transferase (Ach1) in Saccharomyces cerevisiae. Additionally, strains with a constitutively expressed carnitine shuttle were constructed and analyzed. A predominant role of the PDH complex in linking glycolysis and TCA cycle in glucose-grown batch cultures could be functionally replaced by the combined activity of the cytosolic PDH bypass and Cit2. Strongly impaired growth and a high incidence of respiratory deficiency in pda1Δ ach1Δ strains showed that synthesis of intramitochondrial acetyl-CoA as a metabolic precursor requires activity of either the PDH complex or Ach1. Constitutive overexpression of AGP2, HNM1, YAT2, YAT1, CRC1 and CAT2 enabled the carnitine shuttle to efficiently link glycolysis and TCA cycle in l-carnitine-supplemented, glucose-grown batch cultures. Strains in which all known reactions at the glycolysis-TCA cycle interface were inactivated still grew slowly on glucose, indicating additional flexibility at this key metabolic junction.

  8. Alternative reactions at the interface of glycolysis and citric acid cycle in Saccharomyces cerevisiae.

    PubMed

    van Rossum, Harmen M; Kozak, Barbara U; Niemeijer, Matthijs S; Duine, Hendrik J; Luttik, Marijke A H; Boer, Viktor M; Kötter, Peter; Daran, Jean-Marc G; van Maris, Antonius J A; Pronk, Jack T

    2016-05-01

    Pyruvate and acetyl-coenzyme A, located at the interface between glycolysis and TCA cycle, are important intermediates in yeast metabolism and key precursors for industrially relevant products. Rational engineering of their supply requires knowledge of compensatory reactions that replace predominant pathways when these are inactivated. This study investigates effects of individual and combined mutations that inactivate the mitochondrial pyruvate-dehydrogenase (PDH) complex, extramitochondrial citrate synthase (Cit2) and mitochondrial CoA-transferase (Ach1) in Saccharomyces cerevisiae. Additionally, strains with a constitutively expressed carnitine shuttle were constructed and analyzed. A predominant role of the PDH complex in linking glycolysis and TCA cycle in glucose-grown batch cultures could be functionally replaced by the combined activity of the cytosolic PDH bypass and Cit2. Strongly impaired growth and a high incidence of respiratory deficiency in pda1Δ ach1Δ strains showed that synthesis of intramitochondrial acetyl-CoA as a metabolic precursor requires activity of either the PDH complex or Ach1. Constitutive overexpression of AGP2, HNM1, YAT2, YAT1, CRC1 and CAT2 enabled the carnitine shuttle to efficiently link glycolysis and TCA cycle in l-carnitine-supplemented, glucose-grown batch cultures. Strains in which all known reactions at the glycolysis-TCA cycle interface were inactivated still grew slowly on glucose, indicating additional flexibility at this key metabolic junction. PMID:26895788

  9. Fuel cycle centers revisited: Consolidation of fuel cycle activities in a few countries

    SciTech Connect

    Kratzer, M.B.

    1996-07-01

    Despite varied expressions, the general impression remains that the international fuel cycle center concept, whatever its merits, is visionary. It also is quite possibly unattainable in light of strong national pressures toward independence and self-sufficiency in all things nuclear. Is the fuel cycle center an idea that has come and gone? Is it an idea whose time has not yet come? Or is it, as this paper suggests, an idea that has already arrived on the scene, attracting little attention or even acknowledgement of its presence? The difficult in answering this questions arises, in part, from the fact that despite its long and obvious appeal, there has been very little systematic analysis of the concept itself. Such obvious questions as how many and where fuel cycle centers should be located; what characteristics should the hot country or countries possess; and what are the institutional forms or features that endow the concept with enhanced proliferation protection have rarely been seriously and systematically addressed. The title of this paper focuses on limiting the geographic spread of fuel cycle facilities, and some may suggest that doing so does not necessarily call for any type of international or multinational arrangements applicable to those that exist. It is a premise of this paper, however, that a restriction on the number of countries possessing sensitive fuel cycle facilities necessarily involves some degree of multinationalization. This is not only because in every instance a nonproliferation pledge and international or multinational safeguards, or both, will be applied to the facility, but also because a restriction on the number of countries possessing these facilities implies that those in existence will serve a multinational market. This feature in itself is an important form of international auspices. Thus, the two concepts--limitation and multinationalization--if not necessarily one and the same, are at least de facto corollaries.

  10. Active Site, Catalytic Cycle, and Iodination Reactions of Vanadium Iodoperoxidase: A Computational Study.

    PubMed

    Pacios, Luis F; Gálvez, Oscar

    2010-05-11

    A combined computational study using molecular surfaces and Poisson-Boltzmann electrostatic potentials for proteins and quantum calculations on complexes representing the vanadate cofactor throughout the catalytic cycle is employed to study the activity of vanadium iodoperoxidase (VIPO) from alga Laminaria digitata . A model structure of VIPO is compared with available crystal structures of chloroperoxidases (VClPOs) and bromoperoxidases (VBrPOs) focusing on properties of the active site that concern halogen specificity. It is found that VIPO displays distinctive features regarding electrostatic potentials at the site cavity and the local topography of the cavity entrance. Quantum calculations on cofactor stages throughout the catalytic cycle reveal that, while steps involving binding of hydrogen peroxide and halide oxidization agree with available data on VBrPO, final formation and subsequent release of hypohalous acid could follow a different pathway consisting of His476-assisted protonation of bonded hypoiodite and further displacement by a water molecule. Ab initio free energies of reaction computed to explore iodination of organic substrates predict strongly exoergonic reactions with HOI, whereas other possible iodination reagents give thermodynamically disfavored reactions.

  11. Extracellular enzyme activity and biogeochemical cycling in restored prairies

    NASA Astrophysics Data System (ADS)

    Lynch, L.; Hernandez, D.; Schade, J. D.

    2011-12-01

    Winter microbial activity in mid-latitude prairie ecosystems is thermally sensitive and significantly influenced by snow depth. Snow insulates the soil column facilitating microbial processing of complex organic substrates. Previous studies in forests and tundra ecosystems suggest patterns of substrate utilization and limitation are seasonal; above freezing, soil microbes access fresh litter inputs and sugar exudates from plant roots, while under frozen condition they recycle nutrients incorporated in microbial biomass. In order to liberate nutrients required for carbon degradation, soil microbes invest energy in the production of extracellular enzymes that cleave monomers from polymer bonds. The inverse relationship between relative enzyme abundance and substrate availability makes enzyme assays a useful proxy to assess changes in resources over time. Our objective in this study was to assess patterns in microbial biomass, nutrient availability, and extracellular enzyme activity in four snow exclosure sites over a seven-month period. Over the past three years, we have maintained a snow removal experiment on two restored prairies in central Minnesota. In each prairie, snow was continuously removed annually from two 4 x 4 m plots by shoveling after each snow event. Extractable C, N and P, and microbial C, N and P in soil samples were measured in samples collected from these snow removal plots, as well as in adjacent unmanipulated prairie control plots. Pools of C, N, and P were estimated using standard extraction protocols, and microbial pools were estimated using chloroform fumigation direct extraction (CFDE). We conducted fluorometric extracellular enzyme assays (EEA) to assess how the degradation potential of cellulose (cellobiohydrolase, CBH), protein (leucine aminopeptidase, LAP), and phosphate esters (phosphatase, PHOS) changed seasonally. Microbial C and N declined between October and June, while microbial P declined during the fall and winter, but increased

  12. Mitochondrial dysfunctions in cancer: genetic defects and oncogenic signaling impinging on TCA cycle activity.

    PubMed

    Desideri, Enrico; Vegliante, Rolando; Ciriolo, Maria Rosa

    2015-01-28

    The tricarboxylic acid (TCA) cycle is a central route for oxidative metabolism. Besides being responsible for the production of NADH and FADH2, which fuel the mitochondrial electron transport chain to generate ATP, the TCA cycle is also a robust source of metabolic intermediates required for anabolic reactions. This is particularly important for highly proliferating cells, like tumour cells, which require a continuous supply of precursors for the synthesis of lipids, proteins and nucleic acids. A number of mutations among the TCA cycle enzymes have been discovered and their association with some tumour types has been established. In this review we summarise the current knowledge regarding alterations of the TCA cycle in tumours, with particular attention to the three germline mutations of the enzymes succinate dehydrogenase, fumarate hydratase and isocitrate dehydrogenase, which are involved in the pathogenesis of tumours, and to the aberrant regulation of TCA cycle components that are under the control of oncogenes and tumour suppressors. PMID:24614286

  13. DIBROMOACETIC ACID-INDUCED ELEVATIONS OF ESTRADIOL IN THE CYCLING AND OVARIECTOMOZED/ESTRADIOL-IMPLANTED FEMALE RAT

    EPA Science Inventory

    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations of Estradiol in Both Cycling and Ovariectomized / Estradiol-implanted Female Rats

    ABSTRACT
    Haloacetic acids are one of the principal classes of disinfection by-products generated by the chlorination of mun...

  14. The Effect of Light on the Tricarboxylic Acid Cycle in Green Leaves

    PubMed Central

    Chapman, E. A.; Graham, D.

    1974-01-01

    Long term feeding of acetate-2-14C, 14CO2, citrate-1,5-14C, fumarate-2,3-14C, and succinate-2,3-14C to mung bean (Phaseolus aureus L. var. Mungo) leaves in the dark gave labeling predominantly in tricarboxylic acid cycle intermediates. Kinetics of the intermediates during dark/light/dark transitions showed a light-induced interchange of 14C between malate and aspartate, usually resulting in an accumulation of 14C in malate and a decrease of it in aspartate. 14C-Phosphoenolpyruvate also showed a marked decrease during illumination. Changes in other intermediates of the tricarboxylic acid cycle were relatively minor. The kinetic data have been analyzed using the Chance crossover theorem to locate control points during the dark/light/dark transitions. The major apparent control points are located at malate and isocitrate dehydrogenases, and less frequently at citrate synthase and fumarase. These findings are explained in terms of the light-induced changes in adenine nucleotides and nicotinamide adenine dinucleotides. PMID:16658810

  15. Biochar impacts soil microbial community composition and nitrogen cycling in an acidic soil planted with rape.

    PubMed

    Xu, Hui-Juan; Wang, Xiao-Hui; Li, Hu; Yao, Huai-Ying; Su, Jian-Qiang; Zhu, Yong-Guan

    2014-08-19

    Biochar has been suggested to improve acidic soils and to mitigate greenhouse gas emissions. However, little has been done on the role of biochar in ameliorating acidified soils induced by overuse of nitrogen fertilizers. In this study, we designed a pot trial with an acidic soil (pH 4.48) in a greenhouse to study the interconnections between microbial community, soil chemical property changes, and N2O emissions after biochar application. The results showed that biochar increased plant growth, soil pH, total carbon, total nitrogen, C/N ratio, and soil cation exchange capacity. The results of high-throughput sequencing showed that biochar application increased α-diversity significantly and changed the relative abundances of some microbes that are related with carbon and nitrogen cycling at the family level. Biochar amendment stimulated both nitrification and denitrification processes, while reducing N2O emissions overall. Results of redundancy analysis indicated biochar could shift the soil microbial community by changing soil chemical properties, which modulate N-cycling processes and soil N2O emissions. The significantly increased nosZ transcription suggests that biochar decreased soil N2O emissions by enhancing its further reduction to N2. PMID:25054835

  16. THE EFFECT OF ANOLYTE PRODUCT ACID CONCENTRATION ON HYBRID SULFUR CYCLE PERFORMANCE

    SciTech Connect

    Gorensek, M.; Summers, W.

    2010-03-24

    The Hybrid Sulfur (HyS) cycle (Fig. 1) is one of the simplest, all-fluids thermochemical cycles that has been devised for splitting water with a high-temperature nuclear or solar heat source. It was originally patented by Brecher and Wu in 1975 and extensively developed by Westinghouse in the late 1970s and early 1980s. As its name suggests, the only element used besides hydrogen and oxygen is sulfur, which is cycled between the +4 and +6 oxidation states. HyS comprises two steps. One is the thermochemical (>800 C) decomposition of sulfuric acid (H{sub 2}SO{sub 4}) to sulfur dioxide (SO{sub 2}), oxygen (O{sub 2}), and water. H{sub 2}SO{sub 4} = SO{sub 2} + 1/2 O{sub 2} + H{sub 2}O. The other is the SO{sub 2}-depolarized electrolysis of water to H{sub 2}SO{sub 4} and hydrogen (H{sub 2}), SO{sub 2} + 2 H{sub 2}O = H{sub 2}SO{sub 4} + H{sub 2}, E{sup o} = -0.156 V, explaining the 'hybrid' designation. These two steps taken together split water into H{sub 2} and O{sub 2} using heat and electricity. Researchers at the Savannah River National Laboratory (SRNL) and at the University of South Carolina (USC) have successfully demonstrated the use of proton exchange membrane (PEM) electrolyzers (Fig. 2) for the SO{sub 2}-depolarized electrolysis (sulfur oxidation) step, while Sandia National Laboratories (SNL) successfully demonstrated the high-temperature sulfuric acid decomposition (sulfur reduction) step using a bayonet-type reactor (Fig. 3). This latter work was performed as part of the Sulfur-Iodine (SI) cycle Integrated Laboratory Scale demonstration at General Atomics (GA). The combination of these two operations results in a simple process that will be more efficient and cost-effective for the massive production of hydrogen than alkaline electrolysis. Recent developments suggest that the use of PEMs other than Nafion will allow sulfuric acid to be produced at higher concentrations (>60 wt%), offering the possibility of net thermal efficiencies around 50% (HHV basis

  17. Fluxless soldering using activated acid vapors

    SciTech Connect

    Frear, D.R.; Keicher, D.M.

    1992-01-01

    Acid vapors have been used to fluxlessly reduce metal oxides and enhance wetting of solder on metallizations. Dilute solutions of hydrogen, acetic acid and formic acid in an inert carrier gas of nitrogen or argon were used with the sessile drop technique for 60Sn-40 Pb solder on Cu and Au/Ni metallizations. The time to reduce metal oxides and the extent of wetting as a function of acid vapor concentrations were characterized. Acetic and formic acids reduce the surface metal oxides sufficiently to form metallurgically sound solder joints. Hydrogen did not reduce oxides rapidly enough at 220{degree}C to be suitable for soldering applications. The optimum conditions for oxide reduction with formic acid was with an acid vapor concentration in nitrogen carrier gas of 4% for Cu metallizations and 1.6% on Au/Ni. The acetic acid vapor concentration, also in nitrogen, was optimized at 1.5% for both metallizations. Above a vapor concentration of 1.5%, the acetic acid combined with the bare metal to form acetates which increased the wetting time. These results indicate that acid vapor fluxless soldering is a viable alternative to traditional flux soldering.

  18. The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control

    SciTech Connect

    Yang, Yunfeng; McCue, Lee Ann; Parsons, Andrea B.; Feng, Sheng; Zhou, Jizhong

    2010-10-26

    It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. In this study, we showed that a fur deletion mutant of the γ-proteobacterium S. oneidensis could utilize TCA compounds. In addition, expression of the TCA cycle genes acnA and sdhA was not down-regulated in the mutant. To explore this observation further, we identified a ryhB gene in Shewanella species and demonstrated its expression experimentally. Further experiments suggested that RyhB was up-regulated in fur mutant, but that AcnA and SdhA were not controlled by RyhB. This work delineates an important difference of the Fur-RyhB regulatory cycle between S. oneidensis and other γ-proteobacteria.

  19. The tricarboxylic acid cycle in Shewanella oneidensis is independent of Fur and RyhB control

    SciTech Connect

    Yang, Yunfeng; McCue, Lee Ann; Parsons, Andrea; Feng, Sheng; Zhou, Jizhong

    2010-01-01

    Background: It is well established in E. coli and Vibrio cholerae that strains harboring mutations in the ferric uptake regulator gene (fur) are unable to utilize tricarboxylic acid (TCA) compounds, due to the down-regulation of key TCA cycle enzymes, such as AcnA and SdhABCD. This down-regulation is mediated by a Fur-regulated small regulatory RNA named RyhB. It is unclear in the g-proteobacterium S. oneidensis whether TCA is also regulated by Fur and RyhB. Results: In the present study, we showed that a fur deletion mutant of S. oneidensis could utilize TCA compounds. Consistently, expression of the TCA cycle genes acnA and sdhA was not down-regulated in the mutant. To explore this observation further, we identified a ryhB gene in Shewanella species and experimentally demonstrated the gene expression. Further experiments suggested that RyhB was up-regulated in fur mutant, but that AcnA and SdhA were not controlled by RyhB. Conclusions: These cumulative results delineate an important difference of the Fur-RyhB regulatory cycle between S. oneidensis and other g-proteobacteria. This work represents a step forward for understanding the unique regulation in S. oneidensis.

  20. Lactic Acid Bacteria in Durum Wheat Flour Are Endophytic Components of the Plant during Its Entire Life Cycle

    PubMed Central

    Minervini, Fabio; Celano, Giuseppe; Lattanzi, Anna; Tedone, Luigi; De Mastro, Giuseppe; De Angelis, Maria

    2015-01-01

    This study aimed at assessing the dynamics of lactic acid bacteria and other Firmicutes associated with durum wheat organs and processed products. 16S rRNA gene-based high-throughput sequencing showed that Lactobacillus, Streptococcus, Enterococcus, and Lactococcus were the main epiphytic and endophytic genera among lactic acid bacteria. Bacillus, Exiguobacterium, Paenibacillus, and Staphylococcus completed the picture of the core genus microbiome. The relative abundance of each lactic acid bacterium genus was affected by cultivars, phenological stages, other Firmicutes genera, environmental temperature, and water activity (aw) of plant organs. Lactobacilli, showing the highest sensitivity to aw, markedly decreased during milk development (Odisseo) and physiological maturity (Saragolla). At these stages, Lactobacillus was mainly replaced by Streptococcus, Lactococcus, and Enterococcus. However, a key sourdough species, Lactobacillus plantarum, was associated with plant organs during the life cycle of Odisseo and Saragolla wheat. The composition of the sourdough microbiota and the overall quality of leavened baked goods are also determined throughout the phenological stages of wheat cultivation, with variations depending on environmental and agronomic factors. PMID:26187970

  1. Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer.

    PubMed

    Schnarrenberger, Claus; Martin, William

    2002-02-01

    The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which provides, among other things, electrons for oxidative phosphorylation in the inner mitochondrial membrane, intermediates for amino-acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in glyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among alpha-proteobacteria, the group of eubacteria as defined under rRNA systematics from which mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previously shown to branch with their homologues from alpha-proteobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories of all of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle using protein maximum likelihood phylogenies, focusing on the evolutionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryotic pathway are most similar to their alpha-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not specifically alpha-proteobacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and (b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it is unrealistic to expect all nuclear genes that were acquired from the alpha-proteobacterial ancestor of mitochondria to branch specifically with their homologues encoded in the genomes of contemporary alpha-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly (which it does not), then some nuclear-encoded proteins that were acquired from the alpha

  2. Evolution of the enzymes of the citric acid cycle and the glyoxylate cycle of higher plants. A case study of endosymbiotic gene transfer.

    PubMed

    Schnarrenberger, Claus; Martin, William

    2002-02-01

    The citric acid or tricarboxylic acid cycle is a central element of higher-plant carbon metabolism which provides, among other things, electrons for oxidative phosphorylation in the inner mitochondrial membrane, intermediates for amino-acid biosynthesis, and oxaloacetate for gluconeogenesis from succinate derived from fatty acids via the glyoxylate cycle in glyoxysomes. The tricarboxylic acid cycle is a typical mitochondrial pathway and is widespread among alpha-proteobacteria, the group of eubacteria as defined under rRNA systematics from which mitochondria arose. Most of the enzymes of the tricarboxylic acid cycle are encoded in the nucleus in higher eukaryotes, and several have been previously shown to branch with their homologues from alpha-proteobacteria, indicating that the eukaryotic nuclear genes were acquired from the mitochondrial genome during the course of evolution. Here, we investigate the individual evolutionary histories of all of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle using protein maximum likelihood phylogenies, focusing on the evolutionary origin of the nuclear-encoded proteins in higher plants. The results indicate that about half of the proteins involved in this eukaryotic pathway are most similar to their alpha-proteobacterial homologues, whereas the remainder are most similar to eubacterial, but not specifically alpha-proteobacterial, homologues. A consideration of (a) the process of lateral gene transfer among free-living prokaryotes and (b) the mechanistics of endosymbiotic (symbiont-to-host) gene transfer reveals that it is unrealistic to expect all nuclear genes that were acquired from the alpha-proteobacterial ancestor of mitochondria to branch specifically with their homologues encoded in the genomes of contemporary alpha-proteobacteria. Rather, even if molecular phylogenetics were to work perfectly (which it does not), then some nuclear-encoded proteins that were acquired from the alpha

  3. Life cycle assessment of active and passive groundwater remediation technologies

    NASA Astrophysics Data System (ADS)

    Bayer, Peter; Finkel, Michael

    2006-02-01

    Groundwater remediation technologies, such as pump-and-treat (PTS) and funnel-and-gate systems (FGS), aim at reducing locally appearing contaminations. Therefore, these methodologies are basically evaluated with respect to their capability to yield local improvements of an environmental situation, commonly neglecting that their application is also associated with secondary impacts. Life cycle assessment (LCA) represents a widely accepted method of assessing the environmental aspects and potential impacts related to a product, process or service. This study presents the set-up of a LCA framework in order to compare the secondary impacts caused by two conceptually different technologies at the site of a former manufactured gas plant in the city of Karlsruhe, Germany. As a FGS is already operating at this site, a hypothetical PTS of the same functionality is adopted. During the LCA, the remediation systems are evaluated by focusing on the main technical elements and their significance with respect to resource depletion and potential adverse effects on ecological quality, as well as on human health. Seven impact categories are distinguished to address a broad spectrum of possible environmental loads. A main point of discussion is the reliability of technical assumptions and performance predictions for the future. It is obvious that a high uncertainty exists when estimating impact specific indicator values over operation times of decades. An uncertainty analysis is conducted to include the imprecision of the underlying emission and consumption data and a scenario analysis is utilised to contrast various possible technological variants. Though the results of the study are highly site-specific, a generalised relative evaluation of potential impacts and their main sources is the principle objective rather than a discussion of the calculated absolute impacts. A crucial finding that can be applied to any other site is the central role of steel, which particularly derogates

  4. Life cycle assessment of active and passive groundwater remediation technologies.

    PubMed

    Bayer, Peter; Finkel, Michael

    2006-02-10

    Groundwater remediation technologies, such as pump-and-treat (PTS) and funnel-and-gate systems (FGS), aim at reducing locally appearing contaminations. Therefore, these methodologies are basically evaluated with respect to their capability to yield local improvements of an environmental situation, commonly neglecting that their application is also associated with secondary impacts. Life cycle assessment (LCA) represents a widely accepted method of assessing the environmental aspects and potential impacts related to a product, process or service. This study presents the set-up of a LCA framework in order to compare the secondary impacts caused by two conceptually different technologies at the site of a former manufactured gas plant in the city of Karlsruhe, Germany. As a FGS is already operating at this site, a hypothetical PTS of the same functionality is adopted. During the LCA, the remediation systems are evaluated by focusing on the main technical elements and their significance with respect to resource depletion and potential adverse effects on ecological quality, as well as on human health. Seven impact categories are distinguished to address a broad spectrum of possible environmental loads. A main point of discussion is the reliability of technical assumptions and performance predictions for the future. It is obvious that a high uncertainty exists when estimating impact specific indicator values over operation times of decades. An uncertainty analysis is conducted to include the imprecision of the underlying emission and consumption data and a scenario analysis is utilised to contrast various possible technological variants. Though the results of the study are highly site-specific, a generalised relative evaluation of potential impacts and their main sources is the principle objective rather than a discussion of the calculated absolute impacts. A crucial finding that can be applied to any other site is the central role of steel, which particularly derogates

  5. Staphylococcal Enterotoxin O Exhibits Cell Cycle Modulating Activity

    PubMed Central

    Hodille, Elisabeth; Alekseeva, Ludmila; Berkova, Nadia; Serrier, Asma; Badiou, Cedric; Gilquin, Benoit; Brun, Virginie; Vandenesch, François; Terman, David S.; Lina, Gerard

    2016-01-01

    Maintenance of an intact epithelial barrier constitutes a pivotal defense mechanism against infections. Staphylococcus aureus is a versatile pathogen that produces multiple factors including exotoxins that promote tissue alterations. The aim of the present study is to investigate the cytopathic effect of staphylococcal exotoxins SEA, SEG, SEI, SElM, SElN and SElO on the cell cycle of various human cell lines. Among all tested exotoxins only SEIO inhibited the proliferation of a broad panel of human tumor cell lines in vitro. Evaluation of a LDH release and a DNA fragmentation of host cells exposed to SEIO revealed that the toxin does not induce necrosis or apoptosis. Analysis of the DNA content of tumor cells synchronized by serum starvation after exposure to SEIO showed G0/G1 cell cycle delay. The cell cycle modulating feature of SEIO was confirmed by the flow cytometry analysis of synchronized cells exposed to supernatants of isogenic S. aureus strains wherein only supernatant of the SElO producing strain induced G0/G1 phase delay. The results of yeast-two-hybrid analysis indicated that SEIO’s potential partner is cullin-3, involved in the transition from G1 to S phase. In conclusion, we provide evidence that SEIO inhibits cell proliferation without inducing cell death, by delaying host cell entry into the G0/G1 phase of the cell cycle. We speculate that this unique cell cycle modulating feature allows SEIO producing bacteria to gain advantage by arresting the cell cycle of target cells as part of a broader invasive strategy. PMID:27148168

  6. Activated Carbon Catalysts for the Production of Hydrogen for the Sulfur-Iodine Thermochemical Water Splitting Cycle

    SciTech Connect

    Lucia M. Petkovic; Daniel M. Ginosar; Harry W. Rollins; Kyle C Burch; Cristina Deiana; Hugo S. Silva; Maria F. Sardella; Dolly Granados

    2009-05-01

    Seven activated carbon catalysts obtained from a variety of raw material sources and preparation methods were examined for their catalytic activity to decompose hydroiodic acid (HI) to produce hydrogen; a key reaction in the sulfur-iodine (S-I) thermochemical water splitting cycle. Activity was examined under a temperature ramp from 473 to 773 K. Within the group of ligno-cellulosic steam-activated carbon catalysts, activity increased with surface area. However, both a mineral-based steam-activated carbon and a ligno-cellulosic chemically-activated carbon displayed activities lower than expected based on their higher surface areas. In general, ash content was detrimental to catalytic activity while total acid sites, as determined by Bohem’s titrations, seemed to favor higher catalytic activity within the group of steam-activated carbons. These results suggest, one more time, that activated carbon raw materials and preparation methods may have played a significant role in the development of surface characteristics that eventually dictated catalyst activity and stability as well.

  7. Quantifying Rates of Complete Microbial Iron Redox Cycling in Acidic Hot Springs

    NASA Astrophysics Data System (ADS)

    St Clair, B.; Pottenger, J. W.; Shock, E.

    2013-12-01

    concentrations of ferrous iron. Experimental design allowed us to measure biological and abiological rates independently. Results indicate a relatively consistent rate of biological iron oxidation between 20-100 ng Fe2+(gm wet sediment)-1 (second)-1 where oxide accumulations occur. Abiological oxidation rates increase significantly with increasing pH, and greatly limit soluble ferrous iron above a pH of 3.5 at high temperatures. Rates of biological iron reduction are typically comparable to oxidation, and can often double oxidation rates when supplemented with organic carbon. Abiological iron reduction rates are inconsequential when the pH is greater than 2, but increase sharply below this point. Results indicate that comparable rates of microbial oxidation and reduction are common in springs where biogenic iron oxide accumulates. It appears that the interplay of temperature, oxygen availability, and supply of organic carbon determines the extent and history of iron oxide accumulation. Taken together, our results show that complete microbial iron redox cycles are active in acidic hot springs wherever biogenic iron oxides accumulate.

  8. Physiological activities of hydroxyl fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the search of value-added products from surplus soybean oil, we produced many new hydroxy fatty acids through microbial bioconversion. Hydroxy fatty acids are used in a wide range of industrial products, such as resins, waxes, nylons plastics, lubricants, cosmetics, and additives in coatings and...

  9. Environmental Life Cycle Assessment of Diets with Improved Omega-3 Fatty Acid Profiles

    PubMed Central

    Coelho, Carla R. V.; Pernollet, Franck; van der Werf, Hayo M. G.

    2016-01-01

    A high incidence of cardiovascular disease is observed worldwide, and dietary habits are one of the risk factors for these diseases. Omega-3 polyunsaturated fatty acids in the diet help to prevent cardiovascular disease. We used life cycle assessment to analyse the potential of two strategies to improve the nutritional and environmental characteristics of French diets: 1) modifying diets by changing the quantities and proportions of foods and 2) increasing the omega-3 contents in diets by replacing mainly animal foods with equivalent animal foods having higher omega-3 contents. We also investigated other possibilities for reducing environmental impacts. Our results showed that a diet compliant with nutritional recommendations for macronutrients had fewer environmental impacts than the current average French diet. Moving from an omnivorous to a vegetarian diet further reduced environmental impacts. Increasing the omega-3 contents in animal rations increased Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) in animal food products. Providing these enriched animal foods in human diets increased their EPA and DHA contents without affecting their environmental impacts. However, in diets that did not contain fish, EPA and DHA contents were well below the levels recommended by health authorities, despite the inclusion of animal products enriched in EPA and DHA. Reducing meat consumption and avoidable waste at home are two main avenues for reducing environmental impacts of diets. PMID:27504959

  10. Environmental Life Cycle Assessment of Diets with Improved Omega-3 Fatty Acid Profiles.

    PubMed

    Coelho, Carla R V; Pernollet, Franck; van der Werf, Hayo M G

    2016-01-01

    A high incidence of cardiovascular disease is observed worldwide, and dietary habits are one of the risk factors for these diseases. Omega-3 polyunsaturated fatty acids in the diet help to prevent cardiovascular disease. We used life cycle assessment to analyse the potential of two strategies to improve the nutritional and environmental characteristics of French diets: 1) modifying diets by changing the quantities and proportions of foods and 2) increasing the omega-3 contents in diets by replacing mainly animal foods with equivalent animal foods having higher omega-3 contents. We also investigated other possibilities for reducing environmental impacts. Our results showed that a diet compliant with nutritional recommendations for macronutrients had fewer environmental impacts than the current average French diet. Moving from an omnivorous to a vegetarian diet further reduced environmental impacts. Increasing the omega-3 contents in animal rations increased Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) in animal food products. Providing these enriched animal foods in human diets increased their EPA and DHA contents without affecting their environmental impacts. However, in diets that did not contain fish, EPA and DHA contents were well below the levels recommended by health authorities, despite the inclusion of animal products enriched in EPA and DHA. Reducing meat consumption and avoidable waste at home are two main avenues for reducing environmental impacts of diets. PMID:27504959

  11. Physical activity as a determinant of fecal bile acid levels

    PubMed Central

    Wertheim, Betsy C.; Martínez, María Elena; Ashbeck, Erin L.; Roe, Denise J.; Jacobs, Elizabeth T.; Alberts, David S.; Thompson, Patricia A.

    2009-01-01

    Physical activity is protective against colon cancer, whereas colonic bile acid exposure is a suspected risk factor. While likely related, the association between physical activity and bile acid levels has not been well studied. Furthermore, the effect of triglycerides, which are known to modify bile acid levels, on this relationship has not been investigated. We conducted a cross-sectional analysis of baseline fecal bile acid levels for 735 colorectal adenoma formers obtained from participants in a phase III ursodeoxycholic acid chemoprevention trial. Compared to the lowest quartile of recreational physical activity duration, the highest quartile was associated with a 17% lower fecal bile acid concentration, adjusted for age, sex, dietary fiber intake, and body mass index (P = 0.042). Furthermore, consistent with a previously established relationship between serum triglyceride levels and bile acid metabolism, we stratified by triglyceride level and observed a 34% lower fecal bile acid concentration (highest versus lowest quartiles of physical activity) in individuals with low triglycerides (< 136 mg/dL; P = 0.002). In contrast, no association between physical activity and fecal bile acid concentration was observed for subjects with high triglycerides (≥ 136 mg/dL). Our results suggest that the biological mechanism responsible for the protective effect of physical activity on the incidence of colon cancer may be partially mediated by decreasing colonic bile acid exposure. However, this effect may be limited to individuals with lower triglyceride levels. PMID:19383885

  12. Teaching Ecosystems and Matter Cycles with Creative Drama Activities

    ERIC Educational Resources Information Center

    Cokadar, Hulusi; Yilmaz, Gulcin Cihan

    2010-01-01

    The purpose of this study is to examine the effect of creative drama-based instruction on seventh graders' science achievements in the ecology and matter cycles unit and their attitudes toward science. The study is an experimental study carried out in one of the public elementary schools in Turkey during 2005-2006 schooling year. An ecological…

  13. Computational estimation of tricarboxylic acid cycle fluxes using noisy NMR data from cardiac biopsies

    PubMed Central

    2013-01-01

    Background The aerobic energy metabolism of cardiac muscle cells is of major importance for the contractile function of the heart. Because energy metabolism is very heterogeneously distributed in heart tissue, especially during coronary disease, a method to quantify metabolic fluxes in small tissue samples is desirable. Taking tissue biopsies after infusion of substrates labeled with stable carbon isotopes makes this possible in animal experiments. However, the appreciable noise level in NMR spectra of extracted tissue samples makes computational estimation of metabolic fluxes challenging and a good method to define confidence regions was not yet available. Results Here we present a computational analysis method for nuclear magnetic resonance (NMR) measurements of tricarboxylic acid (TCA) cycle metabolites. The method was validated using measurements on extracts of single tissue biopsies taken from porcine heart in vivo. Isotopic enrichment of glutamate was measured by NMR spectroscopy in tissue samples taken at a single time point after the timed infusion of 13C labeled substrates for the TCA cycle. The NMR intensities for glutamate were analyzed with a computational model describing carbon transitions in the TCA cycle and carbon exchange with amino acids. The model dynamics depended on five flux parameters, which were optimized to fit the NMR measurements. To determine confidence regions for the estimated fluxes, we used the Metropolis-Hastings algorithm for Markov chain Monte Carlo (MCMC) sampling to generate extensive ensembles of feasible flux combinations that describe the data within measurement precision limits. To validate our method, we compared myocardial oxygen consumption calculated from the TCA cycle flux with in vivo blood gas measurements for 38 hearts under several experimental conditions, e.g. during coronary artery narrowing. Conclusions Despite the appreciable NMR noise level, the oxygen consumption in the tissue samples, estimated from the NMR

  14. Croconaine rotaxane for acid activated photothermal heating and ratiometric photoacoustic imaging of acidic pH†

    PubMed Central

    Guha, Samit; Shaw, Gillian Karen; Mitcham, Trevor M.; Bouchard, Richard R.

    2015-01-01

    Absorption of 808 nm laser light by liposomes containing a pH sensitive, near-infrared croconaine rotaxane dye increases dramatically in weak acid. A stealth liposome composition permits acid activated, photothermal heating and also acts as an effective nanoparticle probe for ratiometric photoacoustic imaging of acidic pH in deep sample locations, including a living mouse. PMID:26502996

  15. Computational Simulation of the Activation Cycle of Gα Subunit in the G Protein Cycle Using an Elastic Network Model

    PubMed Central

    Kim, Min Hyeok; Kim, Young Jin; Kim, Hee Ryung; Jeon, Tae-Joon; Choi, Jae Boong; Chung, Ka Young; Kim, Moon Ki

    2016-01-01

    Agonist-activated G protein-coupled receptors (GPCRs) interact with GDP-bound G protein heterotrimers (Gαβγ) promoting GDP/GTP exchange, which results in dissociation of Gα from the receptor and Gβγ. The GTPase activity of Gα hydrolyzes GTP to GDP, and the GDP-bound Gα interacts with Gβγ, forming a GDP-bound G protein heterotrimer. The G protein cycle is allosterically modulated by conformational changes of the Gα subunit. Although biochemical and biophysical methods have elucidated the structure and dynamics of Gα, the precise conformational mechanisms underlying the G protein cycle are not fully understood yet. Simulation methods could help to provide additional details to gain further insight into G protein signal transduction mechanisms. In this study, using the available X-ray crystal structures of Gα, we simulated the entire G protein cycle and described not only the steric features of the Gα structure, but also conformational changes at each step. Each reference structure in the G protein cycle was modeled as an elastic network model and subjected to normal mode analysis. Our simulation data suggests that activated receptors trigger conformational changes of the Gα subunit that are thermodynamically favorable for opening of the nucleotide-binding pocket and GDP release. Furthermore, the effects of GTP binding and hydrolysis on mobility changes of the C and N termini and switch regions are elucidated. In summary, our simulation results enabled us to provide detailed descriptions of the structural and dynamic features of the G protein cycle. PMID:27483005

  16. Advances in Acid Concentration Membrane Technology for the Sulfur-Iodine Thermochemical Cycle

    SciTech Connect

    Frederick F. Stewart; Christopher J. Orme

    2006-11-01

    One of the most promising cycles for the thermochemical generation of hydrogen is the Sulfur-Iodine (S-I) process, where aqueous HI is thermochemically decomposed into H2 and I2 at approximately 350 degrees Celsius. Regeneration of HI is accomplished by the Bunsen reaction (reaction of SO2, water, and iodine to generate H2SO4 and HI). Furthermore, SO2 is regenerated from the decomposition of H2SO4 at 850 degrees Celsius yielding the SO2 as well as O2. Thus, the cycle actually consists of two concurrent oxidation-reduction loops. As HI is regenerated, co-produced H2SO4 must be separated so that each may be decomposed. Current flowsheets employ a large amount (~83 mol% of the entire mixture) of elemental I2 to cause the HI and the H2SO4 to separate into two phases. To aid in the isolation of HI, which is directly decomposed into hydrogen, water and iodine must be removed. Separation of iodine is facilitated by removal of water. Sulfuric acid concentration is also required to facilitate feed recycling to the sulfuric acid decomposer. Decomposition of the sulfuric acid is an equilibrium limited process that leaves a substantial portion of the acid requiring recycle. Distillation of water from sulfuric acid involves significant corrosion issues at the liquid-vapor interface. Thus, it is desirable to concentrate the acid without boiling. Recent efforts at the INL have concentrated on applying pervaporation through Nafion-117, Nafion-112, and sulfonated poly(etheretherketone) (S-PEEK) membranes for the removal of water from HI/water and HI/Iodine/water feedstreams. In pervaporation, a feed is circulated at low pressure across the upstream side of the membrane, while a vacuum is applied downstream. Selected permeants sorb into the membrane, transport through it, and are vaporized from the backside. Thus, a concentration gradient is established, which provides the driving force for transport. In this work, membrane separations have been performed at temperatures as high as

  17. Potentiometric Acid-Base Titrations with Activated Graphite Electrodes

    NASA Astrophysics Data System (ADS)

    Riyazuddin, P.; Devika, D.

    1997-10-01

    Dry cell graphite (DCG) electrodes activated with potassium permanganate are employed as potentiometric indicator electrodes for acid-base titrations. Special attention is given to an indicator probe comprising activated DCG-non-activiated DCG electrode couple. This combination also proves suitable for the titration of strong or weak acids.

  18. [Bioelectric activity of cervix uteri in normal menstrual cycle and in the syndrome of sclerocystic ovaries].

    PubMed

    Rymashevskiĭ, V K; Kozhin, A A; Chzhan Chun'; Gorchakov, L A

    1974-10-01

    34 20-26 year old women with anovulatory cycles with the Stein syndrome and 5 women with normal menstrual cycles were studied in regard to bioelectric cervical activity by means of a vaginal probe and the micrograph ''Medicore.'' In the control group, an increase of progesterone in the 2nd phase of the cycle led to a decrease in the electromyographic (EMG) amplitude. In the anovulatory cycle, the extended activity of estrogens and minimal amount of progesterone stimulated a high tone of uterine impulses, which was substantiated by a high EMG proved to be effective and useful in the diagnosis of gynecological patients. PMID:4440834

  19. Nitrogen cycling in s subarctic Alaskan watershed: the role of lichens and the potential effects of acid deposition

    SciTech Connect

    Gunther, A.J.

    1987-01-01

    It has been hypothesized that the loss of nitrogen-fixing lichens due to stress from air pollution could have adverse effects upon nitrogen availability, and thus primary productivity, in some ecosystems. There is general agreement, however, that the ecological role of these lichens has not been sufficiently well defined to determine whether they are keystone species. The objectives of this study were: (1) to examine the importance of nitrogen-fixing lichens to the nitrogen cycle in the drainage of Brooks Lake, Alaska, a nitrogen-limited nursery lake for the commercially important sockeye salmon (Oncorhychus nerka); and (2) to investigate the sensitivity of nitrogen fixation by lichens in this ecosystem to acid deposition. Biological nitrogen fixation was found to be the major source of new nitrogen to the Brooks Lake drainage. The rate of fixation is approximately 3 kg N/ha-yr, which compares to 0.3 kg N/ha-yr in precipitation and only 0.02 kg N/ha-yr in returning adult salmon. Cyanophillic lichens contribute about 0.21 kg N/ha-yr. The low levels of nitrogen in precipitation, combined with a lack of nitrogen-fixation activity in open lake waters, indicates that nitrogen in tributary streams is the major source of new nitrogen for Brooks Lake. The measurements of nitrogen inputs, along with estimates of other stocks and flows of nitrogen, were used to construct a steady-state box model of the nitrogen cycle in the drainage.

  20. Performance improvement: an active life cycle product management

    NASA Astrophysics Data System (ADS)

    Cucchiella, Federica; Gastaldi, Massimo; Lenny Koh, S. C.

    2010-03-01

    The management of the supply chain has gained importance in many manufacturing firms. Operational flexibility can be considered a crucial weapon to increase competitiveness in a turbulent marketplace. It reflects the ability of a firm to properly and rapidly respond to a variable and dynamic environment. For the firm operating in a fashion sector, the management of the supply chain is even more complex because the product life cycle is shorter than that of the firm operating in a non-fashion sector. The increase of firm flexibility level can be reached through the application of the real option theory inside the firm network. In fact, real option may increase the project value by allowing managers to more efficiently direct the production. The real option application usually analysed in literature does not take into account that the demands of products are well-defined by the product life cycle. Working on a fashion sector, the life cycle pattern is even more relevant because of an expected demand that grows according to a constant rate that does not capture the demand dynamics of the underlying fashion goods. Thus, the primary research objective of this article is to develop a model useful for the management of investments in a supply chain operating in a fashion sector where the system complexity is increased by the low level of unpredictability and stability that is proper of the mood phenomenon. Moreover, unlike the traditional model, a real option framework is presented here that considers fashion product characterised by uncertain stages of the production cycle.

  1. Natural cinnamic acids, synthetic derivatives and hybrids with antimicrobial activity.

    PubMed

    Guzman, Juan David

    2014-11-25

    Antimicrobial natural preparations involving cinnamon, storax and propolis have been long used topically for treating infections. Cinnamic acids and related molecules are partly responsible for the therapeutic effects observed in these preparations. Most of the cinnamic acids, their esters, amides, aldehydes and alcohols, show significant growth inhibition against one or several bacterial and fungal species. Of particular interest is the potent antitubercular activity observed for some of these cinnamic derivatives, which may be amenable as future drugs for treating tuberculosis. This review intends to summarize the literature data on the antimicrobial activity of the natural cinnamic acids and related derivatives. In addition, selected hybrids between cinnamic acids and biologically active scaffolds with antimicrobial activity were also included. A comprehensive literature search was performed collating the minimum inhibitory concentration (MIC) of each cinnamic acid or derivative against the reported microorganisms. The MIC data allows the relative comparison between series of molecules and the derivation of structure-activity relationships.

  2. Antiproliferative Effect of Ascorbic Acid Is Associated with the Inhibition of Genes Necessary to Cell Cycle Progression

    PubMed Central

    Belin, Sophie; Kaya, Ferdinand; Duisit, Ghislaine; Giacometti, Sarah; Ciccolini, Joseph; Fontés, Michel

    2009-01-01

    Background Ascorbic acid (AA), or Vitamin C, is most well known as a nutritional supplement with antioxidant properties. Recently, we demonstrated that high concentrations of AA act on PMP22 gene expression and partially correct the Charcot-Marie-Tooth disease phenotype in a mouse model. This is due to the capacity of AA, but not other antioxidants, to down-modulate cAMP intracellular concentration by a competitive inhibition of the adenylate cyclase enzymatic activity. Because of the critical role of cAMP in intracellular signalling, we decided to explore the possibility that ascorbic acid could modulate the expression of other genes. Methods and Findings Using human pangenomic microarrays, we found that AA inhibited the expression of two categories of genes necessary for cell cycle progression, tRNA synthetases and translation initiation factor subunits. In in vitro assays, we demonstrated that AA induced the S-phase arrest of proliferative normal and tumor cells. Highest concentrations of AA leaded to necrotic cell death. However, quiescent cells were not susceptible to AA toxicity, suggesting the blockage of protein synthesis was mainly detrimental in metabolically-active cells. Using animal models, we found that high concentrations of AA inhibited tumor progression in nude mice grafted with HT29 cells (derived from human colon carcinoma). Consistently, expression of tRNA synthetases and ieF2 appeared to be specifically decreased in tumors upon AA treatment. Conclusions AA has an antiproliferative activity, at elevated concentration that could be obtained using IV injection. This activity has been observed in vitro as well in vivo and likely results from the inhibition of expression of genes involved in protein synthesis. Implications for a clinical use in anticancer therapies will be discussed. PMID:19197388

  3. Cdk1 activity acts as a quantitative platform for coordinating cell cycle progression with periodic transcription

    PubMed Central

    Banyai, Gabor; Baïdi, Feriel; Coudreuse, Damien; Szilagyi, Zsolt

    2016-01-01

    Cell proliferation is regulated by cyclin-dependent kinases (Cdks) and requires the periodic expression of particular gene clusters in different cell cycle phases. However, the interplay between the networks that generate these transcriptional oscillations and the core cell cycle machinery remains largely unexplored. In this work, we use a synthetic regulable Cdk1 module to demonstrate that periodic expression is governed by quantitative changes in Cdk1 activity, with different clusters directly responding to specific activity levels. We further establish that cell cycle events neither participate in nor interfere with the Cdk1-driven transcriptional program, provided that cells are exposed to the appropriate Cdk1 activities. These findings contrast with current models that propose self-sustained and Cdk1-independent transcriptional oscillations. Our work therefore supports a model in which Cdk1 activity serves as a quantitative platform for coordinating cell cycle transitions with the expression of critical genes to bring about proper cell cycle progression. PMID:27045731

  4. Metabolic bypass of the tricarboxylic acid cycle during lipid mobilization in germinating oilseeds. Regulation Of nad+-dependent isocitrate dehydrogenase versus fumarase

    PubMed

    Falk; Behal; Xiang; Oliver

    1998-06-01

    Biosynthesis of sucrose from triacylglycerol requires the bypass of the CO2-evolving reactions of the tricarboxylic acid (TCA) cycle. The regulation of the TCA cycle bypass during lipid mobilization was examined. Lipid mobilization in Brassica napus was initiated shortly after imbibition of the seed and proceeded until 2 d postimbibition, as measured by in vivo [1-14C]acetate feeding to whole seedlings. The activity of NAD+-isocitrate dehydrogenase (a decarboxylative enzyme) was not detected until 2 d postimbibition. RNA-blot analysis of B. napus seedlings demonstrated that the mRNA for NAD+-isocitrate dehydrogenase was present in dry seeds and that its level increased through the 4 d of the experiment. This suggested that NAD+-isocitrate dehydrogenase activity was regulated by posttranscriptional mechanisms during early seedling development but was controlled by mRNA level after the 2nd or 3rd d. The activity of fumarase (a component of the nonbypassed section of the TCA cycle) was low but detectable in B. napus seedlings at 12 h postimbibition, coincident with germination, and increased for the next 4 d. RNA-blot analysis suggested that fumarase activity was regulated primarily by the level of its mRNA during germination and early seedling development. It is concluded that posttranscriptional regulation of NAD+-isocitrate dehydrogenase activity is one mechanism of restricting carbon flux through the decarboxylative section of the TCA cycle during lipid mobilization in germinating oilseeds.

  5. Microbial Fe cycling and mineralization in sediments of an acidic, hypersaline lake (Lake Tyrell, Victoria, Australia)

    NASA Astrophysics Data System (ADS)

    Roden, E. E.; Blöthe, M.; Shelobolina, E.

    2009-12-01

    Lake Tyrrell is a variably acidic, hypersaline, Fe-rich lake located in Victoria, Australia. Terrestrial acid saline lakes like Lake Tyrrell may be analogs for ancient Martian surface environments, as well as possible extant subsurface environments. To investigate the potential for microbial Fe cycling under acidic conditions and high salt concentration, we collected sediment core samples during three field trips between 2006 and 2008 from the southern, acidic edge of the lake. Materials from the cores were used for chemical and mineralogical analyses, as well as for molecular (16S rRNA genes) and culture-based microbiological studies. Near-surface (< 1 m depth) pore fluids contained low but detectable dissolved oxygen (ca. 50 uM), significant dissolved Fe(II) (ca. 500 uM), and nearly constant pH of around 4 - conditions conducive to enzymatic Fe(II) oxidation. High concentrations of Fe(III) oxides begin accumulate at a depth of ca. 10 cm, and may reflect the starting point for formation of massive iron concretions that are evident at and beneath the sediment surface. MPN analyses revealed low (10-100 cells/mL) but detectable populations of aerobic, halophilic Fe(II)-oxidizing organisms on the sediment surface and in the near-surface ground water. With culture-dependent methods at least three different halotolerant lithoautotrophic cultures growing on Fe(II), thiosulfate, or tetrathionate from different acidic sites were obtained. Analysis of 16S rRNA gene sequences revealed that these organisms are similar to previous described gamma proteobacteria Thiobacillus prosperus (95%), Halothiobacillus kellyi (99%), Salinisphaera shabanense (95%) and a Marinobacter species. (98%). 16S rRNA gene pyrosequencing data from two different sites with a pH range between 3 and 4.5 revealed a dominance of gamma proteobacteria. 16S rRNA gene pyrosequencing libraries from both cores were dominated by sequences related to the Ectothiorhodospiraceae family, which includes the taxa

  6. Prediction of Solar Activity from Solar Background Magnetic Field Variations in Cycles 21-23

    NASA Astrophysics Data System (ADS)

    Shepherd, Simon J.; Zharkov, Sergei I.; Zharkova, Valentina V.

    2014-11-01

    A comprehensive spectral analysis of both the solar background magnetic field (SBMF) in cycles 21-23 and the sunspot magnetic field in cycle 23 reported in our recent paper showed the presence of two principal components (PCs) of SBMF having opposite polarity, e.g., originating in the northern and southern hemispheres, respectively. Over a duration of one solar cycle, both waves are found to travel with an increasing phase shift toward the northern hemisphere in odd cycles 21 and 23 and to the southern hemisphere in even cycle 22. These waves were linked to solar dynamo waves assumed to form in different layers of the solar interior. In this paper, for the first time, the PCs of SBMF in cycles 21-23 are analyzed with the symbolic regression technique using Hamiltonian principles, allowing us to uncover the underlying mathematical laws governing these complex waves in the SBMF presented by PCs and to extrapolate these PCs to cycles 24-26. The PCs predicted for cycle 24 very closely fit (with an accuracy better than 98%) the PCs derived from the SBMF observations in this cycle. This approach also predicts a strong reduction of the SBMF in cycles 25 and 26 and, thus, a reduction of the resulting solar activity. This decrease is accompanied by an increasing phase shift between the two predicted PCs (magnetic waves) in cycle 25 leading to their full separation into the opposite hemispheres in cycle 26. The variations of the modulus summary of the two PCs in SBMF reveals a remarkable resemblance to the average number of sunspots in cycles 21-24 and to predictions of reduced sunspot numbers compared to cycle 24: 80% in cycle 25 and 40% in cycle 26.

  7. Prediction of solar activity from solar background magnetic field variations in cycles 21-23

    SciTech Connect

    Shepherd, Simon J.; Zharkov, Sergei I.; Zharkova, Valentina V. E-mail: s.zharkov@hull.ac.uk

    2014-11-01

    A comprehensive spectral analysis of both the solar background magnetic field (SBMF) in cycles 21-23 and the sunspot magnetic field in cycle 23 reported in our recent paper showed the presence of two principal components (PCs) of SBMF having opposite polarity, e.g., originating in the northern and southern hemispheres, respectively. Over a duration of one solar cycle, both waves are found to travel with an increasing phase shift toward the northern hemisphere in odd cycles 21 and 23 and to the southern hemisphere in even cycle 22. These waves were linked to solar dynamo waves assumed to form in different layers of the solar interior. In this paper, for the first time, the PCs of SBMF in cycles 21-23 are analyzed with the symbolic regression technique using Hamiltonian principles, allowing us to uncover the underlying mathematical laws governing these complex waves in the SBMF presented by PCs and to extrapolate these PCs to cycles 24-26. The PCs predicted for cycle 24 very closely fit (with an accuracy better than 98%) the PCs derived from the SBMF observations in this cycle. This approach also predicts a strong reduction of the SBMF in cycles 25 and 26 and, thus, a reduction of the resulting solar activity. This decrease is accompanied by an increasing phase shift between the two predicted PCs (magnetic waves) in cycle 25 leading to their full separation into the opposite hemispheres in cycle 26. The variations of the modulus summary of the two PCs in SBMF reveals a remarkable resemblance to the average number of sunspots in cycles 21-24 and to predictions of reduced sunspot numbers compared to cycle 24: 80% in cycle 25 and 40% in cycle 26.

  8. Environmental impact associated with activated carbon preparation from olive-waste cake via life cycle assessment.

    PubMed

    Hjaila, K; Baccar, R; Sarrà, M; Gasol, C M; Blánquez, P

    2013-11-30

    The life cycle assessment (LCA) environmental tool was implemented to quantify the potential environmental impacts associated with the activated carbon (AC) production process from olive-waste cakes in Tunisia. On the basis of laboratory investigations for AC preparation, a flowchart was developed and the environmental impacts were determined. The LCA functional unit chosen was the production of 1 kg of AC from by-product olive-waste cakes. The results showed that impregnation using H3PO4 presented the highest environmental impacts for the majority of the indicators tested: acidification potential (62%), eutrophication (96%), ozone depletion potential (44%), human toxicity (64%), fresh water aquatic ecotoxicity (90%) and terrestrial ecotoxicity (92%). One of the highest impacts was found to be the global warming potential (11.096 kg CO2 eq/kg AC), which was equally weighted between the steps involving impregnation, pyrolysis, and drying the washed AC. The cumulative energy demand of the AC production process from the by-product olive-waste cakes was 167.63 MJ contributed by impregnation, pyrolysis, and drying the washed AC steps. The use of phosphoric acid and electricity in the AC production were the main factors responsible for the majority of the impacts. If certain modifications are incorporated into the AC production, such as implementing synthesis gas recovery and reusing it as an energy source and recovery of phosphoric acid after AC washing, additional savings could be realized, and environmental impacts could be minimized.

  9. The viability of a nonenzymatic reductive citric acid cycle - Kinetics and thermochemistry

    USGS Publications Warehouse

    Ross, D.S.

    2007-01-01

    The likelihood of a functioning nonenzymatic reductive citric acid cycle, recently proposed as the precursor to biosynthesis on early Earth, is examined on the basis of the kinetics and thermochemistry of the acetate ??? pyruvate ??? oxaloacetate ??? malate sequence. Using data derived from studies of the Pd-catalyzed phosphinate reduction of carbonyl functions it is shown that the rate of conversion of pyruvate to malate with that system would have been much too slow to have played a role in the early chemistry of life, while naturally occurring reduction systems such as the fayalite-magnetite-quartz and pyrrhotite-pyrite-magnetite mineral assemblages would have provided even slower conversions. It is also shown that the production of pyruvate from acetate is too highly endoergic to be driven by a naturally occurring energy source such as pyrophosphate. It is thus highly doubtful that the cycle can operate at suitable rates without enzymes, and most unlikely that it could have participated in the chemistry leading to life. ?? 2006 Springer Science + Business Media B.V.

  10. The Viability of a Nonenzymatic Reductive Citric Acid Cycle Kinetics and Thermochemistry

    NASA Astrophysics Data System (ADS)

    Ross, David S.

    2007-02-01

    The likelihood of a functioning nonenzymatic reductive citric acid cycle, recently proposed as the precursor to biosynthesis on early Earth, is examined on the basis of the kinetics and thermochemistry of the acetate → pyruvate → oxaloacetate → malate sequence. Using data derived from studies of the Pd-catalyzed phosphinate reduction of carbonyl functions it is shown that the rate of conversion of pyruvate to malate with that system would have been much too slow to have played a role in the early chemistry of life, while naturally occurring reduction systems such as the fayalite magnetite quartz and pyrrhotite pyrite magnetite mineral assemblages would have provided even slower conversions. It is also shown that the production of pyruvate from acetate is too highly endoergic to be driven by a naturally occurring energy source such as pyrophosphate. It is thus highly doubtful that the cycle can operate at suitable rates without enzymes, and most unlikely that it could have participated in the chemistry leading to life.

  11. Bioluminescence regenerative cycle (BRC) system: theoretical considerations for nucleic acid quantification assays.

    PubMed

    Hassibi, Arjang; Contag, Christopher; Vlad, Marcel O; Hafezi, Maryam; Lee, Thomas H; Davis, Ronald W; Pourmand, Nader

    2005-08-01

    A novel application of bioluminescence for nucleic acid quantification, the bioluminescence regenerative cycle (BRC), is described in theoretical terms and supported by preliminary experimental data. In the BRC system, pyrophosphate (PPi) molecules are released during biopolymerization and are counted and correlated to DNA copy number. The enzymes ATP-sulfurylase and firefly luciferase are employed to generate photons quantitatively from PPi. Enzymatic unity-gain positive feedback is implemented to amplify photon generation and to compensate for decay in light intensity by self-regulation. The cumulative total of photons can be orders of magnitude higher than in typical chemiluminescent processes. A system level theoretical model is developed, taking into account the kinetics of the regenerative cycle, contamination, and detector noise. Data and simulations show that the photon generation process achieves steady state for the time range of experimental measurements. Based on chain reaction theory, computations show that BRC is very sensitive to variations in the efficiencies of the chemical reactions involved and less sensitive to variations in the quantum yield of the process. We show that BRC can detect attomolar quantities of DNA (10(-18) mol), and that the useful dynamic range is five orders of magnitude. Sensitivity is not constrained by detector performance but rather by background bioluminescence caused by contamination by either PPi or ATP (adenosine triphosphate).

  12. Altered lower leg muscle activation patterns in patients with cerebral palsy during cycling on an ergometer

    PubMed Central

    Alves-Pinto, Ana; Blumenstein, Tobias; Turova, Varvara; Lampe, Renée

    2016-01-01

    Objective Cycling on a recumbent ergometer constitutes one of the most popular rehabilitation exercises in cerebral palsy (CP). However, no control is performed on how muscles are being used during training. Given that patients with CP present altered muscular activity patterns during cycling or walking, it is possible that an incorrect pattern of muscle activation is being promoted during rehabilitation cycling. This study investigated patterns of muscular activation during cycling on a recumbent ergometer in patients with CP and whether those patterns are determined by the degree of spasticity and of mobility. Methods Electromyographic (EMG) recordings of lower leg muscle activation during cycling on a recumbent ergometer were performed in 14 adult patients diagnosed with CP and five adult healthy participants. EMG recordings were done with an eight-channel EMG system built in the laboratory. The activity of the following muscles was recorded: Musculus rectus femoris, Musculus biceps femoris, Musculus tibialis anterior, and Musculus gastrocnemius. The degree of muscle spasticity and mobility was assessed using the Modified Ashworth Scale and the Gross Motor Function Classification System, respectively. Muscle activation patterns were described in terms of onset and duration of activation as well as duration of cocontractions. Results Muscle activation in CP was characterized by earlier onsets, longer periods of activation, a higher occurrence of agonist–antagonist cocontractions, and a more variable cycling tempo in comparison to healthy participants. The degree of altered muscle activation pattern correlated significantly with the degree of spasticity. Conclusion This study confirmed the occurrence of altered lower leg muscle activation patterns in patients with CP during cycling on a recumbent ergometer. There is a need to develop feedback systems that can inform patients and therapists of an incorrect muscle activation during cycling and support the training

  13. Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2

    PubMed Central

    McCormack, Ryan M; Lyapichev, Kirill; Olsson, Melissa L; Podack, Eckhard R; Munson, George P

    2015-01-01

    Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria. DOI: http://dx.doi.org/10.7554/eLife.06505.001 PMID:26418746

  14. The gamma-aminobutyric acid shunt contributes to closing the tricarboxylic acid cycle in Synechocystis sp PCC 6803

    SciTech Connect

    Xiong, W; Brune, D; Vermaas, WFJ

    2014-07-16

    A traditional 2-oxoglutarate dehydrogenase complex is missing in the cyanobacterial tricarboxylic acid cycle. To determine pathways that convert 2-oxoglutarate into succinate in the cyanobacterium Synechocystis sp. PCC 6803, a series of mutant strains, Delta sll1981, Delta slr0370, Delta slr1022 and combinations thereof, deficient in 2-oxoglutarate decarboxylase (Sll1981), succinate semialdehyde dehydrogenase (Slr0370), and/or in gamma-aminobutyrate metabolism (Slr1022) were constructed. Like in Pseudomonas aeruginosa, N-acetylornithine aminotransferase, encoded by slr1022, was shown to also function as gamma-aminobutyrate aminotransferase, catalysing gamma-aminobutyrate conversion to succinic semialdehyde. As succinic semialdehyde dehydrogenase converts succinic semialdehyde to succinate, an intact gamma-aminobutyrate shunt is present in Synechocystis. The Delta sll1981 strain, lacking 2-oxoglutarate decarboxylase, exhibited a succinate level that was 60% of that in wild type. However, the succinate level in the Delta slr1022 and Delta slr0370 strains and the Delta sll1981/Delta slr1022 and Delta sll1981/Delta slr0370 double mutants was reduced to 20-40% of that in wild type, suggesting that the gamma-aminobutyrate shunt has a larger impact on metabolite flux to succinate than the pathway via 2-oxoglutarate decarboxylase. C-13-stable isotope analysis indicated that the gamma-aminobutyrate shunt catalysed conversion of glutamate to succinate. Independent of the 2-oxoglutarate decarboxylase bypass, the gamma-aminobutyrate shunt is a major contributor to flux from 2-oxoglutarate and glutamate to succinate in Synechocystis sp. PCC 6803.

  15. Respiratory Muscle Activity During Simultaneous Stationary Cycling and Inspiratory Muscle Training.

    PubMed

    Hellyer, Nathan J; Folsom, Ian A; Gaz, Dan V; Kakuk, Alynn C; Mack, Jessica L; Ver Mulm, Jacyln A

    2015-12-01

    Inspiratory muscle training (IMT) strengthens the muscles of respiration, improves breathing efficiency, and increases fitness. The IMT is generally performed independently of aerobic exercise; however, it is not clear whether there is added benefit of performing the IMT while simultaneously performing aerobic exercise in terms of activating and strengthening inspiratory muscles. The purpose of our study was to determine the effect of IMT on respiratory muscle electromyography (EMG) activity during stationary cycling in the upright and drops postures as compared with that when the IMT was performed alone. Diaphragm and sternocleidomastoid EMG activity was measured under different resting and cycling postures, with and without the use of the IMT at 40% maximal inspiratory pressure (n = 10; mean age 37). Cycling in an upright posture while simultaneously performing the IMT resulted in a significantly greater diaphragm EMG activity than while performing the IMT at rest in upright or drops postures (p ≤ 0.05). Cycling in drops postures while performing the IMT had a significantly greater diaphragm EMG activity than when performing the IMT at rest in either upright or drops postures (p ≤ 0.05). Sternocleidomastoid muscle activity increased with both cycling and IMT, although posture had little effect. These results support our hypothesis in that the IMT while cycling increases respiratory EMG activity to a significantly greater extent than when performing the IMT solely at rest, suggesting that the combination of IMT and cycling may provide an additive training effect. PMID:26584054

  16. The Life Cycle of Active Region Magnetic Fields

    NASA Astrophysics Data System (ADS)

    Cheung, M. C. M.; van Driel-Gesztelyi, L.; Martínez Pillet, V.; Thompson, M. J.

    2016-08-01

    We present a contemporary view of how solar active region magnetic fields are understood to be generated, transported and dispersed. Empirical trends of active region properties that guide model development are discussed. Physical principles considered important for active region evolution are introduced and advances in modeling are reviewed.

  17. Artificial Autopolyploidization Modifies the Tricarboxylic Acid Cycle and GABA Shunt in Arabidopsis thaliana Col-0

    PubMed Central

    Vergara, Fredd; Kikuchi, Jun; Breuer, Christian

    2016-01-01

    Autopolyploidy is a process whereby the chromosome set is multiplied and it is a common phenomenon in angiosperms. Autopolyploidy is thought to be an important evolutionary force that has led to the formation of new plant species. Despite its relevance, the consequences of autopolyploidy in plant metabolism are poorly understood. This study compares the metabolic profiles of natural diploids and artificial autotetraploids of Arabidopsis thaliana Col-0. Different physiological parameters are compared between diploids and autotetraploids using nuclear magnetic resonance (NMR), elemental analysis (carbon:nitrogen balance) and quantitative real-time PCR (qRT-PCR). The main difference between diploid and autotetraploid A. thaliana Col-0 is observed in the concentration of metabolites related to the tricarboxylic acid cycle (TCA) and γ-amino butyric acid (GABA) shunt, as shown by multivariate statistical analysis of NMR spectra. qRT-PCR shows that genes related to the TCA and GABA shunt are also differentially expressed between diploids and autotetraploids following similar trends as their corresponding metabolites. Solid evidence is presented to demonstrate that autopolyploidy influences core plant metabolic processes. PMID:27212081

  18. Developments in absorptive glass mat separators for cycling applications and 36 V lead-acid batteries

    NASA Astrophysics Data System (ADS)

    Toniazzo, V.; Lambert, U.

    The major markets for valve-regulated lead-acid (VRLA) batteries are undergoing a radical upheaval. In particular, the telecommunications industry requires more reliable power supplies, and the familiar 12 V electrical system in cars will probably be soon replaced by a 36/42 V system, or by other electrical systems if part of the automotive market is taken over by hybrid electrical vehicles (HEVs). In order to meet these new challenges and enable VRLA batteries to provide a satisfactory life in float and cycling applications in the telecommunication field, or in the high-rate-partial-state-of-charge service required by both 36/42 V automobiles and HEVs, the lead-acid battery industry has to improve substantially the quality of present VRLA batteries based on absorptive glass mat (AGM) technology. Therefore, manufacturing steps and cell components have to be optimized, especially AGM separators as these are key components for better production yields and battery performance. This paper shows how the optimal segregation of the coarse and fine fibres in an AGM separator structure can improve greatly the properties of the material. The superior capillarity, springiness and mechanical properties of the 100% glass Amerglass multilayer separator compared with commercial monolayer counterparts with the same specific surface-area is highlighted.

  19. Heteromeric amino acid transporters. In search of the molecular bases of transport cycle mechanisms.

    PubMed

    Palacín, Manuel; Errasti-Murugarren, Ekaitz; Rosell, Albert

    2016-06-15

    Heteromeric amino acid transporters (HATs) are relevant targets for structural studies. On the one hand, HATs are involved in inherited and acquired human pathologies. On the other hand, these molecules are the only known examples of solute transporters composed of two subunits (heavy and light) linked by a disulfide bridge. Unfortunately, structural knowledge of HATs is scarce and limited to the atomic structure of the ectodomain of a heavy subunit (human 4F2hc-ED) and distant prokaryotic homologues of the light subunits that share a LeuT-fold. Recent data on human 4F2hc/LAT2 at nanometer resolution revealed 4F2hc-ED positioned on top of the external loops of the light subunit LAT2. Improved resolution of the structure of HATs, combined with conformational studies, is essential to establish the structural bases for light subunit recognition and to evaluate the functional relevance of heavy and light subunit interactions for the amino acid transport cycle.

  20. Artificial Autopolyploidization Modifies the Tricarboxylic Acid Cycle and GABA Shunt in Arabidopsis thaliana Col-0

    NASA Astrophysics Data System (ADS)

    Vergara, Fredd; Kikuchi, Jun; Breuer, Christian

    2016-05-01

    Autopolyploidy is a process whereby the chromosome set is multiplied and it is a common phenomenon in angiosperms. Autopolyploidy is thought to be an important evolutionary force that has led to the formation of new plant species. Despite its relevance, the consequences of autopolyploidy in plant metabolism are poorly understood. This study compares the metabolic profiles of natural diploids and artificial autotetraploids of Arabidopsis thaliana Col-0. Different physiological parameters are compared between diploids and autotetraploids using nuclear magnetic resonance (NMR), elemental analysis (carbon:nitrogen balance) and quantitative real-time PCR (qRT-PCR). The main difference between diploid and autotetraploid A. thaliana Col-0 is observed in the concentration of metabolites related to the tricarboxylic acid cycle (TCA) and γ-amino butyric acid (GABA) shunt, as shown by multivariate statistical analysis of NMR spectra. qRT-PCR shows that genes related to the TCA and GABA shunt are also differentially expressed between diploids and autotetraploids following similar trends as their corresponding metabolites. Solid evidence is presented to demonstrate that autopolyploidy influences core plant metabolic processes.

  1. Artificial Autopolyploidization Modifies the Tricarboxylic Acid Cycle and GABA Shunt in Arabidopsis thaliana Col-0.

    PubMed

    Vergara, Fredd; Kikuchi, Jun; Breuer, Christian

    2016-05-23

    Autopolyploidy is a process whereby the chromosome set is multiplied and it is a common phenomenon in angiosperms. Autopolyploidy is thought to be an important evolutionary force that has led to the formation of new plant species. Despite its relevance, the consequences of autopolyploidy in plant metabolism are poorly understood. This study compares the metabolic profiles of natural diploids and artificial autotetraploids of Arabidopsis thaliana Col-0. Different physiological parameters are compared between diploids and autotetraploids using nuclear magnetic resonance (NMR), elemental analysis (carbon:nitrogen balance) and quantitative real-time PCR (qRT-PCR). The main difference between diploid and autotetraploid A. thaliana Col-0 is observed in the concentration of metabolites related to the tricarboxylic acid cycle (TCA) and γ-amino butyric acid (GABA) shunt, as shown by multivariate statistical analysis of NMR spectra. qRT-PCR shows that genes related to the TCA and GABA shunt are also differentially expressed between diploids and autotetraploids following similar trends as their corresponding metabolites. Solid evidence is presented to demonstrate that autopolyploidy influences core plant metabolic processes.

  2. Artificial Autopolyploidization Modifies the Tricarboxylic Acid Cycle and GABA Shunt in Arabidopsis thaliana Col-0.

    PubMed

    Vergara, Fredd; Kikuchi, Jun; Breuer, Christian

    2016-01-01

    Autopolyploidy is a process whereby the chromosome set is multiplied and it is a common phenomenon in angiosperms. Autopolyploidy is thought to be an important evolutionary force that has led to the formation of new plant species. Despite its relevance, the consequences of autopolyploidy in plant metabolism are poorly understood. This study compares the metabolic profiles of natural diploids and artificial autotetraploids of Arabidopsis thaliana Col-0. Different physiological parameters are compared between diploids and autotetraploids using nuclear magnetic resonance (NMR), elemental analysis (carbon:nitrogen balance) and quantitative real-time PCR (qRT-PCR). The main difference between diploid and autotetraploid A. thaliana Col-0 is observed in the concentration of metabolites related to the tricarboxylic acid cycle (TCA) and γ-amino butyric acid (GABA) shunt, as shown by multivariate statistical analysis of NMR spectra. qRT-PCR shows that genes related to the TCA and GABA shunt are also differentially expressed between diploids and autotetraploids following similar trends as their corresponding metabolites. Solid evidence is presented to demonstrate that autopolyploidy influences core plant metabolic processes. PMID:27212081

  3. ιHorologi, the first coronal activity cycle in a young solar-like star

    NASA Astrophysics Data System (ADS)

    Sanz-Forcada, J.; Stelzer, B.; Metcalfe, T. S.

    2013-05-01

    Context. The shortest chromospheric (Ca ii H&K) activity cycle (1.6 yr) has been recently discovered in the young (~600 Myr) solar-like star ι Hor. Coronal X-ray activity cycles have only been discovered in a few stars other than the Sun, all of them with an older age and a lower activity level than ι Hor. Aims: We intended to find the X-ray coronal counterpart of the chromospheric cycle for ι Hor. This represents the first X-ray cycle observed in an active star, as well as the paradigm of the first coronal cycles in the life of a solar-like star. Methods: We monitored ι Hor with XMM-Newton observations spanning almost two years. The spectra of each observation are fit with two-temperature coronal models to study the long-term variability of the star. Results: We find a cyclic behavior in X-rays very similar to the contemporaneous chromospheric cycle. The continuous chromospheric monitoring for more than three cycle lengths shows a trend toward decreasing amplitude, apparently modulated by a longer term trend. The second cycle is disrupted prior to reaching its maximum, followed by a brief episode of chaotic variability before the cyclic behavior resumes, only to be disrupted again after slightly more than one cycle. Conclusions: We confirm the presence of an activity cycle of ~1.6 yr in ι Hor both in X-rays and Ca ii H&K. It is likely subject to the modulation of a longer, not yet constrained second cycle. The 1.6 yr cycle is the shortest coronal one observed to date, and ι Hor represents the most active star for which a coronal activity cycle has been found. This cycle is probably representative of the first coronal cycles in the life of a solar-like star, at the age when life started on Earth. Table 2 is available in electronic form at http://www.aanda.org

  4. [Biological activity of retinoic acid and methylretinoate].

    PubMed

    Dusheĭko, A A; Chernukhina, L A; Blazhevich, M A; Davydova, L P

    1980-01-01

    Vitamin A lack in the diet of chicken produces a significant increase in the glandular stomach as well as formation of erosions and ulcers on the surface of the mucous membrane of the intermediate zone. Replacement of retinyl acetate in the diet by retinoic acid or methyl retionate gives no rise to changes in the morphological integrity of the glandular stomach of the chickens. Moreover, these compounds produce a reverse development of vitamin A-induced changes. It is thus concluded that when the diet lacks vitamin A, both retinoic acid and methyl retionate are capable of maintaining the structural integrity of the stomach.

  5. Nanocrosses of lead sulphate as the negative active material of lead acid batteries

    NASA Astrophysics Data System (ADS)

    Liu, Yi; Gao, Pengran; Bu, Xianfu; Kuang, Guizhi; Liu, Wei; Lei, Lixu

    2014-10-01

    Lead sulphate transforms into PbO2 and Pb in the positive and negative electrodes, respectively, when a lead acid battery is charged, thus, it is an active material. It is also generally acknowledged that sulphation results in the failure of lead acid batteries; therefore, it is very interesting to find out how to make lead sulphate more electrochemically active. Here, we demonstrate that nanocrystalline lead sulphate can be used as excellent negative active material in lead acid batteries. The lead sulphate nanocrystals, which are prepared by a facile chemical precipitation of aqueous lead acetate and sodium sulphate in a few minutes, look like crosses with diameter of each arm being 100 nm to 3 μm. The electrode is effectively formed in much shorter time than traditional technique, yet it discharges a capacity of 103 mA h g-1 at the current density of 120 mA g-1, which is 24% higher than that discharged by the electrode made from leady oxide under the same condition. During 100% DOD cycles, more than 80% of that capacity remains in 550 cycles. These results show that lead sulphate can be a nice negative active material in lead acid batteries.

  6. Application of acid-activated Bauxsol for wastewater treatment with high phosphate concentration: Characterization, adsorption optimization, and desorption behaviors.

    PubMed

    Ye, Jie; Cong, Xiangna; Zhang, Panyue; Zeng, Guangming; Hoffmann, Erhard; Liu, Yang; Wu, Yan; Zhang, Haibo; Fang, Wei; Hahn, Hermann H

    2016-02-01

    Acid-activated Bauxsol was applied to treat wastewater with high phosphate concentration in a batch adsorption system in this paper. The effect of acid activation on the change of Bauxsol structure was systematically investigated. The mineralogical inhomogeneity and intensity of Bauxsol decreased after acid activation, and FeCl3·2H2O and Al(OH)3 became the dominant phases of acid-activated Bauxsol adsorption. Moreover, the BET surface area and total pore volume of Bauxsol increased after acid activation. Interaction of initial solution pH and adsorption temperature on phosphate adsorption onto acid-activated Bauxsol was investigated by using response surface methodology with central composite design. The maximum phosphate adsorption capacity of 192.94 mg g(-1) was achieved with an initial solution pH of 4.19 and an adsorption temperature of 52.18 °C, which increased by 7.61 times compared with that of Bauxsol (22.40 mg g(-1)), and was higher than other adsorbents. Furthermore, the desorption studies demonstrated that the acid-activated Bauxsol was successfully regenerated with 0.5 mol L(-1) HCl solution. The adsorption capacity and desorption efficiency of acid-activated Bauxsol maintained at 80.48% and 93.02% in the fifth adsorption-desorption cycle, respectively, suggesting that the acid-activated Bauxsol could be repeatedly used in wastewater treatment with high phosphate concentration. PMID:26606195

  7. Application of acid-activated Bauxsol for wastewater treatment with high phosphate concentration: Characterization, adsorption optimization, and desorption behaviors.

    PubMed

    Ye, Jie; Cong, Xiangna; Zhang, Panyue; Zeng, Guangming; Hoffmann, Erhard; Liu, Yang; Wu, Yan; Zhang, Haibo; Fang, Wei; Hahn, Hermann H

    2016-02-01

    Acid-activated Bauxsol was applied to treat wastewater with high phosphate concentration in a batch adsorption system in this paper. The effect of acid activation on the change of Bauxsol structure was systematically investigated. The mineralogical inhomogeneity and intensity of Bauxsol decreased after acid activation, and FeCl3·2H2O and Al(OH)3 became the dominant phases of acid-activated Bauxsol adsorption. Moreover, the BET surface area and total pore volume of Bauxsol increased after acid activation. Interaction of initial solution pH and adsorption temperature on phosphate adsorption onto acid-activated Bauxsol was investigated by using response surface methodology with central composite design. The maximum phosphate adsorption capacity of 192.94 mg g(-1) was achieved with an initial solution pH of 4.19 and an adsorption temperature of 52.18 °C, which increased by 7.61 times compared with that of Bauxsol (22.40 mg g(-1)), and was higher than other adsorbents. Furthermore, the desorption studies demonstrated that the acid-activated Bauxsol was successfully regenerated with 0.5 mol L(-1) HCl solution. The adsorption capacity and desorption efficiency of acid-activated Bauxsol maintained at 80.48% and 93.02% in the fifth adsorption-desorption cycle, respectively, suggesting that the acid-activated Bauxsol could be repeatedly used in wastewater treatment with high phosphate concentration.

  8. Cell cycle effects of drugs

    SciTech Connect

    Dethlefsen, L.A.

    1986-01-01

    This book contains 11 chapters. Some of the chapter titles are: Cell Growth and Division Cycle; Cell Cycle Effects of Alkylating Agents; Biological Effects of Folic Acid Antagonists with Antineoplastic Activity; and Bleomycin-Mode of Action with Particular Reference to the Cell Cycle.

  9. A microbial arsenic cycle in sediments of an acidic mine impoundment: Herman Pit, Clear Lake, California

    USGS Publications Warehouse

    Blum, Jodi S.; McCann, Shelley; Bennett, S.; Miller, Laurence G.; Stolz, J. R.; Stoneburner, B.; Saltikov, C.; Oremland, Ronald S.

    2015-01-01

    The involvement of prokaryotes in the redox reactions of arsenic occurring between its +5 [arsenate; As(V)] and +3 [arsenite; As(III)] oxidation states has been well established. Most research to date has focused upon circum-neutral pH environments (e.g., freshwater or estuarine sediments) or arsenic-rich “extreme” environments like hot springs and soda lakes. In contrast, relatively little work has been conducted in acidic environments. With this in mind we conducted experiments with sediments taken from the Herman Pit, an acid mine drainage impoundment of a former mercury (cinnabar) mine. Due to the large adsorptive capacity of the abundant Fe(III)-rich minerals, we were unable to initially detect in solution either As(V) or As(III) added to the aqueous phase of live sediment slurries or autoclaved controls, although the former consumed added electron donors (i.e., lactate, acetate, hydrogen), while the latter did not. This prompted us to conduct further experiments with diluted slurries using the live materials from the first incubation as inoculum. In these experiments we observed reduction of As(V) to As(III) under anoxic conditions and reduction rates were enhanced by addition of electron donors. We also observed oxidation of As(III) to As(V) in oxic slurries as well as in anoxic slurries amended with nitrate. We noted an acid-tolerant trend for sediment slurries in the cases of As(III) oxidation (aerobic and anaerobic) as well as for anaerobic As(V) reduction. These observations indicate the presence of a viable microbial arsenic redox cycle in the sediments of this extreme environment, a result reinforced by the successful amplification of arsenic functional genes (aioA, and arrA) from these materials.

  10. Leg muscle activation and distance setting of the leg cycle ergometer for use by the elderly.

    PubMed

    Kim, Seon-Chill; Lee, Sang-Yeol; Lee, Young-Ik

    2014-10-01

    [Purpose] This study verified the leg muscle activities of elderly subjects performing leg cycle ergometer exercise. [Subjects] Forty-one elderly persons were the subjects of this study. [Methods] For the three distances corresponding to knee flexion angles of 15, 45, and 70, the muscle activities of the rectus femoris, biceps femoris, tibialis anterior and lateral gastrocnemius were measured while the subjects exercised on a cycle ergometer. [Results] The rectus femoris and biceps femoris showed statistically significant increases as the distance between the cycle ergometer and the body increased, and the lateral gastrocnemius muscle activation showed a statistically significant increase as the distance from the body to the cycle ergometer decreased. [Conclusion] When the elderly have limb muscle weakness, leg cycle ergometer distances should be adjusted.

  11. Rhinosporidium seeberi Nuclear Cycle Activities Using Confocal Microscopy.

    PubMed

    Delfino, Darly; Mendoza, Leonel; Vilela, Raquel

    2016-02-01

    Rhinosporidium seeberi is an uncultivated Ichthyosporean infecting animals, including humans. Recent studies suggested R. seeberi undergoes synchronized nuclear division without cytokinesis. We used confocal microscopy to investigate R. seeberi nuclear division cycles in formalin-fixed tissues stained with DAPI and phalloidin. We report that R. seeberi nuclei in juvenile and intermediary sporangia synchronously divided without cytokinesis. Intermediary sporangia display numerous 3-4 μm nuclei at different mitotic stages as well as a thick inner layer with strong affinity for phalloidin. Mature sporangia showed numerous 5-12 μm cell-walled endospores, each containing a 2-4 μm in diameter nucleus. Phalloidin did not bind to the inner layers of mature sporangia or endospores. The development of a "germinative zone" in the inner layer of mature sporangia containing hundreds of nuclei was also confirmed. This study establishes that during the R. seeberi life cycle synchronous nuclear divisions without cytokinesis takes place, resulting in the formation of thousands of nuclei. Cytokinesis, on the other hand, is a 1-time event and occurs in the latest stages of intermediate sporangia, after the formation of thousands of nuclei and just before mature sporangia development. PMID:26461427

  12. Perfluoroalkyl acids : Recent activities and research progress

    EPA Science Inventory

    The perfluoroalkyl acids (PFAAs) are a family of man-made fluorinated organic chemicals consisting of a carbon backbone typically of four to fourteen in length and a charged functional moiety (primarily carboxylate, sulfonate or phosphonate). The two most widely known PFAAs are ...

  13. Cycling for Students with ASD: Self-Regulation Promotes Sustained Physical Activity

    ERIC Educational Resources Information Center

    Todd, Teri; Reid, Greg; Butler-Kisber, Lynn

    2010-01-01

    Individuals with autism often lack motivation to engage in sustained physical activity. Three adolescents with severe autism participated in a 16-week program and each regularly completed 30 min of cycling at the end of program. This study investigated the effect of a self-regulation instructional strategy on sustained cycling, which included…

  14. Tricarboxylic acid cycle-sustained oxidative phosphorylation in isolated myelin vesicles.

    PubMed

    Ravera, Silvia; Bartolucci, Martina; Calzia, Daniela; Aluigi, Maria Grazia; Ramoino, Paola; Morelli, Alessandro; Panfoli, Isabella

    2013-11-01

    The Central Nervous System (CNS) function was shown to be fueled exclusively by oxidative phosphorylation (OXPHOS). This is in line with the sensitivity of brain to hypoxia, but less with the scarcity of the mitochondria in CNS. Consistently with the ectopic expression of FoF1-ATP synthase and the electron transfer chain in myelin, we have reported data demonstrating that isolated myelin vesicles (IMV) conduct OXPHOS. It may suggest that myelin sheath could be a site for the whole aerobic degradation of glucose. In this paper, we assayed the functionality of glycolysis and of TCA cycle enzymes in IMV purified from bovine forebrain. We found the presence and activity of all of the glycolytic and TCA cycle enzymes, comparable to those in mitochondria-enriched fractions, in the same experimental conditions. IMV also contain consistent carbonic anhydrase activity. These data suggest that myelin may be a contributor in energy supply for the axon, performing an extra-mitochondrial aerobic OXPHOS. The vision of myelin as the site of aerobic metabolism may shed a new light on many demyelinating pathologies, that cause an a yet unresolved axonal degeneration and whose clinical onset coincides with myelin development completion.

  15. The cellular and compartmental profile of mouse retinal glycolysis, tricarboxylic acid cycle, oxidative phosphorylation, and ~P transferring kinases

    PubMed Central

    Rueda, Elda M.; Johnson, Jerry E.; Giddabasappa, Anand; Swaroop, Anand; Brooks, Matthew J.; Sigel, Irena; Chaney, Shawnta Y.

    2016-01-01

    Purpose The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases. Our goals were twofold: 1) to characterize the gene expression, protein expression, and activity of key synthesizing and regulating enzymes of energy metabolism in the whole mouse retina, retinal compartments, and/or cells and 2) to provide an integrative analysis of the results related to function. Methods mRNA expression data of energy-related genes were extracted from our whole retinal Affymetrix microarray data. Fixed-frozen retinas from adult C57BL/6N mice were used for immunohistochemistry, laser scanning confocal microscopy, and enzymatic histochemistry. The immunoreactivity levels of well-characterized antibodies, for all major retinal cells and their compartments, were obtained using our established semiquantitative confocal and imaging techniques. Quantitative cytochrome oxidase (COX) and lactate dehydrogenase (LDH) activity was determined histochemically. Results The Affymetrix data revealed varied gene expression patterns of the ATP synthesizing and regulating enzymes found in the muscle, liver, and brain. Confocal studies showed differential cellular and compartmental distribution of isozymes involved in glucose, glutamate, glutamine, lactate, and creatine metabolism. The pattern and intensity of the antibodies and of the COX and LDH activity showed the high capacity of photoreceptors for aerobic glycolysis and OXPHOS. Competition assays with pyruvate revealed that LDH-5 was localized in the photoreceptor

  16. Synthesis of sulfonated porous carbon nanospheres solid acid by a facile chemical activation route

    SciTech Connect

    Chang, Binbin Guo, Yanzhen; Yin, Hang; Zhang, Shouren; Yang, Baocheng

    2015-01-15

    Generally, porous carbon nanospheres materials are usually prepared via a template method, which is a multi-steps and high-cost strategy. Here, we reported a porous carbon nanosphere solid acid with high surface area and superior porosity, as well as uniform nanospheical morphology, which prepared by a facile chemical activation with ZnCl{sub 2} using resorcinol-formaldehyde (RF) resins spheres as precursor. The activation of RF resins spheres by ZnCl{sub 2} at 400 °C brought high surface area and large volume, and simultaneously retained numerous oxygen-containing and hydrogen-containing groups due to the relatively low processing temperature. The presence of these functional groups is favorable for the modification of –SO{sub 3}H groups by a followed sulfonation treating with sulphuric acid and organic sulfonic acid. The results of N{sub 2} adsorption–desorption and electron microscopy clearly showed the preservation of porous structure and nanospherical morphology. Infrared spectra certified the variation of surface functional groups after activation and the successful modification of –SO{sub 3}H groups after sulfonation. The acidities of catalysts were estimated by an indirect titration method and the modified amount of –SO{sub 3}H groups were examined by energy dispersive spectra. The results suggested sulfonated porous carbon nanospheres catalysts possessed high acidities and –SO{sub 3}H densities, which endowed their significantly catalytic activities for biodiesel production. Furthermore, their excellent stability and recycling property were also demonstrated by five consecutive cycles. - Graphical abstract: Sulfonated porous carbon nanospheres with high surface area and superior catalytic performance were prepared by a facile chemical activation route. - Highlights: • Porous carbon spheres solid acid prepared by a facile chemical activation. • It owns high surface area, superior porosity and uniform spherical morphology. • It possesses

  17. Possible chromospheric activity cycles in II Peg, UX Ari and V711 Tau

    NASA Astrophysics Data System (ADS)

    Buccino, Andrea P.; Mauas, Pablo J. D.

    2009-02-01

    We study the Mount Wilson indices we obtained indirectly from IUE high and low resolution spectra of the RS CVn-type systems II Peg (K2IV), UX Ari (K0IV+G5V) and V711 Tau (K1IV+G5V), extensively observed by IUE from 1978 to 1996. We analyze the activity signatures, which correspond to the primary star, with the Lomb-Scargle periodogram. From the analysis of V711 Tau data, we found a possible chromospheric cycle with a period of 18 years and a shorter ~3 year cycle, which could be associated to a chromospheric flip-flop cycle. The data of II Peg also suggest a chromospheric cycle of ~21 years and a flip-flop cycle of ~9 years. Finally, we obtained a possible chromospheric cycle of ~6 years for UX Ari.

  18. A 22-yrs Hurricane Cycle and its Relation to Geomagnetic Activity

    NASA Astrophysics Data System (ADS)

    Mendoza, Blanca; Pazos, Marni

    Applying spectral analysis to the Atlantic and Pacific hurricane time series, we found period-icities that coincide with the main sunspot and magnetic solar cycles. To assess the possibility that these periodicities could be associated to solar activity, we obtain correlations between hurricane occurrence and several solar activity-related phenomena, such as the total solar irra-diance, the cosmic ray flux and the Dst index of geomagnetic activity. Our results indicate that the highest significant correlations are found between the Atlantic and Pacific hurricanes and the Dst index. Most importantly, both oceans present the highest hurricane-Dst correlations during the ascending part of odd solar cycles and the descending phase of even solar cycles. This shows not only the existence of a 22yrs cycle but also the nature of such periodicity. Fur-thermore, we found that the Atlantic hurricanes behave differently from the Pacific hurricanes in relation to the solar activity-related disturbances considered.

  19. Chlorogenic Acid Inhibits Human Platelet Activation and Thrombus Formation

    PubMed Central

    Fuentes, Eduardo; Caballero, Julio; Alarcón, Marcelo; Rojas, Armando; Palomo, Iván

    2014-01-01

    Background Chlorogenic acid is a potent phenolic antioxidant. However, its effect on platelet aggregation, a critical factor in arterial thrombosis, remains unclear. Consequently, chlorogenic acid-action mechanisms in preventing platelet activation and thrombus formation were examined. Methods and Results Chlorogenic acid in a dose-dependent manner (0.1 to 1 mmol/L) inhibited platelet secretion and aggregation induced by ADP, collagen, arachidonic acid and TRAP-6, and diminished platelet firm adhesion/aggregation and platelet-leukocyte interactions under flow conditions. At these concentrations chlorogenic acid significantly decreased platelet inflammatory mediators (sP-selectin, sCD40L, CCL5 and IL-1β) and increased intraplatelet cAMP levels/PKA activation. Interestingly, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent A2A receptor antagonist) attenuated the antiplatelet effect of chlorogenic acid. Chlorogenic acid is compatible to the active site of the adenosine A2A receptor as revealed through molecular modeling. In addition, chlorogenic acid had a significantly lower effect on mouse bleeding time when compared to the same dose of aspirin. Conclusions Antiplatelet and antithrombotic effects of chlorogenic acid are associated with the A2A receptor/adenylate cyclase/cAMP/PKA signaling pathway. PMID:24598787

  20. Krebs cycle intermediates modulate thiobarbituric acid reactive species (TBARS) production in rat brain in vitro.

    PubMed

    Puntel, Robson L; Nogueira, Cristina W; Rocha, João B T

    2005-02-01

    The aim of this study was to investigate the effect of Krebs cycle intermediates on basal and quinolinic acid (QA)- or iron-induced TBARS production in brain membranes. Oxaloacetate, citrate, succinate and malate reduced significantly the basal and QA-induced TBARS production. The potency for basal TBARS inhibition was in the order (IC50 is given in parenthesis as mM) citrate (0.37) > oxaloacetate (1.33) = succinate (1.91) > > malate (12.74). alpha-Ketoglutarate caused an increase in TBARS production without modifying the QA-induced TBARS production. Cyanide (CN-) did not modify the basal or QA-induced TBARS production; however, CN- abolished the antioxidant effects of succinate. QA-induced TBARS production was enhanced by iron ions, and abolished by desferrioxamine (DFO). The intermediates used in this study, except for alpha-ketoglutarate, prevented iron-induced TBARS production. Oxaloacetate, citrate, alpha-ketoglutarate and malate, but no succinate and QA, exhibited significantly iron-chelating properties. Only alpha-ketoglutarate and oxaloacetate protected against hydrogen peroxide-induced deoxyribose degradation, while succinate and malate showed a modest effect against Fe2+/H2O2-induced deoxyribose degradation. Using heat-treated preparations citrate, malate and oxaloacetate protected against basal or QA-induced TBARS production, whereas alpha-ketoglutarate induced TBARS production. Succinate did not offer protection against basal or QA-induced TBARS production. These results suggest that oxaloacetate, malate, succinate, and citrate are effective antioxidants against basal and iron or QA-induced TBARS production, while alpha-ketoglutarate stimulates TBARS production. The mechanism through which Krebs cycle intermediates offer protection against TBARS production is distinct depending on the intermediate used. Thus, under pathological conditions such as ischemia, where citrate concentrations vary it can assume an important role as a modulator of oxidative

  1. Surface-active properties of humic and sulfochlorohumic acids

    SciTech Connect

    Ryabova, I.N.; Mustafina, G.A.; Akkulova, Z.G.; Satymbaeva, A.S.

    2009-10-15

    The surface tension of alkaline solutions of humic acids and their sulfochloroderivatives, which are synthesized by sulfonation of chlorohumic acids isolated from coal chlorinated by the electrochemical method, is investigated. It is established that humic compounds possess weak surface activity. Basic adsorption parameters are calculated.

  2. Hydrogen Peroxide Cycling in Acidic Geothermal Environments and Potential Implications for Oxidative Stress

    NASA Astrophysics Data System (ADS)

    Mesle, M.; Beam, J.; Jay, Z.; Bodle, B.; Bogenschutz, E.; Inskeep, W.

    2014-12-01

    Hydrogen peroxide (H2O2) may be produced in natural waters via photochemical reactions between dissolved oxygen, organic carbon and light. Other reactive oxygen species (ROS) such as superoxide and hydroxyl radicals are potentially formed in environments with high concentrations of ferrous iron (Fe(II), ~10-100 μM) by reaction between H2O2 and Fe(II) (i.e., Fenton chemistry). Thermophilic archaea and bacteria inhabiting acidic iron-oxide mats have defense mechanisms against both extracellular and intracellular peroxide, such as peroxiredoxins (which can degrade H2O2) and against other ROS, such as superoxide dismutases. Biological cycling of H2O2 is not well understood in geothermal ecosystems, and geochemical measurements combined with molecular investigations will contribute to our understanding of microbial response to oxidative stress. We measured H2O2 and other dissolved compounds (Fe(II), Fe(III), H2S, O2), as well as photon flux, pH and temperature, over time in surface geothermal waters of several acidic springs in Norris Geyser Basin, Yellowstone National Park, WY (Beowulf Spring and One Hundred Spring Plain). Iron-oxide mats were sampled in Beowulf Spring for on-going analysis of metatranscriptomes and RT-qPCR assays of specific stress-response gene transcription (e.g., superoxide dismutases, peroxiredoxins, thioredoxins, and peroxidases). In situ analyses show that H2O2 concentrations are lowest in the source waters of sulfidic systems (ca. 1 μM), and increase by two-fold in oxygenated waters corresponding to Fe(III)-oxide mat formation (ca. 2 - 3 μM). Channel transects confirm increases in H2O2 as a function of oxygenation (distance). The temporal dynamics of H2O2, O2, Fe(II), and H2S in Beowulf geothermal waters were also measured during a diel cycle, and increases in H2O2 were observed during peak photon flux. These results suggest that photochemical reactions may contribute to changes in H2O2. We hypothesize that increases in H2O2 and O2

  3. Glycerolipid/free fatty acid cycle and islet β-cell function in health, obesity and diabetes.

    PubMed

    Prentki, Marc; Madiraju, S R Murthy

    2012-04-28

    Pancreatic β-cells secrete insulin in response to fluctuations in blood fuel concentrations, in particular glucose and fatty acids. However, chronic fuel surfeit can overwhelm the metabolic, signaling and secretory capacity of the β-cell leading to its dysfunction and death - often referred to as glucolipotoxicity. In β-cells and many other cells, glucose and lipid metabolic pathways converge into a glycerolipid/free fatty acid (GL/FFA) cycle, which is driven by the substrates, glycerol-3-phosphate and fatty acyl-CoA, derived from glucose and fatty acids, respectively. Although the overall operation of GL/FFA cycle, consisting of lipolysis and lipogenesis, is "futile" in terms of energy expenditure, this metabolic cycle likely plays an indispensable role for various β-cell functions, in particular insulin secretion and excess fuel detoxification. In this review, we discuss the significance of GL/FFA cycle in the β-cell, its regulation and role in generating essential metabolic signals that participate in the lipid amplification arm of glucose stimulated insulin secretion and in β-cell growth. We propose the novel concept that the lipolytic segment of GL/FFA cycle is instrumental in producing signals for insulin secretion, whereas, the lipogenic segment generates signals relevant for β-cell survival/death and growth/proliferation.

  4. The effect of the menstrual cycle and of decompression stress on arachidonic acid-induced platelet aggregation and on intrinsic platelet thromboxane production in women compared with men.

    PubMed

    Markham, S M; Dubin, N H; Rock, J A

    1991-12-01

    Menstrual cycle variations in platelet aggregation and thromboxane production in association with sex steroids have been reported. External stimuli such as decompression sickness have been associated with clotting activity changes, specifically, increased platelet aggregation. Differences in response of platelets from women and men, when subjected to such a stress, have been observed. This study evaluated the ability of washed platelets from women in the proliferative and secretory phases of the menstrual cycle to aggregate in response to arachidonic acid and the aggregation difference between washed platelets from women and men in response to decompression stress and arachidonic acid. Additionally, platelet thromboxane production differences between the assessed platelet populations were compared. Our results indicate no difference in platelet aggregability between phases of the menstrual cycle. A significant aggregation difference between platelets from women and men was noted. Platelets from women were more sensitive to arachidonic acid aggregation. These differences were not affected by decompression stress. No difference in thromboxane B2 production was noted between the platelet populations evaluated.

  5. Radiolabeled acetate as a tracer of myocardial tricarboxylic acid cycle flux

    SciTech Connect

    Buxton, D.B.; Schwaiger, M.; Nguyen, A.; Phelps, M.E.; Schelbert, H.R.

    1988-09-01

    The kinetics of (1-14C)acetate oxidation in isolated perfused rat hearts have been determined over a range of perfusion conditions. Effluent measurements demonstrated that 14CO2 cleared biexponentially over 50 minutes after bolus injection of (1-14C)acetate into normoxic hearts perfused with 5 mM glucose and 10 mU/ml insulin. The clearance half-time (t1/2) for the predominant initial clearance phase was 3.1 +/- 0.5 minutes (n = 4). MVO2 was varied over a fourfold range by hypoxia and phenylephrine stimulation (t1/2, 7.2 +/- 1.2 and 2.2 +/- 0.2 minutes, respectively) and in the presence of alternate substrates (lactate, 2 mM; DL-3-hydroxybutyrate, 20 mM; and palmitate, 0.1 mM), which did not modify either tricarboxylic acid (TCA) cycle flux or acetate kinetics. A good correlation (r = 0.93) was observed between k, the rate constant for the initial phase of 14CO2 clearance, and TCA cycle flux, estimated from oxygen consumption. In contrast to results with (1-14C)acetate, lactate (2 mM) increased t1/2 for 14CO2 clearance from a bolus injection of (1-14C)palmitate from 3.0 +/- 0.4 minutes (n = 3) at control to 4.3 +/- 0.2 minutes (n = 3, p less than 0.01). Addition of acetate in nontracer amounts (0.5 or 5 mM) caused significant underestimation of TCA cycle flux when estimated with (1-14C)acetate. 14CO2 clearance accounted for 88-98% of total effluent 14C between 10 and 20 minutes after (1-14C)acetate bolus injection; rate constants for clearance of 14CO2 and total 14C clearance were very similar during this period, and these two rate constants did not differ significantly from each other under any conditions tested.

  6. Measurement of the water cycle in mixed ammonium acid sulfate particles

    NASA Astrophysics Data System (ADS)

    Spann, J. F.; Richardson, C. B.

    A single ammonium-hydrogen-sulfate particle is levitated in an evacuated quadrupole trap at room temperature and the temperature of an attached tube containing bulk water is slowly cycled introducing then removing water vapor. With increasing pressure the particle dissolves in stages, then grows as a solution droplet by water absorption. With decreasing pressure the droplet supersaturates, crystallizes, then dehydrates completely to return to its initial state. Particle mass, and thus composition, is measured continuously with an electrostatic balance. Twenty-six cycles were studied as solute composition ranged from ammonium bisulfate through letovicite to ammonium sulfate in roughly equal steps. Composition was changed in situ by reaction with ammonia at low partial pressure. With solute composition characterized by x = [NH 4]/[SO 4], deliquescence was found to occur at water activity aw = 0.394-0.029 ( x- 1) for 1 ⩽ x < 1.5 and aw = 0.710-0.023( x-1.5) for 1.5 ⩽ x < 2. Particle growth occurs at deliquescence and subsequently is in excellent agreement with that predicted in a model proposed by Tang for dissolution of a two-component mixed solute. Water activities of the solution droplets are measured up to aw = 0.9. The results are compared with those predicted by the Zdanovskii-Stokes-Robinson method of interpolation from binary data and with those obtained using the mixing rule of Meissner and Kusik. Particle crystallization from supersaturated solution is analyzed thermodynamically using measured water activities, the Gibbs-Duhem equation, and classical nucleation theory. The specific free energy barrier to crystallization, ΔG/ n, is found to increase from near zero to 0.04 eV as composition ranges from x = 1 to 2, where n is the number of formula units in the critical nucleus. New phase diagrams are presented and used to discuss the dynamics of mixed sulfate particles in the atmosphere.

  7. Effects of precipitation on soil acid phosphatase activity in three successional forests in Southern China

    NASA Astrophysics Data System (ADS)

    Huang, W.; Liu, J.; Zhou, G.; Zhang, D.; Deng, Q.

    2011-01-01

    Phosphorus (P) is often a limiting nutrient for plant growth in tropical and subtropical forests. Global climate change has led to alterations in precipitation in the recent years, which inevitably influences P cycling. Soil acid phosphatase plays a vital role in controlling P mineralization, and its activity reflects the capacity of P supply to ecosystems. In order to study the effects of precipitation on soil acid phosphatase activity, an experiment of precipitation treatments (no precipitation, natural precipitation and doubled precipitation) in three forests of early-, mid- and advanced-successional stages in Southern China was carried out. Results showed that driven by seasonality of precipitation, changes in soil acid phosphatase activities coincided with the seasonal climate pattern, with significantly higher values in the wet season than in the dry season. Soil acid phosphatase activities were closely linked to forest successional stages, with enhanced values in the later stages of forest succession. In the dry season, soil acid phosphatase activities in the three forests showed a rising trend with increasing precipitation treatments. In the wet season, no precipitation treatment depressed soil acid phosphatase activity, while doubled precipitation treatment exerted no positive effects on it, and even significantly lowered it in the advanced forest. These indicate the potential transformation rate of organic P might be more dependent on water in the dry season than in the wet season. The negative responses of soil acid phosphatase activity to precipitation suggest that P supply in subtropical ecosystems might be reduced if there was a drought in a whole year or more rainfall in the wet season in the future. NP, no precipitation; Control, natural precipitation; DP, double precipitation.

  8. DIBROMOACETIC ACID-INDUCED ELEVATIONS IN CIRCULATING ESTRADIOL: EFFECTS IN BOTH CYCLING AND OVARIECTOMIZED/STEROID-PRIMED FEMALE RATS

    EPA Science Inventory

    RTD-03-031
    Goldman, JM and Murr, AS. Dibromoacetic Acid-induced Elevations in Circulating Estradiol: Effects in Both Cycling and Ovariectomized/Steroid-primed Female Rats. Reproductive Toxicology (in press).

    Abstract

    Oral exposures to high concentrations of th...

  9. Magnetic Tilts and Polarity Separations in Sunspot Groups and Active Regions the Cycle 23

    NASA Astrophysics Data System (ADS)

    Zharkov, S. I.; Zharkova, V. V.

    2006-08-01

    We present the analysis of magnetic tilts in active regions and sunspot groups for 1996-2005 that are automatically extracted from the Solar Feature Catalogues (http://solar.inf.brad.ac.uk ). We investigate the statistical variations of magnetic field tilt in sunspot groups and whole active regions, their longitudinal and latitudinal distributions, drifts and daily polarity separation during different phases of the solar cycle 23. The classification results are compared with the similar research for the previous cycles and the specifics on the cycle 23 is discussed in conjunction to the solar dynamo theory.

  10. Frowning and Jaw Clenching Muscle Activity Reflects the Perception of Effort During Incremental Workload Cycling

    PubMed Central

    Huang, Ding-Hau; Chou, Shih-Wei; Chen, Yi-Lang; Chiou, Wen-Ko

    2014-01-01

    The present study aimed to investigate whether facial electromyography (EMG) recordings reflect the perception of effort and primary active lower limb muscle activity during incremental workload cycling. The effects of exercise intensity on EMG activity of the corrugator supercilii (CS), masseter and vastus lateralis (VL) muscles, heart rate (HR) and the rating of perceived exertion (RPE) were investigated, and the correlations among these parameters were determined. Eighteen males and 15 females performed continuous incremental workload cycling exercise until exhaustion. CS, masseter and VL muscle activities were continuously recorded using EMG during exercise. HR was also continuously monitored during the test. During the final 30 s of each stage of cycle ergometer exercise, participants were asked to report their feeling of exertion on the adult OMNI-Cycle RPE. HR and EMG activity of the facial muscles and the primary active lower limb muscle were strongly correlated with RPE; they increased with power output. Furthermore, facial muscle activity increased significantly during high-intensity exercise. Masseter muscle activity was strongly and positively correlated with HR, RPE and VL activity. The present investigation supports the view that facial EMG activity reflects the perception of effort. The jaw clenching facial expression can be considered an important factor for improving the reporting of perceived effort during high-intensity exercise in males and females. Key points Frowning and jaw clenching muscle activity reflects the perception of effort during incremental workload cycling. EMG activity of the masseter muscle was strongly and positively correlated with RPE, HR and lower limb EMG activity during incremental workload cycling. The jaw clenching facial expression can be considered an important factor for estimating the intensity of effort. PMID:25435786

  11. Synthesis and evaluation of dioleoyl glyceric acids showing antitrypsin activity.

    PubMed

    Habe, Hiroshi; Fukuoka, Tokuma; Sato, Shun; Kitamoto, Dai; Sakaki, Keiji

    2011-01-01

    Previously, Lešová et al. reported the isolation and identification of metabolite OR-1, showing antitrypsin activity, produced during fermentation by Penicillium funiculosum. The structure of OR-1 was a mixture of glyceric acid (GA), esterified with C(14)-C(18) fatty acids, and oleic acid (C18:1) as the most predominant fatty acid (Folia Microbiol. 46, 21-23, 2001). In this study, dioleoyl D-GA and dioleoyl L-GA were synthesized via diesterification with oleoyl chloride, and their antitrypsin activities were evaluated using both a disk diffusion method and spectral absorption measurements. The results show that both compounds and their equivalent mixtures possess antitrypsin activities; however, their IC(50) values (approximately 2 mM) are much higher than that of OR-1 (4.25 µM), suggesting that dioleoyl GA does not play a major role in the OR-1 antitrypsin activity. PMID:21606621

  12. Multiple forms of acid phosphatase activity in Gaucher's disease.

    PubMed

    Chambers, J P; Peters, S P; Glew, R H; Lee, R E; McCafferty, L R; Mercer, D W; Wenger, D A

    1978-07-01

    Although the primary genetic defect in all individuals with Gaucher's disease is a deficiency in glucocerebrosidase activity, the finding of marked elevations in splenic and serum acid phosphatase activity is almost as consistent a finding. Gaucher spleen and serum contain at least two forms of acid phosphatase that can be readily separated by chromatography on columns containing the cation exchange resin Sulphopropyl Sephadex. The major species of acid phosphatase (designated SP-I) contained in Triton X-100 (1% v/v) extracts of Gaucher spleen accounts for 65%--95% of the total activity and has the following properties: (1) it does not bind to the cation exchange column; (2) it exhibitis a pH optimum of 4.5--5.0; (3) it is inhibited by sodium fluoride (15 mM), L(+)-tartaric acid (20 mM), and beta-mercaptoethanol (2.1 M), and (4) it is resistant to inhibition by sodium dithionite (10 mM). The minor acid phosphatase activity (designated SP-II) present in extracts of Gaucher spleen has properties similar to those of the major species of acid phosphatase activity contained in serum from patients with Gaucher's disease: (1) it binds firmly to cation exchange columns (eluted by 0.5 M sodium chloride); (2) it exhibits a pH optimum of 5.0--6.0; (3) it is inhibited by sodium fluoride and sodium dithionite; and (4) it is resistant to inhibition by beta-mercaptoethanol (2.1 M) and L(+)-tartaric acid (20 mM). In addition, a second form of acid phosphatase that is tartrate resistant was found to be elevated in Gaucher serum. This form of serum acid phosphatase did not bind to Sulphopropyl Sephadex, was found to be significantly resistant to beta-mercaptoethanol (2.1 M), and was only partially inhibited by sodium dithionite (10 mM). The findings reported here indicate that at least three distinct forms of acid phosphatase activity are elevated in Gaucher's disease. Furthermore, the minor acid phosphatase activity contained in spleen homogenates has properties very similar to

  13. A cell cycle-controlled redox switch regulates the topoisomerase IV activity

    PubMed Central

    Narayanan, Sharath; Janakiraman, Balaganesh; Kumar, Lokesh

    2015-01-01

    Topoisomerase IV (topo IV), an essential factor during chromosome segregation, resolves the catenated chromosomes at the end of each replication cycle. How the decatenating activity of the topo IV is regulated during the early stages of the chromosome cycle despite being in continuous association with the chromosome remains poorly understood. Here we report a novel cell cycle-regulated protein in Caulobacter crescentus, NstA (negative switch for topo IV decatenation activity), that inhibits the decatenation activity of the topo IV during early stages of the cell cycle. We demonstrate that in C. crescentus, NstA acts by binding to the ParC DNA-binding subunit of topo IV. Most importantly, we uncover a dynamic oscillation of the intracellular redox state during the cell cycle, which correlates with and controls NstA activity. Thus, we propose that predetermined dynamic intracellular redox fluctuations may act as a global regulatory switch to control cellular development and cell cycle progression and may help retain pathogens in a suitable cell cycle state when encountering redox stress from the host immune response. PMID:26063575

  14. Triglyceride accumulation and fatty acid profile changes in Chlorella (Chlorophyta) during high pH-induced cell cycle inhibition

    SciTech Connect

    Guckert, J.B.; Cooksey, K.E. )

    1990-03-01

    Alkaline pH stress resulted in triglyceride (TG) accumulation in Chlorella CHLOR1 and was independent of medium nitrogen or carbon levels. Based on morphological observations, alkaline pH inhibited autospore release, thus increasing the time for cell cycle completion. Autospore release has been postulated to coincide with TG utilization within the microalgal cell division cycle. The alkaline pH stress affected lipid accumulation by inhibiting the cell division cycle prior to autospore release and, therefore, prior to TG utilization. Cells inhibited in this manner showed an increase in TG accumulation but a decrease in both membrane lipid classes (glycolipid and polar lipid). Unlike TG fatty acid profiles, membrane lipid fatty acid profiles were not stable during TG accumulation. The membrane profiles became similar to the TG, i.e. less unsaturated than in the membrane lipids of unstressed control cells.

  15. Effects of sex and site on amino acid metabolism enzyme gene expression and activity in rat white adipose tissue

    PubMed Central

    Arriarán, Sofía; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio

    2015-01-01

    Background and Objectives. White adipose tissue (WAT) shows marked sex- and diet-dependent differences. However, our metabolic knowledge of WAT, especially on amino acid metabolism, is considerably limited. In the present study, we compared the influence of sex on the amino acid metabolism profile of the four main WAT sites, focused on the paths related to ammonium handling and the urea cycle, as a way to estimate the extent of WAT implication on body amino-nitrogen metabolism. Experimental Design. Adult female and male rats were maintained, undisturbed, under standard conditions for one month. After killing them under isoflurane anesthesia. WAT sites were dissected and weighed. Subcutaneous, perigonadal, retroperitoneal and mesenteric WAT were analyzed for amino acid metabolism gene expression and enzyme activities. Results. There was a considerable stability of the urea cycle activities and expressions, irrespective of sex, and with only limited influence of site. Urea cycle was more resilient to change than other site-specialized metabolic pathways. The control of WAT urea cycle was probably related to the provision of arginine/citrulline, as deduced from the enzyme activity profiles. These data support a generalized role of WAT in overall amino-N handling. In contrast, sex markedly affected WAT ammonium-centered amino acid metabolism in a site-related way, with relatively higher emphasis in males’ subcutaneous WAT. Conclusions. We found that WAT has an active amino acid metabolism. Its gene expressions were lower than those of glucose-lipid interactions, but the differences were quantitatively less important than usually reported. The effects of sex on urea cycle enzymes expression and activity were limited, in contrast with the wider variations observed in other metabolic pathways. The results agree with a centralized control of urea cycle operation affecting the adipose organ as a whole. PMID:26587356

  16. Restoring enzyme activity in nonfunctional low erucic acid Brassica napus fatty acid elongase 1 by a single amino acid substitution.

    PubMed

    Katavic, Vesna; Mietkiewska, Elzbieta; Barton, Dennis L; Giblin, E Michael; Reed, Darwin W; Taylor, David C

    2002-11-01

    Genomic fatty acid elongation 1 (FAE1) clones from high erucic acid (HEA) Brassica napus, Brassica rapa and Brassica oleracea, and low erucic acid (LEA) B. napus cv. Westar, were amplified by PCR and expressed in yeast cells under the control of the strong galactose-inducible promoter. As expected, yeast cells expressing the FAE1 genes from HEA Brassica spp. synthesized very long chain monounsaturated fatty acids that are not normally found in yeast, while fatty acid profiles of yeast cells expressing the FAE1 gene from LEA B. napus were identical to control yeast samples. In agreement with published findings regarding different HEA and LEA B. napus cultivars, comparison of FAE1 protein sequences from HEA and LEA Brassicaceae revealed one crucial amino acid difference: the serine residue at position 282 of the HEA FAE1 sequences is substituted by phenylalanine in LEA B. napus cv. Westar. Using site directed mutagenesis, the phenylalanine 282 residue was substituted with a serine residue in the FAE1 polypeptide from B. napus cv. Westar, the mutated gene was expressed in yeast and GC analysis revealed the presence of very long chain monounsaturated fatty acids (VLCMFAs), indicating that the elongase activity was restored in the LEA FAE1 enzyme by the single amino acid substitution. Thus, for the first time, the low erucic acid trait in canola B. napus can be attributed to a single amino acid substitution which prevents the biosynthesis of the eicosenoic and erucic acids.

  17. Activation of Inactive Nitrogenase by Acid-Treated Component I

    PubMed Central

    Nagatani, H. H.; Shah, Vinod K.; Brill, Winston J.

    1974-01-01

    When Azotobacter vinelandii was derepressed for nitrogenase synthesis in a N-free medium containing tungstate instead of molybdate, an inactive component I was synthesized. Although this inactive component I could be activated in vivo upon addition of molybdate to the medium, it could not be activated in vitro when molybdate was added to the extracts. Activation occurred, however, when an acid-treated component I was added to extracts of cells derepressed in medium containing tungstate. Acid treatment completely abolished component I activity. Mutant strains UW45 and UW10 were unable to fix N2. Both strains synthesized normal levels of component II but produced inactive component I. Acid-treated component I activated inactive component I in extracts of mutant strain UW45 but not mutant strain UW10. This activating factor could be obtained from N2-fixing Klebsiella pneumoniae, Clostridium pasteurianum, and Rhodospirillum rubrum. PMID:4218230

  18. Synthesis and antituberculosis activity of new fatty acid amides.

    PubMed

    D'Oca, Caroline Da Ros Montes; Coelho, Tatiane; Marinho, Tamara Germani; Hack, Carolina Rosa Lopes; Duarte, Rodrigo da Costa; da Silva, Pedro Almeida; D'Oca, Marcelo Gonçalves Montes

    2010-09-01

    This work reports the synthesis of new fatty acid amides from C16:0, 18:0, 18:1, 18:1 (OH), and 18:2 fatty acids families with cyclic and acyclic amines and demonstrate for the first time the activity of these compounds as antituberculosis agents against Mycobacterium tuberculosis H(37)Rv, M. tuberculosis rifampicin resistance (ATCC 35338), and M. tuberculosis isoniazid resistance (ATCC 35822). The fatty acid amides derivate from ricinoleic acid were the most potent one among a series of tested compounds, with a MIC 6.25 microg/mL for resistance strains.

  19. Bioconversion of volatile fatty acids derived from waste activated sludge into lipids by Cryptococcus curvatus.

    PubMed

    Liu, Jia; Liu, Jia-Nan; Yuan, Ming; Shen, Zi-Heng; Peng, Kai-Ming; Lu, Li-Jun; Huang, Xiang-Feng

    2016-07-01

    Pure volatile fatty acid (VFA) solution derived from waste activated sludge (WAS) was used to produce microbial lipids as culture medium in this study, which aimed to realize the resource recovery of WAS and provide low-cost feedstock for biodiesel production simultaneously. Cryptococcus curvatus was selected among three oleaginous yeast to produce lipids with VFAs derived from WAS. In batch cultivation, lipid contents increased from 10.2% to 16.8% when carbon to nitrogen ratio increased from about 3.5 to 165 after removal of ammonia nitrogen by struvite precipitation. The lipid content further increased to 39.6% and the biomass increased from 1.56g/L to 4.53g/L after cultivation for five cycles using sequencing batch culture (SBC) strategy. The lipids produced from WAS-derived VFA solution contained nearly 50% of monounsaturated fatty acids, including palmitic acid, heptadecanoic acid, ginkgolic acid, stearic acid, oleic acid, and linoleic acid, which showed the adequacy of biodiesel production. PMID:27038264

  20. Wastes from selected activities in two light-water reactor fuel cycles

    SciTech Connect

    Palmer, C.R.; Hill, O.F.

    1980-07-01

    This report presents projected volumes and radioactivities of wastes from the production of electrical energy using light-water reactors (LWR). The projections are based upon data developed for a recent environmental impact statement in which the transuranic wastes (i.e., those wastes containing certain long-lived alpha emitters at concentrations of at least 370 becquerels, or 10 nCi, per gram of waste) from fuel cycle activities were characterized. In addition, since the WG.7 assumed that all fuel cycle wastes except mill tailings are placed in a mined geologic repository, the nontransuranic wastes from several activities are included in the projections reported. The LWR fuel cycles considered are the LWR, once-through fuel cycle (Strategy 1), in which spent fuel is packaged in metal canisters and then isolated in geologic formations; and the LWR U/Pu recycle fuel cycle (Strategy 2), wherein spent fuel is reprocessed for recovery and recycle of uranium and plutonium in LWRs. The wastes projected for the two LWR fuel cycles are summarized. The reactor operations and decommissioning were found to dominate the rate of waste generation in each cycle. These activities account for at least 85% of the fuel cycle waste volume (not including head-end wastes) when normalized to per unit electrical energy generated. At 10 years out of reactor, however, spent fuel elements in Strategy 1 represent 98% of the fuel cycle activity but only 4% of the volume. Similarly, the packaged high-level waste, fuel hulls and hardware in Strategy 2 concentrate greater than 95% of the activity in 2% of the waste volume.

  1. Microbial Enzyme Activity and Carbon Cycling in Grassland Soil Fractions

    NASA Astrophysics Data System (ADS)

    Allison, S. D.; Jastrow, J. D.

    2004-12-01

    Extracellular enzymes are necessary to degrade complex organic compounds present in soils. Using physical fractionation procedures, we tested whether old soil carbon is spatially isolated from degradative enzymes across a prairie restoration chronosequence in Illinois, USA. We found that carbon-degrading enzymes were abundant in all soil fractions, including macroaggregates, microaggregates, and the clay fraction, which contains carbon with a mean residence time of ~200 years. The activities of two cellulose-degrading enzymes and a chitin-degrading enzyme were 2-10 times greater in organic matter fractions than in bulk soil, consistent with the rapid turnover of these fractions. Polyphenol oxidase activity was 3 times greater in the clay fraction than in the bulk soil, despite very slow carbon turnover in this fraction. Changes in enzyme activity across the restoration chronosequence were small once adjusted for increases in soil carbon concentration, although polyphenol oxidase activity per unit carbon declined by 50% in native prairie versus cultivated soil. These results are consistent with a `two-pool' model of enzyme and carbon turnover in grassland soils. In light organic matter fractions, enzyme production and carbon turnover both occur rapidly. However, in mineral-dominated fractions, both enzymes and their carbon substrates are immobilized on mineral surfaces, leading to slow turnover. Soil carbon accumulation in the clay fraction and across the prairie restoration chronosequence probably reflects increasing physical isolation of enzymes and substrates on the molecular scale, rather than the micron to millimeter scale.

  2. Life Cycle of the Salmon. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Tarabochia, Kathy

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  3. An Oral Load of [13C3]Glycerol and Blood NMR Analysis Detect Fatty Acid Esterification, Pentose Phosphate Pathway, and Glycerol Metabolism through the Tricarboxylic Acid Cycle in Human Liver.

    PubMed

    Jin, Eunsook S; Sherry, A Dean; Malloy, Craig R

    2016-09-01

    Drugs and other interventions for high impact hepatic diseases often target biochemical pathways such as gluconeogenesis, lipogenesis, or the metabolic response to oxidative stress. However, traditional liver function tests do not provide quantitative data about these pathways. In this study, we developed a simple method to evaluate these processes by NMR analysis of plasma metabolites. Healthy subjects ingested [U-(13)C3]glycerol, and blood was drawn at multiple times. Each subject completed three visits under differing nutritional states. High resolution (13)C NMR spectra of plasma triacylglycerols and glucose provided new insights into a number of hepatic processes including fatty acid esterification, the pentose phosphate pathway, and gluconeogenesis through the tricarboxylic acid cycle. Fasting stimulated pentose phosphate pathway activity and metabolism of [U-(13)C3]glycerol in the tricarboxylic acid cycle prior to gluconeogenesis or glyceroneogenesis. Fatty acid esterification was transient in the fasted state but continuous under fed conditions. We conclude that a simple NMR analysis of blood metabolites provides an important biomarker of pentose phosphate pathway activity, triacylglycerol synthesis, and flux through anaplerotic pathways in mitochondria of human liver.

  4. An Oral Load of [13C3]Glycerol and Blood NMR Analysis Detect Fatty Acid Esterification, Pentose Phosphate Pathway, and Glycerol Metabolism through the Tricarboxylic Acid Cycle in Human Liver.

    PubMed

    Jin, Eunsook S; Sherry, A Dean; Malloy, Craig R

    2016-09-01

    Drugs and other interventions for high impact hepatic diseases often target biochemical pathways such as gluconeogenesis, lipogenesis, or the metabolic response to oxidative stress. However, traditional liver function tests do not provide quantitative data about these pathways. In this study, we developed a simple method to evaluate these processes by NMR analysis of plasma metabolites. Healthy subjects ingested [U-(13)C3]glycerol, and blood was drawn at multiple times. Each subject completed three visits under differing nutritional states. High resolution (13)C NMR spectra of plasma triacylglycerols and glucose provided new insights into a number of hepatic processes including fatty acid esterification, the pentose phosphate pathway, and gluconeogenesis through the tricarboxylic acid cycle. Fasting stimulated pentose phosphate pathway activity and metabolism of [U-(13)C3]glycerol in the tricarboxylic acid cycle prior to gluconeogenesis or glyceroneogenesis. Fatty acid esterification was transient in the fasted state but continuous under fed conditions. We conclude that a simple NMR analysis of blood metabolites provides an important biomarker of pentose phosphate pathway activity, triacylglycerol synthesis, and flux through anaplerotic pathways in mitochondria of human liver. PMID:27432878

  5. Brain and behavioural evidence for rest-activity cycles in Octopus vulgaris.

    PubMed

    Brown, Euan R; Piscopo, Stefania; De Stefano, Rosanna; Giuditta, Antonio

    2006-09-25

    Octopus vulgaris maintained under a 12/12h light/dark cycle exhibit a pronounced nocturnal activity pattern. Animals deprived of rest during the light period show a marked 'rebound' in activity in the following 24h. 'Active' octopuses attack faster than 'quiet' animals and brain activity recorded electrically intensifies during 'quiet' behaviour. Thus, in Octopus as in vertebrates, brain areas involved in memory or 'higher' processes exhibit 'off-line' activity during rest periods.

  6. Translational regulation of mammalian and Drosophila citric acid cycle enzymes via iron-responsive elements.

    PubMed Central

    Gray, N K; Pantopoulos, K; Dandekar, T; Ackrell, B A; Hentze, M W

    1996-01-01

    The posttranscriptional control of iron uptake, storage, and utilization by iron-responsive elements (IREs) and iron regulatory proteins (IRPs) provides a molecular framework for the regulation of iron homeostasis in many animals. We have identified and characterized IREs in the mRNAs for two different mitochondrial citric acid cycle enzymes. Drosophila melanogaster IRP binds to an IRE in the 5' untranslated region of the mRNA encoding the iron-sulfur protein (Ip) subunit of succinate dehydrogenase (SDH). This interaction is developmentally regulated during Drosophila embryogenesis. In a cell-free translation system, recombinant IRP-1 imposes highly specific translational repression on a reporter mRNA bearing the SDH IRE, and the translation of SDH-Ip mRNA is iron regulated in D. melanogaster Schneider cells. In mammals, an IRE was identified in the 5' untranslated regions of mitochondrial aconitase mRNAs from two species. Recombinant IRP-1 represses aconitase synthesis with similar efficiency as ferritin IRE-controlled translation. The interaction between mammalian IRPs and the aconitase IRE is regulated by iron, nitric oxide, and oxidative stress (H2O2), indicating that these three signals can control the expression of mitochondrial aconitase mRNA. Our results identify a regulatory link between energy and iron metabolism in vertebrates and invertebrates, and suggest biological functions for the IRE/IRP regulatory system in addition to the maintenance of iron homeostasis. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8643505

  7. Tricarboxylic acid cycle and one-carbon metabolism pathways are important in Edwardsiella ictaluri virulence.

    PubMed

    Dahal, Neeti; Abdelhamed, Hossam; Lu, Jingjun; Karsi, Attila; Lawrence, Mark L

    2013-01-01

    Edwardsiella ictaluri is a Gram-negative facultative intracellular pathogen causing enteric septicemia of channel catfish (ESC). The disease causes considerable economic losses in the commercial catfish industry in the United States. Although antibiotics are used as feed additive, vaccination is a better alternative for prevention of the disease. Here we report the development and characterization of novel live attenuated E. ictaluri mutants. To accomplish this, several tricarboxylic acid cycle (sdhC, mdh, and frdA) and one-carbon metabolism genes (gcvP and glyA) were deleted in wild type E. ictaluri strain 93-146 by allelic exchange. Following bioluminescence tagging of the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, ΔgcvP, and ΔglyA mutants, their dissemination, attenuation, and vaccine efficacy were determined in catfish fingerlings by in vivo imaging technology. Immunogenicity of each mutant was also determined in catfish fingerlings. Results indicated that all of the E. ictaluri mutants were attenuated significantly in catfish compared to the parent strain as evidenced by 2,265-fold average reduction in bioluminescence signal from all the mutants at 144 h post-infection. Catfish immunized with the E. ictaluri ΔsdhC, Δmdh, ΔfrdA, and ΔglyA mutants had 100% relative percent survival (RPS), while E. ictaluri ΔgcvP vaccinated catfish had 31.23% RPS after re-challenge with the wild type E. ictaluri.

  8. Structural Requirements for the Procoagulant Activity of Nucleic Acids

    PubMed Central

    Gansler, Julia; Jaax, Miriam; Leiting, Silke; Appel, Bettina; Greinacher, Andreas; Fischer, Silvia; Preissner, Klaus T.

    2012-01-01

    Nucleic acids, especially extracellular RNA, are exposed following tissue- or vessel damage and have previously been shown to activate the intrinsic blood coagulation pathway in vitro and in vivo. Yet, no information on structural requirements for the procoagulant activity of nucleic acids is available. A comparison of linear and hairpin-forming RNA- and DNA-oligomers revealed that all tested oligomers forming a stable hairpin structure were protected from degradation in human plasma. In contrast to linear nucleic acids, hairpin forming compounds demonstrated highest procoagulant activities based on the analysis of clotting time in human plasma and in a prekallikrein activation assay. Moreover, the procoagulant activities of the DNA-oligomers correlated well with their binding affinity to high molecular weight kininogen, whereas the binding affinity of all tested oligomers to prekallikrein was low. Furthermore, four DNA-aptamers directed against thrombin, activated protein C, vascular endothelial growth factor and nucleolin as well as the naturally occurring small nucleolar RNA U6snRNA were identified as effective cofactors for prekallikrein auto-activation. Together, we conclude that hairpin-forming nucleic acids are most effective in promoting procoagulant activities, largely mediated by their specific binding to kininogen. Thus, in vivo application of therapeutic nucleic acids like aptamers might have undesired prothrombotic or proinflammatory side effects. PMID:23226277

  9. Notch stimulates growth by direct regulation of genes involved in the control of glycolysis and the tricarboxylic acid cycle

    PubMed Central

    Slaninova, Vera; Krafcikova, Michaela; Perez-Gomez, Raquel; Steffal, Pavel; Trantirek, Lukas; Bray, Sarah J.

    2016-01-01

    Glycolytic shift is a characteristic feature of rapidly proliferating cells, such as cells during development and during immune response or cancer cells, as well as of stem cells. It results in increased glycolysis uncoupled from mitochondrial respiration, also known as the Warburg effect. Notch signalling is active in contexts where cells undergo glycolytic shift. We decided to test whether metabolic genes are direct transcriptional targets of Notch signalling and whether upregulation of metabolic genes can help Notch to induce tissue growth under physiological conditions and in conditions of Notch-induced hyperplasia. We show that genes mediating cellular metabolic changes towards the Warburg effect are direct transcriptional targets of Notch signalling. They include genes encoding proteins involved in glucose uptake, glycolysis, lactate to pyruvate conversion and repression of the tricarboxylic acid cycle. The direct transcriptional upregulation of metabolic genes is PI3K/Akt independent and occurs not only in cells with overactivated Notch but also in cells with endogenous levels of Notch signalling and in vivo. Even a short pulse of Notch activity is able to elicit long-lasting metabolic changes resembling the Warburg effect. Loss of Notch signalling in Drosophila wing discs as well as in human microvascular cells leads to downregulation of glycolytic genes. Notch-driven tissue overgrowth can be rescued by downregulation of genes for glucose metabolism. Notch activity is able to support growth of wing during nutrient-deprivation conditions, independent of the growth of the rest of the body. Notch is active in situations that involve metabolic reprogramming, and the direct regulation of metabolic genes may be a common mechanism that helps Notch to exert its effects in target tissues. PMID:26887408

  10. Do Male And Female Cyclists' Cortical Activity Differ Before and During Cycling Exercise?

    PubMed

    Ludyga, Sebastian; Gronwald, Thomas; Hottenrott, Kuno

    2015-12-01

    Although men and women are suggested to vary in resistance to fatigue, possible sex difference in its central component have rarely been investigated via electroencephalography (EEG). Therefore, we examined differences in cortical activity between male and female cyclists (n = 26) during cycling exercise. Participants performed an incremental test to derive the anaerobic threshold from the lactate power curve. In addition, cyclists' cortical activity was recorded with EEG before and during cycling exercise. Whereas women showed higher frontal alpha and beta activity at rest, no sex-specific differences of relative EEG spectral power occurred during cycling at higher intensity. Women and men's brains respond similarly during submaximal cycling, as both sexes show an inverted U-shaped curve of alpha power. Therefore, sex differences observable at rest vanish after the onset of exercise. PMID:26866769

  11. Do Male And Female Cyclists' Cortical Activity Differ Before and During Cycling Exercise?

    PubMed

    Ludyga, Sebastian; Gronwald, Thomas; Hottenrott, Kuno

    2015-12-01

    Although men and women are suggested to vary in resistance to fatigue, possible sex difference in its central component have rarely been investigated via electroencephalography (EEG). Therefore, we examined differences in cortical activity between male and female cyclists (n = 26) during cycling exercise. Participants performed an incremental test to derive the anaerobic threshold from the lactate power curve. In addition, cyclists' cortical activity was recorded with EEG before and during cycling exercise. Whereas women showed higher frontal alpha and beta activity at rest, no sex-specific differences of relative EEG spectral power occurred during cycling at higher intensity. Women and men's brains respond similarly during submaximal cycling, as both sexes show an inverted U-shaped curve of alpha power. Therefore, sex differences observable at rest vanish after the onset of exercise.

  12. Antiproliferative activity of synthetic fatty acid amides from renewable resources.

    PubMed

    dos Santos, Daiane S; Piovesan, Luciana A; D'Oca, Caroline R Montes; Hack, Carolina R Lopes; Treptow, Tamara G M; Rodrigues, Marieli O; Vendramini-Costa, Débora B; Ruiz, Ana Lucia T G; de Carvalho, João Ernesto; D'Oca, Marcelo G Montes

    2015-01-15

    In the work, the in vitro antiproliferative activity of a series of synthetic fatty acid amides were investigated in seven cancer cell lines. The study revealed that most of the compounds showed antiproliferative activity against tested tumor cell lines, mainly on human glioma cells (U251) and human ovarian cancer cells with a multiple drug-resistant phenotype (NCI-ADR/RES). In addition, the fatty methyl benzylamide derived from ricinoleic acid (with the fatty acid obtained from castor oil, a renewable resource) showed a high selectivity with potent growth inhibition and cell death for the glioma cell line-the most aggressive CNS cancer.

  13. Activation of PPARα by Fatty Acid Accumulation Enhances Fatty Acid Degradation and Sulfatide Synthesis.

    PubMed

    Yang, Yang; Feng, Yuyao; Zhang, Xiaowei; Nakajima, Takero; Tanaka, Naoki; Sugiyama, Eiko; Kamijo, Yuji; Aoyama, Toshifumi

    2016-01-01

    Very-long-chain acyl-CoA dehydrogenase (VLCAD) catalyzes the first reaction in the mitochondrial fatty acid β-oxidation pathway. VLCAD deficiency is associated with the accumulation of fat in multiple organs and tissues, which results in specific clinical features including cardiomyopathy, cardiomegaly, muscle weakness, and hepatic dysfunction in infants. We speculated that the abnormal fatty acid metabolism in VLCAD-deficient individuals might cause cell necrosis by fatty acid toxicity. The accumulation of fatty acids may activate peroxisome proliferator-activated receptor (PPAR), a master regulator of fatty acid metabolism and a potent nuclear receptor for free fatty acids. We examined six skin fibroblast lines, derived from VLCAD-deficient patients and identified fatty acid accumulation and PPARα activation in these cell lines. We then found that the expression levels of three enzymes involved in fatty acid degradation, including long-chain acyl-CoA synthetase (LACS), were increased in a PPARα-dependent manner. This increased expression of LACS might enhance the fatty acyl-CoA supply to fatty acid degradation and sulfatide synthesis pathways. In fact, the first and last reactions in the sulfatide synthesis pathway are regulated by PPARα. Therefore, we also measured the expression levels of enzymes involved in sulfatide metabolism and the regulation of cellular sulfatide content. The levels of these enzymes and cellular sulfatide content both increased in a PPARα-dependent manner. These results indicate that PPARα activation plays defensive and compensative roles by reducing cellular toxicity associated with fatty acids and sulfuric acid. PMID:27644403

  14. Synthesis of sulfonated porous carbon nanospheres solid acid by a facile chemical activation route

    NASA Astrophysics Data System (ADS)

    Chang, Binbin; Guo, Yanzhen; Yin, Hang; Zhang, Shouren; Yang, Baocheng

    2015-01-01

    Generally, porous carbon nanospheres materials are usually prepared via a template method, which is a multi-steps and high-cost strategy. Here, we reported a porous carbon nanosphere solid acid with high surface area and superior porosity, as well as uniform nanospheical morphology, which prepared by a facile chemical activation with ZnCl2 using resorcinol-formaldehyde (RF) resins spheres as precursor. The activation of RF resins spheres by ZnCl2 at 400 °C brought high surface area and large volume, and simultaneously retained numerous oxygen-containing and hydrogen-containing groups due to the relatively low processing temperature. The presence of these functional groups is favorable for the modification of -SO3H groups by a followed sulfonation treating with sulphuric acid and organic sulfonic acid. The results of N2 adsorption-desorption and electron microscopy clearly showed the preservation of porous structure and nanospherical morphology. Infrared spectra certified the variation of surface functional groups after activation and the successful modification of -SO3H groups after sulfonation. The acidities of catalysts were estimated by an indirect titration method and the modified amount of -SO3H groups were examined by energy dispersive spectra. The results suggested sulfonated porous carbon nanospheres catalysts possessed high acidities and -SO3H densities, which endowed their significantly catalytic activities for biodiesel production. Furthermore, their excellent stability and recycling property were also demonstrated by five consecutive cycles.

  15. Novel Bioactivity of Ellagic Acid in Inhibiting Human Platelet Activation

    PubMed Central

    Chang, Yi; Chen, Wei-Fan; Lin, Kuan-Hung; Hsieh, Cheng-Ying; Chou, Duen-Suey; Lin, Li-Jyun; Sheu, Joen-Rong; Chang, Chao-Chien

    2013-01-01

    Pomegranates are widely consumed either as fresh fruit or in beverage form as juice and wine. Ellagic acid possesses potent antioxidative properties; it is known to be an effective phytotherapeutic agent with antimutagenic and anticarcinogenic qualities. Ellagic acid (20 to 80 μM) exhibited a potent activity in inhibiting platelet aggregation stimulated by collagen; however, it did not inhibit platelet aggregation stimulated by thrombin, arachidonic acid, or U46619. Treatment with ellagic acid (50 and 80 μM) significantly inhibited platelet activation stimulated by collagen; this alteration was accompanied by the inhibition of relative [Ca2+]i mobilization, and the phosphorylation of phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinases (MAPKs), and Akt, as well as hydroxyl radical (OH●) formation. In addition, ellagic acid also inhibited p38 MAPK and Akt phosphorylation stimulated by hydrogen peroxide. By contrast, ellagic acid did not significantly affect PKC activation and platelet aggregation stimulated by PDBu. This study is the first to show that, in addition to being considered a possible agent for preventing tumor growth, ellagic acid possesses potent antiplatelet properties. It appears to initially inhibit the PLCγ2-PKC cascade and/or hydroxyl radical formation, followed by decreased phosphorylation of MAPKs and Akt, ultimately inhibiting platelet aggregation. PMID:23533502

  16. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26887328

  17. Biological Activities of Oleanolic Acid Derivatives from Calendula officinalis Seeds.

    PubMed

    Zaki, Ahmed; Ashour, Ahmed; Mira, Amira; Kishikawa, Asuka; Nakagawa, Toshinori; Zhu, Qinchang; Shimizu, Kuniyoshi

    2016-05-01

    Phytochemical examination of butanol fraction of Calendula officinalis seeds led to the isolation of two compounds identified as 28-O-β-D-glucopyranosyl-oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS1) and oleanolic acid 3-O-β-D-glucopyranosyl (1→3)-β-D-glucopyranosiduronic acid (CS2). Biological evaluation was carried out for these two compounds such as melanin biosynthesis inhibitory, hyaluronic acid production activities, anti obesity using lipase inhibition and adipocyte differentiation as well as evaluation of the protective effect against hydrogen peroxide induced neurotoxicity in neuro-2A cells. The results showed that, compound CS2 has a melanin biosynthesis stimulatory activity; however, compound CS1 has a potent stimulatory effect for the production of hyaluronic acid on normal human dermal fibroblast from adult (NHDF-Ad). Both compounds did not show any inhibitory effect on both lipase and adipocyte differentiation. Compound CS2 could protect neuro-2A cells and increased cell viability against H2 O2 . These activities (melanin biosynthesis stimulatory and protective effect against H2 O2 of CS2 and hyaluronic acid productive activities of these triterpene derivatives) have been reported for the first time. Copyright © 2016 John Wiley & Sons, Ltd.

  18. Is the Valles caldera entering a new cycle of activity?

    SciTech Connect

    Wolff, J.A.; Gardner, J.N.

    1995-05-01

    The Valles caldera formed during two major rhyolitic ignimbrite eruptive episodes (the Bandelier Tuff) at 1.61 and 1.22 Ma, after some 12 m.y. of activity in the Jemez Mountains volcanic field, New Mexico. Several subsequent eruptions between 1.22 and 0.52 Ma produced dominantly high-silica rhyolite lava domes and tephras within the caldera. These were followed by a dormancy of 0.46 m.y. prior to the most recent intracaldera activity, the longest hiatus since the inception of the Bandelier magma system at approximately 1.8 Ma. The youngest volcanic activity at approximately 60 ka produced the SW moat rhyolites, a series of lavas and tuffs that display abundant petrologic evidence of being newly generated melts. Petrographic textures conform closely to published predictions for silicic magmas generated by intrusion of basaltic magma into continental crust. The Valles caldera may currently be the site of renewed silicic magma generation, induced by intrusion of mafic magma at depth. Recent seismic investigations revealed the presence of a large low-velocity anomaly in the lower crust beneath the caldera. The generally aseismic character of the caldera, despite abundant regional seismicity, may be attributed to a heated crustal column, the local effect of 13 m.y. of magmatism and emplacement of mid-crustal plutons. 24 refs., 3 figs.

  19. Cell cycle-dependent regulation of RNA polymerase II basal transcription activity.

    PubMed Central

    Yonaha, M; Chibazakura, T; Kitajima, S; Yasukochi, Y

    1995-01-01

    Regulation of transcription by RNA polymerase II (pol II) in eukaryotic cells requires both basal and regulatory transcription factors. In this report we have investigated in vitro pol II basal transcription activity during the cell cycle by using nuclear extracts from synchronized HeLa cells. It is shown that pol II basal transcription activity is low in the S and G2 phases and high in early G1 phase and TFIID is the rate limiting component of pol II basal transcription activity during the cell cycle. Further analyses reveal that TFIID exists as a less active form in the S and G2 phases and nuclear extracts from S and G2 phase cells contain a heat-sensitive repressor(s) of TATA box binding protein (TBP). These results suggest that pol II basal transcription activity is regulated by a qualitative change in the TFIID complex, which could involve repression of TBP, during the cell cycle. Images PMID:7479063

  20. Environmental impact associated with activated carbon preparation from olive-waste cake via life cycle assessment.

    PubMed

    Hjaila, K; Baccar, R; Sarrà, M; Gasol, C M; Blánquez, P

    2013-11-30

    The life cycle assessment (LCA) environmental tool was implemented to quantify the potential environmental impacts associated with the activated carbon (AC) production process from olive-waste cakes in Tunisia. On the basis of laboratory investigations for AC preparation, a flowchart was developed and the environmental impacts were determined. The LCA functional unit chosen was the production of 1 kg of AC from by-product olive-waste cakes. The results showed that impregnation using H3PO4 presented the highest environmental impacts for the majority of the indicators tested: acidification potential (62%), eutrophication (96%), ozone depletion potential (44%), human toxicity (64%), fresh water aquatic ecotoxicity (90%) and terrestrial ecotoxicity (92%). One of the highest impacts was found to be the global warming potential (11.096 kg CO2 eq/kg AC), which was equally weighted between the steps involving impregnation, pyrolysis, and drying the washed AC. The cumulative energy demand of the AC production process from the by-product olive-waste cakes was 167.63 MJ contributed by impregnation, pyrolysis, and drying the washed AC steps. The use of phosphoric acid and electricity in the AC production were the main factors responsible for the majority of the impacts. If certain modifications are incorporated into the AC production, such as implementing synthesis gas recovery and reusing it as an energy source and recovery of phosphoric acid after AC washing, additional savings could be realized, and environmental impacts could be minimized. PMID:24091159

  1. Activity of earthworm in Latosol under simulated acid rain stress.

    PubMed

    Zhang, Jia-En; Yu, Jiayu; Ouyang, Ying

    2015-01-01

    Acid rain is still an issue of environmental concerns. This study investigated the impacts of simulated acid rain (SAR) upon earthworm activity from the Latosol (acidic red soil). Laboratory experiment was performed by leaching the soil columns grown with earthworms (Eisenia fetida) at the SAR pH levels ranged from 2.0 to 6.5 over a 34-day period. Results showed that earthworms tended to escape from the soil and eventually died for the SAR at pH = 2.0 as a result of acid toxicity. The catalase activity in the earthworms decreased with the SAR pH levels, whereas the superoxide dismutases activity in the earthworms showed a fluctuate pattern: decreasing from pH 6.5 to 5.0 and increasing from pH 5.0 to 4.0. Results implied that the growth of earthworms was retarded at the SAR pH ≤ 3.0.

  2. Spectroscopic studies on the antioxidant activity of ellagic acid

    NASA Astrophysics Data System (ADS)

    Kilic, Ismail; Yeşiloğlu, Yeşim; Bayrak, Yüksel

    2014-09-01

    Ellagic acid (EA, C14H6O8) is a natural dietary polyphenol whose benefits in a variety of diseases shown in epidemiological and experimental studies involve anti-inflammation, anti-proliferation, anti-angiogenesis, anticarcinogenesis and anti-oxidation properties. In vitro radical scavenging and antioxidant capacity of EA were clarified using different analytical methodologies such as total antioxidant activity determination by ferric thiocyanate, hydrogen peroxide scavenging, 1,1-diphenyl-2-picryl-hydrazyl free radical (DPPH) scavenging, 2,2‧-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) radical scavenging activity and superoxide anion radical scavenging, ferrous ions (Fe2+) chelating activity and ferric ions (Fe3+) reducing ability. EA inhibited 71.2% lipid peroxidation of a linoleic acid emulsion at 45 μg/mL concentration. On the other hand, butylated hydroxytoluene (BHT), butylated hydroxyanisole (BHA), α-tocopherol and ascorbic acid displayed 69.8%, 66.8%, 64.5% and 59.7% inhibition on the peroxidation of linoleic acid emulsion at the same concentration, respectively. In addition, EA had an effective DPPH• scavenging, ABTSrad + scavenging, superoxide anion radical scavenging, hydrogen peroxide scavenging, ferric ions (Fe3+) reducing power and ferrous ions (Fe2+) chelating activities. Also, those various antioxidant activities were compared to BHA, BHT, α-tocopherol and ascorbic acid as references antioxidant compounds. These results suggested that EA can be used in the pharmacological, food industry and medicine because of these properties.

  3. Phragmites australis response to Cu in terms of low molecular weight organic acids (LMWOAs) exudation: Influence of the physiological cycle

    NASA Astrophysics Data System (ADS)

    Rocha, A. Cristina S.; Almeida, C. Marisa R.; Basto, M. Clara P.; Vasconcelos, M. Teresa S. D.

    2014-06-01

    Plant roots have the ability to produce and secrete substances, such as aliphatic low molecular weight organic acids (ALMWOAs), into the rhizosphere for several purposes, including in response to metal contamination. Despite this, little is yet known about the exudation of such substances from marsh plants roots in response to metal exposure. This work aimed at assessing the influence of the physiological cycle of marsh plants on the exudation of ALMWOAs in response to Cu contamination. In vitro experiments were carried out with Phragmites australis specimens, collected in different seasons. Plant roots were exposed to freshwater contaminated with two different Cu concentrations (67 μg/L and 6.9 mg/L), being the ALMWOAs released by the roots measured. Significant differences (both qualitative and quantitative) were observed during the Phragmites australis life cycle. At growing stage, Cu stimulated the exudation of oxalic and formic acids but no significant stimulation was observed for citric acid. At developing stage, exposure to Cu caused inhibition of oxalic acid exudation whereas citric acid liberation was stimulated but only in the media spiked with the lowest Cu concentration tested. At the decaying stage, no significant variation on oxalic acid was observed, whereas the citric and formic acids release increased as a consequence of the plant exposure to Cu. The physiological cycle of Phragmites australis, and probably also of other marsh plants, is therefore an important feature conditioning plants response to Cu contamination, in terms of ALMWOAs exudation. Hence this aspect should be considered when conducting studies on rhizodeposition involving marsh plants exposed to metals and in the event of using marsh plants for phytoremediation purposes in contaminated estuarine areas.

  4. Active vibration and balance system for closed cycle thermodynamic machines

    NASA Technical Reports Server (NTRS)

    Qiu, Songgang (Inventor); Augenblick, John E. (Inventor); Peterson, Allen A. (Inventor); White, Maurice A. (Inventor)

    2004-01-01

    An active balance system is provided for counterbalancing vibrations of an axially reciprocating machine. The balance system includes a support member, a flexure assembly, a counterbalance mass, and a linear motor or an actuator. The support member is configured for attachment to the machine. The flexure assembly includes at least one flat spring having connections along a central portion and an outer peripheral portion. One of the central portion and the outer peripheral portion is fixedly mounted to the support member. The counterbalance mass is fixedly carried by the flexure assembly along another of the central portion and the outer peripheral portion. The linear motor has one of a stator and a mover fixedly mounted to the support member and another of the stator and the mover fixedly mounted to the counterbalance mass. The linear motor is operative to axially reciprocate the counterbalance mass. A method is also provided.

  5. Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity

    PubMed Central

    Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M.; Park, Jin-Byung

    2016-01-01

    The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass. PMID:27681369

  6. Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle

    PubMed Central

    She, Pengxiang; Reid, Tanya M.; Bronson, Sarah K.; Vary, Thomas C.; Hajnal, Andras; Lynch, Christopher J; Hutson, Susan M.

    2009-01-01

    Summary Leucine is recognized as a nutrient signal, however the long-term in vivo consequences of leucine signaling and the role of branched chain amino acid (BCAA) metabolism in this signaling remains unclear. To investigate these questions, the BCATm gene encoding the enzyme catalyzing the first step in peripheral BCAA metabolism was disrupted. BCATm−/− mice exhibited elevated plasma BCAAs, decreased adiposity and body weight, despite eating more food, along with increased energy expenditure, remarkable improvements in glucose and insulin tolerance, and protection from diet induced obesity. The increased energy expenditure did not seem to be due to altered locomotor activity, uncoupling proteins, sympathetic activity, and thyroid hormones but was strongly associated with food consumption and an active futile cycle of increased protein degradation and synthesis. These observations suggest that either elevated BCAAs and/or loss of BCAA catabolism in peripheral tissues play an important role in regulating insulin sensitivity and energy expenditure. PMID:17767905

  7. Application of citrate as a tricarboxylic acid (TCA) cycle intermediate, prevents diabetic-induced heart damages in mice

    PubMed Central

    Liang, Qianqian; Wang, Baoyu; Pang, Lingxia; Wang, Youpei; Zheng, Meiqin; Wang, Qing; Yan, Jingbin; Xu, Jinzhong

    2016-01-01

    Objective(s): Higher cellular reactive oxygen species (ROS) levels is important in reducing cellular energy charge (EC) by increasing the levels of key metabolic protein, and nitrosative modifications, and have been shown to damage the cardiac tissue of diabetic mice. However, the relation between energy production and heart function is unclear. Materials and Methods: Streptozotocin (STZ, 150 mg/kg body weight) was injected intraperitoneally once to mice that had been fasted overnight for induction of diabetes. After diabetic induction, mice received citrate (5 µg/kg) through intraperitoneal injection every other day for 5 weeks. The caspase-3, plasminogen activator inhibitor 1 (PAI1), protein kinase B (PKB), commonly known as AKT and phosphorylated-AKT (p-AKT) proteins were examined to elucidate inflammation and apoptosis in the heart. For histological analysis, heart samples were fixed with 10% formalin and stained with hematoxylin-eosin (HE) and Sirius red to assess pathological changes and fibrosis. The expression levels[AGA1] of marker proteins, tyrosine nitration, activity of ATP synthase and succinyl-CoA3-ketoacid coenzyme A transferase-1 (SCOT), and EC were measured. Results: Intraperitoneal injection of citrate significantly reduced caspase-3 and PAI-1 protein levels and increased p-AKT level on the 5th week; EC in the heart was found to be increased as well. Further, the expression level, activity, and tyrosine nitration of ATP synthase and SCOT were not affected after induction of diabetes. Conclusion: Results indicate that application of citrate, a tricarboxylic acid (TCA) cycle intermediate, might alleviate cardiac dysfunction by reducing cardiac inflammation, apoptosis, and increasing cardiac EC. PMID:27096063

  8. The antimicrobial activities of the cinnamaldehyde adducts with amino acids.

    PubMed

    Wei, Qing-Yi; Xiong, Jia-Jun; Jiang, Hong; Zhang, Chao; Wen Ye

    2011-11-01

    Cinnamaldehyde is a well-established natural antimicrobial compound. It is probable for cinnamaldehyde to react with amino acid forming Schiff base adduct in real food system. In this paper, 9 such kind of adducts were prepared by the direct reaction of amino acids with cinnamaldehyde at room temperature. Their antimicrobial activities against Bacillus subtilis, Escherichia coli and Saccharomyces cerevisiae were evaluated with benzoic acid as a reference. The adducts showed a dose-dependent activities against the three microbial strains. Both cinnamaldehyde and their adducts were more active against B. subtilis than on E. coli, and their antimicrobial activities were higher at lower pH. Both cinnamaldehyde and its adducts were more active than benzoic acid at the same conditions. The adduct compound A was non-toxic by primary oral acute toxicity study in mice. However, in situ effect of the adduct compound A against E. coli was a little lower than cinnamaldehyde in fish meat. This paper for the first time showed that the cinnamaldehyde adducts with amino acids had similar strong antimicrobial activities as cinnamaldehyde, which may provide alternatives to cinnamaldehyde in food to avoid the strong unacceptable odor of cinnamaldehyde. PMID:21856030

  9. Catalytic Ethanol Dehydration over Different Acid-activated Montmorillonite Clays.

    PubMed

    Krutpijit, Chadaporn; Jongsomjit, Bunjerd

    2016-01-01

    In the present study, the catalytic dehydration of ethanol to obtain ethylene over montmorillonite clays (MMT) with mineral acid activation including H2SO4 (SA-MMT), HCl (HA-MMT) and HNO3 (NA-MMT) was investigated at temperature range of 200 to 400°C. It revealed that HA-MMT exhibited the highest catalytic activity. Ethanol conversion and ethylene selectivity were found to increase with increased reaction temperature. At 400°C, the HA-MMT yielded 82% of ethanol conversion having 78% of ethylene yield. At lower temperature (i.e. 200 to 300°C), diethyl ether (DEE) was a major product. The highest activity obtained from HA-MMT can be attributed to an increase of weak acid sites and acid density by the activation of MMT with HCl. It can be also proven by various characterization techniques that in most case, the main structure of MMT did not alter by acid activation (excepted for NA-MMT). Upon the stability test for 72 h during the reaction, the MMT and HA-MMT showed only slight deactivation due to carbon deposition. Hence, the acid activation of MMT by HCl is promising to enhance the catalytic dehydration of ethanol. PMID:27041515

  10. OECD/NEA Ongoing activities related to the nuclear fuel cycle

    SciTech Connect

    Cornet, S.M.; McCarthy, K.; Chauvin, N.

    2013-07-01

    As part of its role in encouraging international collaboration, the OECD Nuclear Energy Agency is coordinating a series of projects related to the Nuclear Fuel Cycle. The Nuclear Science Committee (NSC) Working Party on Scientific Issues of the Nuclear Fuel Cycle (WPFC) comprises five different expert groups covering all aspects of the fuel cycle from front to back-end. Activities related to fuels, materials, physics, separation chemistry, and fuel cycles scenarios are being undertaken. By publishing state-of-the-art reports and organizing workshops, the groups are able to disseminate recent research advancements to the international community. Current activities mainly focus on advanced nuclear systems, and experts are working on analyzing results and establishing challenges associated to the adoption of new materials and fuels. By comparing different codes, the Expert Group on Advanced Fuel Cycle Scenarios is aiming at gaining further understanding of the scientific issues and specific national needs associated with the implementation of advanced fuel cycles. At the back end of the fuel cycle, separation technologies (aqueous and pyrochemical processing) are being assessed. Current and future activities comprise studies on minor actinides separation and post Fukushima studies. Regular workshops are also organized to discuss recent developments on Partitioning and Transmutation. In addition, the Nuclear Development Committee (NDC) focuses on the analysis of the economics of nuclear power across the fuel cycle in the context of changes of electricity markets, social acceptance and technological advances and assesses the availability of the nuclear fuel and infrastructure required for the deployment of existing and future nuclear power. The Expert Group on the Economics of the Back End of the Nuclear Fuel Cycle (EBENFC), in particular, is looking at assessing economic and financial issues related to the long term management of spent nuclear fuel. (authors)

  11. TGEV nucleocapsid protein induces cell cycle arrest and apoptosis through activation of p53 signaling

    SciTech Connect

    Ding, Li; Huang, Yong; Du, Qian; Dong, Feng; Zhao, Xiaomin; Zhang, Wenlong; Xu, Xingang; Tong, Dewen

    2014-03-07

    Highlights: • TGEV N protein reduces cell viability by inducing cell cycle arrest and apoptosis. • TGEV N protein induces cell cycle arrest and apoptosis by regulating p53 signaling. • TGEV N protein plays important roles in TGEV-induced cell cycle arrest and apoptosis. - Abstract: Our previous studies showed that TGEV infection could induce cell cycle arrest and apoptosis via activation of p53 signaling in cultured host cells. However, it is unclear which viral gene causes these effects. In this study, we investigated the effects of TGEV nucleocapsid (N) protein on PK-15 cells. We found that TGEV N protein suppressed cell proliferation by causing cell cycle arrest at the S and G2/M phases and apoptosis. Characterization of various cellular proteins that are involved in regulating cell cycle progression demonstrated that the expression of N gene resulted in an accumulation of p53 and p21, which suppressed cyclin B1, cdc2 and cdk2 expression. Moreover, the expression of TGEV N gene promoted translocation of Bax to mitochondria, which in turn caused the release of cytochrome c, followed by activation of caspase-3, resulting in cell apoptosis in the transfected PK-15 cells following cell cycle arrest. Further studies showed that p53 inhibitor attenuated TGEV N protein induced cell cycle arrest at S and G2/M phases and apoptosis through reversing the expression changes of cdc2, cdk2 and cyclin B1 and the translocation changes of Bax and cytochrome c induced by TGEV N protein. Taken together, these results demonstrated that TGEV N protein might play an important role in TGEV infection-induced p53 activation and cell cycle arrest at the S and G2/M phases and apoptosis occurrence.

  12. The phase shift between the hemispheres in the solar activity cycle

    NASA Astrophysics Data System (ADS)

    Shibalova, A. S.; Obridko, V. N.; Sokoloff, D. D.

    2016-10-01

    The shift between the solar activity cycles in the northern and southern hemispheres of the Sun is studied using data on sunspot number and area. The data obtained are compared with archival information on episodes of appreciable solar-cycle asymmetry. The small phase shift between recent activity cycles in the northern and southern solar hemispheres differs considerably from the shift for episodes of appreciable deviations from dipolar symmetry in the sunspot distribution detected with various degrees of confidence in archival astronomical data from the 17th-19th centuries. The current time shift between the hemispheres is insignificant, about 6-7 months. This shift has changed its sign twice in recent solar history; this probably corresponds to more or less periodic variations with a timescale close to the duration of the Gleissberg cycle.

  13. Finding year-long activity cycles in ground-based and space-borne photometry

    NASA Astrophysics Data System (ADS)

    Vida, Krisztián; Oláh, Katalin; Szabó, Róbert

    2015-08-01

    Using long­term ground­based photometry of fast­rotating M­-dwarfs (EY Dra, V405 And, GSC 3377­0296 and V374 Peg), all with rotational periods near 0.5 day, but with different internal structures, we found activity cycles in the form of long-­term brightness changes, on the time scales of about one year. Using the cycling stars as templates, we searched for similar, fast rotating (P < 1d), active, late­-type targets in the Kepler Input Catalogue. Analysing the light curves of these 39 stars, we found hints of 300­-900 day­-long cycles in 9 cases detecting small variations in the rotation periods caused by differential rotation and the changing spot emergence latitudes over the cycle (i.e., the butterfly diagram).

  14. Centriole maturation requires regulated Plk1 activity during two consecutive cell cycles.

    PubMed

    Kong, Dong; Farmer, Veronica; Shukla, Anil; James, Jana; Gruskin, Richard; Kiriyama, Shigeo; Loncarek, Jadranka

    2014-09-29

    Newly formed centrioles in cycling cells undergo a maturation process that is almost two cell cycles long before they become competent to function as microtubule-organizing centers and basal bodies. As a result, each cell contains three generations of centrioles, only one of which is able to form cilia. It is not known how this long and complex process is regulated. We show that controlled Plk1 activity is required for gradual biochemical and structural maturation of the centrioles and timely appendage assembly. Inhibition of Plk1 impeded accumulation of appendage proteins and appendage formation. Unscheduled Plk1 activity, either in cycling or interphase-arrested cells, accelerated centriole maturation and appendage and cilia formation on the nascent centrioles, erasing the age difference between centrioles in one cell. These findings provide a new understanding of how the centriole cycle is regulated and how proper cilia and centrosome numbers are maintained in the cells.

  15. Pathways of acid mine drainage to Clear Lake: implications for mercury cycling.

    PubMed

    Shipp, William G; Zierenberg, Robert A

    2008-12-01

    Pore fluids from Clear Lake sediments collected near the abandoned Sulphur Bank Mercury Mine have low pH (locally <4) and elevated sulfate (> or =197 mmol/L), aluminum (> or =52 mmol/L), and iron (> or =28 mmol/L) contents derived from oxidation of sulfide minerals at the mine site. Acid mine drainage (AMD) is entering Clear Lake by advective subsurface flow nearest the mine and by diffusion at greater distances. Oxygen and hydrogen isotope ratios, combined with pore fluid compositions, constrain the sources and pathways of contaminated fluids. Sediment cores taken nearest the mine have the highest concentrations of dissolved sulfate, aluminum, and iron, which are contributed by direct subsurface flow of AMD from sulfide-bearing waste rock. Sediment cores as far as 100 m west of the Clear Lake shoreline show the presence of AMD that originated in the acidic lake that occupies the abandoned Herman Pit at the mine site. High sulfate content in the AMD has the potential to promote the activity of sulfate-reducing bacteria in the organic-rich lake sediments, which leads to methylation of Hg+2, making it both more toxic and bioavailable. Quantitative depletion of pore water sulfate at depth and sulfur isotope values of diagenetic pyrite near 0 per thousand indicate that sulfate availability limits the extent of sulfate reduction in the lake sediments away from the mine. Profiles of pore water sulfate in the sediments near the mine show that excess sulfate is available to support the activity of sulfate-reducing bacteria near the mine site. Enriched isotope values of dissolved sulfate (as high as 17.1 per thousand) and highly depleted isotope values for diagenetic pyrite (as low as -22.6 per thousand) indicate active bacterial sulfate reduction in the AMD-contaminated sediments. Sulfate- and iron-rich acid mine drainage entering Clear Lake by shallow subsurface flow likely needs to be controlled in order to lower the environmental impacts of Hg in the Clear Lake

  16. Pathways of acid mine drainage to Clear Lake: implications for mercury cycling.

    PubMed

    Shipp, William G; Zierenberg, Robert A

    2008-12-01

    Pore fluids from Clear Lake sediments collected near the abandoned Sulphur Bank Mercury Mine have low pH (locally <4) and elevated sulfate (> or =197 mmol/L), aluminum (> or =52 mmol/L), and iron (> or =28 mmol/L) contents derived from oxidation of sulfide minerals at the mine site. Acid mine drainage (AMD) is entering Clear Lake by advective subsurface flow nearest the mine and by diffusion at greater distances. Oxygen and hydrogen isotope ratios, combined with pore fluid compositions, constrain the sources and pathways of contaminated fluids. Sediment cores taken nearest the mine have the highest concentrations of dissolved sulfate, aluminum, and iron, which are contributed by direct subsurface flow of AMD from sulfide-bearing waste rock. Sediment cores as far as 100 m west of the Clear Lake shoreline show the presence of AMD that originated in the acidic lake that occupies the abandoned Herman Pit at the mine site. High sulfate content in the AMD has the potential to promote the activity of sulfate-reducing bacteria in the organic-rich lake sediments, which leads to methylation of Hg+2, making it both more toxic and bioavailable. Quantitative depletion of pore water sulfate at depth and sulfur isotope values of diagenetic pyrite near 0 per thousand indicate that sulfate availability limits the extent of sulfate reduction in the lake sediments away from the mine. Profiles of pore water sulfate in the sediments near the mine show that excess sulfate is available to support the activity of sulfate-reducing bacteria near the mine site. Enriched isotope values of dissolved sulfate (as high as 17.1 per thousand) and highly depleted isotope values for diagenetic pyrite (as low as -22.6 per thousand) indicate active bacterial sulfate reduction in the AMD-contaminated sediments. Sulfate- and iron-rich acid mine drainage entering Clear Lake by shallow subsurface flow likely needs to be controlled in order to lower the environmental impacts of Hg in the Clear Lake

  17. Antileishmanial activity of diterpene acids in copaiba oil

    PubMed Central

    dos Santos, Adriana Oliveira; Izumi, Erika; Ueda-Nakamura, Tânia; Dias-Filho, Benedito Prado; da Veiga-Júnior, Valdir Florêncio; Nakamura, Celso Vataru

    2013-01-01

    Leishmaniasis is a neglected tropical disease. According to the World Health Organization, there are approximately 1.5-two million new cases of cutaneous leishmaniasis each year worldwide. Chemotherapy against leishmaniasis is based on pentavalent antimonials, which were developed more than a century ago. The goals of this study were to investigate the antileishmanial activity of diterpene acids in copaiba oil, as well as some possible targets of their action against Leishmania amazonensis. Methyl copalate and agathic, hydroxycopalic, kaurenoic, pinifolic and polyaltic acids isolated from Copaifera officinales oleoresins were utilised. Ultrastructural changes and the specific organelle targets of diterpenes were investigated with electron microscopy and flow cytometry, respectively. All compounds had some level of activity against L. amazonensis. Hydroxycopalic acid and methyl copalate demonstrated the most activity against promastigotes and had 50% inhibitory concentration (IC50) values of 2.5 and 6.0 µg/mL, respectively. However, pinifolic and kaurenoic acid demonstrated the most activity against axenic amastigote and had IC50 values of 3.5 and 4.0 µg/mL, respectively. Agathic, kaurenoic and pinifolic acid caused significant increases in plasma membrane permeability and mitochondrial membrane depolarisation of the protozoan. In conclusion, copaiba oil and its diterpene acids should be explored for the development of new antileishmanial drugs. PMID:23440116

  18. The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes.

    PubMed

    Yang, Darren; Pornpattananangkul, Dissaya; Nakatsuji, Teruaki; Chan, Michael; Carson, Dennis; Huang, Chun-Ming; Zhang, Liangfang

    2009-10-01

    This study evaluated the antimicrobial activity of lauric acid (LA) and its liposomal derivatives against Propionibacterium acnes (P. acnes), the bacterium that promotes inflammatory acne. First, the antimicrobial study of three free fatty acids (lauric acid, palmitic acid and oleic acid) demonstrated that LA gives the strongest bactericidal activity against P. acnes. However, a setback of using LA as a potential treatment for inflammatory acne is its poor water solubility. Then the LA was incorporated into a liposome formulation to aid its delivery to P. acnes. It was demonstrated that the antimicrobial activity of LA was not only well maintained in its liposomal derivatives but also enhanced at low LA concentration. In addition, the antimicrobial activity of LA-loaded liposomes (LipoLA) mainly depended on the LA loading concentration per single liposomes. Further study found that the LipoLA could fuse with the membranes of P. acnes and release the carried LA directly into the bacterial membranes, thereby killing the bacteria effectively. Since LA is a natural compound that is the main acid in coconut oil and also resides in human breast milk and liposomes have been successfully and widely applied as a drug delivery vehicle in the clinic, the LipoLA developed in this work holds great potential of becoming an innate, safe and effective therapeutic medication for acne vulgaris and other P. acnes associated diseases. PMID:19665786

  19. Urease inhibitory activities of β-boswellic acid derivatives

    PubMed Central

    2013-01-01

    Background and the purpose of the study Boswellia carterii have been used in traditional medicine for many years for management different gastrointestinal disorders. In this study, we wish to report urease inhibitory activity of four isolated compound of boswellic acid derivative. Methods 4 pentacyclic triterpenoid acids were isolated from Boswellia carterii and identified by NMR and Mass spectroscopic analysis (compounds 1, 3-O-acetyl-9,11-dehydro-β-boswellic acid; 2, 3-O-acetyl-11-hydroxy-β-boswellic acid; 3. 3-O- acetyl-11-keto-β-boswellic acid and 4, 11-keto-β-boswellic acid. Their inhibitory activity on Jack bean urease were evaluated. Docking and pharmacophore analysis using AutoDock 4.2 and Ligandscout 3.03 programs were also performed to explain possible mechanism of interaction between isolated compounds and urease enzyme. Results It was found that compound 1 has the strongest inhibitory activity against Jack bean urease (IC50 = 6.27 ± 0.03 μM), compared with thiourea as a standard inhibitor (IC50 = 21.1 ± 0.3 μM). Conclusion The inhibition potency is probably due to the formation of appropriate hydrogen bonds and hydrophobic interactions between the investigated compounds and urease enzyme active site and confirms its traditional usage. PMID:23351363

  20. The solar cycle variation of the rates of CMEs and related activity

    NASA Technical Reports Server (NTRS)

    Webb, David F.

    1991-01-01

    Coronal mass ejections (CMEs) are an important aspect of the physics of the corona and heliosphere. This paper presents results of a study of occurrence frequencies of CMEs and related activity tracers over more than a complete solar activity cycle. To properly estimate occurrence rates, observed CME rates must be corrected for instrument duty cycles, detection efficiencies away from the skyplane, mass detection thresholds, and geometrical considerations. These corrections are evaluated using CME data from 1976-1989 obtained with the Skylab, SMM and SOLWIND coronagraphs and the Helios-2 photometers. The major results are: (1) the occurrence rate of CMEs tends to track the activity cycle in both amplitude and phase; (2) the corrected rates from different instruments are reasonably consistent; and (3) over the long term, no one class of solar activity tracer is better correlated with CME rate than any other (with the possible exception of type II bursts).

  1. Which way does the citric acid cycle turn during hypoxia? The critical role of α-ketoglutarate dehydrogenase complex.

    PubMed

    Chinopoulos, Christos

    2013-08-01

    The citric acid cycle forms a major metabolic hub and as such it is involved in many disease states involving energetic imbalance. In spite of the fact that it is being branded as a "cycle", during hypoxia, when the electron transport chain does not oxidize reducing equivalents, segments of this metabolic pathway remain operational but exhibit opposing directionalities. This serves the purpose of harnessing high-energy phosphates through matrix substrate-level phosphorylation in the absence of oxidative phosphorylation. In this Mini-Review, these segments are appraised, pointing to the critical importance of the α-ketoglutarate dehydrogenase complex dictating their directionalities.

  2. CoRoT Reveals a Magnetic Activity Cycle in a Sun-Like Star

    NASA Astrophysics Data System (ADS)

    García, Rafael A.; Mathur, Savita; Salabert, David; Ballot, Jérôme; Régulo, Clara; Metcalfe, Travis S.; Baglin, Annie

    2010-08-01

    The 11-year activity cycle of the Sun is a consequence of a dynamo process occurring beneath its surface. We analyzed photometric data obtained by the CoRoT space mission, showing solarlike oscillations in the star HD49933, for signatures of stellar magnetic activity. Asteroseismic measurements of global changes in the oscillation frequencies and mode amplitudes reveal a modulation of at least 120 days, with the minimum frequency shift corresponding to maximum amplitude as in the Sun. These observations are evidence of a stellar magnetic activity cycle taking place beneath the surface of HD49933 and provide constraints for stellar dynamo models under conditions different from those of the Sun.

  3. Folic acid supplement use and menstrual cycle characteristics: a cross-sectional study of Danish pregnancy planners

    PubMed Central

    Cueto, Heidi T.; Riis, Anders H.; Hatch, Elizabeth E.; Wise, Lauren A.; Rothman, Kenneth J.; Sørensen, Henrik T.; Mikkelsen, Ellen M.

    2015-01-01

    Purpose To examine the association between folic acid (FA) supplementation obtained through either single FA tablets or multivitamins (MVs) and menstrual cycle characteristics among 5,386 women aged 18–40 years, enrolled in an Internet-based study of Danish women attempting pregnancy during 2007–2011. Methods In a cross-sectional study, we used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of FA supplementation with menstrual cycle regularity, short (<27 days), long (30–33 days), and very long (≥34 days) cycle length, and duration and intensity of menstrual bleeding. Results Compared with non-use, FA supplementation was associated with reduced odds of short cycle length [OR=0.80, 95% CI: 0.68–0.94], and a trend towards increased odds of very long cycle length [OR=1.21, 95% CI: 0.87–1.68] compared with cycle length of 27–29 days. The inverse association with short cycle length was stronger among 18–30 year-old women [OR=0.68, 95% CI: 0.53–0.87], nulliparous women [OR=0.66, 95% CI: 0.52–0.84], and women who used both FA and MVs [OR=0.75, 95% CI: 0.60–0.95]. We found no clear association between FA supplementation and cycle regularity and duration and intensity of menstrual bleeding. Conclusion FA supplementation was inversely associated with short menstrual cycle length. This association was strongest among women aged 18–30 years, nulliparous women, and women who used both FA and MVs. PMID:26123570

  4. A Comparison Between Global Proxies of the Sun's Magnetic Activity Cycle: Inferences from Helioseismology

    NASA Astrophysics Data System (ADS)

    Broomhall, A.-M.; Nakariakov, V. M.

    2015-11-01

    The last solar minimum was, by recent standards, unusually deep and long. We are now close to the maximum of the subsequent solar cycle, which is relatively weak. In this article we make comparisons between different global (unresolved) measures of the Sun's magnetic activity to investigate how they are responding to this weak-activity epoch. We focus on helioseismic data, which are sensitive to conditions, including the characteristics of the magnetic field, in the solar interior. Also considered are measures of the magnetic field in the photosphere (sunspot number and sunspot area), the chromosphere and corona (10.7 cm radio flux and 530.3 nm green coronal index), and two measures of the Sun's magnetic activity closer to Earth (the interplanetary magnetic field and the galactic cosmic-ray intensity). Scaled versions of the activity proxies diverge from the helioseismic data around 2000, indicating a change in relationship between the proxies. The degree of divergence varies from proxy to proxy, with sunspot area and 10.7 cm flux showing only small deviations, while sunspot number, coronal index, and the two interplanetary proxies show much larger departures. In Cycle 24 the deviations in the solar proxies and the helioseismic data decrease, raising the possibility that the deviations observed in Cycle 23 are just symptomatic of a 22-year Hale cycle. However, the deviations in the helioseismic data and the interplanetary proxies increase in Cycle 24. Interestingly, the divergence in the solar proxies and the helioseismic data are not reflected in the shorter-term variations (often referred to as quasi-biennial oscillations) observed on top of the dominant 11-year solar cycle. However, despite being highly correlated in Cycle 22, the short-term variations in the interplanetary proxies show very little correlation with the helioseismic data during Cycles 23 and 24.

  5. BACE1 activity impairs neuronal glucose oxidation: rescue by beta-hydroxybutyrate and lipoic acid

    PubMed Central

    Findlay, John A.; Hamilton, David L.; Ashford, Michael L. J.

    2015-01-01

    Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer's disease (AD) pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE1), responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y) cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD. PMID:26483636

  6. Relationships between solar activity and climate change. [sunspot cycle effects on lower atmosphere

    NASA Technical Reports Server (NTRS)

    Roberts, W. O.

    1974-01-01

    Recurrent droughts are related to the double sunspot cycle. It is suggested that high solar activity generally increases meridional circulations and blocking patterns at high and intermediate latitudes, especially in winter. This effect is related to the sudden formation of cirrus clouds during strong geomagnetic activity that originates in the solar corpuscular emission.

  7. Relationship between skin temperature and muscle activation during incremental cycle exercise.

    PubMed

    Priego Quesada, Jose I; Carpes, Felipe P; Bini, Rodrigo R; Salvador Palmer, Rosario; Pérez-Soriano, Pedro; Cibrián Ortiz de Anda, Rosa M

    2015-02-01

    While different studies showed that better fitness level adds to the efficiency of the thermoregulatory system, the relationship between muscular effort and skin temperature is still unknown. Therefore, the present study assessed the relationship between neuromuscular activation and skin temperature during cycle exercise. Ten physically active participants performed an incremental workload cycling test to exhaustion while neuromuscular activations were recorded (via surface electromyography - EMG) from rectus femoris, vastus lateralis, biceps femoris and gastrocnemius medialis. Thermographic images were recorded before, immediately after and 10 min after finishing the cycling test, at four body regions of interest corresponding to the muscles where neuromuscular activations were monitored. Frequency band analysis was conducted to assess spectral properties of EMG signals in order to infer on priority in recruitment of motor units. Significant inverse relationship between changes in skin temperature and changes in overall neuromuscular activation for vastus lateralis was observed (r<-0.5 and p<0.04). Significant positive relationship was observed between skin temperature and low frequency components of neuromuscular activation from vastus lateralis (r>0.7 and p<0.01). Participants with larger overall activation and reduced low frequency component for vastus lateralis activation presented a better adaptive response of their thermoregulatory system by showing fewer changes in skin temperature after incremental cycling test.

  8. A combined experimental and DFT study of active structures and self-cycle mechanisms of mononuclear tungsten peroxo complexes in oxidation reactions

    NASA Astrophysics Data System (ADS)

    Jin, Peng; Wei, Donghui; Wen, Yiqiang; Luo, Mengfei; Wang, Xiangyu; Tang, Mingsheng

    2011-04-01

    Tungsten peroxo complexes have been widely used in olefin epoxidation, alcohol oxidation, Baeyer-Villiger oxidation and other oxidation reactions, however, there is still not a unanimous viewpoint for the active structure of mononuclear tungsten peroxo complex by now. In this paper, the catalysis of mononuclear tungsten peroxo complexes 0- 5 with or without acidic ligands for the green oxidation of cyclohexene to adipic acid in the absence of organic solvent and phase-transfer catalyst has been researched in experiment. Then we have suggested two possible kinds of active structures of mononuclear tungsten peroxo complexes including peroxo ring ( nA, n = 0-1) and hydroperoxo ( nB, n = 0-1) structures, which have been investigated using density functional theory (DFT). Moreover, the calculations on self-cycle mechanisms involving the two types of active structures of tungsten peroxo complexes with and without oxalic acid ligand have also been carried out at the B3LYP/[LANL2DZ/6-31G(d, p)] level. The highest energy barrier are 26.17 kcal/mol ( 0A, peroxo ring structure without oxalic acid ligand), 23.91 kcal/mol ( 1A, peroxo ring structure with oxalic acid ligand), 18.19 kcal/mol ( 0B, hydroperoxo structure without oxalic acid ligand) and 13.10 kcal/mol ( 1B, hydroperoxo structure with oxalic acid ligand) in the four potential energy profiles, respectively. The results indicate that both the energy barriers of active structure self-cycle processes with oxalic acid ligands are lower than those without oxalic acid ligands, so the active structures with oxalic acid ligands should be easier to recycle, which is in good agreement with our experimental results. However, due to the higher energy of product than that of the reactant, the energy profile of the self-cycle process of 1B shows that the recycle of 1B could not occur at all in theory. Moreover, the crystal data of peroxo ring structure with oxalic acid ligand could be found in some experimental references. Thus

  9. Microbial ecology of a novel sulphur cycling consortia from AMD: implications for acid generation

    NASA Astrophysics Data System (ADS)

    Loiselle, L. M.; Norlund, K. L.; Hitchcock, A. P.; Warren, L. A.

    2009-05-01

    Recent work1 identified a novel microbial consortia consisting of two bacterial strains common to acid mine drainage (AMD) environments (autotrophic sulphur oxidizer Acidithiobacillus ferrooxidans and heterotrophic Acidiphilium spp.) in an environmental enrichment from a mine tailings lake. The two strains showed a specific spatial arrangement within an EPS macrostructure or "pod" allowing linked metabolic redox cycling of sulphur. Sulphur species characterisation of the pods using scanning transmission X-ray microscopy (STXM) indicated that autotrophic tetrathionate disproportionation by A. ferrooxidans producing colloidal elemental sulphur (S0) is coupled to heterotrophic S0 reduction by Acidiphilium spp. Geochemical modelling of the microbial sulphur reactions indicated that if they are widespread in AMD environments, then global AMD-driven CO2 liberation from mineral weathering have been overestimated by 40-90%1. Given the common co-occurrence of these two bacteria in AMD settings, the purpose of this study was to evaluate if these pods could be induced in the laboratory by pure strains and if so, whether their combined sulphur geochemistry mimicked the previous findings. Laboratory batch experiments assessed the development of pods with pure strain type cultures (A. ferrooxidans ATCC 19859 with mixotroph Acidiphilium acidophilum ATCC 738 or strict heterotroph Acp. cryptum ATCC 2158) using fluorescent in situ hybridization (FISH) imaging. The microbial sulphur geochemistry was characterized under autotrophic conditions identical to those used with the environmental AMD enrichment in which the pods were discovered. Results showed that the combined pure strain A. ferrooxidans and Acp. acidophilum form pods identical in structure to the AMD enrichment. To test the hypothesis that these pods form for mutual metabolic benefit, experiments were performed amending pure strain and AMD enrichment bacterial treatments with organic carbon and/or additional sulphur to

  10. Body temperature and physical activity correlates of the menstrual cycle in Chacma Baboons (Papio hamadryas ursinus).

    PubMed

    Nyakudya, Trevor T; Fuller, Andrea; Meyer, Leith C R; Maloney, Shane K; Mitchell, Duncan

    2012-12-01

    We investigated the temporal relationship between abdominal temperature, physical activity, perineal swelling, and urinary progesterone and estradiol concentrations over the menstrual cycle in unrestrained captive baboons. Using a miniature temperature-sensitive data logger surgically implanted in the abdominal cavity and an activity data logger implanted subcutaneously on the trunk, we measured, continuously over 6 months at 10-min intervals, abdominal temperature and physical activity patterns in four female adult baboons Papio hamadryas ursinus (12.9-19.9 kg), in cages in an indoor animal facility (22-25°C). We monitored menstrual bleeding and perineal swelling changes, and measured urinary progesterone and estradiol concentrations, daily for up to 6 months, to ascertain the stage and length of the menstrual cycle. The menstrual cycle was 36 ± 2 days (mean ± SD) long and the baboons exhibited cyclic changes in perineal swellings, abdominal temperature, physical activity, urinary progesterone, and estradiol concentrations over the cycle. Mean 24-hr abdominal temperature during the luteal phase was significantly higher than during the periovulatory phase (ANOVA, F((2, 9)) = 4.7; P = 0.04), but not different to that during the proliferative phase. Physical activity followed a similar pattern, with mean 24-hr physical activity almost twice as high in the luteal than in the periovulatory phase (ANOVA, P = 0.58; F((2, 12)) = 5.8). We have characterized correlates of the menstrual cycle in baboons and shown, for the first time, a rhythm of physical activity and abdominal temperature over the menstrual cycle, with a nadir of temperature and activity at ovulation.

  11. Activation of phosphatidic acid metabolism of human erythrocyte membranes by perfringolysin O

    SciTech Connect

    Saito, M.; Ando, S.; Mitsui, K.; Homma, Y.; Takenawa, T.

    1986-05-29

    The effect of perfringolysin O on the lipid metabolism of human erythrocyte membranes was investigated. Erythrocytes were prelabeled with (/sup 3/H)arachidonic acid and (/sup 32/P)inorganic phosphate. In the presence of calcium ion (5.5 mM), the effect of perfringolysin O on lipid metabolism was very similar to that of an calcium-ionophore A23187. In the absence of calcium ion, the accumulation of phosphatidic acid and its following decreasing trend were observed during the reaction with the toxin. Such changes were not caused by filipin. These results suggest that perfringolysin O causes the activation of a diglyceride-phosphatidic acid cycle, which might be involved in the calcium transport.

  12. Effects of precipitation on soil acid phosphatase activity in three successional forests in southern China

    NASA Astrophysics Data System (ADS)

    Huang, W.; Liu, J.; Zhou, G.; Zhang, D.; Deng, Q.

    2011-07-01

    Phosphorus (P) is often a limiting nutrient for plant growth in tropical and subtropical forests. Global climate change has led to alterations in precipitation in the recent years, which inevitably influences P cycling. Soil acid phosphatase plays a vital role in controlling P mineralization, and its activity reflects the capacity of organic P mineralization potential in soils. In order to study the effects of precipitation on soil acid phosphatase activity, an experiment with precipitation treatments (no precipitation, natural precipitation and doubled precipitation) in three successional forests in southern China was carried out. The three forests include Masson pine forest (MPF), coniferous and broad-leaved mixed forest (MF) and monsoon evergreen broad-leaved forest (MEBF). Results showed that driven by seasonality of precipitation, changes in soil acid phosphatase activities coincided with the seasonal climate pattern, with significantly higher values in the wet season than in the dry season. Soil acid phosphatase activities were closely linked to forest successional stages, with enhanced values in the later stages of forest succession. In the dry season, soil acid phosphatase activities in the three forests showed a rising trend with increasing precipitation treatments. In the wet season, soil acid phosphatase activity was depressed by no precipitation treatment in the three forests. However, doubled precipitation treatment exerted a significantly negative effect on it only in MEBF. These results indicate that the potential transformation rate of organic P might be more dependent on water in the dry season than in the wet season. A decrease in organic P turnover would occur in the three forests if there was a drought in a whole year in the future. More rainfall in the wet season would also be adverse to organic P turnover in MEBF due to its high soil moisture.

  13. Surface electromyographic activities of upper body muscles during high-intensity cycle ergometry.

    PubMed

    McCormick, Marie Clare; Watson, Hugh; Simpson, Alan; Kilgore, Lon; Baker, Julien S

    2014-01-01

    The aim of this study was to investigate upper body muscle activity during a 30 s Wingate test. Eighteen physically active participants performed a Wingate test while muscle activity was recorded from the brachioradialis (BR), biceps brachii (BB), triceps brachii (TB) and upper trapezius (UT). Measurements were obtained at rest, during a function maximal contraction (FMC) and during the 30 s Wingate test, whilst participants were positioned in a seated position on the cycle ergometer. All muscles were significantly active for the duration of the test. When normalized as a %FMC no differences in activity were found between muscles. Across the 30 s, power output was found to significantly decrease, whereas no changes were found in upper body muscle activity. All muscles investigated were active during the Wingate test and therefore confirmed previous findings that the upper body significantly contributes to power profiles obtained during high intensity cycle ergometry in addition to its role in stabilizing the body.

  14. Nitric acid vapor removal by activated, impregnated carbons

    SciTech Connect

    Wood, G.O.

    1996-12-31

    Laboratory and industrial workers can be exposed to vapors of nitric acid, especially in accidents, such as spills. Nitric acid can also be a product of incineration for energy production or waste (e.g., CW agent) disposal. Activated carbons containing impregnants for enhancing vapor and gas removal have been tested for effectiveness in removing vapors of nitric acid from air. The nitric acid vapor was generated from concentrated acid solutions and detected by trapping in a water bubbler for pH measurements. Both low and moderate relative humidity conditions were used. All carbons were effective at vapor contact times representative of air-purifying respirator use. One surprising observation was the desorption of low levels of ammonia from impregnated carbons. This was apparently due to residual ammonia from the impregnation processes.

  15. Tubulin dynamics during the cytoplasmic cohesiveness cycle in artificially activated sea urchin eggs.

    PubMed

    Coffe, G; Foucault, G; Raymond, M N; Pudles, J

    1983-12-01

    Sedimentation studies and [3H]colchicine-binding assays have demonstrated a relationship between the cytoplasmic cohesiveness cycles and the changes in tubulin organization in Paracentrotus lividus eggs activated by 2.5 mM procaine. The same amount of tubulin (20-25% of the total egg tubulin) is involved in these cyclic process and appears to undergo polymerization and depolymerization cycles. Electron microscopy studies reveal that the microtubules formed during these cytoplasmic cohesiveness cycles are under a particulate form which is sedimentable at low speed. Activation experiments carried out in the presence of cytochalasin B (CB) show that the increase in the cytoplasmic cohesiveness is highly reduced while tubulin polymerization and depolymerization cycles and pronuclear centration are not affected. Although tubulin or actin polymerization can be independently triggered in procaine-activated eggs, the increase in cytoplasmic cohesiveness requires the polymerization of both proteins. However, the cytoplasmic cohesiveness cycles appear to be regulated by tubulin polymerization and depolymerization cycles. PMID:6641809

  16. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism.

    PubMed

    Grassian, Alexandra R; Parker, Seth J; Davidson, Shawn M; Divakaruni, Ajit S; Green, Courtney R; Zhang, Xiamei; Slocum, Kelly L; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D; Straub, Christopher; Growney, Joseph D; Vander Heiden, Matthew G; Murphy, Anne N; Pagliarini, Raymond; Metallo, Christian M

    2014-06-15

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.

  17. Synthesis and antimicrobial activities of new higher amino acid Schiff base derivatives of 6-aminopenicillanic acid and 7-aminocephalosporanic acid

    NASA Astrophysics Data System (ADS)

    Özdemir (nee Güngör), Özlem; Gürkan, Perihan; Özçelik, Berrin; Oyardı, Özlem

    2016-02-01

    Novel β-lactam derivatives (1c-3c) (1d-3d) were produced by using 6-aminopenicillanic acid (6-APA), 7-aminocephalosporanic acid (7-ACA) and the higher amino acid Schiff bases. The synthesized compounds were characterized by elemental analysis, IR, 1H/13C NMR and UV-vis spectra. Antibacterial activities of all the higher amino acid Schiff bases (1a-3a) (1b-3b) and β-lactam derivatives were screened against three gram negative bacteria (Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii RSKK 02026), three gram positive bacteria (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 07005, Bacillus subtilis ATCC 6633) and their drug-resistant isolates by using broth microdilution method. Two fungi (Candida albicans and Candida krusei) were used for antifungal activity.

  18. Retinal pigment epithelial acid lipase activity and lipoprotein receptors: effects of dietary omega-3 fatty acids.

    PubMed Central

    Elner, Victor M

    2002-01-01

    PURPOSE: To show that fish oil-derived omega-3 polyunsaturated fatty acids, delivered to the retinal pigment epithelium (RPE) by circulating low-density lipoproteins (LDL), enhance already considerable RPE lysosomal acid lipase activity, providing for more efficient hydrolysis of intralysosomal RPE lipids, an effect that may help prevent development of age-related macular degeneration (ARMD). METHODS: Colorimetric biochemical and histochemical techniques were used to demonstrate RPE acid lipase in situ, in vitro, and after challenge with phagocytic stimuli. Receptor-mediated RPE uptake of fluorescently labeled native, aceto-acetylated, and oxidized LDL was studied in vitro and in vivo. LDL effects on RPE lysosomal enzymes were assessed. Lysosomal enzyme activity was compared in RPE cells from monkeys fed diets rich in fish oil to those from control animals and in cultured RPE cells exposed to sera from these monkeys. RESULTS: RPE acid lipase activity was substantial and comparable to that of mononuclear phagocytes. Acid lipase activity increased significantly following phagocytic challenge with photoreceptor outer segment (POS) membranes. Receptor-mediated RPE uptake of labeled lipoproteins was determined in vitro. Distinctive uptake of labeled lipoproteins occurred in RPE cells and mononuclear phagocytes in vivo. Native LDL enhanced RPE lysosomal enzyme activity. RPE lysosomal enzymes increased significantly in RPE cells from monkeys fed fish oil-rich diets and in cultured RPE cells exposed to their sera. CONCLUSIONS: RPE cells contain substantial acid lipase for efficient metabolism of lipids imbibed by POS phagocytosis and LDL uptake. Diets rich in fish oil-derived omega-3 fatty acids, by enhancing acid lipase, may reduce RPE lipofuscin accumulation, RPE oxidative damage, and the development of ARMD. PMID:12545699

  19. Synthesis and antifungal activity of cinnamic acid esters.

    PubMed

    Tawata, S; Taira, S; Kobamoto, N; Zhu, J; Ishihara, M; Toyama, S

    1996-05-01

    Cinnamic, p-coumaric and ferulic acids were isolated from pineapple stems (Ananas comosus var. Cayenne). Twenty-four kinds of esters were prepared from these acids, alcohols and the components of Alpinia. Isopropyl 4-hydroxycinnamate (11) and butyl 4-hydroxycinnamate (12) were found to have almost the same effectiveness in antifungal activity against Pythium sp. at 10 ppm as that of the commercial fungicide iprobenfos (kitazin P).

  20. Recovery of rhenium from sulfuric acid solutions with activated coals

    SciTech Connect

    Troshkina, I.D.; Naing, K.Z.; Ushanova, O.N.; P'o, V.; Abdusalomov, A.A.

    2006-09-15

    Equilibrium and kinetic characteristics of rhenium sorption from sulfuric acid solutions (pH 2) by activated coals produced from coal raw materials (China) were studied. Constants of the Henry equation describing isotherms of rhenium sorption by activated coals were calculated. The effective diffusion coefficients of rhenium in the coals were determined. The dynamic characteristics of rhenium sorption and desorption were determined for the activated coal with the best capacity and kinetic characteristics.

  1. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection.

    PubMed

    Marrero, Joeli; Rhee, Kyu Y; Schnappinger, Dirk; Pethe, Kevin; Ehrt, Sabine

    2010-05-25

    Metabolic adaptation to the host niche is a defining feature of the pathogenicity of Mycobacterium tuberculosis (Mtb). In vitro, Mtb is able to grow on a variety of carbon sources, but mounting evidence has implicated fatty acids as the major source of carbon and energy for Mtb during infection. When bacterial metabolism is primarily fueled by fatty acids, biosynthesis of sugars from intermediates of the tricarboxylic acid cycle is essential for growth. The role of gluconeogenesis in the pathogenesis of Mtb however remains unaddressed. Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the first committed step of gluconeogenesis. We applied genetic analyses and (13)C carbon tracing to confirm that PEPCK is essential for growth of Mtb on fatty acids and catalyzes carbon flow from tricarboxylic acid cycle-derived metabolites to gluconeogenic intermediates. We further show that PEPCK is required for growth of Mtb in isolated bone marrow-derived murine macrophages and in mice. Importantly, Mtb lacking PEPCK not only failed to replicate in mouse lungs but also failed to survive, and PEPCK depletion during the chronic phase of infection resulted in mycobacterial clearance. Mtb thus relies on gluconeogenesis throughout the infection. PEPCK depletion also attenuated Mtb in IFNgamma-deficient mice, suggesting that this enzyme represents an attractive target for chemotherapy.

  2. Production of tartrates by cyanide-mediated dimerization of glyoxylate: a potential abiotic pathway to the citric acid cycle.

    PubMed

    Butch, Christopher; Cope, Elizabeth D; Pollet, Pamela; Gelbaum, Leslie; Krishnamurthy, Ramanarayanan; Liotta, Charles L

    2013-09-11

    An abiotic formation of meso- and DL-tartrates in 80% yield via the cyanide-catalyzed dimerization of glyoxylate under alkaline conditions is demonstrated. A detailed mechanism for this conversion is proposed, supported by NMR evidence and (13)C-labeled reactions. Simple dehydration of tartrates to oxaloacetate and an ensuing decarboxylation to form pyruvate are known processes that provide a ready feedstock for entry into the citric acid cycle. While glyoxylate and high hydroxide concentration are atypical in the prebiotic literature, there is evidence for natural, abiotic availability of each. It is proposed that this availability, coupled with the remarkable efficiency of tartrate production from glyoxylate, merits consideration of an alternative prebiotic pathway for providing constituents of the citric acid cycle.

  3. Production of Tartrates by Cyanide-Mediated Dimerization of Glyoxylate: A Potential Abiotic Pathway to the Citric Acid Cycle

    PubMed Central

    2013-01-01

    An abiotic formation of meso- and dl-tartrates in 80% yield via the cyanide-catalyzed dimerization of glyoxylate under alkaline conditions is demonstrated. A detailed mechanism for this conversion is proposed, supported by NMR evidence and 13C-labeled reactions. Simple dehydration of tartrates to oxaloacetate and an ensuing decarboxylation to form pyruvate are known processes that provide a ready feedstock for entry into the citric acid cycle. While glyoxylate and high hydroxide concentration are atypical in the prebiotic literature, there is evidence for natural, abiotic availability of each. It is proposed that this availability, coupled with the remarkable efficiency of tartrate production from glyoxylate, merits consideration of an alternative prebiotic pathway for providing constituents of the citric acid cycle. PMID:23914725

  4. Effects of aluminum on activity of krebs cycle enzymes and glutamate dehydrogenase in rat brain homogenate.

    PubMed

    Zatta, P; Lain, E; Cagnolini, C

    2000-05-01

    Aluminum is a neurotoxic agent for animals and humans that has been implicated as an etiological factor in several neurodegenerative diseases and as a destabilizer of cell membranes. Due to its high reactivity, Al3+ is able to interfere with several biological functions, including enzymatic activities in key metabolic pathways. In this paper we report that, among the enzymes that constitute the Krebs cycle, only two are activated by aluminum: alpha-ketoglutarate dehydrogenase and succinate dehydrogenase. In contrast, aconitase, shows decreased activity in the presence of the metal ion. Al3+ also inhibits glutamate dehydrogenase, an allosteric enzyme that is closely linked to the Krebs cycle. A possible correlation between aluminum, the Krebs cycle and aging processes is discussed.

  5. Orbitofrontal cortex activity related to emotional processing changes across the menstrual cycle

    PubMed Central

    Protopopescu, Xenia; Pan, Hong; Altemus, Margaret; Tuescher, Oliver; Polanecsky, Margaret; McEwen, Bruce; Silbersweig, David; Stern, Emily

    2005-01-01

    The orbitofrontal cortex (OFC) has been implicated in the representation of emotional stimuli, assignment of emotional valence/salience to stimuli, stimulus-reinforcement association learning, motivation, and socio-emotional control. Using functional magnetic resonance imaging in female subjects without premenstrual mood symptoms, we found that OFC activity to emotional linguistic stimuli varies depending on the menstrual cycle phase. Specifically, anterior-medial OFC activity for negative vs. neutral stimuli was increased premenstrually and decreased postmenstrually. The inverse pattern was seen in the lateral OFC. These findings suggest that specific subregional OFC activity to emotional stimuli is modulated across the menstrual cycle. The data also demonstrate that menstrual cycle phase is an important consideration in further studies attempting to elucidate the neural substrates of affective representation. PMID:16247013

  6. Cell cycle arrest evidence, parasiticidal and bactericidal properties induced by L-amino acid oxidase from Bothrops atrox snake venom.

    PubMed

    de Melo Alves Paiva, Raquel; de Freitas Figueiredo, Raquel; Antonucci, Gilmara Ausech; Paiva, Helder Henrique; de Lourdes Pires Bianchi, Maria; Rodrigues, Kelly C; Lucarini, Rodrigo; Caetano, Renato Cesar; Linhari Rodrigues Pietro, Rosemeire Cristina; Gomes Martins, Carlos Henrique; de Albuquerque, Sérgio; Sampaio, Suely Vilela

    2011-05-01

    The present article describes an l-amino acid oxidase from Bothrops atrox snake venom as with antiprotozoal activities in Trypanosoma cruzi and in different species of Leishmania (Leishmania braziliensis, Leishmania donovani and Leishmania major). Leishmanicidal effects were inhibited by catalase, suggesting that they are mediated by H(2)O(2) production. Leishmania spp. cause a spectrum of diseases, ranging from self-healing ulcers to disseminated and often fatal infections, depending on the species involved and the host's immune response. BatroxLAAO also displays bactericidal activity against both Gram-positive and Gram-negative bacteria. The apoptosis induced by BatroxLAAO on HL-60 cell lines and PBMC cells was determined by morphological cell evaluation using a mix of fluorescent dyes. As revealed by flow cytometry analysis, suppression of cell proliferation with BatroxLAAO was accompanied by the significant accumulation of cells in the G0/G1 phase boundary in HL-60 cells. BatroxLAAO at 25 μg/mL and 50 μg/mL blocked G0-G1 transition, resulting in G0/G1 phase cell cycle arrest, thereby delaying the progression of cells through S and G2/M phase in HL-60 cells. This was shown by an accentuated decrease in the proportion of cells in S phase, and the almost absence of G2/M phase cell population. BatroxLAAO is an interesting enzyme that provides a better understanding of the ophidian envenomation mechanism, and has biotechnological potential as a model for therapeutic agents. PMID:21300133

  7. Metabolism of glycerol, glucose, and lactate in the citric acid cycle prior to incorporation into hepatic acylglycerols.

    PubMed

    Jin, Eunsook S; Sherry, A Dean; Malloy, Craig R

    2013-05-17

    During hepatic lipogenesis, the glycerol backbone of acylglycerols originates from one of three sources: glucose, glycerol, or substrates passing through the citric acid cycle via glyceroneogenesis. The relative contribution of each substrate source to glycerol in rat liver acylglycerols was determined using (13)C-enriched substrates and NMR. Animals received a fixed mixture of glucose, glycerol, and lactate; one group received [U-(13)C6]glucose, another received [U-(13)C3]glycerol, and the third received [U-(13)C3]lactate. After 3 h, the livers were harvested to extract fats, and the glycerol moiety from hydrolyzed acylglycerols was analyzed by (13)C NMR. In either fed or fasted animals, glucose and glycerol provided the majority of the glycerol backbone carbons, whereas the contribution of lactate was small. In fed animals, glucose contributed >50% of the total newly synthesized glycerol backbone, and 35% of this contribution occurred after glucose had passed through the citric acid cycle. By comparison, the glycerol contribution was ~40%, and of this, 17% of the exogenous glycerol passed first through the cycle. In fasted animals, exogenous glycerol became the major contributor to acylglycerols. The contribution from exogenous lactate did increase in fasted animals, but its overall contribution remained small. The contributions of glucose and glycerol that had passed through the citric acid cycle first increased in fasted animals from 35 to 71% for glucose and from 17 to 24% for glycerol. Thus, a substantial fraction from both substrate sources passed through the cycle prior to incorporation into the glycerol moiety of acylglycerols in the liver.

  8. Influence of tricarboxylic acid cycle intermediates and related metabolites on the biosynthesis of aflatoxin by resting cells of Aspergillus flavus.

    PubMed

    Shantha, T; Murthy, V S

    1981-11-01

    Resting cells of Aspergillus flavus synthesized aflatoxin from acetate as the sole carbon source after 36 h of incubation. Addition of pyruvate (5.5 mg/m) as cosubstrate to [1-14C]acetate and unlabeled acetate considerably reduced toxin production but increased the radioactivity on the tricarboxylic acid intermediates. This suggests that high tricarboxylic acid activity drastically affected toxin synthesis.

  9. Low-intensity cycling affects the muscle activation pattern of consequent countermovement jumps.

    PubMed

    Marquez, Gonzalo J; Mon, Javier; Acero, Rafael M; Sanchez, Jose A; Fernandez-del-Olmo, Miguel

    2009-08-01

    Players (eg, basketball, soccer, and football) often use a static bicycle during a game to maintain warming. However, the effectiveness of this procedure has not been addressed in the literature. Thus, it remains unknown whether low-intensity cycling movement can affect explosive movement performance. In this study, 10 male subjects performed countermovement jumps before and after a 15-minutes cycling bout at 35% of their maximal power output. Three sessions were tested for 3 different cadences of cycling: freely chosen cadence, 20% lower than freely chosen cadence (FCC-20%), and 20% higher than freely chosen cadence (FCC+20%). Jump height, kinematics, and electromyogram were recorded simultaneously during the countermovement jumps. The results showed a significant decreasing in the height of countermovement jump after cycling at freely chosen cadence and FCC-20% (p = 0.03 and p = 0.04, respectively), but not for FCC+20% cadences. The electromyographic parameters suggest that changes in the countermovement jump after cycling can be attributed to alteration of the pattern of activation and may be modulated by the preceding cycling cadence. Our study indicates that to avoid a possible negative effect of the cycling in the subsequent explosive movements, a cadence 20% higher than the preferred cadence must be used.

  10. The role of the ω-3 fatty acid DHA in the human life cycle.

    PubMed

    Carlson, Sarah J; Fallon, Erica M; Kalish, Brian T; Gura, Kathleen M; Puder, Mark

    2013-01-01

    Dietary consumption of the essential fatty acids linoleic acid (LA; ω-6) and α-linolenic acid (ALA; ω-3) is necessary for human growth and development. In the past 150 years, the average Western diet has changed dramatically such that humans today consume a much higher proportion of ω-6 fatty acids relative to ω-3 fatty acids than ever before. The importance of ω-3 fatty acids in human development has been well established in fetal and neonatal development, with brain and retinal tissues highly dependent on ω-3 fatty acids, specifically docosahexaenoic acid (DHA) for membrane fluidity and signal transduction. In childhood, ω-3s have been shown to contribute to ongoing cognitive development and may be involved in metabolic programming of bone turnover and adipogenesis. ω-3s may also play important roles in adult neurophysiology and disease prevention.

  11. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis

    PubMed Central

    Srivastava, Shikha; Somasagara, Ranganatha R.; Hegde, Mahesh; Nishana, Mayilaadumveettil; Tadi, Satish Kumar; Srivastava, Mrinal; Choudhary, Bibha; Raghavan, Sathees C.

    2016-01-01

    Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy. PMID:27068577

  12. Quercetin, a Natural Flavonoid Interacts with DNA, Arrests Cell Cycle and Causes Tumor Regression by Activating Mitochondrial Pathway of Apoptosis.

    PubMed

    Srivastava, Shikha; Somasagara, Ranganatha R; Hegde, Mahesh; Nishana, Mayilaadumveettil; Tadi, Satish Kumar; Srivastava, Mrinal; Choudhary, Bibha; Raghavan, Sathees C

    2016-01-01

    Naturally occurring compounds are considered as attractive candidates for cancer treatment and prevention. Quercetin and ellagic acid are naturally occurring flavonoids abundantly seen in several fruits and vegetables. In the present study, we evaluate and compare antitumor efficacies of quercetin and ellagic acid in animal models and cancer cell lines in a comprehensive manner. We found that quercetin induced cytotoxicity in leukemic cells in a dose-dependent manner, while ellagic acid showed only limited toxicity. Besides leukemic cells, quercetin also induced cytotoxicity in breast cancer cells, however, its effect on normal cells was limited or none. Further, quercetin caused S phase arrest during cell cycle progression in tested cancer cells. Quercetin induced tumor regression in mice at a concentration 3-fold lower than ellagic acid. Importantly, administration of quercetin lead to ~5 fold increase in the life span in tumor bearing mice compared to that of untreated controls. Further, we found that quercetin interacts with DNA directly, and could be one of the mechanisms for inducing apoptosis in both, cancer cell lines and tumor tissues by activating the intrinsic pathway. Thus, our data suggests that quercetin can be further explored for its potential to be used in cancer therapeutics and combination therapy. PMID:27068577

  13. Dihydroasparagusic acid: antioxidant and tyrosinase inhibitory activities and improved synthesis.

    PubMed

    Venditti, Alessandro; Mandrone, Manuela; Serrilli, Anna Maria; Bianco, Armandodoriano; Iannello, Carmelina; Poli, Ferruccio; Antognoni, Fabiana

    2013-07-17

    Dihydroasparagusic acid (DHAA) is the reduced form of asparagusic acid, a sulfur-containing flavor component produced by Asparagus plants. In this work, DHAA was synthetically produced by modifying some published protocols, and the synthesized molecule was tested in several in vitro assays (DPPH, ABTS, FRAP-ferrozine, BCB, deoxyribose assays) to evaluate its radical scavenging activity. Results show that DHAA is endowed with a significant in vitro antioxidant activity, comparable to that of Trolox. DHAA was also evaluated for its inhibitory activity toward tyrosinase, an enzyme involved, among others, in melanogenesis and in browning processes of plant-derived foods. DHAA was shown to exert an inhibitory effect on tyrosinase activity, and the inhibitor kinetics, analyzed by a Lineweaver-Burk plot, exhibited a competitive mechanism. Taken together, these results suggest that DHAA may be considered as a potentially active molecule for use in various fields of application, such as pharmaceutical, cosmetics, agronomic and food. PMID:23790134

  14. The Immunomodulatory Activity of Jacaric Acid, a Conjugated Linolenic Acid Isomer, on Murine Peritoneal Macrophages.

    PubMed

    Liu, Wai Nam; Leung, Kwok Nam

    2015-01-01

    This study aims at demonstrating the immunomodulatory property of jacaric acid, a conjugated linolenic acid (CLNA) isomer that is present in jacaranda seed oil, on murine peritoneal macrophages. Our results showed that jacaric acid exhibited no significant cytotoxicity on the thioglycollate-elicited murine peritoneal macrophages as revealed by the neutral red uptake assay, but markedly increased their cytostatic activity on the T-cell lymphoma MBL-2 cells as measured by the fluorometric CyQuant® NF Cell Proliferation Assay Kit. Flow cytometric analysis indicated that jacaric acid could enhance the endocytic activity of macrophages and elevated their intracellular production of superoxide anion. Moreover, jacaric acid-treated macrophages showed an increase in the production of nitric oxide which was accompanied by an increase in the expression level of inducible nitric oxide synthase protein. In addition, the secretion of several pro-inflammatory cytokines, including interferon-γ, interleukin-1β and tumor necrosis factor-α, was up-regulated. Collectively, our results indicated that the naturally-occurring CLNA isomer, jacaric acid, could exhibit immunomodulating activity on the murine peritoneal macrophages in vitro, suggesting that this CLNA isomer may act as an immunopotentiator which can be exploited for the treatment of some immunological disorders with minimal toxicity and fewer side effects.

  15. The Immunomodulatory Activity of Jacaric Acid, a Conjugated Linolenic Acid Isomer, on Murine Peritoneal Macrophages

    PubMed Central

    Liu, Wai Nam; Leung, Kwok Nam

    2015-01-01

    This study aims at demonstrating the immunomodulatory property of jacaric acid, a conjugated linolenic acid (CLNA) isomer that is present in jacaranda seed oil, on murine peritoneal macrophages. Our results showed that jacaric acid exhibited no significant cytotoxicity on the thioglycollate-elicited murine peritoneal macrophages as revealed by the neutral red uptake assay, but markedly increased their cytostatic activity on the T-cell lymphoma MBL-2 cells as measured by the fluorometric CyQuant® NF Cell Proliferation Assay Kit. Flow cytometric analysis indicated that jacaric acid could enhance the endocytic activity of macrophages and elevated their intracellular production of superoxide anion. Moreover, jacaric acid-treated macrophages showed an increase in the production of nitric oxide which was accompanied by an increase in the expression level of inducible nitric oxide synthase protein. In addition, the secretion of several pro-inflammatory cytokines, including interferon-γ, interleukin-1β and tumor necrosis factor-α, was up-regulated. Collectively, our results indicated that the naturally-occurring CLNA isomer, jacaric acid, could exhibit immunomodulating activity on the murine peritoneal macrophages in vitro, suggesting that this CLNA isomer may act as an immunopotentiator which can be exploited for the treatment of some immunological disorders with minimal toxicity and fewer side effects. PMID:26629697

  16. Oleanolic acid and ursolic acid: novel hepatitis C virus antivirals that inhibit NS5B activity.

    PubMed

    Kong, Lingbao; Li, Shanshan; Liao, Qingjiao; Zhang, Yanni; Sun, Ruina; Zhu, Xiangdong; Zhang, Qinghua; Wang, Jun; Wu, Xiaoyu; Fang, Xiaonan; Zhu, Ying

    2013-04-01

    Hepatitis C virus (HCV) infects up to 170 million people worldwide and causes significant morbidity and mortality. Unfortunately, current therapy is only curative in approximately 50% of HCV patients and has adverse side effects, which warrants the need to develop novel and effective antivirals against HCV. We have previously reported that the Chinese herb Fructus Ligustri Lucidi (FLL) directly inhibited HCV NS5B RNA-dependent RNA polymerase (RdRp) activity (Kong et al., 2007). In this study, we found that the FLL aqueous extract strongly suppressed HCV replication. Further high-performance liquid chromatography (HPLC) analysis combined with inhibitory assays indicates that oleanolic acid and ursolic acid are two antiviral components within FLL aqueous extract that significantly suppressed the replication of HCV genotype 1b replicon and HCV genotype 2a JFH1 virus. Moreover, oleanolic acid and ursolic acid exhibited anti-HCV activity at least partly through suppressing HCV NS5B RdRp activity as noncompetitive inhibitors. Therefore, our results for the first time demonstrated that natural products oleanolic acid and ursolic acid could be used as potential HCV antivirals that can be applied to clinic trials either as monotherapy or in combination with other HCV antivirals. PMID:23422646

  17. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern.

    PubMed

    Yang, Lili; Kasumov, Takhar; Kombu, Rajan S; Zhu, Shu-Han; Cendrowski, Andrea V; David, France; Anderson, Vernon E; Kelleher, Joanne K; Brunengraber, Henri

    2008-08-01

    In this second of two companion articles, we compare the mass isotopomer distribution of metabolites of liver gluconeogenesis and citric acid cycle labeled from NaH(13)CO(3) or dimethyl [1,4-(13)C(2)]succinate. The mass isotopomer distribution of intermediates reveals the reversibility of the isocitrate dehydrogenase + aconitase reactions, even in the absence of a source of alpha-ketoglutarate. In addition, in many cases, a number of labeling incompatibilities were found as follows: (i) glucose versus triose phosphates and phosphoenolpyruvate; (ii) differences in the labeling ratios C-4/C-3 of glucose versus (glyceraldehyde 3-phosphate)/(dihydroxyacetone phosphate); and (iii) labeling of citric acid cycle intermediates in tissue versus effluent perfusate. Overall, our data show that gluconeogenic and citric acid cycle intermediates cannot be considered as sets of homogeneously labeled pools. This probably results from the zonation of hepatic metabolism and, in some cases, from differences in the labeling pattern of mitochondrial versus extramitochondrial metabolites. Our data have implications for the use of labeling patterns for the calculation of metabolic rates or fractional syntheses in liver, as well as for modeling liver intermediary metabolism.

  18. Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

    PubMed Central

    Jazi, Marie Saghaeian; Mohammadi, Saeed; Yazdani, Yaghoub; Sedighi, Sima; Memarian, Ali; Aghaei, Mehrdad

    2016-01-01

    Objective(s): T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.

  19. Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

    PubMed Central

    Jazi, Marie Saghaeian; Mohammadi, Saeed; Yazdani, Yaghoub; Sedighi, Sima; Memarian, Ali; Aghaei, Mehrdad

    2016-01-01

    Objective(s): T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA) as a recently emerged anti-neoplastic histone deacetylase (HDAC) inhibitor and pioglitazone (PGZ) as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ) agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after 24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A) phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27) expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies. PMID:27635203

  20. Acid activation of bentonites and polymer-clay nanocomposites.

    SciTech Connect

    Carrado, K. A.; Komadel, P.; Center for Nanoscale Materials; Slovak Academy of Sciences

    2009-04-01

    Modified bentonites are of widespread technological importance. Common modifications include acid activation and organic treatment. Acid activation has been used for decades to prepare bleaching earths for adsorbing impurities from edible and industrial oils. Organic treatment has sparked an explosive interest in a class of materials called polymer-clay nanocomposites (PCNs). The most commonly used clay mineral in PCNs is montmorillonite, which is the main constituent of bentonite. PCN materials are used for structural reinforcement and mechanical strength, for gas permeability barriers, as flame retardants, and to minimize surface erosion (ablation). Other specialty applications include use as conducting nanocomposites and bionanocomposites.

  1. A new method for assembling metabolic networks, with application to the Krebs citric acid cycle.

    PubMed

    Mittenthal, J E; Clarke, B; Waddell, T G; Fawcett, G

    2001-02-01

    To understand why a molecular network has a particular connectivity one can generate an ensemble of alternative networks, all of which meet the same performance criteria as the real network. We have generated alternatives to the Krebs cycle, allowing group transfers and B(12)-mediated shifts that were excluded in previous work. Our algorithm does not use a reaction list, but determines the reactants and products in generic reactions. It generates networks in order of increasing number of reaction steps. We find that alternatives to the Krebs cycle are very likely to be cycles. Many of the alternatives produce toxic or unstable compounds and use group transfer reactions, which have unfavorable consequences. Although alternatives are better than the Krebs cycle in some respects, the Krebs cycle has the most favorable combination of traits.

  2. Characterization of nano-lead-doped active carbon and its application in lead-acid battery

    NASA Astrophysics Data System (ADS)

    Hong, Bo; Jiang, Liangxing; Xue, Haitao; Liu, Fangyang; Jia, Ming; Li, Jie; Liu, Yexiang

    2014-12-01

    In this paper, nano-lead-doped active carbon (nano-Pb/AC) composite with low hydrogen evolution current for lead-acid battery was prepared by ultrasonic-absorption and chemical-precipitate method. The nano-Pb/AC composite was characterized by SEM, EDS and TEM. The electrochemical characterizations are performed by linear sweep voltammetry (LSV), electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) in a three-electrode system. Since intermediate adsorption is the rate-determining step, the hydrogen evolution reaction (HER) is markedly inhibited as the intermediate adsorption impedance of nano-Pb/AC increased. Meanwhile, the working potential of nano-Pb/AC is widened to the whole potential region of Pb negative plate (from -1.36 V to -0.86 V vs. Hg/HgSO4) in lead-acid battery. In addition, nano-Pb can improve the interfacial compatibility between AC and Pb paste, accordingly relieve the symptoms of carbon floatation. Finally, 2.0 V single-cell flooded lead-acid batteries with 1.0 wt.% nano-Pb/AC or 1.0 wt.% AC addition in negative active materials are assembled. The cell performances test results show that the 3 h rate capacity, quick charging performance, high current discharging performance and cycling performance of nano-Pb/AC modified battery are all improved compared with regular lead-acid battery and AC modified lead-acid battery.

  3. Effects of physical activity on pupil cycle time (PCT) in healthy Indian male.

    PubMed

    Ghosh, Suparna; Avadhany, Sandhya T

    2014-01-01

    Globally, physical inactivity is an important risk factor for the development of non-communicable disease consisting of coronary artery disease, as well as, other diseases including hypertension, diabetes, obesity, osteoporosis, and certain types of cancers. Parasympathetic nervous system (PNS) activity in the eye is determined by the pupil cycle time (PCT) can be comparable with cardiac parasympathetic response and thereby determine the morbidity and mortality among individuals. The PCT is measured by throwing white light on the edge of the pupil. Pupil cycling is a feature of pupillary reflex arc. The aim of this study is to establish the effect of physical activity on the PCT. The counting of PCT was done for 90 cycles and average one count is considered a single PCT. The physical activity level (PAL) was determined by administering a physical activity level questionnaire developed in the Division of Nutrition, St. John's Medical College, Bangalore. The PAL is classified as < 1.4 as sedentary, 1.55 to 1.75 moderately active, and > 1.75 heavily active. Thirty healthy male volunteers in the age group of 18-50 years and with BMI of 18.5 kg/m2-30 kg/m2 were studied. We obtained PCT of 962.00 ± 105.72 msec in sedentary, 896.77 ± 85.88 msec in moderately active and 889.45 ± 68.71 msec in heavily active individuals. Linear regression analysis shows there is statistically significant difference between the three different groups of physical activity level with a b value of 0 and R2 being 0.19. Increase in physical activity led to decrease in the PCT i.e. increase in the parasympathetic tone in the eye. Pupil cycle time (PCT) is a simple noninvasive tool to assess and differentiate the PNS function in different activity level of individual. PMID:25906609

  4. Antimicrobial activity of poly(acrylic acid) block copolymers.

    PubMed

    Gratzl, Günther; Paulik, Christian; Hild, Sabine; Guggenbichler, Josef P; Lackner, Maximilian

    2014-05-01

    The increasing number of antibiotic-resistant bacterial strains has developed into a major health problem. In particular, biofilms are the main reason for hospital-acquired infections and diseases. Once formed, biofilms are difficult to remove as they have specific defense mechanisms against antimicrobial agents. Antimicrobial surfaces must therefore kill or repel bacteria before they can settle to form a biofilm. In this study, we describe that poly(acrylic acid) (PAA) containing diblock copolymers can kill bacteria and prevent from biofilm formation. The PAA diblock copolymers with poly(styrene) and poly(methyl methacrylate) were synthesized via anionic polymerization of tert-butyl acrylate with styrene or methyl methacrylate and subsequent acid-catalyzed hydrolysis of the tert-butyl ester. The copolymers were characterized via nuclear magnetic resonance spectroscopy (NMR), size-exclusion chromatography (SEC), Fourier transform infrared spectroscopy (FTIR), elemental analysis, and acid-base titrations. Copolymer films with a variety of acrylic acid contents were produced by solvent casting, characterized by atomic force microscopy (AFM) and tested for their antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The antimicrobial activity of the acidic diblock copolymers increased with increasing acrylic acid content, independent of the copolymer-partner, the chain length and the nanostructure.

  5. Statistical properties of Hα flares in relation to sunspots and active regions in the cycle 23

    NASA Astrophysics Data System (ADS)

    Zharkov, S. I.; Zharkova, V. V.

    2011-02-01

    The statistical properties of Hα flare occurrences compared with those of sunspot and active region areas in the cycle 23. The flare numbers in the cycle 23 of all significances and locations were obtained from the Solar Geophysical Data (SGD) and the other data were taken from the automated Solar Feature Catalogues (SFC, http://solar.inf.brad.ac.uk). The average monthly flare occurrences during the whole cycle correlate closely with the total and cumulative areas of active regions and sunspots. The cumulative distribution of solar flare occurrences at different latitudes in the northern and southern hemispheres versus the time reveal a strong asymmetry with a domination of one or other hemispheres similar to the cumulative distributions of sunspots and active regions. Although the sunspot area asymmetry lags the flare occurrence asymmetry by about a few months at the ascending phase of the cycle and up to 12 months in the descending one. The latitudinal distribution of flare occurrences in the whole period reveals a well defined maximum at 18∘ in the northern and two maxima at 14∘ and 20∘ in the southern hemisphere. The longitudinal distributions of flare occurrence residuals of the running values and those averaged with a one year filter reveal a set of persistent longitudes in the opposite hemispheres lasting for about 1.0-1.5 years and changing quickly a few times over the cycle phases.

  6. [The development of the activity-rest cycle in the rabbit fetus].

    PubMed

    Belich, A I; Nazarova, L A

    1988-01-01

    On 25-30-day rabbit foetuses, in chronic experiments using constant synchronous recording of the motor activity and heart rate, studies have been made of temporal organization of the activity-rest cycle. Already in 25-day foetus, three functional conditions may be distinguished: active, intermediate and resting ones, the duration of the latter increasing to the end of gestation up to 8-10 min, whereas the duration of the intermediate phase decreases, reaching its minimum to the 30th day if not being completely reduced. Cyclic pattern of active and resting phases is observed in 28-day foetuses; to the 29th-30th day, these phases from a unique activity-rest cycle, its duration reaching 20-30 min to the end of intrauterine period. It is suggested that the resting phase in foetal rabbits serves as a basis for the development of polyphasic sleep in adult animals. PMID:3414220

  7. Menstrual cycle phase does not affect sympathetic neural activity in women with postural orthostatic tachycardia syndrome

    PubMed Central

    Stickford, Abigail SL; VanGundy, Tiffany B; Levine, Benjamin D; Fu, Qi

    2015-01-01

    Abstract Patients with the postural orthostatic tachycardia syndrome (POTS) are primarily premenopausal women, which may be attributed to female sex hormones. We tested the hypothesis that hormonal fluctuations of the menstrual cycle alter sympathetic neural activity and orthostatic tolerance in POTS women. Ten POTS women were studied during the early follicular (EF) and mid-luteal (ML) phases of the menstrual cycle. Haemodynamics and muscle sympathetic nerve activity (MSNA) were measured when supine, during 60 deg upright tilt for 45 min or until presyncope, and during the cold pressor test (CPT) and Valsalva manoeuvres. Blood pressure and total peripheral resistance were higher during rest and tilting in the ML than EF phase; however, heart rate, stroke volume and cardiac output were similar between phases. There were no mean ± SD differences in MSNA burst frequency (8 ± 8 EF phase vs. 10 ± 10 bursts min–1 ML phase at rest; 34 ± 15 EF phase vs. 36 ± 16 bursts min–1 ML phase at 5 min tilt), burst incidence or total activity, nor any differences in the cardiovagal and sympathetic baroreflex sensitivities between phases under any condition. The incidence of presyncope was also the same between phases. There were no differences in haemodynamic or sympathetic responses to CPT or Valsalva. These results suggest that the menstrual cycle does not affect sympathetic neural activity but modulates blood pressure and vasoconstriction in POTS women during tilting. Thus, factors other than sympathetic neural activity are probably responsible for the symptoms of orthostatic intolerance across the menstrual cycle in women with POTS. Key points Women with the postural orthostatic tachycardia syndrome (POTS) report fluctuations in orthostatic tolerance throughout the menstrual cycle. The mechanism(s) underlying blood pressure control across the menstrual cycle in women with POTS are unknown. The findings of the present study indicate that the menstrual

  8. beta-Sitosterol activates the sphingomyelin cycle and induces apoptosis in LNCaP human prostate cancer cells.

    PubMed

    von Holtz, R L; Fink, C S; Awad, A B

    1998-01-01

    Epidemiological evidence has shown that men consuming a low-fat, high-fiber diet containing high amounts of plant products have a lower risk of prostate cancer than men consuming a Western diet. One of the main differences between these two diets is the type of dietary fat, including dietary sterols. This study was undertaken to compare the effect of two dietary sterols on prostate cancer cells in vitro. beta-Sitosterol (SIT), the most common plant sterol, and cholesterol, an animal sterol, were compared for effect on LNCaP cell growth, differentiation, apoptosis, and sphingomyelin cycle intermediates. Cells were treated for up to seven days with sterols delivered by a cyclodextrin vehicle. Compared with cholesterol, SIT (16 microM) decreased growth by 24% and induced apoptosis fourfold, which was accompanied by cell rounding and a 50% increase in ceramide production. No effect was observed on differentiation as measured by prostate-specific antigen and prostatic acid phosphatase, although total acid phosphatase increased with SIT treatment for up to seven days. The results suggest that the decrease in cell number and increase in apoptosis associated with SIT treatment are mediated by activating the sphingomyelin cycle.

  9. Solar Magnetic Activity Cycles, Coronal Potential Field Models and Eruption Rates

    NASA Astrophysics Data System (ADS)

    Petrie, G. J. D.

    2013-05-01

    We study the evolution of the observed photospheric magnetic field and the modeled global coronal magnetic field during the past 3 1/2 solar activity cycles observed since the mid-1970s. We use synoptic magnetograms and extrapolated potential-field models based on longitudinal full-disk photospheric magnetograms from the National Solar Observatory's three magnetographs at Kitt Peak, the Synoptic Optical Long-term Investigations of the Sun vector spectro-magnetograph, the spectro-magnetograph and the 512-channel magnetograph instruments, and from Stanford University's Wilcox Solar Observatory. The associated multipole field components are used to study the dominant length scales and symmetries of the coronal field. Polar field changes are found to be well correlated with active fields over most of the period studied, except between 2003 and 2006 when the active fields did not produce significant polar field changes. Of the axisymmetric multipoles, only the dipole and octupole follow the poles whereas the higher orders follow the activity cycle. All non-axisymmetric multipole strengths are well correlated with the activity cycle. The tilt of the solar dipole is therefore almost entirely due to active-region fields. The axial dipole and octupole are the largest contributors to the global field except while the polar fields are reversing. This influence of the polar fields extends to modulating eruption rates. According to the Computer Aided CME Tracking, Solar Eruptive Event Detection System, and Nobeyama radioheliograph prominence eruption catalogs, the rate of solar eruptions is found to be systematically higher for active years between 2003 and 2012 than for those between 1997 and 2002. This behavior appears to be connected with the weakness of the late-cycle 23 polar fields as suggested by Luhmann. We see evidence that the process of cycle 24 field reversal is well advanced at both poles.

  10. SOLAR MAGNETIC ACTIVITY CYCLES, CORONAL POTENTIAL FIELD MODELS AND ERUPTION RATES

    SciTech Connect

    Petrie, G. J. D.

    2013-05-10

    We study the evolution of the observed photospheric magnetic field and the modeled global coronal magnetic field during the past 3 1/2 solar activity cycles observed since the mid-1970s. We use synoptic magnetograms and extrapolated potential-field models based on longitudinal full-disk photospheric magnetograms from the National Solar Observatory's three magnetographs at Kitt Peak, the Synoptic Optical Long-term Investigations of the Sun vector spectro-magnetograph, the spectro-magnetograph and the 512-channel magnetograph instruments, and from Stanford University's Wilcox Solar Observatory. The associated multipole field components are used to study the dominant length scales and symmetries of the coronal field. Polar field changes are found to be well correlated with active fields over most of the period studied, except between 2003 and 2006 when the active fields did not produce significant polar field changes. Of the axisymmetric multipoles, only the dipole and octupole follow the poles whereas the higher orders follow the activity cycle. All non-axisymmetric multipole strengths are well correlated with the activity cycle. The tilt of the solar dipole is therefore almost entirely due to active-region fields. The axial dipole and octupole are the largest contributors to the global field except while the polar fields are reversing. This influence of the polar fields extends to modulating eruption rates. According to the Computer Aided CME Tracking, Solar Eruptive Event Detection System, and Nobeyama radioheliograph prominence eruption catalogs, the rate of solar eruptions is found to be systematically higher for active years between 2003 and 2012 than for those between 1997 and 2002. This behavior appears to be connected with the weakness of the late-cycle 23 polar fields as suggested by Luhmann. We see evidence that the process of cycle 24 field reversal is well advanced at both poles.

  11. Amphipathic β2,2-Amino Acid Derivatives Suppress Infectivity and Disrupt the Intracellular Replication Cycle of Chlamydia pneumoniae

    PubMed Central

    Tiirola, Terttu M.; Strøm, Morten B.; Vuorela, Pia M.

    2016-01-01

    We demonstrate in the current work that small cationic antimicrobial β2,2-amino acid derivatives (Mw < 500 Da) are highly potent against Chlamydia pneumoniae at clinical relevant concentrations (< 5 μM, i.e. < 3.4 μg/mL). C. pneumoniae is an atypical respiratory pathogen associated with frequent treatment failures and persistent infections. This gram-negative bacterium has a biphasic life cycle as infectious elementary bodies and proliferating reticulate bodies, and efficient treatment is challenging because of its long and obligate intracellular replication cycle within specialized inclusion vacuoles. Chlamydicidal effect of the β2,2-amino acid derivatives in infected human epithelial cells was confirmed by transmission electron microscopy. Images of infected host cells treated with our lead derivative A2 revealed affected chlamydial inclusion vacuoles 24 hours post infection. Only remnants of elementary and reticulate bodies were detected at later time points. Neither the EM studies nor resazurin-based cell viability assays showed toxic effects on uninfected host cells or cell organelles after A2 treatment. Besides the effects on early intracellular inclusion vacuoles, the ability of these β2,2-amino acid derivatives to suppress Chlamydia pneumoniae infectivity upon treatment of elementary bodies suggested also a direct interaction with bacterial membranes. Synthetic β2,2-amino acid derivatives that target C. pneumoniae represent promising lead molecules for development of antimicrobial agents against this hard-to-treat intracellular pathogen. PMID:27280777

  12. Metaproteomic survey of six aquatic habitats: discovering the identities of microbial populations active in biogeochemical cycling.

    PubMed

    Hanson, Buck T; Hewson, Ian; Madsen, Eugene L

    2014-04-01

    Our goal is to strengthen the foundations of metaproteomics as a microbial community analysis tool that links the functional identity of actively expressed gene products with host phylogeny. We used shotgun metaproteomics to survey waters in six disparate aquatic habitats (Cayuga Lake, NY; Oneida Lake, NY; Gulf of Maine; Chesapeake Bay, MD; Gulf of Mexico; and the South Pacific). Peptide pools prepared from filter-gathered microbial biomass, analyzed by nano-liquid chromatography-mass spectrometry (MS/MS) generating 9,693 ± 1,073 mass spectra identified 326 ± 107 bacterial proteins per sample. Distribution of proteobacterial (Alpha and Beta) and cyanobacterial (Prochlorococcus and Synechococcus spp.) protein hosts across all six samples was consistent with the previously published biogeography for these microorganisms. Marine samples were enriched in transport proteins (TRAP-type for dicarboxylates and ATP binding cassette (ABC)-type for amino acids and carbohydrates) compared with the freshwater samples. We were able to match in situ expression of many key proteins catalyzing C-, N-, and S-cycle processes with their bacterial hosts across all six habitats. Pelagibacter was identified as the host of ABC-type sugar-, organic polyanion-, and glycine betaine-transport proteins; this extends previously published studies of Pelagibacter's in situ biogeochemical role in marine C- and N-metabolism. Proteins matched to Ruegeria confirmed these organism's role in marine waters oxidizing both carbon monoxide and sulfide. By documenting both processes expressed in situ and the identity of host cells, metaproteomics tested several existing hypotheses about ecophysiological processes and provided fodder for new ones. PMID:24425229

  13. Annual cycle and spatial trends in fatty acid composition of suspended particulate organic matter across the Beaufort Sea shelf

    NASA Astrophysics Data System (ADS)

    Connelly, Tara L.; Businski, Tara N.; Deibel, Don; Parrish, Christopher C.; Trela, Piotr

    2016-11-01

    Fatty acid profiles of suspended particulate organic matter (POM) were determined over an annual cycle (September 2003 to August 2004) on the Beaufort Sea shelf, Canadian Arctic. Special emphasis was placed on the nutritional quality of the fatty acid pool available to zooplankton by examining spatial and temporal patterns in the proportions of total polyunsaturated fatty acids (PUFA) and the essential fatty acids 22:6n-3 (DHA) and 20:5n-3 (EPA). EPA and DHA were the two most abundant PUFA throughout the study period. A log-ratio multivariate (LRA) analysis revealed strong structure in fatty acid profiles related to season and depth. Dominant fatty acids accounting for the observed trend included 18:5n-3, 18:4n-3, 16:1n-7, 20:5n-3, 18:0 and 20:3n-3. We observed a shift in fatty acid profiles from summer to autumn (e.g., from 16:1n-7 and EPA to 18:5n-3 and 18:4n-3) that likely corresponded to a shift in the relative importance of diatoms versus dinoflagellates, prymnesiophytes and/or prasinophytes to the POM pool. Fatty acid composition during winter was dominated by more refractory saturated fatty acids. A surprising finding was the depth and seasonal trend of 20:3n-3, which was higher in winter, aligned with 18:0 in the LRA, but behaved differently than other n-3 PUFA. We interpret fatty acid profiles during summer to be predominantly driven by phytoplankton inputs, whereas fatty acid profiles in winter were dominated by fatty acids that were left over after consumption and/or were generated by heterotrophs. The highest diatom inputs (EPA, the diatom fatty acid marker), n-3/n-6 ratios, and C16 PUFA index were located in an upwelling region off Cape Bathurst. This study is the first annual time series of fatty acid profiles of POM in Arctic seas, expanding our knowledge of the composition of POM throughout the dark season.

  14. Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity.

    PubMed

    Chatterjee, Sayanti; Paine, Tapan Kanti

    2015-10-19

    Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant.

  15. Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity.

    PubMed

    Chatterjee, Sayanti; Paine, Tapan Kanti

    2015-10-19

    Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant. PMID:26430780

  16. Estradiol levels modulate brain activity and negative responses to psychosocial stress across the menstrual cycle.

    PubMed

    Albert, Kimberly; Pruessner, Jens; Newhouse, Paul

    2015-09-01

    Although ovarian hormones are thought to have a potential role in the well-known sex difference in mood and anxiety disorders, the mechanisms through which ovarian hormone changes contribute to stress regulation are not well understood. One mechanism by which ovarian hormones might impact mood regulation is by mediating the effect of psychosocial stress, which often precedes depressive episodes and may have mood consequences that are particularly relevant in women. In the current study, brain activity and mood response to psychosocial stress was examined in healthy, normally cycling women at either the high or low estradiol phase of the menstrual cycle. Twenty eight women were exposed to the Montreal Imaging Stress Task (MIST), with brain activity determined through functional magnetic resonance imaging, and behavioral response assessed with subjective mood and stress measures. Brain activity responses to psychosocial stress differed between women in the low versus high estrogen phase of the menstrual cycle: women with high estradiol levels showed significantly less deactivation in limbic regions during psychosocial stress compared to women with low estradiol levels. Additionally, women with higher estradiol levels also had less subjective distress in response to the MIST than women with lower estradiol levels. The results of this study suggest that, in normally cycling premenopausal women, high estradiol levels attenuate the brain activation changes and negative mood response to psychosocial stress. Normal ovarian hormone fluctuations may alter the impact of psychosocially stressful events by presenting periods of increased vulnerability to psychosocial stress during low estradiol phases of the menstrual cycle. This menstrual cycle-related fluctuation in stress vulnerability may be relevant to the greater risk for affective disorder or post-traumatic stress disorder in women.

  17. Analysis of trace inorganic anions in weak acid salts by single pump cycling-column-switching ion chromatography.

    PubMed

    Huang, Zhongping; Ni, Chengzhu; Zhu, Zhuyi; Pan, Zaifa; Wang, Lili; Zhu, Yan

    2015-05-01

    The application of ion chromatography with the single pump cycling-column-switching technique was described for the analysis of trace inorganic anions in weak acid salts within a single run. Due to the hydrogen ions provided by an anion suppressor electrolyzing water, weak acid anions could be transformed into weak acids, existing as molecules, after passing through the suppressor. Therefore, an anion suppressor and ion-exclusion column were adopted to achieve on-line matrix elimination of weak acid anions with high concentration for the analysis of trace inorganic anions in weak acid salts. A series of standard solutions consisting of target anions of various concentrations from 0.005 to 10 mg/L were analyzed, with correlation coefficients r ≥ 0.9990. The limits of detection were in the range of 0.67 to 1.51 μg/L, based on the signal-to-noise ratio of 3 and a 25 μL injection volume. Relative standard deviations for retention time, peak area, and peak height were all less than 2.01%. A spiking study was performed with satisfactory recoveries between 90.3 and 104.4% for all anions. The chromatographic system was successfully applied to the analysis of trace inorganic anions in five weak acid salts.

  18. Structure-activity relationship of caffeoylquinic acids on the accelerating activity on ATP production.

    PubMed

    Miyamae, Yusaku; Kurisu, Manami; Han, Junkyu; Isoda, Hiroko; Shigemori, Hideyuki

    2011-01-01

    Caffeoylquinic acid (CQA) is one of the phenylpropanoids which have various bioactivities such as antioxidant, antibacterial, anticancer, antihistamic, and other biological effects. We previously reported that 3,5-di-O-caffeoylquinic acid inhibited amyloid β(1-42)-induced cellular toxicity on human neuroblastoma SH-SY5Y cells and increased the mRNA expression level of glycolytic enzymes and the intracellular ATP level. To investigate structure-activity relationship on the accelerating activity on ATP production, we synthesized 1,4,5-tri-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, 3,4,5-tri-O-caffeoylquinic acid, and other derivatives. Additionally, we evaluated intracellular ATP level in SH-SY5Y treated with each CQA derivative. As a result, 3,4,5-tri-O-caffeoylquinic acid showed the highest accelerating activity on ATP production among tested compounds. It was suggested that caffeoyl groups bound to quinic acid are important for activity and the more caffeoyl groups are bound to quinic acid, the higher accelerating activity on ATP production exhibits.

  19. Tandem dissolution of UO 3 in amide-based acidic ionic liquid and in situ electrodeposition of UO 2 with regeneration of the ionic liquid: a closed cycle

    DOE PAGES

    Wanigasekara, Eranda; Freiderich, John W.; Sun, Xiao-Guang; Meisner, Roberta A.; Luo, Huimin; Delmau, Lætitia H.; Dai, Sheng; Moyer, Bruce A.

    2016-05-19

    A closed cycle is demonstrated for the tandem dissolution and electroreduction of UO3 to UO2 with regeneration of the acidic ionic liquid. The dissolution is achieved by use of the acidic ionic liquid N,N-dimethylacetimidium bis(trifluoromethanesulfonimide) in 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonimide) serving as the diluent. Bulk electrolysis performed at 1.0 V vs. Ag reference yields a dark brown-black uranium deposit (UO2) on the cathode. Anodic oxidation of water in the presence of dimethylacetamide regenerates the acidic ionic liquid. We have demonstrated the individual steps in the cycle together with a sequential dissolution, electroreduction, and regeneration cycle.

  20. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2012-10-16

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  1. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2014-09-30

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  2. Teacher's Resource Guide on Acidic Precipitation with Laboratory Activities.

    ERIC Educational Resources Information Center

    Barrow, Lloyd H.

    The purpose of this teacher's resource guide is to help science teachers incorporate the topic of acidic precipitation into their curricula. A survey of recent junior high school science textbooks found a maximum of one paragraph devoted to the subject; in addition, none of these books had any related laboratory activities. It was on the basis of…

  3. Interconnection between tricarboxylic acid cycle and energy generation in microbial fuel cell performed by desulfuromonas acetoxidans IMV B-7384

    NASA Astrophysics Data System (ADS)

    Vasyliv, Oresta M.; Maslovska, Olga D.; Ferensovych, Yaroslav P.; Bilyy, Oleksandr I.; Hnatush, Svitlana O.

    2015-05-01

    Desulfuromonas acetoxidans IMV B-7384 is exoelectrogenic obligate anaerobic sulfur-reducing bacterium. Its one of the first described electrogenic bacterium that performs complete oxidation of an organic substrate with electron transfer directly to the electrode in microbial fuel cell (MFC). This bacterium is very promising for MFC development because of inexpensive cultivation medium, high survival rate and selective resistance to various heavy metal ions. The size of D. acetoxidans IMV B-7384 cells is comparatively small (0.4-0.8×1-2 μm) that is highly beneficial while application of porous anode material because of complete bacterial cover of an electrode area with further significant improvement of the effectiveness of its usage. The interconnection between functioning of reductive stage of tricarboxylic acid (TCA) cycle under anaerobic conditions, and MFC performance was established. Malic, pyruvic, fumaric and succinic acids in concentration 42 mM were separately added into the anode chamber of MFC as the redox agents. Application of malic acid caused the most stabile and the highest power generation in comparison with other investigated organic acids. Its maximum equaled 10.07±0.17mW/m2 on 136 hour of bacterial cultivation. Under addition of pyruvic, succinic and fumaric acids into the anode chamber of MFC the maximal power values equaled 5.80±0.25 mW/m2; 3.2±0.11 mW/m2, and 2.14±0.19 mW/m2 respectively on 40, 56 and 32 hour of bacterial cultivation. Hence the malic acid conversion via reductive stage of TCA cycle is shown to be the most efficient process in terms of electricity generation by D. acetoxidans IMV B-7384 in MFC under anaerobic conditions.

  4. US Activities in Making Life Cycle Inventory Data More Available to Users

    EPA Science Inventory

    The demand for LCA studies continues to grow, although, the lack of reliable, transparent Life Cycle Inventory (LCI) data is hampering the wide-spread application of LCA. This paper will present activities related to the development and accessibility of process LCI data in the U...

  5. Geomagnetic activity during 10 - 11 solar cycles that has been observed by old Russian observatories.

    NASA Astrophysics Data System (ADS)

    Seredyn, Tomasz; Wysokinski, Arkadiusz; Kobylinski, Zbigniew; Bialy, Jerzy

    2016-07-01

    A good knowledge of solar-terrestrial relations during past solar activity cycles could give the appropriate tools for a correct space weather forecast. The paper focuses on the analysis of the historical collections of the ground based magnetic observations and their operational indices from the period of two sunspot solar cycles 10 - 11, period 1856 - 1878 (Bartels rotations 324 - 635). We use hourly observations of H and D geomagnetic field components registered at Russian stations: St. Petersburg - Pavlovsk, Barnaul, Ekaterinburg, Nertshinsk, Sitka, and compare them to the data obtained from the Helsinki observatory. We compare directly these records and also calculated from the data of the every above mentioned station IHV indices introduced by Svalgaard (2003), which have been used for further comparisons in epochs of assumed different polarity of the heliospheric magnetic field. We used also local index C9 derived by Zosimovich (1981) from St. Petersburg - Pavlovsk data. Solar activity is represented by sunspot numbers. The correlative and continuous wavelet analyses are applied for estimation of the correctness of records from different magnetic stations. We have specially regard to magnetic storms in the investigated period and the special Carrington event of 1-2 Sep 1859. Generally studied magnetic time series correctly show variability of the geomagnetic activity. Geomagnetic activity presents some delay in relation to solar one as it is seen especially during descending and minimum phase of the even 11-year cycle. This pattern looks similarly in the case of 16 - 17 solar cycles.

  6. The Development of a New Practical Activity: Using Microorganisms to Model Gas Cycling

    ERIC Educational Resources Information Center

    Redfern, James; Burdass, Dariel; Verran, Joanna

    2014-01-01

    For many in the school science classroom, the term "microbiology" has become synonymous with "bacteriology". By overlooking other microbes, teachers may miss out on powerful practical tools. This article describes the development of an activity that uses algae and yeast to demonstrate gas cycling, and presents full instructions…

  7. Conformational Itinerary of Pseudomonas aeruginosa 1,6-Anhydro-N-acetylmuramic Acid Kinase during Its Catalytic Cycle*

    PubMed Central

    Bacik, John-Paul; Tavassoli, Marjan; Patel, Trushar R.; McKenna, Sean A.; Vocadlo, David J.; Khajehpour, Mazdak; Mark, Brian L.

    2014-01-01

    Anhydro-sugar kinases are unique from other sugar kinases in that they must cleave the 1,6-anhydro ring of their sugar substrate to phosphorylate it using ATP. Here we show that the peptidoglycan recycling enzyme 1,6-anhydro-N-acetylmuramic acid kinase (AnmK) from Pseudomonas aeruginosa undergoes large conformational changes during its catalytic cycle, with its two domains rotating apart by up to 32° around two hinge regions to expose an active site cleft into which the substrates 1,6-anhydroMurNAc and ATP can bind. X-ray structures of the open state bound to a nonhydrolyzable ATP analog (AMPPCP) and 1,6-anhydroMurNAc provide detailed insight into a ternary complex that forms preceding an operative Michaelis complex. Structural analysis of the hinge regions demonstrates a role for nucleotide binding and possible cross-talk between the bound ligands to modulate the opening and closing of AnmK. Although AnmK was found to exhibit similar binding affinities for ATP, ADP, and AMPPCP according to fluorescence spectroscopy, small angle x-ray scattering analyses revealed that AnmK adopts an open conformation in solution in the absence of ligand and that it remains in this open state after binding AMPPCP, as we had observed for our crystal structure of this complex. In contrast, the enzyme favored a closed conformation when bound to ADP in solution, consistent with a previous crystal structure of this complex. Together, our findings show that the open conformation of AnmK facilitates binding of both the sugar and nucleotide substrates and that large structural rearrangements must occur upon closure of the enzyme to correctly align the substrates and residues of the enzyme for catalysis. PMID:24362022

  8. Enoyl-acyl carrier protein reductase (fabI) plays a determinant role in completing cycles of fatty acid elongation in Escherichia coli.

    PubMed

    Heath, R J; Rock, C O

    1995-11-01

    The role of enoyl-acyl carrier protein (ACP) reductase (E.C. 1.3.1.9), the product of the fabI gene, was investigated in the type II, dissociated, fatty acid synthase system of Escherichia coli. All of the proteins required to catalyze one cycle of fatty acid synthesis from acetyl-CoA plus malonyl-CoA to butyryl-ACP in vitro were purified. These proteins were malonyl-CoA:ACP transacylase (fabD), beta-ketoacyl-ACP synthase III (fabH), beta-ketoacyl-ACP reductase (fabG), beta-hydroxydecanoyl-ACP dehydrase (fabA), and enoyl-ACP reductase (fabI). Unlike the other enzymes in the cycle, FabA did not efficiently convert its substrate beta-hydroxybutyryl-ACP to crotonyl-ACP, but rather the equilibrium favored formation of beta-hydroxybutyryl-ACP over crotonyl-ACP by a ratio of 9:1. The amount of butyryl-ACP formed depended on the amount of FabI protein added to the assay. Extracts from fabI(Ts) mutants accumulated beta-hydroxybutyryl-ACP, and the addition of FabI protein to the fabI(Ts) extract restored both butyryl-ACP and long-chain acyl-ACP synthesis. FabI was verified to be the only enoyl-ACP reductase required for the synthesis of fatty acids by demonstrating that purified FabI was required for the elongation of both long-chain saturated and unsaturated fatty acids. These results were corroborated by analysis of the intracellular ACP pool composition in fabI(Ts) mutants that showed beta-hydroxybutyryl-ACP and crotonyl-ACP accumulated at the nonpermissive temperature in the same ratio found in the fabI(Ts) extracts and in the in vitro reconstruction experiments that lacked FabI. We conclude that FabI is the only enoyl-ACP reductase involved in fatty acid synthesis in E. coli and that the activity of this enzyme plays a determinant role in completing cycles of fatty acid biosynthesis.

  9. Solar activity cycle and the incidence of foetal chromosome abnormalities detected at prenatal diagnosis

    NASA Astrophysics Data System (ADS)

    Halpern, Gabrielle J.; Stoupel, Eliahu G.; Barkai, Gad; Chaki, Rina; Legum, Cyril; Fejgin, Moshe D.; Shohat, Mordechai

    1995-06-01

    We studied 2001 foetuses during the period of minimal solar activity of solar cycle 21 and 2265 foetuses during the period of maximal solar activity of solar cycle 22, in all women aged 37 years and over who underwent free prenatal diagnosis in four hospitals in the greater Tel Aviv area. There were no significant differences in the total incidence of chromosomal abnormalities or of trisomy between the two periods (2.15% and 1.8% versus 2.34% and 2.12%, respectively). However, the trend of excessive incidence of chromosomal abnormalities in the period of maximal solar activity suggests that a prospective study in a large population would be required to rule out any possible effect of extreme solar activity.

  10. Actors of the main activity in large complex centres during the 23 solar cycle maximum

    NASA Astrophysics Data System (ADS)

    Schmieder, B.; Démoulin, P.; Pariat, E.; Török, T.; Molodij, G.; Mandrini, C. H.; Dasso, S.; Chandra, R.; Uddin, W.; Kumar, P.; Manoharan, P. K.; Venkatakrishnan, P.; Srivastava, N.

    2011-06-01

    During the maximum of Solar Cycle 23, large active regions had a long life, spanning several solar rotations, and produced large numbers of X-class flares and CMEs, some of them associated to magnetic clouds (MCs). This is the case for the Halloween active regions in 2003. The most geoeffective MC of the cycle (Dst = -457) had its source during the disk passage of one of these active regions (NOAA 10501) on 18 November 2003. Such an activity was presumably due to continuous emerging magnetic flux that was observed during this passage. Moreover, the region exhibited a complex topology with multiple domains of different magnetic helicities. The complexity was observed to reach such unprecedented levels that a detailed multi-wavelength analysis is necessary to precisely identify the solar sources of CMEs and MCs. Magnetic clouds are identified using in situ measurements and interplanetary scintillation (IPS) data. Results from these two different sets of data are also compared.

  11. Lewis acid promoted titanium alkylidene formation: off-cycle intermediates relevant to olefin trimerization catalysis.

    PubMed

    Sattler, Aaron; VanderVelde, David G; Labinger, Jay A; Bercaw, John E

    2014-07-30

    Two new precatalysts for ethylene and α-olefin trimerization, (FI)Ti(CH2SiMe3)2Me and (FI)Ti(CH2CMe3)2Me (FI = phenoxy-imine), have been synthesized and structurally characterized by X-ray diffraction. (FI)Ti(CH2SiMe3)2Me can be activated with 1 equiv of B(C6F5)3 at room temperature to give the solvent-separated ion pair [(FI)Ti(CH2SiMe3)2][MeB(C6F5)3], which catalytically trimerizes ethylene or 1-pentene to produce 1-hexene or C15 olefins, respectively. The neopentyl analogue (FI)Ti(CH2CMe3)2Me is unstable toward activation with B(C6F5)3 at room temperature, giving no discernible diamagnetic titanium complexes, but at -30 °C the following can be observed by NMR spectroscopy: (i) formation of the bis-neopentyl cation [(FI)Ti(CH2CMe3)2](+), (ii) α-elimination of neopentane to give the neopentylidene complex [(FI)Ti(═CHCMe3)](+), and (iii) subsequent conversion to the imido-olefin complex [(MeOAr2N═)Ti(OArHC═CHCMe3)](+) via an intramolecular metathesis reaction with the imine fragment of the (FI) ligand. If the reaction is carried out at low temperature in the presence of ethylene, catalytic production of 1-hexene is observed, in addition to the titanacyclobutane complex [(FI)Ti(CH(CMe3)CH2CH2)](+), resulting from addition of ethylene to the neopentylidene [(FI)Ti(═CHCMe3)](+). None of the complexes observed spectroscopically subsequent to [(FI)Ti(CH2CMe3)2](+) is an intermediate or precursor for ethylene trimerization, but notwithstanding these off-cycle pathways, [(FI)Ti(CH2CMe3)2](+) is a precatalyst that undergoes rapid initiation to generate a catalyst for trimerizing ethylene or 1-pentene.

  12. Procyclic Trypanosoma brucei do not use Krebs cycle activity for energy generation.

    PubMed

    van Weelden, Susanne W H; Fast, Beate; Vogt, Achim; van der Meer, Pieter; Saas, Joachim; van Hellemond, Jaap J; Tielens, Aloysius G M; Boshart, Michael

    2003-04-11

    The importance of a functional Krebs cycle for energy generation in the procyclic stage of Trypanosoma brucei was investigated under physiological conditions during logarithmic phase growth of a pleomorphic parasite strain. Wild type procyclic cells and mutants with targeted deletion of the gene coding for aconitase were derived by synchronous in vitro differentiation from wild type and mutant (Delta aco::NEO/Delta aco::HYG) bloodstream stage parasites, respectively, where aconitase is not expressed and is dispensable. No differences in intracellular levels of glycolytic and Krebs cycle intermediates were found in procyclic wild type and mutant cells, except for citrate that accumulated up to 90-fold in the mutants, confirming the absence of aconitase activity. Surprisingly, deletion of aconitase did not change differentiation nor the growth rate or the intracellular ATP/ADP ratio in those cells. Metabolic studies using radioactively labeled substrates and NMR analysis demonstrated that glucose and proline were not degraded via the Krebs cycle to CO(2). Instead, glucose was degraded to acetate, succinate, and alanine, whereas proline was degraded to succinate. Importantly, there was absolutely no difference in the metabolic products released by wild type and aconitase knockout parasites, and both were for survival strictly dependent on respiration via the mitochondrial electron transport chain. Hence, although the Krebs cycle enzymes are present, procyclic T. brucei do not use Krebs cycle activity for energy generation, but the mitochondrial respiratory chain is essential for survival and growth. We therefore propose a revised model of the energy metabolism of procyclic T. brucei.

  13. Cycling induced by electrical stimulation improves muscle activation and symmetry during pedaling in hemiparetic patients.

    PubMed

    Ambrosini, Emilia; Ferrante, Simona; Ferrigno, Giancarlo; Molteni, Franco; Pedrocchi, Alessandra

    2012-05-01

    A randomized controlled trial, involving 35 post-acute hemiparetic patients, demonstrated that a four-week treatment of cycling induced by functional electrical stimulation (FES-cycling) promotes motor recovery. Analyzing additional data acquired during that study, the present work investigated whether these improvements were associated to changes in muscle strength and motor coordination. Participants were randomized to receive FES-cycling or placebo FES-cycling. Clinical outcome measures were: the Motricity Index (MI), the gait speed, the electromyography activation of the rectus femoris and biceps femoris, and the mechanical work produced by each leg during voluntary pedaling. To provide a comparison with normal values, healthy adults also carried out the pedaling test. Patients were evaluated before, after training, and at follow-up visits. A significant treatment effect in favor of FES-treated patients was found in terms of MI scores and unbalance in mechanical works, while differences in gait speed were not significant (ANCOVA). Significant improvements in the activation of the paretic muscles were highlighted in the FES group, while no significant change was found in the placebo group (Friedman test). Our findings suggested that improvements in motor functions induced by FES-cycling training were associated with a more symmetrical involvement of the two legs and an improved motor coordination. PMID:22514205

  14. Microbial activities and phosphorus cycling: An application of oxygen isotope ratios in phosphate

    NASA Astrophysics Data System (ADS)

    Stout, Lisa M.; Joshi, Sunendra R.; Kana, Todd M.; Jaisi, Deb P.

    2014-08-01

    Microorganisms carry out biochemical transformations of nutrients that make up their cells. Therefore, understanding how these nutrients are transformed or cycled in natural environments requires knowledge of microbial activity. Commonly used indicators for microbial activity typically include determining microbial respiration by O2/CO2 measurements, cell counts, and measurement of enzyme activities. However, coupled studies on nutrient cycling and microbial activity are not given enough emphasis. Here we apply phosphate oxygen isotope ratios (δ18OP) as a tool for measurement of microbial activity and compare the rate of isotope exchange with methods of measuring microbial activities that are more commonly applied in environmental studies including respiration, dehydrogenase activity, alkaline phosphatase activity, and cell counts. Our results show that different bacteria may have different strategies for P uptake, storage and release, their respiration and consequently expression of DHA and APase activities, but in general the trend of their enzyme activities are comparable. Phosphate δ18OP values correlated well with these other parameters used to measure microbial activity with the strongest linear relationships between δ18OP and CO2 evolution (r = -0.99). Even though the rate of isotope exchange for each microorganism used in this study is different, the rate per unit CO2 respiration showed one general trend, where δ18OP values move towards equilibrium while CO2 is generated. While this suggests that P cycling among microorganisms used in this study can be generalized, further research is needed to determine whether the microorganism-specific isotope exchange trend may occur in natural environments. In summary, phosphate oxygen isotope measurements may offer an alternative for use as a tracer to measure microbial activity in soils, sediments, and many other natural environments.

  15. 10-oxo-12(Z)-octadecenoic acid, a linoleic acid metabolite produced by gut lactic acid bacteria, potently activates PPARγ and stimulates adipogenesis

    SciTech Connect

    Goto, Tsuyoshi; Kim, Young-Il; Furuzono, Tomoya; Takahashi, Nobuyuki; Yamakuni, Kanae; Yang, Ha-Eun; Li, Yongjia; Ohue, Ryuji; Nomura, Wataru; Sugawara, Tatsuya; Yu, Rina; Kitamura, Nahoko; and others

    2015-04-17

    Our previous study has shown that gut lactic acid bacteria generate various kinds of fatty acids from polyunsaturated fatty acids such as linoleic acid (LA). In this study, we investigated the effects of LA and LA-derived fatty acids on the activation of peroxisome proliferator-activated receptors (PPARs) which regulate whole-body energy metabolism. None of the fatty acids activated PPARδ, whereas almost all activated PPARα in luciferase assays. Two fatty acids potently activated PPARγ, a master regulator of adipocyte differentiation, with 10-oxo-12(Z)-octadecenoic acid (KetoA) having the most potency. In 3T3-L1 cells, KetoA induced adipocyte differentiation via the activation of PPARγ, and increased adiponectin production and insulin-stimulated glucose uptake. These findings suggest that fatty acids, including KetoA, generated in gut by lactic acid bacteria may be involved in the regulation of host energy metabolism. - Highlights: • Most LA-derived fatty acids from gut lactic acid bacteria potently activated PPARα. • Among tested fatty acids, KetoA and KetoC significantly activated PPARγ. • KetoA induced adipocyte differentiation via the activation of PPARγ. • KetoA enhanced adiponectin production and glucose uptake during adipogenesis.

  16. Inhibition of bacterial activity in acid mine drainage

    NASA Astrophysics Data System (ADS)

    Singh, Gurdeep; Bhatnagar, Miss Mridula

    1988-12-01

    Acid mine drainage water give rise to rapid growth and activity of an iron- and sulphur- oxidizing bacterium Thiobacillus ferrooxidians which greatly accelerate acid producing reactions by oxidation of pyrite material associated with coal and adjoining strata. The role of this bacterium in production of acid mine drainage is described. This study presents the data which demonstrate the inhibitory effect of certain organic acids, sodium benzoate, sodium lauryl sulphate, quarternary ammonium compounds on the growth of the acidophilic aerobic autotroph Thiobacillus ferrooxidians. In each experiment, 10 milli-litres of laboratory developed culture of Thiobacillus ferrooxidians was added to 250 milli-litres Erlenmeyer flask containing 90 milli-litres of 9-k media supplemented with FeSO4 7H2O and organic compounds at various concentrations. Control experiments were also carried out. The treated and untreated (control) samples analysed at various time intervals for Ferrous Iron and pH levels. Results from this investigation showed that some organic acids, sodium benzoate, sodium lauryl sulphate and quarternary ammonium compounds at low concentration (10-2 M, 10-50 ppm concentration levels) are effective bactericides and able to inhibit and reduce the Ferrous Iron oxidation and acidity formation by inhibiting the growth of Thiobacillus ferrooxidians is also discussed and presented

  17. Monitoring Kinase and Phosphatase Activities Through the Cell Cycle by Ratiometric FRET

    PubMed Central

    Hukasova, Elvira; Silva Cascales, Helena; Kumar, Shravan R.; Lindqvist, Arne

    2012-01-01

    Förster resonance energy transfer (FRET)-based reporters1 allow the assessment of endogenous kinase and phosphatase activities in living cells. Such probes typically consist of variants of CFP and YFP, intervened by a phosphorylatable sequence and a phospho-binding domain. Upon phosphorylation, the probe changes conformation, which results in a change of the distance or orientation between CFP and YFP, leading to a change in FRET efficiency (Fig 1). Several probes have been published during the last decade, monitoring the activity balance of multiple kinases and phosphatases, including reporters of PKA2, PKB3, PKC4, PKD5, ERK6, JNK7, Cdk18, Aurora B9 and Plk19. Given the modular design, additional probes are likely to emerge in the near future10. Progression through the cell cycle is affected by stress signaling pathways 11. Notably, the cell cycle is regulated differently during unperturbed growth compared to when cells are recovering from stress12.Time-lapse imaging of cells through the cell cycle therefore requires particular caution. This becomes a problem particularly when employing ratiometric imaging, since two images with a high signal to noise ratio are required to correctly interpret the results. Ratiometric FRET imaging of cell cycle dependent changes in kinase and phosphatase activities has predominately been restricted to sub-sections of the cell cycle8,9,13,14. Here, we discuss a method to monitor FRET-based probes using ratiometric imaging throughout the human cell cycle. The method relies on equipment that is available to many researchers in life sciences and does not require expert knowledge of microscopy or image processing. PMID:22314640

  18. gamma-Linolenic acid blocks cell cycle progression by regulating phosphorylation of p27kip1 and p57kip2 and their interactions with other cycle regulators in cancer cells.

    PubMed

    Jiang, W G; Bryce, R P; Horrobin, D F; Mansel, R E

    1998-09-01

    gamma-Linolenic acid (gamma-LA), a n-6 essential fatty acid, has been previously shown to affect cell cycle and growth of cancer cells. This study examined the effects of gamma-LA on the cell cycle and cycle regulators in human colon cancer HT115 and breast cancer MCF7 cells. Brief treatment of cancer cells (<2 h) with gamma-LA resulted in a decrease in the phosphorylation of both cell cycle inhibitors, p27kip1 and p57kip2 as shown by immunoprecipitation and Western blotting. Protein levels of both inhibitors were increased following a prolonged culture of cells with the fatty acid. A co-precipitation study showed that in cells treated with gamma-LA there was an increase in the binding of these inhibitors with CDK4, CDC2, and cyclin E. Flow cytometry study indicated an inhibition of cell cycle progression by gamma-LA (G0/G1 -45.4%, S - 34.6%, G2+M - 20.0% in control, and 70.5%, 21.0%, and 8.5%, respectively, in gamma-LA treated cells). It is concluded that gamma-linolenic acid inhibits cell cycle progression in the cancer cell lines investigated, via its regulation of the phosphorylation and subsequent degradation of p27kip1 and p57kip2 and their interactions with other cycle regulators. PMID:9683802

  19. Male prairie voles display cardiovascular dipping associated with an ultradian activity cycle.

    PubMed

    Lewis, Robert; Curtis, J Thomas

    2016-03-15

    Mammals typically display alternating active and resting phases and, in most species, these rhythms follow a circadian pattern. The active and resting phases often are accompanied by corresponding physiological changes. In humans, blood pressure decreases during the resting phase of the activity cycle, and the magnitude of that "nocturnal dipping" has been used to stratify patients according to the risk for cardiovascular disease. However, in contrast to most mammals, prairie voles (Microtus ochrogaster) have periods of activity and rest that follow an ultradian rhythm with period lengths significantly <24h. While rhythmic changes in blood pressure across a circadian activity cycle have been well-documented, blood pressure patterns in species that display ultradian rhythms in activity are less well-studied. In the current study, we implanted pressure-sensitive radiotelemetry devices in male prairie voles and recorded activity, mean arterial pressure (MAP), and heart rate (HR) continuously for 3days. Visualization of the ultradian rhythms was enhanced using a 1h running average to filter the dataset. Positive correlations were found between activity and MAP and between activity and HR. During the inactive period of the ultradian cycle, blood pressure decreased by about 15%, which parallels the nocturnal dipping pattern seen in healthy humans. Further, the duration of inactivity did not affect any of the cardiovascular measures, so the differences in blood pressure values between the active and inactive periods are likely driven by ultradian oscillations in hormones and autonomic function. Finally, specific behavioral patterns also were examined. Both the instrumented animal and his non-instrumented cagemate appeared to show synchronized activity patterns, with both animals displaying sleep-like behavior for more than 90% of the inactive period. We propose that the prairie vole ultradian rhythm in blood pressure is an analogue for circadian blood pressure variability

  20. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    PubMed

    Li, Zhining; Yuan, Penghui; Xing, Meng; He, Zhumei; Dong, Chuanfu; Cao, Yongchang; Liu, Qiuyun

    2013-04-01

    Antimicrobial peptides are small molecules that play a crucial role in innate immunity in multi-cellular organisms, and usually expressed and secreted constantly at basal levels to prevent infection, but local production can be augmented upon an infection. The clock is ticking as rising antibiotic abuse has led to the emergence of many drug resistance bacteria. Due to their broad spectrum antibiotic and antifungal activities as well as anti-viral and anti-tumor activities, efforts are being made to develop antimicrobial peptides into future microbial agents. This article describes some of the recent patents on antimicrobial peptides with fatty acid conjugation. Potency and selectivity of antimicrobial peptide can be modulated with fatty acid tails of variable length. Interaction between membranes and antimicrobial peptides was affected by fatty acid conjugation. At concentrations above the critical miscelle concentration (CMC), propensity of solution selfassembly hampered binding of the peptide to cell membranes. Overall, fatty acid conjugation has enhanced the activities of antimicrobial peptides, and occasionally it rendered inactive antimicrobial peptides to be bioactive. Antimicrobial peptides can not only be used as medicine but also as food additives.

  1. Activity of earthworm in Latosol under simulated acid rain stress.

    PubMed

    Zhang, Jia-En; Yu, Jiayu; Ouyang, Ying

    2015-01-01

    Acid rain is still an issue of environmental concerns. This study investigated the impacts of simulated acid rain (SAR) upon earthworm activity from the Latosol (acidic red soil). Laboratory experiment was performed by leaching the soil columns grown with earthworms (Eisenia fetida) at the SAR pH levels ranged from 2.0 to 6.5 over a 34-day period. Results showed that earthworms tended to escape from the soil and eventually died for the SAR at pH = 2.0 as a result of acid toxicity. The catalase activity in the earthworms decreased with the SAR pH levels, whereas the superoxide dismutases activity in the earthworms showed a fluctuate pattern: decreasing from pH 6.5 to 5.0 and increasing from pH 5.0 to 4.0. Results implied that the growth of earthworms was retarded at the SAR pH ≤ 3.0. PMID:25351717

  2. Study of Distribution and Asymmetry of Solar Active Prominences during Solar Cycle 23

    NASA Astrophysics Data System (ADS)

    Joshi, Navin Chandra; Bankoti, Neeraj Singh; Pande, Seema; Pande, Bimal; Pandey, Kavita

    2009-12-01

    In this article we present the results of a study of the spatial distribution and asymmetry of solar active prominences (SAP) for the period 1996 through 2007 (solar cycle 23). For more meaningful statistical analysis we analyzed the distribution and asymmetry of SAP in two subdivisions viz. Group1 (ADF, APR, DSF, CRN, CAP) and Group2 (AFS, ASR, BSD, BSL, DSD, SPY, LPS). The North - South (N - S) latitudinal distribution shows that the SAP events are most prolific in the 21° to 30° slice in the Northern and Southern Hemispheres; the East - West (E - W) longitudinal distribution study shows that the SAP events are most prolific (best observable) in the 81° to 90° slice in the Eastern and Western Hemispheres. It was found that the SAP activity during this cycle is low compared to previous solar cycles. The present study indicates that during the rising phase of the cycle the number of SAP events are roughly equal in the Northern and Southern Hemispheres. However, activity in the Southern Hemisphere has been dominant since 1999. Our statistical study shows that the N - S asymmetry is more significant then the E - W asymmetry.

  3. Stellar activity cycles from long-term data by robotic telescopes

    NASA Astrophysics Data System (ADS)

    Oláh, K.

    2014-03-01

    All results about stellar activity cycles stem from decades-long systematic observations that were done by small telescopes. Without these equipments we would not know much, if anything, about stellar activity cycles, like those we see and observe easily on the nearest star, the Sun. In the early 80's of the last century systematic photometric monitoring of active stars began with automated photometric telescopes (APTs), some of which continue the observations to date. The Vienna-Potsdam APT now works for about two decades (Strassmeier et al. 1997), similarly to the 4-College Consortium APT (Dukes et al. 1995), while the Catania APT (Rodono et al. 2001) was closed down a few years ago. These small tools with the same setups for decades do not cost much and are relatively cheap to maintain. The longest continuous photometric datasets of a few objects from APTs span now over 30 years, which, together with earlier, manually-obtained data allow to study those activity cycles of stars which are in the order of 10 years or shorter: to be sure in the timescale of a cycle it should be observed repeatedly at least 2-3 times. The spectroscopic automated telescope STELLA (Strassmeier et al. 2004), built in the first decade of this century, measured already a few dozens of radial velocity curves for long-period binary stars and measured their activity levels (Strassmeier et al. 2012); these results can be gathered only by robotic telescopes. Only with STELLA it is possible to study the decades-long behavior of starspots on active giants with long rotational periods via Doppler Imaging. As the databases were growing it became clear that stars, just as the Sun, had multiple cycles. It was also found that stellar cycles showed systematic changes and that the cycle lengths correlated with the rotational periods of the stars. Extensive summaries of stellar activity cycles are found in Baliunas et al. (1995) using the Mt. Wilson Ca-index survey, and Oláh et al. (2009) based on

  4. p38α Activates Purine Metabolism to Initiate Hematopoietic Stem/Progenitor Cell Cycling in Response to Stress.

    PubMed

    Karigane, Daiki; Kobayashi, Hiroshi; Morikawa, Takayuki; Ootomo, Yukako; Sakai, Mashito; Nagamatsu, Go; Kubota, Yoshiaki; Goda, Nobuhito; Matsumoto, Michihiro; Nishimura, Emi K; Soga, Tomoyoshi; Otsu, Kinya; Suematsu, Makoto; Okamoto, Shinichiro; Suda, Toshio; Takubo, Keiyo

    2016-08-01

    Hematopoietic stem cells (HSCs) maintain quiescence by activating specific metabolic pathways, including glycolysis. We do not yet have a clear understanding of how this metabolic activity changes during stress hematopoiesis, such as bone marrow transplantation. Here, we report a critical role for the p38MAPK family isoform p38α in initiating hematopoietic stem and progenitor cell (HSPC) proliferation during stress hematopoiesis in mice. We found that p38MAPK is immediately phosphorylated in HSPCs after a hematological stress, preceding increased HSPC cycling. Conditional deletion of p38α led to defective recovery from hematological stress and a delay in initiation of HSPC proliferation. Mechanistically, p38α signaling increases expression of inosine-5'-monophosphate dehydrogenase 2 in HSPCs, leading to altered levels of amino acids and purine-related metabolites and changes in cell-cycle progression in vitro and in vivo. Our studies have therefore uncovered a p38α-mediated pathway that alters HSPC metabolism to respond to stress and promote recovery. PMID:27345838

  5. Trichloroacetic acid cycling in Sitka spruce saplings and effects on sapling health following long term exposure.

    PubMed

    Dickey, C A; Heal, K V; Stidson, R T; Koren, R; Schröder, P; Cape, J N; Heal, M R

    2004-07-01

    Trichloroacetic acid (TCA, CCl(3)COOH) has been associated with forest damage but the source of TCA to trees is poorly characterised. To investigate the routes and effects of TCA uptake in conifers, 120 Sitka spruce (Picea sitchensis (Bong.) Carr) saplings were exposed to control, 10 or 100 microg l(-1) solutions of TCA applied twice weekly to foliage only or soil only over two consecutive 5-month growing seasons. At the end of each growing season similar elevated TCA concentrations (approximate range 200-300 ng g(-1) dwt) were detected in both foliage and soil-dosed saplings exposed to 100 microg l(-1) TCA solutions showing that TCA uptake can occur from both exposure routes. Higher TCA concentrations in branchwood of foliage-dosed saplings suggest that atmospheric TCA in solution is taken up indirectly into conifer needles via branch and stemwood. TCA concentrations in needles declined slowly by only 25-30% over 6 months of winter without dosing. No effect of TCA exposure on sapling growth was measured during the experiment. However at the end of the first growing season needles of saplings exposed to 10 or 100 microg l(-1) foliage-applied TCA showed significantly more visible damage, higher activities of some detoxifying enzymes, lower protein contents and poorer water control than needles of saplings dosed with the same TCA concentrations to the soil. At the end of each growing season the combined TCA storage in needles, stemwood, branchwood and soil of each sapling was <6% of TCA applied. Even with an estimated half-life of tens of days for within-sapling elimination of TCA during the growing season, this indicates that TCA is eliminated rapidly before uptake or accumulates in another compartment. Although TCA stored in sapling needles accounted for only a small proportion of TCA stored in the sapling/soil system it appears to significantly affect some measures of sapling health.

  6. Gluconeogenic carbon flow of tricarboxylic acid cycle intermediates is critical for Mycobacterium tuberculosis to establish and maintain infection

    PubMed Central

    Marrero, Joeli; Rhee, Kyu Y.; Schnappinger, Dirk; Pethe, Kevin; Ehrt, Sabine

    2010-01-01

    Metabolic adaptation to the host niche is a defining feature of the pathogenicity of Mycobacterium tuberculosis (Mtb). In vitro, Mtb is able to grow on a variety of carbon sources, but mounting evidence has implicated fatty acids as the major source of carbon and energy for Mtb during infection. When bacterial metabolism is primarily fueled by fatty acids, biosynthesis of sugars from intermediates of the tricarboxylic acid cycle is essential for growth. The role of gluconeogenesis in the pathogenesis of Mtb however remains unaddressed. Phosphoenolpyruvate carboxykinase (PEPCK) catalyzes the first committed step of gluconeogenesis. We applied genetic analyses and 13C carbon tracing to confirm that PEPCK is essential for growth of Mtb on fatty acids and catalyzes carbon flow from tricarboxylic acid cycle–derived metabolites to gluconeogenic intermediates. We further show that PEPCK is required for growth of Mtb in isolated bone marrow–derived murine macrophages and in mice. Importantly, Mtb lacking PEPCK not only failed to replicate in mouse lungs but also failed to survive, and PEPCK depletion during the chronic phase of infection resulted in mycobacterial clearance. Mtb thus relies on gluconeogenesis throughout the infection. PEPCK depletion also attenuated Mtb in IFNγ-deficient mice, suggesting that this enzyme represents an attractive target for chemotherapy. PMID:20439709

  7. Deoxycholic acid and selenium metabolite methylselenol exert common and distinct effects on cell cycle, apoptosis, and MAP kinase pathway in HCT116 human colon cancer cells.

    PubMed

    Zeng, Huawei; Botnen, James H; Briske-Anderson, Mary

    2010-01-01

    The cell growth inhibition induced by bile acid deoxycholic acid (DCA) may cause compensatory hyperproliferation of colonic epithelial cells and consequently increase colon cancer risk. On the other hand, there is increasing evidence for the efficacy of certain forms of selenium (Se) as anticancer nutrients. Methylselenol has been hypothesized to be a critical Se metabolite for anticancer activity in vivo. In this study, we demonstrated that both DCA (75-300 micromol/l) and submicromolar methylselenol inhibited colon cancer cell proliferation by up to 64% and 63%, respectively. In addition, DCA and methylselenol each increased colon cancer cell apoptosis rate by up to twofold. Cell cycle analyses revealed that DCA induced an increase in only the G1 fraction with a concomitant drop in G2 and S-phase; in contrast, methylselenol led to an increase in the G1 and G2 fractions with a concomitant drop only in the S-phase. Although both DCA and methylselenol significantly promoted apoptosis and inhibited cell growth, examination of mitogen-activated protein kinase (MAPK) pathway activation showed that DCA, but not methylselenol, induced SAPK/JNK1/2, p38 MAPK, ERK1/2 activation. Thus, our data provide, for the first time, the molecular basis for opposite effects of methylselenol and DCA on colon tumorigenesis.

  8. Metabolomics approach to assessing plasma 13- and 9-hydroxy-octadecadienoic acid and linoleic acid metabolite responses to 75-km cycling.

    PubMed

    Nieman, David C; Shanely, R Andrew; Luo, Beibei; Meaney, Mary Pat; Dew, Dustin A; Pappan, Kirk L

    2014-07-01

    Bioactive oxidized linoleic acid metabolites (OXLAMs) include 13- and 9-hydroxy-octadecadienoic acid (13-HODE + 9-HODE) and have been linked to oxidative stress, inflammation, and numerous pathological and physiological states. The purpose of this study was to measure changes in plasma 13-HODE + 9-HODE following a 75-km cycling bout and identify potential linkages to linoleate metabolism and established biomarkers of oxidative stress (F2-isoprostanes) and inflammation (cytokines) using a metabolomics approach. Trained male cyclists (N = 19, age 38.0 ± 1.6 yr, wattsmax 304 ± 10.5) engaged in a 75-km cycling time trial on their own bicycles using electromagnetically braked cycling ergometers (2.71 ± 0.07 h). Blood samples were collected preexercise, immediately post-, 1.5 h post-, and 21 h postexercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, granulocyte colony-stimulating factor), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). 13-HODE + 9-HODE increased 3.1-fold and 1.7-fold immediately post- and 1.5 h postexercise (both P < 0.001) and returned to preexercise levels by 21-h postexercise. Post-75-km cycling plasma levels of 13-HODE + 9-HODE were not significantly correlated with increases in plasma cytokines but were positively correlated with postexercise F2-isoprostanes (r = 0.75, P < 0.001), linoleate (r = 0.54, P = 0.016), arachidate (r = 0.77, P < 0.001), 12,13-dihydroxy-9Z-octadecenoate (12,13-DiHOME) (r = 0.60, P = 0.006), dihomo-linolenate (r = 0.57, P = 0.011), and adrenate (r = 0.56, P = 0.013). These findings indicate that prolonged and intensive exercise caused a transient, 3.1-fold increase in the stable linoleic acid oxidation product 13-HODE + 9-HODE and was related to increases in F2-isoprostanes, linoleate, and fatty acids in the linoleate

  9. Solar magnetic activity cycles, coronal potential field models and eruption rates

    NASA Astrophysics Data System (ADS)

    Petrie, Gordon

    2013-07-01

    We study the evolution of the observed photospheric magnetic field and the modeled global coronal magnetic field during the past 3 1/2 solar activity cycles observed since the mid-1970s. We use synoptic magnetograms and extrapolated potential-field models based on longitudinal full-disk photospheric magnetograms from the NSO's three magnetographs at Kitt Peak, the Synoptic Optical Long-term Investigations of the Sun (SOLIS) vector spectro-magnetograph (VSM), the spectro-magnetograph and the 512-channel magnetograph instruments, and from the U. Stanford's Wilcox Solar Observatory. The associated multipole field components are used to study the dominant length scales and symmetries of the coronal field. Of the axisymmetric multipoles, only the dipole and octupole follow the poles whereas the higher orders follow the activity cycle. All non-axisymmetric multipole strengths are well correlated with the activity cycle. The axial dipole and octupole are the largest contributors to the global field except while the polar fields are reversing. This influence of the polar fields extends to modulating eruption rates. According to the Computer Aided CME Tracking (CACTus), Solar Eruptive Event Detection System (SEEDS), and Nobeyama radioheliograph prominence eruption catalogs, the rate of solar eruptions is found to be systematically higher for active years between 2003-2012 than for those between 1997-2002. This behavior appears to be connected with the weakness of the late-cycle 23 polar fields as suggested by Luhmann. We see evidence that the process of cycle 24 field reversal is well advanced at both poles.

  10. A potential plant-derived antifungal acetylenic acid mediates its activity by interfering with fatty acid homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    6-Nonadecynoic acid (6-NDA), a plant-derived acetylenic acid, exhibits strong inhibitory activity against the human fungal pathogens Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes. In the present study, transcriptional profiling coupled with mutant and biochemical analyses...

  11. CoRoT reveals a magnetic activity cycle in a Sun-like star.

    PubMed

    García, Rafael A; Mathur, Savita; Salabert, David; Ballot, Jérôme; Régulo, Clara; Metcalfe, Travis S; Baglin, Annie

    2010-08-27

    The 11-year activity cycle of the Sun is a consequence of a dynamo process occurring beneath its surface. We analyzed photometric data obtained by the CoRoT space mission, showing solarlike oscillations in the star HD49933, for signatures of stellar magnetic activity. Asteroseismic measurements of global changes in the oscillation frequencies and mode amplitudes reveal a modulation of at least 120 days, with the minimum frequency shift corresponding to maximum amplitude as in the Sun. These observations are evidence of a stellar magnetic activity cycle taking place beneath the surface of HD49933 and provide constraints for stellar dynamo models under conditions different from those of the Sun. PMID:20798310

  12. Past and future trends in stellar activity cycle research: beyond Ca II H&K

    NASA Astrophysics Data System (ADS)

    Hall, Jeffrey C.

    2002-06-01

    Olin C. Wilson began stellar activity cycle research in 1966, and work has since proceeded along a number of observational and theoretical lines. Long-term ground-based spectroscopic monitoring of the Ca II H&K activity proxies has demonstrated the existence of varying types of stellar cycles, while complementary photometric studies have revealed luminosity variations both in phase and in antiphase with chromospheric activity. Beginning in the late 1970s, space-based observations greatly affected our understanding of stellar chromospheres, spurring a complementary evolution in interpretation of the ground-based results. Excellent recent reviews of the results of these programs have appeared, so in this paper, I will summarize the results and review them in the broad context of the development of our present state of knowledge, current outstanding questions and pitfalls facing workers in the field today, and the lines of investigation likely to be fruitful in the next decade.

  13. Effects of Space Weather on Biomedical Parameters during the Solar Activity Cycles 23-24.

    PubMed

    Ragul'skaya, M V; Rudenchik, E A; Chibisov, S M; Gromozova, E N

    2015-06-01

    The results of long-term (1998-2012) biomedical monitoring of the biotropic effects of space weather are discussed. A drastic change in statistical distribution parameters in the middle of 2005 was revealed that did not conform to usual sinusoidal distribution of the biomedical data reflecting changes in the number of solar spots over a solar activity cycle. The dynamics of space weather of 2001-2012 is analyzed. The authors hypothesize that the actual change in statistical distributions corresponds to the adaptation reaction of the biosphere to nonstandard geophysical characteristics of the 24th solar activity cycle and the probable long-term decrease in solar activity up to 2067. PMID:26085362

  14. Magnetic activity of red secondaries: clues from the outburst cycle variations of dwarf novae

    NASA Astrophysics Data System (ADS)

    Chinarova, L. L.

    Photometric variations of 6 dwarf novae stars are studied based on the photographic observations from the Odessa, Moscow and Sonneberg plate collections and published visual monitoring data from the AFOEV database (Schweitzer E.: 1993, Bull. AFOEV, 64, 14). The moments of maxima are determined by using the "running parabola" fit (Andronov I.L., 1990, Kinematika Fizika Nebesn. Tel., v.6,,N 6, 87) with automatically determined filter half-width (Andronov I.L., 1997, As.Ap. Suppl., in press). All investigated stars exhibit significant changes not only from cycle-to-cycle, but from season-to-season as well. Secondary decade-scale cycles of smooth variations (Bianchini A., 1990, AJ 99, 1941) and abrupt switchings (Andronov I.L., Shakun L.I., 1990, ASS 169, 237) were interpreted by a solar-type activity of the red dwarf secondary in a binary system and may argue for existence of two different subgroups of the dwarf novae.

  15. Surface flux transport simulations. Inflows towards active regions and the modulation of the solar cycle.

    NASA Astrophysics Data System (ADS)

    Martin-Belda, David; Cameron, Robert

    2016-07-01

    Aims. We investigate the way near-surface converging flows towards active regions affect the build-up of magnetic field at the Sun's polar caps. In the Babcock-Leighton dynamo framework, this modulation of the polar fields could explain the variability of the solar cycle. Methods. We develop a surface flux transport code incorporating a parametrized model of the inflows and run simulations spanning several cycles. We carry out a parameter study to test how the strength and extension of the inflows affect the amplitude of the polar fields. Results. Inflows are seen to play an important role in the build-up of the polar fields, and can act as the non-linearity feedback mechanism required to limit the strength of the solar cycles in the Babcock-Leighton dynamo framework.

  16. PKC theta and p38 MAPK activate the EBV lytic cycle through autophagy induction.

    PubMed

    Gonnella, Roberta; Granato, Marisa; Farina, Antonella; Santarelli, Roberta; Faggioni, Alberto; Cirone, Mara

    2015-07-01

    PKC activation by combining TPA with sodium butyrate (T/B) represents the most effective and widely used strategy to induce the Epstein-Barr virus (EBV) lytic cycle. The results obtained in this study show that novel PKCθ is involved in such process and that it acts through the activation of p38 MAPK and autophagy induction. Autophagy, a mechanism of cellular defense in stressful conditions, is manipulated by EBV to enhance viral replication. Besides promoting the EBV lytic cycle, the activation of p38 and autophagy resulted in a pro-survival effect, as indicated by p38 or ATG5 knocking down experiments. However, this pro-survival role was counteracted by a pro-death activity of PKCθ, due to the dephosphorylation of AKT. In conclusion, this study reports, for the first time, that T/B activates a PKCθ-p38 MAPK axis in EBV infected B cells, that promotes the viral lytic cycle and cell survival and dephosphorylates AKT, balancing cell life and cell death. PMID:25827954

  17. Daytime spikes in dopaminergic activity drive rapid mood-cycling in mice

    PubMed Central

    Sidor, Michelle M.; Spencer, Sade M.; Dzirasa, Kafui; Parekh, Puja K.; Tye, Kay M.; Warden, Melissa R.; Arey, Rachel N.; Enwright, John F; Jacobsen, Jacob PR; Kumar, Sunil; Remillard, Erin M; Caron, Marc G.; Deisseroth, Karl; McClung, Colleen A

    2014-01-01

    Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here we find that mice with a mutation in the circadian Clock gene (ClockΔ19) exhibit rapid mood-cycling, with a profound manic-like phenotype emerging during the day following a period of euthymia at night. Mood cycling coincides with abnormal daytime spikes in ventral tegmental area (VTA) dopaminergic activity, tyrosine hydroxylase (TH) levels, and dopamine synthesis. To determine the significance of daytime increases in VTA dopamine activity to manic behaviors, we developed a novel optogenetic stimulation paradigm that produces a sustained increase in dopamine neuronal activity and find that this induces a manic-like behavioral state. Time-dependent dampening of TH activity during the day reverses manic-related behaviours in ClockΔ19 mice. Finally, we show that CLOCK acts as a negative regulator of TH transcription, revealing a novel molecular mechanism underlying cyclic changes in mood-related behaviour. Taken together, these studies have identified a mechanistic connection between circadian gene disruption and the precipitation of manic episodes in bipolar disorder. PMID:25560763

  18. PKC theta and p38 MAPK activate the EBV lytic cycle through autophagy induction.

    PubMed

    Gonnella, Roberta; Granato, Marisa; Farina, Antonella; Santarelli, Roberta; Faggioni, Alberto; Cirone, Mara

    2015-07-01

    PKC activation by combining TPA with sodium butyrate (T/B) represents the most effective and widely used strategy to induce the Epstein-Barr virus (EBV) lytic cycle. The results obtained in this study show that novel PKCθ is involved in such process and that it acts through the activation of p38 MAPK and autophagy induction. Autophagy, a mechanism of cellular defense in stressful conditions, is manipulated by EBV to enhance viral replication. Besides promoting the EBV lytic cycle, the activation of p38 and autophagy resulted in a pro-survival effect, as indicated by p38 or ATG5 knocking down experiments. However, this pro-survival role was counteracted by a pro-death activity of PKCθ, due to the dephosphorylation of AKT. In conclusion, this study reports, for the first time, that T/B activates a PKCθ-p38 MAPK axis in EBV infected B cells, that promotes the viral lytic cycle and cell survival and dephosphorylates AKT, balancing cell life and cell death.

  19. Photosynthesis in Rhodospirillum rubrum. III. Metabolic Control of Reductive Pentose Phosphate and Tricarboxylic Acid Cycle Enzymes 1

    PubMed Central

    Anderson, Louise; Fuller, R. C.

    1967-01-01

    Enzymes of the reductive pentose phosphate cycle including ribulose-diphosphate carboxylase, ribulose-5-phosphate kinase, ribose-5-phosphate isomerase, aldolase, glyceraldehyde-3-phosphate dehydrogenase and alkaline fructose-1,6-diphos-phatase were shown to be present in autotrophically grown Rhodospirillum rubrum. Enzyme levels were measured in this organism grown photo- and dark heterotrophically as well. Several, but not all, of these enzymes appeared to be under metabolic control, mediated by exogenous carbon and nitrogen compounds. Light had no effect on the presence or levels of any of these enzymes in this photosynthetic bacterium. The enzymes of the tricarboxylic acid cycle and enolase were shown to be present in R. rubrum cultured aerobically, autotrophically, or photoheterotrophically, both in cultures evolving hydrogen and under conditions where hydrogen evolution is not observed. Light had no clearly demonstrable effect on the presence or levels of any of these enzymes. PMID:6042359

  20. Jasmonic acid and salicylic acid activate a common defense system in rice

    PubMed Central

    Tamaoki, Daisuke; Seo, Shigemi; Yamada, Shoko; Kano, Akihito; Miyamoto, Ayumi; Shishido, Hodaka; Miyoshi, Seika; Taniguchi, Shiduku; Akimitsu, Kazuya; Gomi, Kenji

    2013-01-01

    Jasmonic acid (JA) and salicylic acid (SA) play important roles in plant defense systems. JA and SA signaling pathways interact antagonistically in dicotyledonous plants, but, the status of crosstalk between JA and SA signaling is unknown in monocots. Our rice microarray analysis showed that more than half of the genes upregulated by the SA analog BTH are also upregulated by JA, suggesting that a major portion of the SA-upregulated genes are regulated by JA-dependent signaling in rice. A common defense system that is activated by both JA and SA is thus proposed which plays an important role in pathogen defense responses in rice. PMID:23518581

  1. Cell cycle dependent regulation of deoxycytidine kinase, deoxyguanosine kinase, and cytosolic 5'-nucleotidase I activity in MOLT-4 cells.

    PubMed

    Fyrberg, A; Mirzaee, S; Lotfi, K

    2006-01-01

    Activation of nucleoside analogues is dependent on kinases and 5'-nucleotidases and the balance between the activity of these enzymes. The purpose of this study was to analyze deoxycytidine kinase, deoxyguanosine kinase, and 4 different 5'-nucleotidases during cell cycle progression in MOLT-4 cells. The activity of both kinases was cell cycle dependent and increased during proliferation while the activity of cytosolic 5'-nucleotidase I decreased. We could show that the kinase activity was higher than the total nucleotidase activity, which was unchanged or decreased during cell cycle progression. These data may be important in designing modern combination therapy with nucleoside analogues.

  2. A specialized citric acid cycle requiring succinyl-coenzyme A (CoA):acetate CoA-transferase (AarC) confers acetic acid resistance on the acidophile Acetobacter aceti.

    PubMed

    Mullins, Elwood A; Francois, Julie A; Kappock, T Joseph

    2008-07-01

    Microbes tailor macromolecules and metabolism to overcome specific environmental challenges. Acetic acid bacteria perform the aerobic oxidation of ethanol to acetic acid and are generally resistant to high levels of these two membrane-permeable poisons. The citric acid cycle (CAC) is linked to acetic acid resistance in Acetobacter aceti by several observations, among them the oxidation of acetate to CO2 by highly resistant acetic acid bacteria and the previously unexplained role of A. aceti citrate synthase (AarA) in acetic acid resistance at a low pH. Here we assign specific biochemical roles to the other components of the A. aceti strain 1023 aarABC region. AarC is succinyl-coenzyme A (CoA):acetate CoA-transferase, which replaces succinyl-CoA synthetase in a variant CAC. This new bypass appears to reduce metabolic demand for free CoA, reliance upon nucleotide pools, and the likely effect of variable cytoplasmic pH upon CAC flux. The putative aarB gene is reassigned to SixA, a known activator of CAC flux. Carbon overflow pathways are triggered in many bacteria during metabolic limitation, which typically leads to the production and diffusive loss of acetate. Since acetate overflow is not feasible for A. aceti, a CO(2) loss strategy that allows acetic acid removal without substrate-level (de)phosphorylation may instead be employed. All three aar genes, therefore, support flux through a complete but unorthodox CAC that is needed to lower cytoplasmic acetate levels.

  3. SdhE-dependent formation of a functional Acetobacter pasteurianus succinate dehydrogenase in Gluconobacter oxydans--a first step toward a complete tricarboxylic acid cycle.

    PubMed

    Kiefler, Ines; Bringer, Stephanie; Bott, Michael

    2015-11-01

    The obligatory aerobic α-proteobacterium Gluconobacter oxydans 621H possesses an unusual metabolism in which the majority of the carbohydrate substrates are incompletely oxidized in the periplasm and only a small fraction is metabolized in the cytoplasm. The cytoplasmic oxidation capabilities are limited due to an incomplete tricarboxylic acid (TCA) cycle caused by the lack of succinate dehydrogenase (Sdh) and succinyl-CoA synthetase. As a first step to test the consequences of a functional TCA cycle for growth, metabolism, and bioenergetics of G. oxydans, we attempted to establish a heterologous Sdh in this species. Expression of Acetobacter pasteurianus sdhCDAB in G. oxydans did not yield an active succinate dehydrogenase. Co-expression of a putative sdhE gene from A. pasteurianus, which was assumed to encode an assembly factor for covalent attachment of flavin adenine dinucleotide (FAD) to SdhA, stimulated Sdh activity up to 400-fold to 4.0 ± 0.4 U (mg membrane protein)(‒1). The succinate/oxygen reductase activity of membranes was 0.68 ± 0.04 U (mg membrane protein)(‒1), indicating the formation of functional Sdh complex capable of transferring electrons from succinate to ubiquinone. A. pasteurianus SdhE could be functionally replaced by SdhE from the γ-proteobacterium Serratia sp. According to these results, the accessory protein SdhE was necessary and sufficient for heterologous synthesis of an active A. pasteurianus Sdh in G. oxydans. Studies with the Sdh-positive G. oxydans strain provided evidence for a limited functionality of the TCA cycle despite the absence of succinyl-CoA synthetase.

  4. The sleep-wake cycle and motor activity, but not temperature, are disrupted over the light-dark cycle in mice genetically depleted of serotonin

    PubMed Central

    Solarewicz, Julia Z.; Angoa-Perez, Mariana; Kuhn, Donald M.; Mateika, Jason H.

    2016-01-01

    We examined the role that serotonin has in the modulation of sleep and wakefulness across a 12-h:12-h light-dark cycle and determined whether temperature and motor activity are directly responsible for potential disruptions to arousal state. Telemetry transmitters were implanted in 24 wild-type mice (Tph2+/+) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2−/−). After surgery, electroencephalography, core body temperature, and motor activity were recorded for 24 h. Temperature for a given arousal state (quiet and active wake, non-rapid eye movement, and paradoxical sleep) was similar in the Tph2+/+ and Tph2−/− mice across the light-dark cycle. The percentage of time spent in active wakefulness, along with motor activity, was decreased in the Tph2+/+ compared with the Tph2−/− mice at the start and end of the dark cycle. This difference persisted into the light cycle. In contrast, the time spent in a given arousal state was similar at the remaining time points. Despite this similarity, periods of non-rapid-eye-movement sleep and wakefulness were less consolidated in the Tph2+/+ compared with the Tph2−/− mice throughout the light-dark cycle. We conclude that the depletion of serotonin does not disrupt the diurnal variation in the sleep-wake cycle, motor activity, and temperature. However, serotonin may suppress photic and nonphotic inputs that manifest at light-dark transitions and serve to shorten the ultraradian duration of wakefulness and non-rapid-eye-movement sleep. Finally, alterations in the sleep-wake cycle following depletion of serotonin are unrelated to disruptions in the modulation of temperature. PMID:25394829

  5. The sleep-wake cycle and motor activity, but not temperature, are disrupted over the light-dark cycle in mice genetically depleted of serotonin.

    PubMed

    Solarewicz, Julia Z; Angoa-Perez, Mariana; Kuhn, Donald M; Mateika, Jason H

    2015-01-01

    We examined the role that serotonin has in the modulation of sleep and wakefulness across a 12-h:12-h light-dark cycle and determined whether temperature and motor activity are directly responsible for potential disruptions to arousal state. Telemetry transmitters were implanted in 24 wild-type mice (Tph2(+/+)) and 24 mice with a null mutation for tryptophan hydroxylase 2 (Tph2(-/-)). After surgery, electroencephalography, core body temperature, and motor activity were recorded for 24 h. Temperature for a given arousal state (quiet and active wake, non-rapid eye movement, and paradoxical sleep) was similar in the Tph2(+/+) and Tph2(-/-) mice across the light-dark cycle. The percentage of time spent in active wakefulness, along with motor activity, was decreased in the Tph2(+/+) compared with the Tph2(-/-) mice at the start and end of the dark cycle. This difference persisted into the light cycle. In contrast, the time spent in a given arousal state was similar at the remaining time points. Despite this similarity, periods of non-rapid-eye-movement sleep and wakefulness were less consolidated in the Tph2(+/+) compared with the Tph2(-/-) mice throughout the light-dark cycle. We conclude that the depletion of serotonin does not disrupt the diurnal variation in the sleep-wake cycle, motor activity, and temperature. However, serotonin may suppress photic and nonphotic inputs that manifest at light-dark transitions and serve to shorten the ultraradian duration of wakefulness and non-rapid-eye-movement sleep. Finally, alterations in the sleep-wake cycle following depletion of serotonin are unrelated to disruptions in the modulation of temperature.

  6. Antiplatelet activity of a novel formula composed of malic acid, succinic acid and citric acid from Cornus officinalis fruit.

    PubMed

    Zhang, Qi-Chun; Zhao, Yue; Bian, Hui-Min

    2013-12-01

    The present study investigated the antiplatelet activity of a novel formula composed by malic acid, succinic acid and citric acid with a ratio of 3:2:2. The IC50 and inhibition of platelet aggregation induced by various agonists as well as platelet adhesion were evaluated in vitro. Of note, the IC50 for the formula inhibiting adenosine diphosphate (ADP)-induced platelet aggregation was 0.185 mg/mL. Meanwhile, the formula showed more potent inhibitory effect on platelet aggregation induced by ADP and thrombin than the single component at same concentration (0.37 mg/mL). Moreover, the formula could prevent platelet adhesion significantly without influence on platelet viability.

  7. Reconciling Ligase Ribozyme Activity with Fatty Acid Vesicle Stability

    PubMed Central

    Anella, Fabrizio; Danelon, Christophe

    2014-01-01

    The “RNA world” and the “Lipid world” theories for the origin of cellular life are often considered incompatible due to the differences in the environmental conditions at which they can emerge. One obstacle resides in the conflicting requirements for divalent metal ions, in particular Mg2+, with respect to optimal ribozyme activity, fatty acid vesicle stability and protection against RNA strand cleavage. Here, we report on the activity of a short L1 ligase ribozyme in the presence of myristoleic acid (MA) vesicles at varying concentrations of Mg2+. The ligation rate is significantly lower at low-Mg2+ conditions. However, the loss of activity is overcompensated by the increased stability of RNA leading to a larger amount of intact ligated substrate after long reaction periods. Combining RNA ligation assays with fatty acid vesicles we found that MA vesicles made of 5 mM amphiphile are stable and do not impair ligase ribozyme activity in the presence of approximately 2 mM Mg2+. These results provide a scenario in which catalytic RNA and primordial membrane assembly can coexist in the same environment. PMID:25513761

  8. SILAC-based proteomic analysis reveals that salidroside antagonizes cobalt chloride-induced hypoxic effects by restoring the tricarboxylic acid cycle in cardiomyocytes.

    PubMed

    Xu, Zhong-Wei; Chen, Xi; Jin, Xiao-Han; Meng, Xiang-Yan; Zhou, Xin; Fan, Feng-Xu; Mao, Shi-Yun; Wang, Yue; Zhang, Wen-Cheng; Shan, Na-Na; Li, Yu-Ming; Xu, Rui-Cheng

    2016-01-01

    Hypoxic status alters the energy metabolism and induces cell injury in cardiomyocytes, and it further triggers the occurrence and development of cardiovascular diseases. Our previous studies have shown that salidroside (SAL) exhibits anti-hypoxic activity. However, the mechanisms remain obscure. In the present study, we successfully screened 92 different expression proteins in CoCl2-induced hypoxic conditions, 106 different expression proteins in the SAL-mediated anti-hypoxic group were compared with the hypoxic group using quantitative proteomics strategy, respectively. We confirmed that SAL showed a positive protective function involving the acetyl-CoA metabolic, tricarboxylic acid (TCA) cycle using bioinformatics analysis. We also demonstrated that SAL plays a critical role in restoring the TCA cycle and in protecting cardiomyocytes from oxidative injury via up-regulation expressions of PDHE1-B, ACO2, SUCLG1, SUCLG2 and down-regulation of MDH2. SAL also inhibited H9c2 cell apoptosis by inhibiting the activation of pro-apoptotic molecules caspase 3 and caspase 9 as well as activation of the anti-apoptotic molecular Bcl-2. Additionally, SAL also improved mitochondrial membrane potential (ΔΨm), reduced reactive oxygen species (ROS) and intercellular Ca(2+) concentration ([Ca(2+)]i) accumulation and inhibited the excessive consumption of ATP in H9c2 cells. PMID:26435418

  9. SILAC-based proteomic analysis reveals that salidroside antagonizes cobalt chloride-induced hypoxic effects by restoring the tricarboxylic acid cycle in cardiomyocytes.

    PubMed

    Xu, Zhong-Wei; Chen, Xi; Jin, Xiao-Han; Meng, Xiang-Yan; Zhou, Xin; Fan, Feng-Xu; Mao, Shi-Yun; Wang, Yue; Zhang, Wen-Cheng; Shan, Na-Na; Li, Yu-Ming; Xu, Rui-Cheng

    2016-01-01

    Hypoxic status alters the energy metabolism and induces cell injury in cardiomyocytes, and it further triggers the occurrence and development of cardiovascular diseases. Our previous studies have shown that salidroside (SAL) exhibits anti-hypoxic activity. However, the mechanisms remain obscure. In the present study, we successfully screened 92 different expression proteins in CoCl2-induced hypoxic conditions, 106 different expression proteins in the SAL-mediated anti-hypoxic group were compared with the hypoxic group using quantitative proteomics strategy, respectively. We confirmed that SAL showed a positive protective function involving the acetyl-CoA metabolic, tricarboxylic acid (TCA) cycle using bioinformatics analysis. We also demonstrated that SAL plays a critical role in restoring the TCA cycle and in protecting cardiomyocytes from oxidative injury via up-regulation expressions of PDHE1-B, ACO2, SUCLG1, SUCLG2 and down-regulation of MDH2. SAL also inhibited H9c2 cell apoptosis by inhibiting the activation of pro-apoptotic molecules caspase 3 and caspase 9 as well as activation of the anti-apoptotic molecular Bcl-2. Additionally, SAL also improved mitochondrial membrane potential (ΔΨm), reduced reactive oxygen species (ROS) and intercellular Ca(2+) concentration ([Ca(2+)]i) accumulation and inhibited the excessive consumption of ATP in H9c2 cells.

  10. ENERGY EFFICIENCY LIMITS FOR A RECUPERATIVE BAYONET SULFURIC ACID DECOMPOSITION REACTOR FOR SULFUR CYCLE THERMOCHEMICAL HYDROGEN PRODUCTION

    SciTech Connect

    Gorensek, M.; Edwards, T.

    2009-06-11

    A recuperative bayonet reactor design for the high-temperature sulfuric acid decomposition step in sulfur-based thermochemical hydrogen cycles was evaluated using pinch analysis in conjunction with statistical methods. The objective was to establish the minimum energy requirement. Taking hydrogen production via alkaline electrolysis with nuclear power as the benchmark, the acid decomposition step can consume no more than 450 kJ/mol SO{sub 2} for sulfur cycles to be competitive. The lowest value of the minimum heating target, 320.9 kJ/mol SO{sub 2}, was found at the highest pressure (90 bar) and peak process temperature (900 C) considered, and at a feed concentration of 42.5 mol% H{sub 2}SO{sub 4}. This should be low enough for a practical water-splitting process, even including the additional energy required to concentrate the acid feed. Lower temperatures consistently gave higher minimum heating targets. The lowest peak process temperature that could meet the 450-kJ/mol SO{sub 2} benchmark was 750 C. If the decomposition reactor were to be heated indirectly by an advanced gas-cooled reactor heat source (50 C temperature difference between primary and secondary coolants, 25 C minimum temperature difference between the secondary coolant and the process), then sulfur cycles using this concept could be competitive with alkaline electrolysis provided the primary heat source temperature is at least 825 C. The bayonet design will not be practical if the (primary heat source) reactor outlet temperature is below 825 C.

  11. Impact of dietary aromatic amino acids on osteoclastic activity.

    PubMed

    Refaey, Mona El; Zhong, Qing; Ding, Ke-Hong; Shi, Xing-Ming; Xu, Jianrui; Bollag, Wendy B; Hill, William D; Chutkan, Norman; Robbins, Richard; Nadeau, Hugh; Johnson, Maribeth; Hamrick, Mark W; Isales, Carlos M

    2014-08-01

    We had shown that aromatic amino acid (phenylalanine, tyrosine, and tryptophan) supplementation prevented bone loss in an aging C57BL/6 mice model. In vivo results from the markers of bone breakdown suggested an inhibition of osteoclastic activity or differentiation. To assess osteoclastic differentiation, we examined the effects of aromatic amino acids on early /structural markers as vitronectin receptor, calcitonin receptor, and carbonic anhydrase II as well as, late/functional differentiation markers; cathepsin K and matrix metalloproteinase 9 (MMP-9). Our data demonstrate that the aromatic amino acids down-regulated early and late osteoclastic differentiation markers as measured by real time PCR. Our data also suggest a link between the vitronectin receptor and the secreted cathepsin K that both showed consistent effects to the aromatic amino acid treatment. However, the non-attachment related proteins, calcitonin receptor, and carbonic anhydrase II, demonstrated less consistent effects in response to treatment. Our data are consistent with aromatic amino acids down-regulating osteoclastic differentiation by suppressing remodeling gene expression thus contributing initially to the net increase in bone mass seen in vivo.