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Sample records for acid enhances skeletal

  1. AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice

    DEFF Research Database (Denmark)

    Fentz, Joachim; Kjøbsted, Rasmus; Birk, Jesper B.;

    2015-01-01

    The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα md......) and FABPpm (plasma membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA transport capacity and FA transport protein translocation...

  2. Enhanced fatty acid oxidation and FATP4 protein expression after endurance exercise training in human skeletal muscle

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Jordy, Andreas B; Sjøberg, Kim A;

    2012-01-01

    FATP1 and FATP4 appear to be important for the cellular uptake and handling of long chain fatty acids (LCFA). These findings were obtained from loss- or gain of function models. However, reports on FATP1 and FATP4 in human skeletal muscle are limited. Aerobic training enhances lipid oxidation...

  3. Acetic acid enhances endurance capacity of exercise-trained mice by increasing skeletal muscle oxidative properties.

    Science.gov (United States)

    Pan, Jeong Hoon; Kim, Jun Ho; Kim, Hyung Min; Lee, Eui Seop; Shin, Dong-Hoon; Kim, Seongpil; Shin, Minkyeong; Kim, Sang Ho; Lee, Jin Hyup; Kim, Young Jun

    2015-01-01

    Acetic acid has been shown to promote glycogen replenishment in skeletal muscle during exercise training. In this study, we investigated the effects of acetic acid on endurance capacity and muscle oxidative metabolism in the exercise training using in vivo mice model. In exercised mice, acetic acid induced a significant increase in endurance capacity accompanying a reduction in visceral adipose depots. Serum levels of non-esterified fatty acid and urea nitrogen were significantly lower in acetic acid-fed mice in the exercised mice. Importantly, in the mice, acetic acid significantly increased the muscle expression of key enzymes involved in fatty acid oxidation and glycolytic-to-oxidative fiber-type transformation. Taken together, these findings suggest that acetic acid improves endurance exercise capacity by promoting muscle oxidative properties, in part through the AMPK-mediated fatty acid oxidation and provide an important basis for the application of acetic acid as a major component of novel ergogenic aids.

  4. Short-term ursolic acid promotes skeletal muscle rejuvenation through enhancing of SIRT1 expression and satellite cells proliferation.

    Science.gov (United States)

    Bakhtiari, Nuredin; Hosseinkhani, Saman; Soleimani, Masoud; Hemmati, Roohullah; Noori-Zadeh, Ali; Javan, Mohammad; Tashakor, Amin

    2016-03-01

    Ursolic acid (UA) is a triterpenoid compound, which exerts its influences on the skeletal muscles. However, the mechanisms underlying these effects are still unclear. In this study, muscle satellite cells were isolated and purified by high-throughput pre-plating method (∼>60%) from 10 days old mice skeletal muscles. Evaluation of paired-box 7 (Pax7) expressions then confirmed the purification. Treatment of the cells with UA showed that UA up-regulated SIRT1 (∼35 folds) and overexpressed PGC-1α (∼175 folds) gene significantly. Moreover, the number of muscle satellite cells, which accompanied by initiation of neomyogenesis in the animal skeletal muscles, was increased (∼3.4 times). We also evaluated UA-mediated changes in the cellular energy status in the skeletal muscles. The results revealed that in the UA-treated mice, ATP and ADP contents in the various skeletal muscle tissue types, including: Gastrocnemius (Gas), Tibialis Anterior (Tib) and Gluteus Maximus (Glu) have been significantly decreased (P≤0.001); 2.2, 3.2, 2 times for ATP, and 9.6, 35.7, 11.6 times for ADP, respectively; however to compensate this process mitochondrial biogenesis occurred (12.33%±1.5 times). Furthermore, a rise in ATP/ADP ratio was observed 2.5, 4.5, 2.05 times for Gas, Tib and Glu muscles, respectively (P≤0.001). Alternatively, UA enhanced the expression of myoglobin (∼2 folds) in concert with remodeling of glycolytic muscle fibers to mainly fast IIA (∼30%) and slow-twitch (∼4%) types as well. Finally, our study indicated that UA indirectly mimicked beneficial effects of short-term calorie restriction and exercise (fast-oxidative) by directing the skeletal muscle composition toward oxidative metabolism.

  5. Amino acids in healthy aging skeletal muscle.

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    Riddle, Emily S; Stipanuk, Martha H; Thalacker-Mercer, Anna E

    2016-01-01

    Life expectancy in the U.S. and globally continues to increase. Despite increased life expectancy quality of life is not enhanced, and older adults often experience chronic age-related disease and functional disability, including frailty. Additionally, changes in body composition such as the involuntary loss of skeletal muscle mass (i.e. sarcopenia) and subsequent increases in adipose tissue can augment disease and disability in this population. Furthermore, increased oxidative stress and decreased antioxidant concentrations may also lead to metabolic dysfunction in older adults. Specific amino acids, including leucine, cysteine and its derivative taurine, and arginine can play various roles in healthy aging, especially in regards to skeletal muscle health. Leucine and arginine play important roles in muscle protein synthesis and cell growth while cysteine and arginine play important roles in quenching oxidative stress. Evidence suggests that supplemental doses of each of these amino acids may improve the aging phenotype. However, additional research is required to establish the doses required to achieve positive outcomes in humans.

  6. Impact of Conjugated Linoleic Acid (CLA) on Skeletal Muscle Metabolism.

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    Kim, Yoo; Kim, Jonggun; Whang, Kwang-Youn; Park, Yeonhwa

    2016-02-01

    Conjugated linoleic acid (CLA) has garnered special attention as a food bioactive compound that prevents and attenuates obesity. Although most studies on the effects of CLA on obesity have focused on the reduction of body fat, a number of studies have demonstrated that CLA also increases lean body mass and enhances physical performances. It has been suggested that these effects may be due in part to physiological changes in the skeletal muscle, such as changes in the muscle fiber type transformation, alteration of the intracellular signaling pathways in muscle metabolism, or energy metabolism. However, the mode of action for CLA in muscle metabolism is not completely understood. The purpose of this review is to summarize the current knowledge of the effects of CLA on skeletal muscle metabolism. Given that CLA not only reduces body fat, but also improves lean mass, there is great potential for the use of CLA to improve muscle metabolism, which would have a significant health impact.

  7. Omega-3 Fatty Acids and Skeletal Muscle Health.

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    Jeromson, Stewart; Gallagher, Iain J; Galloway, Stuart D R; Hamilton, D Lee

    2015-11-19

    Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  8. Omega-3 Fatty Acids and Skeletal Muscle Health

    Directory of Open Access Journals (Sweden)

    Stewart Jeromson

    2015-11-01

    Full Text Available Skeletal muscle is a plastic tissue capable of adapting and mal-adapting to physical activity and diet. The response of skeletal muscle to adaptive stimuli, such as exercise, can be modified by the prior nutritional status of the muscle. The influence of nutrition on skeletal muscle has the potential to substantially impact physical function and whole body metabolism. Animal and cell based models show that omega-3 fatty acids, in particular those of marine origin, can influence skeletal muscle metabolism. Furthermore, recent human studies demonstrate that omega-3 fatty acids of marine origin can influence the exercise and nutritional response of skeletal muscle. These studies show that the prior omega-3 status influences not only the metabolic response of muscle to nutrition, but also the functional response to a period of exercise training. Omega-3 fatty acids of marine origin therefore have the potential to alter the trajectory of a number of human diseases including the physical decline associated with aging. We explore the potential molecular mechanisms by which omega-3 fatty acids may act in skeletal muscle, considering the n-3/n-6 ratio, inflammation and lipidomic remodelling as possible mechanisms of action. Finally, we suggest some avenues for further research to clarify how omega-3 fatty acids may be exerting their biological action in skeletal muscle.

  9. Compatibility of hyaluronic acid hydrogel and skeletal muscle myoblasts

    Energy Technology Data Exchange (ETDEWEB)

    Wang Wei; Zhang Li; Sun Liang; Wang Chengyue [Jinzhou Central Hospital, Jinzhou 121000 (China); Fan Ming; Liu Shuhong, E-mail: Weiwang_Ly@yahoo.com.c [Institute of Basic Medical Sciences, Academy of Military Medical Science, Beijing 100850 (China)

    2009-04-15

    Compatibility of hyaluronic acid hydrogel (HAH) and skeletal muscle myoblasts has been investigated for the first time in the present paper. Skeletal muscle myoblasts were separated from skeletons of rats and incubated with a HAH-containing culture medium. Cell morphology, hydrophilicity and cell adhesion of the HAH scaffold were investigated using optical microscopy, scanning electron microscopy, Hoechest33258 fluorescent staining, the immunocytochemistry method and water adsorption rate measurement. It was found that at a proper concentration (around 0.5%) of hyaluronic acid, the hydrogel possessed good compatibility with skeletal muscle myoblasts. The hydrogel can create a three-dimensional structure for the growth of skeletal muscle myoblasts and benefit cell attachment to provide a novel scaffold material for the tissue engineering of skeletal muscle.

  10. Tiliroside, a glycosidic flavonoid, ameliorates obesity-induced metabolic disorders via activation of adiponectin signaling followed by enhancement of fatty acid oxidation in liver and skeletal muscle in obese-diabetic mice.

    Science.gov (United States)

    Goto, Tsuyoshi; Teraminami, Aki; Lee, Joo-Young; Ohyama, Kana; Funakoshi, Kozue; Kim, Young-Il; Hirai, Shizuka; Uemura, Taku; Yu, Rina; Takahashi, Nobuyuki; Kawada, Teruo

    2012-07-01

    Tiliroside contained in several dietary plants, such as rose hips, strawberry and raspberry, is a glycosidic flavonoid and possesses anti-inflammatory, antioxidant, anticarcinogenic and hepatoprotective activities. Recently, it has been reported that the administration of tiliroside significantly inhibited body weight gain and visceral fat accumulation in normal mice. In this study, we evaluated the effects of tiliroside on obesity-induced metabolic disorders in obese-diabetic KK-A(y) mice. In KK-A(y) mice, the administration of tiliroside (100 mg/kg body weight/day) for 21 days failed to suppress body weight gain and visceral fat accumulation. Although tiliroside did not affect oxygen consumption, respiratory exchange ratio was significantly decreased in mice treated with tiliroside. In the analysis of metabolic characteristics, it was shown that plasma insulin, free fatty acid and triglyceride levels were decreased, and plasma adiponectin levels were increased in mice administered tiliroside. The messenger RNA expression levels of hepatic adiponectin receptor (AdipoR)-1 and AdipoR2 and skeletal muscular AdipoR1 were up-regulated by tiliroside treatment. Furthermore, it was indicated that tiliroside treatment activated AMP-activated protein kinase in both the liver and skeletal muscle and peroxisome proliferator-activated receptor α in the liver. Finally, tiliroside inhibited obesity-induced hepatic and muscular triglyceride accumulation. These findings suggest that tiliroside enhances fatty acid oxidation via the enhancement adiponectin signaling associated with the activation of both AMP-activated protein kinase and peroxisome proliferator-activated receptor α and ameliorates obesity-induced metabolic disorders, such as hyperinsulinemia and hyperlipidemia, although it does not suppress body weight gain and visceral fat accumulation in obese-diabetic model mice.

  11. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

  12. Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement.

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    Barazzoni, Rocco; Short, Kevin R; Asmann, Yan; Coenen-Schimke, Jill M; Robinson, Matthew M; Nair, K Sreekumaran

    2012-11-01

    Systemic insulin administration causes hypoaminoacidemia by inhibiting protein degradation, which may in turn inhibit muscle protein synthesis (PS). Insulin enhances muscle mitochondrial PS and ATP production when hypoaminoacidemia is prevented by exogenous amino acid (AA) replacement. We determined whether insulin would stimulate mitochondrial PS and ATP production in the absence of AA replacement. Using l-[1,2-¹³C]leucine as a tracer, we measured the fractional synthetic rate of mitochondrial as well as sarcoplasmic and mixed muscle proteins in 18 participants during sustained (7-h) insulin or saline infusion (n = 9 each). We also measured muscle ATP production, mitochondrial enzyme activities, mRNA levels of mitochondrial genes, and phosphorylation of signaling proteins regulating protein synthesis. The concentration of circulating essential AA decreased during insulin infusion. Mitochondrial, sarcoplasmic, and mixed muscle PS rates were also lower during insulin (2-7 h) than during saline infusions despite increased mRNA levels of selected mitochondrial genes. Under these conditions, insulin did not alter mitochondrial enzyme activities and ATP production. These effects were associated with enhanced phosphorylation of Akt but not of protein synthesis activators mTOR, p70(S6K), and 4EBP1. In conclusion, sustained physiological hyperinsulinemia without AA replacement did not stimulate PS of mixed muscle or protein subfractions and did not alter muscle mitochondrial ATP production in healthy humans. These results support that insulin and AA act in conjunction to stimulate muscle mitochondrial function and mitochondrial protein synthesis.

  13. Protein and amino acid metabolism in skeletal muscle

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    Wu, Guoyao.

    1989-01-01

    Isolated chick extensor digitorum communis (EDC) muscles and, in some experiments, rat skeletal muscles were used to study a number of aspects of protein and amino acid metabolism. (1) Chick EDC muscles synthesize and release large amounts of alanine and glutamine, which indirectly obtain their amino groups from branched-chain amino acids (BCAA). (2) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) decrease (P < 0.01) alanine synthesis and BCAA transamination in EDC muscles from 24-h fasted chicks by decreasing (P < 0.01) intracellular concentrations of pyruvate due to inhibition of glycolysis. (3) Glutamine is extensively degraded in skeletal muscles from both chicks and rats, thus challenging the traditional view that glutamine oxidation is negligible in skeletal muscle. The cytosolic glutamine aminotransferases L and K in the rat and the mitochondrial phosphate-activated glutaminase in the chick play important roles in the conversion of glutamine to {alpha}-ketoglutarate for further oxidation. (4) Although methionine has been reported to be extensively transaminated in rat skeletal muscle preparations in the absence of other amino acids, transamination of methionine is absent or negligible in chick and rat skeletal muscles in the presence of physiological concentrations of amino acids. (5) Glutamine at 1.0-15 mM increases (P < 0.01) protein synthesis ({sup 3}H-phenylalanine incorporation), and at 10.0-15.0 mM decreases (P < 0.05) protein degradation ({sup 3}H-phenylalanine release from prelabelled protein in vivo) in EDC muscles from fed chicks as compared to muscles incubated in the absence of glutamine. (6) Acetoacetate or DL-{beta}-hydroxybutyrate (4 mM) has a small but significant inhibitory effect (P < 0.05) on the rate of protein synthesis, but has no effect (P > 0.05) on the rate of protein degradation in EDC muscles from fed chicks.

  14. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  15. Effects of different fatty acid chain lengths on fatty acid oxidation-related protein expression levels in rat skeletal muscles.

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    Ishizawa, Rie; Masuda, Kazumi; Sakata, Susumu; Nakatani, Akira

    2015-01-01

    Skeletal muscles can adapt to dietary interventions that affect energy metabolism. Dietary intake of medium-chain fatty acids (MCFAs) enhances mitochondrial oxidation of fatty acids (FAO) in type IIa skeletal muscle fibers. However, the effect of MCFAs diet on mitochondrial or cytoplasmic FAO-related protein expression levels in different types of muscle fibers remains unclear. This study aims to examine the effects of a high-fat diet, containing MCFAs, on mitochondrial enzyme activities and heart-type fatty acid-binding protein (H-FABP) levels in different types of skeletal muscle fibers. Five-week-old male Wistar rats were assigned to one of the following three dietary conditions: standard chow (SC, 12% of calories from fat), high-fat MCFA, or high-fat long-chain fatty acids (LCFAs) diet (60% of calories from fat for both). The animals were provided food and water ad libitum for 4 weeks, following which citrate synthase (CS) activity and H-FABP concentration were analyzed. The epididymal fat pads (EFP) were significantly smaller in the MCFA group than in the LCFA group (p increase in CS activity compared with that observed in SC-fed controls in all types of skeletal muscle fibers (triceps, surface portion of gastrocnemius (gasS), deep portion of gastrocnemius (gasD), and soleus; p increase the expression of the mitochondrial enzyme CS, but not that of H-FABP, in both fast- and slow-twitch muscle fibers, suggesting that H-FABP expression is dependent on the chain length of fatty acids in the cytoplasm of skeletal muscles cells.

  16. Hyperinsulinemia and skeletal muscle fatty acid trafficking.

    Science.gov (United States)

    Kanaley, Jill A; Shadid, Samyah; Sheehan, Michael T; Guo, ZengKui; Jensen, Michael D

    2013-08-15

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-¹³C]palmitate (0400-0900 h) and [U-¹³C]oleate (0800-1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass⁻¹·min⁻¹) clamp (0800-1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-¹³C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ~1/10th of that observed in the previous saline control studies (P women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin.

  17. Hyperinsulinemia and skeletal muscle fatty acid trafficking

    Science.gov (United States)

    Kanaley, Jill A.; Shadid, Samyah; Sheehan, Michael T.; Guo, ZengKui

    2013-01-01

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-13C]palmitate (0400–0900 h) and [U-13C]oleate (0800–1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass−1·min−1) clamp (0800–1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-13C]palmitate incorporation into imTG-palmitate and palmitoylcarnitine were similar to those we reported in overnight postabsorptive adults (saline control); the intramyocellular palmitoylcarnitine enrichment was not different from and correlated with imTG-palmitate enrichment for both the morning (r = 0.38, P = 0.02) and afternoon (r = 0.44, P = 0.006) biopsy samples. Plasma FFA concentrations, flux, and the incorporation of plasma oleate into imTG-oleate during hyperinsulinemia were ∼1/10th of that observed in the previous saline control studies (P < 0.001). At the time of the second biopsy, the enrichment in oleoylcarnitine was <25% of that in imTG-oleate and was not correlated with imTG-oleate enrichment. The intramyocellular nonesterified fatty acid-palmitate-to-imTG-palmitate enrichment ratio was greater (P < 0.05) in women than men, suggesting that sex differences in intramyocellular palmitate trafficking may occur under hyperinsulinemic conditions. We conclude that plasma FFA trafficking into imTG during hyperinsulinemia is markedly suppressed, and these newly incorporated FFA fatty acids do not readily enter the LCAC preoxidative pools. Hyperinsulinemia does not seem to inhibit the entry of fatty acids from imTG pools that were labeled under fasting conditions, possibly reflecting the presence of two distinct imTG pools that are differentially regulated by insulin. PMID:23820622

  18. Hyperinsulinemia and skeletal muscle fatty acid trafficking

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    Kanaley, Jill A.; Shadid, Samyah; Sheehan, Michael T.; Guo, ZengKui; Jensen, Michael D

    2013-01-01

    We hypothesized that insulin alters plasma free fatty acid (FFA) trafficking into intramyocellular (im) long-chain acylcarnitines (imLCAC) and triglycerides (imTG). Overnight-fasted adults (n = 41) received intravenous infusions of [U-13C]palmitate (0400–0900 h) and [U-13C]oleate (0800–1400 h) to label imTG and imLCAC. A euglycemic-hyperinsulinemic (1.0 mU·kg fat-free mass−1·min−1) clamp (0800–1400 h) and two muscle biopsies (0900 h, 1400 h) were performed. The patterns of [U-13C]palmitate in...

  19. Leucine elicits myotube hypertrophy and enhances maximal contractile force in tissue engineered skeletal muscle in vitro.

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    Martin, Neil R W; Turner, Mark C; Farrington, Robert; Player, Darren J; Lewis, Mark P

    2017-10-01

    The amino acid leucine is thought to be important for skeletal muscle growth by virtue of its ability to acutely activate mTORC1 and enhance muscle protein synthesis, yet little data exist regarding its impact on skeletal muscle size and its ability to produce force. We utilized a tissue engineering approach in order to test whether supplementing culture medium with leucine could enhance mTORC1 signaling, myotube growth, and muscle function. Phosphorylation of the mTORC1 target proteins 4EBP-1 and rpS6 and myotube hypertrophy appeared to occur in a dose dependent manner, with 5 and 20 mM of leucine inducing similar effects, which were greater than those seen with 1 mM. Maximal contractile force was also elevated with leucine supplementation; however, although this did not appear to be enhanced with increasing leucine doses, this effect was completely ablated by co-incubation with the mTOR inhibitor rapamycin, showing that the augmented force production in the presence of leucine was mTOR sensitive. Finally, by using electrical stimulation to induce chronic (24 hr) contraction of engineered skeletal muscle constructs, we were able to show that the effects of leucine and muscle contraction are additive, since the two stimuli had cumulative effects on maximal contractile force production. These results extend our current knowledge of the efficacy of leucine as an anabolic nutritional aid showing for the first time that leucine supplementation may augment skeletal muscle functional capacity, and furthermore validates the use of engineered skeletal muscle for highly-controlled investigations into nutritional regulation of muscle physiology. © 2017 The Authors. Journal of Cellular Physiology Published by wiley periodicals, Inc.

  20. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation

    DEFF Research Database (Denmark)

    Dzamko, Nicolas; Schertzer, Jonathan D.; Ryall, James G.

    2008-01-01

    , malonyl-CoA levels were reduced and rates of fatty acid oxidation were comparable between genotypes. During treadmill exercise both KD and WT mice had similar values of respiratory exchange ratio. These studies suggested the presence of an alternative ACC2 kinase(s). Using a phosphoproteomics......The activation of AMP-activated protein kinase (AMPK) and phosphorylation/inhibition of acetyl-CoA carboxylase 2 (ACC2) is believed to be the principal pathway regulating fatty acid oxidation. However, during exercise AMPK activity and ACC Ser-221 phosphorylation does not always correlate...... with rates of fatty acid oxidation. To address this issue we have investigated the requirement for skeletal muscle AMPK in controlling aminoimidazole-4-carboxymide-1-beta-d-ribofuranoside (AICAR) and contraction-stimulated fatty acid oxidation utilizing transgenic mice expressing a muscle-specific kinase...

  1. Ursolic acid ameliorates aging-metabolic phenotype through promoting of skeletal muscle rejuvenation.

    Science.gov (United States)

    Bakhtiari, Nuredin; Hosseinkhani, Saman; Tashakor, Amin; Hemmati, Roohullah

    2015-07-01

    Ursolic acid (UA) is a lipophilic compound, which highly found in apple peels. UA has some certain features, of the most important is its anabolic effects on skeletal muscles, which in turn plays a prominent role in the aging process, encouraged us to evaluate skeletal muscle rejuvenation. This study seeks to address the two following questions: primarily, we wonder to know if UA increases anti-aging biomarkers (SIRT1 and PGC-1α) in the isolated satellite cells, to pave the way for satellite cells proliferation. The results revealed that UA elevated the expression of SIRT1 (∼ 35 folds) and PGC-1α (∼ 175 folds) genes. The other question that needs to be asked, however, is to understand whether it is possible to generalize the in vitro findings to in vivo. For this, a study was designed to investigate the effects of UA on the cellular energy status in the animal models (C57BL/6 mice). We found that UA decreased cellular energy charges such as ATP (∼ 3 times) and ADP (∼ 18 times). With respect to the role of UA in energy expenditure and as an anti-aging biomarker, one might wonder to elucidate skeletal muscle rejuvenation as well as satellite cells proliferation and neomyogenesis. The results illustrated that UA boosted neomyogenesis through enhancing the number of satellite cells. In addition, rejuvenation effects of UA on the skeletal muscle promptly encouraged us to reexamine the performance of skeletal muscles. The results indicated that UA through increasing myoglobin expression (∼ 2 folds) accompanied with transforming of glycolytic to fast oxidative status chiefly and slow-twitch muscle fibers. To the best of our knowledge, it seems that UA might be considered as a potential candidate for treatment of pathological conditions associated with muscular atrophy and dysfunction, including skeletal muscle atrophy, amyotrophic lateral sclerosis (ALS), sarcopenia and metabolic diseases of the muscles.

  2. Erythropoietin treatment enhances mitochondrial function in human skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ulla ePlenge

    2012-03-01

    Full Text Available Abstract Erythropoietin (Epo treatment has been shown to induce mitochondrial biogenesis in cardiac muscle along with enhanced mitochondrial capacity in mice. We hypothesized that recombinant human Epo (rhEpo treatment enhances skeletal muscle mitochondrial oxidative phosphorylation (OXPHOS capacity in humans. In six healthy volunteers rhEpo was administered by sub-cutaneous injection over eight weeks with oral iron (100 mg supplementation taken daily. Mitochondrial OXPHOS was quantified by high-resolution respirometry in saponin-permeabilized muscle fibers obtained from biopsies of the vastus lateralis before and after rhEpo treatment. OXPHOS was determined with the mitochondrial complex I substrates malate, glutamate, pyruvate and complex II substrate succinate in the presence of saturating ADP concentrations, while maximal electron transport capacity (ETS was assessed by addition of an uncoupler. rhEpo treatment increased OXPHOS (from 92±5 to 113±7 pmol.sec-1.mg-1 and ETS (107±4 to 143±14 pmol.sec-1.mg-1, P<0.05, demonstrating that Epo treatment induces an upregulation of OXPHOS and ETS in human skeletal muscle.

  3. Magnetofection Enhances Adenoviral Vector-based Gene Delivery in Skeletal Muscle Cells

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    Pereyra, Andrea Soledad; Mykhaylyk, Olga; Lockhart, Eugenia Falomir; Taylor, Jackson Richard; Delbono, Osvaldo; Goya, Rodolfo Gustavo; Plank, Christian; Hereñu, Claudia Beatriz

    2016-01-01

    The goal of magnetic field-assisted gene transfer is to enhance internalization of exogenous nucleic acids by association with magnetic nanoparticles (MNPs). This technique named magnetofection is particularly useful in difficult-to-transfect cells. It is well known that human, mouse, and rat skeletal muscle cells suffer a maturation-dependent loss of susceptibility to Recombinant Adenoviral vector (RAd) uptake. In postnatal, fully differentiated myofibers, the expression of the primary Coxsackie and Adenoviral membrane receptor (CAR) is severely downregulated representing a main hurdle for the use of these vectors in gene transfer/therapy. Here we demonstrate that assembling of Recombinant Adenoviral vectors with suitable iron oxide MNPs into magneto-adenovectors (RAd-MNP) and further exposure to a gradient magnetic field enables to efficiently overcome transduction resistance in skeletal muscle cells. Expression of Green Fluorescent Protein and Insulin-like Growth Factor 1 was significantly enhanced after magnetofection with RAd-MNPs complexes in C2C12 myotubes in vitro and mouse skeletal muscle in vivo when compared to transduction with naked virus. These results provide evidence that magnetofection, mainly due to its membrane-receptor independent mechanism, constitutes a simple and effective alternative to current methods for gene transfer into traditionally hard-to-transfect biological models. PMID:27274908

  4. Peroxisome proliferator-activated receptor γ decouples fatty acid uptake from lipid inhibition of insulin signaling in skeletal muscle.

    Science.gov (United States)

    Hu, Shanming; Yao, Jianrong; Howe, Alexander A; Menke, Brandon M; Sivitz, William I; Spector, Arthur A; Norris, Andrew W

    2012-06-01

    Peroxisome proliferator-activated receptor γ (PPARγ) is expressed at low levels in skeletal muscle, where it protects against adiposity and insulin resistance via unclear mechanisms. To test the hypothesis that PPARγ directly modulates skeletal muscle metabolism, we created two models that isolate direct PPARγ actions on skeletal myocytes. PPARγ was overexpressed in murine myotubes by adenotransfection and in mouse skeletal muscle by plasmid electroporation. In cultured myotubes, PPARγ action increased fatty acid uptake and incorporation into myocellular lipids, dependent upon a 154 ± 20-fold up-regulation of CD36 expression. PPARγ overexpression more than doubled insulin-stimulated thymoma viral proto-oncogene (AKT) phosphorylation during low lipid availability. Furthermore, in myotubes exposed to palmitate levels that inhibit insulin signaling, PPARγ overexpression increased insulin-stimulated AKT phosphorylation and glycogen synthesis over 3-fold despite simultaneously increasing myocellular palmitate uptake. The insulin signaling enhancement was associated with an increase in activating phosphorylation of phosphoinositide-dependent protein kinase 1 and a normalized expression of palmitate-induced genes that antagonize AKT phosphorylation. In vivo, PPARγ overexpression more than doubled insulin-dependent AKT phosphorylation in lipid-treated mice but did not augment insulin-stimulated glucose uptake. We conclude that direct PPARγ action promotes myocellular storage of energy by increasing fatty acid uptake and esterification while simultaneously enhancing insulin signaling and glycogen formation. However, direct PPARγ action in skeletal muscle is not sufficient to account for the hypoglycemic actions of PPARγ agonists during lipotoxicity.

  5. The mechanistic and ergogenic effects of phosphatidic acid in skeletal muscle.

    Science.gov (United States)

    Shad, Brandon James; Smeuninx, Benoit; Atherton, Philip James; Breen, Leigh

    2015-12-01

    Skeletal muscle mass plays a vital role in locomotion, whole-body metabolic health, and is a positive predictor of longevity. It is well established the mammalian target of rapamycin (mTOR) is a central regulator of skeletal muscle protein turnover. The pursuit to find novel nutrient compounds or functional food sources that possess the ability to activate mTOR and promote skeletal muscle protein accretion has been on going. Over the last decade, a key role has been proposed for the phospholipid phosphatidic acid (PA) in mTOR activation. Mechanical load-induced (i.e., resistance exercise) intramuscular PA can directly bind to and activate mTOR. In addition, PA provided exogenously in cell culture heightens mTOR activity, albeit indirectly. Thus, endogenously generated PA and exogenous provision of PA appear to act through distinct mechanisms that converge on mTOR and, potentially, may amplify muscle protein synthesis. In support of this notion, limited evidence from humans suggests that resistance exercise training combined with oral supplemental PA enhances strength gains and muscle hypertrophy. However, the precise mechanisms underpinning the augmented muscle remodelling response with supplemental PA remain elusive. In this review, we will critically examine available evidence from cell cultures and animal and human experimental models to provide an overview of the mechanisms through which endogenous and exogenous PA may act to promote muscle anabolism, and discuss the potential for PA as a therapeutic tool to maintain or restore skeletal muscle mass in the context of ageing and disease.

  6. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  7. AXIAL SKELETAL AND HOX EXPRESSION DOMAIN ALTERATIONS INDUCED BY RETINOIC ACID, VALPROIC ACID AND BROMOXYNIL DURING MURINE DEVELOPMENT

    Science.gov (United States)

    ABSTRACT Retinoic acid (RA) alters the developmental fate of the axial skeletal anlage. "Anteriorizations" or "posteriorizations", the assumption of characteristics of embryonic areas normally anterior or posterior to the affected tissues, are correlated with altered emb...

  8. Arterio-venous balance studies of skeletal muscle fatty acid metabolism: what can we believe?

    OpenAIRE

    Guo, ZengKui; Jensen, Michael D

    2013-01-01

    The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infus...

  9. Folic acid ingestion improves skeletal muscle blood flow during graded handgrip and plantar flexion exercise in aged humans.

    Science.gov (United States)

    Romero, Steven A; Gagnon, Daniel; Adams, Amy N; Moralez, Gilbert; Kouda, Ken; Jaffery, Manall F; Cramer, Matthew N; Crandall, Craig G

    2017-09-01

    Skeletal muscle blood flow is attenuated in aged humans performing dynamic exercise, which is due, in part, to impaired local vasodilatory mechanisms. Recent evidence suggests that folic acid improves cutaneous vasodilation during localized and whole body heating through nitric oxide-dependent mechanisms. However, it is unclear whether folic acid improves vasodilation in other vascular beds during conditions of increased metabolism (i.e., exercise). The purpose of this study was to test the hypothesis that folic acid ingestion improves skeletal muscle blood flow in aged adults performing graded handgrip and plantar flexion exercise via increased vascular conductance. Nine healthy, aged adults (two men and seven women; age: 68 ± 5 yr) performed graded handgrip and plantar flexion exercise before (control), 2 h after (acute, 5 mg), and after 6 wk (chronic, 5 mg/day) folic acid ingestion. Forearm (brachial artery) and leg (superficial femoral artery) blood velocity and diameter were measured via Duplex ultrasonography and used to calculate blood flow. Acute and chronic folic acid ingestion increased serum folate (both P < 0.05 vs. control). During handgrip exercise, acute and chronic folic acid ingestion increased forearm blood flow (both conditions P < 0.05 vs. control) and vascular conductance (both P < 0.05 vs. control). During plantar flexion exercise, acute and chronic folic acid ingestion increased leg blood flow (both P < 0.05 vs. control), but only acute folic acid ingestion increased vascular conductance (P < 0.05 vs. control). Taken together, folic acid ingestion increases blood flow to active skeletal muscle primarily via improved local vasodilation in aged adults.NEW & NOTEWORTHY Our findings demonstrate that folic acid ingestion improves blood flow via enhanced vascular conductance in the exercising skeletal muscle of aged humans. These findings provide evidence for the therapeutic use of folic acid to improve skeletal muscle blood flow, and perhaps

  10. Human skeletal muscle fatty acid and glycerol metabolism during rest, exercise and recovery

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; Sacchetti, M; Rådegran, G

    2002-01-01

    This study was conducted to investigate skeletal muscle fatty acid (FA) and glycerol kinetics and to determine the contribution of skeletal muscle to whole body FA and glycerol turnover during rest, 2 h of one-leg knee-extensor exercise at 65 % of maximal leg power output, and 3 h of recovery....... To this aim, the leg femoral arterial-venous difference technique was used in combination with a continuous infusion of [U-(13)C]palmitate and [(2)H(5)]glycerol in five post-absorptive healthy volunteers (22 +/- 3 years). The influence of contamination from non-skeletal muscle tissues, skin and subcutaneous...... glycerol uptake was observed, which was substantially higher during exercise. Total body skeletal muscle FA and glycerol uptake/release was estimated to account for 18-25 % of whole body R(d) or R(a). In conclusion: (1) skeletal muscle FA and glycerol metabolism, using the leg arterial-venous difference...

  11. Regulation of skeletal muscle insulin action in relation to dietary fatty acids and gender

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas

    -rich diet enriched in long-chain saturated fatty acids, whole body insulin sensitivity (19%) and insulin stimulated glucose uptake in skeletal muscle (24%) were also reduced, whereas no changes was observed after a diet enriched in medium-chain saturated fatty acids and carbohydrates. These findings show...... in skeletal muscle could rather be ascribed to attenuated GLUT4 translocation to the plasma surface membrane after the unsaturated (23%) and long-chain saturated fatty acid diet (26%) compared with the control diet (52%)(investigated in rats). Furthermore, the present data suggest that mechanisms regulating...

  12. Does Branched-Chain Amino Acids Supplementation Modulate Skeletal Muscle Remodeling through Inflammation Modulation? Possible Mechanisms of Action

    Directory of Open Access Journals (Sweden)

    Humberto Nicastro

    2012-01-01

    Full Text Available Skeletal muscle protein turnover is modulated by intracellular signaling pathways involved in protein synthesis, degradation, and inflammation. The proinflammatory status of muscle cells, observed in pathological conditions such as cancer, aging, and sepsis, can directly modulate protein translation initiation and muscle proteolysis, contributing to negative protein turnover. In this context, branched-chain amino acids (BCAAs, especially leucine, have been described as a strong nutritional stimulus able to enhance protein translation initiation and attenuate proteolysis. Furthermore, under inflammatory conditions, BCAA can be transaminated to glutamate in order to increase glutamine synthesis, which is a substrate highly consumed by inflammatory cells such as macrophages. The present paper describes the role of inflammation on muscle remodeling and the possible metabolic and cellular effects of BCAA supplementation in the modulation of inflammatory status of skeletal muscle and the consequences on protein synthesis and degradation.

  13. Regulation of skeletal muscle insulin action in relation to dietary fatty acids and gender

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas

    or dietary fatty acid quality and/or chain-length, 3) to investigate molecular mechanisms underlying lipid-induced insulin resistance. Results from studies provided in this thesis showed that insulin stimulated glucose uptake in skeletal muscle was higher in women than in matched men. When increasing fatty......-body level compared with men. After consuming a hypercaloric fat-rich diet (80 E%) enriched in unsaturated fatty acids for three days, reduced insulin stimulated whole-body (20%) and skeletal muscle glucose uptake (28%) were observed in men compared with a isocaloric control diet. After consuming a fat...... that insulin sensitivity was influenced by quality and chain-length of fatty acids rather than energy surplus per se. The lipid-induced reduction in skeletal muscle insulin sensitivity was observed without changes in the proximal insulin signaling cascade. The lipid-induced decrease in insulin sensitivity...

  14. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass.

    Science.gov (United States)

    Goodman, Craig A; Hornberger, Troy A

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mass. Fortunately, our knowledge is rapidly advancing, and in this review, we will summarize recent studies that have expanded our understanding of the roles that Smad signaling and the synthesis of phosphatidic acid play in the regulation of skeletal muscle mass.

  15. Skeletal myotube formation enhanced by electrospun polyurethane carbon nanotube scaffolds

    Science.gov (United States)

    Sirivisoot, Sirinrath; Harrison, Benjamin S

    2011-01-01

    Background This study examined the effects of electrically conductive materials made from electrospun single- or multiwalled carbon nanotubes with polyurethane to promote myoblast differentiation into myotubes in the presence and absence of electrical stimulation. Methods and results After electrical stimulation, the number of multinucleated myotubes on the electrospun polyurethane carbon nanotube scaffolds was significantly larger than that on nonconductive electrospun polyurethane scaffolds (5% and 10% w/v polyurethane). In the absence of electrical stimulation, myoblasts also differentiated on the electrospun polyurethane carbon nanotube scaffolds, as evidenced by expression of Myf-5 and myosin heavy chains. The myotube number and length were significantly greater on the electrospun carbon nanotubes with 10% w/v polyurethane than on those with 5% w/v polyurethane. The results suggest that, in the absence of electrical stimulation, skeletal myotube formation is dependent on the morphology of the electrospun scaffolds, while with electrical stimulation it is dependent on the electrical conductivity of the scaffolds. Conclusion This study indicates that electrospun polyurethane carbon nanotubes can be used to modulate skeletal myotube formation with or without application of electrical stimulation. PMID:22072883

  16. Arterio-venous balance studies of skeletal muscle fatty acid metabolism: what can we believe?

    Science.gov (United States)

    Guo, ZengKui

    2013-01-01

    The arterio-venous balance (A-V balance/difference) technique has been used by a number of groups, including ours, to study skeletal muscle fatty acid metabolism. Several lines of evidence indicate that, like glycogen, intramyocellular triglycerides (imcTG) are an energy source for local use. As such, the report that increased release of free fatty acids (FFA) via lipolysis from skeletal muscle, but not from adipose tissue, is responsible for the increased systemic lipolysis during IL-6 infusion in healthy humans is somewhat unexpected (26). It appears that given the complex anatomy of human limbs, as to be discussed in this review, it is virtually impossible to determine whether any fatty acids being released into the venous circulation of an arm or leg derive from the lipolysis of intermuscular fat residing between muscle groups, intramuscular fat residing within muscle groups (between epimysium and perimysium, or bundles), or the intramyocellular triglyceride droplets (imcTG). In many cases, it may even be difficult to be confident that there is no contribution of FFA from subcutaneous adipose tissue. This question is fundamentally important as one attempts to interpret the results of skeletal muscle fatty acid metabolism studies using the A-V balance technique. In this Perspectives article, we examine the reported results of fatty acid kinetics obtained using the techniques to evaluate the degree of and how to minimize contamination when attempting to sample skeletal muscle-specific fatty acids. PMID:23941872

  17. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Directory of Open Access Journals (Sweden)

    Steven D Kunkel

    Full Text Available Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II, blood vessel recruitment (Vegfa and autocrine/paracrine IGF-I signaling (Igf1. As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  18. Ursolic acid increases skeletal muscle and brown fat and decreases diet-induced obesity, glucose intolerance and fatty liver disease.

    Science.gov (United States)

    Kunkel, Steven D; Elmore, Christopher J; Bongers, Kale S; Ebert, Scott M; Fox, Daniel K; Dyle, Michael C; Bullard, Steven A; Adams, Christopher M

    2012-01-01

    Skeletal muscle Akt activity stimulates muscle growth and imparts resistance to obesity, glucose intolerance and fatty liver disease. We recently found that ursolic acid increases skeletal muscle Akt activity and stimulates muscle growth in non-obese mice. Here, we tested the hypothesis that ursolic acid might increase skeletal muscle Akt activity in a mouse model of diet-induced obesity. We studied mice that consumed a high fat diet lacking or containing ursolic acid. In skeletal muscle, ursolic acid increased Akt activity, as well as downstream mRNAs that promote glucose utilization (hexokinase-II), blood vessel recruitment (Vegfa) and autocrine/paracrine IGF-I signaling (Igf1). As a result, ursolic acid increased skeletal muscle mass, fast and slow muscle fiber size, grip strength and exercise capacity. Interestingly, ursolic acid also increased brown fat, a tissue that shares developmental origins with skeletal muscle. Consistent with increased skeletal muscle and brown fat, ursolic acid increased energy expenditure, leading to reduced obesity, improved glucose tolerance and decreased hepatic steatosis. These data support a model in which ursolic acid reduces obesity, glucose intolerance and fatty liver disease by increasing skeletal muscle and brown fat, and suggest ursolic acid as a potential therapeutic approach for obesity and obesity-related illness.

  19. Branched-chain amino acid-rich diet improves skeletal muscle wasting caused by cigarette smoke in rats.

    Science.gov (United States)

    Tomoda, Koichi; Kubo, Kaoru; Hino, Kazuo; Kondoh, Yasunori; Nishii, Yasue; Koyama, Noriko; Yamamoto, Yoshifumi; Yoshikawa, Masanori; Kimura, Hiroshi

    2014-04-01

    Cigarette smoke induces skeletal muscle wasting by a mechanism not yet fully elucidated. Branched-chain amino acids (BCAA) in the skeletal muscles are useful energy sources during exercise or systemic stresses. We investigated the relationship between skeletal muscle wasting caused by cigarette smoke and changes in BCAA levels in the plasma and skeletal muscles of rats. Furthermore, the effects of BCAA-rich diet on muscle wasting caused by cigarette smoke were also investigated. Wistar Kyoto (WKY) rats that were fed with a control or a BCAA-rich diet were exposed to cigarette smoke for four weeks. After the exposure, the skeletal muscle weight and BCAA levels in plasma and the skeletal muscles were measured. Cigarette smoke significantly decreased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles, while a BCAA-rich diet increased the skeletal muscle weight and BCAA levels in both plasma and skeletal muscles that had decreased by cigarette smoke exposure. In conclusion, skeletal muscle wasting caused by cigarette smoke was related to the decrease of BCAA levels in the skeletal muscles, while a BCAA-rich diet may improve cases of cigarette smoke-induced skeletal muscle wasting.

  20. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Yukino Hatazawa

    Full Text Available Peroxisome proliferator-activated receptor (PPAR γ coactivator 1α (PGC-1α is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT 2, branched-chain α-keto acid dehydrogenase (BCKDH, which catabolize BCAA. The expression of BCKDH kinase (BCKDK, which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  1. PGC-1α-mediated branched-chain amino acid metabolism in the skeletal muscle.

    Science.gov (United States)

    Hatazawa, Yukino; Tadaishi, Miki; Nagaike, Yuta; Morita, Akihito; Ogawa, Yoshihiro; Ezaki, Osamu; Takai-Igarashi, Takako; Kitaura, Yasuyuki; Shimomura, Yoshiharu; Kamei, Yasutomi; Miura, Shinji

    2014-01-01

    Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1α (PGC-1α) is a coactivator of various nuclear receptors and other transcription factors, which is involved in the regulation of energy metabolism, thermogenesis, and other biological processes that control phenotypic characteristics of various organ systems including skeletal muscle. PGC-1α in skeletal muscle is considered to be involved in contractile protein function, mitochondrial function, metabolic regulation, intracellular signaling, and transcriptional responses. Branched-chain amino acid (BCAA) metabolism mainly occurs in skeletal muscle mitochondria, and enzymes related to BCAA metabolism are increased by exercise. Using murine skeletal muscle overexpressing PGC-1α and cultured cells, we investigated whether PGC-1α stimulates BCAA metabolism by increasing the expression of enzymes involved in BCAA metabolism. Transgenic mice overexpressing PGC-1α specifically in the skeletal muscle had increased the expression of branched-chain aminotransferase (BCAT) 2, branched-chain α-keto acid dehydrogenase (BCKDH), which catabolize BCAA. The expression of BCKDH kinase (BCKDK), which phosphorylates BCKDH and suppresses its enzymatic activity, was unchanged. The amount of BCAA in the skeletal muscle was significantly decreased in the transgenic mice compared with that in the wild-type mice. The amount of glutamic acid, a metabolite of BCAA catabolism, was increased in the transgenic mice, suggesting the activation of muscle BCAA metabolism by PGC-1α. In C2C12 cells, the overexpression of PGC-1α significantly increased the expression of BCAT2 and BCKDH but not BCKDK. Thus, PGC-1α in the skeletal muscle is considered to significantly contribute to BCAA metabolism.

  2. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.

    Science.gov (United States)

    Jessen, N; Selmer Buhl, E; Pold, R; Schmitz, O; Lund, S

    2008-04-01

    Type 2 diabetes is preceded by the presence of skeletal muscle insulin resistance, and drugs that increase insulin sensitivity in skeletal muscle prevent the disease. S15511 is an original compound with demonstrated effects on insulin sensitivity in animal models of insulin resistance. However, the mechanisms behind the insulin-sensitizing effect of S15511 are unknown. The aim of our study was to explore whether S15511 improves insulin sensitivity in skeletal muscles. Insulin sensitivity was assessed in skeletal muscles from S15511-treated rats by measuring intracellular insulin-signaling activity and insulin-stimulated glucose transport in isolated muscles. In addition, GLUT4 expression and glycogen levels were assessed after treatment. S15511 treatment was associated with an increase in insulin-stimulated glucose transport in type IIb fibers, while type I fibers were unaffected. The enhanced glucose transport was mirrored by a fiber type-specific increase in GLUT4 expression, while no improvement in insulin-signaling activity was observed. S15511 is a novel insulin sensitizer that is capable of improving glucose homeostasis in nondiabetic rats. The compound enhances skeletal muscle insulin sensitivity and specifically targets type IIb muscle fibers by increasing GLUT4 expression. Together these data show S15511 to be a potentially promising new drug in the treatment and prevention of type 2 diabetes.

  3. Selective modification of the pyruvate dehydrogenase kinase isoform profile in skeletal muscle in hyperthyroidism: implications for the regulatory impact of glucose on fatty acid oxidation.

    Science.gov (United States)

    Sugden, M C; Lall, H S; Harris, R A; Holness, M J

    2000-11-01

    The pyruvate dehydrogenase kinases (PDK1-4) regulate glucose oxidation through inhibitory phosphorylation of the pyruvate dehydrogenase complex (PDC). Immunoblot analysis with antibodies raised against recombinant PDK isoforms demonstrated changes in PDK isoform expression in response to experimental hyperthyroidism (100 microg/100 g body weight; 3 days) that was selective for fast-twitch vs slow-twitch skeletal muscle in that PDK2 expression was increased in the fast-twitch skeletal muscle (the anterior tibialis) (by 1. 6-fold; P lactate --> glucose (Cori) and glucose --> alanine --> glucose cycles. We also propose that enhanced relative expression of the pyruvate-insensitive PDK isoform (PDK4) in skeletal muscle in hyperthyroidism uncouples glycolytic flux from pyruvate oxidation, sparing pyruvate for non-oxidative entry into the tricarboxylic acid (TCA) cycle, and thereby supporting entry of acetyl-CoA (derived from fatty acid oxidation) into the TCA cycle.

  4. Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle.

    Science.gov (United States)

    Morash, Andrea J; Kotwica, Aleksandra O; Murray, Andrew J

    2013-09-01

    Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O₂) on the transcription factor peroxisome proliferator-activated receptor α (PPARα) and its targets in mouse cardiac and skeletal muscle. In the heart, PPARα expression was 40% higher than in normoxia after 1 and 7 days of hypoxia. Activities of carnitine palmitoyltransferase (CPT) I and β-hydroxyacyl-CoA dehydrogenase (HOAD) were 75% and 35% lower, respectively, after 1 day of hypoxia, returning to normoxic levels after 7 days. Oxidative phosphorylation respiration rates using palmitoyl-carnitine followed a similar pattern, while respiration using pyruvate decreased. In skeletal muscle, PPARα expression and CPT I activity were 20% and 65% lower, respectively, after 1 day of hypoxia, remaining at this level after 7 days with no change in HOAD activity. Oxidative phosphorylation respiration rates using palmitoyl-carnitine were lower in skeletal muscle throughout hypoxia, while respiration using pyruvate remained unchanged. The rate of CO₂ production from palmitate oxidation was significantly lower in both tissues throughout hypoxia. Thus cardiac muscle may remain reliant on fatty acids during sustained hypoxia, while skeletal muscle decreases fatty acid oxidation and maintains pyruvate oxidation.

  5. The omega-3 fatty acid, eicosapentaenoic acid (EPA, prevents the damaging effects of tumour necrosis factor (TNF-alpha during murine skeletal muscle cell differentiation

    Directory of Open Access Journals (Sweden)

    Pearson Stephen

    2008-07-01

    Full Text Available Abstract Background Eicosapentaenoic acid (EPA is a ώ-3 polyunsaturated fatty acid with anti-inflammatory and anti-cachetic properties that may have potential benefits with regards to skeletal muscle atrophy conditions where inflammation is present. It is also reported that pathologic levels of the pro-inflammatory cytokine tumour necrosis factor (TNF-α are associated with muscle wasting, exerted through inhibition of myogenic differentiation and enhanced apoptosis. These findings led us to hypothesize that EPA may have a protective effect against skeletal muscle damage induced by the actions of TNF-α. Results The deleterious effects of TNF-α on C2C12 myogenesis were completely inhibited by co-treatment with EPA. Thus, EPA prevented the TNF-mediated loss of MyHC expression and significantly increased myogenic fusion (p p p p p p Conclusion In conclusion, EPA has a protective action against the damaging effects of TNF-α on C2C12 myogenesis. These findings support further investigations of EPA as a potential therapeutic agent during skeletal muscle regeneration following injury.

  6. Enhancement of colposcopic image by sulphosalicylic acid.

    Directory of Open Access Journals (Sweden)

    Khilnani P

    1993-01-01

    Full Text Available Acetic acid is used conventionally for enhancement of the colposcopic image. We used sulphosalicylic acid instead of acetic acid in 50 normal cases. The normal appearance was enhanced in all cases. The image was also enhanced in 70% cases of cervical intraepithelial neoplasia and 90% cases of cervical condyloma accuminata. The image was not inferior to that with acetic acid in any of the cases.

  7. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats.

    Science.gov (United States)

    Acevedo, Luz M; Raya, Ana I; Martínez-Moreno, Julio M; Aguilera-Tejero, Escolástico; Rivero, José-Luis L

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats.

  8. Mangiferin protects against adverse skeletal muscle changes and enhances muscle oxidative capacity in obese rats

    Science.gov (United States)

    Acevedo, Luz M.; Raya, Ana I.; Martínez-Moreno, Julio M.

    2017-01-01

    Obesity-related skeletal muscle changes include muscle atrophy, slow-to-fast fiber-type transformation, and impaired mitochondrial oxidative capacity. These changes relate with increased risk of insulin resistance. Mangiferin, the major component of the plant Mangifera indica, is a well-known anti-inflammatory, anti-diabetic, and antihyperlipidemic agent. This study tested the hypothesis that mangiferin treatment counteracts obesity-induced fiber atrophy and slow-to-fast fiber transition, and favors an oxidative phenotype in skeletal muscle of obese rats. Obese Zucker rats were fed gelatin pellets with (15 mg/kg BW/day) or without (placebo group) mangiferin for 8 weeks. Lean Zucker rats received the same gelatin pellets without mangiferin and served as non-obese and non-diabetic controls. Lesser diameter, fiber composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of myosin-based fiber-types were assessed in soleus and tibialis cranialis muscles. A multivariate discriminant analysis encompassing all fiber-type features indicated that obese rats treated with mangiferin displayed skeletal muscle phenotypes significantly different compared with both lean and obese control rats. Mangiferin significantly decreased inflammatory cytokines, preserved skeletal muscle mass, fiber cross-sectional size, and fiber-type composition, and enhanced muscle fiber oxidative capacity. These data demonstrate that mangiferin attenuated adverse skeletal muscle changes in obese rats. PMID:28253314

  9. Induction of amino acid transporters expression by endurance exercise in rat skeletal muscle

    Energy Technology Data Exchange (ETDEWEB)

    Murakami, Taro, E-mail: tamuraka@sgk.ac.jp; Yoshinaga, Mariko

    2013-10-04

    Highlights: •Regulation of amino acid transporter expression in working muscle remains unclear. •Expression of amino acid transporters for leucine were induced by a bout of exercise. •Requirement of leucine in muscle cells might regulate expression of its transporters. •This information is beneficial for understanding the muscle remodeling by exercise. -- Abstract: We here investigated whether an acute bout of endurance exercise would induce the expression of amino acid transporters that regulate leucine transport across plasma and lysosomal membranes in rat skeletal muscle. Rats ran on a motor-driven treadmill at a speed of 28 m/min for 90 min. Immediately after the exercise, we observed that expression of mRNAs encoding L-type amino acid transporter 1 (LAT1) and CD98 was induced in the gastrocnemius, soleus, and extensor digitorum longus (EDL) muscles. Sodium-coupled neutral amino acid transporter 2 (SNAT2) mRNA was also induced by the exercise in those three muscles. Expression of proton-assisted amino acid transporter 1 (PAT1) mRNA was slightly but not significantly induced by a single bout of exercise in soleus and EDL muscles. Exercise-induced mRNA expression of these amino acid transporters appeared to be attenuated by repeated bouts of the exercise. These results suggested that the expression of amino acid transporters for leucine may be induced in response to an increase in the requirement for this amino acid in the cells of working skeletal muscles.

  10. The role of membrane fatty-acid transporters in regulating skeletal muscle substrate use during exercise.

    Science.gov (United States)

    Pelsers, Maurice M A L; Stellingwerff, Trent; van Loon, Luc J C

    2008-01-01

    While endogenous carbohydrates form the main substrate source during high-intensity exercise, long-chain fatty acids (LCFA) represent the main substrate source during more prolonged low- to moderate-intensity exercise. Adipose tissue lipolysis is responsible for the supply of LCFA to the contracting muscle. Once taken up by skeletal muscle tissue, LCFA can either serve as a substrate for oxidative phosphorylation or can be directed towards esterification into triacylglycerol. Myocellular uptake of LCFA comprises a complex and incompletely understood process. Although LCFA can enter the cell via passive diffusion, more recent reports indicate that LCFA uptake is tightly regulated by plasma membrane-located transport proteins (fatty acid translocase [FAT/CD36], plasmalemmal-located fatty acid binding protein [FABPpm] and fatty acid transport protein [FATP]). Depending on cardiac and skeletal muscle energy demands, some of these LCFA transporters can translocate rapidly from intracellular pools to the plasma membrane to allow greater LCFA uptake. This translocation process can be induced by insulin and/or muscle contraction. However, the precise signalling pathways responsible for activating the translocation machinery remain to be elucidated. This article will provide an overview on the effects of diet, acute exercise and exercise training on the expression and/or translocation of the various LCFA transporters in skeletal muscle tissue (FAT/CD36, FABPpm, FATP).

  11. Dietary supplementation of β-guanidinopropionic acid (βGPA) reduces whole-body and skeletal muscle growth in young CD-1 mice.

    Science.gov (United States)

    Baumgarner, Bradley L; Nagle, Alison M; Quinn, Meagan R; Farmer, A Elaine; Kinsey, Stephen T

    2015-05-01

    Increased AMP-activated protein kinase (AMPK) activity leads to enhanced fatty acid utilization, while also promoting increased ubiquitin-dependent proteolysis (UDP) in mammalian skeletal muscle. β-guanidinopropionic acid (βGPA) is a commercially available dietary supplement that has been shown to promote an AMPK-dependent increase in fatty acid utilization and aerobic capacity in mammals by compromising creatine kinase function. However, it remains unknown if continuous βGPA supplementation can negatively impact skeletal muscle growth in a rapidly growing juvenile. The current study was conducted to examine the effect of βGPA supplementation on whole-body and skeletal muscle growth in juvenile and young adult mice. Three-week old, post weanling CD-1 mice were fed a standard rodent chow that was supplemented with either 2% (w/w) α-cellulose (control) or βGPA. Control and βGPA-fed mice (n = 6) were sampled after 2, 4, and 8 weeks. Whole-body and hindlimb muscle masses were significantly (P muscle-specific ubiquitin ligase MAFbx/Atrogin-1 protein and total protein ubiquitination in the gastrocnemius of βGPA versus control mice at the 8-week time point. Our data indicate that feeding juvenile mice a βGPA-supplemented diet significantly reduced whole-body and skeletal muscle growth that was due, at least in part, to an AMPK-independent increase in UDP.

  12. Taurine: the appeal of a safe amino acid for skeletal muscle disorders

    OpenAIRE

    De Luca, Annamaria; Pierno, Sabata; Camerino, Diana Conte

    2015-01-01

    Taurine is a natural amino acid present as free form in many mammalian tissues and in particular in skeletal muscle. Taurine exerts many physiological functions, including membrane stabilization, osmoregulation and cytoprotective effects, antioxidant and anti-inflammatory actions as well as modulation of intracellular calcium concentration and ion channel function. In addition taurine may control muscle metabolism and gene expression, through yet unclear mechanisms. This review summarizes the...

  13. Conjugated linoleic acid (CLA) prevents age associated skeletal muscle loss

    OpenAIRE

    Rahman, Md M; Halade, Ganesh V.; Jamali, Amina El; Fernandes, Gabriel

    2009-01-01

    In this study, we examined the effect of CLA isomers in preventing age-associated muscle loss and the mechanisms underlying this effect, using 12 months old C57BL/6 mice fed 10% corn oil (CO) or a diet supplemented with 0.5% c9t11-CLA, t10c12-CLA or c9t11-CLA+t10c12-CLA (CLA-mix) for 6 months. Both t10c12-CLA and CLA-mix groups showed significantly higher muscle mass, as compared to CO and c9t11-CLA groups, measured by dual-energy-Xray-absorptiometry and muscle wet weight. Enhanced mitochondr...

  14. Association of an ACSL1 gene variant with polyunsaturated fatty acids in bovine skeletal muscle

    Directory of Open Access Journals (Sweden)

    Widmann Philipp

    2011-11-01

    Full Text Available Abstract Background The intramuscular fat deposition and the fatty acid profiles of beef affect meat quality. High proportions of unsaturated fatty acids are related to beef flavor and are beneficial for the nutritional value of meat. Moreover, a variety of clinical and epidemiologic studies showed that particularly long-chain omega-3 fatty acids from animal sources have a positive impact on human health and disease. Results To screen for genetic factors affecting fatty acid profiles in beef, we initially performed a microsatellite-based genome scan in a F2 Charolais × German Holstein resource population and identified a quantitative trait locus (QTL for fatty acid composition in a region on bovine chromosome 27 where previously QTL affecting marbling score had been detected in beef cattle populations. The long-chain acyl-CoA synthetase 1 (ACSL1 gene was identified as the most plausible functional and positional candidate gene in the QTL interval due to its direct impact on fatty acid metabolism and its position in the QTL interval. ACSL1 is necessary for synthesis of long-chain acyl-CoA esters, fatty acid degradation and phospholipid remodeling. We validated the genomic annotation of the bovine ACSL1 gene by in silico comparative sequence analysis and experimental verification. Re-sequencing of the complete coding, exon-flanking intronic sequences, 3' untranslated region (3'UTR and partial promoter region of the ACSL1 gene revealed three synonymous mutations in exons 6, 7, and 20, six noncoding intronic gene variants, six polymorphisms in the promoter region, and four variants in the 3' UTR region. The association analysis identified the gene variant in intron 5 of the ACSL1 gene (c.481-233A>G to be significantly associated with the relative content of distinct fractions and ratios of fatty acids (e.g., n-3 fatty acids, polyunsaturated, n-3 long-chain polyunsaturated fatty acids, trans vaccenic acid in skeletal muscle. A tentative association

  15. Skeletal Muscle-specific G Protein-coupled Receptor Kinase 2 Ablation Alters Isolated Skeletal Muscle Mechanics and Enhances Clenbuterol-stimulated Hypertrophy.

    Science.gov (United States)

    Woodall, Benjamin P; Woodall, Meryl C; Luongo, Timothy S; Grisanti, Laurel A; Tilley, Douglas G; Elrod, John W; Koch, Walter J

    2016-10-14

    GRK2, a G protein-coupled receptor kinase, plays a critical role in cardiac physiology. Adrenergic receptors are the primary target for GRK2 activity in the heart; phosphorylation by GRK2 leads to desensitization of these receptors. As such, levels of GRK2 activity in the heart directly correlate with cardiac contractile function. Furthermore, increased expression of GRK2 after cardiac insult exacerbates injury and speeds progression to heart failure. Despite the importance of this kinase in both the physiology and pathophysiology of the heart, relatively little is known about the role of GRK2 in skeletal muscle function and disease. In this study we generated a novel skeletal muscle-specific GRK2 knock-out (KO) mouse (MLC-Cre:GRK2(fl/fl)) to gain a better understanding of the role of GRK2 in skeletal muscle physiology. In isolated muscle mechanics testing, GRK2 ablation caused a significant decrease in the specific force of contraction of the fast-twitch extensor digitorum longus muscle yet had no effect on the slow-twitch soleus muscle. Despite these effects in isolated muscle, exercise capacity was not altered in MLC-Cre:GRK2(fl/fl) mice compared with wild-type controls. Skeletal muscle hypertrophy stimulated by clenbuterol, a β2-adrenergic receptor (β2AR) agonist, was significantly enhanced in MLC-Cre:GRK2(fl/fl) mice; mechanistically, this seems to be due to increased clenbuterol-stimulated pro-hypertrophic Akt signaling in the GRK2 KO skeletal muscle. In summary, our study provides the first insights into the role of GRK2 in skeletal muscle physiology and points to a role for GRK2 as a modulator of contractile properties in skeletal muscle as well as β2AR-induced hypertrophy. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

    Energy Technology Data Exchange (ETDEWEB)

    Sisti, Karin E., E-mail: karinellensisti@gmail.com [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Federal University of Mato Grosso do Sul (UFMS), Campo Grande (Brazil); Andrés, María C. de; Johnston, David [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Almeida-Filho, Edson; Guastaldi, Antonio C. [Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Oreffo, Richard O.C. [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom)

    2016-05-06

    Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv) LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell

  17. Does phototherapy enhance skeletal muscle contractile function and postexercise recovery? A systematic review.

    Science.gov (United States)

    Borsa, Paul A; Larkin, Kelly A; True, Jerry M

    2013-01-01

    Recently, researchers have shown that phototherapy administered to skeletal muscle immediately before resistance exercise can enhance contractile function, prevent exercise-induced cell damage, and improve postexercise recovery of strength and function. To critically evaluate original research addressing the ability of phototherapeutic devices, such as lasers and light-emitting diodes (LEDs), to enhance skeletal muscle contractile function, reduce exercise-induced muscle fatigue, and facilitate postexercise recovery. We searched the electronic databases PubMed, SPORTDiscus, Web of Science, Scopus, and Rehabilitation & Physical Medicine without date limitations for the following key words: laser therapy, phototherapy, fatigue, exercise, circulation, microcirculation, and photobiomodulation. Eligible studies had to be original research published in English as full papers, involve human participants, and receive a minimum score of 7 out of 10 on the Physiotherapy Evidence Database (PEDro) scale. Data of interest included elapsed time to fatigue, total number of repetitions to fatigue, total work performed, maximal voluntary isometric contraction (strength), electromyographic activity, and postexercise biomarker levels. We recorded the PEDro scores, beam characteristics, and treatment variables and calculated the therapeutic outcomes and effect sizes for the data sets. In total, 12 randomized controlled trials met the inclusion criteria. However, we excluded data from 2 studies, leaving 32 data sets from 10 studies. Twenty-four of the 32 data sets contained differences between active phototherapy and sham (placebo-control) treatment conditions for the various outcome measures. Exposing skeletal muscle to single-diode and multidiode laser or multidiode LED therapy was shown to positively affect physical performance by delaying the onset of fatigue, reducing the fatigue response, improving postexercise recovery, and protecting cells from exercise-induced damage

  18. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery.

    Science.gov (United States)

    Albers, Peter H; Bojsen-Møller, Kirstine N; Dirksen, Carsten; Serup, Annette K; Kristensen, Dorte E; Frystyk, Jan; Clausen, Trine R; Kiens, Bente; Richter, Erik A; Madsbad, Sten; Wojtaszewski, Jørgen F P

    2015-09-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose-tolerant and type 2 diabetic subjects at fasting and during a hyperinsulinemic-euglycemic clamp before as well as 1 wk and 3 and 12 mo after RYGB were analyzed for relevant insulin effector proteins/signaling components. Improvement in peripheral insulin sensitivity mainly occurred at 12 mo postsurgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4, as well as insulin-induced changes in phosphorylation of Akt and glycogen synthase activity were enhanced 12 mo postsurgery. In adipose tissue, protein expression of GLUT4, Akt2, TBC1D4, and acetyl-CoA carboxylase (ACC), phosphorylated levels of AMP-activated protein kinase and ACC, as well as insulin-induced changes in phosphorylation of Akt and TBC1D4, were enhanced 12 mo postsurgery. Adipose tissue from glucose-tolerant subjects was the most responsive to RYGB compared with type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin-sensitive phenotype of skeletal muscle and adipose tissue appears to contribute to the improved whole body insulin action following a substantial weight loss after RYGB. Copyright © 2015 the American Physiological Society.

  19. Ameliorative effects of polyunsaturated fatty acids against palmitic acid-induced insulin resistance in L6 skeletal muscle cells

    Directory of Open Access Journals (Sweden)

    Sawada Keisuke

    2012-03-01

    Full Text Available Abstract Background Fatty acid-induced insulin resistance and impaired glucose uptake activity in muscle cells are fundamental events in the development of type 2 diabetes and hyperglycemia. There is an increasing demand for compounds including drugs and functional foods that can prevent myocellular insulin resistance. Methods In this study, we established a high-throughput assay to screen for compounds that can improve myocellular insulin resistance, which was based on a previously reported non-radioisotope 2-deoxyglucose (2DG uptake assay. Insulin-resistant muscle cells were prepared by treating rat L6 skeletal muscle cells with 750 μM palmitic acid for 14 h. Using the established assay, the impacts of several fatty acids on myocellular insulin resistance were determined. Results In normal L6 cells, treatment with saturated palmitic or stearic acid alone decreased 2DG uptake, whereas unsaturated fatty acids did not. Moreover, co-treatment with oleic acid canceled the palmitic acid-induced decrease in 2DG uptake activity. Using the developed assay with palmitic acid-induced insulin-resistant L6 cells, we determined the effects of other unsaturated fatty acids. We found that arachidonic, eicosapentaenoic and docosahexaenoic acids improved palmitic acid-decreased 2DG uptake at lower concentrations than the other unsaturated fatty acids, including oleic acid, as 10 μM arachidonic acid showed similar effects to 750 μM oleic acid. Conclusions We have found that polyunsaturated fatty acids, in particular arachidonic and eicosapentaenoic acids prevent palmitic acid-induced myocellular insulin resistance.

  20. Taurine: the appeal of a safe amino acid for skeletal muscle disorders.

    Science.gov (United States)

    De Luca, Annamaria; Pierno, Sabata; Camerino, Diana Conte

    2015-07-25

    Taurine is a natural amino acid present as free form in many mammalian tissues and in particular in skeletal muscle. Taurine exerts many physiological functions, including membrane stabilization, osmoregulation and cytoprotective effects, antioxidant and anti-inflammatory actions as well as modulation of intracellular calcium concentration and ion channel function. In addition taurine may control muscle metabolism and gene expression, through yet unclear mechanisms. This review summarizes the effects of taurine on specific muscle targets and pathways as well as its therapeutic potential to restore skeletal muscle function and performance in various pathological conditions. Evidences support the link between alteration of intracellular taurine level in skeletal muscle and different pathophysiological conditions, such as disuse-induced muscle atrophy, muscular dystrophy and/or senescence, reinforcing the interest towards its exogenous supplementation. In addition, taurine treatment can be beneficial to reduce sarcolemmal hyper-excitability in myotonia-related syndromes. Although further studies are necessary to fill the gaps between animals and humans, the benefit of the amino acid appears to be due to its multiple actions on cellular functions while toxicity seems relatively low. Human clinical trials using taurine in various pathologies such as diabetes, cardiovascular and neurological disorders have been performed and may represent a guide-line for designing specific studies in patients of neuromuscular diseases.

  1. Effect of protein/essential amino acids and resistance training on skeletal muscle hypertrophy: A case for whey protein

    Directory of Open Access Journals (Sweden)

    Stout Jeffrey R

    2010-06-01

    Full Text Available Abstract Regardless of age or gender, resistance training or provision of adequate amounts of dietary protein (PRO or essential amino acids (EAA can increase muscle protein synthesis (MPS in healthy adults. Combined PRO or EAA ingestion proximal to resistance training, however, can augment the post-exercise MPS response and has been shown to elicit a greater anabolic effect than exercise plus carbohydrate. Unfortunately, chronic/adaptive response data comparing the effects of different protein sources is limited. A growing body of evidence does, however, suggest that dairy PRO, and whey in particular may: 1 stimulate the greatest rise in MPS, 2 result in greater muscle cross-sectional area when combined with chronic resistance training, and 3 at least in younger individuals, enhance exercise recovery. Therefore, this review will focus on whey protein supplementation and its effects on skeletal muscle mass when combined with heavy resistance training.

  2. Laminin α2-secreting fibroblasts enhance the therapeutic effect of skeletal myoblast sheets.

    Science.gov (United States)

    Uchinaka, Ayako; Tasaka, Kanako; Mizuno, Yoko; Maeno, Yoshitaka; Ban, Tsuyoshi; Mori, Seiji; Hamada, Yoshinosuke; Miyagawa, Shigeru; Saito, Atsuhiro; Sawa, Yoshiki; Matsuura, Nariaki; Nagata, Kohzo; Yamamoto, Hirofumi; Kawaguchi, Naomasa

    2017-03-01

    Skeletal myoblast sheet (SMB) transplantation, a method used for treating failing hearts, results in the secretion of cytokines that improve heart function. Enhancing the survival rate of implanted myoblasts should yield more continuous and effective therapies. We hypothesized that laminin-211 (merosin), a major component of skeletal muscle extracellular matrix (ECM), which mediates cell-to-ECM adhesion by binding to α -dystroglycan ( α DG) on muscle cells, could inhibit detachment of implanted myoblasts from host myocardia. Multilayered sheets composed of fibroblasts expressing laminin G-module (LG)4-5 of α 2 and skeletal myoblasts were transplanted into ischemic cardiomyopathy model rats. Animals were divided into four groups: the ligation only (Control) group, and those transplanted with SMB alone, with both myoblasts and control fibroblast sheets (SMB + normal Fb), or with myoblasts and laminin α 2 LG4-5-expressing fibroblast sheets (SMB + laminin Fb). Quantitative estimation of nebulin mRNA levels indicated that the transplanted myoblasts in SMB + laminin Fb group exhibited significantly higher survival rates than those in the other groups. Consistent with these findings, the myoblasts in SMB + laminin Fb group exhibited elevated expression of growth factors, while SMB + laminin Fb rats also showed significant improvements in percent fractional shortening (%FS) and left ventricular remodelling, compared to the other groups. Laminin secreted by implanted fibroblasts inhibited the detachment of implanted myoblasts from grafted myocardia, resulting in more permanent therapeutic effects upon myoblast sheet transplantation.

  3. Condensation of Plasmid DNA Enhances Mitochondrial Association in Skeletal Muscle Following Hydrodynamic Limb Vein Injection

    Directory of Open Access Journals (Sweden)

    Yukari Yasuzaki

    2014-08-01

    Full Text Available Mitochondrial gene therapy and diagnosis have the potential to provide substantial medical benefits. However, the utility of this approach has not yet been realized because the technology available for mitochondrial gene delivery continues to be a bottleneck. We previously reported on mitochondrial gene delivery in skeletal muscle using hydrodynamic limb vein (HLV injection. HLV injection, a useful method for nuclear transgene expression, involves the rapid injection of a large volume of naked plasmid DNA (pDNA. Moreover, the use of a condensed form of pDNA enhances the nuclear transgene expression by the HLV injection. The purpose of this study was to compare naked pDNA and condensed pDNA for mitochondrial association in skeletal muscle, when used in conjunction with HLV injection. PCR analysis showed that the use of condensed pDNA rather than naked pDNA resulted in a more effective mitochondrial association with pDNA, suggesting that the physicochemical state of pDNA plays a key role. Moreover, no mitochondrial toxicities in skeletal muscle following the HLV injection of condensed pDNA were confirmed, as evidenced by cytochrome c oxidase activity and mitochondrial membrane potential. These findings have the potential to contribute to the development for in vivo mitochondrial gene delivery system.

  4. The role of phospholipase D and phosphatidic acid in the mechanical activation of mTOR signaling in skeletal muscle.

    Science.gov (United States)

    Hornberger, T A; Chu, W K; Mak, Y W; Hsiung, J W; Huang, S A; Chien, S

    2006-03-21

    Signaling by the mammalian target of rapamycin (mTOR) has been reported to be necessary for mechanical load-induced growth of skeletal muscle. The mechanisms involved in the mechanical activation of mTOR signaling are not known, but several studies indicate that a unique [phosphotidylinositol-3-kinase (PI3K)- and nutrient-independent] mechanism is involved. In this study, we have demonstrated that a regulatory pathway for mTOR signaling that involves phospholipase D (PLD) and the lipid second messenger phosphatidic acid (PA) plays a critical role in the mechanical activation of mTOR signaling. First, an elevation in PA concentration was sufficient for the activation of mTOR signaling. Second, the isozymes of PLD (PLD1 and PLD2) are localized to the z-band in skeletal muscle (a critical site of mechanical force transmission). Third, mechanical stimulation of skeletal muscle with intermittent passive stretch ex vivo induced PLD activation, PA accumulation, and mTOR signaling. Finally, pharmacological inhibition of PLD blocked the mechanically induced increase in PA and the activation of mTOR signaling. Combined, these results indicate that mechanical stimuli activate mTOR signaling through a PLD-dependent increase in PA. Furthermore, we showed that mTOR signaling was partially resistant to rapamycin in muscles subjected to mechanical stimulation. Because rapamycin and PA compete for binding to the FRB domain on mTOR, these results suggest that mechanical stimuli activate mTOR signaling through an enhanced binding of PA to the FRB domain on mTOR.

  5. Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome.

    Science.gov (United States)

    van Hees, A M J; Saris, W H M; Hul, G B; Schaper, N C; Timmerman, B E; Lovegrove, J A; Roche, H M; Blaak, E E

    2010-05-01

    In the metabolic syndrome (MetS), increased fat storage in 'nonadipose' tissues such as skeletal muscle may be related to insulin resistance ('lipid overflow' hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn-3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [(2)H(2)]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-(13)C]-palmitate to label chylomicron-TAG. Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn-3 group compared to the HSFA group (DeltaiAUC -139+/-67 vs 167+/-70 micromol l(-1) min(-1), P=0.009), together with decreased concentrations of [U-(13)C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn-3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.

  6. Nanometer-thin TiO2 enhances skeletal muscle cell phenotype and behavior

    Directory of Open Access Journals (Sweden)

    Ishizaki K

    2011-10-01

    Full Text Available Ken Ishizaki*, Yoshihiko Sugita*, Fuminori Iwasa, Hajime Minamikawa, Takeshi Ueno, Masahiro Yamada, Takeo Suzuki, Takahiro OgawaLaboratory for Bone and Implant Sciences, The Jane and Jerry Weintraub Center for Reconstructive Biotechnology, Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry, UCLA School of Dentistry, Los Angeles, CA, USA*Authors contributed equally to this workBackground: The independent role of the surface chemistry of titanium in determining its biological properties is yet to be determined. Although titanium implants are often in contact with muscle tissue, the interaction of muscle cells with titanium is largely unknown. This study tested the hypotheses that the surface chemistry of clinically established microroughened titanium surfaces could be controllably varied by coating with a minimally thin layer of TiO2 (ideally pico-to-nanometer in thickness without altering the existing topographical and roughness features, and that the change in superficial chemistry of titanium is effective in improving the biological properties of titanium.Methods and results: Acid-etched microroughened titanium surfaces were coated with TiO2 using slow-rate sputter deposition of molten TiO2 nanoparticles. A TiO2 coating of 300 pm to 6.3 nm increased the surface oxygen on the titanium substrates in a controllable manner, but did not alter the existing microscale architecture and roughness of the substrates. Cells derived from rat skeletal muscles showed increased attachment, spread, adhesion strength, proliferation, gene expression, and collagen production at the initial and early stage of culture on 6.3 nm thick TiO2-coated microroughened titanium surfaces compared with uncoated titanium surfaces.Conclusion: Using an exemplary slow-rate sputter deposition technique of molten TiO2 nanoparticles, this study demonstrated that titanium substrates, even with microscale roughness, can be sufficiently chemically modified to

  7. Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

    DEFF Research Database (Denmark)

    Matthews, V B; Åström, Maj-Brit; Chan, M H S

    2009-01-01

    AIMS/HYPOTHESIS: Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF. METHODS: We first examined whether exercise induced BDNF expression in humans. Next, C2......(79)) were analysed, as was fatty acid oxidation (FAO). Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice. RESULTS: BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released...... into the circulation. Bdnf mRNA and protein expression was increased in muscle cells that were electrically stimulated. BDNF increased phosphorylation of AMPK and ACCbeta and enhanced FAO both in vitro and ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected...

  8. Regular exercise enhances insulin activation of IRS-1-associated PI3-kinase in human skeletal muscle.

    Science.gov (United States)

    Kirwan, J P; del Aguila, L F; Hernandez, J M; Williamson, D L; O'Gorman, D J; Lewis, R; Krishnan, R K

    2000-02-01

    Insulin action in skeletal muscle is enhanced by regular exercise. Whether insulin signaling in human skeletal muscle is affected by habitual exercise is not well understood. Phosphatidylinositol 3-kinase (PI3-kinase) activation is an important step in the insulin-signaling pathway and appears to regulate glucose metabolism via GLUT-4 translocation in skeletal muscle. To examine the effects of regular exercise on PI3-kinase activation, 2-h hyperinsulinemic (40 mU. m(-2). min(-1))-euglycemic (5.0 mM) clamps were performed on eight healthy exercise-trained [24 +/- 1 yr, 71.8 +/- 2.0 kg, maximal O(2) uptake (VO(2 max)) of 56.1 +/- 2.5 ml. kg(-1). min(-1)] and eight healthy sedentary men and women (24 +/- 1 yr, 64.7 +/- 4.4 kg, VO(2 max) of 44.4 +/- 2.7 ml. kg(-1). min(-1)). A [6, 6-(2)H]glucose tracer was used to measure hepatic glucose output. A muscle biopsy was obtained from the vastus lateralis muscle at basal and at 2 h of hyperinsulinemia to measure insulin receptor substrate-1(IRS-1)-associated PI3-kinase activation. Insulin concentrations during hyperinsulinemia were similar for both groups (293 +/- 22 and 311 +/- 22 pM for trained and sedentary, respectively). Insulin-mediated glucose disposal rates (GDR) were greater (P exercise-trained compared with the sedentary control group (9.22 +/- 0.95 vs. 6.36 +/- 0.57 mg. kg fat-free mass(-1). min(-1)). Insulin-stimulated PI3-kinase activation was also greater (P < 0.004) in the trained compared with the sedentary group (3.8 +/- 0.5- vs. 1.8 +/- 0.2-fold increase from basal). Endurance capacity (VO(2 max)) was positively correlated with PI3-kinase activation (r = 0.53, P < 0.04). There was no correlation between PI3-kinase and muscle morphology. However, increases in GDR were positively related to PI3-kinase activation (r = 0.60, P < 0.02). We conclude that regular exercise leads to greater insulin-stimulated IRS-1-associated PI3-kinase activation in human skeletal muscle, thus facilitating enhanced insulin

  9. Carnosic acid stimulates glucose uptake in skeletal muscle cells via a PME-1/PP2A/PKB signalling axis.

    Science.gov (United States)

    Lipina, Christopher; Hundal, Harinder S

    2014-11-01

    Carnosic acid (CA) is a major constituent of the labiate herbal plant Rosemary (Rosmarinus officinalis), which has been shown to exhibit a number of beneficial health properties. In particular, recently there has been growing interest into the anti-obesity effects conveyed by CA, including its ability to counteract obesity-associated hyperglycaemia and insulin resistance. However, the mechanisms underlying its anti-diabetic responses are not fully understood. In this study, we hypothesized that CA may act to improve glycaemic status through enhancing peripheral glucose clearance. Herein, we demonstrate that CA acts to mimic the metabolic actions of insulin by directly stimulating glucose uptake in rat skeletal L6 myotubes, concomitant with increased translocation of the GLUT4 glucose transporter to the plasma membrane. Mechanistically, CA-induced glucose transport was found to be dependent on protein kinase B (PKB/Akt) but not AMPK, despite both kinases being activated by CA. Crucially, in accordance with its ability to activate PKB and stimulate glucose uptake, we show that CA conveys these effects through a pathway involving PME-1 (protein phosphatase methylesterase-1), a key negative regulator of the serine/threonine phosphatase PP2A (protein phosphatase 2A). Herein, we demonstrate that CA promotes PME-1 mediated demethylation of the PP2A catalytic subunit leading to its suppressed activity, and in doing so, alleviates the repressive action of PP2A towards PKB. Collectively, our findings provide new insight into how CA may improve glucose homeostasis through enhancing peripheral glucose clearance in tissues such as skeletal muscle through a PME-1/PP2A/PKB signalling axis, thereby mitigating pathological effects associated with the hyperglycaemic state.

  10. Niflumic acid differentially modulates two types of skeletal ryanodine-sensitive Ca(2+)-release channels.

    Science.gov (United States)

    Oba, T

    1997-11-01

    The effects of niflumic acid on ryanodine receptors (RyRs) of frog skeletal muscle were studied by incorporating sarcoplasmic reticulum (SR) vesicles into planar lipid bilayers. Frog muscle had two distinct types of RyRs in the SR: one showed a bell-shaped channel activation curve against cytoplasmic Ca2+ or niflumic acid, and its mean open probability (Po) was increased by perchlorate at 20-30 mM (termed "alpha-like" RyR); the other showed a sigmoidal activation curve against Ca2+ or niflumic acid, with no effect on perchlorate (termed "beta-like" RyR). The unitary conductance and reversal potential of both channel types were unaffected after exposure to niflumic acid when clamped at 0 mV. When clamped at more positive potentials, the beta-like RyR channel rectified this, increasing the unitary current. Treatment with niflumic acid did not inhibit the response of both channels to Ca2+ release channel modulators such as caffeine, ryanodine, and ruthenium red. The different effects of niflumic acid on Po and the unitary current amplitude in both types of channels may be attributable to the lack or the presence of inactivation sites and/or distinct responses to agonists.

  11. The skeletal muscle arachidonic acid cascade in health and inflammatory disease.

    Science.gov (United States)

    Korotkova, Marina; Lundberg, Ingrid E

    2014-05-01

    Muscle atrophy and weakness are often observed in patients with chronic inflammatory diseases, and are the major clinical features of the autoimmune myopathies, polymyositis and dermatomyositis. A general understanding of the pathogenesis of muscle atrophy and the impaired muscle function associated with chronic inflammatory diseases has not been clarified. In this context, arachidonic acid metabolites, such as the prostaglandin and leukotriene subfamilies, are of interest because they contribute to immune and nonimmune processes. Accumulating evidence suggests that prostaglandins and leukotrienes are involved in causing muscular pain and inflammation, and also in myogenesis and the repair of muscles. In this Review, we summarize novel findings that implicate prostaglandins and leukotrienes in the muscle atrophy and weakness that occur in inflammatory diseases of the muscles, with a focus on inflammatory myopathies. We discuss the role of the arachidonic acid cascade in skeletal muscle growth and function, and individual metabolites as potential therapeutic targets for the treatment of inflammatory muscle diseases.

  12. Palmitoleic acid prevents palmitic acid-induced macrophage activation and consequent p38 MAPK-mediated skeletal muscle insulin resistance.

    Science.gov (United States)

    Talbot, Nicola A; Wheeler-Jones, Caroline P; Cleasby, Mark E

    2014-08-05

    Obesity and saturated fatty acid (SFA) treatment are both associated with skeletal muscle insulin resistance (IR) and increased macrophage infiltration. However, the relative effects of SFA and unsaturated fatty acid (UFA)-activated macrophages on muscle are unknown. Here, macrophages were treated with palmitic acid, palmitoleic acid or both and the effects of the conditioned medium (CM) on C2C12 myotubes investigated. CM from palmitic acid-treated J774s (palm-mac-CM) impaired insulin signalling and insulin-stimulated glycogen synthesis, reduced Inhibitor κBα and increased phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase in myotubes. p38 MAPK inhibition or siRNA partially ameliorated these defects, as did addition of tumour necrosis factor-α blocking antibody to the CM. Macrophages incubated with both FAs generated CM that did not induce IR, while palmitoleic acid-mac-CM alone was insulin sensitising. Thus UFAs may improve muscle insulin sensitivity and counteract SFA-mediated IR through an effect on macrophage activation.

  13. Creb coactivators direct anabolic responses and enhance performance of skeletal muscle.

    Science.gov (United States)

    Bruno, Nelson E; Kelly, Kimberly A; Hawkins, Richard; Bramah-Lawani, Mariam; Amelio, Antonio L; Nwachukwu, Jerome C; Nettles, Kendall W; Conkright, Michael D

    2014-05-01

    During the stress response to intense exercise, the sympathetic nervous system (SNS) induces rapid catabolism of energy reserves through the release of catecholamines and subsequent activation of protein kinase A (PKA). Paradoxically, chronic administration of sympathomimetic drugs (β-agonists) leads to anabolic adaptations in skeletal muscle, suggesting that sympathetic outflow also regulates myofiber remodeling. Here, we show that β-agonists or catecholamines released during intense exercise induce Creb-mediated transcriptional programs through activation of its obligate coactivators Crtc2 and Crtc3. In contrast to the catabolic activity normally associated with SNS function, activation of the Crtc/Creb transcriptional complex by conditional overexpression of Crtc2 in the skeletal muscle of transgenic mice fostered an anabolic state of energy and protein balance. Crtc2-overexpressing mice have increased myofiber cross-sectional area, greater intramuscular triglycerides and glycogen content. Moreover, maximal exercise capacity was enhanced after induction of Crtc2 expression in transgenic mice. Collectively these findings demonstrate that the SNS-adrenergic signaling cascade coordinates a transient catabolic stress response during high-intensity exercise, which is followed by transcriptional reprogramming that directs anabolic changes for recovery and that augments subsequent exercise performance.

  14. Effect of exercise and obesity on skeletal muscle amino acid uptake

    Energy Technology Data Exchange (ETDEWEB)

    Friedman, J.E.

    1988-01-01

    To determine if amino acid uptake by muscle of the obese Zucker rat is impaired, epitrochlearis (EPI) and soleus strip (SOL) muscles from 32 pairs of female lean (Fa/-) and obese (fa/fa) Zucker rats were incubated using ({sup 14}C){alpha}-aminoisobutyric acid (AIB). Because contractile activity also influences amino acid uptake, the effect of acute endurance exercise on amino acid uptake by skeletal muscle from lean and obese rats was also studied. Muscle wet and dry weights were similar in lean and obese rats. However, both muscle protein content and concentration from obese rats were significantly reduced. In preliminary studies, pinning EPI at resting length during incubation significantly increased AIB uptake and reduced muscle water accumulation. AIB uptake was similar in stripped and intact SOL. Lean and obese rats were studied at rest or following a 1 hr treadmill run at 8% grade Muscles were pinned, and preincubated for 30 min at 37{degree}C in Krebs Ringer bicarbonate buffer (KRB) containing 5mM glucose under 95:5 O{sub 2}/CO{sub 2}, followed by 30, 60, 120, or 180 min of incubation in KRB with 0.5 mM AIB, ({sup 14}C)-AIB to measure amino acid, and ({sup 3}H)-inulin to determine extracellular water.

  15. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle

    DEFF Research Database (Denmark)

    Bultot, Laurent; Jensen, Thomas Elbenhardt; Lai, Yu-Chiang

    2016-01-01

    be beneficial for both purposes. Here, we investigated if a recently described potent AMPK activator called 991, in combination with the commonly used activator 5-aminoimidazole-4-carboxamide riboside or contraction, further enhances AMPK activity and glucose transport in mouse skeletal muscle ex vivo. Given...... that the γ3-subunit is exclusively expressed in skeletal muscle and has been implicated in contraction-induced glucose transport, we measured the activity of AMPKγ3 as well as ubiquitously expressed γ1-containing complexes. We initially validated the specificity of the antibodies for the assessment...... profoundly enhanced AMPKγ1/γ3 complex activation and glucose transport compared with any of the single treatments. The study demonstrates the utility of a dual activator approach to achieve a greater activation of AMPK and downstream physiological responses in various cell types, including skeletal muscle....

  16. Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria.

    Science.gov (United States)

    Messer, Jeffrey I; Jackman, Matthew R; Willis, Wayne T

    2004-03-01

    Carbohydrate depletion precipitates fatigue in skeletal muscle, but, because pyruvate provides both acetyl-CoA for mainline oxidation and anaplerotic carbon to the citric acid cycle (CAC), the mechanism remains obscure. Thus pyruvate and CAC kinetic parameters were independently quantified in mitochondria isolated from rat mixed skeletal muscle. Mitochondrial oxygen consumption rate (Jo) was measured polarographically while either pyruvate or malate was added stepwise in the presence of a saturating concentration of the other substrate. These substrate titrations were carried out across a physiological range of fixed extramitochondrial ATP free energy states (DeltaGP), established with a creatine kinase energy clamp, and also at saturating [ADP]. The apparent Km,malate for mitochondrial Jo ranged from 21 to 32 microM, and the apparent Km,pyruvate ranged from 12 to 26 microM, with both substrate Km values increasing as DeltaGP declined. Vmax for both substrates also increased as DeltaGP fell, reflecting thermodynamic control of Jo. Reported in vivo skeletal muscle [malate] are >10-fold greater than the Km,malate determined in this study. In marked contrast, the K(m,pyruvate) determined is near the [pyruvate] reported in muscle approaching exhaustion associated with glycogen depletion. When data were evaluated in the context of a linear thermodynamic force-flow (DeltaGP-Jo) relationship, the DeltaGP-Jo slope was essentially insensitive to changes in [malate] in the range observed in vivo but decreased markedly with declining [pyruvate] across the physiological range. Mitochondrial respiration is particularly sensitive to variations in [pyruvate] in the physiological range. In contrast, physiological [malate] exerts very little, if any, influence on mitochondrial pyruvate oxidation measured in vitro.

  17. Cardiolipin linoleic acid content and mitochondrial cytochrome c oxidase activity are associated in rat skeletal muscle.

    Science.gov (United States)

    Fajardo, Val Andrew; McMeekin, Lauren; Saint, Caitlin; LeBlanc, Paul J

    2015-04-01

    Cardiolipin (CL) is an inner-mitochondrial membrane phospholipid that is important for optimal mitochondrial function. Specifically, CL and CL linoleic (18:2ω6) content are known to be positively associated with cytochrome c oxidase (COX) activity. However, this association has not been examined in skeletal muscle. In this study, rats were fed high-fat diets with a naturally occurring gradient in linoleic acid (coconut oil [CO], 5.8%; flaxseed oil [FO], 13.2%; safflower oil [SO], 75.1%) in an attempt to alter both mitochondrial CL fatty acyl composition and COX activity in rat mixed hind-limb muscle. In general, mitochondrial membrane lipid composition was fairly resistant to dietary treatments as only modest changes in fatty acyl composition were detected in CL and other major mitochondrial phospholipids such as phosphatidylcholine (PC) and phosphatidylethanolamine (PE). As a result of this resistance, CL 18:2ω6 content was not different between the dietary groups. Consistent with the lack of changes in CL 18:2ω6 content, mitochondrial COX activity was also not different between the dietary groups. However, correlational analysis using data obtained from rats across the dietary groups showed a significant relationship (p = 0.009, R(2) = 0.21). Specifically, our results suggest that CL 18:2ω6 content may positively influence mitochondrial COX activity thereby making this lipid molecule a potential factor related to mitochondrial health and function in skeletal muscle.

  18. Overexpression of PGC-1α Increases Fatty Acid Oxidative Capacity of Human Skeletal Muscle Cells

    Directory of Open Access Journals (Sweden)

    Nataša Nikolić

    2012-01-01

    Full Text Available We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deoxyglucose uptake were decreased, possibly due to upregulation of PDK4 mRNA. Expression of fast fiber-type gene marker (MHCIIa was decreased. Compared to skeletal muscle in vivo, PGC-1α overexpression increased expression of several genes, which were downregulated during the process of cell isolation and culturing. In conclusion, PGC-1α overexpression increased oxidative capacity of cultured myotubes by improving lipid metabolism, increasing expression of genes involved in regulation of mitochondrial function and biogenesis, and decreasing expression of MHCIIa. These results suggest that therapies aimed at increasing PGC-1α expression may have utility in treatment of obesity and obesity-related diseases.

  19. Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle

    DEFF Research Database (Denmark)

    Sacchetti, M; Saltin, B; Osada, T

    2002-01-01

    The present study was undertaken to investigate the fate of blood-borne non-esterified fatty acids (NEFA) entering contracting and non-contracting knee extensor muscles of healthy young individuals. [U-(13)C]-palmitate was infused into a forearm vein during 5 h of one-legged knee extensor exercise.......05) in the contracting muscle, whereas it was unchanged in the non-contracting muscle. The uptake of plasma NEFA, as well as the proportion directed towards oxidation, was higher in the exercising compared to the non-exercising leg, whereas the rate of palmitate incorporation into mTAG was fourfold lower (0.70 +/- 0.......14 vs. 0.17 +/- 0.04 micromol (g dry wt)(-1) h(-1); P contracting and non-contracting muscle, respectively. These findings demonstrate that mTAG in human skeletal muscle is continuously synthesised...

  20. Skeletal cell differentiation is enhanced by atmospheric dielectric barrier discharge plasma treatment.

    Directory of Open Access Journals (Sweden)

    Marla J Steinbeck

    signaling to enhance differentiation, and suggest this technology could be used to enhance bone fusion and improve healing after skeletal injury.

  1. Skeletal cell differentiation is enhanced by atmospheric dielectric barrier discharge plasma treatment.

    Science.gov (United States)

    Steinbeck, Marla J; Chernets, Natalie; Zhang, Jun; Kurpad, Deepa S; Fridman, Gregory; Fridman, Alexander; Freeman, Theresa A

    2013-01-01

    differentiation, and suggest this technology could be used to enhance bone fusion and improve healing after skeletal injury.

  2. Distinct amino acid-sensing mTOR pathways regulate skeletal myogenesis.

    Science.gov (United States)

    Yoon, Mee-Sup; Chen, Jie

    2013-12-01

    Signaling through the mammalian target of rapamycin (mTOR) in response to amino acid availability controls many cellular and developmental processes. mTOR is a master regulator of myogenic differentiation, but the pathways mediating amino acid signals in this process are not known. Here we examine the Rag GTPases and the class III phosphoinositide 3-kinase (PI3K) Vps34, two mediators of amino acid signals upstream of mTOR complex 1 (mTORC1) in cell growth regulation, for their potential involvement in myogenesis. We find that, although both Rag and Vps34 mediate amino acid activation of mTORC1 in C2C12 myoblasts, they have opposing functions in myogenic differentiation. Knockdown of RagA/B enhances, whereas overexpression of active RagB/C mutants impairs, differentiation, and this inhibitory function of Rag is mediated by mTORC1 suppression of the IRS1-PI3K-Akt pathway. On the other hand, Vps34 is required for myogenic differentiation. Amino acids activate a Vps34-phospholipase D1 (PLD1) pathway that controls the production of insulin-like growth factor II, an autocrine inducer of differentiation, through the Igf2 muscle enhancer. The product of PLD, phosphatidic acid, activates the enhancer in a rapamycin-sensitive but mTOR kinase-independent manner. Our results uncover amino acid-sensing mechanisms controlling the homeostasis of myogenesis and underline the versatility and context dependence of mTOR signaling.

  3. Effect of ascorbic acid on fatigue of skeletal muscle fibres in long-term cold exposed Sprague Dawley rats.

    Science.gov (United States)

    Rashid, Aneeqa; Khan, Umar Ali; Ayub, Muhammad

    2011-01-01

    On exposure to prolonged cold temperature, the body responds for effective heat production both by shivering and non-shivering thermogenesis. Cold exposure increases the production of reactive oxygen species which influence the sarcoplasmic reticulum Ca++ release from the skeletal muscles and affect their contractile properties. The role of ascorbic acid supplementation on force of contraction during fatigue of cold exposed skeletal muscles was evaluated in this study. Ninety healthy, male Sprague Dawley rats were randomly divided into three groups of control (I), cold exposed (II), and cold exposed with ascorbic acid 500 mg/L supplementation mixed in drinking water (III). Group II and III were given cold exposure by keeping their cages in ice-filled tubs for 1 hr/day for one month. After one month, the extensor digitorum longus muscle was dissected out and force of contraction during fatigue in the skeletal muscle fibres was analysed on a computerised data acquisition system. The cold exposed group showed a significant delay in the force of contraction during fatigue of skeletal muscle fibres compared to control group. Group III showed easy fatigability and a better force of contraction than the cold exposed group. Ascorbic acid increases the force of contraction and decreases resistance to fatigue in the muscles exposed to chronic cold.

  4. Enhanced acid tolerance of Rhizopus oryzae during fumaric acid production.

    Science.gov (United States)

    Liu, Ying; Lv, Chunwei; Xu, Qing; Li, Shuang; Huang, He; Ouyang, Pingkai

    2015-02-01

    Ensuring a suitable pH in the culture broth is a major problem in microorganism-assisted industrial fermentation of organic acids. To address this issue, we investigated the physiological changes in Rhizopus oryzae at different extracellular pH levels and attempted to solve the issue of cell shortage under low pH conditions. We compared various parameters, such as membrane fatty acids' composition, intracellular pH, and adenosine triphosphate (ATP) concentration. It was found that the shortage of intracellular ATP might be the main reason for the low rate of fumaric acid production by R. oryzae under low pH conditions. When 1 g/l citrate was added to the culture medium at pH 3.0, the intracellular ATP concentration increased from 0.4 to 0.7 µmol/mg, and the fumaric acid titer was enhanced by 63% compared with the control (pH 3.0 without citrate addition). The final fumaric acid concentration at pH 3.0 reached 21.9 g/l after 96 h of fermentation. This strategy is simple and feasible for industrial fumaric acid production under low pH conditions.

  5. Fatty Acid Incubation of Myotubues from Humans with Type 2 Diabetes Leads to Enhanced Release of Beta Oxidation Products Due to Impaired Fatty Acid Oxidation

    DEFF Research Database (Denmark)

    Wensaas, Andreas J; Rustan, Arild C; Just, Marlene

    2008-01-01

    Objective: Increased availability of fatty acids is important for accumulation of intracellular lipids and development of insulin resistance in human myotubes. It is unknown whether different types of fatty acids like eicosapentaenoic acid (EPA) or tetradecylthioacetic acid (TTA) influence...... these processes. Research Design and Methods: We examined fatty acid and glucose metabolism, and gene expression in cultured human skeletal muscle cells from control and T2D individuals after four days preincubation with EPA or TTA. Results: T2D myotubes exhibited reduced formation of CO(2) from palmitic acid (PA....... EPA markedly enhanced TAG accumulation in myotubes, more pronounced in T2D cells. TAG accumulation and fatty acid oxidation were inversely correlated only after EPA preincubation, and total level of acyl-CoA was reduced. Glucose oxidation (CO(2) formation) was enhanced and lactate production decreased...

  6. Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus

    OpenAIRE

    Brown, Laura D.; Rozance, Paul J.; Barry, James S.; Friedman, Jacob E.; Hay, William W.

    2008-01-01

    During late gestation, amino acids and insulin promote skeletal muscle protein synthesis. However, the independent effects of amino acids and insulin on the regulation of mRNA translation initiation in the fetus are relatively unknown. The purpose of this study was to determine whether acute amino acid infusion in the late-gestation ovine fetus, with and without a simultaneous increase in fetal insulin concentration, activates translation initiation pathway(s) in skeletal muscle. Fetuses rece...

  7. Protective Effect of Unsaturated Fatty Acids on Palmitic Acid-Induced Toxicity in Skeletal Muscle Cells is not Mediated by PPARδ Activation.

    Science.gov (United States)

    Tumova, Jana; Malisova, Lucia; Andel, Michal; Trnka, Jan

    2015-10-01

    Unsaturated free fatty acids (FFA) are able to prevent deleterious effects of saturated FFA in skeletal muscle cells although the mechanisms involved are still not completely understood. FFA act as endogenous ligands of peroxisome proliferator-activated receptors (PPAR), transcription factors regulating the expression of genes involved in lipid metabolism. The aim of this study was to determine whether activation of PPARδ, the most common PPAR subtype in skeletal muscle, plays a role in mediating the protective effect of unsaturated FFA on saturated FFA-induced damage in skeletal muscle cells and to examine an impact on mitochondrial respiration. Mouse C2C12 myotubes were treated for 24 h with different concentrations of saturated FFA (palmitic acid), unsaturated FFA (oleic, linoleic and α-linolenic acid), and their combinations. PPARδ agonist GW501516 and antagonist GSK0660 were also used. Both mono- and polyunsaturated FFA, but not GW501516, prevented palmitic acid-induced cell death. Mono- and polyunsaturated FFA proved to be effective activators of PPARδ compared to saturated palmitic acid; however, in combination with palmitic acid their effect on PPARδ activation was blocked and stayed at the levels observed for palmitic acid alone. Unsaturated FFA at moderate physiological concentrations as well as GW501516, but not palmitic acid, mildly uncoupled mitochondrial respiration. Our results indicate that although unsaturated FFA are effective activators of PPARδ, their protective effect on palmitic acid-induced toxicity is not mediated by PPARδ activation and subsequent induction of lipid regulatory genes in skeletal muscle cells. Other mechanisms, such as mitochondrial uncoupling, may underlie their effect.

  8. Enhanced Myogenesis in adult skeletal muscle by transgenic expression of Myostatin Propeptide

    Science.gov (United States)

    Skeletal muscle growth and maintenance are essential for human health. One of the muscle regulatory genes, namely myostatin, a member of transforming growth factor-ß, plays a dominant role in the genetic control of muscle mass. Transgenic expression of myostatin propeptide in skeletal muscle showed ...

  9. Effects of dietary omega-3 polyunsaturated Fatty acids on the skeletal-muscle blood-flow response to exercise in rats.

    Science.gov (United States)

    Stebbins, Charles L; Hammel, Lauren E; Marshal, Benjamin J; Spangenberg, Espen E; Musch, Timothy I

    2010-12-01

    The polyunsaturated fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) affect vascular relaxation and involve factors (e.g., nitric oxide) that contribute to exercise-induced increases in skeletal-muscle blood flow (Q). The authors investigated whether DHA and EPA supplementation augments skeletal-muscle Q and vascular conductance (VC) and attenuates renal and splanchnic Q and VC in exercising rats. Rats were fed a diet of 5% lipids by weight, of which 20% was DHA and 30% EPA (PUFA group, n = 9), or 5% safflower oil (SO group, n = 8) for 6 wk. Heart rate (HR), blood pressure (MAP), and hind-limb, renal, and splanchnic Q were measured at rest and during moderate treadmill running. MAP, HR, and renal and splanchnic Q and VC were similar between the 2 groups at rest and during exercise. In the PUFA group, Q (158 ± 27 vs. 128 ± 28 ml × min⁻¹ × 100 g⁻¹) and VC (1.16 ± 0.21 vs. 0.92 ± 0.23 ml × min⁻¹ × 100 g⁻¹ × mm Hg⁻¹) were greater in the exercising hind-limb muscle. Q and VC were also higher in 8 of 28 and 11 of 28 muscles and muscle parts, respectively. These increases were positively correlated to the percent sum of Types I and IIa fibers. Results suggest that DHA+EPA (a) enhances Q and VC in active skeletal muscle (especially Type I and IIa fibers) and that the increase in Q is due to an increase in cardiac output secondary to increases in VC and (b) has no apparent influence on vasoconstriction in renal and splanchnic tissue.

  10. Glutamine deficiency in extracellular fluid exerts adverse effects on protein and amino acid metabolism in skeletal muscle of healthy, laparotomized, and septic rats.

    Science.gov (United States)

    Holecek, Milan; Sispera, Ludek

    2014-05-01

    Characteristic feature of critical illness, such as trauma and sepsis, is muscle wasting associated with activated oxidation of branched-chain amino acids (valine, leucine, isoleucine) and enhanced release of glutamine (GLN) to the blood. GLN consumption in visceral tissues frequently exceeds its release from muscle resulting in GLN deficiency that may exert adverse effects on the course of the disease. In the present study, we investigated the effects of GLN depletion in extracellular fluid on GLN production and protein and amino acid metabolism in skeletal muscle of healthy, laparotomized, and septic rats. Cecal ligation and puncture (CLP) was used as a model of sepsis. After 24 h, soleus muscle (SOL, slow-twitch, red muscle) and extensor digitorum longus (EDL, fast-twitch, white muscle) were isolated and incubated in a medium containing 0.5 mM GLN or without GLN. L-[1-(14)C]leucine was used to estimate protein synthesis and leucine oxidation, 3-methylhistidine release was used to evaluate myofibrillar protein breakdown. CLP increased GLN release from muscle, protein breakdown and leucine oxidation, and decreased protein synthesis. The effects were more pronounced in EDL. Alterations induced by laparotomy were similar to those observed in sepsis, but of a lower extent. GLN deficiency in medium enhanced GLN release and decreased intramuscular GLN concentration, decreased protein synthesis in muscles of intact and laparotomized rats, and enhanced leucine oxidation in SOL of intact and protein breakdown in SOL of laparotomized rats. It is concluded that (1) fast-twitch fibers are more sensitive to septic stimuli than slow-twitch fibers, (2) extracellular GLN deficiency may exert adverse effects on protein and amino acid metabolism in skeletal muscle, and (3) muscles of healthy and laparotomized animals are more sensitive to GLN deficiency than muscles of septic animals.

  11. Dietary fish oil delays hypoxic skeletal muscle fatigue and enhances caffeine-stimulated contractile recovery in the rat in vivo hindlimb.

    Science.gov (United States)

    Peoples, Gregory E; McLennan, Peter L

    2017-06-01

    Oxygen efficiency influences skeletal muscle contractile function during physiological hypoxia. Dietary fish oil, providing docosahexaenoic acid (DHA), reduces the oxygen cost of muscle contraction. This study used an autologous perfused rat hindlimb model to examine the effects of a fish oil diet on skeletal muscle fatigue during an acute hypoxic challenge. Male Wistar rats were fed a diet rich in saturated fat (SF), long-chain (LC) n-6 polyunsaturated fatty acids (n-6 PUFA), or LC n-3 PUFA DHA from fish oil (FO) (8 weeks). During anaesthetised and ventilated conditions (normoxia 21% O2 (SaO2-98%) and hypoxia 14% O2 (SaO2-89%)) the hindlimb was perfused at a constant flow and the gastrocnemius-plantaris-soleus muscle bundle was stimulated via sciatic nerve (2 Hz, 6-12V, 0.05 ms) to established fatigue. Caffeine (2.5, 5, 10 mM) was supplied to the contracting muscle bundle via the arterial cannula to assess force recovery. Hypoxia, independent of diet, attenuated maximal twitch tension (normoxia: 82 ± 8; hypoxia: 41 ± 2 g·g(-1) tissue w.w.). However, rats fed FO sustained higher peak twitch tension compared with the SF and n-6 PUFA groups (P recovery was enhanced in the FO-fed animals (SF: 41 ± 3; n-6 PUFA: 40 ± 4; FO: 52 ± 7% recovery; P < 0.05). These results support a physiological role of DHA in skeletal muscle membranes when exposed to low-oxygen stress that is consistent with the attenuation of muscle fatigue under physiologically normoxic conditions.

  12. Ca2+ effects on glucose transport and fatty acid oxidation in L6 skeletal muscle cell cultures

    Directory of Open Access Journals (Sweden)

    Darrick Balu

    2016-03-01

    We did find a Ca2+ stimulation (using either caffeine or ionomycin of fatty acid oxidation. This was observed in the absence (but not the presence of added glucose. We conclude that Ca2+ stimulates fatty acid oxidation at a mitochondrial site, secondary to malonyl CoA inhibition (represented by the presence of glucose in our experiments. In summary, the experiments resolve a controversy on Ca2+ stimulation of glucose transport by skeletal muscle, introduce an important experimental consideration for the measurement of glucose transport, and uncover a new site of action for Ca2+ stimulation of fatty acid oxidation.

  13. Heat shock pretreatment enhances porcine myoblasts survival after autotransplantation in intact skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    YANG Sheng; Thomas LAUMONIER; Jacques MENETREY

    2007-01-01

    Myoblast transplantation (MT) is a cell-based gene therapy treatment, representing a potential treatment for Duchenne muscular dystrophy (DMD), cardiac failure and muscle trauma. The rapid and massive death of transplanted cells after MT is considered as a major hurdle which limits the efficacy of MT treatment. Heat shock proteins (HSPs) are overexpressed when cells undergo various insults. HSPs have been described to protect cells in vivo and in vitro against diverse insults. The aim of our study is to investigate whether HSP overexpression could increase myoblast survival after autotransplantation in pig intact skeletal muscle. HSP expression was induced by warming the cells at 42℃ for 1 h. HSP70 expression was quantified by Western blot and flow cytometry 24 h after the treatment. To investigate the myogenic characteristics of myoblasts, desmin and CD56 were analysed by Western blot and flow cytometry; and the fusion index was measured. We also quantified cell survival after autologous transplantation in pig intact skeletal muscle and followed cell integration. Results showed that heat shock treatment of myoblasts induced a significative overexpression of the HSP70 (P<0.01) without loss of their myogenic characteristics as assessed by FACS and fusion index. In vivo (n=7), the myoblast survival rate was not significantly different at 24 h between heat shock treated and nontreated cells (67.69%±8.35% versus 58.79%±8.35%, P>0.05). However, the myoblast survival rate in the heat shocked cells increased by twofold at 48 h (53.32%±8.22% versus 28.27%±6.32%, P<0.01)and more than threefold at 120 h (26.33%±5.54% versus 8.79%±2.51%, P<0.01). Histological analysis showed the presence of non-heat shocked and heat shocked donor myoblasts fused with host myoblasts. These results suggested that heat shock pretreatment increased the HSP70 expression in porcine myoblasts, and improved the survival rate after autologous transplantation. Therefore, heat shock

  14. Heat shock pretreatment enhances porcine myoblasts survival after autotransplantation in intact skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Myoblast transplantation (MT) is a cell-based gene therapy treatment, representing a potential treat-ment for Duchenne muscular dystrophy (DMD), cardiac failure and muscle trauma. The rapid and mas-sive death of transplanted cells after MT is considered as a major hurdle which limits the efficacy of MT treatment. Heat shock proteins (HSPs) are overexpressed when cells undergo various insults. HSPs have been described to protect cells in vivo and in vitro against diverse insults. The aim of our study is to investigate whether HSP overexpression could increase myoblast survival after autotransplantation in pig intact skeletal muscle. HSP expression was induced by warming the cells at 42℃ for 1 h. HSP70 expression was quantified by Western blot and flow cytometry 24 h after the treatment. To investigate the myogenic characteristics of myoblasts, desmin and CD56 were analysed by Western blot and flow cytometry; and the fusion index was measured. We also quantified cell survival after autologous transplantation in pig intact skeletal muscle and followed cell integration. Results showed that heat shock treatment of myoblasts induced a significative overexpression of the HSP70 (P < 0.01) without loss of their myogenic characteristics as assessed by FACS and fusion index. In vivo (n=7), the myoblast survival rate was not significantly different at 24 h between heat shock treated and non- treated cells (67.69% ± 8.35% versus 58.79% ± 8.35%, P > 0.05). However, the myoblast survival rate in the heat shocked cells increased by twofold at 48 h (53.32% ± 8.22% versus 28.27% ± 6.32%, P < 0.01) and more than threefold at 120 h (26.33% ± 5.54% versus 8.79% ± 2.51%, P < 0.01). Histological analy-sis showed the presence of non-heat shocked and heat shocked donor myoblasts fused with host myoblasts. These results suggested that heat shock pretreatment increased the HSP70 expression in porcine myoblasts, and improved the survival rate after autologous transplantation

  15. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    OpenAIRE

    Hirotaka Yamamoto; Katsutaro Morino; Lemecha Mengistu; Taishi Ishibashi; Kohei Kiriyama; Takao Ikami; Hiroshi Maegawa

    2016-01-01

    Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mi...

  16. Cacao liquor procyanidin extract improves glucose tolerance by enhancing GLUT4 translocation and glucose uptake in skeletal muscle

    OpenAIRE

    Yamashita, Yoko; Okabe, Masaaki; Natsume, Midori; Ashida, Hitoshi

    2012-01-01

    Hyperglycaemia and insulin resistance are associated with the increased risk of the metabolic syndrome and other severe health problems. The insulin-sensitive GLUT4 regulates glucose homoeostasis in skeletal muscle and adipose tissue. In this study, we investigated whether cacao liquor procyanidin (CLPr) extract, which contains epicatechin, catechin and other procyanidins, improves glucose tolerance by promoting GLUT4 translocation and enhances glucose uptake in muscle cells. Our results demo...

  17. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata

    Directory of Open Access Journals (Sweden)

    Md. Shahidul Haque

    2014-06-01

    Full Text Available Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the skeletal muscle and the increased protein in the skeletal muscle was reduced significantly. The results appear to indicate that cold acclimation induces a metabolic change involving cellular protein content tissue specifically and arsenic might be involved in impairment of the cold-induced effect. To clarify the molecular mechanism, groups of fish exposed to cold for 1 h and 2 h had significantly increased RNA in the skeletal muscle compared to control fish, however, a higher level was found after 2 h of treatment and the enhanced RNA induced by cold was almost completely prevented by Na2HAsO4. Our findings will give a new insight into the survival process of this species while toxic arsenic prevents this cellular bioprocess.

  18. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway

    Science.gov (United States)

    Feng, Xiaoli; Luo, Zhidan; Ma, Liqun; Ma, Shuangtao; Yang, Dachun; Zhao, Zhigang; Yan, Zhencheng; He, Hongbo; Cao, Tingbing; Liu, Daoyan; Zhu, Zhiming

    2011-01-01

    Abstract Clinical trials have shown that angiotensin II receptor blockers reduce the new onset of diabetes in hypertensives; however, the underlying mechanisms remain unknown. We investigated the effects of telmisartan on peroxisome proliferator activated receptor γ (PPAR-δ) and the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in cultured myotubes, as well as on the running endurance of wild-type and PPAR-δ-deficient mice. Administration of telmisartan up-regulated levels of PPAR-δ and phospho-AMPKα in cultured myotubes. However, PPAR-δ gene deficiency completely abolished the telmisartan effect on phospho-AMPKαin vitro. Chronic administration of telmisartan remarkably prevented weight gain, enhanced running endurance and post-exercise oxygen consumption, and increased slow-twitch skeletal muscle fibres in wild-type mice, but these effects were absent in PPAR-δ-deficient mice. The mechanism is involved in PPAR-δ-mediated stimulation of the AMPK pathway. Compared to the control mice, phospho-AMPKα level in skeletal muscle was up-regulated in mice treated with telmisartan. In contrast, phospho-AMPKα expression in skeletal muscle was unchanged in PPAR-δ-deficient mice treated with telmisartan. These findings highlight the ability of telmisartan to improve skeletal muscle function, and they implicate PPAR-δ as a potential therapeutic target for the prevention of type 2 diabetes. PMID:20477906

  19. Regulation of protein degradation pathways by amino acids and insulin in skeletal muscle of neonatal pigs

    Institute of Scientific and Technical Information of China (English)

    Agus Suryawan; Teresa ADavis

    2014-01-01

    Background:The rapid gain in lean mass in neonates requires greater rates of protein synthesis than degradation. We previously delineated the molecular mechanisms by which insulin and amino acids, especially leucine, modulate skeletal muscle protein synthesis and how this changes with development. In the current study, we identified mechanisms involved in protein degradation regulation. In experiment 1, 6-and 26-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic, 2) euinsulinemic-euglycemic-hyperaminoacidemic, and 3) hyperinsulinemic-euglycemic-euaminoacidemic clamps for 2 h. In experiment 2, 5-d-old pigs were studied during 1) euinsulinemic-euglycemic-euaminoacidemic-euleucinemic, 2) euinsulinemic-euglycemic-hypoaminoacidemic-hyperleucinemic, and 3) euinsulinemic-euglycemic-euaminoacidemic-hyperleucinemic clamps for 24 h. We determined in muscle indices of ubiquitin-proteasome, i.e., atrogin-1 (MAFbx) and muscle RING-finger protein-1 (MuRF1) and autophagy-lysosome systems, i.e., unc51-like kinase 1 (UKL1), microtubule-associated protein light chain 3 (LC3), and lysosomal-associated membrane protein 2 (Lamp-2). For comparison, we measured ribosomal protein S6 (rpS6) and eukaryotic initiation factor 4E (eIF4E) activation, components of translation initiation. Results:Abundance of atrogin-1, but not MuRF1, was greater in 26-than 6-d-old pigs and was not affected by insulin, amino acids, or leucine. Abundance of ULK1 and LC3 was higher in younger pigs and not affected by treatment. The LC3-II/LC3-I ratio was reduced and ULK1 phosphorylation increased by insulin, amino acids, and leucine. These responses were more profound in younger pigs. Abundance of Lamp-2 was not affected by treatment or development. Abundance of eIF4E, but not rpS6, was higher in 6-than 26-d-old-pigs but unaffected by treatment. Phosphorylation of eIF4E was not affected by treatment, however, insulin, amino acids, and leucine stimulated rpS6 phosphorylation, and the

  20. Genes associated with long-chain omega-3 fatty acids in bovine skeletal muscle.

    Science.gov (United States)

    Perez, R; Cañón, J; Dunner, S

    2010-01-01

    Long-chain omega-3 fatty acids (n-3 FAs) influence meat tenderness, juiciness, and flavor, and are beneficial to human health. The percentage of long-chain n-3 FAs in total FAs is termed the omega-3 index (O3I). It is thus of great interest to favor rising this index in bovine skeletal muscle, to obtain healthier, tastier, and more nutritive meat. This study was aimed to detect transcriptomic variations related to O3I in muscles in 15-month-old males of 4 Spanish cattle breeds raised under the same conditions. Through the analysis of extreme O3I phenotypes, 3 genes of interest (AANAT, UCP2 and AHA1) were identified. AANAT and UCP2 were strongly up-regulated, while AHA1 was repressed in animals with a high O3I. Moreover, gene expression differed between GDF8-null animal muscles (tested for nt821del11 and Q204X mutations) and the wild-type muscles for genes GDH1, IGF2R, FADS1, ASPH, and AIM1, all showing down-regulation in Asturiana de los Valles calves with muscle hypertrophy (GDF8-null). This shows that in GDF8-null animals other pathways are used for FA synthesis.

  1. Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo.

    Science.gov (United States)

    Mai, Knut; Andres, Janin; Bobbert, Thomas; Assmann, Anke; Biedasek, Katrin; Diederich, Sven; Graham, Ian; Larson, Tony R; Pfeiffer, Andreas F H; Spranger, Joachim

    2012-01-01

    The ratio of unsaturated to saturated long-chain fatty acids (LC-FAs) in skeletal muscle has been associated with insulin resistance. Some animal data suggest a modulatory effect of peroxisome proliferator receptor γ (PPARγ) stimulation on stearoyl-CoA desaturase 1 (SCD1) and LC-FA composition in skeletal muscle, but human data are rare. We here investigate whether treatment with a PPARγ agonist affects myocellular SCD1 expression and modulates the intramyocellular fatty acid profile in individuals with impaired glucose tolerance. Muscle biopsies and hyperinsulinemic-euglycemic clamps were performed in 7 men before and after 8 weeks of rosiglitazone treatment. Intramyocellular saturated, monounsaturated, and polyunsaturated intramuscular fatty acid profiles were measured by gas chromatography. Effects on SCD1 messenger RNA expression were analyzed in C2C12 cells and in human biopsies before and after rosiglitazone treatment. As expected, treatment with the PPARγ activator rosiglitazone improved insulin sensitivity in humans. Myocellular SCD1 messenger RNA expression was increased in human biopsies and C2C12 cells. Although the total content of myocellular LC-FA was unchanged, a relative shift from saturated LC-FAs to unsaturated LC-FAs was observed in human biopsies. Particularly, the amount of stearate was reduced, whereas the amounts of palmitoleate as well as oleate and vaccenate were increased, after rosiglitazone therapy. These changes resulted in an increased fatty acid Δ9-desaturation index (16:1/16:0 and 18:1/18:0) in skeletal muscle and a decreased elongase activity index (18:0/16:0). The PPARγ associated phenotypes may be partially explained by an increased Δ9-desaturation and a decreased elongase activity of skeletal muscle. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

    Directory of Open Access Journals (Sweden)

    Hiroyuki Kato

    2016-06-01

    Full Text Available Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

  3. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running.

    Science.gov (United States)

    Kato, Hiroyuki; Suzuki, Hiromi; Inoue, Yoshiko; Suzuki, Katsuya; Kobayashi, Hisamine

    2016-06-28

    Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d₃-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

  4. Enhanced insulin signaling in human skeletal muscle and adipose tissue following gastric bypass surgery

    DEFF Research Database (Denmark)

    Albers, Peter H; Bojsen-Møller, Kirstine N; Dirksen, Carsten

    2015-01-01

    Roux-en-Y gastric bypass (RYGB) leads to increased peripheral insulin sensitivity. The aim of this study was to investigate the effect of RYGB on expression and regulation of proteins involved in regulation of peripheral glucose metabolism. Skeletal muscle and adipose tissue biopsies from glucose......-surgery when major weight loss was evident and occurred concomitantly with alterations in plasma adiponectin and in protein expression/signaling in peripheral tissues. In skeletal muscle, protein expression of GLUT4, phosphorylated levels of TBC1D4 as well as insulin-induced changes in phosphorylation of Akt...... 12 months post-surgery. Adipose tissue from glucose tolerant subjects was the most responsive to RYGB compared to type 2 diabetic patients, whereas changes in skeletal muscle were largely similar in these two groups. In conclusion, an improved molecular insulin sensitive phenotype of skeletal muscle...

  5. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass

    OpenAIRE

    Goodman, Craig A.; Hornberger, Troy A.

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mas...

  6. New roles for Smad signaling and phosphatidic acid in the regulation of skeletal muscle mass

    OpenAIRE

    Goodman, Craig A.; Hornberger, Troy A.

    2014-01-01

    Skeletal muscle is essential for normal bodily function and the loss of skeletal muscle (i.e. muscle atrophy/wasting) can have a major impact on mobility, whole-body metabolism, disease resistance, and quality of life. Thus, there is a clear need for the development of therapies that can prevent the loss, or increase, of skeletal muscle mass. However, in order to develop such therapies, we will first have to develop a thorough understanding of the molecular mechanisms that regulate muscle mas...

  7. Modulation of visceral fat adipokine secretion by dietary fatty acids and ensuing changes in skeletal muscle inflammation.

    Science.gov (United States)

    Tishinsky, Justine M; De Boer, Anna A; Dyck, David J; Robinson, Lindsay E

    2014-01-01

    Given the link between obesity and insulin resistance, the role of adipose-derived factors in communicating with skeletal muscle to affect its function is important. We sought to determine if high fat diets modulate visceral adipose tissue (VAT) adipokines with subsequent effects on skeletal muscle inflammation and insulin sensitivity. Rats were fed (i) low fat (LF), (ii) high saturated fatty acid (SFA), or (iii) high SFA with n-3 polyunsaturated fatty acid (SFA/n-3 PUFA) diets for 4 weeks. VAT-derived adipokines were measured in adipose conditioned medium (ACM) after 72 h. Next, skeletal muscles from LF-fed rats were incubated for 8 h in (i) control buffer (CON), (ii) CON with 2 mmol·L(-1) palmitate (PALM, positive control), (iii) ACM from LF, (iv) ACM from SFA, or (v) ACM from SFA/n-3 PUFA. ACM from rats fed SFA and SFA/n-3 PUFA had increased (P ≤ 0.05) interleukin-6 (IL-6) (+31%) and monocyte chemoattractant protein-1 (MCP-1) (+30%). Adiponectin was decreased (-29%, P ≤ 0.05) in ACM from SFA, and this was prevented in SFA/n-3 PUFA ACM. Toll-like receptor 4 (TLR4) gene expression was increased (P ≤ 0.05) in PALM soleus muscle (+356%) and all ACM groups (+175%-191%). MCP-1 gene expression was elevated (P ≤ 0.05) in PALM soleus muscle (+163%) and soleus muscle incubated in ACM from animals fed SFA (+159%) and SFA/n-3 PUFA (+151%). Glucose transport was impaired (P ≤ 0.05) in PALM muscles but preserved in ACM groups. Acute exposure of muscle to fatty acid modulated adipokines affects skeletal muscle inflammatory gene expression but not insulin sensitivity.

  8. Uniaxial cyclic strain enhances adipose-derived stem cell fusion with skeletal myocytes

    Energy Technology Data Exchange (ETDEWEB)

    Andersen, Jens Isak; Juhl, Morten; Nielsen, Thøger; Emmersen, Jeppe; Fink, Trine; Zachar, Vladimir; Pennisi, Cristian Pablo, E-mail: cpennisi@hst.aau.dk

    2014-07-25

    Highlights: • Uniaxial cyclic tensile strain (CTS) applied to ASCs alone or in coculture with myogenic precursors. • CTS promoted the formation of a highly ordered array of parallel ASCs. • Without biochemical supplements, CTS did not support advanced myogenic differentiation of ASCs. • Mechanical stimulation of cocultures boosted fusion of ASCs with skeletal myoblasts. - Abstract: Although adult muscle tissue possesses an exceptional capacity for regeneration, in the case of large defects, the restoration to original state is not possible. A well-known source for the de novo regeneration is the adipose-derived stem cells (ASCs), which can be readily isolated and have been shown to have a broad differentiation and regenerative potential. In this work, we employed uniaxial cyclic tensile strain (CTS), to mechanically stimulate human ASCs to participate in the formation skeletal myotubes in an in vitro model of myogenesis. The application of CTS for 48 h resulted in the formation of a highly ordered array of parallel ASCs, but failed to support skeletal muscle terminal differentiation. When the same stimulation paradigm was applied to cocultures with mouse skeletal muscle myoblasts, the percentage of ASCs contributing to the formation of myotubes significantly exceeded the levels reported in the literature hitherto. In perspective, the mechanical strain may be used to increase the efficiency of incorporation of ASCs in the skeletal muscles, which could be found useful in diverse traumatic or pathologic scenarios.

  9. Method for enhancing amidohydrolase activity of fatty acid amide hydrolase

    Energy Technology Data Exchange (ETDEWEB)

    John, George; Nagarajan, Subbiah; Chapman, Kent; Faure, Lionel; Koulen, Peter

    2016-10-25

    A method for enhancing amidohydrolase activity of Fatty Acid Amide Hydrolase (FAAH) is disclosed. The method comprising administering a phenoxyacylethanolamide that causes the enhanced activity. The enhanced activity can have numerous effects on biological organisms including, for example, enhancing the growth of certain seedlings. The subject matter disclosed herein relates to enhancers of amidohydrolase activity.

  10. Dilinoleoyl-phosphatidic acid mediates reduced IRS-1 tyrosine phosphorylation in rat skeletal muscle cells and mouse muscle.

    Science.gov (United States)

    Cazzolli, R; Mitchell, T W; Burchfield, J G; Pedersen, D J; Turner, N; Biden, T J; Schmitz-Peiffer, C

    2007-08-01

    Insulin resistance in skeletal muscle is strongly associated with lipid oversupply, but the intracellular metabolites and underlying mechanisms are unclear. We therefore sought to identify the lipid intermediates through which the common unsaturated fatty acid linoleate causes defects in IRS-1 signalling in L6 myotubes and mouse skeletal muscle. Cells were pre-treated with 1 mmol/l linoleate for 24 h. Subsequent insulin-stimulated IRS-1 tyrosine phosphorylation and its association with the p85 subunit of phosphatidylinositol 3-kinase were determined by immunoblotting. Intracellular lipid species and protein kinase C activation were modulated by overexpression of diacylglycerol kinase epsilon, which preferentially converts unsaturated diacylglycerol into phosphatidic acid, or by inhibition of lysophosphatidic acid acyl transferase with lisofylline, which reduces phosphatidic acid synthesis. Phosphatidic acid species in linoleate-treated cells or muscle from insulin-resistant mice fed a safflower oil-based high-fat diet that was rich in linoleate were analysed by mass spectrometry. Linoleate pretreatment reduced IRS-1 tyrosine phosphorylation and p85 association. Overexpression of diacylglycerol kinase epsilon reversed the activation of protein kinase C isoforms by linoleate, but paradoxically further diminished IRS-1 tyrosine phosphorylation. Conversely, lisofylline treatment restored IRS-1 phosphorylation. Mass spectrometry indicated that the dilinoleoyl-phosphatidic acid content increased from undetectable levels to almost 20% of total phosphatidic acid in L6 cells and to 8% of total in the muscle of mice fed a high-fat diet. Micelles containing dilinoleoyl-phosphatidic acid specifically inhibited IRS-1 tyrosine phosphorylation and glycogen synthesis in L6 cells. These data indicate that linoleate-derived phosphatidic acid is a novel lipid species that contributes independently of protein kinase C to IRS-1 signalling defects in muscle cells in response to lipid

  11. Effects of Different High Fat Diets on Fatty Acid Composition of Skeletal Muscle and Liver in Nude Mice Bearing Pancreatic Cancer

    Institute of Scientific and Technical Information of China (English)

    Yi-jie DUAN; Feng WANG; Zhong-wen LIU; Ming YU

    2014-01-01

    Objective To investigate the impacts of different dietary fatty acids on fatty acid composition in skeletal muscle and liver in nude mice bearing pancreatic cancer.MethodsSixty C57BL/6 nude mice were randomly divided into 6 groups: saturated fatty acid-fed group (SFA group), monounsaturated fatty acid-fed group (MUFA group), n-6 polyunsaturated fatty acid-fed group (n-6 PUFA group), n-3 polyunsaturated fatty acid-fed group (n-3 PUFA group), iso-caloric control (ISO-C) and normal control (NC). Four high fat diets containing 15% oils derived from coconut (SFA group), olive (MUFA group), soybean (n-6 PUFA group) andflaxseed (n-3 PUFA group) respectively, were prepared. ISO-C and NC groups were fed diet containing 4%-5% soybean oil. After one week of feeding, HPAF-Ⅱ human pancreatic cancer cells were transplanted orthotopically. The mice were fed corresponding diets in the following 14 weeks and then sacrificed. Skeletal muscle and liver tissues were sampled. Fatty acids in the samples were analyzed by gas chromatography-mass spectrometry.ResultsFatty acid composition of skeletal muscle and liver were similar between ISO-C group and NC group.Compared to ISO-C group, the contents of fatty acids in skeletal muscle were: (1) palmitic acid (C16:0), hepentadecane acid (C17:0), stearic acid (C18:0) and arachidonic acid (C20:0) increased inSFA group (P< 0.05); (2)oleic acid (C18:1) increased in MUFA group (P< 0.05); (3)γ-linolenic acid (γ-C18:3) increased in n-6 PUFA group (P<0.05);(4) linolenic acid (C18:3), eicosapentaenoic acid (C20:5) and clupanodonic acid (C22:5) increased in n-3 PUFA group (P<0.05). In the liver, the contents of fatty acids were: (1) saturated fatty acids not increased in SFA group; (2) eicosenoic acid (C20:1) increased in MUFA group (P< 0.05); (3) eicosadienoic acid (C20:2) and arachidonic acid (C20:4) increased in n-6 PUFA group (P < 0.05); (4) linolenic acid, eicosapentaenoic acid, clupanodonic acid and docosahexaenoic acid increased in n-3 PUFA

  12. Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle.

    Science.gov (United States)

    Ikeda, Shin-Ichi; Tamura, Yoshifumi; Kakehi, Saori; Sanada, Hiromi; Kawamori, Ryuzo; Watada, Hirotaka

    2016-05-13

    A single bout of exercise is known to increase the insulin sensitivity of skeletal muscle; however, the underlying mechanism of this phenomenon is not fully understood. Because a single bout of exercise induces a transient increase in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of insulin sensitivity after a single bout of exercise in skeletal muscle is mediated at least in part through IL-6-dependent mechanisms. To test this hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6 neutralizing antibody before exercise. Twenty-four hours after a single bout of exercise, the plantaris muscle was harvested to measure insulin sensitivity and glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with sedentary mice, mice that performed exercise showed enhanced IL-6 concentration, insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle. The enhanced insulin sensitivity and GLUT4 expression were canceled by injection of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4 expression in differentiated C2C12 myotubes. In summary, these results suggested that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play a role in the post-exercise enhancement of insulin sensitivity in skeletal muscle.

  13. Enhancement of Skeletal Muscle in Aged Rats Following High-Intensity Stretch-Shortening Contraction Training.

    Science.gov (United States)

    Rader, Erik P; Naimo, Marshall A; Layner, Kayla N; Triscuit, Alyssa M; Chetlin, Robert D; Ensey, James; Baker, Brent A

    2016-08-03

    Exercise is the most accessible, efficacious, and multifactorial intervention to improve health and treat chronic disease. High-intensity resistance exercise, in particular, also maximizes skeletal muscle size and strength-outcomes crucial at advanced age. However, such training is capable of inducing muscle maladaptation when misapplied at old age. Therefore, characterization of parameters (e.g., mode and frequency) that foster adaptation is an active research area. To address this issue, we utilized a rodent model that allowed training at maximal intensity in terms of muscle activation and tested the hypothesis that muscles of old rats adapt to stretch-shortening contraction (SSC) training, provided the training frequency is sufficiently low. At termination of training, normalized muscle mass (i.e., muscle mass divided by tibia length) and muscle quality (isometric force divided by normalized muscle mass) were determined. For young rats, normalized muscle mass increased by ∼20% regardless of training frequency. No difference was observed for muscle quality values after 2 days versus 3 days per week training (0.65 ± 0.09 N/mg/mm vs. 0.59 ± 0.05 N/mg/mm, respectively). For old rats following 3 days per week training, normalized muscle mass was unaltered and muscle quality was 30% lower than young levels. Following 2 days per week training at old age, normalized muscle mass increased by 17% and muscle quality was restored to young levels. To investigate this enhanced response, oxidative stress was assessed by lipid peroxidation quantification. For young rats, lipid peroxidation levels were unaltered by training. With aging, baseline levels of lipid peroxidation increased by 1.5-fold. For old rats, only 2 days per week training decreased lipid peroxidation to levels indistinguishable from young values. These results imply that, appropriately scheduled high-intensity SSC training at old age is capable of restoring muscle to a younger phenotype in terms

  14. Biocompatible Elastic Conductive Films Significantly Enhanced Myogenic Differentiation of Myoblast for Skeletal Muscle Regeneration.

    Science.gov (United States)

    Dong, Ruonan; Zhao, Xin; Guo, Baolin; Ma, Peter X

    2017-09-11

    The key factor in skeletal muscle tissue engineering is regeneration of the functional skeletal muscles. Materials that could promote the myoblast proliferation and myogenic differentiation are promising candidates in skeletal muscle tissue engineering. Herein, we developed an elastic conductive poly(ethylene glycol)-co-poly(glycerol sebacate) (PEGS) grafted aniline pentamer (AP) copolymer that could promote the formation of myotubes by differentiating the C2C12 myoblast cells. The results of hydration behavior and water contact angle suggested that by adjusting the poly(ethylene glycol) (PEG) and AP content, this film showed a proper surface hydrophilicity for cell attachment. Additionally, these films showed tunable conductivity and mechanical properties that can be altered by changing the AP content. The maximum conductivity of the films was 1.84 × 10(-4) S/cm and the Young's modulus of these films ranged from 14.58 ± 1.35 MPa to 24.62 ± 0.61 MPa. Our findings indicate that the PEGS-AP films promote the proliferation and myogenic differentiation of C2C12 cells, suggesting that they are promising biomaterials for skeletal muscle tissue engineering.

  15. Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults

    Science.gov (United States)

    Lamon, Séverine; Zacharewicz, Evelyn; Arentson-Lantz, Emily; Gatta, Paul A. Della; Ghobrial, Lobna; Gerlinger-Romero, Frederico; Garnham, Andrew; Paddon-Jones, Douglas; Russell, Aaron P.

    2016-01-01

    Purpose: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway. Methods: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C6] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis. Results: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects. Conclusions: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways. PMID:27458387

  16. Enhanced GLUT4-Dependent Glucose Transport Relieves Nutrient Stress in Obese Mice Through Changes in Lipid and Amino Acid Metabolism.

    Science.gov (United States)

    Gurley, Jami M; Ilkayeva, Olga; Jackson, Robert M; Griesel, Beth A; White, Phillip; Matsuzaki, Satochi; Qaisar, Rizwan; Van Remmen, Holly; Humphries, Kenneth M; Newgard, Christopher B; Olson, Ann Louise

    2016-12-01

    Impaired GLUT4-dependent glucose uptake is a contributing factor in the development of whole-body insulin resistance in obese patients and obese animal models. Previously, we demonstrated that transgenic mice engineered to express the human GLUT4 gene under the control of the human GLUT4 promoter (i.e., transgenic [TG] mice) are resistant to obesity-induced insulin resistance. A likely mechanism underlying increased insulin sensitivity is increased glucose uptake in skeletal muscle. The purpose of this study was to investigate the broader metabolic consequences of enhanced glucose uptake into muscle. We observed that the expression of several nuclear and mitochondrially encoded mitochondrial enzymes was decreased in TG mice but that mitochondrial number, size, and fatty acid respiration rates were unchanged. Interestingly, both pyruvate and glutamate respiration rates were decreased in TG mice. Metabolomics analyses of skeletal muscle samples revealed that increased GLUT4 transgene expression was associated with decreased levels of some tricarboxylic acid intermediates and amino acids, whereas the levels of several glucogenic amino acids were elevated. Furthermore, fasting acyl carnitines in obese TG mice were decreased, indicating that increased GLUT4-dependent glucose flux decreases nutrient stress by altering lipid and amino acid metabolism in skeletal muscle.

  17. A multi-scale continuum model of skeletal muscle mechanics predicting force enhancement based on actin-titin interaction.

    Science.gov (United States)

    Heidlauf, Thomas; Klotz, Thomas; Rode, Christian; Altan, Ekin; Bleiler, Christian; Siebert, Tobias; Röhrle, Oliver

    2016-12-01

    Although recent research emphasises the possible role of titin in skeletal muscle force enhancement, this property is commonly ignored in current computational models. This work presents the first biophysically based continuum-mechanical model of skeletal muscle that considers, in addition to actin-myosin interactions, force enhancement based on actin-titin interactions. During activation, titin attaches to actin filaments, which results in a significant reduction in titin's free molecular spring length and therefore results in increased titin forces during a subsequent stretch. The mechanical behaviour of titin is included on the microscopic half-sarcomere level of a multi-scale chemo-electro-mechanical muscle model, which is based on the classic sliding-filament and cross-bridge theories. In addition to titin stress contributions in the muscle fibre direction, the continuum-mechanical constitutive relation accounts for geometrically motivated, titin-induced stresses acting in the muscle's cross-fibre directions. Representative simulations of active stretches under maximal and submaximal activation levels predict realistic magnitudes of force enhancement in fibre direction. For example, stretching the model by 20 % from optimal length increased the isometric force at the target length by about 30 %. Predicted titin-induced stresses in the muscle's cross-fibre directions are rather insignificant. Including the presented development in future continuum-mechanical models of muscle function in dynamic situations will lead to more accurate model predictions during and after lengthening contractions.

  18. Secreted Protein Acidic and Rich in Cysteine (SPARC) in Human Skeletal Muscle

    DEFF Research Database (Denmark)

    Jørgensen, Louise H; Petersson, Stine J; Sellathurai, Jeeva

    2009-01-01

    indicated a function of SPARC in skeletal muscle. We therefore found it of interest to study SPARC expression in human skeletal muscle during development and in biopsies from Duchenne and Becker muscular dystrophy and congenital muscular dystrophy, congenital myopathy, inclusion body myositis...... in the majority of analyzed muscle biopsies (23 of 24), mainly in mononuclear cells of which few were pax7 positive. Myotubes and regenerating myofibers also expressed SPARC. The expression-degree seemed to reflect the severity of the lesion. In accordance with these in vivo findings, primary human...

  19. Feeding enhances skeletal growth and energetic stores of an Atlantic coral under significantly elevated CO2

    Science.gov (United States)

    Drenkard, L.; Cohen, A. L.; McCorkle, D. C.; dePutron, S.; Zicht, A.

    2011-12-01

    Many corals living under the relatively acidic conditions of naturally high-CO2 reefs are calcifying as fast or faster than their conspecifics on naturally low CO2 reefs. These observations are inconsistent with most experimental work that shows a negative impact of ocean acidification on coral calcification. We investigated the link between coral nutritional (energetic) status and the calcification response to significantly elevated CO2. Juveniles of the Atlantic brooding coral, Favia fragum were reared for three weeks under fully crossed CO2 and feeding conditions: ambient (μar =1.6+-0.2) and high CO2 (μar =3.7+-0.3); fed and unfed. In most measured parameters, the effect of feeding is much stronger than the effect of CO2. Nutritionally enhanced (fed) corals, regardless of CO2 condition, have higher concentrations of total lipid and their skeletons are both significantly larger and more developmentally advanced than those of corals relying solely on autotrophy. In measurements of corallite weight, where the impact of CO2 is most apparent, no statistical difference is observed between unfed corals under ambient CO2 conditions and fed corals reared under 1600 ppm CO2. Our results suggest that coral energetic status, which can be enhanced by heterotrophic feeding but depleted by stressors such as bleaching, will play a key role in the coral response to ocean acidification and thus, in the resilience of reef ecosystems under climate change.

  20. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice.

    Directory of Open Access Journals (Sweden)

    Jonas M Kristensen

    Full Text Available Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK signaling. We investigated this by two weeks of oral metformin treatment of muscle specific kinase dead α(2 (KD AMPK mice and wild type (WT littermates. We measured mitochondrial respiration and protein activity and expressions of key enzymes involved in mitochondrial carbohydrate and fat metabolism and oxidative phosphorylation. Mitochondrial respiration, HAD and CS activity, PDH and complex I-V and cytochrome c protein expression were all reduced in AMPK KD compared to WT tibialis anterior muscles. Surprisingly, metformin treatment only enhanced respiration in AMPK KD mice and thereby rescued the respiration defect compared to the WT mice. Metformin did not influence protein activities or expressions in either WT or AMPK KD mice.We conclude that two weeks of in vivo metformin treatment enhances mitochondrial respiration in the mitochondrial deficient AMPK KD but not WT mice. The improvement seems to be unrelated to AMPK, and does not involve changes in key mitochondrial proteins.

  1. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  2. Enhanced Development of Skeletal Myotubes from Porcine Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Genovese, Nicholas J; Domeier, Timothy L; Telugu, Bhanu Prakash V L; Roberts, R Michael

    2017-02-06

    The pig is recognized as a valuable model in biomedical research in addition to its agricultural importance. Here we describe a means for generating skeletal muscle efficiently from porcine induced pluripotent stem cells (piPSC) in vitro thereby providing a versatile platform for applications ranging from regenerative biology to the ex vivo cultivation of meat. The GSK3B inhibitor, CHIR99021 was employed to suppress apoptosis, elicit WNT signaling events and drive naïve-type piPSC along the mesoderm lineage, and, in combination with the DNA methylation inhibitor 5-aza-cytidine, to activate an early skeletal muscle transcription program. Terminal differentiation was then induced by activation of an ectopically expressed MYOD1. Myotubes, characterized by myofibril development and both spontaneous and stimuli-elicited excitation-contraction coupling cycles appeared within 11 days. Efficient lineage-specific differentiation was confirmed by uniform NCAM1 and myosin heavy chain expression. These results provide an approach for generating skeletal muscle that is potentially applicable to other pluripotent cell lines and to generating other forms of muscle.

  3. Differential effects of docoosahexaenoic and arachidonic acid on fatty acid composition and myosin heavy chain-related genes of slow- and fast-twitch skeletal muscle tissues.

    Science.gov (United States)

    Hashimoto, Michio; Inoue, Takayuki; Katakura, Masanori; Hossain, Shahdat; Mamun, Abdullah Al; Matsuzaki, Kentaro; Arai, Hiroyuki; Shido, Osamu

    2016-04-01

    Myosin heavy chain (MHC) mediates the metabolic and contractile responses of skeletal muscles. MHC displays different isoforms, each of which has different characteristics. To better understand the effect of polyunsaturated fatty acids in skeletal muscles, rats were fed with control-, docosahexaenoic acid (DHA)-, and arachidonic acid (ARA)-oil, and the effects on plasma and muscular fatty acid profile, oxidative stress, mRNA levels of myosin heavy chain isoforms MHC1 of slow-twitch muscle (SO) and MHC2A, MHC2X, and MHCB isoforms of extensor digitorum longus (EDL) of fast-twitch muscle were evaluated. Concomitantly, mRNA levels of anti-oxidative enzymes, such as, catalase, glutathione peroxidase (GPx) and superoxide dismutase (SOD were determined. The expressions of MHC1, MHC2A, MHC2X, and MHC2B were lower in the SO of the DHA-fed rats. In the EDL muscles of DHA-fed rats, the expressions of MHC1 and MHC2A increased; however, the expressions of MHC2X increased and that of the MHC2 were not altered. Oxidative stress, as indicated by the levels of LPO, was significantly higher in the plasma of the ARA-fed rats, when compared with that of the DHA-fed rats. The LPO levels were higher both in the SO and EDL muscles of ARA-fed rats. Compared with ARA oil intake, DHA oil showed higher mRNA levels of GPx and SOD. Catalase expression was higher only in the EDL but not in the SO-type muscles. Our studies finally indicate that DHA and ARA differentially affect the regulation of contractile and metabolic properties of slow- and fast-twitch skeletal muscles.

  4. A Modified method for reducing renal injury in zoledronic acid treatment of hypercalcemia and adverse skeletal events

    Directory of Open Access Journals (Sweden)

    Jiang Liu

    2013-01-01

    Full Text Available Aims: In this paper, we have reported a previously undescribed risk factor of deterioration of renal function in zoledronic acid treatment of skeletal metastasis - high serum calcium level. Based on this consideration, a modified method of treatment of hypercalcemia (HCM with zoledronic acid is suggested in this paper. Material and Methods: Bone scan findings of 1090 cancer patients were analyzed, of which 26 had intense renal parenchymal uptake as a result of HCM or bone metastases. Subsequently, a total of 56 bone metastases patients with zoledronic acid treatment were divided into three groups: HCM group who were pre-treated to normal serum calcium level (13 patients, HCM group (19 patients, and normal serum calcium group (24 patients. Results: More patients with intense renal parenchymal uptake were hyperglycemic, statistically significantly (18/26 versus 19/1064, P = 2.1, E-78. No more patients with intense renal parenchymal uptake were associated with bone metastases (14/26 versus 438/1064, P = 0.20. Subsequently, more HCM patients receiving zoledronic acid treatment showed renal injury compared to patients with normal serum calcium level (5/15 versus 2/24, P < 0.05 and HCM patients with pre-treatment to normal serum calcium level (5/15 versus 1/17, P < 0.05. Conclusions: Intense renal parenchymal uptake of bisphosphonates is closely related to HCM rather than to bone metastases in cancer patients. The serum calcium should be measured and reduced to normal level before zoledronic acid is used in managements of adverse skeletal events in order to decrease the risk of renal injury.

  5. Evaluation of skeletal tissue repair, part 2: enhancement of skeletal tissue repair through dual-growth-factor-releasing hydrogels within an ex vivo chick femur defect model.

    Science.gov (United States)

    Smith, E L; Kanczler, J M; Gothard, D; Roberts, C A; Wells, J A; White, L J; Qutachi, O; Sawkins, M J; Peto, H; Rashidi, H; Rojo, L; Stevens, M M; El Haj, A J; Rose, F R A J; Shakesheff, K M; Oreffo, R O C

    2014-10-01

    There is an unmet need for improved, effective tissue engineering strategies to replace or repair bone damaged through disease or injury. Recent research has focused on developing biomaterial scaffolds capable of spatially and temporally releasing combinations of bioactive growth factors, rather than individual molecules, to recapitulate repair pathways present in vivo. We have developed an ex vivo embryonic chick femur critical size defect model and applied the model in the study of novel extracellular matrix (ECM) hydrogel scaffolds containing spatio-temporal combinatorial growth factor-releasing microparticles and skeletal stem cells for bone regeneration. Alginate/bovine bone ECM (bECM) hydrogels combined with poly(d,l-lactic-co-glycolic acid) (PDLLGA)/triblock copolymer (10-30% PDLLGA-PEG-PLDLGA) microparticles releasing dual combinations of vascular endothelial growth factor (VEGF), chondrogenic transforming growth factor beta 3 (TGF-β3) and the bone morphogenetic protein BMP2, with human adult Stro-1+bone marrow stromal cells (HBMSCs), were placed into 2mm central segmental defects in embryonic day 11 chick femurs and organotypically cultured. Hydrogels loaded with VEGF combinations induced host cell migration and type I collagen deposition. Combinations of TGF-β3/BMP2, particularly with Stro-1+HBMSCs, induced significant formation of structured bone matrix, evidenced by increased Sirius red-stained matrix together with collagen expression demonstrating birefringent alignment within hydrogels. This study demonstrates the successful use of the chick femur organotypic culture system as a high-throughput test model for scaffold/cell/growth factor therapies in regenerative medicine. Temporal release of dual growth factors, combined with enriched Stro-1+HBMSCs, improved the formation of a highly structured bone matrix compared to single release modalities. These studies highlight the potential of a unique alginate/bECM hydrogel dual growth factor release

  6. An ethanol extract of Artemisia iwayomogi activates PPARδ leading to activation of fatty acid oxidation in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Si Young Cho

    Full Text Available Although Artemisia iwayomogi (AI has been shown to improve the lipid metabolism, its mode of action is poorly understood. In this study, a 95% ethanol extract of AI (95EEAI was identified as a potent ligand of peroxisome proliferator-activated receptorδ (PPARδ using ligand binding analysis and cell-based reporter assay. In cultured primary human skeletal muscle cells, treatment of 95EEAI increased expression of two important PPARδ-regulated genes, carnitine palmitoyl-transferase-1 (CPT1 and pyruvate dehydrogenase kinase isozyme 4 (PDK4, and several genes acting in lipid efflux and energy expenditure. Furthermore, 95EEAI stimulated fatty acid oxidation in a PPARδ-dependent manner. High-fat diet-induced obese mice model further indicated that administration of 95EEAI attenuated diet-induced obesity through the activation of fatty acid oxidation in skeletal muscle. These results suggest that a 95% ethanol extract of AI may have a role as a new functional food material for the prevention and/or treatment of hyperlipidermia and obesity.

  7. Long-chain fatty acid combustion rate is associated with unique metabolite profiles in skeletal muscle mitochondria.

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    Erin L Seifert

    Full Text Available BACKGROUND/AIM: Incomplete or limited long-chain fatty acid (LCFA combustion in skeletal muscle has been associated with insulin resistance. Signals that are responsive to shifts in LCFA beta-oxidation rate or degree of intramitochondrial catabolism are hypothesized to regulate second messenger systems downstream of the insulin receptor. Recent evidence supports a causal link between mitochondrial LCFA combustion in skeletal muscle and insulin resistance. We have used unbiased metabolite profiling of mouse muscle mitochondria with the aim of identifying candidate metabolites within or effluxed from mitochondria and that are shifted with LCFA combustion rate. METHODOLOGY/PRINCIPAL FINDINGS: Large-scale unbiased metabolomics analysis was performed using GC/TOF-MS on buffer and mitochondrial matrix fractions obtained prior to and after 20 min of palmitate catabolism (n = 7 mice/condition. Three palmitate concentrations (2, 9 and 19 microM; corresponding to low, intermediate and high oxidation rates and 9 microM palmitate plus tricarboxylic acid (TCA cycle and electron transport chain inhibitors were each tested and compared to zero palmitate control incubations. Paired comparisons of the 0 and 20 min samples were made by Student's t-test. False discovery rate were estimated and Type I error rates assigned. Major metabolite groups were organic acids, amines and amino acids, free fatty acids and sugar phosphates. Palmitate oxidation was associated with unique profiles of metabolites, a subset of which correlated to palmitate oxidation rate. In particular, palmitate oxidation rate was associated with distinct changes in the levels of TCA cycle intermediates within and effluxed from mitochondria. CONCLUSIONS/SIGNIFICANCE: This proof-of-principle study establishes that large-scale metabolomics methods can be applied to organelle-level models to discover metabolite patterns reflective of LCFA combustion, which may lead to identification of molecules

  8. Tissue-specific changes in fatty acid oxidation in hypoxic heart and skeletal muscle

    OpenAIRE

    Morash, Andrea J.; Kotwica, Aleksandra O; Murray, Andrew J.

    2013-01-01

    Exposure to hypobaric hypoxia is sufficient to decrease cardiac PCr/ATP and alters skeletal muscle energetics in humans. Cellular mechanisms underlying the different metabolic responses of these tissues and the time-dependent nature of these changes are currently unknown, but altered substrate utilization and mitochondrial function may be a contributory factor. We therefore sought to investigate the effects of acute (1 day) and more sustained (7 days) hypoxia (13% O2) on the transcription fac...

  9. High-intensity interval training increases intrinsic rates of mitochondrial fatty acid oxidation in rat red and white skeletal muscle.

    Science.gov (United States)

    Hoshino, Daisuke; Yoshida, Yuko; Kitaoka, Yu; Hatta, Hideo; Bonen, Arend

    2013-03-01

    High-intensity interval training (HIIT) can increase mitochondrial volume in skeletal muscle. However, it is unclear whether HIIT alters the intrinsic capacity of mitochondrial fatty acid oxidation, or whether such changes are associated with changes in mitochondrial FAT/CD36, a regulator of fatty acid oxidation, or with reciprocal changes in the nuclear receptor coactivator (peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1α)) and the corepressor (receptor-interacting protein 140 (RIP140)). We examined whether HIIT alters fatty acid oxidation rates in the isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria of red and white skeletal muscle and (or) induces changes in muscle PGC-1α and RIP140 proteins and mitochondrial FAT/CD36 protein content. Rats were divided into untrained or HIIT-trained groups. HIIT animals performed 10 bouts of 1-min high-intensity treadmill running (30-55 m·min(-1)), separated by 2 min of rest, for 5 days a week for 4 weeks. As expected, after the training period, HIIT increased mitochondrial enzymes (citrate synthase, COXIV, and β-hydroxyacyl CoA dehydrogenase) in red and white muscle, indicating that muscle mitochondrial volume had increased. HIIT also increased the rates of palmitate oxidation in mitochondria of red (37% for SS and 19% for IMF) and white (36% for SS and 12% for IMF) muscle. No changes occurred in SS and IMF mitochondrial FAT/CD36 proteins, despite increasing FAT/CD36 at the whole-muscle level (27% for red and 22% for white). Concurrently, muscle PGC-1α protein was increased in red (22%) and white (16%) muscle, but RIP140 was not altered. These results indicate that increases in SS and IMF mitochondrial fatty acid oxidation induced by HIIT are accompanied by an increase in PGC-1α, but not RIP140 or FAT/CD36.

  10. No effect of short-term amino acid supplementation on variables related to skeletal muscle damage in 100 km ultra-runners - a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Rosemann Thomas

    2011-04-01

    Full Text Available Abstract Background The purpose of this study was to investigate the effect of short-term supplementation of amino acids before and during a 100 km ultra-marathon on variables of skeletal muscle damage and muscle soreness. We hypothesized that the supplementation of amino acids before and during an ultra-marathon would lead to a reduction in the variables of skeletal muscle damage, a decrease in muscle soreness and an improved performance. Methods Twenty-eight experienced male ultra-runners were divided into two groups, one with amino acid supplementation and the other as a control group. The amino acid group was supplemented a total of 52.5 g of an amino acid concentrate before and during the 100 km ultra-marathon. Pre- and post-race, creatine kinase, urea and myoglobin were determined. At the same time, the athletes were asked for subjective feelings of muscle soreness. Results Race time was not different between the groups when controlled for personal best time in a 100 km ultra-marathon. The increases in creatine kinase, urea and myoglobin were not different in both groups. Subjective feelings of skeletal muscle soreness were not different between the groups. Conclusions We concluded that short-term supplementation of amino acids before and during a 100 km ultra-marathon had no effect on variables of skeletal muscle damage and muscle soreness.

  11. Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

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    Ling Yang

    2016-01-01

    Full Text Available Calorie restriction (CR retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3–15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001. HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to controls. Our data indicate that CR in humans is associated with sustained rises in serum cortisol, reduced inflammation, and increases in key molecular chaperones and autophagic mediators involved in cellular protein quality control and removal of dysfunctional proteins and organelles.

  12. Exercise but not prostanoids enhance levels of vascular endothelial growth factor and other proliferative agents in human skeletal muscle interstitium

    DEFF Research Database (Denmark)

    Höffner, Lotte; Nielsen, Jens Jung; Langberg, Henning

    2003-01-01

    In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained...... either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy......Da dialysate from resting muscle than with perfusate and was 5.8-fold higher (P muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9-fold higher (P

  13. Acute ascorbic acid ingestion increases skeletal muscle blood flow and oxygen consumption via local vasodilation during graded handgrip exercise in older adults.

    Science.gov (United States)

    Richards, Jennifer C; Crecelius, Anne R; Larson, Dennis G; Dinenno, Frank A

    2015-07-15

    Human aging is associated with reduced skeletal muscle perfusion during exercise, which may be a result of impaired endothelium-dependent dilation and/or attenuated ability to blunt sympathetically mediated vasoconstriction. Intra-arterial infusion of ascorbic acid (AA) increases nitric oxide-mediated vasodilation and forearm blood flow (FBF) during handgrip exercise in older adults, yet it remains unknown whether an acute oral dose can similarly improve FBF or enhance the ability to blunt sympathetic vasoconstriction during exercise. We hypothesized that 1) acute oral AA would improve FBF (Doppler ultrasound) and oxygen consumption (V̇o2) via local vasodilation during graded rhythmic handgrip exercise in older adults (protocol 1), and 2) AA ingestion would not enhance sympatholysis in older adults during handgrip exercise (protocol 2). In protocol 1 (n = 8; 65 ± 3 yr), AA did not influence FBF or V̇o2 during rest or 5% maximal voluntary contraction (MVC) exercise, but increased FBF (199 ± 13 vs. 248 ± 16 ml/min and 343 ± 24 vs. 403 ± 33 ml/min; P vasodilation.

  14. Effects of eccentric exercise on branched-chain amino acid profiles in rat serum and skeletal muscle.

    Science.gov (United States)

    Qun, Z; Xinkai, Y; Jing, W

    2014-04-01

    Supplementation of branched-chain amino acid (BCAA) is often used to attenuate exercise-induced skeletal muscle damage and promote adaptation, but no definitive conclusion on the benefits of BCAA on muscle recovery after injurious exercise can be drawn. Exploration of the systematic BCAA alteration in muscular injury-repair stage per se without any BCAA supplement should provide some useful information in favour of BCAA application in muscle regeneration after injury. One bout of 90-min downhill-running exercise was performed to cause rat skeletal muscle injury. After exercise, myofibrillar BCAA concentrations showed minor changes compared with exercise before, while serum concentrations of BCAA were lower after exercise. Especially, serum leucine, isoleucine and total BCAA concentrations 2 weeks post-run were significantly lower than normal values of exercise before (p = 0.008, p = 0.041, p = 0.015). The data demonstrate that a single eccentric exercise can significantly decrease the serum BCAA concentrations, which mean high utilization of BCAA for myogenesis after injurious exercise.

  15. Enhanced procollagen processing in skeletal muscle after a single bout of eccentric loading in humans

    DEFF Research Database (Denmark)

    Crameri, Regina M; Langberg, Henning; Teisner, Børge

    2004-01-01

    young healthy male subjects performed a single bout of unaccustomed high intensity eccentric exercise on one leg, with the contralateral leg being the control. A significant increase in the muscle interstitial concentration of the N-terminal propeptide of procollagen type I (PINP) was observed (day 0: 1...... mechanical load and inflammation. This study shows that following a single bout of high intensity eccentric exercise there is an increase in procollagen processing within skeletal muscle in humans........96 +/- 0.44 ng ml(-1), day 2: 1.94 +/- 0.32 ng ml(-1), day 4: 3.90 +/- 1.03 ng ml(-1), day 8: 7.23 +/- 2.34 ng ml(-1)*, *P exercise, an increase in the histological immunoreactivity of PINP and the N...

  16. Pioglitazone enhances mitochondrial biogenesis and ribosomal protein biosynthesis in skeletal muscle in polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2008-01-01

    Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated...... by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp....... Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P

  17. Chromium picolinate enhances skeletal muscle cellular insulin signaling in vivo in obese, insulin-resistant JCR:LA-cp rats.

    Science.gov (United States)

    Wang, Zhong Q; Zhang, Xian H; Russell, James C; Hulver, Matthew; Cefalu, William T

    2006-02-01

    Chromium is one of the few trace minerals for which a specific cellular mechanism of action has not been identified. Recent in vitro studies suggest that chromium supplementation may improve insulin sensitivity by enhancing insulin receptor signaling, but this has not been demonstrated in vivo. We investigated the effect of chromium supplementation on insulin receptor signaling in an insulin-resistant rat model, the JCR:LA-corpulent rat. Male JCR:LA-cp rats (4 mo of age) were randomly assigned to receive chromium picolinate (CrPic) (obese n=6, lean n=5) or vehicle (obese n=5, lean n=5) for 3 mo. The CrPic was provided in the water, and based on calculated water intake, rats randomized to CrPic received 80 microg/(kg.d). At the end of the study, skeletal muscle (vastus lateralis) biopsies were obtained at baseline and at 5, 15, and 30 min postinsulin stimulation to assess insulin signaling. Obese rats treated with CrPic had significantly improved glucose disposal rates and demonstrated a significant increase in insulin-stimulated phosphorylation of insulin receptor substrate (IRS)-1 and phosphatidylinositol (PI)-3 kinase activity in skeletal muscle compared with obese controls. The increase in cellular signaling was not associated with increased protein levels of the IRS proteins, PI-3 kinase or Akt. However, protein tyrosine phosphatase 1B (PTP1B) levels were significantly lower in obese rats administered CrPic than obese controls. When corrected for protein content, PTP1B activity was also significantly lower in obese rats administered CrPic than obese controls. Our data suggest that chromium supplementation of obese, insulin-resistant rats may improve insulin action by enhancing intracellular signaling.

  18. The Role of Diacylglycerol Kinase ζ and Phosphatidic Acid in the Mechanical Activation of Mammalian Target of Rapamycin (mTOR) Signaling and Skeletal Muscle Hypertrophy*

    Science.gov (United States)

    You, Jae-Sung; Lincoln, Hannah C.; Kim, Chan-Ran; Frey, John W.; Goodman, Craig A.; Zhong, Xiao-Ping; Hornberger, Troy A.

    2014-01-01

    The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass. PMID:24302719

  19. The role of diacylglycerol kinase ζ and phosphatidic acid in the mechanical activation of mammalian target of rapamycin (mTOR) signaling and skeletal muscle hypertrophy.

    Science.gov (United States)

    You, Jae-Sung; Lincoln, Hannah C; Kim, Chan-Ran; Frey, John W; Goodman, Craig A; Zhong, Xiao-Ping; Hornberger, Troy A

    2014-01-17

    The activation of mTOR signaling is essential for mechanically induced changes in skeletal muscle mass, and previous studies have suggested that mechanical stimuli activate mTOR (mammalian target of rapamycin) signaling through a phospholipase D (PLD)-dependent increase in the concentration of phosphatidic acid (PA). Consistent with this conclusion, we obtained evidence which further suggests that mechanical stimuli utilize PA as a direct upstream activator of mTOR signaling. Unexpectedly though, we found that the activation of PLD is not necessary for the mechanically induced increases in PA or mTOR signaling. Motivated by this observation, we performed experiments that were aimed at identifying the enzyme(s) that promotes the increase in PA. These experiments revealed that mechanical stimulation increases the concentration of diacylglycerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures. Furthermore, using knock-out mice, we determined that the ζ isoform of DGK (DGKζ) is necessary for the mechanically induced increase in PA. We also determined that DGKζ significantly contributes to the mechanical activation of mTOR signaling, and this is likely driven by an enhanced binding of PA to mTOR. Last, we found that the overexpression of DGKζ is sufficient to induce muscle fiber hypertrophy through an mTOR-dependent mechanism, and this event requires DGKζ kinase activity (i.e. the synthesis of PA). Combined, these results indicate that DGKζ, but not PLD, plays an important role in mechanically induced increases in PA and mTOR signaling. Furthermore, this study suggests that DGKζ could be a fundamental component of the mechanism(s) through which mechanical stimuli regulate skeletal muscle mass.

  20. Enhanced Eryptosis Following Exposure to Carnosic Acid

    Directory of Open Access Journals (Sweden)

    Katja Stockinger

    2015-11-01

    Full Text Available Background/Aims: The phenolic abietane diterpene component of rosemary and sage, carnosic acid, may either induce or inhibit apoptosis of nucleated cells. The mechanisms involved in the effects of carnosic acid include altered mitochondrial function and gene expression. Human erythrocytes lack mitochondria and nuclei but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Cellular mechanisms involved in the stimulation of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i, and ceramide formation. The present study explored, whether and how carnosic acid induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ROS formation from DCFDA dependent fluorescence and ceramide abundance utilizing specific antibodies. Results: A 48 hours exposure of human erythrocytes to carnosic acid significantly increased the percentage of annexin-V-binding cells (2.5 µg/ml, significantly decreased forward scatter (10 µg/ml, significantly increased Fluo3 fluorescence (10 µg/ml, significantly increased ceramide abundance (10 µg/ml, significantly increased hemolysis (10 µg/ml, but significantly decreased DCFDA fluorescence (10 µg/ml. The effect of carnosic acid on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. Conclusion: Carnosic acid triggers cell shrinkage and phospholipid scrambling of the human erythrocyte cell membrane, an effect paralleled by and/or in part due to Ca2+ entry and increased ceramide abundance.

  1. Skeletal isomerisation of oleic acid over ferrierite in the presence and absence of triphenylphosphine : Pore mouth catalysis and related deactivation mechanisms

    NARCIS (Netherlands)

    Wiedemann, Sophie C C; Stewart, Joseph A.; Soulimani, Fouad|info:eu-repo/dai/nl/313889449; Van Bergen-Brenkman, Tanja; Langelaar, Stephan; Wels, Bas; De Peinder, Peter|info:eu-repo/dai/nl/325810818; Bruijnincx, Pieter C A|info:eu-repo/dai/nl/33799529X; Weckhuysen, Bert M.|info:eu-repo/dai/nl/285484397

    2014-01-01

    The formation and nature of coke (precursor) species has been studied during the skeletal isomerisation of oleic acid catalysed by protonated ferrierite, in the presence and absence of a triphenylphosphine promoter. UV-Vis and FT-IR spectroscopic analyses of the spent catalyst materials,

  2. Enhanced Acid/Base Catalysis in High Temperature Liquid Water

    Institute of Scientific and Technical Information of China (English)

    Xiu Yang LU; Qi JING; Zhun LI; Lei YUAN; Fei GAO; Xin LIU

    2006-01-01

    Two novel and environmentally benign solvent systems, organic acids-enriched high temperature liquid water (HTLW) and NH3-enriched HTLW, were developed, which can enhance the reaction rate of acid/base-catalyzed organic reactions in HTLW. We investigated the decomposition of fructose in organic acids-enriched HTLW, hydrolysis of cinnamaldehyde and aldol condensation of phenylaldehyde with acetaldehyde in NH3-enriched HTLW. The experimental results demonstrated that organic acids-enriched or NH3-enriched HTLW can greatly accelerate acid/base-catalyzed organic reactions in HTLW.

  3. Insulin is required for amino acid stimulation of dual pathways for translational control in skeletal muscle in the late-gestation ovine fetus.

    Science.gov (United States)

    Brown, Laura D; Rozance, Paul J; Barry, James S; Friedman, Jacob E; Hay, William W

    2009-01-01

    During late gestation, amino acids and insulin promote skeletal muscle protein synthesis. However, the independent effects of amino acids and insulin on the regulation of mRNA translation initiation in the fetus are relatively unknown. The purpose of this study was to determine whether acute amino acid infusion in the late-gestation ovine fetus, with and without a simultaneous increase in fetal insulin concentration, activates translation initiation pathway(s) in skeletal muscle. Fetuses received saline (C), mixed amino acid infusion plus somatostatin infusion to suppress amino acid-stimulated fetal insulin secretion (AA+S), mixed amino acid infusion with concomitant physiological increase in fetal insulin (AA), or high-dose insulin infusion with euglycemia and euaminoacidemia (HI). After a 2-h infusion period, fetal skeletal muscle was harvested under in vivo steady-state conditions and frozen for quantification of proteins both upstream and downstream of mammalian target of rapamycin (mTOR). In the AA group, we found a threefold increase in ribosomal protein S6 kinase (p70(S6k)) and Erk1/2 phosphorylation; however, blocking the physiological rise in insulin with somatostatin in the AA+S group prevented this increase. In the HI group, Akt, Erk1/2, p70(S6k), and ribosomal protein S6 were highly phosphorylated and 4E-binding protein 1 (4E-BP1) associated with eukaryotic initiation factor (eIF)4E decreased by 30%. These data show that insulin is a significant regulator of intermediates involved in translation initiation in ovine fetal skeletal muscle. Furthermore, the effect of amino acids is dependent on a concomitant increase in fetal insulin concentrations, because amino acid infusion upregulates p70(S6k) and Erk only when amino acid-stimulated increase in insulin occurs.

  4. The Effect of Pueraria Lobata/Rehmannia Glutinosa and Exercise on Fatty Acid Transporters Expression in Ovariectomized Rats Skeletal Muscles

    Science.gov (United States)

    Kim, Hye Jin; Yoon, Hae Min; Kwon, Oran; Lee, Won Jun

    2016-01-01

    [Purpose] Pueraria lobata/rehmannia glutinosa (PR) and exercise have been receiving a lot of attention from postmenopausal women, as a result of the side effects of estrogen replacement therapy. However, the effects of PR and exercise on fatty acid transporters (FATPs), which play essential role in fatty acid transport, have not been studied. In this study, we evaluated the effects of PR and aerobic exercise on FATP1, FABPpm and FAT/CD36 expression in ovariectomized rat skeletal muscles. [Methods] Sixty rats were randomly divided into 6 groups: (1)HSV; high fat diet (HFD)+sedentary+vehicle, (2)HSP; HFD+sedentary+PR, (3)HSH; HFD+sedentary+17β-estradiol, (4)HEV; HFD+exercise+vehicle, (5) HEP; HFD+exercise+PR, (6)HEH; HFD+exercise+17β-estradiol. Exercise consisted of treadmill exercise (1-4th week: 15 m/min for 30 min, 5-8th week: 18 m/min for 40 min, 5 times/week). [Results] Exercise does not alter FATP1 and FAT/CD36 gene levels in soleus and plantaris muscles. In contrast, exercise had main effect on up-regulation of FABPpm mRNA expression in both muscles. However, FABPpm level was not increased by exercise combined with treatments, indicative of no additive effects of PR or hormone on FABPpm gene expression. On the other hand, immunohistochemistry result showed that translocation of FATPs proteins to plasma membrane were higher in PR, exercise groups, and exercise combined with PR groups in both muscles. [Conclusion] These result showed that aerobic exercise and PR may help increase fat-oxidation through the induction of FABPpm, a muscle specific transporter, in OVX rat skeletal muscles. In addition, FABPpm expression is possibly regulated post-transcriptionally in exercise, or pre-translationally in PR. PMID:27757385

  5. Maternal Betaine Supplementation during Gestation Enhances Expression of mtDNA-Encoded Genes through D-Loop DNA Hypomethylation in the Skeletal Muscle of Newborn Piglets.

    Science.gov (United States)

    Jia, Yimin; Song, Haogang; Gao, Guichao; Cai, Demin; Yang, Xiaojing; Zhao, Ruqian

    2015-11-25

    Betaine has been widely used in animal and human nutrition to promote muscle growth and performance, yet it remains unknown whether maternal betaine supplementation during gestation affects the metabolic characteristics of neonatal skeletal muscles. In the present study, feeding sows with betaine-supplemented diets throughout gestation significantly upregulated the expression of mtDNA-encoded OXPHOS genes (p betaine supplementation increased the plasma betaine concentration and muscle expression of methyl transfer enzymes (p betaine supplementation during gestation enhances expression of mtDNA-encoded genes through D-loop DNA hypomethylation in the skeletal muscle of newborn piglets.

  6. Enhancement of glucose uptake in skeletal muscle L6 cells and insulin secretion in pancreatic hamster-insulinoma-transfected cells by application of non-thermal plasma jet

    Science.gov (United States)

    Kumar, Naresh; Kaushik, Nagendra K.; Park, Gyungsoon; Choi, Eun H.; Uhm, Han S.

    2013-11-01

    Type-II diabetes Mellitus is characterized by defects in insulin action on peripheral tissues, such as skeletal muscle, adipose tissue, and liver and pancreatic beta cells. Since the skeletal muscle accounts for approximately 75% of insulin-stimulated glucose-uptake in our body, impaired insulin secretion from defected beta cell plays a major role in the afflicted glucose homoeostasis. It was shown that the intracellular reactive oxygen species and nitric oxide level was increased by non-thermal-plasma treatment in ambient air. These increased intracellular reactive species may enhance glucose uptake and insulin secretion through the activation of intracellular calcium (Ca+) and cAMP production.

  7. Trehalose accumulation enhances tolerance of Saccharomyces cerevisiae to acetic acid.

    Science.gov (United States)

    Yoshiyama, Yoko; Tanaka, Koichi; Yoshiyama, Kohei; Hibi, Makoto; Ogawa, Jun; Shima, Jun

    2015-02-01

    Trehalose confers protection against various environmental stresses on yeast cells. In this study, trehalase gene deletion mutants that accumulate trehalose at high levels showed significant stress tolerance to acetic acid. The enhancement of trehalose accumulation can thus be considered a target in the breeding of acetic acid-tolerant yeast strains.

  8. Ca2+ Influx via the Na+/Ca2+ Exchanger Is Enhanced in Malignant Hyperthermia Skeletal Muscle*

    Science.gov (United States)

    Altamirano, Francisco; Eltit, José M.; Robin, Gaëlle; Linares, Nancy; Ding, Xudong; Pessah, Isaac N.; Allen, Paul D.; López, José R.

    2014-01-01

    Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca2+ dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca2+ depending on cellular activity. Resting intracellular calcium ([Ca2+]r) and sodium ([Na+]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na+]e elevates [Ca2+]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca2+ or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca2+]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca2+]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca2+]r in MHS muscle fibers and decreases the amplitude of [Ca2+]r rise triggered by halothane, but had no effect on [Ca2+]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca2+ transient elicited by high [K+]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca2+]r and the Ca2+ transient area induced by high [K+]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca2+ transients associated with K+-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers. PMID:24847052

  9. Ca2+ influx via the Na+/Ca2+ exchanger is enhanced in malignant hyperthermia skeletal muscle.

    Science.gov (United States)

    Altamirano, Francisco; Eltit, José M; Robin, Gaëlle; Linares, Nancy; Ding, Xudong; Pessah, Isaac N; Allen, Paul D; López, José R

    2014-07-04

    Malignant hyperthermia (MH) is potentially fatal pharmacogenetic disorder of skeletal muscle caused by intracellular Ca(2+) dysregulation. NCX is a bidirectional transporter that effluxes (forward mode) or influxes (reverse mode) Ca(2+) depending on cellular activity. Resting intracellular calcium ([Ca(2+)]r) and sodium ([Na(+)]r) concentrations are elevated in MH susceptible (MHS) swine and murine muscles compared with their normal (MHN) counterparts, although the contribution of NCX is unclear. Lowering [Na(+)]e elevates [Ca(2+)]r in both MHN and MHS swine muscle fibers and it is prevented by removal of extracellular Ca(2+) or reduced by t-tubule disruption, in both genotypes. KB-R7943, a nonselective NCX3 blocker, reduced [Ca(2+)]r in both swine and murine MHN and MHS muscle fibers at rest and decreased the magnitude of the elevation of [Ca(2+)]r observed in MHS fibers after exposure to halothane. YM-244769, a high affinity reverse mode NCX3 blocker, reduces [Ca(2+)]r in MHS muscle fibers and decreases the amplitude of [Ca(2+)]r rise triggered by halothane, but had no effect on [Ca(2+)]r in MHN muscle. In addition, YM-244769 reduced the peak and area under the curve of the Ca(2+) transient elicited by high [K(+)]e and increased its rate of decay in MHS muscle fibers. siRNA knockdown of NCX3 in MHS myotubes reduced [Ca(2+)]r and the Ca(2+) transient area induced by high [K(+)]e. These results demonstrate a functional NCX3 in skeletal muscle whose activity is enhanced in MHS. Moreover reverse mode NCX3 contributes to the Ca(2+) transients associated with K(+)-induced depolarization and the halothane-triggered MH episode in MHS muscle fibers.

  10. Short-term calorie restriction enhances skeletal muscle stem cell function

    National Research Council Canada - National Science Library

    Cerletti, Massimiliano; Jang, Young C; Finley, Lydia W S; Haigis, Marcia C; Wagers, Amy J

    2012-01-01

    ... metabolic and longevity regulators. Moreover, CR enhanced endogenous muscle repair and CR initiated in either donor or recipient animals improved the contribution of donor cells to regenerating muscle after transplant...

  11. Whey protein hydrolysate enhances HSP90 but does not alter HSP60 and HSP25 in skeletal muscle of rats.

    Directory of Open Access Journals (Sweden)

    Carolina Soares Moura

    Full Text Available Whey protein hydrolysate (WPH intake has shown to increase HSP70 expression. The aim of the present study was to investigate whether WPH intake would also influences HSP90, HSP60 and HSP25 expression, as well as associated parameters. Forty-eight male Wistar rats were divided into sedentary (unstressed and exercised (stressed groups, and were fed with three different sources of protein: whey protein (WP, whey protein hydrolysate (WPH and casein (CAS as a control, based on the AIN93G diet for 3 weeks. WPH intake increased HSP90 expression in both sedentary and exercised animals compared to WP or CAS, however no alteration was found from exercise or diet to HSP60 or HSP25. Co-chaperone Aha1 and p-HSF1 were also increased in the exercised animals fed with WPH in comparison with WP or CAS, consistent with enhanced HSP90 expression. VEGF and p-AKT were increased in the WPH exercised group. No alteration was found in BCKDH, PI3-Kinase (p85, GFAT, OGT or PGC for diet or exercise. The antioxidant system GPx, catalase and SOD showed different responses to diet and exercise. The data indicate that WPH intake enhanced factors related to cell survival, such as HSP90 and VEGF, but does not alter HSP60 or HSP25 in rat skeletal muscle.

  12. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    Directory of Open Access Journals (Sweden)

    Hirotaka Yamamoto

    2016-01-01

    Full Text Available Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders.

  13. Amla Enhances Mitochondrial Spare Respiratory Capacity by Increasing Mitochondrial Biogenesis and Antioxidant Systems in a Murine Skeletal Muscle Cell Line

    Science.gov (United States)

    Yamamoto, Hirotaka; Morino, Katsutaro; Mengistu, Lemecha; Ishibashi, Taishi; Kiriyama, Kohei; Ikami, Takao; Maegawa, Hiroshi

    2016-01-01

    Amla is one of the most important plants in Indian traditional medicine and has been shown to improve various age-related disorders while decreasing oxidative stress. Mitochondrial dysfunction is a proposed cause of aging through elevated oxidative stress. In this study, we investigated the effects of Amla on mitochondrial function in C2C12 myotubes, a murine skeletal muscle cell model with abundant mitochondria. Based on cell flux analysis, treatment with an extract of Amla fruit enhanced mitochondrial spare respiratory capacity, which enables cells to overcome various stresses. To further explore the mechanisms underlying these effects on mitochondrial function, we analyzed mitochondrial biogenesis and antioxidant systems, both proposed regulators of mitochondrial spare respiratory capacity. We found that Amla treatment stimulated both systems accompanied by AMPK and Nrf2 activation. Furthermore, we found that Amla treatment exhibited cytoprotective effects and lowered reactive oxygen species (ROS) levels in cells subjected to t-BHP-induced oxidative stress. These effects were accompanied by increased oxygen consumption, suggesting that Amla protected cells against oxidative stress by using enhanced spare respiratory capacity to produce more energy. Thus we identified protective effects of Amla, involving activation of mitochondrial function, which potentially explain its various effects on age-related disorders. PMID:27340504

  14. Supplementation with branched-chain amino acids ameliorates hypoalbuminemia, prevents sarcopenia, and reduces fat accumulation in the skeletal muscles of patients with liver cirrhosis.

    Science.gov (United States)

    Kitajima, Yoichiro; Takahashi, Hirokazu; Akiyama, Takumi; Murayama, Kenichiro; Iwane, Shinji; Kuwashiro, Takuya; Tanaka, Kenichi; Kawazoe, Seiji; Ono, Naofumi; Eguchi, Takahisa; Anzai, Keizo; Eguchi, Yuichiro

    2017-07-24

    Liver cirrhosis induces marked metabolic disorders, protein-energy malnutrition, and sarcopenia. The objective of the study reported here was to investigate the effects of dietary branched-chain amino acids (BCAAs) on systemic glucose metabolism, skeletal muscle, and prognosis of patients with liver cirrhosis. Japanese patients with liver cirrhosis (n = 21) were enrolled into a longitudinal study in which their diets were supplemented with BCAAs. We evaluated glucose metabolism and analyzed the skeletal muscle area index (SAI) and intramuscular adipose tissue content (IMAC) using computed tomography. After 48 weeks of supplementation with BCAAs, there were no changes in glucose metabolism and skeletal muscle findings. In patients with ameliorated hypoalbuminemia, IMAC was significantly decreased and SAI was preserved concomitant with decreasing 90- and 120-min post-challenge plasma glucose levels (P increased albumin levels, IMAC was significantly increased and the SAI was significantly decreased (P decreased IMAC and 20.0% in patients with increased IMAC. Amelioration of hypoalbuminemia associated with BCAA supplementation correlated with decreased fat accumulation in skeletal muscle, maintenance of skeletal muscle mass, and improved glucose sensitivity, all factors which may contribute to improving the survival of patients with liver cirrhosis.

  15. Effects of thapsigargin and cyclopiazonic acid on the sarcoplasmic reticulum Ca2+ pump of skinned fibres from frog skeletal muscle.

    Science.gov (United States)

    Du, G G; Ashley, C C; Lea, T J

    1994-12-01

    Thapsigargin has been reported to inhibit ATP-dependent Ca2+ uptake by isolated sarcoplasmic reticulum (SR) vesicles of vertebrate skeletal muscle fibres at nanomolar concentrations. There have been no reports confirming this effect in skinned muscle fibre preparations. We have examined the ability of thapsigargin to inhibit the uptake of Ca2+ by the SR in mechanically skinned fibres of frog iliofibularis muscles, using the size of the caffeine-induced contracture to assess the Ca2+ content of the SR. The SR was first depleted of Ca2+ and then reloaded for 1 min at pCa 6.2 in the presence and absence of thapsigargin. When 5 min were allowed for diffusion, a thapsigargin concentration of at least 131 microM was required to inhibit Ca2+ loading by 50%. In contrast, another SR Ca2+ uptake inhibitor, cyclopiazonic acid, was more effective, producing 50% inhibition at 7.0 microM and total inhibition at 50 microM. When cyclopiazonic acid (100 microM) was applied after, rather than during, Ca2+ loading, the caffeine-induced contracture was not changed. Thapsigargin (300 microM), on the other hand, caused some reduction in the peak amplitude of the caffeine-induced contracture when applied after Ca2+ loading. The poor effectiveness of thapsigargin in the skinned fibres, compared with in SR vesicles, is attributed to its slow diffusion into the skinned fibres, perhaps as a result of binding to myofibrillar components.

  16. Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs

    Science.gov (United States)

    Infants unable to maintain oral feeding can be nourished by orogastric tube. We have shown that orogastric continuous feeding restricts muscle protein synthesis compared with intermittent bolus feeding in neonatal pigs. To determine whether leucine leu infusion can be used to enhance protein synthes...

  17. Metabolic engineering as a tool for enhanced lactic acid production.

    Science.gov (United States)

    Upadhyaya, Bikram P; DeVeaux, Linda C; Christopher, Lew P

    2014-12-01

    Metabolic engineering is a powerful biotechnological tool that finds, among others, increased use in constructing microbial strains for higher lactic acid productivity, lower costs and reduced pollution. Engineering the metabolic pathways has concentrated on improving the lactic acid fermentation parameters, enhancing the acid tolerance of production organisms and their abilities to utilize a broad range of substrates, including fermentable biomass-derived sugars. Recent efforts have focused on metabolic engineering of lactic acid bacteria as they produce high yields and have a small genome size that facilitates their genetic manipulation. We summarize here the current trends in metabolic engineering techniques and strategies for manipulating lactic acid producing organisms developed to address and overcome major challenges in the lactic acid production process.

  18. Weak acidity of vinyl CH bonds enhanced by halogen substitution.

    Science.gov (United States)

    Craig, Norman C; Matlin, Albert R

    2014-02-21

    As shown by the rates of proton-deuteron exchange in ethylenes with halogen substituents, the weak acidity of vinyl CH bonds is enhanced by halogen substitution. Relative rates of exchange in basic deuterium oxide reflect the relative acidities. Substitution in the α position has the strongest effect. Less electronegative halogens such as bromine increase the acidity more than does fluorine. The vinyl CH acid strengths correlate closely with the energies of deprotonation of isolated molecules into isolated anions, as computed with the MP2/cc-pVQZ model. The smaller deprotonation energies are associated with the stronger acids. Atomic charges from a natural bond order analysis done with the MP2/aug-cc-pVQZ model show that the negative charge becomes more dispersed in the anions of the stronger acids. Results are given for 13 haloethylenes and for 6 halogen-substituted butadienes, cyclopropenes, and a cyclobutene.

  19. Nectar amino acids enhance reproduction in male butterflies.

    Science.gov (United States)

    Cahenzli, Fabian; Erhardt, Andreas

    2013-01-01

    After over 30 years of research, it was recently shown that nectar amino acids increase female butterfly fecundity. However, little attention has been paid to the effect of nectar amino acids on male butterfly reproduction. Here, we show that larval food conditions (nitrogen-rich vs. nitrogen-poor host plants) and adult diet quality (nectar with or without amino acids) affected the amount of consumed nectar in Coenonympha pamphilus males. Furthermore, amino acids in the nectar diet of males increased progeny's larval hatching mass, irrespective of paternal larval reserves. Our study takes the whole reproductive cycle of male butterflies into account, and also considers the role of females in passing male nutrients to offspring, as males' realized reproduction was examined indirectly via nuptial gifts, by female performance. With this comprehensive approach, we demonstrate for the first time that nectar amino acids can improve male butterfly reproduction, supporting the old postulate that nectar amino acids generally enhance butterfly fitness.

  20. Enhancing charge storage of conjugated polymer electrodes with phenolic acids

    Science.gov (United States)

    Wagner, Michal; Rębiś, Tomasz; Inganäs, Olle

    2016-01-01

    We here present studies of electrochemical doping of poly(1-aminoanthraquinone) (PAAQ) films with three structurally different phenolic acids. The examined phenolic acids (sinapic, ferulic and syringic acid) were selected due to their resemblance to redox active groups, which can be found in lignin. The outstanding electrochemical stability of PAAQ films synthesized for this work enabled extensive cycling of phenolic acid-doped PAAQ films. Potentiodynamic and charge-discharge studies revealed that phenolic acid-doped PAAQ films exhibited enhanced capacitance in comparison to undoped PAAQ films, together with appearance of redox activity characteristics specific for each dopant. Electrochemical kinetic studies performed on microelectrodes affirmed the fast electron transfer for hydroquinone-to-quinone reactions with these phenolic compounds. These results imply the potential application of phenolic acids in cheap and degradable energy storage devices.

  1. Conjugated linoleic acid or omega 3 fatty acids increase mitochondrial biosynthesis and metabolism in skeletal muscle cells

    OpenAIRE

    Vaughan Roger A; Garcia-Smith Randi; Bisoffi Marco; Conn Carole A; Trujillo Kristina A

    2012-01-01

    Abstract Background Polyunsaturated fatty acids are popular dietary supplements advertised to contribute to weight loss by increasing fat metabolism in liver, but the effects on overall muscle metabolism are less established. We evaluated the effects of conjugated linoleic acid (CLA) or combination omega 3 on metabolic characteristics in muscle cells. Methods Human rhabdomyosarcoma cells were treated with either DMSO control, or CLA or combination omega 3 for 24 or 48 hours. RNA was determine...

  2. Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling

    DEFF Research Database (Denmark)

    Jafari, Abbas; Siersbæk, Majken; Chen, Li;

    2015-01-01

    for several malignant and nonmalignant conditions. We screened a library of kinase inhibitors to identify small molecules that enhance bone formation by human skeletal (stromal or mesenchymal) stem cells (hMSC). We identified H-8 (known to inhibit protein kinases A, C, and G) as a potent enhancer of ex vivo......Development of novel approaches to enhance bone regeneration is needed for efficient treatment of bone defects. Protein kinases play a key role in regulation of intracellular signal transduction pathways, and pharmacological targeting of protein kinases has led to development of novel treatments...

  3. Phytanic acid stimulates glucose uptake in a model of skeletal muscles, the primary porcine myotubes

    DEFF Research Database (Denmark)

    Che, Brita Ngum; Oksbjerg, Niels; Hellgren, Lars;

    2013-01-01

    ABSTRACT: BACKGROUND: Phytanic acid (PA) is a chlorophyll metabolite with potentials in regulating glucose metabolism, as it is a natural ligand of the peroxisome proliferator-activated receptor (PPAR) that is known to regulate hepatic glucose homeostasis. This study aimed to establish primary...

  4. Acid tolerance response (ATR) of microbial communities during the enhanced biohydrogen process via cascade acid stress.

    Science.gov (United States)

    Lin, Xiaoqin; Xia, Yan; Yan, Qun; Shen, Wei; Zhao, Mingxing

    2014-03-01

    Enhanced biohydrogen production via cascade acid stress on microbial communities, structure patterns of the microbial communities revealed by PLFAs, and the succession of biohydrogen related species against cascade acid stress were all investigated. It was found that hydrogen production could be improved from 48.7 to 79.4mL/gVS after cascade acid stress. In addition, the Gram negative (G(-)) bacteria were found to be more tolerant to organic acids than those of the Gram positive (G(+)) bacteria, regardless of the dominance of G(+) bacteria within the microbial communities. Moreover, Clostridium butyricum, Clostridium aciditolerans and Azospira oryzae, were proved to be enriched, and then might play indispensable roles for the enhanced biohydrogen production after cascade acid stress, as which were responsible for the biohydrogen accumulation, acid tolerance and nitrogen removal, respectively.

  5. Enhancement of adipogenesis and fibrogenesis in skeletal muscle of Wagyu compared with Angus cattle.

    Science.gov (United States)

    Duarte, M S; Paulino, P V R; Das, A K; Wei, S; Serão, N V L; Fu, X; Harris, S M; Dodson, M V; Du, M

    2013-06-01

    Intramuscular fat and collagen content are major factors affecting beef quality, but mechanisms regulating intramuscular adipose and connective tissue deposition are far from clear. Japanese Wagyu cattle are well known for their extremely high marbling. The objective of this study was to evaluate intramuscular fat (IMF) and collagen deposition in the muscle of Wagyu compared with Angus cattle. Animals were managed under the same condition and slaughtered at an averaging 585 ± 12.1 kg of BW. Samples of sternomandibularis muscle were collected from Wagyu (n = 3) and Angus (n = 3) for molecular and histological investigations of adipogenesis and fibrogenesis. With exception of C/EBPβ (P = 0.2864), the expression of the adipogenic markers C/EBPα (P = 0.008), PPARγ (P = 0.028), and zip finger protein 423 (Zfp423; P = 0.047) in Wagyu were greater than in Angus muscle, which was consistent with greater IMF deposition in Wagyu (P Angus cattle. These results clearly show that both IMF and collagen contents are enhanced in Wagyu cattle and more adipogenic cells are detected in Wagyu muscle, indicating intramuscular adipogenesis is enhanced in Wagyu compared with Angus muscle.

  6. Branched-chain amino acid-containing dipeptides, identified from whey protein hydrolysates, stimulate glucose uptake rate in L6 myotubes and isolated skeletal muscles.

    Science.gov (United States)

    Morifuji, Masashi; Koga, Jinichiro; Kawanaka, Kentaro; Higuchi, Mitsuru

    2009-02-01

    In earlier studies we showed that dietary whey protein increased skeletal muscle and liver glycogen content in exercise-trained rats. However, little is known about whether ingredients of whey protein stimulate skeletal muscle glycogen accumulation. The aim of this study was to identify bioactive peptides in whey protein hydrolysates (WPH) which stimulated glucose uptake and glycogen synthesis rate in skeletal muscles. Branched-chain amino acid (BCAA)-containing dipeptides in WPH were identified using LC/MS/MS. L6 myotubes and isolated epitrochlearis muscles were used for the glucose uptake assays. The myotubes and muscles were incubated with or without 1 mM dipeptides, LY294002 a phosphoinositide 3-kinase (PI3-kinase) inhibitor, or GF102903X an atypical protein kinase C (aPKC) inhibitor, followed by measurement of 2-deoxyglucose uptake. Isolated muscles were incubated for 3 h with or without 1 mM Ile-Leu to determine glycogen synthesis rate. The BCAA-containing dipeptides, Ile-Val, Leu-Val, Val-Leu, Ile-Ile, Leu-Ile, Ile-Leu, and Leu-Leu were detected in the WPH by LC/MS/MS. These dipeptides caused significant stimulation in glucose uptake rate in the L6 myotubes. Ile-Leu, the main component in WPH, also stimulated glucose uptake in isolated skeletal muscles. Stimulation of glucose uptake by Ile-Leu was completely inhibited by treatment with either LY294002, or GF109203X in both L6 cells and isolated muscles. Ile-Leu increased glycogen contents in isolated muscles. These results suggest that BCAA-containing bioactive dipeptides in WPH stimulate glucose uptake in skeletal muscles via the PI3-kinase and aPKC pathways, resulting in increased skeletal muscle glycogen contents.

  7. An Effective Acid Combination for Enhanced Properties and Corrosion Control of Acidizing Sandstone Formation

    Science.gov (United States)

    Umer Shafiq, Mian; Khaled Ben Mahmud, Hisham

    2016-03-01

    To fulfill the demand of the world energy, more technologies to enhance the recovery of oil production are being developed. Sandstone acidizing has been introduced and it acts as one of the important means to increase oil and gas production. Sandstone acidizing operation generally uses acids, which create or enlarge the flow channels of formation around the wellbore. In sandstone matrix acidizing, acids are injected into the formation at a pressure below the formation fracturing pressure, in which the injected acids react with mineral particles that may restrict the flow of hydrocarbons. Most common combination is Hydrofluoric Acid - Hydrochloric with concentration (3% HF - 12% HCl) known as mud acid. But there are some problems associated with the use of mud acid i.e., corrosion, precipitation. In this paper several new combinations of acids were experimentally screened to identify the most effective combination. The combinations used consist of fluoboric, phosphoric, formic and hydrofluoric acids. Cores were allowed to react with these combinations and results are compared with the mud acid. The parameters, which are analyzed, are Improved Permeability Ratio, strength and mineralogy. The analysis showed that the new acid combination has the potential to be used in sandstone acidizing.

  8. Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-Aged Mice to Diet-Induced Insulin Resistance

    NARCIS (Netherlands)

    Koonen, Debby P. Y.; Sung, Miranda M. Y.; Kao, Cindy K. C.; Dolinsky, Vernon W.; Koves, Timothy R.; Ilkayeva, Olga; Jacobs, Rene L.; Vance, Dennis E.; Light, Peter E.; Muoio, Deborah M.; Febbraio, Maria; Dyck, Jason R. B.

    2010-01-01

    OBJECTIVE-Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal m

  9. Alterations in Skeletal Muscle Fatty Acid Handling Predisposes Middle-Aged Mice to Diet-Induced Insulin Resistance

    NARCIS (Netherlands)

    Koonen, Debby P. Y.; Sung, Miranda M. Y.; Kao, Cindy K. C.; Dolinsky, Vernon W.; Koves, Timothy R.; Ilkayeva, Olga; Jacobs, Rene L.; Vance, Dennis E.; Light, Peter E.; Muoio, Deborah M.; Febbraio, Maria; Dyck, Jason R. B.

    OBJECTIVE-Although advanced age is a risk factor for type 2 diabetes, a clear understanding of the changes that occur during middle age that contribute to the development of skeletal muscle insulin resistance is currently lacking. Therefore, we sought to investigate how middle age impacts skeletal

  10. Resistance Training Enhances Skeletal Muscle Innervation Without Modifying the Number of Satellite Cells or their Myofiber Association in Obese Older Adults.

    Science.gov (United States)

    Messi, María Laura; Li, Tao; Wang, Zhong-Min; Marsh, Anthony P; Nicklas, Barbara; Delbono, Osvaldo

    2016-10-01

    Studies in humans and animal models provide compelling evidence for age-related skeletal muscle denervation, which may contribute to muscle fiber atrophy and loss. Skeletal muscle denervation seems relentless; however, long-term, high-intensity physical activity appears to promote muscle reinnervation. Whether 5-month resistance training (RT) enhances skeletal muscle innervation in obese older adults is unknown. This study found that neural cell-adhesion molecule, NCAM+ muscle area decreased with RT and was inversely correlated with muscle strength. NCAM1 and RUNX1 gene transcripts significantly decreased with the intervention. Type I and type II fiber grouping in the vastus lateralis did not change significantly but increases in leg press and knee extensor strength inversely correlated with type I, but not with type II, fiber grouping. RT did not modify the total number of satellite cells, their number per area, or the number associated with specific fiber subtypes or innervated/denervated fibers. Our results suggest that RT has a beneficial impact on skeletal innervation, even when started late in life by sedentary obese older adults.

  11. Amino acid sequence of myoglobin from emu (Dromaius novaehollandiae) skeletal muscle.

    Science.gov (United States)

    Suman, S P; Joseph, P; Li, S; Beach, C M; Fontaine, M; Steinke, L

    2010-11-01

    The objective of the present study was to characterize the primary structure of emu myoglobin (Mb). Emu Mb was isolated from Iliofibularis muscle employing gel-filtration chromatography. Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry was employed to determine the exact molecular mass of emu Mb in comparison with horse Mb, and Edman degradation was utilized to characterize the amino acid sequence. The molecular mass of emu Mb was 17,380 Da and was close to those reported for ratite and poultry myoglobins. Similar to myoglobins from meat-producing livestock and birds, emu Mb has 153 amino acids. Emu Mb contains 9 histidines. Proximal and distal histidines, responsible for coordinating oxygen-binding property of Mb, are conserved in emu. Emu Mb shared more than 90% homology with ratite and chicken myoglobins, whereas it demonstrated only less than 70% sequence similarity with ruminant myoglobins.

  12. Contrasting metabolic effects of medium- versus long-chain fatty acids in skeletal muscle.

    Science.gov (United States)

    Montgomery, Magdalene K; Osborne, Brenna; Brown, Simon H J; Small, Lewin; Mitchell, Todd W; Cooney, Gregory J; Turner, Nigel

    2013-12-01

    Dietary intake of long-chain fatty acids (LCFAs) plays a causative role in insulin resistance and risk of diabetes. Whereas LCFAs promote lipid accumulation and insulin resistance, diets rich in medium-chain fatty acids (MCFAs) have been associated with increased oxidative metabolism and reduced adiposity, with few deleterious effects on insulin action. The molecular mechanisms underlying these differences between dietary fat subtypes are poorly understood. To investigate this further, we treated C2C12 myotubes with various LCFAs (16:0, 18:1n9, and 18:2n6) and MCFAs (10:0 and 12:0), as well as fed mice diets rich in LCFAs or MCFAs, and investigated fatty acid-induced changes in mitochondrial metabolism and oxidative stress. MCFA-treated cells displayed less lipid accumulation, increased mitochondrial oxidative capacity, and less oxidative stress than LCFA-treated cells. These changes were associated with improved insulin action in MCFA-treated myotubes. MCFA-fed mice exhibited increased energy expenditure, reduced adiposity, and better glucose tolerance compared with LCFA-fed mice. Dietary MCFAs increased respiration in isolated mitochondria, with a simultaneous reduction in reactive oxygen species generation, and subsequently low oxidative damage. Collectively our findings indicate that in contrast to LCFAs, MCFAs increase the intrinsic respiratory capacity of mitochondria without increasing oxidative stress. These effects potentially contribute to the beneficial metabolic actions of dietary MCFAs.

  13. [THE EXCESS OF PALMITIC FATTY ACID IN FOOD AS MAIN CAUSE OF LIPOIDOSIS OF INSULIN-DEPENDENT CELLS: SKELETAL MYOCYTES, CARDIO-MYOCYTES, PERIPORTAL HEPATOCYTES, KUPFFER MACROPHAGES AND B-CELLS OF PANCREAS].

    Science.gov (United States)

    Titov, V N

    2016-02-01

    In phylogenesis, becoming of biologicalfunctions and biological reactions proceeds with the purpose ofpermanent increasing of "kinetic perfection ". The main role belongs to factors ofphysical, chemical and biological kinetics, their evaluation using systemic approach technique under permanent effect of natural selection. The late-in-phylogenesis insulin, proceeded with, in development of biological function of locomotion, specialization of insulin-dependent cells: skeletal myocytes, syncytium of cardiomyocytes, subcutaneous adipocytes, periportal hepatocytes, Kupffer's macrophages and β-cells of islets of pancreas. The insulin initiated formation of new, late in phylogenesis, large pool of fatty cells-subcutaneous adipocytes that increased kinetic parameters of biological function of locomotion. In realization of biological function of locomotion only adipocytes absorb exogenous mono unsaturated and saturated fatty acids in the form of triglycerides in composition of oleic and palmitic lipoproteins of very low density using apoE/B-100 endocytosis. The rest of insulin-dependent cells absorb fatty acids in the form of unesterified fatty acids from associates with albumin and under effect of CD36 of translocase offatty acids. The insulin in all insulin-depended cells inhibits biological reaction of lipolysis enhancing contributing into development of lipoidosis. The insulin expresses transfer offatty acids in the form of unsaturated fatty acids from adipocytes into matrix of mitochondria. The insulin supplies insulin-dependent cells with substrates for acquiring energy subject to that in pool of unsaturated fatty acids in adipocytes prevails hydrophobic palmitic unsaturated fatiy acid that slowly passes into matrix through external membrane ofmitochondria; oxidases of mitochondria so slowly implement its β-oxidation that content of exogenous palmitic unsaturatedfatty acid can't be higher than phylogenetic, physiological level - 15% of all amount offatty acids

  14. Effects of oral phosphatidic acid feeding with or without whey protein on muscle protein synthesis and anabolic signaling in rodent skeletal muscle.

    Science.gov (United States)

    Mobley, C Brooks; Hornberger, Troy A; Fox, Carlton D; Healy, James C; Ferguson, Brian S; Lowery, Ryan P; McNally, Rachel M; Lockwood, Christopher M; Stout, Jeffrey R; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2015-01-01

    Phosphatidic acid (PA) is a diacyl-glycerophospholipid that acts as a signaling molecule in numerous cellular processes. Recently, PA has been proposed to stimulate skeletal muscle protein accretion, but mechanistic studies are lacking. Furthermore, it is unknown whether co-ingesting PA with other leucine-containing ingredients can enhance intramuscular anabolic signaling mechanisms. Thus, the purpose of this study was to examine if oral PA feeding acutely increases anabolic signaling markers and muscle protein synthesis (MPS) in gastrocnemius with and without whey protein concentrate (WPC). Overnight fasted male Wistar rats (~250 g) were randomly assigned to four groups: control (CON, n = 6-13), PA (29 mg; n = 8), WPC (197 mg; n = 8), or PA + WPC (n = 8). Three hours post-feeding, gastrocnemius muscle was removed for markers of Akt-mTOR signaling, gene expression patterns related to skeletal muscle mass regulation and metabolism, and MPS analysis via the SUnSET method. Compared to CON rats, PA, WPC and PA + WPC resulted in a significant elevation in the phosphorylation of mTOR (Ser2481) and rps6 (Ser235/236) (p < 0.05) in the gastrocnemius though there were no differences between the supplemented groups. MPS levels in the gastrocnemius were significantly (p < 0.05) elevated in WPC versus CON rats, and tended to be elevated in PA versus CON rats (p = 0.08), though MPS was less in PA + WPC versus WPC rats (p < 0.05) in spite of robust increases in mTOR pathway activity markers in the former group. C2C12 myoblast data agreed with the in vivo data herein showing that PA increased MPS levels 51% (p < 0.001) phosphorylated p70s6k (Thr389) levels 67% (p < 0.001). Our results are the first in vivo evidence to demonstrate that PA tends to increases MPS 3 h post-feeding, though PA may delay WPC-mediated MPS kinetics within a 3 h post-feeding window.

  15. Tetanic contraction induces enhancement of fatigability and sarcomeric damage in atrophic skeletal muscle and its underlying molecular mechanisms.

    Science.gov (United States)

    Yu, Zhi-Bin

    2013-11-01

    Muscle unloading due to long-term exposure of weightlessness or simulated weightlessness causes atrophy, loss of functional capacity, impaired locomotor coordination, and decreased resistance to fatigue in the antigravity muscles of the lower limbs. Besides reducing astronauts' mobility in space and on returning to a gravity environment, the molecular mechanisms for the adaptation of skeletal muscle to unloading also play an important medical role in conditions such as disuse and paralysis. The tail-suspended rat model was used to simulate the effects of weightlessness on skeletal muscles and to induce muscle unloading in the rat hindlimb. Our series studies have shown that the maximum of twitch tension and the twitch duration decreased significantly in the atrophic soleus muscles, the maximal tension of high-frequency tetanic contraction was significantly reduced in 2-week unloaded soleus muscles, however, the fatigability of high-frequency tetanic contraction increased after one week of unloading. The maximal isometric tension of intermittent tetanic contraction at optimal stimulating frequency did not alter in 1- and 2-week unloaded soleus, but significantly decreased in 4-week unloaded soleus. The 1-week unloaded soleus, but not extensor digitorum longus (EDL), was more susceptible to fatigue during intermittent tetanic contraction than the synchronous controls. The changes in K+ channel characteristics may increase the fatigability during high-frequency tetanic contraction in atrophic soleus muscles. High fatigability of intermittent tetanic contraction may be involved in enhanced activity of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and switching from slow to fast isoform of myosin heavy chain, tropomyosin, troponin I and T subunit in atrophic soleus muscles. Unloaded soleus muscle also showed a decreased protein level of neuronal nitric oxide synthase (nNOS), and the reduction in nNOS-derived NO increased frequency of calcium sparks and elevated

  16. Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term

    OpenAIRE

    Sales, Francisco; Pacheco, David; Blair, Hugh; Kenyon, Paul; McCoard, Sue

    2013-01-01

    Twin sheep fetuses have reduced skeletal muscle weight near birth relative to singles as a result of restricted muscle hypertrophy. Intracellular free amino acids (FAA) are reported to regulate metabolic pathways which control muscle protein accretion, whereby reduced intracellular content of specific FAA may reduce their activation and therefore, muscle hypertrophy. The aim of this study was to determine whether differences in muscle weight between singleton and twin fetuses, under different...

  17. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2017-09-05

    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.

  18. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2016-08-09

    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.

  19. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Regular postexercise cooling enhances mitochondrial biogenesis through AMPK and p38 MAPK in human skeletal muscle.

    Science.gov (United States)

    Ihsan, Mohammed; Markworth, James F; Watson, Greig; Choo, Hui Cheng; Govus, Andrew; Pham, Toan; Hickey, Anthony; Cameron-Smith, David; Abbiss, Chris R

    2015-08-01

    This study investigated the effect of regular postexercise cold water immersion (CWI) on muscle aerobic adaptations to endurance training. Eight males performed 3 sessions/wk of endurance training for 4 wk. Following each session, subjects immersed one leg in a cold water bath (10°C; COLD) for 15 min, while the contralateral leg served as a control (CON). Muscle biopsies were obtained from vastus lateralis of both CON and COLD legs prior to training and 48 h following the last training session. Samples were analyzed for signaling kinases: p38 MAPK and AMPK, peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), enzyme activities indicative of mitochondrial biogenesis, and protein subunits representative of respiratory chain complexes I-V. Following training, subjects' peak oxygen uptake and running velocity were improved by 5.9% and 6.2%, respectively (P 0.8) were noted with changes in protein content of p38 (d = 1.02, P = 0.064), PGC-1α (d = 0.99, P = 0.079), and peroxisome proliferator-activated receptor α (d = 0.93, P = 0.10) in COLD compared with CON. No differences between conditions were observed in the representative protein subunits of respiratory complexes II, IV, and V and in the activities of several mitochondrial enzymes (P > 0.05). These findings indicate that regular CWI enhances p38, AMPK, and possibly mitochondrial biogenesis. Copyright © 2015 the American Physiological Society.

  1. Electroporation-enhanced delivery of nucleic acid vaccines.

    Science.gov (United States)

    Broderick, Kate E; Humeau, Laurent M

    2015-02-01

    The naked delivery of nucleic acid vaccines is notoriously inefficient, and an enabling delivery technology is required to direct efficiently these constructs intracellularly. A delivery technology capable of enhancing nucleic acid uptake in both cells in tissues and in culture is electroporation (EP). EP is a physical delivery mechanism that increases the permeability of mammalian cell membranes and allows the trafficking of large macromolecules into the cell. EP has now been used extensively in the clinic and been shown to be an effective method to increase both the uptake of the construct and the breadth and magnitude of the resulting immune responses. Excitingly, 2014 saw the announcement of the first EP-enhanced DNA vaccine Phase II trial demonstrating clinical efficacy. This review seeks to introduce the reader to EP as a technology to enhance the delivery of DNA and RNA vaccines and highlight several published clinical trials using this delivery modality.

  2. Coaxial electrospun poly(ε-caprolactone), multiwalled carbon nanotubes, and polyacrylic acid/polyvinyl alcohol scaffold for skeletal muscle tissue engineering.

    Science.gov (United States)

    McKeon-Fischer, K D; Flagg, D H; Freeman, J W

    2011-12-01

    Skeletal muscle repair after injury usually results in scar tissue and decreased functionality. In this study, we coaxially electrospun poly(ε-caprolactone), multiwalled carbon nanotubes, and a hydrogel consisting of polyvinyl alcohol and polyacrylic acid (PCL-MWCNT-H) to create a self-contained nanoactuating scaffold for skeletal muscle tissue replacement. This was then compared to electrospun PCL and PCL-MWCNT scaffolds. All scaffolds displayed some conductivity; however, MWCNT incorporation increased the conductivity. Only the PCL-MWCNT-H actuated when stimulated with 15 and 20 V. The PCL, PCL-MWCNT, and hydrogel only scaffolds demonstrated no reaction when 5, 8, 10, 15, and 20 V were applied. Thus, all components of the PCL-MWCNT-H scaffold are essential for movement. All three PCL-containing scaffolds were biocompatible, but the PCL-MWCNT-H scaffolds displayed more multinucleated cells with actin interaction. After tensile testing, the MWCNT-containing scaffolds had higher strength than the rat and pig skeletal muscle. Although the mechanical properties were higher than muscle, the PCL-MWCNT-H scaffold shows promise as a potential bioartificial nanoactuator for skeletal muscle.

  3. Attenuation of skeletal muscle reperfusion injury with intravenous 12 amino acid peptides that bind to pathogenic IgM.

    Science.gov (United States)

    Chan, Rodney K; Verna, Nicola; Afnan, Jalil; Zhang, Ming; Ibrahim, Shahrul; Carroll, Michael C; Moore, Francis D

    2006-02-01

    The injury sustained by reperfused skeletal muscle is inflammatory and is initiated by binding of pre-formed IgM to involved tissue, followed by local complement activation and further inflammation. A clone of natural IgM has been described that initiates this injury, suggesting that specific antigens are exposed on ischemic tissues that act as ligands for this pathogenic antibody. In these experiments, we examine the properties of short peptide sequences, and their homologues, that bind to the antigen-combining site of this pathogenic IgM clone. A 12-mer phage display library was biopanned with the pathogenic IgM clone and then negatively selected against an inactive natural IgM clone. All 8 clones that bound specifically to the pathogenic IgM had closely related amino acid sequences. P8 is the clone that bound most avidly. Tissue lysates from ischemic tissue were reacted with pathogenic IgM, and immune complexes isolated and analyzed on SDS-PAGE. Bands were excised and sequenced, identifying non-muscle myosin as the protein reacting with pathogenic antibody in ischemic gut and glycogen phosphorylase as the counterpart in ischemic skeletal muscle. Both proteins contain sequence homologous to P8; N2 and GP1 are the natural 12-mers homologues that are contained within non-muscle myosin and glycogen phosphorylase, respectively. Wild-type C57/Bl6 mice, divided into groups receiving saline, P8, N2, GP1, or a random peptide at the start of the experiment, were subjected to 2 hours of tourniquet induced hind limb ischemia and 3 hours of reperfusion. Muscle was assessed for injury with histology and for immune activation with histochemistry. Intravenous administration of P8, N2, and GP1 led to significant attenuation of muscle injury (13 +/- 1.8 injured fibers/50 counted, 12 +/- 0.81, 8.0 +/- 0.73 respectively) after reperfusion injury compared to animals receiving saline (26 +/- 2.3) or the same mass of a random peptide (22 +/- 2.3), P less than .05. This level of

  4. Increased VLDL-TG fatty acid storage in skeletal muscle in men with type 2 diabetes

    DEFF Research Database (Denmark)

    Andersen, Iben R; Søndergaard, Esben; Sørensen, Lars P

    2016-01-01

    -TG storage rate and LPL activity or other storage factors in muscle or adipose tissue. However, LPL activity correlated with fractional VLDL-TG storage in abdominal fat (p=0.04). CONCLUSIONS: Men with type 2 diabetes have increased VLDL-TG storage in muscle tissue, potentially contributing to increased......CONTEXT: Lipoprotein lipase (LPL) activity is considered the rate-limiting step of very-low-density-lipoprotein triglycerides (VLDL-TG) tissue storage, and has been suggested to relate to the development of obesity as well as insulin resistance and type 2 diabetes. OBJECTIVE: The objective...... of the study was to assess the relationship between the quantitative storage of VLDL-TG fatty acids and LPL activity and other storage factors in muscle and adipose tissue. In addition, we examine whether such relations were influenced by type 2 diabetes. DESIGN: 23 men (12 with type 2 diabetes, 11 non...

  5. Ursolic acid regulates aging process through enhancing of metabolic sensor proteins level.

    Science.gov (United States)

    Bahrami, Soroush Alaghehband; Bakhtiari, Nuredin

    2016-08-01

    We previously reported that Ursolic Acid (UA) ameliorates skeletal muscle performance through satellite cells proliferation and cellular energy status. In studying the potential role of the hypothalamus in aging, we developed a strategy to pursue UA effects on the hypothalamus anti-aging proteins such as; SIRT1, SIRT6, PGC-1β and α-Klotho. In this study, we used a model of aging animals (C57BL/6). UA dissolved in Corn oil (20mg/ml) and then administrated (200mg/Kg i.p injection) to mice, twice daily for 7days. After treatment times, the mice perfused and the hypothalamus isolated for preparing of tissue to Immunofluorescence microscopy. The data illustrated that UA significantly increased SIRT1 (∼3.5±0.3 folds) and SIRT-6 (∼1.5±0.2 folds) proteins overexpression (Presults showed that UA enhanced α-Klotho (∼3.3±0.3) and PGC-1β (∼2.6±0.2 folds) proteins levels (PUA through enhancing of anti-aging biomarkers (SIRT1 and SIRT6) and PGC-1β in hypothalamus regulates aging-process and attenuates mitochondrial-related diseases. In regard to the key role of α-Klotho in aging, our data indicate that UA may be on the horizon to forestall diseases of aging.

  6. Enhanced formic acid oxidation on Cu-Pd nanoparticles

    Science.gov (United States)

    Dai, Lin; Zou, Shouzhong

    Developing catalysts with high activity and high resistance to surface poisoning remains a challenge in direct formic acid fuel cell research. In this work, copper-palladium nanoparticles were formed through a galvanic replacement process. After electrochemically selective dissolution of surface Cu, Pd-enriched Cu-Pd nanoparticles were formed. These particles exhibit much higher formic acid oxidation activities than that on pure Pd nanoparticles, and they are much more resistant to the surface poisoning. Possible mechanisms of catalytic activity enhancement are briefly discussed.

  7. Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

    Science.gov (United States)

    Badeau, Robert M.; Honka, Miikka-Juhani; Bucci, Marco; Iozzo, Patricia; Eriksson, Johan G.; Nuutila, Pirjo

    2017-01-01

    Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR) and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (p = 0.015). DHA/FA associated significantly with skeletal muscle glucose uptake (GU) (p = 0.031) and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value) in the OLM group only (p = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers. PMID:28165405

  8. Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

    Directory of Open Access Journals (Sweden)

    Robert M. Badeau

    2017-02-01

    Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

  9. Disturbance of mitochondrial functions provoked by the major long-chain 3-hydroxylated fatty acids accumulating in MTP and LCHAD deficiencies in skeletal muscle.

    Science.gov (United States)

    Cecatto, Cristiane; Godoy, Kálita Dos Santos; da Silva, Janaína Camacho; Amaral, Alexandre Umpierrez; Wajner, Moacir

    2016-10-01

    The pathogenesis of the muscular symptoms and recurrent rhabdomyolysis that are commonly manifested in patients with mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxy-acyl-CoA dehydrogenase (LCHAD) deficiencies is still unknown. In this study we investigated the effects of the major long-chain monocarboxylic 3-hydroxylated fatty acids (LCHFA) accumulating in these disorders, namely 3-hydroxytetradecanoic (3HTA) and 3-hydroxypalmitic (3HPA) acids, on important mitochondrial functions in rat skeletal muscle mitochondria. 3HTA and 3HPA markedly increased resting (state 4) and decreased ADP-stimulated (state 3) and CCCP-stimulated (uncoupled) respiration. 3HPA provoked similar effects in permeabilized skeletal muscle fibers, validating the results obtained in purified mitochondria. Furthermore, 3HTA and 3HPA markedly diminished mitochondrial membrane potential, NAD(P)H content and Ca(2+) retention capacity in Ca(2+)-loaded mitochondria. Mitochondrial permeability transition (mPT) induction probably underlie these effects since they were totally prevented by cyclosporin A and ADP. In contrast, the dicarboxylic analogue of 3HTA did not alter the tested parameters. Our data strongly indicate that 3HTA and 3HPA behave as metabolic inhibitors, uncouplers of oxidative phosphorylation and mPT inducers in skeletal muscle. It is proposed that these pathomechanisms disrupting mitochondrial homeostasis may be involved in the muscle alterations characteristic of MTP and LCHAD deficiencies.

  10. Nucleic acid molecules conferring enhanced ethanol tolerance and microorganisms having enhanced tolerance to ethanol

    Science.gov (United States)

    Brown, Steven; Guss, Adam; Yang, Shihui; Karpinets, Tatiana; Lynd, Lee; Shao, Xiongjun

    2014-01-14

    The present invention provides isolated nucleic acid molecules which encode a mutant acetaldehyde-CoA/alcohol dehydrogenase or mutant alcohol dehydrogenase and confer enhanced tolerance to ethanol. The invention also provides related expression vectors, genetically engineered microorganisms having enhanced tolerance to ethanol, as well as methods of making and using such genetically modified microorganisms for production of biofuels based on fermentation of biomass materials.

  11. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Larsen, Steen; Helge, Jørn Wulff;

    2013-01-01

    Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic...... for diabetic muscles. The molecular mechanism behind the effect of metformin is not fully clarified but inhibition of complex I in the mitochondria and also activation of the 5'AMP activated protein kinase (AMPK) has been reported in muscle. Furthermore, both AMPK activation and metformin treatment have been...... associated with stimulation of mitochondrial function and biogenesis. However, a causal relationship in skeletal muscle has not been investigated. We hypothesized that potential effects of in vivo metformin treatment on mitochondrial function and protein expressions in skeletal muscle are dependent upon AMPK...

  12. ALS skeletal muscle shows enhanced TGF-β signaling, fibrosis and induction of fibro/adipogenic progenitor markers

    Science.gov (United States)

    Gonzalez, David; Contreras, Osvaldo; Rebolledo, Daniela L.; Espinoza, Juan Pablo; van Zundert, Brigitte

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which upper and lower motoneurons degenerate leading to muscle wasting, paralysis and eventually death from respiratory failure. Several studies indicate that skeletal muscle contributes to disease progression; however the molecular mechanisms remain elusive. Fibrosis is a common feature in skeletal muscle under chronic damage conditions such as those caused by muscular dystrophies or denervation. However, the exact mechanisms of fibrosis induction and the cellular bases of this pathological response are unknown. We show that extracellular matrix (ECM) components are augmented in skeletal muscles of symptomatic hSOD1G93A mice, a widely used murine model of ALS. These mice also show increased TGF-β1 mRNA levels, total Smad3 protein levels and p-Smad3 positive nuclei. Furthermore, platelet-derived growth factor receptor-α (PDGFRα), Tcf4 and α-smooth muscle actin (α-SMA) levels are augmented in the skeletal muscle of symptomatic hSOD1G93A mice. Additionally, the fibro/adipogenic progenitors (FAPs), which are the main producers of ECM constituents, are also increased in these pathogenic conditions. Therefore, FAPs and ECM components are more abundant in symptomatic stages of the disease than in pre-symptomatic stages. We present evidence that fibrosis observed in skeletal muscle of symptomatic hSOD1G93A mice is accompanied with an induction of TGF-β signaling, and also that FAPs might be involved in triggering a fibrotic response. Co-localization of p-Smad3 positive cells together with PDGFRα was observed in the interstitial cells of skeletal muscles from symptomatic hSOD1G93A mice. Finally, the targeting of pro-fibrotic factors such as TGF-β, CTGF/CCN2 and platelet-derived growth factor (PDGF) signaling pathway might be a suitable therapeutic approach to improve muscle function in several degenerative diseases. PMID:28520806

  13. Lewis acidity enhancement of triarylborane by appended phosphine oxide groups.

    Science.gov (United States)

    Kwak, Jaewoo; Nghia, Nguyen Van; Lee, Junseong; Kim, Hyoseok; Park, Myung Hwan; Lee, Min Hyung

    2015-03-14

    A series of mono-, di-, and tri-phosphine oxide substituted triarylboranes, Mes2BAr (1), MesBAr2 (2), and BAr3 (3) (Ar = 4-(Ph2PO)-2,6-Me2-C6H2) were prepared to investigate the effect of a phosphine oxide group (Ph2PO) on Lewis acidity enhancement of triarylboranes. The X-ray crystal structure of 3 revealed peripheral decoration of Ph2PO groups with a C3-axis perpendicular to the trigonal boron center. UV/Vis absorption and PL spectra indicated a significant contribution of π(Mes or phenylene) → pπ(B) charge transfer in the lower-energy electronic transition. The reduction potential measured by cyclic voltammetry showed apparent LUMO stabilization by introduction of phosphine oxide groups, the extent of which gradually increased with the increasing number of phosphine oxide groups. Lewis acidity enhancement was also supported by the gradual increase in fluoride ion affinity in the order 3 > 2 > 1. Theoretical calculations suggest that introduction of a Ph2PO group into a triarylborane significantly enhances the Lewis acidity of the boron center via an inductive electron-withdrawing effect and this effect is additive for multiple phosphine oxide groups.

  14. Enhance decarboxylation reaction of carboxylic acids in clay minerals

    Energy Technology Data Exchange (ETDEWEB)

    Negron-Mendoza, A.; Ramos, S.; Albarran, G. [Instituto de Ciencias y Artes, Chiapas (Mexico). Escuela de Biologia

    1995-10-01

    Clay minerals are important constituents of the Earth`s crust. These minerals catalyze reactions in several ways: by energy transfer processes, redox reactions, stabilization of intermediates and by Broensted or Lewis acidity behavior. Important set of organic reactions can be improved in the precedence of clay minerals. Besides the properties of clays to catalyze chemical reactions, it is possible to enhance some of its reactions by using ionizing radiation. The phenomenon of radiation-induced catalysis may be connected with ionizing process in the solid and with the trapped non-equilibrium charge carriers. In this paper we are reporting the decarboxylation reaction of carboxylic acids catalyzed by clay and by irradiation of the system acid-clay. We studied the behaviour of several carboxylic acids and analyzed them by gas chromatography, X-ray and infrared spectroscopy. The results showed that decarboxylation of the target compound is the dominating pathway. The reaction is enhanced by gamma radiation in several orders of magnitude. (author).

  15. Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng

    2016-12-01

    Full Text Available Supplementation of branched-chain amino acids (BCAA has been demonstrated to promote skeletal muscle mass gain, but the mechanisms underlying this observation are still unknown. Since the regulation of muscle mass depends on a dynamic equilibrium (fasted losses–fed gains in protein turnover, the aim of this study was to investigate the effects of BCAA supplementation on muscle protein synthesis and degradation in fed/fasted states and the related mechanisms. Fourteen 26- (Experiment 1 and 28-day-old (Experiment 2 piglets were fed reduced-protein diets without or with supplemental BCAA. After a four-week acclimation period, skeletal muscle mass and components of anabolic and catabolic signaling in muscle samples after overnight fasting were determined in Experiment 1. Pigs in Experiment 2 were implanted with carotid arterial, jugular venous, femoral arterial and venous catheters, and fed once hourly along with the intravenous infusion of NaH13CO3 for 2 h, followed by a 6-h infusion of [1-13C]leucine. Muscle leucine kinetics were measured using arteriovenous difference technique. The mass of most muscles was increased by BCAA supplementation. During feeding, BCAA supplementation increased leucine uptake, protein synthesis, protein degradation and net transamination. The greater increase in protein synthesis than in protein degradation resulted in elevated protein deposition. Protein synthesis was strongly and positively correlated with the intramuscular net production of α-ketoisocaproate (KIC and protein degradation. Moreover, BCAA supplementation enhanced the fasted-state phosphorylation of protein translation initiation factors and inhibited the protein-degradation signaling of ubiquitin-proteasome and autophagy-lysosome systems. In conclusion, supplementation of BCAA to reduced-protein diet increases fed-state protein synthesis and inhibits fasted-state protein degradation, both of which could contribute to the elevation of skeletal muscle

  16. Effects of Supplementation of Branched-Chain Amino Acids to Reduced-Protein Diet on Skeletal Muscle Protein Synthesis and Degradation in the Fed and Fasted States in a Piglet Model.

    Science.gov (United States)

    Zheng, Liufeng; Wei, Hongkui; He, Pingli; Zhao, Shengjun; Xiang, Quanhang; Pang, Jiaman; Peng, Jian

    2016-12-28

    Supplementation of branched-chain amino acids (BCAA) has been demonstrated to promote skeletal muscle mass gain, but the mechanisms underlying this observation are still unknown. Since the regulation of muscle mass depends on a dynamic equilibrium (fasted losses-fed gains) in protein turnover, the aim of this study was to investigate the effects of BCAA supplementation on muscle protein synthesis and degradation in fed/fasted states and the related mechanisms. Fourteen 26- (Experiment 1) and 28-day-old (Experiment 2) piglets were fed reduced-protein diets without or with supplemental BCAA. After a four-week acclimation period, skeletal muscle mass and components of anabolic and catabolic signaling in muscle samples after overnight fasting were determined in Experiment 1. Pigs in Experiment 2 were implanted with carotid arterial, jugular venous, femoral arterial and venous catheters, and fed once hourly along with the intravenous infusion of NaH(13)CO₃ for 2 h, followed by a 6-h infusion of [1-(13)C]leucine. Muscle leucine kinetics were measured using arteriovenous difference technique. The mass of most muscles was increased by BCAA supplementation. During feeding, BCAA supplementation increased leucine uptake, protein synthesis, protein degradation and net transamination. The greater increase in protein synthesis than in protein degradation resulted in elevated protein deposition. Protein synthesis was strongly and positively correlated with the intramuscular net production of α-ketoisocaproate (KIC) and protein degradation. Moreover, BCAA supplementation enhanced the fasted-state phosphorylation of protein translation initiation factors and inhibited the protein-degradation signaling of ubiquitin-proteasome and autophagy-lysosome systems. In conclusion, supplementation of BCAA to reduced-protein diet increases fed-state protein synthesis and inhibits fasted-state protein degradation, both of which could contribute to the elevation of skeletal muscle mass in

  17. Exploring unsaturated fatty acid cholesteryl esters as transdermal permeation enhancers.

    Science.gov (United States)

    Rambharose, Sanjeev; Kalhapure, Rahul S; Jadhav, Mahantesh; Govender, Thirumala

    2017-04-01

    The intrinsic protective barrier property of skin, one of the major challenges in the design of transdermal drug delivery systems, can be overcome through the use of chemical permeation enhancers (CPEs). Herein, we explore the potential of unsaturated fatty acid (UFA) esters of cholesterol (Chol) viz., oleate, linoleate and linolenate, as transdermal CPEs using tenofovir (TNF) as a model drug. All Chol UFA esters at 1% w/w were found to be more effective enhancers when compared to their respective parent fatty acids (FAs) and saturated FA counterparts. Cholesteryl linolenate (Chol-LLA) showed the most superior performance (enhancement ratio (ER) = 3.71). The greatest ER for Chol-LLA (5.93) was achieved at a concentration of 2% w/w. The histomorphological and transepithelial electrical resistance (TEER) evaluations supported the results of the permeability studies. These findings showed no significant loss in the integrity of the epidermis, with drug and enhancer treatment having temporary effects on the barrier property of the epidermis. Chol UFA esters can therefore be considered as new CPEs for exploitation in topical formulations for various classes of drugs.

  18. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata)

    National Research Council Canada - National Science Library

    Md. Shahidul Haque; Md. Asraful Haque; Swapan Kumar Roy; M.M.H. Khan; Md. Mosharrof Hossain

    2014-01-01

    .... They were exposed to cold (4–8 °C) for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle...

  19. Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice

    DEFF Research Database (Denmark)

    Kristensen, Jonas Møller; Larsen, Steen; Helge, Jørn Wulff

    2013-01-01

    Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for ...

  20. Formic acid electrooxidation on Pd in acidic solutions studied by surface-enhanced infrared absorption spectroscopy.

    Science.gov (United States)

    Miyake, Hiroto; Okada, Tatsuhiro; Samjeské, Gabor; Osawa, Masatoshi

    2008-07-07

    A mechanistic study of electrocatalytic oxidation of formic acid on Pd in sulfuric and perchloric acids is reported. Surface-enhanced infrared absorption spectroscopy in the attenuated total reflection mode (ATR-SEIRAS) shows the adsorption of CO, bridge-bonded formate, bicarbonate, and supporting anions on the electrode surface. Poisoning of the Pd surface by CO, formed by dehydration of formic acid, is very slow and scarcely affects formic acid oxidation. The anions are adsorbed more strongly in the order of (bi)sulfate > bicarbonate > perchlorate, among which the most strongly adsorbed (bi)sulfate considerably suppresses formic acid oxidation in the double layer region. The oxidation is suppressed also at higher potentials in both acids by the oxidation of the Pd surface. Adsorbed formate is detected only when formic acid oxidation is suppressed. The results show that formate is a short-lived reactive intermediate in formic acid oxidation and is hence detected when its decomposition yielding CO(2) is suppressed. The high electrocatalytic activity of Pd can be ascribed to the high tolerance to CO contamination and also high catalytic activity toward formate decomposition.

  1. Effect of Enhancing Urea-Humic Acid Mixture with Refined Acid Sulphate Soil

    Directory of Open Access Journals (Sweden)

    Mohd T.M. Yusuff

    2009-01-01

    Full Text Available Problem statement: Acid Sulphate Soil (ASS is a problem soil partly because of its high acidity. This low pH could be exploited to reduce ammonia loss from urea by reducing soil microsite pH. The use Humic Acid (HA to control ammonia loss from urea has been reported but the cost of this material is high. This laboratory study compared the effect of enhancing urea-humic acid mixtures with acid sulphate soil on NH3 loss, pH, exchangeable ammonium and available nitrate contents. Approach: Humic acid, acid sulfate soil and soil used in the incubation study were analyzed for selected soil physical-chemical properties using standard procedures. Urea-HA-ASS mixtures were prepared and ammonia volatilization of the mixtures was evaluated by the closed-dynamic air flow system. The treatments were evaluated in a randomized complete block design with 3 replications. Standard procedures were used to determine ammonia loss, soil pH, exchangeable ammonium and available nitrate at 22 days of incubation. Data obtained were analyzed using analysis of variance and Duncan's test using Statistical Analysis System (SAS version 9.2. Results: Urea amended with 0.75 g ASS significantly reduced ammonia volatilization. Although the use of appropriate amount of acid sulphate soil to control ammonia loss is possible, excessive use of this material is not recommended because of Fe in it. Conclusion: Urea amended with 0.75 g ASS reduced ammonia.

  2. Study of Valproic Acid-Enhanced Hepatocyte Steatosis

    Directory of Open Access Journals (Sweden)

    Renin Chang

    2016-01-01

    Full Text Available Valproic acid (VPA is one of the most widely used antiepilepsy drugs. However, several side effects, including weight gain and fatty liver, have been reported in patients following VPA treatment. In this study, we explored the molecular mechanisms of VPA-induced hepatic steatosis using FL83B cell line-based in vitro model. Using fluorescent lipid staining technique, we found that VPA enhanced oleic acid- (OLA- induced lipid accumulation in a dose-dependent manner in hepatocytes; this may be due to upregulated lipid uptake, triacylglycerol (TAG synthesis, and lipid droplet formation. Real-time PCR results showed that, following VPA treatment, the expression levels of genes encoding cluster of differentiation 36 (Cd36, low-density lipoprotein receptor-related protein 1 (Lrp1, diacylglycerol acyltransferase 2 (Dgat2, and perilipin 2 (Plin2 were increased, that of carnitine palmitoyltransferase I a (Cpt1a was not affected, and those of acetyl-Co A carboxylase α (Acca and fatty acid synthase (Fasn were decreased. Furthermore, using immunofluorescence staining and flow cytometry analyses, we found that VPA also induced peroxisome proliferator-activated receptor γ (PPARγ nuclear translocation and increased levels of cell-surface CD36. Based on these results, we propose that VPA may enhance OLA-induced hepatocyte steatosis through the upregulation of PPARγ- and CD36-dependent lipid uptake, TAG synthesis, and lipid droplet formation.

  3. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Directory of Open Access Journals (Sweden)

    Anusuya Das

    Full Text Available In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid (PLAGA microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2 improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3 via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1 mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  4. Delivery of bioactive lipids from composite microgel-microsphere injectable scaffolds enhances stem cell recruitment and skeletal repair.

    Science.gov (United States)

    Das, Anusuya; Barker, Daniel A; Wang, Tiffany; Lau, Cheryl M; Lin, Yong; Botchwey, Edward A

    2014-01-01

    In this study, a microgel composed of chitosan and inorganic phosphates was used to deliver poly(lactic-co-glycolic acid) (PLAGA) microspheres loaded with sphingolipid growth factor FTY720 to critical size cranial defects in Sprague Dawley rats. We show that sustained release of FTY720 from injected microspheres used alone or in combination with recombinant human bone morphogenic protein-2 (rhBMP2) improves defect vascularization and bone formation in the presence and absence of rhBMP2 as evaluated by quantitative microCT and histological measurements. Moreover, sustained delivery of FTY720 from PLAGA and local targeting of sphingosine 1-phosphate (S1P) receptors reduces CD45+ inflammatory cell infiltration, promotes endogenous recruitment of CD29+CD90+ bone progenitor cells and enhances the efficacy of rhBMP2 from chitosan microgels. Companion in vitro studies suggest that selective activation of sphingosine receptor subtype-3 (S1P3) via FTY720 treatment induces smad-1 phosphorylation in bone-marrow stromal cells. Additionally, FTY720 enhances stromal cell-derived factor-1 (SDF-1) mediated chemotaxis of CD90+CD11B-CD45- bone progenitor cells in vitro after stimulation with rhBMP2. We believe that use of such small molecule delivery formulations to recruit endogenous bone progenitors may be an attractive alternative to exogenous cell-based therapy.

  5. Enhancing and targeting nucleic acid delivery by magnetic force.

    Science.gov (United States)

    Plank, Christian; Anton, Martina; Rudolph, Carsten; Rosenecker, Joseph; Krötz, Florian

    2003-08-01

    Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.

  6. Fatty acid conjugation enhances the activities of antimicrobial peptides.

    Science.gov (United States)

    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.

  7. Transcutaneous delivery of levodopa: enhancement by fatty acid synthesis inhibition.

    Science.gov (United States)

    Babita, Kumar; Tiwary, Ashok K

    2005-01-01

    The present investigation aimed at evaluating the role of fatty acid synthesis inhibition in enhancing transcutaneous delivery of levodopa (LD). Rat epidermis was treated with ethanol and various doses of cerulenin (an inhibitor of fatty acid synthase enzyme system) for reducing the normal level of fatty acids. Calcium chloride (0.1 mM) and/or verapamil (1 microM) were coapplied to cerulenin treated skin in order to modulate duration of epidermal perturbation. These treated skin portions were used for estimation of altered triglyceride content (an indicator of fatty acid synthesis), differential scanning calorimetry (DSC) analysis, and in vitro permeation of LD. Plasma concentration of LD was monitored in rats following topical application of various transdermal formulations. Application of cerulenin (0.1 or 0.15 mM/7 cm(2)) to viable rat skin inhibited approximately 60% triglyceride synthesis with respect to control at 2 h. Coapplication of calcium chloride (0.1 mM) significantly increased this inhibition, whereas verapamil application reduced this effect. The decrease in triglyceride content reduced the enthalpy of the lipid endothermic transition. The in vitro permeation of LD was enhanced 3-fold across skin excised after treatment with cerulenin. LD did not permeate across normal skin. The effective plasma concentration (C(eff)) of LD was achieved within 3 h and maintained till 10 h by a single topical application of a carbidopa-levodopa combination (1:4) to ethanol-perturbed cerulenin-treated skin. Coapplication of calcium chloride reduced the time lag to achieve C(eff) to 2 h and maintained it till 24 h. A single transdermal LD (64 mg) patch formulated with calcium chloride (0.1 mM) and cerulenin (0.1 mM) dissolved in a propylene glycol:ethanol (7:3) mixture seems to offer a noninvasive approach for transcutaneous delivery of levodopa.

  8. Significant enhancement of formic acid oxidation using rhodium nanostructures.

    Science.gov (United States)

    Balan, Beena K; Sathe, Bhaskar R

    2012-12-01

    The electrocatalytic activity of as-synthesized shape selective Rh nanostructures has been demonstrated using cyclic voltammetry, revealing unique shape-dependant performance towards HCOOH oxidation. Interestingly, the enhancement factor (R) for different shapes of Rh with respect to that of commercial Rh towards formic acid oxidation ranges up to 20,000% for cubes as compared to 17,500% for pyramids and 11,000% for hexagons respectively. Mechanistic pathway for comparatively better sensitivity of cubes as compared to other shapes has been correlated with the results of X-ray diffraction.

  9. Pipecolic acid enhances resistance to bacterial infection and primes salicylic acid and nicotine accumulation in tobacco.

    Science.gov (United States)

    Vogel-Adghough, Drissia; Stahl, Elia; Návarová, Hana; Zeier, Juergen

    2013-11-01

    Distinct amino acid metabolic pathways constitute integral parts of the plant immune system. We have recently identified pipecolic acid (Pip), a lysine-derived non-protein amino acid, as a critical regulator of systemic acquired resistance (SAR) and basal immunity to bacterial infection in Arabidopsis thaliana. In Arabidopsis, Pip acts as an endogenous mediator of defense amplification and priming. For instance, Pip conditions plants for effective biosynthesis of the phenolic defense signal salicylic acid (SA), accumulation of the phytoalexin camalexin, and expression of defense-related genes. Here, we show that tobacco plants respond to leaf infection by the compatible bacterial pathogen Pseudomonas syringae pv tabaci (Pstb) with a significant accumulation of several amino acids, including Lys, branched-chain, aromatic, and amide group amino acids. Moreover, Pstb strongly triggers, alongside the biosynthesis of SA and increases in the defensive alkaloid nicotine, the production of the Lys catabolites Pip and α-aminoadipic acid. Exogenous application of Pip to tobacco plants provides significant protection to infection by adapted Pstb or by non-adapted, hypersensitive cell death-inducing P. syringae pv maculicola. Pip thereby primes tobacco for rapid and strong accumulation of SA and nicotine following bacterial infection. Thus, our study indicates that the role of Pip as an amplifier of immune responses is conserved between members of the rosid and asterid groups of eudicot plants and suggests a broad practical applicability for Pip as a natural enhancer of plant disease resistance.

  10. Potential role of TBC1D4 in enhanced post-exercise insulin action in human skeletal muscle

    DEFF Research Database (Denmark)

    Treebak, Jonas Thue; Frøsig, Christian; Pehmøller, Christian

    2009-01-01

    AIMS/HYPOTHESIS: TBC1 domain family, member 4 (TBC1D4; also known as AS160) is a cellular signalling intermediate to glucose transport regulated by insulin-dependent and -independent mechanisms. Skeletal muscle insulin sensitivity is increased after acute exercise by an unknown mechanism that does.......01). However, TBC1D4 phosphorylation on Ser-318, Ser-341, Ser-588 and Ser-751 was higher in the previously exercised leg, both in the absence and in the presence of insulin (p power = 0.39). 14-3-3 binding capacity for TBC1D4 increased equally (p ... insulin stimulation. CONCLUSION/INTERPRETATION: We provide evidence for site-specific phosphorylation of TBC1D4 in human skeletal muscle in response to physiological hyperinsulinaemia. The data support the idea that TBC1D4 is a nexus for insulin- and exercise-responsive signals that may mediate increased...

  11. Folic acid induces salicylic acid-dependent immunity in Arabidopsis and enhances susceptibility to Alternaria brassicicola.

    Science.gov (United States)

    Wittek, Finni; Kanawati, Basem; Wenig, Marion; Hoffmann, Thomas; Franz-Oberdorf, Katrin; Schwab, Wilfried; Schmitt-Kopplin, Philippe; Vlot, A Corina

    2015-08-01

    Folates are essential for one-carbon transfer reactions in all organisms and contribute, for example, to de novo DNA synthesis. Here, we detected the folate precursors 7,8-dihydropteroate (DHP) and 4-amino-4-deoxychorismate (ADC) in extracts from Arabidopsis thaliana plants by Fourier transform ion cyclotron resonance-mass spectrometry. The accumulation of DHP, but not ADC, was induced after infection of plants with Pseudomonas syringae delivering the effector protein AvrRpm1. Application of folic acid or the DHP precursor 7,8-dihydroneopterin (DHN) enhanced resistance in Arabidopsis to P. syringae and elevated the transcript accumulation of the salicylic acid (SA) marker gene pathogenesis-related1 in both the treated and systemic untreated leaves. DHN- and folic acid-induced systemic resistance was dependent on SA biosynthesis and signalling. Similar to SA, folic acid application locally enhanced Arabidopsis susceptibility to the necrotrophic fungus Alternaria brassicicola. Together, the data associate the folic acid pathway with innate immunity in Arabidopsis, simultaneously activating local and systemic SA-dependent resistance to P. syringae and suppressing local resistance to A. brassicicola.

  12. Upregulation of skeletal muscle PGC-1α through the elevation of cyclic AMP levels by Cyanidin-3-glucoside enhances exercise performance

    Science.gov (United States)

    Matsukawa, Toshiya; Motojima, Hideko; Sato, Yuki; Takahashi, Shinya; Villareal, Myra O.; Isoda, Hiroko

    2017-01-01

    Regular exercise and physical training enhance physiological capacity and improve metabolic diseases. Skeletal muscles require peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) in the process of their adaptation to exercise owing to PGC-1α’s ability to regulate mitochondrial biogenesis, angiogenesis, and oxidative metabolism. Cyanidin-3-glucoside (Cy3G) is a natural polyphenol and a nutraceutical factor, which has several beneficial effects on human health. Here, the effect of Cy3G on exercise performance and the underlying mechanisms involved were investigated. ICR mice were given Cy3G (1 mg/kg, orally) everyday and made to perform weight-loaded swimming exercise for 15 days. The endurance of mice orally administered with Cy3G was improved, enabling them to swim longer (time) and while the levels of exercise-induced lactate and fatigue markers (urea nitrogen, creatinine and total ketone bodies) were reduced. Additionally, the expression of lactate metabolism-related genes (lactate dehydrogenase B and monocarboxylate transporter 1) in gastrocnemius and biceps femoris muscles was increased in response to Cy3G-induced PGC-1α upregulation. In vitro, using C2C12 myotubes, Cy3G-induced elevation of intracellular cyclic AMP levels increased PGC-1α expression via the Ca2+/calmodulin-dependent protein kinase kinase pathway. This study demonstrates that Cy3G enhances exercise performance by activating lactate metabolism through skeletal muscle PGC-1α upregulation. PMID:28317895

  13. Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages.

    Science.gov (United States)

    Liu, Yingying; Li, Fengna; Kong, Xiangfeng; Tan, Bie; Li, Yinghui; Duan, Yehui; Blachier, François; Hu, Chien-An A; Yin, Yulong

    2015-01-01

    Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA) pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet)- or higher/NRC (National Research Council)-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I) and longissimus dorsi muscle (LDM, type II) were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR) signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (Ppigs had generally higher (Ppigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (Ppigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K), and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (Ppig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (Ppigs, but repressed (Ppigs. The higher protein-NRC diet increased ratio of p-mTOR/mTOR in Landrace pigs. These findings indicated that the dynamic consequences of AA profile and protein deposition in muscle tissues are the concerted effort of distinctive genotype, nutrient status, age, and

  14. Short-duration intermittent hypoxia enhances endurance capacity by improving muscle fatty acid metabolism in mice.

    Science.gov (United States)

    Suzuki, Junichi

    2016-04-01

    This study was designed to (1) investigate the effects of acute short-duration intermittent hypoxia on musclemRNAand microRNAexpression levels; and (2) clarify the mechanisms by which short-duration intermittent hypoxia improves endurance capacity. Experiment-1: Male mice were subjected to either acute 1-h hypoxia (12% O2), acute short-duration intermittent hypoxia (12% O2for 15 min, room air for 10 min, 4 times, Int-Hypo), or acute endurance exercise (Ex). The expression of vascular endothelial growth factor-AmRNAwas significantly greater than the control at 0 h post Ex and 6 h post Int-Hypo in the deep red region of the gastrocnemius muscle. miR-16 expression levels were significantly lower at 6 and 10 h post Int-Hypo. Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α)mRNAlevels were significantly greater than the control at 3 h post Ex and 6 h post Int-Hypo. miR-23a expression levels were lower than the control at 6-24 h post Int-Hypo. Experiment-2: Mice were subjected to normoxic exercise training with or without intermittent hypoxia for 3 weeks. Increases in maximal exercise capacity were significantly greater by training with short-duration intermittent hypoxia (IntTr) than without hypoxia. Both 3-Hydroxyacyl-CoA-dehydrogenase and total carnitine palmitoyl transferase activities were significantly enhanced in IntTr. Peroxisome proliferator-activated receptor delta andPGC-1α mRNAlevels were both significantly greater in IntTr than in the sedentary controls. These results suggest that exercise training under normoxic conditions with exposure to short-duration intermittent hypoxia represents a beneficial strategy for increasing endurance performance by enhancing fatty acid metabolism in skeletal muscle.

  15. Exercise- and training-induced upregulation of skeletal muscle fatty acid oxidation are not solely dependent on mitochondrial machinery and biogenesis.

    Science.gov (United States)

    Yoshida, Yuko; Jain, Swati S; McFarlan, Jay T; Snook, Laelie A; Chabowski, Adrian; Bonen, Arend

    2013-09-15

      Regulation of skeletal muscle fatty acid oxidation (FAO) and adaptation to exercise training have long been thought to depend on delivery of fatty acids (FAs) to muscle, their diffusion into muscle, and muscle mitochondrial content and biochemical machinery. However, FA entry into muscle occurs via a regulatable, protein-mediated mechanism, involving several transport proteins. Among these CD36 is key. Muscle contraction and pharmacological agents induce CD36 to translocate to the cell surface, a response that regulates FA transport, and hence FAO. In exercising CD36 KO mice, exercise duration (-44%), and FA transport (-41%) and oxidation (-37%) are comparably impaired, while carbohydrate metabolism is augmented. In trained CD36 KO mice, training-induced upregulation of FAO is not observed, despite normal training-induced increases in mitochondrial density and enzymes. Transfecting CD36 into sedentary WT muscle (+41%), comparable to training-induced CD36 increases (+44%) in WT muscle, markedly upregulates FAO to rates observed in trained WT mice, but without any changes in mitochondrial density and enzymes. Evidently, in vivo CD36-mediated FA transport is key for muscle fuel selection and training-induced FAO upregulation, independent of mitochondrial adaptations. This CD36 molecular mechanism challenges the view that skeletal muscle FAO is solely regulated by muscle mitochondrial content and machinery.

  16. Investigation of the interaction of polyamidoamine dendrimers with nicotinic acid as solubility enhancer

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective Polyamidoamine(PAMAM) dendrimers enhance the solubility of nicotinic acid. Methods PAMAM dendrimers of generation 1 to 6 were prepared and the effect of pH and concentration of the dendrimers on the solubility enhancement of nicotinic acid was investigated. Results The pH and concentration of the dendrimers influence the solubility enhancement of nicotinic acid. Conclusions Electrostatic interaction between the carboxyl group of the nicotinic acid and the amine groups of the dendrimers is involved.

  17. Salicylic acid enhances Staphylococcus aureus extracellular adhesin protein expression.

    Science.gov (United States)

    Alvarez, Lucía P; Barbagelata, María S; Cheung, Ambrose L; Sordelli, Daniel O; Buzzola, Fernanda R

    2011-11-01

    One of the virulence factors required by Staphylococcus aureus at the early stages of infection is Eap, a secreted adhesin that binds many host proteins and is upregulated by the two-component regulatory system saeRS. The S. aureus Newman strain harbors a mutation in saeS that is thought to be responsible for the high level of Eap expression in this strain. This study was designed to ascertain whether salicylic acid (SAL) affects the expression of Eap and the internalization of S. aureus into epithelial cells. The strain Newman treated with SAL exhibited increased levels of eap transcription and protein expression. Furthermore, SAL treatment increased the eap promoter activity. SAL treatment enhanced Eap expression in the Newman and in other S. aureus strains that do not carry the mutation in saeS. Internalization of S. aureus eap and sae mutants into the MAC-T epithelial cells was significantly decreased compared with the wild-type counterparts. In conclusion, we demonstrated that a low concentration of SAL increased S. aureus Eap expression possibly due to enhancement of sae. SAL may create the conditions for S. aureus persistence in the host, not only by decreasing the capsular polysaccharide expression as shown before, but also by enhancing Eap expression.

  18. Regulatory mechanism on enhancing protein synthesis in skeletal muscles of cold exposed fresh water fish (Channa punctata)

    OpenAIRE

    Md Shahidul Haque; Md. Asraful Haque; Swapan Kumar Roy; M M H Khan; Md Mosharrof Hossain

    2014-01-01

    Channa punctata varieties of fish are energetic and survive in critical environment although the molecular mechanism is not known. They were exposed to cold (4–8 °C) for 30 min, 1 h, 2 h and 4 h and the total protein contents in the liver were not significantly changed up to 4 h of cold exposure while a significantly increased protein level in the skeletal muscle was noted and maximal at 2 h. Groups of fish were exposed to Na2HAsO4 to examine its role on cold-induced protein synthesis in the ...

  19. Hybrid retroviral vector with MCK enhancers inserted in LTR for stable and specific expression of human factor IX in skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    WANG Jian-min 王健民; HOU Jun 侯军; QIU Xin-fang 邱信芳; Kurachi Kotoku; XUE Jing-lun 薛京伦

    2004-01-01

    Background Retroviral vectors have been widely used to introduce foreign into various target cells in vitro, thus showing relatively high systemic delivery efficiency of various transgene products. The authors investigated the stability and efficiency of skeletal muscle-specific hybrid retroviral vectors in expression of human factor IX (FIX) in vitro and iv vivo. Methods FIX cDNA in LIXSN vector was replaced with a FIX minigene containing splicing donor and splicing acceptor sequence of first intron of human FIX gene. Two copies of muscle creatine kinase enhancer (MCK, Me2) were inserted in forward or reverse orientation at NheI site of 3' long terminal repeat (LTR), resulting in two hybrid vectors, which were designated as LMe2IXm2SN(F) and LMe2IXm2SN(R), respectively. The vectors were tested in vitro and in vivo for stability and muscle-specificity of factor IX expression with SCID mice. Results Muscle cells carrying vector with Me2 expressed significantly higher levels of FIX (up to 1800 ng/106.24h) than those without Me2, thus suggesting that Me2 could specifically increase expression level of FIX in muscle cells. Myoblasts transduced with LMe2IXm2SN(R) produced much less FIX in vivo in SCID mice than LMe2IXm2SN(F). One or two copies of Me2 sequence were deleted in myoblasts transduced with LMe2IXm2SN(R) without changing the orientation of Me2. Conclusions LTR inserted with MCK enhancers can specifically increase human FIX expression in skeletal muscle cells in vitro and in vivo, and MCK enhancer should be positioned in the same orientation as that of LTR promoter.

  20. The expression of Ldh-c in the skeletal muscle of plateau pika (Ochotona curzoniae enhances adaptation to a hypoxic environment

    Directory of Open Access Journals (Sweden)

    Zhi F. An

    2017-09-01

    Full Text Available The plateau pika (Ochotona curzoniae is a species of sprint-running alpine animals in the Qinghai-Tibet Plateau, which is a harsh highland hypoxic environment. Ldh-c is expressed in the testis, sperm and somatic tissues of plateau pika. To reveal the role and physiological mechanisms of sperm-specific lactate dehydrogenase (LDH-C4, in plateau pika to adapt to hypoxic environment, an adenoviral line of pMultiRNAi-Ldhc was constructed and injected into the bilateral biceps femoris of the hind legs. The swimming times of the pikas, and the Ldh-c expression levels, total LDH activities and ATP levels in skeletal muscle, were measured after the pikas were raised in the trapped site for 5 days. Our results showed that after Ldh-c was silenced, the sprint-running ability (swimming time of the plateau pikas was significant decreased, and the total LDH activities and ATP levels were reduced by 28.21% and 27.88%, respectively. Our results indicated that expression of Ldh-c in the skeletal muscle of plateau pika increased anaerobic glycolysis and enhanced adaptation to highland hypoxic environments.

  1. Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika’s Sprint-Running Capacity in Hypoxic Environment

    Science.gov (United States)

    Wang, Yang; Wei, Lian; Wei, Dengbang; Li, Xiao; Xu, Lina; Wei, Linna

    2015-01-01

    LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai

  2. Testis-Specific Lactate Dehydrogenase (LDH-C4 in Skeletal Muscle Enhances Apika’s Sprint-Running Capacity in Hypoxic Environment

    Directory of Open Access Journals (Sweden)

    Yang Wang

    2015-08-01

    Full Text Available LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae, which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000–5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in

  3. Testis-Specific Lactate Dehydrogenase (LDH-C4) in Skeletal Muscle Enhances a Pika's Sprint-Running Capacity in Hypoxic Environment.

    Science.gov (United States)

    Wang, Yang; Wei, Lian; Wei, Dengbang; Li, Xiao; Xu, Lina; Wei, Linna

    2015-08-07

    LDH-C4 is a lactate dehydrogenase that catalyzes the conversion of pyruvate to lactate. In mammals, ldh-c was originally thought to be expressed only in testis and spermatozoa. Plateau pika (Ochotona curzoniae), which belongs to the genus Ochotona of the Ochotonidea family, is a hypoxia tolerant mammal living 3000-5000 m above sea level on the Qinghai-Tibet Plateau, an environment which is strongly hypoxic. Ldh-c is expressed not only in testis and sperm but also in somatic tissues of plateau pika. In this study, the effects of N-propyl oxamate and N-isopropyl oxamate on LDH isozyme kinetics were compared to screens for a selective inhibitor of LDH-C4. To reveal the role and physiological mechanism of LDH-C4 in skeletal muscle of plateau pika, we investigated the effect of N-isopropyl oxamate on the pika exercise tolerance as well as the physiological mechanism. Our results show that Ki of N-propyl oxamate and N-isopropyl oxamate for LDH-A4, LDH-B4, and LDH-C4 were 0.094 mmol/L and 0.462 mmol/L, 0.119 mmol/L and 0.248 mmol/L, and 0.015 mmol/L and 0.013 mmol/L, respectively. N-isopropyl oxamate is a powerful selective inhibitor of plateau pika LDH-C4. In our exercise tolerance experiment, groups treated with inhibitors had significantly lower swimming times than the uninhibited control group. The inhibition rates of LDH, LD, and ATP were 37.12%, 66.27%, and 32.42%, respectively. Our results suggested that ldh-c is expressed in the skeletal muscle of plateau pika, and at least 32.42% of ATP in the skeletal muscle is catalyzed by LDH-C4 by anaerobic glycolysis. This suggests that pika has reduced dependence on oxygen and enhanced adaptation to hypoxic environment due to increased anaerobic glycolysis by LDH-C4 in skeletal muscle. LDH-C4 in plateau pika plays the crucial role in anaerobic glycolysis and generates ATP rapidly since this is the role of LDH-A4 in most species on plain land, which provide evidence that the native humans and animals in Qinghai-Tibet plateau

  4. Nitrogen Isotopic Composition of Proteinaceous Coral Skeletal Amino Acids Records Change in Source Nitrate to the Euphotic Zone in the Western Tropical Pacific

    Science.gov (United States)

    Williams, B.; Thibodeau, B.; Chikaraishi, Y.; Ohkouchi, N.; Grottoli, A. G.

    2014-12-01

    Instrumental and proxy data and global climate model experiments indicate a multi-decadal shoaling of the western tropical Pacific (WTP) thermocline potentially related to a shift in ENSO frequency. In the WTP, the nutricline coincides with the thermocline, and a shoaling of the nutricline brings more nitrate-rich seawater higher in the water column and within the sunlit euphotic zone. In the nutrient-poor WTP, this incursion of nitrate-rich water at the bottom of the euphotic zone may stimulate productivity in the water column. However, there is a general paucity of measurements below the surface with which to investigate recent changes in seawater chemistry. Nitrogen isotope (δ15N) measurements of particulate organic matter (POM) can elucidate the source of nitrogen to the WTP and related trophic dynamics. This POM is the food source to the long-lived proteinaceous corals, and drives the nitrogen isotopic composition of their skeleton. Here, we report time series δ15N values from the banded skeletons of proteinaceous corals from offshore Palau in the WTP that provide proxy information about past changes in euphotic zone nitrogen dynamics. Bulk skeletal δ15N values declined between 1977 and 2010 suggesting a progressively increasing contribution of deep water with isotopically-light nitrate to the euphotic zone and/or a shortening of the planktonic food web. Since only some amino acids are enriched in δ15N with each trophic transfer in a food web, we measured the δ15N composition of seven individual amino acids in the same coral skeleton. The δ15N time series of the individual amino acids also declined over time, mirroring the bulk values. These new data indicate that the changes in the source nitrogen to the base of the euphotic zone drives a decline in coral skeletal δ15N values, consistent with the shoaling nutricline, with no coinciding alteration of the trophic structure in the WTP.

  5. Effect of high fat diet enriched with unsaturated and diet rich in saturated fatty acids on sphingolipid metabolism in rat skeletal muscle.

    Science.gov (United States)

    Blachnio-Zabielska, Agnieszka; Baranowski, Marcin; Zabielski, Piotr; Gorski, Jan

    2010-11-01

    Consumption of high fat diet leads to muscle lipid accumulation which is an important factor involved in induction of insulin resistance. Ceramide is likely to partially inhibit insulin signaling cascade. The aim of this study was to examine the effect of different high fat diets on ceramide metabolism in rat skeletal muscles. The experiments were carried out on rats fed for 5 weeks: (1) a standard chow and (2) high fat diet rich in polyunsaturated fatty acids (PUFA) and (3) diet enriched with saturated fatty acids (SAT). Assays were performed on three types of muscles: slow-twitch oxidative (soleus), fast-twitch oxidative-glycolytic, and fast-twitch glycolytic (red and white section of the gastrocnemius, respectively). The activity of serine palmitoyltransferase (SPT), neutral and acid sphingomyelinase (n- and aSMase), and neutral and alkaline ceramidase (n- and alCDase) was examined. The content of ceramide, sphinganine, sphingosine, and sphingosine-1-phosphate was also measured. The ceramide content did not change in any muscle from PUFA diet group but increased in the SAT diet group by 46% and 52% in the soleus and red section of the gastrocnemius, respectively. Elevated ceramide content in the SAT diet group could be a result of increased SPT activity and simultaneously decreased activity of nCDase. Unchanged ceramide content in the PUFA diet group might be a result of increased activity of SPT and alCDase and simultaneously decreased activity of SMases. We conclude that regulation of muscle ceramide level depends on the diet and type of skeletal muscle. © 2010 Wiley-Liss, Inc.

  6. Abscisic acid enhances resistance to Alternaria solani in tomato seedlings.

    Science.gov (United States)

    Song, Weiwei; Ma, Xinrong; Tan, Hong; Zhou, Jinyan

    2011-07-01

    The plant hormone abscisic acid (ABA) is an important regulator in many aspects of plant growth and development, as well as stress resistance. Here, we investigated the effects of exogenous ABA application on the interaction between tomato (Solanum lycopersicon L.) and Alternaria solani (early blight). Foliar spraying of 7.58 μM ABA was effective in reducing disease severity in tomato plants. Previously, increased activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO) and peroxidase (POD) were observed in exogenous ABA-treated tomato leaves. Moreover, these enzyme activities were maintained at higher levels in ABA-pretreated and A. solani challenged tomato plants. Tomato defense genes, such as PR1, β-1, 3-glucanase (GLU), PPO, POD, and superoxide dismutase (SOD), were rapidly and significantly up-regulated by exogenous ABA treatment. Furthermore, a subsequent challenge of ABA-pretreated plants with the pathogen A. solani resulted in higher expression of defense genes, compared to water-treated or A. solani inoculated plants. Therefore, our results suggest that exogenous ABA could enhance disease resistance against A. solani infection in tomato through the activation of defense genes and via the enhancement of defense-related enzymatic activities.

  7. Oleic Acid: Natural variation and potential enhancement in oilseed crops.

    Science.gov (United States)

    Oleic acid is a monounsaturated omega 9 fatty acid (MUFA, C18:1) which can be found in various plant lipids and animal fats. Unlike omega 3 (a-linolenic acid, C18:3) and omega 6 (linoleic acid, C18:2) fatty acids which are essential because they cannot be synthesized by humans and must be obtained f...

  8. Enhanced Glycogen Storage of a Subcellular Hot Spot in Human Skeletal Muscle during Early Recovery from Eccentric Contractions

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Farup, Jean; Rahbek, Stine Klejs

    2015-01-01

    Unaccustomed eccentric exercise is accompanied by muscle damage and impaired glucose uptake and glycogen synthesis during subsequent recovery. Recently, it was shown that the role and regulation of glycogen in skeletal muscle are dependent on its subcellular localization, and that glycogen...... content during post-exercise recovery from eccentric contractions. Analysis was completed on five male subjects performing an exercise bout consisting of 15 x 10 maximal eccentric contractions. Carbohydrate-rich drinks were subsequently ingested throughout a 48 h recovery period and muscle biopsies...... in both type I and II fibers were lower in the exercise leg compared with the control leg, and this was associated with a smaller size of the glycogen particles. We conclude that in the carbohydrate-supplemented state, the effect of eccentric contractions on glycogen metabolism depends on the subcellular...

  9. Enhancement of neutrophil-mediated killing of Plasmodium falciparum asexual blood forms by fatty acids: importance of fatty acid structure.

    Science.gov (United States)

    Kumaratilake, L M; Ferrante, A; Robinson, B S; Jaeger, T; Poulos, A

    1997-10-01

    Effects of fatty acids on human neutrophil-mediated killing of Plasmodium falciparum asexual blood forms were investigated by using a quantitative radiometric assay. The results showed that the antiparasitic activity of neutrophils can be greatly increased (>threefold) by short-term treatment with fatty acids with 20 to 24 carbon atoms and at least three double bonds. In particular, the n-3 polyenoic fatty acids, eicosapentaenoic and docosahexaenoic acids, and the n-6 fatty acid, arachidonic acid, significantly enhanced neutrophil antiparasitic activity. This effect was >1.5-fold higher than that induced by an optical concentration of the known agonist cytokine tumor necrosis factor alpha (TNF-alpha). At suboptimal concentrations, the combination of arachidonic acid and TNF-alpha caused a synergistic increase in neutrophil-mediated parasite killing. The fatty acid-induced effect was independent of the availability of serum opsonins but dependent on the structure of the fatty acids. The length of the carbon chain, degree of unsaturation, and availability of a free carboxyl group were important determinants of fatty acid activity. The fatty acids which increased neutrophil-mediated killing primed the enhanced superoxide radical generation of neutrophils in response to P. falciparum as detected by chemiluminescence. Scavengers of oxygen radicals significantly reduced the fatty acid-enhanced parasite killing, but cyclooxygenase and lipoxygenase inhibitors had no effect. These findings have identified a new class of immunoenhancers that could be exploited to increase resistance against Plasmodium species.

  10. Enhancement of twitch force by stretch in a nerve-skeletal muscle preparation of the frog Rana porosa brevipoda and the effects of temperature on it.

    Science.gov (United States)

    Ishii, Yoshiki; Watari, Takashi; Tsuchiya, Teizo

    2004-12-01

    We investigated the mechanism of the enhancement of twitch force by stretch and the effects of temperature on it in nerve-skeletal muscle preparations of whole iliofibularis muscles isolated from the frog Rana brevipoda. When a preparation was stimulated indirectly and stretched, the twitch force after the stretch was enhanced remarkably in comparison to that observed before a stretch at low temperature. The enhanced force obtained by a stretch of 20% resting muscle length (l0) at low temperature was as high as the force obtained by direct stimulation. The phenomenon was not dependent on the velocity but on the amplitude of stretch. The enhanced force obeyed the length-force relationship when a stretch was long enough. The above results were observed when the frogs were kept at room temperature (20-22 degrees C). Measurements were also taken at low temperature (4 degrees C); when frogs were kept at low temperature for more than 2 months, twitch force obtained without stretch was considerably higher at l0. The amplitude of the action potential recorded extracellularly from the muscle surface increased remarkably after a stretch, but was same before and after a stretch when recorded from the nerve innervating muscle. The effects of temperature on twitch and tetanic force by direct or indirect stimulation without stretch were also studied as basic data of the stretch experiment. The results from this study suggest that stretch-induced force enhancement in a nerve-muscle preparation is caused by an increase in the transmission rate between nerve and muscle, and the amplitude of the enhanced force is determined by the length-force relationship of the muscle. The phenomenon is also strongly affected by the temperature at which the frogs are kept.

  11. Lewis acid enhanced switching of the 1,1-dicyanodihydroazulene/vinylheptafulvene photo/thermoswitch

    DEFF Research Database (Denmark)

    Parker, Christian Richard; Tortzen, Christian Gregers; Broman, Søren Lindbæk

    2011-01-01

    Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion.......Mild Lewis acids enhance the rate of the thermal conversion of vinylheptafulvene (VHF) to dihydroazulene (DHA). In the absence of light, stronger Lewis acids promote the otherwise photoinduced DHA to VHF conversion....

  12. Dietary intervention increases n-3 long-chain polyunsaturated fatty acids in skeletal muscle membrane phospholipids of obese subjects. Implications for insulin sensitivity

    DEFF Research Database (Denmark)

    Haugaard, S.B.; Madsbad, S.; Høy, Carl-Erik

    2006-01-01

    Objective Cross-sectional studies suggest that the fatty acid (FA) composition of phospholipids in skeletal muscle cell membrane may modulate insulin sensitivity in humans. We examined the impact of a hypocaloric low-fat dietary intervention on membrane FA composition and insulin sensitivity...... analysis that included changes in weight, fat mass, waist circumference, plasma lipids, PUFA, SFA and long-chain PUFAn-3 indicated that SFA and long-chain PUFAn-3 were independent predictors of HOMA-IR (R-2 = 0.33, P fat dietary intervention programme increased....... Design Muscle membrane FA profiles were determined in muscle (vastus lateralis) biopsies from 21 obese subjects before and after 6 months of dietary restriction. Diet instructions emphasized low intake of FA of marine origin by recommending lean fish and prohibiting fatty fish and fish oil supplements...

  13. Gibberellic Acid enhancement of DNA turnover in barley aleurone cells.

    Science.gov (United States)

    Taiz, L; Starks, J E

    1977-08-01

    When imbibed, deembryonated halfseeds from barley (Hordeum vulgare L., var. Himalaya) are incubated in buffer, the DNA content of the aleurone layer increases 25 to 40% over a 24-hour period. In contrast, the DNA of isolated aleurone layers declines by 20% over the same time period. Gibberellic acid (GA) causes a reduction in DNA levels in both halfseed aleurone layers and isolated aleurone layers. GA also increases the specific radioactivity of [(3)H]thymidine-labeled halfseed aleurone layer DNA during the first 12 hours of treatment. Pulse-chase studies demonstrated that the newly synthesized DNA is metabolically labile.The buoyant density on CsCl density gradients of hormone-treated aleurone DNA is identical with that of DNA extracted from whole seedlings. After density-labeling halfseed DNA with 5-bromodeoxyuridine, a bimodal absorption profile is obtained in neutral CsCl. The light band (1.70 g/ml) corresponds to unsubstituted DNA, while the heavy band (1.725-1.74 g/ml) corresponds to a hybrid density-labeled species. GA increases the relative amount of the heavy (hybrid) peak in halfseed aleurone layer DNA, further suggesting that the hormone enhances semiconservative replication in halfseeds.DNA methylation was also demonstrated. Over 60% of the radioactivity from [(3)H-Me]methionine is incorporated into 5-methylcytosine. GA has no effect on the percentage distribution of label among the bases.It was concluded that GA enhances the rate of DNA degradation and DNA synthesis (turnover) in halfseeds, but primarily DNA degradation in isolated aleurone layers. Incorporation by isolated aleurone layers is due to DNA repair. Semiconservative replication apparently plays no physiological role in the hormone response, since both isolated aleurone layers and gamma-irradiated halfseeds respond normally. The hypothesis was advanced that endoreduplication and DNA degradation are means by which the seed stores and mobilizes deoxyribonucleotides for the embryo during

  14. Fenton-enhanced {gamma}-radiolysis of cyanuric acid

    Energy Technology Data Exchange (ETDEWEB)

    Varghese, Rani [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India); Aravind, Usha K. [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India); Aravindakumar, Charuvila T. [School of Chemical Sciences, Mahatma Gandhi University, Kottayam 686560, Kerala (India)]. E-mail: CT-Aravindakumar@rocketmail.com

    2007-04-02

    Degradation of cyanuric acid (OOOT), a stable end product of oxidative decomposition of atrazine, is investigated in a combined field of gamma radiolysis and fenton reaction. The reaction of hydroxyl radical ({center_dot}OH) at pH 6 was carried out by irradiating N{sub 2}O saturated aqueous solutions containing OOOT (1 x 10{sup -3} mol dm{sup -3}), and this resulted only a marginal degradation (20%). However, when the same reaction was carried out in the presence of varying concentrations of ferrous sulfate ((5-10) x 10{sup -5} mol dm{sup -3}), the decay of OOOT has been enhanced to more than 80%. This decay followed a first order kinetics. Nearly similar effects were observed with another triazine derivative, 2,4-dioxohexahydro-1,3,5-triazine (DHT). Two major reaction mechanisms are proposed for the enhanced decay of OOOT. The formation of unstable hydroxyl radical adducts from the reaction of {center_dot}OH which is the result of gamma radiolysis and the Fenton reaction (resulting from the reaction of the added Fe(II) and of the H{sub 2}O{sub 2} from the radiolysis of water), is proposed as the first mechanism. The second mechanism, which is likely the major contributor to degradation, is proposed as the reaction of a nucleophilic adduct, Fe(II)OOH, which could directly react with the electron deficient triazine ring. It is highlighted that such degradation reactions must be explored for the complete degradation of the byproducts of the oxidative decomposition of atrazine.

  15. Mechanism involved in enhancement of osteoblast differentiation by hyaluronic acid

    Energy Technology Data Exchange (ETDEWEB)

    Kawano, Michinao [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Ariyoshi, Wataru [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Iwanaga, Kenjiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Okinaga, Toshinori [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Habu, Manabu [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Yoshioka, Izumi [Division of Oral and Maxillofacial Surgery, Department of Medicine of Sensory and Motor Organs, University of Miyazaki, Kiyotake, Miyazaki 889-1692 (Japan); Tominaga, Kazuhiro [Division of Maxillofacial Diagnostic and Surgical Science, Department of Oral and Maxillofacial Surgery, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Nishihara, Tatsuji, E-mail: tatsujin@kyu-dent.ac.jp [Division of Infections and Molecular Biology, Department of Health Promotion, Kyushu Dental College, Kitakyushu 803-8580 (Japan); Oral Bioresearch Center, Kyushu Dental College, Kitakyushu 803-8580 (Japan)

    2011-02-25

    Research highlights: {yields} In this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. {yields} MG63 cells were incubated with BMP-2 and HA for various time periods. {yields} Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. {yields} HA enhanced BMP-2 induces osteoblastic differentiation in MG63 cells via down-regulation of BMP-2 antagonists and ERK phosphorylation. -- Abstract: Objectives: Bone morphogenetic protein-2 (BMP-2) is expected to be utilized to fill bone defects and promote healing of fractures. However, it is unable to generate an adequate clinical response for use in bone regeneration. Recently, it was reported that glycosaminoglycans, including heparin, heparan sulfate, keratan sulfate, dermatan sulfate, chondroitin-4-sulfate, chondroitin-6-sulfate, and hyaluronic acid (HA), regulate BMP-2 activity, though the mechanism by which HA regulates osteogenic activities has not been fully elucidated. The aim of this study was to investigate the effects of HA on osteoblast differentiation induced by BMP-2. Materials and methods: Monolayer cultures of osteoblastic lineage MG63 cells were incubated with BMP-2 and HA for various time periods. To determine osteoblastic differentiation, alkaline phosphatase (ALP) activity in the cell lysates was quantified. Phosphorylation of Smad 1/5/8, p38, and ERK proteins was determined by Western blot analysis. To elucidate the nuclear translocation of phosphorylated Smad 1/5/8, stimulated cells were subjected to immunofluorescence microscopy. To further elucidate the role of HA in enhancement of BMP-2-induced Smad signaling, mRNA expressions of the BMP-2 receptor antagonists noggin and follistatin were detected using real-time RT-PCR. Results: BMP-2-induced ALP activation, Smad 1/5/8 phosphorylation, and

  16. Creatine, L-carnitine, and ω3 polyunsaturated fatty acid supplementation from healthy to diseased skeletal muscle.

    Science.gov (United States)

    D'Antona, Giuseppe; Nabavi, Seyed Mohammad; Micheletti, Piero; Di Lorenzo, Arianna; Aquilani, Roberto; Nisoli, Enzo; Rondanelli, Mariangela; Daglia, Maria

    2014-01-01

    Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.

  17. Creatine, L-Carnitine, and ω3 Polyunsaturated Fatty Acid Supplementation from Healthy to Diseased Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Giuseppe D’Antona

    2014-01-01

    Full Text Available Myopathies are chronic degenerative pathologies that induce the deterioration of the structure and function of skeletal muscle. So far a definitive therapy has not yet been developed and the main aim of myopathy treatment is to slow the progression of the disease. Current nonpharmacological therapies include rehabilitation, ventilator assistance, and nutritional supplements, all of which aim to delay the onset of the disease and relieve its symptoms. Besides an adequate diet, nutritional supplements could play an important role in the treatment of myopathic patients. Here we review the most recent in vitro and in vivo studies investigating the role supplementation with creatine, L-carnitine, and ω3 PUFAs plays in myopathy treatment. Our results suggest that these dietary supplements could have beneficial effects; nevertheless continued studies are required before they could be recommended as a routine treatment in muscle diseases.

  18. Skeletal muscle

    Science.gov (United States)

    There are approximately 650-850 muscles in the human body these include skeletal (striated), smooth and cardiac muscle. The approximation is based on what some anatomists consider separate muscle or muscle systems. Muscles are classified based on their anatomy (striated vs. smooth) and if they are v...

  19. Signaling Pathways Related to Protein Synthesis and Amino Acid Concentration in Pig Skeletal Muscles Depend on the Dietary Protein Level, Genotype and Developmental Stages.

    Directory of Open Access Journals (Sweden)

    Yingying Liu

    Full Text Available Muscle growth is regulated by the homeostatic balance of the biosynthesis and degradation of muscle proteins. To elucidate the molecular interactions among diet, pig genotype, and physiological stage, we examined the effect of dietary protein concentration, pig genotype, and physiological stages on amino acid (AA pools, protein deposition, and related signaling pathways in different types of skeletal muscles. The study used 48 Landrace pigs and 48 pure-bred Bama mini-pigs assigned to each of 2 dietary treatments: lower/GB (Chinese conventional diet- or higher/NRC (National Research Council-protein diet. Diets were fed from 5 weeks of age to respective market weights of each genotype. Samples of biceps femoris muscle (BFM, type I and longissimus dorsi muscle (LDM, type II were collected at nursery, growing, and finishing phases according to the physiological stage of each genotype, to determine the AA concentrations, mRNA levels for growth-related genes in muscles, and protein abundances of mechanistic target of rapamycin (mTOR signaling pathway. Our data showed that the concentrations of most AAs in LDM and BFM of pigs increased (P<0.05 gradually with increasing age. Bama mini-pigs had generally higher (P<0.05 muscle concentrations of flavor-related AA, including Met, Phe, Tyr, Pro, and Ser, compared with Landrace pigs. The mRNA levels for myogenic determining factor, myogenin, myocyte-specific enhancer binding factor 2 A, and myostatin of Bama mini-pigs were higher (P<0.05 than those of Landrace pigs, while total and phosphorylated protein levels for protein kinase B, mTOR, and p70 ribosomal protein S6 kinases (p70S6K, and ratios of p-mTOR/mTOR, p-AKT/AKT, and p-p70S6K/p70S6K were lower (P<0.05. There was a significant pig genotype-dependent effect of dietary protein on the levels for mTOR and p70S6K. When compared with the higher protein-NRC diet, the lower protein-GB diet increased (P<0.05 the levels for mTOR and p70S6K in Bama mini-pigs, but

  20. Enantioseparation of Amino Acids by Micelle-Enhanced Ultrafiltration : Experimental and Theoretical Studies of Copper(II) Amino Acid Interactions

    NARCIS (Netherlands)

    Bruin, de T.J.M.

    2000-01-01

    A micelle-enhanced ultrafiltration system, which can potentially be used for large scale separations, has been used to investigate the resolution of amino acid enantiomers. For this purpose amino acid derivatives were synthesized, which in combination with copper(II) ions were used as chiral selecto

  1. Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running

    OpenAIRE

    2016-01-01

    Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential a...

  2. Accumulation of eicosapolyenoic acids enhances sensitivity to abscisic acid and mitigates the effects of drought in transgenic Arabidopsis thaliana.

    Science.gov (United States)

    Yuan, Xiaowei; Li, Yaxiao; Liu, Shiyang; Xia, Fei; Li, Xinzheng; Qi, Baoxiu

    2014-04-01

    IgASE1, a C₁₈ Δ(9)-specific polyunsaturated fatty acid elongase from the marine microalga Isochrysis galbana, is able to convert linoleic acid and α-linolenic acid to eicosadienoic acid and eicosatrienoic acid in Arabidopsis. Eicosadienoic acid and eicosatrienoic acid are precursors of arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid, which are synthesized via the Δ(8) desaturation biosynthetic pathways. This study shows that the IgASE1-expressing transgenic Arabidopsis exhibited altered morphology (decreased leaf area and biomass) and enhanced drought resistance compared to wild-type plants. The transgenic Arabidopsis were hypersensitive to abscisic acid (ABA) during seed germination, post-germination growth, and seedling development. They had elevated leaf ABA levels under well-watered and dehydrated conditions and their stomata were more sensitive to ABA. Exogenous application of eicosadienoic acid and eicosatrienoic acid can mimic ABA and drought responses in the wild type plants, similar to that found in the transgenic ones. The transcript levels of genes involved in the biosynthesis of ABA (NCED3, ABA1, AAO3) as well as other stress-related genes were upregulated in this transgenic line upon osmotic stress (300 mM mannitol). Taken together, these results indicate that these two eicosapolyenoic acids or their derived metabolites can mitigate the effects of drought in transgenic Arabidopsis, at least in part, through the action of ABA.

  3. Adapted physical exercise enhances activation and differentiation potential of satellite cells in the skeletal muscle of old mice.

    Science.gov (United States)

    Cisterna, Barbara; Giagnacovo, Marzia; Costanzo, Manuela; Fattoretti, Patrizia; Zancanaro, Carlo; Pellicciari, Carlo; Malatesta, Manuela

    2016-05-01

    During ageing, a progressive loss of skeletal muscle mass and a decrease in muscle strength and endurance take place, in the condition termed sarcopenia. The mechanisms of sarcopenia are complex and still unclear; however, it is known that muscle atrophy is associated with a decline in the number and/or efficiency of satellite cells, the main contributors to muscle regeneration. Physical exercise proved beneficial in sarcopenia; however, knowledge of the effect of adapted physical exercise on the myogenic properties of satellite cells in aged muscles is limited. In this study the amount and activation state of satellite cells as well as their proliferation and differentiation potential were assessed in situ by morphology, morphometry and immunocytochemistry at light and transmission electron microscopy on 28-month-old mice submitted to adapted aerobic physical exercise on a treadmill. Sedentary age-matched mice served as controls, and sedentary adult mice were used as a reference for an unperturbed control at an age when the capability of muscle regeneration is still high. The effect of physical exercise in aged muscles was further analysed by comparing the myogenic potential of satellite cells isolated from old running and old sedentary mice using an in vitro system that allows observation of the differentiation process under controlled experimental conditions. The results of this ex vivo and in vitro study demonstrated that adapted physical exercise increases the number and activation of satellite cells as well as their capability to differentiate into structurally and functionally correct myotubes (even though the age-related impairment in myotube formation is not fully reversed): this evidence further supports adapted physical exercise as a powerful, non-pharmacological approach to counteract sarcopenia and the age-related deterioration of satellite cell capabilities even at very advanced age.

  4. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity

    Directory of Open Access Journals (Sweden)

    Zulezwan A. Malik

    2013-12-01

    Full Text Available Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC coupled to mass spectrometry (MS affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group bred as either high- or low-capacity runners (HCR and LCR, respectively that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p < 0.0001 in running capacity during a standardized treadmill test. Soluble muscle proteins were extracted, digested with trypsin and individual biological replicates (50 ng of tryptic peptides subjected to LC-MS profiling. Proteins were identified by triplicate LC-MS/MS analysis of a pooled sample of each biological replicate. Differential expression profiling was performed on relative abundances (RA of parent ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897 and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5. Sixteen proteins were significantly (p < 0.05 more abundant in HCR muscle and hierarchal clustering of the profiling data highlighted two protein subgroups, which encompassed proteins associated with either the respiratory chain or fatty acid oxidation. Heart-type fatty acid binding protein (FABPH was 1

  5. Enhancing tolerance of rice (Oryza sativa) to simulated acid rain by exogenous abscisic acid.

    Science.gov (United States)

    Wu, Xi; Liang, Chanjuan

    2016-12-16

    Abscisic acid (ABA) regulates much important plant physiological and biochemical processes and induces tolerance to different stresses. Here, we studied the regulation of exogenous ABA on adaptation of rice seedlings to simulated acid rain (SAR) stress by measuring biomass dry weight, stomatal conductance, net photosynthesis rate, nutrient elements, and endogenous hormones. The application of 10 μM ABA alleviated the SAR-induced inhibition on growth, stomatal conductance, net photosynthesis rate, and decreases in contents of nutrient (K, Mg, N, and P) and hormone (auxin, gibberellins, and zeatin). Moreover, 10 μM ABA could stimulate the Ca content as signaling molecules under SAR stress. Contrarily, the application of 100 μM ABA aggravated the SAR-induced inhibition on growth, stomatal conductance, net photosynthesis rate, and contents of nutrient and hormone. The results got after a 5-day recovery (without SAR) show that exogenous 10 μM ABA can promote self-restoration process in rice whereas 100 μM ABA hindered the restoration by increasing deficiency of nutrients and disturbing the balance of hormones. These results confirmed that exogenous ABA at proper concentration could enhance the tolerance of rice to SAR stress.

  6. Lowering of phytic acid content by enhancement of phytase and acid phosphatase activities during sunflower germination

    Directory of Open Access Journals (Sweden)

    Juliana da Silva Agostini

    2010-08-01

    Full Text Available The objective of this work was to investigate the germination of hybrid sunflowers BRS191 and C11 as a means of lowering phytic acid (PA content by enhancing the activity of endogenous phytase and acid phosphatase. The concentration of PA in hybrid sunflower achenes varied from 2.16 to 2.83g/100g of sample (p O objetivo deste trabalho foi investigar a germinação de girassóis híbridos BRS 191 e C11 com finalidade de reduzir o teor de AF e aumentar as atividades de phytases e fosfatases endógenas. A concentração do AF nos aquênios de girassóis híbridos variou de 2,16 a 2,83 g /100g de amostra (p< 0,005. As atividades de fitases e fosfatases de girassóis BRS191 e C11 foram elevadas no 4º e 5º dia de germinação, respectivamente, com liberação do fósforo necessário para o desenvolvimento da semente. Estes resultados indicam que o AF do girassol hibrido reduz e a atividade de phytase aumenta em períodos distintos da germinação, possibilitando assim a aplicação desta enzima no controle do teor de AF em cereais, melhorando o seu valor nutricional.

  7. An optimized probucol microencapsulated formulation integrating a secondary bile acid (deoxycholic acid as a permeation enhancer

    Directory of Open Access Journals (Sweden)

    Mooranian A

    2014-09-01

    Full Text Available Armin Mooranian,1 Rebecca Negrulj,1 Nigel Chen-Tan,2 Gerald F Watts,3 Frank Arfuso,4 Hani Al-Salami11Biotechnology and Drug Development Research Laboratory, School of Pharmacy, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, 2Faculty of Science and Engineering, Curtin University, 3School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, 4School of Biomedical Science, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Perth, AustraliaAbstract: The authors have previously designed, developed, and characterized a novel microencapsulated formulation as a platform for the targeted delivery of therapeutics in an animal model of type 2 diabetes, using the drug probucol (PB. The aim of this study was to optimize PB microcapsules by incorporating the bile acid deoxycholic acid (DCA, which has good permeation-enhancing properties, and to examine its effect on microcapsules’ morphology, rheology, structural and surface characteristics, and excipients’ chemical and thermal compatibilities. Microencapsulation was carried out using a BÜCHI-based microencapsulating system established in the authors’ laboratory. Using the polymer sodium alginate (SA, two microencapsulated formulations were prepared: PB-SA (control and PB-DCA-SA (test at a constant ratio (1:30 and 1:3:30, respectively. Complete characterization of the microcapsules was carried out. The incorporation of DCA resulted in better structural and surface characteristics, uniform morphology, and stable chemical and thermal profiles, while size and rheological parameters remained similar to control. In addition, PB-DCA-SA microcapsules showed good excipients’ compatibilities, which were supported by data from differential scanning calorimetry, Fourier transform infrared spectroscopy, scanning electron microscopy, and energy dispersive X-ray studies, suggesting

  8. Enhanced Androgen Signaling With Androgen Receptor Overexpression in the Osteoblast Lineage Controls Skeletal Turnover, Matrix Quality and Bone Architecture

    Science.gov (United States)

    2007-12-01

    transforming growth factor-ß steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells. Endocrinology 128:2723-2730 37... osteosarcoma cells. Biochem Biophys Res Commun 204:905-911 39. Gray C, Colston K, Mackay A, Taylor M, Arnett T 1992 Interaction of androgen and 1,25...J, Gehler J, Cantz M 1976 The radiographic features of mannosidosis. Radiology 119:401-407 46. O’Sullivan S, Naot D, Callon K, Porteous F, Horne A

  9. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    Science.gov (United States)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  10. Long-term insulin-like growth factor-I expression in skeletal muscles attenuates the enhanced in vitro proliferation ability of the resident satellite cells in transgenic mice

    Science.gov (United States)

    Chakravarthy, M. V.; Fiorotto, M. L.; Schwartz, R. J.; Booth, F. W.

    2001-01-01

    Insulin-like growth factor-I (IGF-I) overexpression for 1-month in mouse skeletal muscle increases satellite cell proliferation potential. However, it is unknown whether this beneficial enhancement by IGF-I expression would persist over a longer-term duration in aged mice. This is an important issue to address if a prolonged course of IGF-I is to be used clinically in muscle-wasting conditions where satellite cells may become limiting. Using the IGF-I transgenic (IGF-I Tg) mouse that selectively expresses the IGF-I transgene in striated muscles, we found that 18-months of continuous IGF-I overexpression led to a loss in the enhanced in vitro proliferative capacity of satellite cells from Tg skeletal muscles. Also 18-month-old IGF-I Tg satellite cells lost the enhanced BrdU incorporation, greater pRb and Akt phosphorylations, and decreased p27(Kip1) levels initially observed in cells from 1-month-old IGF-I Tg mice. The levels of those biochemical markers reverted to similar values seen in the 18-months WT littermates. These findings, therefore, suggest that there is no further beneficial effect on enhancing satellite cell proliferation ability with persistent long-term expression of IGF-I in skeletal muscles of these transgenic mice.

  11. Enhanced functional properties of tannic acid after thermal hydrolysis

    Science.gov (United States)

    Thermal hydrolysis processing of fresh tannic acid was carried out in a closed reactor at four different temperatures (65, 100, 150 and 200°C). Pressures reached in the system were 1.3 and 4.8 MPa at 150 and 200°C, respectively. Hydrolysis products (gallic acid and pyrogallol) were separated and qua...

  12. Genetic Engineering of Rhizopus for Enhancing Lactic Acid Production

    Science.gov (United States)

    The fungus Rhizopus is frequently used to convert, or ferment sugars obtained from agricultural crops to lactic acid. This natural product has long been utilized by the food industry as an additive for preservation, flavor, and acidity. Additionally, it is used for the manufacture of environmental...

  13. Enhanced Production of Carboxylic Acids by Engineering of Rhizopus

    Science.gov (United States)

    The fungus Rhizopus is frequently used to convert, or ferment sugars obtained from agricultural crops to lactic acid. This natural product has long been utilized by the food industry as an additive for preservation, flavor, and acidity. Additionally, it is used for the manufacture of environmental...

  14. Increased Production of Fatty Acids and Triglycerides in Aspergillus oryzae by Enhancing Expressions of Fatty Acid Synthesis-Related Genes

    Energy Technology Data Exchange (ETDEWEB)

    Tamano, Koichi; Bruno, Kenneth S.; Karagiosis, Sue A.; Culley, David E.; Deng, Shuang; Collett, James R.; Umemura, Myco; Koike, Hideaki; Baker, Scott E.; Machida, Masa

    2013-01-01

    Microbial production of fats and oils is being developedas a means of converting biomass to biofuels. Here we investigate enhancing expression of enzymes involved in the production of fatty acids and triglycerides as a means to increase production of these compounds in Aspergillusoryzae. Examination of the A.oryzaegenome demonstrates that it contains twofatty acid synthases and several other genes that are predicted to be part of this biosynthetic pathway. We enhancedthe expressionof fatty acid synthesis-related genes by replacing their promoters with thepromoter fromthe constitutively highly expressedgene tef1. We demonstrate that by simply increasing the expression of the fatty acid synthasegenes we successfullyincreasedtheproduction of fatty acids and triglyceridesby more than two fold. Enhancement of expression of the fatty acid pathway genes ATP-citrate lyase and palmitoyl-ACP thioesteraseincreasedproductivity to a lesser extent.Increasing expression ofacetyl-CoA carboxylase caused no detectable change in fatty acid levels. Increases in message level for each gene were monitored usingquantitative real-time RT-PCR. Our data demonstrates that a simple increase in the abundance of fatty acid synthase genes can increase the detectable amount of fatty acids.

  15. Disruption of ATP-sensitive potassium channel function in skeletal muscles promotes production and secretion of musclin

    Energy Technology Data Exchange (ETDEWEB)

    Sierra, Ana, E-mail: ana-sierra@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Subbotina, Ekaterina, E-mail: ekaterina-subbotina@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Zhu, Zhiyong, E-mail: zhiyong-zhu@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Gao, Zhan, E-mail: zhan-gao@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Koganti, Siva Rama Krishna, E-mail: sivaramakrishna.koganti@ttuhc.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Coetzee, William A., E-mail: william.coetzee@nyumc.org [Department of Pediatrics, NYU School of Medicine, New York, NY 10016 (United States); Goldhamer, David J., E-mail: david.goldhamer@uconn.edu [Center for Regenerative Biology, Department of Molecular and Cell Biology, Advanced Technology Laboratory, University of Connecticut, 1392 Storrs Road Unit 4243, Storrs, Connecticut 06269 (United States); Hodgson-Zingman, Denice M., E-mail: denice-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Zingman, Leonid V., E-mail: leonid-zingman@uiowa.edu [Department of Internal Medicine, University of Iowa, Carver College of Medicine, Iowa City, IA 52242 (United States); Fraternal Order of Eagles Diabetes Research Center, Carver College of Medicine, Iowa City, IA 52242 (United States); Department of Veterans Affairs, Medical Center, Iowa City, IA 52242 (United States)

    2016-02-26

    Sarcolemmal ATP-sensitive potassium (K{sub ATP}) channels control skeletal muscle energy use through their ability to adjust membrane excitability and related cell functions in accordance with cellular metabolic status. Mice with disrupted skeletal muscle K{sub ATP} channels exhibit reduced adipocyte size and increased fatty acid release into the circulation. As yet, the molecular mechanisms underlying this link between skeletal muscle K{sub ATP} channel function and adipose mobilization have not been established. Here, we demonstrate that skeletal muscle-specific disruption of K{sub ATP} channel function in transgenic (TG) mice promotes production and secretion of musclin. Musclin is a myokine with high homology to atrial natriuretic peptide (ANP) that enhances ANP signaling by competing for elimination. Augmented musclin production in TG mice is driven by a molecular cascade resulting in enhanced acetylation and nuclear exclusion of the transcription factor forkhead box O1 (FOXO1) – an inhibitor of transcription of the musclin encoding gene. Musclin production/secretion in TG is paired with increased mobilization of fatty acids and a clear trend toward increased circulating ANP, an activator of lipolysis. These data establish K{sub ATP} channel-dependent musclin production as a potential mechanistic link coupling “local” skeletal muscle energy consumption with mobilization of bodily resources from fat. Understanding such mechanisms is an important step toward designing interventions to manage metabolic disorders including those related to excess body fat and associated co-morbidities. - Highlights: • ATP-sensitive K{sup +} channels regulate musclin production by skeletal muscles. • Lipolytic ANP signaling is promoted by augmented skeletal muscle musclin production. • Skeletal muscle musclin transcription is promoted by a CaMKII/HDAC/FOXO1 pathway. • Musclin links adipose mobilization to energy use in K{sub ATP} channel deficient skeletal muscle.

  16. Cloning of human RTEF-1, a transcriptional enhancer factor-1-related gene preferentially expressed in skeletal muscle: evidence for an ancient multigene family.

    Science.gov (United States)

    Stewart, A F; Richard, C W; Suzow, J; Stephan, D; Weremowicz, S; Morton, C C; Adra, C N

    1996-10-01

    Transcriptional Enhancer Factor-1 (TEF-1) is a transcription factor required for cardiac muscle gene activation. Since ablation of TEF-1 does not abolish cardiac gene expression, we sought to identify a human gene related to TEF-1 (RTEF-1) that might also participate in cardiac gene regulation. A human heart cDNA library was screened to obtain a full-length RTEF-1 cDNA. Fluorescence in situ hybridization assigned the RTEF-1 gene to chromosome 12p13.2-p13.3. In contrast, PCR screening of human/rodent cell hybrid panels identified TEF-1 on chromosome 11p15.2, between D11S1315 and D11S1334, extending a region of known synteny between human chromosomes 11 and 12 and arguing for an ancient divergence between these two closely related genes. Northern blot analysis revealed a striking similarity in the tissue distribution of RTEF-1 and TEF-1 mRNAs; skeletal muscle showed the highest abundance of both mRNAs, with lower levels detected in pancreas, placenta, and heart. Phylogenetic analysis of all known TEF-1-related proteins identified human RTEF-1 as one of four vertebrate members of this multigene family and further suggests that these genes diverged in the earliest metazoan ancestors.

  17. Craniosynostosis and Multiple Skeletal Anomalies in Humans and Zebrafish Result from a Defect in the Localized Degradation of Retinoic Acid

    NARCIS (Netherlands)

    Laue, Kathrin; Pogoda, Hans-Martin; Daniel, Philip B.; van Haeringen, Arie; Alanay, Yasemin; von Ameln, Simon; Rachwalski, Martin; Morgan, Tim; Gray, Mary J.; Breuning, Martijn H.; Sawyer, Gregory M.; Sutherland-Smith, Andrew J.; Nikkels, Peter G.; Kubisch, Christian; Bloch, Wilhelm; Wollnik, Bernd; Hammerschmidt, Matthias; Robertson, Stephen P.

    2011-01-01

    Excess exogenous retinoic acid (RA) has been well documented to have teratogenic effects in the limb and craniofacial skeleton. Malformations that have been observed in this context include craniosynostosis, a common developmental defect of the skull that occurs in 1 in 2500 individuals and results

  18. Selective transport of long-chain fatty acids by FAT/CD36 in skeletal muscle of broilers.

    Science.gov (United States)

    Guo, J; Shu, G; Zhou, L; Zhu, X; Liao, W; Wang, S; Yang, J; Zhou, G; Xi, Q; Gao, P; Zhang, Y; Zhang, S; Yuan, L; Jiang, Q

    2013-03-01

    Fatty acid translocase (FAT/CD36) is a membrane receptor that facilitates long-chain fatty acid uptake. To investigate its role in the regulation of long-chain fatty acid composition in muscle tissue, we studied and compared FAT/CD36 gene expression in muscle tissues of commercial broiler chickens and Chinese local Silky fowls. The results from gas chromatography-mass spectrometry analysis of muscle samples demonstrated that Chinese local Silky fowls had significantly higher (P FAT/CD36 and caveolin-1) in the m. ipsilateral pectoralis and biceps femoris were analyzed by Q-PCR, and FAT/CD36 expression levels showed significant differences between these types of chickens (P FAT/CD36 expression are positively correlated with LA content (r = 0.567, P FAT/CD36 cDNA demonstrated that overexpression of FAT/CD36 improves total FA uptake with a significant increase in the proportion of LA and AA, and a decreased proportion of palmitic acid. These results suggest that chicken FAT/CD36 may selectively transport LA and AA, which may lead to the higher LA deposition in muscle tissue.

  19. T tubules and surface membranes provide equally effective pathways of carbonic anhydrase-facilitated lactic acid transport in skeletal muscle.

    Directory of Open Access Journals (Sweden)

    Janine Hallerdei

    Full Text Available We have studied lactic acid transport in the fast mouse extensor digitorum longus muscles (EDL by intracellular and cell surface pH microelectrodes. The role of membrane-bound carbonic anhydrases (CA of EDL in lactic acid transport was investigated by measuring lactate flux in muscles from wildtype, CAIV-, CAIX- and CAXIV-single ko, CAIV-CAXIV double ko and CAIV-CAIX-CAXIV-triple ko mice. This was complemented by immunocytochemical studies of the subcellular localization of CAIV, CAIX and CAXIV in mouse EDL. We find that CAXIV and CAIX single ko EDL exhibit markedly but not maximally reduced lactate fluxes, whereas triple ko and double ko EDL show maximal or near-maximal inhibition of CA-dependent lactate flux. Interpretation of the flux measurements in the light of the immunocytochemical results leads to the following conclusions. CAXIV, which is homogeneously distributed across the surface membrane of EDL fibers, facilitates lactic acid transport across this membrane. CAIX, which is associated only with T tubular membranes, facilitates lactic acid transport across the T tubule membrane. The removal of lactic acid from the lumen of T tubuli towards the interstitial space involves a CO2-HCO3- diffusional shuttle that is maintained cooperatively by CAIX within the T tubule and, besides CAXIV, by the CAIV, which is strategically located at the opening of the T tubules. The data suggest that about half the CA-dependent muscular lactate flux occurs across the surface membrane, while the other half occurs across the membranes of the T tubuli.

  20. Enhancing the crystalline degree of carbon nanotubes by acid treatment, air oxidization and heat treatment

    Institute of Scientific and Technical Information of China (English)

    Chensha Li; Baoyou Zhang; Xingjuan Chen; Xiaoqing Hu; Ji Liang

    2005-01-01

    Three approaches of treating carbon nanotubes (CNTs) including acid treatment, air oxidization and heat treatment at high temperature were studied to enhance the crystalline degree of carbon nanotubes. High temperature heat-treatment elevates the crystalline degree of carbon nanotubes. Acid treatment removes parts of amorphous carbonaceous matter through its oxidization effect.Air oxidization disperses carbon nanotubes and amorphous carbonaceous matter. The treatment of combining acid treatment with heat-treatment further elevates the crystalline degree of carbon nanotubes comparing with acid treatment or heat-treatment. The combination of the three treatments creates the thorough effects of enhancing the crystalline degree of carbon nanotubes.

  1. Noninvasive optical diagnostics of enhanced green fluorescent protein expression in skeletal muscle for comparison of electroporation and sonoporation efficiencies

    Science.gov (United States)

    Tamošiūnas, Mindaugas; Kadikis, Roberts; Saknīte, Inga; Baltušnikas, Juozas; Kilikevičius, Audrius; Lihachev, Alexey; Petrovska, Ramona; Jakovels, Dainis; Šatkauskas, Saulius

    2016-04-01

    We highlight the options available for noninvasive optical diagnostics of reporter gene expression in mouse tibialis cranialis muscle. An in vivo multispectral imaging technique combined with fluorescence spectroscopy point measurements has been used for the transcutaneous detection of enhanced green fluorescent protein (EGFP) expression, providing information on location and duration of EGFP expression and allowing quantification of EGFP expression levels. For EGFP coding plasmid (pEGFP-Nuc Vector, 10 μg/50 ml) transfection, we used electroporation or ultrasound enhanced microbubble cavitation [sonoporation (SP)]. The transcutaneous EGFP fluorescence in live mice was monitored over a period of one year using the described parameters: area of EGFP positive fibers, integral intensity, and mean intensity of EGFP fluorescence. The most efficient transfection of EGFP coding plasmid was achieved, when one high voltage and four low voltage electric pulses were applied. This protocol resulted in the highest short-term and long-term EGFP expression. Other electric pulse protocols as well as SP resulted in lower fluorescence intensities of EGFP in the transfected area. We conclude that noninvasive multispectral imaging technique combined with fluorescence spectroscopy point measurements is a suitable method to estimate the dynamics and efficiency of reporter gene transfection in vivo.

  2. Enhanced recovery from contraction-induced damage in skeletal muscles of old mice following treatment with the heat shock protein inducer 17-(allylamino)-17-demethoxygeldanamycin.

    Science.gov (United States)

    Kayani, Anna C; Close, Graeme L; Broome, Caroline S; Jackson, Malcolm J; McArdle, Anne

    2008-12-01

    Unlike muscles of young mice, skeletal muscles of old mice fail to recover completely following contraction-induced damage. The mechanisms by which this occurs are not fully understood. The ability of muscles of old mice to adapt following exercise by the increased production of heat shock proteins (HSPs) is blunted. Studies using transgenic mice have shown that this inability to produce HSPs has a major effect on muscle regeneration. Overexpression of HSP70 facilitated complete recovery of maximum tetanic force generation in muscles of old transgenic mice following contraction induced-damage in comparison with a deficit in muscles of old wild-type (WT) mice. We hypothesized that pharmacological induction of HSP70 in muscles of old WT mice would result in enhanced recovery from contraction-induced damage. A single dose of 40 mg/kg of 17-(allylamino)-17-demethoxygeldanamycin (17AAG) resulted in a significant increase in the HSP70 content of extensor digitorum longus muscles of adult C57BL6/J mice 3 days following treatment compared with vehicle-treated mice. Four weekly treatments of adult and old mice resulted in a two- to four-fold increase in muscle HSP70 content. Treatment of old mice with 17AAG at 3 days prior to and weekly for 4 weeks following a severely damaging contraction protocol resulted in enhanced recovery of force generation at 28 days postdamage compared with muscles of vehicle-treated mice. Data suggest that 17AAG overcomes the mechanism by which activation of the stress response fails in muscles of old mice and may have therapeutic benefit in the recovery following damage in muscles of older individuals.

  3. Addition of Mesenchymal Stem Cells Enhances the Therapeutic Effects of Skeletal Myoblast Cell-Sheet Transplantation in a Rat Ischemic Cardiomyopathy Model

    Science.gov (United States)

    Shudo, Yasuhiro; Miyagawa, Shigeru; Ohkura, Hanayuki; Fukushima, Satsuki; Saito, Atsuhiro; Shiozaki, Motoko; Kawaguchi, Naomasa; Matsuura, Nariaki; Shimizu, Tatsuya; Okano, Teruo; Matsuyama, Akifumi

    2014-01-01

    Introduction: Functional skeletal myoblasts (SMBs) are transplanted into the heart effectively and safely as cell sheets, which induce functional recovery in myocardial infarction (MI) patients without lethal arrhythmia. However, their therapeutic effect is limited by ischemia. Mesenchymal stem cells (MSCs) have prosurvival/proliferation and antiapoptotic effects on co-cultured cells in vitro. We hypothesized that adding MSCs to the SMB cell sheets might enhance SMB survival post-transplantation and improve their therapeutic effects. Methods and Results: Cell sheets of primary SMBs of male Lewis rats (r-SMBs), primary MSCs of human female fat tissues (h-MSCs), and their co-cultures were generated using temperature-responsive dishes. The levels of candidate paracrine factors, rat hepatocyte growth factor and vascular endothelial growth factor, in vitro were significantly greater in the h-MSC/r-SMB co-cultures than in those containing r-SMBs only, by real-time PCR and enzyme-linked immunosorbent assay (ELISA). MI was generated by left-coronary artery occlusion in female athymic nude rats. Two weeks later, co-cultured r-SMB or h-MSC cell sheets were implanted or no treatment was performed (n=10 each). Eight weeks later, systolic and diastolic function parameters were improved in all three treatment groups compared to no treatment, with the greatest improvement in the co-cultured cell sheet transplantation group. Consistent results were found for capillary density, collagen accumulation, myocyte hypertrophy, Akt-signaling, STAT3 signaling, and survival of transplanted cells of rat origin, and were related to poly (ADP-ribose) polymerase-dependent signal transduction. Conclusions: Adding MSCs to SMB cell sheets enhanced the sheets' angiogenesis-related paracrine mechanics and, consequently, functional recovery in a rat MI model, suggesting a possible strategy for clinical applications. PMID:24164292

  4. Oral chromium picolinate improves carbohydrate and lipid metabolism and enhances skeletal muscle Glut-4 translocation in obese, hyperinsulinemic (JCR-LA corpulent) rats.

    Science.gov (United States)

    Cefalu, William T; Wang, Zhong Q; Zhang, Xian H; Baldor, Linda C; Russell, James C

    2002-06-01

    Human studies suggest that chromium picolinate (CrPic) decreases insulin levels and improves glucose disposal in obese and type 2 diabetic populations. To evaluate whether CrPic may aid in treatment of the insulin resistance syndrome, we assessed its effects in JCR:LA-corpulent rats, a model of this syndrome. Male lean and obese hyperinsulinemic rats were randomly assigned to receive oral CrPic [80 microg/(kg. d); n = 5 or 6, respectively) in water or to control conditions (water, n = 5). After 3 mo, a 120-min intraperitoneal glucose tolerance test (IPGTT) and a 30-min insulin tolerance test were performed. Obese rats administered CrPic had significantly lower fasting insulin levels (1848 +/- 102 vs. 2688 +/- 234 pmol/L; P < 0.001; mean +/- SEM) and significantly improved glucose disappearance (P < 0.001) compared with obese controls. Glucose and insulin areas under the curve for IPGTT were significantly less for obese CrPic-treated rats than in obese controls (P < 0.001). Obese CrPic-treated rats had lower plasma total cholesterol (3.57 +/- 0.28 vs. 4.11 +/- 0.47 mmol/L, P < 0.05) and higher HDL cholesterol levels (1.92 +/- 0.09 vs. 1.37 +/- 0.36 mmol/L, P < 0.01) than obese controls. CrPic did not alter plasma glucose or cholesterol levels in lean rats. Total skeletal muscle glucose transporter (Glut)-4 did not differ among groups; however, CrPic significantly enhanced membrane-associated Glut-4 in obese rats after insulin stimulation. Thus, CrPic supplementation enhances insulin sensitivity and glucose disappearance, and improves lipids in male obese hyperinsulinemic JCR:LA-corpulent rats.

  5. Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content.

    NARCIS (Netherlands)

    Kempen, K.P.G.; Saris, W.H.M.; Kuipers, H.; Glatz, J.F.; van der Vusse, G.J.

    1998-01-01

    University of Maastricht, Maastricht, The Netherlands. BACKGROUND: Skeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscl

  6. The memory-enhancing effect of erucic acid on scopolamine-induced cognitive impairment in mice.

    Science.gov (United States)

    Kim, Eunji; Ko, Hae Ju; Jeon, Se Jin; Lee, Sunhee; Lee, Hyung Eun; Kim, Ha Neul; Woo, Eun-Rhan; Ryu, Jong Hoon

    2016-03-01

    Erucic acid is a monounsaturated omega-9 fatty acid isolated from the seed of Raphanus sativus L. that is known to normalize the accumulation of very long chain fatty acids in the brains of patients suffering from X-linked adrenoleukodystrophy. Here, we investigated whether erucic acid enhanced cognitive function or ameliorated scopolamine-induced memory impairment using the passive avoidance, Y-maze and Morris water maze tasks. Erucic acid (3mg/kg, p.o.) enhanced memory performance in normal naïve mice. In addition, erucic acid (3mg/kg, p.o.) ameliorated scopolamine-induced memory impairment, as assessed via the behavioral tasks. We then investigated the underlying mechanism of the memory-enhancing effect of erucic acid. The administration of erucic acid increased the phosphorylation levels of phosphatidylinositide 3-kinase (PI3K), protein kinase C zeta (PKCζ), extracellular signal-regulated kinase (ERK), cAMP response element-binding protein (CREB) and additional protein kinase B (Akt) in the hippocampus. These results suggest that erucic acid has an ameliorative effect in mice with scopolamine-induced memory deficits and that the effect of erucic acid is partially due to the activation of PI3K-PKCζ-ERK-CREB signaling as well as an increase in phosphorylated Akt in the hippocampus. Therefore, erucic acid may be a novel therapeutic agent for diseases associated with cognitive deficits, such as Alzheimer's disease.

  7. Rapamycin blocks leucine-induced protein synthesis by suppressing mTORC1 activation in skeletal muscle of neonatal pigs

    Science.gov (United States)

    Skeletal muscle in the neonate grows at a rapid rate due in part to an enhanced sensitivity to the postprandial rise in amino acids, particularly leucine (Leu). To elucidate the molecular mechanism by which Leu stimulates protein synthesis in neonatal muscle, overnight fasted 7-day-old piglets were...

  8. High altitude exposure alters gene expression levels of DNA repair enzymes, and modulates fatty acid metabolism by SIRT4 induction in human skeletal muscle.

    Science.gov (United States)

    Acs, Zoltan; Bori, Zoltan; Takeda, Masaki; Osvath, Peter; Berkes, Istvan; Taylor, Albert W; Yang, Hu; Radak, Zsolt

    2014-06-01

    We hypothesized that high altitude exposure and physical activity associated with the attack to Mt Everest could alter mRNA levels of DNA repair and metabolic enzymes and cause oxidative stress-related challenges in human skeletal muscle. Therefore, we have tested eight male mountaineers (25-40 years old) before and after five weeks of exposure to high altitude, which included attacks to peaks above 8000m. Data gained from biopsy samples from vastus lateralis revealed increased mRNA levels of both cytosolic and mitochondrial superoxide dismutase. On the other hand 8-oxoguanine DNA glycosylase (OGG1) mRNA levels tended to decrease while Ku70 mRNA levels and SIRT6 decreased with altitude exposure. The levels of SIRT1 and SIRT3 mRNA did not change significantly. However, SIRT4 mRNA level increased significantly, which could indicate decreases in fatty acid metabolism, since SIRT4 is one of the important regulators of this process. Within the limitations of this human study, data suggest that combined effects of high altitude exposure and physical activity climbing to Mt. Everest, could jeopardize the integrity of the particular chromosome. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Biological and Tribological Assessment of Poly(Ethylene Oxide Terephthalate)/Poly(Butylene Terephthalate), Polycaprolactone, and Poly (L\\DL) Lactic Acid Plotted Scaffolds for Skeletal Tissue Regeneration.

    Science.gov (United States)

    Hendrikson, Wilhelmus J; Zeng, Xiangqiong; Rouwkema, Jeroen; van Blitterswijk, Clemens A; van der Heide, Emile; Moroni, Lorenzo

    2016-01-21

    Additive manufactured scaffolds are fabricated from three commonly used biomaterials, polycaprolactone (PCL), poly (L\\DL) lactic acid (P(L\\DL)LA), and poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT). Scaffolds are compared biologically and tribologically. Cell-seeded PEOT/PBT scaffolds cultured in osteogenic and chondrogenic differentiation media show statistical significantly higher alkaline phosphatase (ALP) activity/DNA and glycosaminoglycans (GAG)/DNA ratios, followed by PCL and P(L\\DL)LA scaffolds, respectively. The tribological performance is assessed by determining the friction coefficients of the scaffolds at different loads and sliding velocities. With increasing load or decreasing sliding velocity, the friction coefficient value decreases. PEOT/PBT show to have the lowest friction coefficient value, followed by PCL and P(L\\DL)LA. The influence of the scaffold architecture is further determined with PEOT/PBT. Reducing of the fiber spacing results in a lower friction coefficient value. The best and the worst performing scaffold architecture are chosen to investigate the effect of cell culture on the friction coefficient. Matrix deposition is low in the cell-seeded scaffolds and the effect is, therefore, undetermined. Taken together, our studies show that PEOT/PBT scaffolds support better skeletal differentiation of seeded stromal cells and lower friction coefficient compared to PCL and P(L/DL)A scaffolds.

  10. Effects of dietary eicosapentaenoic acid (EPA) supplementation in high-fat fed mice on lipid metabolism and apelin/APJ system in skeletal muscle.

    Science.gov (United States)

    Bertrand, Chantal; Pignalosa, Angelica; Wanecq, Estelle; Rancoule, Chloé; Batut, Aurélie; Deleruyelle, Simon; Lionetti, Lillà; Valet, Philippe; Castan-Laurell, Isabelle

    2013-01-01

    Various studies have shown that eicosapentaenoic acid (EPA) has beneficial effects on obesity and associated disorders. Apelin, the ligand of APJ receptor also exerts insulin-sensitizing effects especially by improving muscle metabolism. EPA has been shown to increase apelin production in adipose tissue but its effects in muscle have not been addressed. Thus, the effects of EPA supplementation (36 g/kg EPA) in high-fat diet (HFD) (45% fat, 20% protein, 35% carbohydrate) were studied in mice with focus on muscle lipid metabolism and apelin/APJ expression. Compared with HFD mice, HFD+EPA mice had significantly less weight gain, fat mass, lower blood glucose, insulinemia and hepatic steatosis after 10 weeks of diet. In addition, EPA prevented muscle metabolism alterations since intramuscular triglycerides were decreased and β-oxidation increased. In soleus muscles of HFD+EPA mice, apelin and APJ expression were significantly increased compared to HFD mice. However, plasma apelin concentrations in HFD and HFD+EPA mice were similar. EPA-induced apelin expression was confirmed in differentiated C2C12 myocytes but in this model, apelin secretion was also increased in response to EPA treatment. In conclusion, EPA supplementation in HFD prevents obesity and metabolic alterations in mice, especially in skeletal muscle. Since EPA increases apelin/APJ expression in muscle, apelin may act in a paracrine/autocrine manner to contribute to these benefical effects.

  11. Rapid loss of adiponectin-stimulated fatty acid oxidation in skeletal muscle of rats fed a high fat diet is not due to altered muscle redox state.

    Science.gov (United States)

    Ritchie, Ian R W; Dyck, David J

    2012-01-01

    A high fat (HF) diet rapidly impairs the ability of adiponectin (Ad) to stimulate fatty acid (FA) oxidation in oxidative soleus muscle, but the underlying mechanism remains elusive. Mere days of HF feeding also increase the muscle's production and accumulation of reactive oxygen species (ROS) and shift cellular redox to a more oxidized state. It seems plausible that this shift towards a more oxidized state might act as negative feedback to suppress the ability of Ad to stimulate FA oxidation and generate more ROS. Therefore, we sought to determine whether i) a shift towards a more oxidized redox state (reduction in GSH/2GSSG) coincided with impaired Ad-stimulated palmitate oxidation in oxidative and glycolytic rodent muscle after 5 days of HF feeding (60% kCal), and ii) if supplementation with the antioxidant, N-acetylcysteine (NAC) could prevent the HF-diet induced impairment in Ad-response. Globular Ad (gAd) increased palmitate oxidation in isolated soleus and EDL muscles by 42% and 34%, respectively (pmuscles. HF feeding decreased total GSH (-26%, pmuscle. Furthermore, direct incubations with H(2)O(2) did not impair Ad-stimulated FA oxidation in either muscle. In conclusion, our data indicates that skeletal muscle Ad resistance is rapidly induced in both oxidative and glycolytic muscle, independently of altered cellular redox state.

  12. Expression of perilipins in human skeletal muscle in vitro and in vivo in relation to diet, exercise and energy balance

    DEFF Research Database (Denmark)

    Gjelstad, I M F; Haugen, F; Gulseth, H L

    2011-01-01

    , enhanced the expression of perilipin 2 and 3. Perilipin 1 mRNA correlated positively with body fat mass, whereas none of the perilipins were associated with insulin sensitivity. In conclusion, all perilipins mRNAs were expressed in human skeletal muscle. Diet as well as endurance exercise modulated......The perilipin proteins enclose intracellular lipid droplets. We describe the mRNA expression of the five perilipins in human skeletal muscle in relation to fatty acid supply, exercise and energy balance. We observed that all perilipins were expressed in skeletal muscle biopsies with the highest m......RNA levels of perilipin 2, 4 and 5. Cultured myotubes predominantly expressed perilipin 2 and 3. In vitro, incubation of myotubes with fatty acids enhanced mRNA expression of perilipin 1, 2 and 4. In vivo, low fat diet increased mRNA levels of perilipin 3 and 4. Endurance training, but not strength training...

  13. Enhanced expression of aconitase raises acetic acid resistance in Acetobacter aceti.

    Science.gov (United States)

    Nakano, Shigeru; Fukaya, Masahiro; Horinouchi, Sueharu

    2004-06-15

    Acetobacter spp. are used for industrial vinegar production because of their high ability to oxidize ethanol to acetic acid and high resistance to acetic acid. Two-dimensional gel electrophoretic analysis of a soluble fraction of Acetobacter aceti revealed the presence of several proteins whose production was enhanced, to various extents, in response to acetic acid in the medium. A protein with an apparent molecular mass of 100 kDa was significantly enhanced in amount by acetic acid and identified to be aconitase by NH2-terminal amino acid sequencing and subsequent gene cloning. Amplification of the aconitase gene by use of a multicopy plasmid in A. aceti enhanced the enzymatic activity and acetic acid resistance. These results showed that aconitase is concerned with acetic acid resistance. Enhancement of the aconitase activity turned out to be practically useful for acetic acid fermentation, because the A. aceti transformant harboring multiple copies of the aconitase gene produced a higher concentration of acetic acid with a reduced growth lag-time.

  14. Systematic Procedure for Integrated Process Operation: Reverse Electro-Enhanced Dialysis (REED) during Lactic Acid Fermentation

    DEFF Research Database (Denmark)

    Prado Rubio, Oscar Andres; Jørgensen, Sten Bay; Jonsson, Gunnar Eigil

    2011-01-01

    The integration of lactic acid fermentation and Reverse Electro-Enhanced Dialysis (REED) is investigated based upon previously developed mathematical models. A goal driven process and operation design procedure is proposed and partially investigated. The conceptual analysis of the processes...

  15. Muscle free amino acid profiles are related to differences in skeletal muscle growth between single and twin ovine fetuses near term.

    Science.gov (United States)

    Sales, Francisco; Pacheco, David; Blair, Hugh; Kenyon, Paul; McCoard, Sue

    2013-01-01

    Twin sheep fetuses have reduced skeletal muscle weight near birth relative to singles as a result of restricted muscle hypertrophy. Intracellular free amino acids (FAA) are reported to regulate metabolic pathways which control muscle protein accretion, whereby reduced intracellular content of specific FAA may reduce their activation and therefore, muscle hypertrophy. The aim of this study was to determine whether differences in muscle weight between singleton and twin fetuses, under different maternal conditions is associated with reduced concentration of specific FAA. The FAA content in the semitendinosus muscle (ST) in singleton and twin fetuses (rank) at 140 days of gestation from heavy (H) or light (L) ewes fed ad libitum (A) or maintenance (M) level of nutrition was measured. Muscle weight was reduced in twin fetuses compared to singletons in all groups. Reduced concentrations of leucine, threonine and valine, but higher concentrations of methionine, ornithine, lysine and serine were found in twin fetuses compared to singletons. Maternal size and nutrition interaction with rank resulted in reduced glutamine in twins from HM-ewes (H-ewes under M nutrition) compared to their singleton counterparts. Maternal weight interaction with pregnancy rank reduced the concentration of arginine in twins, with a larger effect on H-ewes compared with L-ewes. Maternal size interaction with pregnancy rank resulted in twins from M-ewes to have lower alanine, while twins from A-ewes had lower aspartic acid concentration compared to singletons. The ST muscle weight was positively correlated only with arginine concentration after taking into account rank, size and nutrition. The present results indicate that reduced concentrations of specific intracellular FAA, such as arginine, leucine, valine, glutamine, which are known to play a role in muscle growth, could be acting as limiting factors for muscle hypertrophy in twin fetuses during late gestation. Ewe size and nutrition can

  16. Fe-nitrilotriacetic acid coordination polymer nanowires: an effective sensing platform for fluorescence-enhanced nucleic acid detection

    Science.gov (United States)

    Zhou, Yunchun; Liu, Qian; Sun, Xuping; Kong, Rongmei

    2017-02-01

    The determination of specific nucleic acid sequences is key in identifying disease-causing pathogens and genetic diseases. In this paper we report the utilization of Fe-nitrilotriacetic acid coordination polymer nanowires as an effective nanoquencher for fluorescence-enhanced nucleic acid detection. The detection is fast and the whole process can be completed within 15 min. This nanosensor shows a low detection limit of 0.2 nM with selectivity down to single-base mismatch. This work provides us with an attractive sensing platform for applications.

  17. Enhanced production of polyunsaturated fatty acid docosahexaenoic acid by thraustochytrid protists

    Digital Repository Service at National Institute of Oceanography (India)

    Jain, R.; Raghukumar, S.; Chandramohan, D.

    The polyunsaturated fatty acid docosahexaenoic acid (DHA) is an important requirement in the human diet. It is also essential in the nutrition of crustaceans and aquaculture animals. Of the sources available for commercial production of DHA...

  18. Identification of the gene-regulatory landscape in skeletal development and potential links to skeletal regeneration

    Directory of Open Access Journals (Sweden)

    Hironori Hojo

    2017-06-01

    Full Text Available A class of gene-regulatory elements called enhancers are the main mediators controlling quantitative, temporal and spatial gene expressions. In the course of evolution, the enhancer landscape of higher organisms such as mammals has become quite complex, exerting biological functions precisely and coordinately. In mammalian skeletal development, the master transcription factors Sox9, Runx2 and Sp7/Osterix function primarily through enhancers on the genome to achieve specification and differentiation of skeletal cells. Recently developed genome-scale analyses have shed light on multiple layers of gene regulations, uncovering not only the primary mode of actions of these transcription factors on skeletal enhancers, but also the relation of the epigenetic landscape to three-dimensional chromatin architecture. Here, we review findings on the emerging framework of gene-regulatory networks involved in skeletal development. We further discuss the power of genome-scale analyses to provide new insights into genetic diseases and regenerative medicine in skeletal tissues.

  19. Reversal learning enhanced by lysergic acid diethylamide (LSD)

    Science.gov (United States)

    King, A.R.; Martin, I.L.; Arabella Melville, K.

    1974-01-01

    1 Small doses of lysergic acid diethylamide (LSD) (12.5-50 μg/kg) consistently facilitated learning of a brightness discrimination reversal. 2 2-Bromo-lysergic acid diethylamide (BOL-148), a structural analogue of LSD, with similar peripheral anti-5-hydroxytrypamine activity but no psychotomimetic properties, had no effect in this learning situation at a similar dose (25 μg/kg). 3 LSD, but not BOL-148, caused a small but significant increase in brain 5-hydroxytryptamine levels, but had no effect on the levels of catecholamines in the brain at 25 μg/kg. PMID:4458849

  20. Deamination of amino acids as a source for ammonia production in human skeletal muscle during prolonged exercise

    DEFF Research Database (Denmark)

    Van Hall, Gerrit; van der Vusse, G J; Söderlund, K;

    1995-01-01

    1. The influence of pre-exercise muscle glycogen content on ammonia production, adenine nucleotide breakdown and amino acid metabolism was investigated during prolonged exercise in six subjects having one leg with a normal and one leg with a low muscle glycogen content. One-leg knee-extensor exer......1. The influence of pre-exercise muscle glycogen content on ammonia production, adenine nucleotide breakdown and amino acid metabolism was investigated during prolonged exercise in six subjects having one leg with a normal and one leg with a low muscle glycogen content. One-leg knee......-extensor exercise was performed for 90 min, at a workload of 60-65% of the maximal power output, first with one leg and then with the other. 2. During exercise ammonia was released in gradually increasing amounts and plateaued after 1 h exercise at a rate of approximately 80 mumol min-1. The total ammonia...... production was 9.1 +/- 0.4 and 9.5 +/- 1.4 mmol (kg dry muscle)-1 in the normal and low glycogen content leg, respectively. 3. Levels of muscle phosphocreatine (PC), total adenine nucleotides and inosine monophosphate (IMP) were similar at rest and after 90 min of exercise. 4. Only minor differences were...

  1. Large Ferrierite Crystals as Models for Catalyst Deactivation during Skeletal Isomerisation of Oleic Acid: Evidence for Pore Mouth Catalysis.

    Science.gov (United States)

    Wiedemann, Sophie C C; Ristanović, Zoran; Whiting, Gareth T; Reddy Marthala, V R; Kärger, Jörg; Weitkamp, Jens; Wels, Bas; Bruijnincx, Pieter C A; Weckhuysen, Bert M

    2016-01-04

    Large zeolite crystals of ferrierite have been used to study the deactivation, at the single particle level, of the alkyl isomerisation catalysis of oleic acid and elaidic acid by a combination of visible micro-spectroscopy and fluorescence microscopy (both polarised wide-field and confocal modes). The large crystals did show the desired activity, albeit only traces of the isomerisation product were obtained and low conversions were achieved compared to commercial ferrierite powders. This limited activity is in line with their lower external non-basal surface area, supporting the hypothesis of pore mouth catalysis. Further evidence for the latter comes from visible micro-spectroscopy, which shows that the accumulation of aromatic species is limited to the crystal edges, while fluorescence microscopy strongly suggests the presence of polyenylic carbocations. Light polarisation associated with the spatial resolution of fluorescence microscopy reveals that these carbonaceous deposits are aligned only in the larger 10-MR channels of ferrierite at all crystal edges. The reaction is hence further limited to these specific pore mouths.

  2. PNW cetacean muscle biochemistry - Muscle Myoglobin Content and Acid Buffering Capacity of Cetaceans from the Pacific Northwest to Assess Dive Capacity and the Development of Diving Capabilities

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — This project assesses the development of two important skeletal muscle adaptations for diving (enhanced myoglobin content and acid buffering capacities) in a range...

  3. Branched-chain amino acids increase arterial blood ammonia in spite of enhanced intrinsic muscle ammonia metabolism in patients with cirrhosis and healthy subjects

    DEFF Research Database (Denmark)

    Dam, Gitte; Keiding, Susanne; Munk, Ole Lajord

    2011-01-01

    Branched-chain amino acids (BCAA) are used in attempts to reduce blood ammonia in patients with cirrhosis and intermittent hepatic encephalopathy based on the hypothesis that BCAA stimulate muscle ammonia detoxification. We studied the effects of an oral dose of BCAA on the skeletal muscle...... the metabolism of blood-supplied ammonia and the A-V measurements were used to measure the total ammonia metabolism across the thigh muscle. After intake of BCAA, blood ammonia increased more than 30% in both groups of subjects (both P ....05). BCAA intake led to a massive glutamine release from the muscle (cirrhotic patients, P BCAA enhanced the intrinsic muscle metabolism of ammonia but not the metabolism of blood-supplied ammonia in both the patients with cirrhosis and in the healthy...

  4. Boric acid-enhanced embedding medium for cryomicrotomy.

    Science.gov (United States)

    Lim, Jin Ik; Park, Hun-Kuk

    2012-05-01

    A polyvinyl alcohol (PVA)/polyethylene glycol (PEG)-based resin is commonly used as a cryoembedding medium for the histological analysis of frozen tissue sections. However, it is not easy to obtain sufficient numbers of satisfactory reproducible sections owing to the differences between the mechanical properties of the medium and embedded tissue and the low cohesive force of the medium. We describe a modified PVA-based cryoembedding medium, composed of PVA (10wt% and 15wt%) with the addition of boric acid (from 0 to 5wt%), that can improve the sectioning properties and efficiency of frozen tissue for histological analysis. The amount of load under the same compressive displacement as well as cohesive force increased with increasing boric acid and PVA contents. 15wt% PVA and 3wt% boric acid was determined as an optimal composition for cryoembedding material based on the sectioning efficiency measured by the numbers of unimpaired sectioned slices and the amount of load under the same compressive displacement test. On the basis of the results of routine hematoxylin and eosin staining of cryosections of tissue embedded in a medium with 3wt% boric acid and PVA, it was concluded that the modified PVA cryoembedding medium can improve the efficiency of cryosectioning for subsequent histological or histochemical analysis of various tissues. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. CO2-enhanced extraction of acetic acid from fermented wastewater

    NARCIS (Netherlands)

    Reyhanitash, Ehsan; Zaalberg, B.; IJmker, H.M.; Kersten, Sascha R.A.; Schuur, Boelo

    2015-01-01

    The industrial process of recovering fermentation-based volatile fatty acids (VFAs) utilizes H2SO4 to acidify the fermentation broth containing VFA-salts [e.g. Ca(CH3COO)2] to enable formation of molecular VFAs. Molecular VFAs are then recovered by liquid–liquid extraction. However, acidification

  6. CO2-enhanced extraction of acetic acid from fermented wastewater

    NARCIS (Netherlands)

    Reyhanitash, E.; Zaalberg, B.; IJmker, H.M.; Kersten, S.R.A.; Schuur, B.

    2015-01-01

    The industrial process of recovering fermentation-based volatile fatty acids (VFAs) utilizes H2SO4 to acidify the fermentation broth containing VFA-salts [e.g. Ca(CH3COO)2] to enable formation of molecular VFAs. Molecular VFAs are then recovered by liquid–liquid extraction. However, acidification wi

  7. Peptide Nucleic Acids Having Enhanced Binding Affinity and Sequence Specificity

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. Methods of increasing binding affinity and sequence specificity of peptide nucleic aci...

  8. Enhancement of the ferromagnetic order of graphite after sulphuric acid treatment

    OpenAIRE

    Barzola-Quiquia, J.; Böhlmann, W.; Esquinazi, P.; Schadewitz, A.; Ballestar, A.; Dusari, S.; Schultze-Nobre, L.; Kersting, B.

    2011-01-01

    We have studied the changes in the ferromagnetic behavior of graphite powder and graphite flakes after treatment with diluted sulphuric acid. We show that this kind of acid treatment enhances substantially the ferromagnetic magnetization of virgin graphite micrometer size powder as well as in graphite flakes. The anisotropic magnetoresistance (AMR) amplitude at 300 K measured in a micrometer size thin graphite flake after acid treatment reaches values comparable to polycrystalline cobalt.

  9. Summer-to-Winter Phenotypic Flexibility of Fatty Acid Transport and Catabolism in Skeletal Muscle and Heart of Small Birds.

    Science.gov (United States)

    Zhang, Yufeng; King, Marisa O; Harmon, Erin; Swanson, David L

    2015-01-01

    Prolonged shivering in birds is mainly fueled by lipids. Consequently, lipid transport and catabolism are vital for thermogenic performance and could be upregulated along with thermogenic capacity as part of the winter phenotype. We investigated summer-to-winter variation in lipid transport and catabolism by measuring mRNA expression, protein levels, and enzyme activities for several key steps of lipid transport and catabolic pathways in pectoralis muscle and heart in two small temperate-zone resident birds, American goldfinches (Spinus tristis) and black-capped chickadees (Poecile atricapillus). Cytosolic fatty acid binding protein (FABPc; a key component of intramyocyte lipid transport) mRNA and/or protein levels were generally higher in winter for pectoralis muscle and heart for both species. However, seasonal variation in plasma membrane lipid transporters, fatty acyl translocase, and plasma membrane fatty acid binding protein in pectoralis and heart differed between the two species, with winter increases for chickadees and seasonal stability or summer increases for goldfinches. Catabolic enzyme activities generally showed limited seasonal differences for both tissues and both species. These data suggest that FABPc is an important target of upregulation for the winter phenotype in pectoralis and heart of both species. Plasma membrane lipid transporters and lipid catabolic capacity were also elevated in winter for chickadees but not for goldfinches. Because the two species show differential regulation of distinct aspects of lipid transport and catabolism, these data are consistent with other recent studies documenting that different bird species or populations employ a variety of strategies to promote elevated winter thermogenic capacity.

  10. Lactic Acid Recovery in Electro-Enhanced Dialysis: Modelling and Validation

    DEFF Research Database (Denmark)

    Prado Rubio, Oscar Andres; Jørgensen, Sten Bay; Jonsson, Gunnar Eigil

    2009-01-01

    and migration across the boundary layers and membranes. The model is validated for Donnan dialysis recovery of different monoprotic carboxylic acids. Simulations are used to evaluate the potential enhancement of lactate fluxes under current load conditions, referred as Electro-Enhanced Dialysis operation...

  11. Degradation of fructans and production of propionic acid by Bacteroides thetaiotaomicron are enhanced by shortage of amino acids

    Directory of Open Access Journals (Sweden)

    Signe eAdamberg

    2014-12-01

    Full Text Available Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by the catabolism of various polysaccharides. A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. The polyfructans inulin (from chicory and levan (synthesized using levansucrase from Pseudomonas syringae, two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. The calorimetric power-time curves were substrate specific and typically multiauxic. A surplus of amino acids reduced the consumption of longer oligosaccharides (DP > 3. Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h, followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. In the medium supplemented with 20 amino acids, the highest production of D-lactate (82 ± 33 mmol/gDW occurred in parallel with extensive consumption (up to 17 mmol/gDW of amino acids, especially Ser, Thr and Asp. The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. The effect of levan on balancing or modifying colon microbiota will be studied in

  12. Degradation of Fructans and Production of Propionic Acid by Bacteroides thetaiotaomicron are Enhanced by the Shortage of Amino Acids.

    Science.gov (United States)

    Adamberg, Signe; Tomson, Katrin; Vija, Heiki; Puurand, Marju; Kabanova, Natalja; Visnapuu, Triinu; Jõgi, Eerik; Alamäe, Tiina; Adamberg, Kaarel

    2014-01-01

    Bacteroides thetaiotaomicron is commonly found in the human colon and stabilizes its ecosystem by catabolism of various polysaccharides. A model of cross-talk between the metabolism of amino acids and fructans in B. thetaiotaomicron was proposed. The growth of B. thetaiotaomicron DSM 2079 in two defined media containing mineral salts and vitamins, and supplemented with either 20 or 2 amino acids, was studied in an isothermal microcalorimeter. The polyfructans inulin (from chicory) and levan (synthesized using levansucrase from Pseudomonas syringae), two fructooligosaccharide preparations with different composition, sucrose and fructose were tested as substrates. The calorimetric power-time curves were substrate specific and typically multiauxic. A surplus of amino acids reduced the consumption of longer oligosaccharides (degree of polymerization > 3). Bacterial growth was not detected either in the carbohydrate free medium containing amino acids or in the medium with inulin as a sole carbohydrate. In amino acid-restricted medium, fermentation leading to acetic acid formation was dominant at the beginning of growth (up to 24 h), followed by increased lactic acid production, and mainly propionic and succinic acids were produced at the end of fermentation. In the medium supplemented with 20 amino acids, the highest production of d-lactate (82 ± 33 mmol/gDW) occurred in parallel with extensive consumption (up to 17 mmol/gDW) of amino acids, especially Ser, Thr, and Asp. The production of Ala and Glu was observed at growth on all substrates, and the production was enhanced under amino acid deficiency. The study revealed the influence of amino acids on fructan metabolism in B. thetaiotaomicron and showed that defined growth media are invaluable in elucidating quantitative metabolic profiles of the bacteria. Levan was shown to act as an easily degradable substrate for B. thetaiotaomicron. The effect of levan on balancing or modifying colon microbiota will

  13. Afferent signalling from the acid-challenged rat stomach is inhibited and gastric acid elimination is enhanced by lafutidine

    Directory of Open Access Journals (Sweden)

    Holzer Peter

    2009-06-01

    Full Text Available Abstract Background Lafutidine is a histamine H2 receptor antagonist, the gastroprotective effect of which is related to its antisecretory activity and its ability to activate a sensory neuron-dependent mechanism of defence. The present study investigated whether intragastric administration of lafutidine (10 and 30 mg/kg modifies vagal afferent signalling, mucosal injury, intragastric acidity and gastric emptying after gastric acid challenge. Methods Adult rats were treated with vehicle, lafutidine (10 – 30 mg/kg or cimetidine (10 mg/kg, and 30 min later their stomachs were exposed to exogenous HCl (0.25 M. During the period of 2 h post-HCl, intragastric pH, gastric volume, gastric acidity and extent of macroscopic gastric mucosal injury were determined and the activation of neurons in the brainstem was visualized by c-Fos immunocytochemistry. Results Gastric acid challenge enhanced the expression of c-Fos in the nucleus tractus solitarii but caused only minimal damage to the gastric mucosa. Lafutidine reduced the HCl-evoked expression of c-Fos in the NTS and elevated the intragastric pH following intragastric administration of excess HCl. Further analysis showed that the gastroprotective effect of lafutidine against excess acid was delayed and went in parallel with facilitation of gastric emptying, measured indirectly via gastric volume changes, and a reduction of gastric acidity. The H2 receptor antagonist cimetidine had similar but weaker effects. Conclusion These observations indicate that lafutidine inhibits the vagal afferent signalling of a gastric acid insult, which may reflect an inhibitory action on acid-induced gastric pain. The ability of lafutidine to decrease intragastric acidity following exposure to excess HCl cannot be explained by its antisecretory activity but appears to reflect dilution and/or emptying of the acid load into the duodenum. This profile of actions emphasizes the notion that H2 receptor antagonists can protect

  14. Enhanced silicate weathering is not limited by silicic acid saturation

    NARCIS (Netherlands)

    Schuiling, R.D.; Wilson, S.A.; Power, I.M.

    2011-01-01

    Enhanced weathering of olivine as a means of sequestering carbon is investigated by Köhler et al. (1). Specifically, the study discusses the potential distribution of fine olivine powder, obtained from dunite mines, in the humid tropic regions of the Amazon and Congo River catchments. Olivine (forst

  15. Validation of Interstitial Fractional Volume Quantification by Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging in Porcine Skeletal Muscles.

    Science.gov (United States)

    Hindel, Stefan; Söhner, Anika; Maa, Marc; Sauerwein, Wolfgang; Baba, Hideo Andreas; Kramer, Martin; Lüdemann, Lutz

    2017-01-01

    The aim of our study was to assess the accuracy of fractional interstitial volume determination in low perfused and low vascularized tissue by using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The fractional interstitial volume (ve) was determined in the medial thigh muscle of 12 female pigs by using a 3-dimensional gradient echo sequence with k-space sharing and administering gadolinium-based contrast agent (gadoterate meglumine). Analysis was performed using 3 pharmacokinetic models: the simple Tofts model (TM), the extended TM (ETM), and the 2-compartment exchange model (2CXM). We investigated the effect of varying acquisition durations (ADs) on the model parameter estimates of the 3 models and compared the ve values with the results of histological examinations of muscle sections of the medial thigh muscle. Histological measurements yielded a median value (25%-75% quartile) of 4.8% (3.7%-6.2%) for ve. The interstitial fractional volume determined by DCE-MRI was comparable to the histological results but varied strongly with AD for the TM and ETM. For the TM and the ETM, the results were virtually the same. Choosing arterial hematocrit to Hcta = 0.4, the lowest median ve value determined by DCE-MRI was 5.2% (3.3%-6.1%) for the ETM at a 6-minute AD. The maximum ve value determined with the ETM at a 15-minute AD was 7.7% (4.5%-9.0%). The variation with AD of median ve values obtained with the 2CXM was much smaller: 6.2% (3.1%-9.2%) for the 6-minute AD and 6.3% (4.3%-9.8%) for the 15-minute AD. The best fit for the 2CXM was found at the 10-minute AD with ve values of 6.6% (3.7%-8.2%). No significant correlation between the histological and any DCE-MRI modeling results was found. Considering the expected accuracy of histological measurements, the medians of the MR modeling results were in good agreement with the histological prediction. A parameter determination uncertainty was identified with the use of the TMs. This is due to underfitting and

  16. In vivo, fatty acid translocase (CD36) critically regulates skeletal muscle fuel selection, exercise performance, and training-induced adaptation of fatty acid oxidation.

    Science.gov (United States)

    McFarlan, Jay T; Yoshida, Yuko; Jain, Swati S; Han, Xioa-Xia; Snook, Laelie A; Lally, James; Smith, Brennan K; Glatz, Jan F C; Luiken, Joost J F P; Sayer, Ryan A; Tupling, A Russell; Chabowski, Adrian; Holloway, Graham P; Bonen, Arend

    2012-07-06

    For ~40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (-21%) and oxidation (-25%), intramuscular lipids (less than or equal to -31%), and hepatic glycogen (-20%); but muscle glycogen, VO(2max), and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO(2max)) CD36-KO mice, fatty acid transport (-41%), oxidation (-37%), and exercise duration (-44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27-55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84-90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO.

  17. In Vivo, Fatty Acid Translocase (CD36) Critically Regulates Skeletal Muscle Fuel Selection, Exercise Performance, and Training-induced Adaptation of Fatty Acid Oxidation*

    Science.gov (United States)

    McFarlan, Jay T.; Yoshida, Yuko; Jain, Swati S.; Han, Xioa-Xia; Snook, Laelie A.; Lally, James; Smith, Brennan K.; Glatz, Jan F. C.; Luiken, Joost J. F. P.; Sayer, Ryan A.; Tupling, A. Russell; Chabowski, Adrian; Holloway, Graham P.; Bonen, Arend

    2012-01-01

    For ∼40 years it has been widely accepted that (i) the exercise-induced increase in muscle fatty acid oxidation (FAO) is dependent on the increased delivery of circulating fatty acids, and (ii) exercise training-induced FAO up-regulation is largely attributable to muscle mitochondrial biogenesis. These long standing concepts were developed prior to the recent recognition that fatty acid entry into muscle occurs via a regulatable sarcolemmal CD36-mediated mechanism. We examined the role of CD36 in muscle fuel selection under basal conditions, during a metabolic challenge (exercise), and after exercise training. We also investigated whether CD36 overexpression, independent of mitochondrial changes, mimicked exercise training-induced FAO up-regulation. Under basal conditions CD36-KO versus WT mice displayed reduced fatty acid transport (−21%) and oxidation (−25%), intramuscular lipids (less than or equal to −31%), and hepatic glycogen (−20%); but muscle glycogen, VO2max, and mitochondrial content and enzymes did not differ. In acutely exercised (78% VO2max) CD36-KO mice, fatty acid transport (−41%), oxidation (−37%), and exercise duration (−44%) were reduced, whereas muscle and hepatic glycogen depletions were accelerated by 27–55%, revealing 2-fold greater carbohydrate use. Exercise training increased mtDNA and β-hydroxyacyl-CoA dehydrogenase similarly in WT and CD36-KO muscles, but FAO was increased only in WT muscle (+90%). Comparable CD36 increases, induced by exercise training (+44%) or by CD36 overexpression (+41%), increased FAO similarly (84–90%), either when mitochondrial biogenesis and FAO enzymes were up-regulated (exercise training) or when these were unaltered (CD36 overexpression). Thus, sarcolemmal CD36 has a key role in muscle fuel selection, exercise performance, and training-induced muscle FAO adaptation, challenging long held views of mechanisms involved in acute and adaptive regulation of muscle FAO. PMID:22584574

  18. Enhanced fatty acid flux triggered by adiponectin overexpression.

    Science.gov (United States)

    Shetty, Shoba; Ramos-Roman, Maria A; Cho, You-Ree; Brown, Jonathan; Plutzky, Jorge; Muise, Eric S; Horton, Jay D; Scherer, Philipp E; Parks, Elizabeth J

    2012-01-01

    Adiponectin overexpression in mice increases insulin sensitivity independent of adiposity. Here, we combined stable isotope infusion and in vivo measurements of lipid flux with transcriptomic analysis to characterize fatty acid metabolism in transgenic mice that overexpress adiponectin via the aP2-promoter (ADNTg). Compared with controls, fasted ADNTg mice demonstrated a 31% reduction in plasma free fatty acid concentrations (P = 0.008), a doubling of ketones (P = 0.028), and a 68% increase in free fatty acid turnover in plasma (15.1 ± 1.5 vs. 25.3 ± 6.8 mg/kg · min, P = 0.011). ADNTg mice had 2-fold more brown adipose tissue mass, and triglyceride synthesis and turnover were 5-fold greater in this organ (P = 0.046). Epididymal white adipose tissue was slightly reduced, possibly due to the approximately 1.5-fold increase in the expression of genes involved in oxidation (peroxisome proliferator-activated receptor α, peroxisome proliferator-activated receptor-γ coactivator 1α, and uncoupling protein 3). In ADNTg liver, lipogenic gene expression was reduced, but there was an unexpected increase in the expression of retinoid pathway genes (hepatic retinol binding protein 1 and retinoic acid receptor beta and adipose Cyp26A1) and liver retinyl ester content (64% higher, P < 0.02). Combined, these data support a physiological link between adiponectin signaling and increased efficiency of triglyceride synthesis and hydrolysis, a process that can be controlled by retinoids. Interactions between adiponectin and retinoids may underlie adiponectin's effects on intermediary metabolism.

  19. Performance enhancement of phosphoric acid fuel cell using phosphosilicate gel based electrolyte

    Institute of Scientific and Technical Information of China (English)

    Kajari Kargupta; Swati Saha; Dipali Banerjee; Mrinal Seal; Saibal Ganguly

    2012-01-01

    Replacement of phosphoric acid electrolyte by phosphosilicate gel based electrolytes is proposed for performance enhancement of phosphoric acid fuel cell (PAFG).Phosphosilicate gel in paste form and in powder form is synthesized from tetraethoxysilane and orthophosphoric acid using sol-gel method for two different P/Si ratio of 5 and 1.5 respectively.Replacement of phosphoric acid electrolyte by phosphosilicate gel paste enhances the peak power generation of the fuel cell by 133% at 120 ℃ cell temperature; increases the voltage generation in the ohmic regime and extends the maximum possible load current.Polyinyl alcohol (PVA) is used to bind the phosphosilicate gel powder and to form the hybrid crosslinked gel polymer electrolyte membrane.Soaking the membrane with phosphoric acid solution,instead of that with water improves the proton conductivity of the membrane,enhances the voltage and power generation by the fuel cell and extends the maximum possible operating temperature.At lower operating temperature of 70 ℃,peak power produced by phosphosilicate gel polymer electrolyte membrane fuel cell ( PGMFC ) is increased by 40% compared to that generated by phosphoric acid fuel cell ( PAFC ).However,the performance of composite membrane diminishes as the cell temperature increases.Thus phosphosilicate gel in paste form is found to be a good alternative of phosphoric acid electrolyte at medium operating temperature range while phosphosilicate gel-PVA composite offers performance enhancement at low operating temperatures.

  20. Interactive effects of glutamine and gamma-aminobutyric acid on growth performance and skeletal muscle amino acid metabolism of 22-42-day-old broilers exposed to hot environment

    Science.gov (United States)

    Hu, Hong; Bai, Xi; Shah, Assar Ali; Dai, Sifa; Wang, Like; Hua, Jinling; Che, Chuanyan; He, Shaojun; Wen, Aiyou; Jiang, Jinpeng

    2016-06-01

    The present experiment was conducted to investigate the interactive effects between dietary glutamine (Gln, 0 and 5 g/kg) and gamma-aminobutyric acid (GABA, 0 and 100 mg/kg) on growth performance and amino acid (AA) metabolism of broilers under hot environment. A total of 360 22-day-old Arbor Acres male chickens were randomly assigned to five treatment groups under thermoneutral chamber (PC, 23 °C) and cyclic heat stress (HS, 30-34 °C cycling) conditions. Compared with the PC group, cyclic HS decreased ( P muscle at 28, 35, and 42 days, while it increased ( P muscle, the Gln supplementation increased ( P muscle Gln concentrations, glutaminase activities, GS activities at 28 and 35 days, and DWG, GABA concentrations, and GABA-T activities at 28, 35, and 42 days in broilers under cyclic HS. In conclusion, the present results indicated that the interactions of exogenous Gln and GABA could offer a potential nutritional strategy to prevent HS-related depression in skeletal muscle Gln and GABA metabolism of broilers.

  1. Engineering acyl carrier protein to enhance production of shortened fatty acids.

    Science.gov (United States)

    Liu, Xueliang; Hicks, Wade M; Silver, Pamela A; Way, Jeffrey C

    2016-01-01

    The acyl carrier protein (ACP) is an essential and ubiquitous component of microbial synthesis of fatty acids, the natural precursor to biofuels. Natural fatty acids usually contain long chains of 16 or more carbon atoms. Shorter carbon chains, with increased fuel volatility, are desired for internal combustion engines. Engineering the length specificity of key proteins in fatty acid metabolism, such as ACP, may enable microbial synthesis of these shorter chain fatty acids. We constructed a homology model of the Synechococcus elongatus ACP, showing a hydrophobic pocket harboring the growing acyl chain. Amino acids within the pocket were mutated to increase steric hindrance to the acyl chain. Certain mutant ACPs, when over-expressed in Escherichia coli, increased the proportion of shorter chain lipids; I75 W and I75Y showed the strongest effects. Expression of I75 W and I75Y mutant ACPs also increased production of lauric acid in E. coli that expressed the C12-specific acyl-ACP thioesterase from Cuphea palustris. We engineered the specificity of the ACP, an essential protein of fatty acid metabolism, to alter the E. coli lipid pool and enhance production of medium-chain fatty acids as biofuel precursors. These results indicate that modification of ACP itself could be combined with enzymes affecting length specificity in fatty acid synthesis to enhance production of commodity chemicals based on fatty acids.

  2. PPAR{delta} is a fatty acid sensor, which enhances mitochondrial oxidation in insulin

    DEFF Research Database (Denmark)

    Ravnskjaer, Kim; Frigerio, Francesca; Boergesen, Michael;

    2010-01-01

    against adverse effects on GSIS associated with prolonged fatty acid exposure. The presented results indicate that the nuclear receptor PPARdelta is a fatty acid sensor that adapts beta-cell mitochondrial function to long-term changes in unsaturated fatty acid levels. As maintenance of mitochondrial...... is the PPAR subtype expressed at the highest level in insulinoma cells and rat pancreatic islets. Furthermore, PPARdelta displays high transcriptional activity and acts in pronounced synergy with RXR. Interestingly, unsaturated fatty acids mimic the effects of synthetic PPARdelta agonists. Using sh......RNA-mediated knockdown we demonstrate that the ability of unsaturated fatty acids to stimulate fatty acid metabolism is dependent on PPARdelta. Activation of PPARdelta increases the fatty acid oxidation potential in INS-1E beta-cells, enhances glucose-stimulated insulin secretion (GSIS) from islets, and protects GSIS...

  3. Gallic Acid Is an Antagonist of Semen Amyloid Fibrils That Enhance HIV-1 Infection.

    Science.gov (United States)

    LoRicco, Josephine G; Xu, Changmingzi Sherry; Neidleman, Jason; Bergkvist, Magnus; Greene, Warner C; Roan, Nadia R; Makhatadze, George I

    2016-07-01

    Recent in vitro studies have demonstrated that amyloid fibrils found in semen from healthy and HIV-infected men, as well as semen itself, can markedly enhance HIV infection rates. Semen fibrils are made up of multiple naturally occurring peptide fragments derived from semen. The best characterized of these fibrils are SEVI (semen-derived enhancer of viral infection), made up of residues 248-286 of prostatic acidic phosphatase, and the SEM1 fibrils, made up of residues 86-107 of semenogelin 1. A small molecule screen for antagonists of semen fibrils identified four compounds that lowered semen-mediated enhancement of HIV-1 infectivity. One of the four, gallic acid, was previously reported to antagonize other amyloids and to exert anti-inflammatory effects. To better understand the mechanism by which gallic acid modifies the properties of semen amyloids, we performed biophysical measurements (atomic force microscopy, electron microscopy, confocal microscopy, thioflavin T and Congo Red fluorescence assays, zeta potential measurements) and quantitative assays on the effects of gallic acid on semen-mediated enhancement of HIV infection and inflammation. Our results demonstrate that gallic acid binds to both SEVI and SEM1 fibrils and modifies their surface electrostatics to render them less cationic. In addition, gallic acid decreased semen-mediated enhancement of HIV infection but did not decrease the inflammatory response induced by semen. Together, these observations identify gallic acid as a non-polyanionic compound that inhibits semen-mediated enhancement of HIV infection and suggest the potential utility of incorporating gallic acid into a multicomponent microbicide targeting both the HIV virus and host components that promote viral infection.

  4. Plasmon resonance enhancement of nonlinear properties of amino acids

    Science.gov (United States)

    de Araujo, Renato E.; Rativa, Diego; Gomes, Anderson S. L.

    2007-02-01

    Here we analyze the influence of 9 nm (mean diameter) silver particles on the nonlinear properties of intrinsic cell molecules. A novel high sensitivity thermal managed eclipse Z-scan technique with a femtosecond laser system was used to analyze the nonlinear susceptibility of water solution of fluorescent and non-fluorescent amino acids (Tryptophan, Tyrosine, Phenylalanine, Proline and Histidine) with different concentration of silver nanoparticles. The generalized Maxwell Garnett model is used to explain the behavior of the measured nonlinear refractive index with the change of the nanoparticles concentration in the sample.

  5. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-01-01

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

  6. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking.

    Science.gov (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B

    2011-10-24

    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  7. Dietary Salba (Salvia hispanica L) seed rich in α-linolenic acid improves adipose tissue dysfunction and the altered skeletal muscle glucose and lipid metabolism in dyslipidemic insulin-resistant rats.

    Science.gov (United States)

    Oliva, M E; Ferreira, M R; Chicco, A; Lombardo, Y B

    2013-10-01

    This work reports the effect of dietary Salba (chia) seed rich in n-3 α-linolenic acid on the morphological and metabolic aspects involved in adipose tissue dysfunction and the mechanisms underlying the impaired glucose and lipid metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while in the other half, corn oil (CO) was replaced by chia seed for 3 months (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size distribution, improved lipogenic enzyme activities, lipolysis and the anti-lipolytic action of insulin. In the skeletal muscle lipid storage, glucose phosphorylation and oxidation were normalized. Chia seed reversed the impaired insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and GLUT-4 protein levels as well as insulin resistance and dyslipidemia.

  8. Water-dispersible ascorbic-acid-coated magnetite nanoparticles for contrast enhancement in MRI

    Science.gov (United States)

    Sreeja, V.; Jayaprabha, K. N.; Joy, P. A.

    2015-04-01

    Superparamagnetic iron oxide nanoparticles of size ~5 nm surface functionalized with ascorbic acid (vitamin C) form a stable dispersion in water with a hydrodynamic size of ~30 nm. The anti-oxidant property of ascorbic acid is retained after capping, as evidenced from the capability of converting methylene blue to its reduced leuco form. NMR relaxivity studies show that the ascorbic-acid-coated superparamagnetic iron oxide aqueous nanofluid is suitable as a contrast enhancement agent for MRI applications, coupled with the excellent biocompatibility and medicinal values of ascorbic acid.

  9. Combined gadoxetic acid and gadofosveset enhanced liver MRI for detection and characterization of liver metastases

    Energy Technology Data Exchange (ETDEWEB)

    Bannas, Peter [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University Medical Center Hamburg-Eppendorf, Department of Radiology, University Hospital, Hamburg (Germany); Bookwalter, Candice A.; Ziemlewicz, Tim; Munoz del Rio, Alejandro; Potretzke, Theodora A. [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); Motosugi, Utaroh [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Yamanashi, Department of Radiology, Yamanashi (Japan); Nagle, Scott K. [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin-Madison, Department of Pediatrics, Madison, WI (United States); Reeder, Scott B. [University of Wisconsin-Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin-Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin-Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin-Madison, Department of Medicine, Madison, WI (United States); University of Wisconsin-Madison, Department of Emergency Medicine, Madison, WI (United States)

    2017-01-15

    To compare gadoxetic acid alone and combined gadoxetic acid/gadofosveset trisodium-enhanced liver MRI for detection of metastases and differentiation of metastases from haemangiomas. Ninety-one patients underwent gadoxetic acid-enhanced liver MRI before and after additional injection of gadofosveset. First, two readers retrospectively identified metastases on gadoxetic acid alone enhanced delayed hepatobiliary phase T1-weighted images together with all other MR images (dynamic images, T2-weighted images, diffusion-weighted images). Second, readers assessed additional T1-weighted images obtained after administration of gadofosveset trisodium. For both interpretations, readers rated lesion conspicuity and confidence in differentiating metastases from haemangiomas. Results were compared using alternative free-response receiver-operating characteristic (AFROC) and conventional ROC methods. Histology and follow-up served as reference standard. There were 145 metastases and 16 haemangiomas. Both readers detected more metastases using combined gadoxetic acid/gadofosveset (reader 1 = 130; reader 2 = 124) compared to gadoxetic acid alone (reader 1 = 104; reader 2 = 103). Sensitivity of combined gadoxetic acid/gadofosveset (reader 1 = 90 %; reader 2 = 86 %) was higher than that of gadoxetic acid alone (reader 1 = 72 %; reader 2 = 71 %, both P < 0.01). AFROC-AUC was higher for the combined technique (0.92 vs. 0.86, P < 0.001). Sensitivity for correct differentiation of metastases from haemangiomas was higher for the combined technique (reader 1 = 98 %; reader 2 = 99 % vs. reader 1 = 86 %; reader 2 = 91 %, both P < 0.01). ROC-AUC was significantly higher for the combined technique (reader 1 = 1.00; reader 2 = 1.00 vs. reader 1 = 0.87; reader 2 = 0.92, both P < 0.01). Combined gadoxetic acid/gadofosveset-enhanced MRI improves detection and characterization of liver metastases compared to gadoxetic acid alone. (orig.)

  10. Hydroxycinnamic acid derivatives in an aquatic liverwort as possible bioindicators of enhanced UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Arroniz-Crespo, M.; Nunez-Olivera, E. [Universidad de La Rioja, Complejo Cientifico-Tecnologico, Avda. Madre de Dios 51, 26006 Logrono (La Rioja) (Spain); Martinez-Abaigar, J. [Universidad de La Rioja, Complejo Cientifico-Tecnologico, Avda. Madre de Dios 51, 26006 Logrono (La Rioja) (Spain)], E-mail: javier.martinez@unirioja.es

    2008-01-15

    We examined, under laboratory conditions, the physiological responses of the aquatic liverwort Jungermannia exsertifolia subsp. cordifolia to artificially enhanced ultraviolet (UV) radiation for 82 days, especially considering the responses of five hydroxycinnamic acid derivatives. This species lives in mountain streams, where it is exposed to low temperatures and high UV levels, and this combination is believed to increase the adverse effects of UV. Enhanced UV radiation hardly caused any change in several physiological variables indicative of vitality, such as F{sub v}/F{sub m} and chlorophylls/phaeopigments ratio (OD430/OD410). Thus, this liverwort seemed to be tolerant to UV radiation, probably due to the accumulation of three UV-absorbing hydroxycinnamic acid derivatives: p-coumaroylmalic acid, 5''-(7'',8''-dihydroxycoumaroyl)-2-caffeoylmalic acid, and 5''-(7'',8''-dihydroxy-7-O-{beta}-glucosyl-coumaroyl)-2-caffeoylmalic acid. These compounds might serve as bioindicators of enhanced UV radiation. - Several hydroxycinnamic acid derivatives of an aquatic liverwort are induced by enhanced UV radiation and might serve as bioindicators of changes in UV levels.

  11. Skeletal Muscle Tissue Engineering: Methods to Form Skeletal Myotubes and Their Applications

    Science.gov (United States)

    Ostrovidov, Serge; Hosseini, Vahid; Ahadian, Samad; Fujie, Toshinori; Parthiban, Selvakumar Prakash; Ramalingam, Murugan; Bae, Hojae; Kaji, Hirokazu

    2014-01-01

    Skeletal muscle tissue engineering (SMTE) aims to repair or regenerate defective skeletal muscle tissue lost by traumatic injury, tumor ablation, or muscular disease. However, two decades after the introduction of SMTE, the engineering of functional skeletal muscle in the laboratory still remains a great challenge, and numerous techniques for growing functional muscle tissues are constantly being developed. This article reviews the recent findings regarding the methodology and various technical aspects of SMTE, including cell alignment and differentiation. We describe the structure and organization of muscle and discuss the methods for myoblast alignment cultured in vitro. To better understand muscle formation and to enhance the engineering of skeletal muscle, we also address the molecular basics of myogenesis and discuss different methods to induce myoblast differentiation into myotubes. We then provide an overview of different coculture systems involving skeletal muscle cells, and highlight major applications of engineered skeletal muscle tissues. Finally, potential challenges and future research directions for SMTE are outlined. PMID:24320971

  12. Reduced Burst Release and Enhanced Oral Bioavailability in Shikimic Acid-Loaded Polylactic Acid Submicron Particles by Coaxial Electrospray.

    Science.gov (United States)

    Wang, Miaomiao; Wang, Yuanwen; Omari-Siaw, Emmanuel; Wang, Shengli; Zhu, Yuan; Xu, Ximing

    2016-08-01

    In this study, using the coaxial electrospray method, we prepared submicron particles of the water-soluble drug shikimic acid (SA) with polylactic acid (PLA) as a polymer, to reduce the burst release and enhance the oral bioavailability. In vitro release study performed in HCl solution (pH 1.2) showed that the coaxial electrospray submicron particles could reduce burst release effect and presented a sustained release profile, compared with free SA and the particles prepared by electrospray method. The absorption of SA in the intestinal tract, studied using an in situ perfusion method in rats, also revealed jejunum as the main absorptive segment followed by duodenum and ileum. Moreover, the SA-loaded particles greatly enhanced the absorption of SA in the tested intestinal segments. The intestinal absorption rate was not enhanced with increasing drug concentration (5-15 μg/mL) which suggested that active transport or facilitated diffusion could play vital role in SA absorption. In addition, the SA-loaded PLA coaxial electrospray particle exhibited a prolonged plasma circulation with enhanced bioavailability after oral administration. In all, the coaxial electrospray technique could provide notable advantages for the oral delivery of SA, thereby enhancing its clinical application.

  13. Fish oil prevents essential fatty acid deficiency and enhances growth: clinical and biochemical implications.

    Science.gov (United States)

    Strijbosch, Robert A M; Lee, Sang; Arsenault, Danielle A; Andersson, Charlotte; Gura, Kathleen M; Bistrian, Bruce R; Puder, Mark

    2008-05-01

    Fish oil, a rich source of omega-3 fatty acids, has never been used as the sole source of lipid in clinical practice for fear of development of essential fatty acid deficiency, as it lacks the believed requisite levels of linoleic acid, an omega-6 fatty acid. The objectives of this study were to establish biochemical standards for fish oil as the sole fat and to test the hypothesis that fish oil contains adequate amounts of omega-6 fatty acids to prevent essential fatty acid deficiency. Forty mice were divided into 2 groups that were either pair fed or allowed to eat ad libitum. In each group, 4 subgroups of 5 mice were fed 1%, 5%, and 10% fish oil diets by weight or a control soybean diet for 9 weeks. Blood was collected at 4 time points, and fatty acid analysis was performed. Food intake and weight status were monitored. All groups but the pair-fed 1% fish oil group gained weight, and the 5% fish oil group showed the highest caloric efficiency in both pair-fed and ad libitum groups. Fatty acid profiles for the 1% fish oil group displayed clear essential fatty acid deficiency, 5% fish oil appeared marginal, and 10% and soybean oil diets were found to prevent essential fatty acid deficiency. Fish oil enhances growth through higher caloric efficiency. We established a total omega-6 fatty acid requirement of between 0.30% and 0.56% of dietary energy, approximately half of the conventionally believed 1% as linoleic acid. This can presumably be attributed to the fact that fish oil contains not only a small amount of linoleic acid, but also arachidonic acid, which has greater efficiency to meet omega-6 fatty acid requirements.

  14. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

    Science.gov (United States)

    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  15. Insulin-like growth factor-I extends in vitro replicative life span of skeletal muscle satellite cells by enhancing G1/S cell cycle progression via the activation of phosphatidylinositol 3'-kinase/Akt signaling pathway

    Science.gov (United States)

    Chakravarthy, M. V.; Abraha, T. W.; Schwartz, R. J.; Fiorotto, M. L.; Booth, F. W.

    2000-01-01

    Interest is growing in methods to extend replicative life span of non-immortalized stem cells. Using the insulin-like growth factor I (IGF-I) transgenic mouse in which the IGF-I transgene is expressed during skeletal muscle development and maturation prior to isolation and during culture of satellite cells (the myogenic stem cells of mature skeletal muscle fibers) as a model system, we elucidated the underlying molecular mechanisms of IGF-I-mediated enhancement of proliferative potential of these cells. Satellite cells from IGF-I transgenic muscles achieved at least five additional population doublings above the maximum that was attained by wild type satellite cells. This IGF-I-induced increase in proliferative potential was mediated via activation of the phosphatidylinositol 3'-kinase/Akt pathway, independent of mitogen-activated protein kinase activity, facilitating G(1)/S cell cycle progression via a down-regulation of p27(Kip1). Adenovirally mediated ectopic overexpression of p27(Kip1) in exponentially growing IGF-I transgenic satellite cells reversed the increase in cyclin E-cdk2 kinase activity, pRb phosphorylation, and cyclin A protein abundance, thereby implicating an important role for p27(Kip1) in promoting satellite cell senescence. These observations provide a more complete dissection of molecular events by which increased local expression of a growth factor in mature skeletal muscle fibers extends replicative life span of primary stem cells than previously known.

  16. Enhanced uptake of water by oxidatively processed oleic acid

    Directory of Open Access Journals (Sweden)

    A. Asad

    2004-01-01

    Full Text Available A quartz crystal microbalance apparatus has been used to measure the room temperature uptake of water vapour by thin films of oleic acid as a function of relative humidity, both before and following exposure of the films to various partial pressures of gas phase ozone. A rapid increase in the water-sorbing ability of the film is observed as its exposure to ozone is increased, followed by a plateau region in which additional water is taken up more gradually. In this fully-processed region the mass of water taken up by the film is about 4 times that of the unprocessed film. Infrared spectra of the films, measured after variable exposures to ozone, show dramatic increases in both the 'free' and hydrogen-bonded O-H stretching regions, and a decrease in the intensity of olefinic features. These results are consistent with the formation of an oxygenated polymeric product or products, as well as the gas phase products previously identified.

  17. Enhanced crystallization of poly (lactic acid) through reactive aliphatic bisamide

    Science.gov (United States)

    Nanthananon, P.; Seadan, M.; Pivsa-Art, S.; Suttiruengwong, S.

    2015-07-01

    The poor crystallization rate of poly (lactic acid) (PLA) is a major drawback in terms of controlling the properties of final products. To overcome this, a nucleating agent is normally applied. In this work, the aliphatic bisamide, N, N'-(1,3-propylene) bis(10-undecenamide) (PBU), having reactive functional groups is used as a crystallization promoter for PLA by adding PBU in various concentration (0.1-0.7 wt%) into PLA together with peroxide via reactive melt blending. The conventional ethylene bis-stearamide(EBS) is used for a comparison. The extruded samples are characterized for gel content and FT-IR spectroscopy. The crystallization behaviour and rate, and spherulites morphology are investigated by differential scanning calorimetry (DSC) and polarized optical microscopy (POM), respectively. It is found that the addition of PBU into PLA results in the dramatic increase in crystallinity and crystallization rate of PLA compared with neat PLA and PLA added EBS. The crystallinity increases to 24.9-28.3% higher than neat PLA under even cooling rate of 7°C/min. The addition of 0.7 wt% PBU shows the fastest crystallization rate with t1/2 value isothermally crystallized at 130°C of only 6 min. POM images indicate the increase in the nucleation density and very fine spherulitesof PLA added PBU, promoting the fast crystallization.

  18. Enhanced uptake of water by oxidatively processed oleic acid

    Directory of Open Access Journals (Sweden)

    A. Asad

    2004-07-01

    Full Text Available A quartz crystal microbalance apparatus has been used to measure the room temperature uptake of water vapour by thin films of oleic acid as a function of relative humidity, both before and following exposure of the films to various partial pressures of gas phase ozone. A rapid increase in the water-sorbing ability of the film is observed as its exposure to ozone is increased, followed by a plateau region in which no additional water is taken up. In this fully-processed region the mass of water taken up by the film is about 4 times that of the unprocessed film. Infrared spectra of the films, measured after variable exposures to ozone, show dramatic increases in both the "free" and hydrogen-bonded O-H stretching regions, and a decrease in the intensity of olefinic features. These results are consistent with the formation of an oxygenated polymeric product or products, as well as the gas phase products previously identified.

  19. Ferulic Acid Enhances Peripheral Nerve Regeneration across Long Gaps

    Directory of Open Access Journals (Sweden)

    Sheng-Chi Lee

    2013-01-01

    Full Text Available This study investigated the effect of ferulic acid (FA on peripheral nerve injury. In the in vitro test, the effect of FA on viability of Schwann cells was studied. In the in vivo test, right sciatic nerves of the rats were transected, and a 15 mm nerve defect was created. A nerve conduit made of silicone rubber tube filled with FA (5 and 25 μg/mL, or saline (control, was implanted into the nerve defect. Results show that the number of proliferating Schwann cells increased significantly in the FA-treated group at 25 μg/mL compared to that in the control group. After 8 weeks, the FA-treated group at 25 μg/mL had a higher rate of successful regeneration across the wide gap, a significantly calcitonin gene-related peptide (CGRP staining of the lamina I-II regions in the dorsal horn ipsilateral to the injury, a significantly diminished number of macrophages recruited, and a significantly shortening of the latency and an acceleration of the nerve conductive velocity (NCV of the evoked muscle action potentials (MAPs compared with the controls. In summary, the FA may be useful in the development of future strategies for the treatment of peripheral nerve injury.

  20. Capacity of lactic acid bacteria in immunity enhancement and cancer prevention.

    Science.gov (United States)

    Riaz Rajoka, Muhammad Shahid; Shi, Junling; Zhu, Jing; Shao, Dongyan; Huang, Qingsheng; Yang, Hui; Jin, Mingliang

    2017-01-01

    Lactic acid bacteria are associated with the human gastrointestinal tract. They are important for maintaining the balance of microflora in the human gut. An increasing number of published research reports in recent years have denoted the importance of producing interferon-gamma and IgA for treatment of disease. These agents can enhance the specific and nonspecific immune systems that are dependent on specific bacterial strains. The mechanisms of these effects were revealed in this investigation, where the cell walls of these bacteria were modulated by the cytokine pathways, while the whole bacterial cell mediated the host cell immune system and regulated the production of tumor necrosis factors and interleukins. A supplement of highly active lactic acid bacteria strains provided significant potential to enhance host's immunity, offering prevention from many diseases including some cancers. This review summarizes the current understanding of the function of lactic acid bacteria immunity enhancement and cancer prevention.

  1. Lauric acid dependent enhancement in hepatic SCPx protein requires an insulin deficient environment.

    Science.gov (United States)

    Lopez, Dayami; Niesen, Melissa; Bedi, Mohini; McLean, Mark P

    2008-02-01

    Sterol carrier protein X (SCPx) is a peroxisomal protein with both lipid transfer and thiolase activity. Treating with the fatty acid, lauric acid, induced SCPx mRNA levels in rat liver and in rat hepatoma H4IIE cells but enhanced protein levels of SCPx and the thiolase produced as a post-translational modification of SCPx were only seen in H4IIE cells. Further investigation revealed that the presence of insulin can mask lauric acid effects on the SCPx gene especially at the protein level. These data are in agreement with the findings that diabetes, a medical condition characterized by high levels of fatty acids in an insulin deficient environment, enhances the hepatic expression of SCPx.

  2. Enhanced high temperature thermoelectric response of sulphuric acid treated conducting polymer thin films

    KAUST Repository

    Sarath Kumar, S. R.

    2015-11-24

    We report the high temperature thermoelectric properties of solution processed pristine and sulphuric acid treated poly(3, 4-ethylenedioxythiophene):poly(4-styrenesulfonate) (or PEDOT:PSS) films. The acid treatment is shown to simultaneously enhance the electrical conductivity and Seebeck coefficient of the metal-like films, resulting in a five-fold increase in thermoelectric power factor (0.052 W/m. K ) at 460 K, compared to the pristine film. By using atomic force micrographs, Raman and impedance spectra and using a series heterogeneous model for electrical conductivity, we demonstrate that acid treatment results in the removal of PSS from the films, leading to the quenching of accumulated charge-induced energy barriers that prevent hopping conduction. The continuous removal of PSS with duration of acid treatment also alters the local band structure of PEDOT:PSS, resulting in simultaneous enhancement in Seebeck coefficient.

  3. Elucidating the role of ferrous ion cocatalyst in enhancing dilute acid pretreatment of lignocellulosic biomass

    Directory of Open Access Journals (Sweden)

    Wei Hui

    2011-11-01

    Full Text Available Abstract Background Recently developed iron cocatalyst enhancement of dilute acid pretreatment of biomass is a promising approach for enhancing sugar release from recalcitrant lignocellulosic biomass. However, very little is known about the underlying mechanisms of this enhancement. In the current study, our aim was to identify several essential factors that contribute to ferrous ion-enhanced efficiency during dilute acid pretreatment of biomass and to initiate the investigation of the mechanisms that result in this enhancement. Results During dilute acid and ferrous ion cocatalyst pretreatments, we observed concomitant increases in solubilized sugars in the hydrolysate and reducing sugars in the (insoluble biomass residues. We also observed enhancements in sugar release during subsequent enzymatic saccharification of iron cocatalyst-pretreated biomass. Fourier transform Raman spectroscopy showed that major peaks representing the C-O-C and C-H bonds in cellulose are significantly attenuated by iron cocatalyst pretreatment. Imaging using Prussian blue staining indicated that Fe2+ ions associate with both cellulose/xylan and lignin in untreated as well as dilute acid/Fe2+ ion-pretreated corn stover samples. Analyses by scanning electron microscopy and transmission electron microscopy revealed structural details of biomass after dilute acid/Fe2+ ion pretreatment, in which delamination and fibrillation of the cell wall were observed. Conclusions By using this multimodal approach, we have revealed that (1 acid-ferrous ion-assisted pretreatment increases solubilization and enzymatic digestion of both cellulose and xylan to monomers and (2 this pretreatment likely targets multiple chemistries in plant cell wall polymer networks, including those represented by the C-O-C and C-H bonds in cellulose.

  4. DSSR-enhanced visualization of nucleic acid structures in Jmol.

    Science.gov (United States)

    Hanson, Robert M; Lu, Xiang-Jun

    2017-05-03

    Sophisticated and interactive visualizations are essential for making sense of the intricate 3D structures of macromolecules. For proteins, secondary structural components are routinely featured in molecular graphics visualizations. However, the field of RNA structural bioinformatics is still lagging behind; for example, current molecular graphics tools lack built-in support even for base pairs, double helices, or hairpin loops. DSSR (Dissecting the Spatial Structure of RNA) is an integrated and automated command-line tool for the analysis and annotation of RNA tertiary structures. It calculates a comprehensive and unique set of features for characterizing RNA, as well as DNA structures. Jmol is a widely used, open-source Java viewer for 3D structures, with a powerful scripting language. JSmol, its reincarnation based on native JavaScript, has a predominant position in the post Java-applet era for web-based visualization of molecular structures. The DSSR-Jmol integration presented here makes salient features of DSSR readily accessible, either via the Java-based Jmol application itself, or its HTML5-based equivalent, JSmol. The DSSR web service accepts 3D coordinate files (in mmCIF or PDB format) initiated from a Jmol or JSmol session and returns DSSR-derived structural features in JSON format. This seamless combination of DSSR and Jmol/JSmol brings the molecular graphics of 3D RNA structures to a similar level as that for proteins, and enables a much deeper analysis of structural characteristics. It fills a gap in RNA structural bioinformatics, and is freely accessible (via the Jmol application or the JSmol-based website http://jmol.x3dna.org). © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  5. The enhancement mechanism of glycolic acid on the formation of atmospheric sulfuric acid-ammonia molecular clusters

    Science.gov (United States)

    Zhang, Haijie; Kupiainen-Määttä, Oona; Zhang, Xiuhui; Molinero, Valeria; Zhang, Yunhong; Li, Zesheng

    2017-05-01

    Highly oxidized multifunctional organic molecules, which span a wide range of low volatilities, are capable of driving particle formation as well as the initial growth of particles in the atmosphere. However, their participant mechanism in new particle formation still remains largely ambiguous. Here we present an investigation of the potentially participant mechanism of the simplest hydroxyl acid, glycolic acid (GA) on clusters formation by sulfuric acid (SA) and ammonia (A). Density functional theory calculations at the M062X/6-311++G(3df,3pd) level of theory combining with atmospheric cluster dynamics code simulations of (𝐒𝐀)xṡ𝐀yṡ(𝐆𝐀)z cluster (y≤x + z ≤ 3) systems at different temperatures (298, 278, 258, 238, and 218 K) give direct evidence of the enhancement effect of GA on the formation rates of SA-A-based clusters at high concentration of GA and T = 238 K and 218 K. Moreover, within GA's enhancement concentrations, the enhancement strength R of GA presents a positive dependence on its atmospheric concentrations and a negative dependence on temperature. A competitive relationship between SA and GA has been identified through the negative dependence of R on the concentrations of SA. The influence of A on R is more complex that R first increases, reaching a maximum value, and then decreases with the increasing concentration of A. Finally, the combination of the traced growth paths of the system with the enhancement strength of GA suggests a "catalytic" enhancement mechanism of GA where GA acts as a mediate bridge for the formation of pure SA-A-based clusters.

  6. Peptide Nucleic Acids Having Enhanced Binding Affinity, Sequence Specificity and Solubility

    DEFF Research Database (Denmark)

    1998-01-01

    A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting of naturally......-occurring nucleobases and non-naturally-occurring nucleobases attached to a polyamide backbone, and contain C1-C8 alkylamine side chains. Methods of enhancing the solubility, binding affinity and sequence specificity of PNAs are provided....

  7. Unsaturated fatty acids lactose esters: cytotoxicity, permeability enhancement and antimicrobial activity.

    Science.gov (United States)

    Lucarini, Simone; Fagioli, Laura; Campana, Raffaella; Cole, Hannah; Duranti, Andrea; Baffone, Wally; Vllasaliu, Driton; Casettari, Luca

    2016-10-01

    Sugar based surfactants conjugated with fatty acid chains are an emerging broad group of highly biocompatible and biodegradable compounds with established and potential future applications in the pharmaceutical, cosmetic and food industries. In this work, we investigated absorption enhancing and antimicrobial properties of disaccharide lactose, monoesterified with unsaturated fatty acids through an enzymatic synthetic approach. After chemical and cytotoxicity characterizations, their permeability enhancing activity was demonstrated using intestinal Caco-2 monolayers through transepithelial electrical resistance (TEER) and permeability studies. The synthesized compounds, namely lactose palmitoleate (URB1076) and lactose nervonate (URB1077), were shown to exhibit antimicrobial activity versus eight pathogenic species belonging to Gram-positive, Gram-negative microorganisms and fungi.

  8. Synthesis and assembly of Pd nanoparticles on graphene for enhanced electrooxidation of formic acid

    Science.gov (United States)

    Jin, Tao; Guo, Shaojun; Zuo, Jing-Lin; Sun, Shouheng

    2012-12-01

    Monodisperse 4.5 nm Pd nanoparticles (NPs) were synthesized by solution phase reduction of palladium acetylacetonate with morpholine borane in a mixture of oleylamine and 1-octadecene. These NPs were assembled on graphene uniformly in the form of a monolayer, and showed much enhanced catalysis for electrooxidation of formic acid. The work demonstrates the great potential of graphene as a support to enhance NP catalysis and stability for important chemical oxidation reactions.Monodisperse 4.5 nm Pd nanoparticles (NPs) were synthesized by solution phase reduction of palladium acetylacetonate with morpholine borane in a mixture of oleylamine and 1-octadecene. These NPs were assembled on graphene uniformly in the form of a monolayer, and showed much enhanced catalysis for electrooxidation of formic acid. The work demonstrates the great potential of graphene as a support to enhance NP catalysis and stability for important chemical oxidation reactions. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr33060a

  9. The suppression of enhanced bitterness intensity of macrolide dry syrup mixed with an acidic powder.

    Science.gov (United States)

    Ishizaka, Toshihiko; Okada, Sachie; Takemoto, Eri; Tokuyama, Emi; Tsuji, Eriko; Mukai, Junji; Uchida, Takahiro

    2007-10-01

    The aim of the present study was to identify a medicine which strongly enhanced the bitterness of clarithromycin dry syrup (CAMD) when administered concomitantly and to develop a method to suppress this enhanced bitterness. The bitterness enhancement was evaluated not only by gustatory sensation tests but also using pH and taste sensor measurements of the mixed sample. A remarkable bitterness enhancement was found when CAMD was mixed with the acidic powder L-carbocysteine. The acidic pH (pH 3.40) of the suspension made from these two preparations, seemed to be due to enhanced release of clarithromycin caused by the dissolution of the alkaline polymer film-coating. Several methods for preventing this bitterness enhancement were investigated. Neither increasing the volume of water taken with the mixture, nor changing the ratio of CAMD:L-carbocysteine in the mixture, were effective in reducing the bitterness intensity of the CAMD/L-carbocysteine mixture. The best way to achieve taste masking was to first administer CAMD mixed with chocolate jelly, which has a neutral pH, followed by the L-carbocysteine suspension. Similar results were obtained for the bitterness suppression of azithromycin fine granules with L-carbocysteine. The chocolate jelly will be useful for taste masking of bitter macrolide drug formulations, when they need to be administered together with acidic drug formulations.

  10. Gadoxetic acid enhanced MRI for differentiation of FNH and HCA: a single centre experience

    Energy Technology Data Exchange (ETDEWEB)

    Grieser, Christian; Steffen, Ingo G.; Perez Fernandez, Carmen Maria; Hamm, Bernd; Denecke, Timm [Klinik fuer Radiologie, Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Berlin (Germany); Kramme, Incken-Birthe; Blaeker, Hendrik; Kilic, Ergin [Institut fuer Pathologie, Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Berlin (Germany); Seehofer, Daniel [Klinik fuer Allgemein, Viszeral- und Transplantationschirurgie, Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Berlin (Germany); Schott, Eckart [Medizinische Klinik m.S. Hepatologie und Gastroenterologie, Campus Virchow-Klinikum, Charite - Universitaetsmedizin Berlin, Berlin (Germany)

    2014-06-15

    Evaluation of enhancement characteristics of histopathologically confirmed focal nodular hyperplasias (FNHs) and hepatocellular adenomas (HCAs) with gadoxetic acid-enhanced MRI. Sixty-eight patients with 115 histopathologically proven lesions (FNHs, n = 44; HCAs, n = 71) examined with gadoxetic acid-enhanced MRI were retrospectively enrolled (standard of reference: surgical resection, n = 53 patients (lesions: FNHs, n = 37; HCAs, n = 53); biopsy, n = 15 (lesions: FNHs, n = 7; HCAs, n = 18)). Two radiologists evaluated all MR images regarding morphological features as well as the vascular and hepatocyte-specific enhancement in consensus. For the hepatobiliary phase, relative enhancement of the lesions and lesion to liver enhancement were significantly lower for HCAs (mean, 48.7 (±48.4) % and 49.4 (±33.9) %) compared to FNHs (159.3 (±92.5) %; and 151.7 (±79) %; accuracy of 89 % and 90 %, respectively; P < 0.001). Visual strong uptake of FNHs vs. hypointensity of HCAs in the hepatobiliary phase resulted in an accuracy of 92 %. This parameter was superior to all other morphological and dynamic vascular criteria alone and in combination (accuracy, 54-85 %). For differentiation of FNHs and HCAs by means of MRI, gadoxetic acid uptake in the hepatobiliary phase was found to be superior to all other criteria alone and in combination. (orig.)

  11. Betaine and beet molasses enhance L-lactic acid production by Bacillus coagulans.

    Directory of Open Access Journals (Sweden)

    Ke Xu

    Full Text Available Lactic acid is an important chemical with various industrial applications, and it can be efficiently produced by fermentation, in which Bacillus coagulans strains present excellent performance. Betaine can promote lactic acid fermentation as an effective osmoprotectant. Here, positive effect of betaine on fermentation by B. coagulans is revealed. Betaine could enhance lactic acid production by protecting l-LDH activity and cell growth from osmotic inhibition, especially under high glucose concentrations and with poor organic nitrogen nutrients. The fermentation with 0.05 g/L betaine could produce 17.9% more lactic acid compared to the fermentation without betaine. Beet molasses, which is rich in sucrose and betaine, was utilized in a co-feeding fermentation and raised the productivity by 22%. The efficient lactic acid fermentation by B. coagulans is thus developed by using betaine and beet molasses.

  12. Betaine and beet molasses enhance L-lactic acid production by Bacillus coagulans.

    Science.gov (United States)

    Xu, Ke; Xu, Ping

    2014-01-01

    Lactic acid is an important chemical with various industrial applications, and it can be efficiently produced by fermentation, in which Bacillus coagulans strains present excellent performance. Betaine can promote lactic acid fermentation as an effective osmoprotectant. Here, positive effect of betaine on fermentation by B. coagulans is revealed. Betaine could enhance lactic acid production by protecting l-LDH activity and cell growth from osmotic inhibition, especially under high glucose concentrations and with poor organic nitrogen nutrients. The fermentation with 0.05 g/L betaine could produce 17.9% more lactic acid compared to the fermentation without betaine. Beet molasses, which is rich in sucrose and betaine, was utilized in a co-feeding fermentation and raised the productivity by 22%. The efficient lactic acid fermentation by B. coagulans is thus developed by using betaine and beet molasses.

  13. Enhanced butyric acid tolerance and bioproduction by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor.

    Science.gov (United States)

    Jiang, Ling; Wang, Jufang; Liang, Shizhong; Cai, Jin; Xu, Zhinan; Cen, Peilin; Yang, Shangtian; Li, Shuang

    2011-01-01

    Repeated fed-batch fermentation of glucose by Clostridium tyrobutyricum immobilized in a fibrous bed bioreactor (FBB) was successfully employed to produce butyric acid at a high final concentration as well as to adapt a butyric-acid-tolerant strain. At the end of the eighth fed-batch fermentation, the butyric acid concentration reached 86.9 ± 2.17 g/L, which to our knowledge is the highest butyric acid concentration ever produced in the traditional fermentation process. To understand the mechanism and factors contributing to the improved butyric acid production and enhanced acid tolerance, adapted strains were harvested from the FBB and characterized for their physiological properties, including specific growth rate, acid-forming enzymes, intracellular pH, membrane-bound ATPase and cell morphology. Compared with the original culture used to seed the bioreactor, the adapted culture showed significantly reduced inhibition effects of butyric acid on specific growth rate, cellular activities of butyric-acid-forming enzyme phosphotransbutyrylase (PTB) and ATPase, together with elevated intracellular pH, and elongated rod morphology.

  14. Low muscle glycogen and elevated plasma free fatty acid modify but do not prevent exercise-induced PDH activation in human skeletal muscle

    DEFF Research Database (Denmark)

    Kiilerich, Kristian; Gudmundsson, Mikkel; Birk, Jesper Bratz;

    2010-01-01

    Objective: Test the hypothesis that FFA and muscle glycogen modify exercise-induced regulation of PDH in human skeletal muscle through regulation of PDK4 expression. Research Design and Methods: On two occasions, healthy male subjects lowered (by exercise) muscle glycogen in one leg (LOW) relativ...

  15. ENHANCED DISEASE SUSCEPTIBILITY 1 and SALICYLIC ACID act redundantly to regulate resistance gene-mediated signaling

    Science.gov (United States)

    Resistance (R) protein–associated pathways are well known to participate in defense against a variety of microbial pathogens. Salicylic acid (SA) and its associated proteinaceous signaling components, including enhanced disease susceptibility 1 (EDS1), non–race-specific disease resistance 1 (NDR1), ...

  16. The Histone Deacetylase Inhibitor Valproic Acid Enhances Acquisition, Extinction, and Reconsolidation of Conditioned Fear

    Science.gov (United States)

    Bredy, Timothy W.; Barad, Mark

    2008-01-01

    Histone modifications contribute to the epigenetic regulation of gene expression, a process now recognized to be important for the consolidation of long-term memory. Valproic acid (VPA), used for many years as an anticonvulsant and a mood stabilizer, has effects on learning and memory and enhances the extinction of conditioned fear through its…

  17. Recombinant host cells and nucleic acid constructs encoding polypeptides having cellulolytic enhancing activity

    Energy Technology Data Exchange (ETDEWEB)

    Schnorr, Kirk; Kramer, Randall

    2017-03-28

    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 of producing and using the polypeptides.

  18. Exercise Promotes Healthy Aging of Skeletal Muscle

    DEFF Research Database (Denmark)

    Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M

    2016-01-01

    caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial...... respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle....

  19. Enhanced lignin monomer production caused by cinnamic Acid and its hydroxylated derivatives inhibits soybean root growth.

    Directory of Open Access Journals (Sweden)

    Rogério Barbosa Lima

    Full Text Available Cinnamic acid and its hydroxylated derivatives (p-coumaric, caffeic, ferulic and sinapic acids are known allelochemicals that affect the seed germination and root growth of many plant species. Recent studies have indicated that the reduction of root growth by these allelochemicals is associated with premature cell wall lignification. We hypothesized that an influx of these compounds into the phenylpropanoid pathway increases the lignin monomer content and reduces the root growth. To confirm this hypothesis, we evaluated the effects of cinnamic, p-coumaric, caffeic, ferulic and sinapic acids on soybean root growth, lignin and the composition of p-hydroxyphenyl (H, guaiacyl (G and syringyl (S monomers. To this end, three-day-old seedlings were cultivated in nutrient solution with or without allelochemical (or selective enzymatic inhibitors of the phenylpropanoid pathway in a growth chamber for 24 h. In general, the results showed that 1 cinnamic, p-coumaric, caffeic and ferulic acids reduced root growth and increased lignin content; 2 cinnamic and p-coumaric acids increased p-hydroxyphenyl (H monomer content, whereas p-coumaric, caffeic and ferulic acids increased guaiacyl (G content, and sinapic acid increased sinapyl (S content; 3 when applied in conjunction with piperonylic acid (PIP, an inhibitor of the cinnamate 4-hydroxylase, C4H, cinnamic acid reduced H, G and S contents; and 4 when applied in conjunction with 3,4-(methylenedioxycinnamic acid (MDCA, an inhibitor of the 4-coumarate:CoA ligase, 4CL, p-coumaric acid reduced H, G and S contents, whereas caffeic, ferulic and sinapic acids reduced G and S contents. These results confirm our hypothesis that exogenously applied allelochemicals are channeled into the phenylpropanoid pathway causing excessive production of lignin and its main monomers. By consequence, an enhanced stiffening of the cell wall restricts soybean root growth.

  20. Gallic Acid, the Active Ingredient of Terminalia bellirica, Enhances Adipocyte Differentiation and Adiponectin Secretion.

    Science.gov (United States)

    Makihara, Hiroko; Koike, Yuka; Ohta, Masatomi; Horiguchi-Babamoto, Emi; Tsubata, Masahito; Kinoshita, Kaoru; Akase, Tomoko; Goshima, Yoshio; Aburada, Masaki; Shimada, Tsutomu

    2016-01-01

    Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10-30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

  1. Gadoxetic Acid (Gd-EOB-DTPA)-Enhanced MRI versus Gadobenate Dimeglumine (Gd-BOPTA)-Enhanced MRI for Preoperatively Detecting Hepatocellular Carcinoma: an Initial Experience

    Energy Technology Data Exchange (ETDEWEB)

    Park, Yu Lri; Kim, Seong Hyun; Kim, Seung Hoon; Choi, Dong Il; Lee, Won Jae; Kim, Hee Jung; Koo, Ji Hyun; Lim, Hyo Keun [Samsung Medical Center, Seoul (Korea, Republic of); Jeon, Yong Hwan [Kangwon National University Hospital, Chuncheon (Korea, Republic of); Lee, Jong Mee; Kim, Min Ju [Korea University College of Medicine, Korea University Guro Hospital, Seoul (Korea, Republic of)

    2010-08-15

    This study was designed to compare the diagnostic performance of gadoxetic acid-enhanced magnetic resonance imaging (MRI) with gadobenate dimeglumine-enhanced MRI for preoperatively detecting hepatocellular carcinoma (HCC). Eighteen consecutive patients (17 men and one woman, age range: 31-73 years) with 22 HCCs underwent examinations with gadoxetic acid enhanced MRI and gadobenate dimeglumine-enhanced MRI on a 3.0-Tesla unit. The diagnosis of HCC was established after surgical resection and pathological conformation. Three observers independently reviewed each MR image in a random order on a tumor-by-tumor basis. The diagnostic accuracy of these techniques for the detection of HCC was assessed by performing an alternative free-response receiver operating characteristic (ROC) analysis. The sensitivity and positive predictive values were evaluated. The average value of the area under the ROC curve (Az) for gadoxetic acid enhanced MRI (0.887) was not significantly different from the Az (0.899) for gadobenate dimeglumine-enhanced MRI (p > 0.05). The overall sensitivities of gadoxetic acid enhanced MRI and gadobenate dimeglumine-enhanced MRI were 80% and 83%, respectively, with no significant difference (p > 0.05). The differences of the positive predictive values for the two contrast agents for each observer were not statistically significant (p > 0.05). The diagnostic performance of gadoxetic acid-enhanced MRI and gadobenate dimeglumine-enhanced MRI for preoperatively detecting HCC is quite similar

  2. Enhancement of the Electrical Properties of CVD-Grown Graphene with Ascorbic Acid Treatment

    Science.gov (United States)

    Tang, Chunmiao; Chen, Zhiying; Zhang, Haoran; Zhang, Yaqian; Zhang, Yanhui; Sui, Yanping; Yu, Guanghui; Cao, Yijiang

    2016-02-01

    Ascorbic acid was used to modify to chemical vapor deposition (CVD)-grown graphene films transferred onto SiO2 substrate. Residual polymer (polymethyl methacrylate), Fe3+, Cl-, H2O, and O2 affected the electrical and thermal properties on graphene during the transfer or device fabrication processes. Exposure of transferred graphene to ascorbic acid resulted in significantly enhanced electrical properties with increased charge carrier mobility. All devices exhibited more than 30% improvement in room temperature carrier mobility in air. The carrier mobility of the treated graphene did not significantly decrease in 21 days. This result can be attributed to electron donation to graphene through the -OH functional group in ascorbic acid that is absorbed in graphene. This work provides a method to enhance the electrical properties of CVD-grown graphene.

  3. SKIN PERMEATION ENHANCEMENT EFFECTS OF ASCORBIC ACID AND TRIETHYL CITRATE ON ROFECOXIB

    Directory of Open Access Journals (Sweden)

    MALAY K. DAS

    2008-01-01

    Full Text Available The enhancing effect of ascorbic acid and triethyl citrate (TEC on the in vitro skin permeation of rofecoxib across rat epidermis was investigated. Skin pre-treatment with ascorbic acid and TEC at different concentrations, followed by application of rofecoxib gel, showed higher permeation flux than the control condition. The mechanism underlying this permeation enhancement was probed with fourier transform infrared spectroscopy (FTIR. The FTIR spectra of rat epidermis treated with ascorbic acid revealed that ascorbic acid at low concentration appears to interact with dermal keratin, whereas at higher concentration it appears to interact with both dermal proteins and lipids. The FTIR spectra of rat epidermis treated with TEC showed a decrease in peak heights for both asymmetric and symmetric C-H stretching absorbance, indicating a change in the fluidity of alkyl chains in the intercellular lipids in the stratum corneum (SC. The protein disruption effect of TEC was probably due to the solvation of keratin by the formation of hydrogen bonds between TEC hydroxyl groups and keratin chain C=O groups. Skin pre-treatment with different concentrations of permeation enhancers did not show any significant change in lag time in comparison to control. The amount of rofecoxib retained in the skin after skin pre-treatment with enhancers was found to be higher than in the experiment without skin pre-treatment. Scanning electron microscopy (SEM confirmed the maintenance of skin integrity throughout the permeation experiment. The observed permeation enhancing effects of ascorbic acid and TEC in the present study indicate that a rapid percutaneous absorption of rofecoxib at effective therapeutic levels may facilitate faster anti-inflammatory activity.

  4. Remediation of TCE-contaminated groundwater using acid/BOF slag enhanced chemical oxidation.

    Science.gov (United States)

    Tsai, T T; Kao, C M; Wang, J Y

    2011-04-01

    The objective of this study was to evaluate the potential of applying acid/H(2)O(2)/basic oxygen furnace slag (BOF slag) and acid/S(2)O(8)(2-)/BOF slag systems to enhance the chemical oxidation of trichloroethylene (TCE)-contaminated groundwater. Results from the bench-scale study indicate that TCE oxidation via the Fenton-like oxidation process can be enhanced with the addition of BOF slag at low pH (pH=2-5.2) and neutral (pH=7.1) conditions. Because the BOF slag has iron abundant properties (14% of FeO and 6% of Fe(2)O(3)), it can be sustainably reused for the supplement of iron minerals during the Fenton-like or persulfate oxidation processes. Results indicate that higher TCE removal efficiency (84%) was obtained with the addition of inorganic acid for the activation of Fenton-like reaction compared with the experiments with organic acids addition (with efficiency of 10-15% lower) (BOF slag=10gL(-1); initial pH=5.2). This could be due to the fact that organic acids would compete with TCE for available oxidants. Results also indicate that the pH value had a linear correlation with the observed first-order decay constant of TCE, and thus, lower pH caused a higher TCE oxidation rate.

  5. The Hip Functional Retrieval after Elective Surgery May Be Enhanced by Supplemented Essential Amino Acids

    Directory of Open Access Journals (Sweden)

    Eleonora Baldissarro

    2016-01-01

    Full Text Available It is not known whether postsurgery systemic inflammation and plasma amino acid abnormalities are still present during rehabilitation of individuals after elective hip arthroplasty (EHA. Sixty subjects (36 females; age 66.58±8.37 years were randomized to receive 14-day oral EAAs (8 g/day or a placebo (maltodextrin. At admission to and discharge from the rehabilitation center, serum C-reactive protein (CRP and venous plasma amino acid concentrations were determined. Post-EHA hip function was evaluated by Harris hip score (HHS test. Ten matched healthy subjects served as controls. At baseline, all patients had high CRP levels, considerable reduction in several amino acids, and severely reduced hip function (HHS 40.78±2.70 scores. After treatment, inflammation decreased both in the EAA group and in the placebo group. Only EAA patients significantly improved their levels of glycine, alanine, tyrosine, and total amino acids. In addition, they enhanced the rate of hip function recovery (HHS (from baseline 41.8±1.15 to 76.37±6.6 versus baseline 39.78±4.89 to 70.0±7.1 in placebo one; p=0.006. The study documents the persistence of inflammation and plasma amino acid abnormalities in post-EHA rehabilitation phase. EAAs enhance hip function retrieval and improve plasma amino acid abnormalities.

  6. The Hip Functional Retrieval after Elective Surgery May Be Enhanced by Supplemented Essential Amino Acids

    Science.gov (United States)

    Baldissarro, Eleonora; Aquilani, Roberto; Boschi, Federica; Baiardi, Paola; Iadarola, Paolo; Fumagalli, Marco; Pasini, Evasio; Verri, Manuela; Dossena, Maurizia; Gambino, Arianna; Cammisuli, Sharon; Viglio, Simona

    2016-01-01

    It is not known whether postsurgery systemic inflammation and plasma amino acid abnormalities are still present during rehabilitation of individuals after elective hip arthroplasty (EHA). Sixty subjects (36 females; age 66.58 ± 8.37 years) were randomized to receive 14-day oral EAAs (8 g/day) or a placebo (maltodextrin). At admission to and discharge from the rehabilitation center, serum C-reactive protein (CRP) and venous plasma amino acid concentrations were determined. Post-EHA hip function was evaluated by Harris hip score (HHS) test. Ten matched healthy subjects served as controls. At baseline, all patients had high CRP levels, considerable reduction in several amino acids, and severely reduced hip function (HHS 40.78 ± 2.70 scores). After treatment, inflammation decreased both in the EAA group and in the placebo group. Only EAA patients significantly improved their levels of glycine, alanine, tyrosine, and total amino acids. In addition, they enhanced the rate of hip function recovery (HHS) (from baseline 41.8 ± 1.15 to 76.37 ± 6.6 versus baseline 39.78 ± 4.89 to 70.0 ± 7.1 in placebo one; p = 0.006). The study documents the persistence of inflammation and plasma amino acid abnormalities in post-EHA rehabilitation phase. EAAs enhance hip function retrieval and improve plasma amino acid abnormalities. PMID:27110573

  7. Optimization of culture media for enhancing gamma-linolenic acid production by Mucor hiemalis

    Directory of Open Access Journals (Sweden)

    Mina Mohammadi Nasr

    2016-03-01

    Full Text Available Introduction: g-linolenic acid is an essential fatty acid in human nutrition. In the present study, production of g-linolenic acid by Mucor hiemalis PTCC 5292 was evaluated in submerged fermentation. Materials and methods: The fermentation variables were chosen according to the fractional factorial design and further optimized via full factorial method. Four significant variables, glucose, peptone, ammonium nitrate and pH were selected for the optimization studies. The design consisted of total 16 runs consisting of runs at two levels for each factor with three replications of the center points. Results: The analysis of variance and three-dimensional response surface plot of effects indicated that variables were regarded to be significant for production of g-linolenic acid by Mucor hiemalis. Results indicated that fermentation at the optimum conditions (100 g/l glucose concentration; 1 g/l peptone; 1 g/l ammonium nitrate, and pH of 4.5 enhanced the g-linolenic acid production up to 709 mg/l. Discussion and conclusion: The results of this study indicated that higher g-linolenic acid yield can be achieved in a simple medium at high glucose and ammonium nitrate, low peptone concentrations and acidic pH by Mucor hiemalis PTCC 5292. This simple and low cost optimization condition of culture media can be applied for g-linolenic acid production at higher scale for pharmaceutical and nutritional industries. 

  8. Regulation of PDH, GS and insulin signalling in skeletal muscle

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup

    as decreased protein level of HKII and GLUT4 in skeletal muscle. Iαn addition, the ability of acute exercise to increase insulin-stimulated glucose extraction was maintained after 7 days of bed rest. However, acute exercise after bed rest did not fully normalize the ability of skeletal muscle to extract....... Study IV demonstrated that an IL-6 injection reduced PDHa activity in skeletal muscle from fed mice and increased the PDHa activity in skeletal muscle from fasted mice without any change in phosphorylation level. An IL-6 injection increased AMPK and ACC phosphorylation in mouse skeletal muscle only...... with physical inactivity in humans, and physical inactivity did not affect the ability of exercise to enhance insulinmediated skeletal muscle glucose extraction. 2) Exercise training-improved glucose handling in aged human skeletal muscle was associated with increased content of key proteins in glucose...

  9. Enhanced succinic acid production in Aspergillus saccharolyticus by heterologous expression of fumarate reductase from Trypanosoma brucei.

    Science.gov (United States)

    Yang, Lei; Lübeck, Mette; Ahring, Birgitte K; Lübeck, Peter S

    2016-02-01

    Aspergillus saccharolyticus exhibits great potential as a cell factory for industrial production of dicarboxylic acids. In the analysis of the organic acid profile, A. saccharolyticus was cultivated in an acid production medium using two different pH conditions. The specific activities of the enzymes, pyruvate carboxylase (PYC), malate dehydrogenase (MDH), and fumarase (FUM), involved in the reductive tricarboxylic acid (rTCA) branch, were examined and compared in cells harvested from the acid production medium and a complete medium. The results showed that ambient pH had a significant impact on the pattern and the amount of organic acids produced by A. saccharolyticus. The wild-type strain produced higher amount of malic acid and succinic acid in the pH buffered condition (pH 6.5) compared with the pH non-buffered condition. The enzyme assays showed that the rTCA branch was active in the acid production medium as well as the complete medium, but the measured enzyme activities were different depending on the media. Furthermore, a soluble NADH-dependent fumarate reductase gene (frd) from Trypanosoma brucei was inserted and expressed in A. saccharolyticus. The expression of the frd gene led to an enhanced production of succinic acid in frd transformants compared with the wild-type in both pH buffered and pH non-buffered conditions with highest amount produced in the pH buffered condition (16.2 ± 0.5 g/L). This study demonstrates the feasibility of increasing succinic acid production through the cytosolic reductive pathway by genetic engineering in A. saccharolyticus.

  10. Enhanced cell viability in hyaluronic acid coated poly(lactic-co-glycolic acid) porous scaffolds within microfluidic channels.

    Science.gov (United States)

    Zamboni, Fernanda; Keays, Marie; Hayes, Sheri; Albadarin, Ahmad B; Walker, Gavin M; Kiely, Patrick A; Collins, Maurice N

    2017-10-30

    The concept of the present work is to produce porous optimised scaffolds of poly(lactic-co-glycolic acid) (PLGA) coated with hyaluronic acid (HA), to provide a suitable microenvironment for cellular proliferation. Freeze dried scaffolds were produced from PLGA with varying lactic acid and glycolic acid ratios along the polymer backbone, as follows: 50:50 ester terminated, 50:50 carboxylate end-group and 85:15 ester terminated. Subsequently, these scaffolds were immersed in crosslinked HA in order for the coating to enhance biological performance. Scaffolds were fully characterized with respect to surface morphology, physical and chemical properties. The biocompatibility of the scaffolds was firstly evaluated using standard L929 fibroblast cells in static culture and subsequently MCF-7 breast cancer cells were seeded on scaffolds which were incorporated within a microfluidic device. The results show that cells were attracted to and adhered to the scaffolds, with a higher affinity for HA coated scaffolds. In our system, cell viability was maintained up to 48h. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Study on the Enhancement of Proton Affinity by N-Diisopropyloxy Phosphorylation of Amino Acid in Mass Spectrometry

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    With introduction of a diisopropyloxy phosphoryl group into the N terminal of amino acids, it was found that proton affinity (PA) of amino acid was enhanced in mass spectrometry. Density functional theory calculations showed that the energy for protonation of DIPP-amino acid is lower than that of amino acid, which means PA of DIPP-AA is higher than that of corresponding amino acid. These results, coincident with our empirical results, offer a useful interpretation of experimental observations.

  12. Activation of AMP-Activated Protein Kinase and Stimulation of Energy Metabolism by Acetic Acid in L6 Myotube Cells.

    Science.gov (United States)

    Maruta, Hitomi; Yoshimura, Yukihiro; Araki, Aya; Kimoto, Masumi; Takahashi, Yoshitaka; Yamashita, Hiromi

    2016-01-01

    Previously, we found that orally administered acetic acid decreased lipogenesis in the liver and suppressed lipid accumulation in adipose tissue of Otsuka Long-Evans Tokushima Fatty rats, which exhibit hyperglycemic obesity with hyperinsulinemia and insulin resistance. Administered acetic acid led to increased phosphorylation of AMP-activated protein kinase (AMPK) in both liver and skeletal muscle cells, and increased transcripts of myoglobin and glucose transporter 4 (GLUT4) genes in skeletal muscle of the rats. It was suggested that acetic acid improved the lipid metabolism in skeletal muscles. In this study, we examined the activation of AMPK and the stimulation of GLUT4 and myoglobin expression by acetic acid in skeletal muscle cells to clarify the physiological function of acetic acid in skeletal muscle cells. Acetic acid added to culture medium was taken up rapidly by L6 cells, and AMPK was phosphorylated upon treatment with acetic acid. We observed increased gene and protein expression of GLUT4 and myoglobin. Uptake of glucose and fatty acids by L6 cells were increased, while triglyceride accumulation was lower in treated cells compared to untreated cells. Furthermore, treated cells also showed increased gene and protein expression of myocyte enhancer factor 2A (MEF2A), which is a well-known transcription factor involved in the expression of myoglobin and GLUT4 genes. These results indicate that acetic acid enhances glucose uptake and fatty acid metabolism through the activation of AMPK, and increases expression of GLUT4 and myoglobin.

  13. Enhanced rosmarinic acid production in cultured plants of two species of Mentha.

    Science.gov (United States)

    Roy, Debleena; Mukhopadhyay, Sandip

    2012-11-01

    In the present investigation an attempt has been made to enhance rosmarinic acid level in plants, grown in vitro, of 2 species of Mentha in presence of 2 precursors in the nutrient media during culture. For in vitro culture establishment and shoot bud multiplication, MS basal media were used supplemented with different concentrations and combinations of different growth regulator like NAA (alpha-napthaleneacetic acid), BAP (6-benzylaminopurine). The medium containing NAA (0.25 mg/L) and BAP (2.5 mg/L) gave the highest potentiality of shoot formation (average 58.0 numbers of shoots) per explant for Mentha piperita L. and the medium containing BAP (2.0 mg/L) gave the highest potentiality of shoot (average 19.2 numbers of shoots) formation per explant for Mentha arvensis L. The complete plants were regenerated in above mentioned media after 8 weeks of subculture. For in vitro enhancement of rosmarinic acid production, the 2 precursors tyrosine (Tyr) and phenylalanine (Phe) were added in the nutrient media at different levels (0.5 mg/L to 15.0 mg/L). Tyrosine was found to be very effective for augmenting rosmarinic acid content in Mentha piperita L. It nearly increased the production up to 1.77 times. In case of Mentha arvensis L., phenylalanine significantly affected the production of rosmarinic acid and the production was nearly 2.03 times more than the control. No significant increase in biomass was observed after addition of these precursors indicating that the added amino acids acting as precursors for rosmarinic acid synthesis were readily utilized in producing rosmarinic acid without promoting growth. Total protein profile also revealed the presence of a specific band in polyacrylamide gel electrophoresis.

  14. Genetic analysis of pathway regulation for enhancing branched-chain amino acid biosynthesis in plants

    KAUST Repository

    Chen, Hao

    2010-08-01

    The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that play critical roles in animal growth and development. Animals cannot synthesize these amino acids and must obtain them from their diet. Plants are the ultimate source of these essential nutrients, and they synthesize BCAAs through a conserved pathway that is inhibited by its end products. This feedback inhibition has prevented scientists from engineering plants that accumulate high levels of BCAAs by simply over-expressing the respective biosynthetic genes. To identify components critical for this feedback regulation, we performed a genetic screen for Arabidopsis mutants that exhibit enhanced resistance to BCAAs. Multiple dominant allelic mutations in the VALINE-TOLERANT 1 (VAT1) gene were identified that conferred plant resistance to valine inhibition. Map-based cloning revealed that VAT1 encodes a regulatory subunit of acetohydroxy acid synthase (AHAS), the first committed enzyme in the BCAA biosynthesis pathway. The VAT1 gene is highly expressed in young, rapidly growing tissues. When reconstituted with the catalytic subunit in vitro, the vat1 mutant-containing AHAS holoenzyme exhibits increased resistance to valine. Importantly, transgenic plants expressing the mutated vat1 gene exhibit valine tolerance and accumulate higher levels of BCAAs. Our studies not only uncovered regulatory characteristics of plant AHAS, but also identified a method to enhance BCAA accumulation in crop plants that will significantly enhance the nutritional value of food and feed. © 2010 Blackwell Publishing Ltd.

  15. The enhancement of pipemidic acid permeation into the pig urinary bladder wall.

    Science.gov (United States)

    Kerec, M; Svigelj, V; Bogataj, M; Mrhar, A

    2002-06-20

    The influence of interactions between polycarbophil and calcium on a model drug permeation into the pig urinary bladder wall was investigated. Pipemidic acid was used as a model drug. One percent w/v polycarbophil dispersion significantly increases the permeation of pipemidic acid into the urinary bladder wall. The enhanced absorption of pipemidic acid caused by polycarbophil is significantly less pronounced in polycarbophil dispersions containing calcium. The enhancement of pipemidic acid permeation into the urinary bladder wall could be due to the opening of tight junctions, which causes higher paracellular permeability. In the case of polycarbophil dispersion with calcium some carboxylic groups of polymer are already occupied with calcium, present in the dispersions. As a consequence extracellular calcium binds to polycarbophil in lower extent if compared with polycarbophil dispersion without calcium and transport is increased to a lesser degree. We concluded that the mechanism of drug absorption enhancement caused by polycarbophil could be similar for urinary bladder as described in the literature for intestinal mucosa.

  16. A new self-emulsifying formulation of mefenamic acid with enhanced drug dissolution

    Directory of Open Access Journals (Sweden)

    Pornsak Sriamornsak

    2015-04-01

    Full Text Available To enhance the dissolution of poorly soluble mefenamic acid, self-emulsifying formulation (SEF, composing of oil, surfactant and co-surfactant, was formulated. Among the oils and surfactants studied, Imwitor® 742, Tween® 60, Cremophore® EL and Transcutol® HP were selected as they showed maximal solubility to mefenamic acid. The ternary phase diagram was constructed to find optimal concentration that provided the highest drug loading. The droplet size after dispersion and drug dissolution of selected formulations were investigated. The results showed that the formulation containing Imwitor® 742, Tween® 60 and Transcutol® HP (10:30:60 can encapsulate high amount of mefenamic acid. The dissolution study demonstrated that, in the medium containing surfactant, nearly 100% of mefenamic acid were dissolved from SEF within 5 min while 80% of drugs were dissolved from the commercial product in 45 min. In phosphate buffer (without surfactant, 80% of drug were dissolved from the developed SEF within 5 min while only about 13% of drug were dissolved in 45 min, from the commercial product. The results suggested that the SEF can enhance the dissolution of poorly soluble drug and has a potential to enhance drug absorption and improve bioavailability of drug.

  17. Intrahepatic mass-forming cholangiocarcinoma: prognostic value of preoperative gadoxetic acid-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Koh, Jieun; Chung, Yong Eun; Kim, Myeong-Jin; Choi, Jin-Young [Yonsei University, College of Medicine, Department of Radiology, Research Institute of Radiological Science, Seoul (Korea, Republic of); Nahm, Ji Hae; Park, Young Nyun [Yonsei University, College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Kim, Ha Yan [Yonsei University, College of Medicine, Biostatistics Collaboration Unit, Severance Hospital, Seoul (Korea, Republic of); Kim, Kyung-Sik [Yonsei University, College of Medicine, Department of General Surgery, Seoul (Korea, Republic of)

    2016-02-15

    To assess whether gadoxetic acid-enhanced MRI could be used as a prognostic factor for intrahepatic mass-forming cholangiocarcinomas (IMCCs). Forty-one patients with pathologically proven IMCCs who underwent preoperative gadoxetic acid-enhanced MRI were included. The signal intensity of the IMCCs on hepatobiliary phase (HBP) MRI was qualitatively analyzed by two radiologists, and categorized into intermediate or hypointense groups. Analysis of clinicopathological prognostic factors and correlations of imaging and histology were also performed. Survival time and time to recurrence (TTR) were analyzed. Of the 41 IMCCs, 23 were in the intermediate group and 18 were in the hypointense group on HBP MRI. IMCCs in the intermediate group were associated with shorter survival time (P = 0.048) and TTR (P = 0.002) than the IMCCs of the hypointense group. Only the intermediate group on HBP MRI had a significantly shorter TTR on multivariate analysis (P = 0.012). The IMCCs of the intermediate group showed a tendency for more abundant tumour fibrous stroma than those of the hypointense group (P = 0.027). The enhancement of IMCCs on HBP gadoxetic acid-enhanced MRI appears to correlate with tumour aggressiveness and outcomes due to the tumour fibrous stromal component. Thus, HBP images could be a useful prognostic factor for IMCCs after surgery. (orig.)

  18. Central injection of GALR1 agonist M617 attenuates diabetic rat skeletal muscle insulin resistance through the Akt/AS160/GLUT4 pathway.

    Science.gov (United States)

    Fang, Penghua; Yu, Mei; He, Biao; Guo, Lili; Huang, Xiaoli; Kong, Guimei; Shi, Mingyi; Zhu, Yan; Bo, Ping; Zhang, Zhenwen

    2017-03-01

    Insulin resistance of skeletal muscle plays an important role in the pathogenesis of type 2 diabetes. Galanin, a 29/30-amino-acid neuropeptide, plays multiple biological actions, including anti-diabetic effects. Although recent results of our study showed that administration of galanin could mitigate insulin resistance by promoting glucose transporter 4 (GLUT4) expression and translocation in skeletal muscle of rats, there is no literature available regarding to the effect of type 1 of galanin receptors (GALR1) on insulin resistance in skeletal muscle of type 2 diabetic rats. Herein, we intended to survey the central effect of GALR1 agonist M617 on insulin resistance in skeletal muscle and its underlying mechanisms. We found that the intracerebroventricular injection of M617 increased glucose infusion rates in hyperinsulinemic euglycemic clamp tests, but attenuated the plasma insulin and glucose concentrations of diabetic rats. Furthermore, administration of M617 markedly increased GLUT4 mRNA expression and GLUT4 translocation in skeletal muscle of diabetic rats. Last, perfusion of M617 increased phosphorylated Akt and phosphorylated AS160 levels in the skeletal muscle of diabetic rats. In conclusion, central injection of M617 mitigated insulin resistance of skeletal muscle by enhancing GLUT4 translocation from intracellular pools to plasma membranes via the activation of the Akt/AS160/GLUT4 signaling pathway.

  19. Enhanced Synthesis of Alkyl Amino Acids in Miller's 1958 H2S Experiment

    Science.gov (United States)

    Parker, Eric T.; Cleaves, H. James; Callahan, Michael P.; Dworkin, James P.; Glavin, Daniel P.; Lazcano, Antonio; Bada, Jeffrey L.

    2011-01-01

    Stanley Miller's 1958 H2S-containing experiment, which included a simulated prebiotic atmosphere of methane (CH4), ammonia (NH3), carbon dioxide (CO2), and hydrogen sulfide (H2S) produced several alkyl amino acids, including the alpha-, beta-, and gamma-isomers of aminobutyric acid (ABA) in greater relative yields than had previously been reported from his spark discharge experiments. In the presence of H2S, aspariic and glutamic acids could yield alkyl amino acids via the formation of thioimide intermediates. Radical chemistry initiated by passing H2S through a spark discharge could have also enhanced alkyl amino acid synthesis by generating alkyl radicals that can help form the aldehyde and ketone precursors to these amino acids. We propose mechanisms that may have influenced the synthesis of certain amino acids in localized environments rich in H2S and lightning discharges, similar to conditions near volcanic systems on the early Earth, thus contributing to the prebiotic chemical inventory of the primordial Earth.

  20. Carnosic acid and fisetin combination therapy enhances inhibition of lung cancer through apoptosis induction.

    Science.gov (United States)

    Shi, Bin; Wang, Li-Fang; Meng, Wen-Shu; Chen, Liang; Meng, Zi-Li

    2017-06-01

    Carnosic acid is a phenolic diterpene with anti-inflammation, anticancer, anti-bacterial, anti-diabetic, as well as neuroprotective properties, which is generated by many species from Lamiaceae family. Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally flavonoid is abundantly produced in different vegetables and fruits. Fisetin has been reported to have various positive biological effects, including anti-proliferative, anticancer, anti-oxidative and neuroprotective effects. Lung cancer is reported as the most common neoplasm in human world-wide. In the present study, the possible benefits of carnosic acid combined with fisetin on lung cancer in vitro and in vivo was explored. Carnosic acid and fisetin combination led to apoptosis in lung cancer cells. Caspase-3 signaling pathway was promoted in carnosic acid and fisetin co-treatment, which was accompanied by anti-apoptotic proteins of Bcl-2 and Bcl-xl decreasing and pro-apoptotic signals of Bax and Bad increasing. The death receptor (DR) of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was enhanced in carnosic acid and fisetin combined treatment. Furthermore, the mouse xenograft model in vivo suggested that carnosic acid and fisetin combined treatment inhibited lung cancer growth in comparison to the carnosic acid or fisetin monotherapy. This study supplies a novel therapy to induce apoptosis to inhibit lung cancer through caspase-3 activation.

  1. Enhanced Synthesis of Alkyl Amino Acids in Miller's 1958 H2S Experiment

    Science.gov (United States)

    Parker, Eric T.; Cleaves, H. James; Callahan, Michael P.; Dworkin, James P.; Glavin, Daniel P.; Lazcano, Antonio; Bada, Jeffrey L.

    2011-01-01

    Stanley Miller's 1958 H2S-containing experiment, which included a simulated prebiotic atmosphere of methane (CH4), ammonia (NH3), carbon dioxide (CO2), and hydrogen sulfide (H2S) produced several alkyl amino acids, including the alpha-, beta-, and gamma-isomers of aminobutyric acid (ABA) in greater relative yields than had previously been reported from his spark discharge experiments. In the presence of H2S, aspariic and glutamic acids could yield alkyl amino acids via the formation of thioimide intermediates. Radical chemistry initiated by passing H2S through a spark discharge could have also enhanced alkyl amino acid synthesis by generating alkyl radicals that can help form the aldehyde and ketone precursors to these amino acids. We propose mechanisms that may have influenced the synthesis of certain amino acids in localized environments rich in H2S and lightning discharges, similar to conditions near volcanic systems on the early Earth, thus contributing to the prebiotic chemical inventory of the primordial Earth.

  2. Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.

    Science.gov (United States)

    Lam, Y Y; Hatzinikolas, G; Weir, J M; Janovská, A; McAinch, A J; Game, P; Meikle, P J; Wittert, G A

    2011-01-01

    The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle. L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured. PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA. PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Biodegradability enhancement of purified terephthalic acid wastewater by coagulation-flocculation process as pretreatment.

    Science.gov (United States)

    Karthik, Manikavasagam; Dafale, Nishant; Pathe, Pradyumna; Nandy, Tapas

    2008-06-15

    In this work, the coagulation-flocculation process was used as pretreatment for purified terephthalic acid (PTA) wastewater with the objective of improving its overall biodegradability. PTA production generates wastewaters with toxicants p-xylene [1,4-dimethyl-benzene (C8H10)], a major raw material used in the production process, along with some of the intermediates, viz., p-toluic acid, benzoic acid, 4-carboxybenzaldehyde, phthalic acid and terephthalic acid. These compounds affect the bio-oxidation process of wastewater treatment; hence removal of these constituents is necessary, prior to conventional aerobic treatment. This paper addresses the application of coagulation-flocculation process using chemical coagulants, viz., aluminium sulphate (alum), polyaluminium chloride (PAC), ferrous sulphate and ferric chloride in combination with anionic polyelectrolyte. Polyaluminium chloride (PAC) in conjunction with lime and polyelectrolyte removed about 63.1% chemical oxygen demand (COD) and 45.2% biochemical oxygen demand (BOD) from PTA wastewater. Coagulation-flocculation process coupled with aerobic bio-oxidation treatment of PTA wastewater achieved, COD & BOD removals of 97.4% and 99.4%, respectively. The biodegradability enhancement evaluated in terms of the BOD5/COD ratio, increased from 0.45 to 0.67 at the optimum conditions. The results obtained from these studies indicate that the coagulation-flocculation process could be a suitable pretreatment method in reducing toxicity of PTA wastewater whilst enhancing biodegradability for aerobic biological treatment scheme.

  4. Enhancing the functionality of biobased polyester coating resins through modification with citric acid.

    Science.gov (United States)

    Noordover, Bart A J; Duchateau, Robbert; van Benthem, Rolf A T M; Ming, Weihua; Koning, Cor E

    2007-12-01

    Citric acid (CA) was evaluated as a functionality-enhancing monomer in biobased polyesters suitable for coating applications. Model reactions of CA with several primary and secondary alcohols and diols, including the 1,4:3,6-dianhydrohexitols, revealed that titanium(IV) n-butoxide catalyzed esterification reactions involving these compounds proceed at relatively low temperatures, often via anhydride intermediates. Interestingly, the facile anhydride formation from CA at temperatures around CA's melting temperature ( T m = 153 degrees C) proved to be crucial in modifying sterically hindered secondary hydroxyl end groups. OH-functional polyesters were reacted with CA in the melt between 150 and 165 degrees C, yielding slightly branched carboxylic acid functional materials with strongly enhanced functionality. The acid/epoxy curing reaction of the acid-functional polymers was simulated with a monofunctional glycidyl ether. Finally, the CA-modified polyesters were applied as coatings, using conventional cross-linking agents. The formulations showed rapid curing, resulting in chemically and mechanically stable coatings. These results demonstrate that citric acid can be applied in a new way, making use of its anhydride formation to functionalize OH-functional polyesters, which is an important new step toward fully biobased coating systems.

  5. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  6. Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid.

    Science.gov (United States)

    Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E; Schwab, Wilfried; Vlot, A Corina

    2014-11-01

    Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation.

  7. Amino-Functional Polybenzimidazole Blends with Enhanced Phosphoric Acid Mediated Proton Conductivity as Fuel Cell Electrolytes

    DEFF Research Database (Denmark)

    Aili, David; Javakhishvili, Irakli; Han, Junyoung;

    2016-01-01

    A new amino-functional polybenzimidazole copolymer is synthesized by homogeneous solution condensation polymerization from a novel monomer, N,N′-bis (2,4-diaminophenyl)-1,3-diaminopropane. The copolymer readily dissolves in organic solvents and shows good film forming characteristics. To balance...... the phosphoric acid uptake and to obtain mechanically robust membranes, the amino-functional polybenzimidazole derivative is blended with high molecular weight poly [2,2′-(m-phenylene)-5,5′-bisbenzimidazole] at different ratios. Due to the high acid uptake, the homogenous blend membranes show enhanced proton...

  8. Morphology-dependent Electrochemical Enhancements of Porous Carbon as Sensitive Determination Platform for Ascorbic Acid, Dopamine and Uric Acid

    Science.gov (United States)

    Cheng, Qin; Ji, Liudi; Wu, Kangbing; Zhang, Weikang

    2016-02-01

    Using starch as the carbon precursor and different-sized ZnO naoparticles as the hard template, a series of porous carbon materials for electrochemical sensing were prepared. Experiments of scanning electron microscopy, transmission electron microscopy and Nitrogen adsorption-desorption isotherms reveal that the particle size of ZnO has big impacts on the porous morphology and surface area of the resulting carbon materials. Through ultrasonic dispersion of porous carbon and subsequent solvent evaporation, different sensing interfaces were constructed on the surface of glassy carbon electrode (GCE). The electrochemical behaviors of ascorbic acid (AA), dopamine (DA) and uric acid (UA) were studied. On the surface of porous carbon materials, the accumulation efficiency and electron transfer ability of AA, DA and UA are improved, and consequently their oxidation signals enhance greatly. Moreover, the interface enhancement effects of porous carbon are also controlled by the particle size of hard template. The constructed porous carbon interface displays strong signal amplification ability and holds great promise in constructing a sensitive platform for the simultaneous determination of AA, DA and UA.

  9. Diffraction enhanced imaging of a rat model of gastric acid aspiration pneumonitis.

    Science.gov (United States)

    Connor, Dean M; Zhong, Zhong; Foda, Hussein D; Wiebe, Sheldon; Parham, Christopher A; Dilmanian, F Avraham; Cole, Elodia B; Pisano, Etta D

    2011-12-01

    Diffraction-enhanced imaging (DEI) is a type of phase contrast x-ray imaging that has improved image contrast at a lower dose than conventional radiography for many imaging applications, but no studies have been done to determine if DEI might be useful for diagnosing lung injury. The goals of this study were to determine if DEI could differentiate between healthy and injured lungs for a rat model of gastric aspiration and to compare diffraction-enhanced images with chest radiographs. Radiographs and diffraction-enhanced chest images of adult Sprague Dawley rats were obtained before and 4 hours after the aspiration of 0.4 mL/kg of 0.1 mol/L hydrochloric acid. Lung damage was confirmed with histopathology. The radiographs and diffraction-enhanced peak images revealed regions of atelectasis in the injured rat lung. The diffraction-enhanced peak images revealed the full extent of the lung with improved clarity relative to the chest radiographs, especially in the portion of the lower lobe that extended behind the diaphragm on the anteroposterior projection. For a rat model of gastric acid aspiration, DEI is capable of distinguishing between a healthy and an injured lung and more clearly than radiography reveals the full extent of the lung and the lung damage. Copyright © 2011 AUR. All rights reserved.

  10. Effect of GABA on oxidative stress in the skeletal muscles and plasma free amino acids in mice fed high-fat diet.

    Science.gov (United States)

    Xie, Z X; Xia, S F; Qiao, Y; Shi, Y H; Le, G W

    2015-06-01

    Increased levels of plasma free amino acids (pFAAs) can disturb the blood glucose levels in patients with obesity, diabetes mellitus and metabolic syndrome (MS) and are associated with enhanced protein oxidation. Oxidation of proteins, especially in the muscles, can promote protein degradation and elevate the levels of pFAAs. Gamma-aminobutyric acid (GABA), a food additive, can reduce high-fat diet (HFD)-induced hyperglycaemia; however, the mechanisms remain unclear. The aim of this study was to evaluate the effects of GABA on protein oxidation and pFAAs changes. One hundred male C57BL/6 mice were randomly divided into five groups that were fed with control diet, HFD and HFD supplied with 0.2%, 0.12% and 0.06% GABA in drinking water for 20 weeks respectively. HFD feeding led to muscular oxidative stress, protein oxidation, pFAA disorders, hyperglycaemia and augmented plasma GABA levels. Treatment with GABA restored normally fasting blood glucose level and dose-dependently inhibited body weight gains, muscular oxidation and protein degradation. While medium and low doses of GABA mitigated HFD-induced pFAA disorders, the high dose of GABA deteriorated the pFAA disorders. Medium dose of GABA increased the levels of GABA, but high dose of GABA reduced the levels of plasma GABA and increased the activity of succinic semialdehyde dehydrogenase in the liver. Therefore, treatment with GABA mitigated HFD-induced hyperglycaemia probably by repairing HFD-induced muscular oxidative stress and pFAA disorders in mice. Our data also suggest that an optimal dose of GABA is crucial for the prevention of excess GABA-related decrease in the levels of pFAA and GABA as well as obesity.

  11. Atractylenolide III Enhances Energy Metabolism by Increasing the SIRT-1 and PGC1α Expression with AMPK Phosphorylation in C2C12 Mouse Skeletal Muscle Cells.

    Science.gov (United States)

    Song, Mi Young; Jung, Hyo Won; Kang, Seok Yong; Park, Yong-Ki

    2017-01-01

    Targeting energy expenditure provides a potential alternative strategy for achieving energy balance to combat obesity and the development of type 2 diabetes mellitus (T2DM). In the present study, we investigated whether atractylenolide III (AIII) regulates energy metabolism in skeletal muscle cells. Differentiated C2C12 myotubes were treated with AIII (10, 20, or 50 µM) or metformin (2.5 mM) for indicated times. The levels of glucose uptake, the expressions of key mitochondrial biogenesis-related factors and their target genes were measured in C2C12 myotubes. AIII significantly increased the glucose uptake levels, and significantly increased the expressions of peroxisome proliferator-activated receptor coactivator-1α (PGC1α) and mitochondrial biogenesis-related markers, such as, nuclear respiratory factor-1 (NRF-1), and mitochondrial transcription factor A (TFAM) and mitochondrial mass and total ATP contents. In addition, AIII significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and the expression of sirtuin1 (SIRT1). These results suggest that AIII may have beneficial effects on obesity and T2DM by improving energy metabolism in skeletal muscle.

  12. Enhancement of taxol-induced apoptosis by inhibition of NF-κB with ursorlic acid

    Science.gov (United States)

    Li, Yunlong; Xing, Da

    2007-05-01

    Taxol is known to inhibit cell growth and triggers significant apoptosis in various cancer cells, and activation of proliferation factor NF-κB during Taxol-induced apoptosis is regarded as a main reason resulting in tumor cells resistance to Taxol. It has been found that ursorlic acid can inhibit the activation of NF-κB. In order to study whether ursorlic acid can enhance the Taxol-induced apoptosis, we use fluorescence resonance energy transfer (FRET) technique and probe SCAT3 to compare the difference of caspase-3 activation between Taxol alone and Taxol combined ursorlic acid. With laser scanning confocal microscopy, we find that ursorlic acid, a nontoxic food component, sensitizes ASTC-a-1 cells more efficiently to Taxol-induced apoptosis by advanced activation of caspase 3. The result also suggests that there would be a synergistic effect between Taxol and ursorlic acid, and the more detailed mechanism of synergistic effect needs to be clarified further, such as the correlations among NF-κB, Akt, caspase 8, which leads to the advanced activation of caspase 3 during combined treatment of Taxol and ursorlic acid. Moreover, this may be a new way to improve Taxol-dependent tumor therapy.

  13. Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

    Science.gov (United States)

    Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

    2017-06-01

    This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Enhanced succinic acid production from corncob hydrolysate by microbial electrolysis cells.

    Science.gov (United States)

    Zhao, Yan; Cao, Weijia; Wang, Zhen; Zhang, Bowen; Chen, Kequan; Ouyang, Pingkai

    2016-02-01

    In this study, Actinobacillus succinogenes NJ113 microbial electrolysis cells (MECs) were used to enhance the reducing power responsible for succinic acid production from corncob hydrolysate. During corncob hydrolysate fermentation, electric MECs resulted in a 1.31-fold increase in succinic acid production and a 1.33-fold increase in the reducing power compared with those in non-electric MECs. When the hydrolysate was detoxified by combining Ca(OH)2, NaOH, and activated carbon, succinic acid production increased from 3.47 to 6.95 g/l. Using a constant potential of -1.8 V further increased succinic acid production to 7.18 g/l. A total of 18.09 g/l of succinic acid and a yield of 0.60 g/g total sugar were obtained after a 60-h fermentation when NaOH was used as a pH regulator. The improved succinic acid yield from corncob hydrolysate fermentation using A. succinogenes NJ113 in electric MECs demonstrates the great potential of using biomass as a feedstock to cost-effectively produce succinate.

  15. Intraluminal duodenal diverticulum: CT and gadoxetic acid-enhanced MRI findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Myeong; Lee, Nam Kyung; Kim, Suk; Kim, Dong Uk; Kim, Tae Un [Dept. of Radiology, Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of)

    2015-03-15

    Intraluminal duodenal diverticulum (IDD) is a rare congenital anomaly. IDD can become symptomatic in 20% to 25% of cases when complicated by intestinal obstruction, pancreatitis, or hemorrhage. We report the case of a 21-year-old female presenting with IDD mimicking duodenoduodenal intussusception. We describe the imaging features of IDD on the gadoxetic acid-enhanced magnetic resonance image as well as computed tomography.

  16. Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression

    DEFF Research Database (Denmark)

    Agudelo, Leandro Z; Femenía, Teresa; Orhan, Funda

    2014-01-01

    Depression is a debilitating condition with a profound impact on quality of life for millions of people worldwide. Physical exercise is used as a treatment strategy for many patients, but the mechanisms that underlie its beneficial effects remain unknown. Here, we describe a mechanism by which...... skeletal muscle PGC-1α1 induced by exercise training changes kynurenine metabolism and protects from stress-induced depression. Activation of the PGC-1α1-PPARα/δ pathway increases skeletal muscle expression of kynurenine aminotransferases, thus enhancing the conversion of kynurenine into kynurenic acid......, a metabolite unable to cross the blood-brain barrier. Reducing plasma kynurenine protects the brain from stress-induced changes associated with depression and renders skeletal muscle-specific PGC-1α1 transgenic mice resistant to depression induced by chronic mild stress or direct kynurenine administration...

  17. Enhanced Biocide Mitigation of Field Biofilm Consortia by a Mixture of D-Amino Acids

    Science.gov (United States)

    Li, Yingchao; Jia, Ru; Al-Mahamedh, Hussain H.; Xu, Dake; Gu, Tingyue

    2016-01-01

    Microbiologically influenced corrosion (MIC) is a major problem in the oil and gas industry as well as in many other industries. Current treatment methods rely mostly on pigging and biocide dosing. Biocide resistance is a growing concern. Thus, it is desirable to use biocide enhancers to improve the efficacy of existing biocides. D-Amino acids are naturally occurring. Our previous work demonstrated that some D-amino acids are biocide enhancers. Under a biocide stress of 50 ppm (w/w) hydroxymethyl phosphonium sulfate (THPS) biocide, 1 ppm D-tyrosine and 100 ppm D-methionine used separately successfully mitigated the Desulfovibrio vulgaris biofilm on carbon steel coupons. The data reported in this work revealed that 50 ppm of an equimolar mixture of D-methionine, D-tyrosine, D-leucine, and D-tryptophan greatly enhanced 50 ppm THPS biocide treatment of two recalcitrant biofilm consortia containing sulfate reducing bacteria (SRB), nitrate reducing bacteria (NRB), and fermentative bacteria, etc., from oil-field operations. The data also indicated that individual D-amino acids were inadequate for the biofilm consortia. PMID:27379039

  18. Enhanced charge transport in highly conducting PEDOT-PSS films after acid treatment

    Science.gov (United States)

    Shiva, V. Akshaya; Bhatia, Ravi; Menon, Reghu

    The high electrical conductivity, good stability, high strength, flexibility and good transparency of poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT-PSS), make it useful for many applications including polymeric anodes for organic photovoltaics, light-emitting diodes, flexible electrodes, supercapacitors, electrochromic devices, field-effect transistors and antistatic-coatings. However, the electrical conductivity of PEDOT-PSS has to be increased significantly for replacement of indium tin oxide (ITO) as the transparent electrode in optoelectronic devices. The as prepared (pristine) PEDOT-PSS film prepared from the PEDOT-PSS aqueous solution usually has conductivity below 1Scm-1, remarkably lower than ITO. Significant conductivity enhancement has been observed on transparent and conductive PEDOT-PSS films after a treatment with inorganic acids. Our study investigates the charge transport in pristine and H2SO4, HNO3, HCl treated PEDOT-PSS films. We have treated the films with various concentrations of acids to probe the effect of the acid treatment on the conduction mechanism. The study includes the measurement of dc and electric field dependent conductivity of films in the temperature range of 4.2K-300K. We have also performed magneto-resistance measurements in the range of 0-5T. An enhancement by a factor of~103 has been observed in the room temperature conductivity. The detailed magneto-transport studies explain the various mechanisms for the conductivity enhancement observed.

  19. Enhanced Biocide Mitigation of Field Biofilm Consortia by a Mixture of D-Amino Acids.

    Science.gov (United States)

    Li, Yingchao; Jia, Ru; Al-Mahamedh, Hussain H; Xu, Dake; Gu, Tingyue

    2016-01-01

    Microbiologically influenced corrosion (MIC) is a major problem in the oil and gas industry as well as in many other industries. Current treatment methods rely mostly on pigging and biocide dosing. Biocide resistance is a growing concern. Thus, it is desirable to use biocide enhancers to improve the efficacy of existing biocides. D-Amino acids are naturally occurring. Our previous work demonstrated that some D-amino acids are biocide enhancers. Under a biocide stress of 50 ppm (w/w) hydroxymethyl phosphonium sulfate (THPS) biocide, 1 ppm D-tyrosine and 100 ppm D-methionine used separately successfully mitigated the Desulfovibrio vulgaris biofilm on carbon steel coupons. The data reported in this work revealed that 50 ppm of an equimolar mixture of D-methionine, D-tyrosine, D-leucine, and D-tryptophan greatly enhanced 50 ppm THPS biocide treatment of two recalcitrant biofilm consortia containing sulfate reducing bacteria (SRB), nitrate reducing bacteria (NRB), and fermentative bacteria, etc., from oil-field operations. The data also indicated that individual D-amino acids were inadequate for the biofilm consortia.

  20. Organic acid enhanced electrodialytic extraction of lead from contaminated soil fines in suspension

    DEFF Research Database (Denmark)

    Jensen, Pernille Erland; Ahring, Birgitte Kiær; Ottosen, Lisbeth M.

    2007-01-01

    The implementation of soil washing technology for the treatment of heavy metal contaminated soils is limited by the toxicity and unwieldiness of the remaining heavy metal contaminated sludge. In this work, the feasibility of combining electrodialytic remediation with heterotrophic leaching...... for decontamination of the sludge was investigated. The ability of 11 organic acids to extract Pb from the fine fraction of contaminated soil (grains ... was tested. Five of the acids showed the ability to extract Ph from the soil fines in excess of the effect caused solely by pH changes. Addition of the acids, however, severely impeded EDR, hence promotion of EDR by combination with heterotrophic leaching was rejected. In contrast, enhancement of EDR...

  1. Skeletally Dugundji spaces

    OpenAIRE

    2012-01-01

    We introduce and investigate the class of skeletally Dugundji spaces as a skeletal analogue of Dugundji space. The main result states that the following conditions are equivalent for a given space $X$: (i) $X$ is skeletally Dugundji; (ii) Every compactification of $X$ is co-absolute to a Dugundji space; (iii) Every $C^*$-embedding of the absolute $p(X)$ in another space is strongly $\\pi$-regular; (iv) $X$ has a multiplicative lattice in the sense of Shchepin \\cite{s76} consisting of skeletal ...

  2. The iron-chelating agent picolinic acid enhances transferrin receptors expression in human erythroleukaemic cell lines.

    Science.gov (United States)

    Testa, U; Louache, F; Titeux, M; Thomopoulos, P; Rochant, H

    1985-07-01

    Picolinic acid, a metal chelating molecule, was administered to human erythroleukaemic cell lines (K 562 and HEL) that were grown in serum-containing media. Picolinic acid inhibited both iron uptake and cell growth. Furthermore, picolinic acid was shown to markedly decrease the level of ferritin in the cells. In spite of the inhibition of cell growth, picolinic acid induced a marked increase in the transferrin-binding capacity of the cells. This phenomenon was due to a two-five-fold enhancement of the rate of transferrin receptor biosynthesis. Other iron-chelating compounds, capable of reducing the level of intracellular iron, also elicited a marked enhancement of the transferrin-binding capacity of the cells. However, the addition of iron, as ferric ammonium citrate, in the culture medium elicited a marked increase in the level of ferritin and a strong decrease in the transferrin-binding capacity of the cells. On the basis of these data we propose that a feed-back mechanism is involved in the regulation of transferrin receptors: when the cells accumulate iron they decrease the number of transferrin receptors in order to prevent further accumulation of iron; when no or low iron is available to the cells, the number of transferrin receptors markedly increases as a compensatory mechanism.

  3. Surface modification of activated carbon for enhanced adsorption of perfluoroalkyl acids from aqueous solutions.

    Science.gov (United States)

    Zhi, Yue; Liu, Jinxia

    2016-02-01

    The objective of the research was to examine the effect of increasing carbon surface basicity on uptake of perfluorooctane sulfonic (PFOS) and carboxylic acids (PFOA) by activated carbon. Granular activated carbons made from coal, coconut shell, wood, and phenolic-polymer-based activated carbon fibers were modified through high-temperature and ammonia gas treatments to facilitate systematical evaluation of the impact of basicity of different origins. Comparison of adsorption isotherms and adsorption distribution coefficients showed that the ammonia gas treatment was more effective than the high-temperature treatment in enhancing surface basicity. The resultant higher point of zero charges and total basicity (measured by total HCl uptake) correlated with improved adsorption affinity for PFOS and PFOA. The effectiveness of surface modification to enhance adsorption varied with carbon raw material. Wood-based carbons and activated carbon fibers showed enhancement by one to three orders of magnitudes while other materials could experience reduction in adsorption towards either PFOS or PFOA.

  4. Label-Free LC-MS Profiling of Skeletal Muscle Reveals Heart-Type Fatty Acid Binding Protein as a Candidate Biomarker of Aerobic Capacity.

    Science.gov (United States)

    Malik, Zulezwan Ab; Cobley, James N; Morton, James P; Close, Graeme L; Edwards, Ben J; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2013-12-01

    Two-dimensional gel electrophoresis provides robust comparative analysis of skeletal muscle, but this technique is laborious and limited by its inability to resolve all proteins. In contrast, orthogonal separation by SDS-PAGE and reverse-phase liquid chromatography (RPLC) coupled to mass spectrometry (MS) affords deep mining of the muscle proteome, but differential analysis between samples is challenging due to the greater level of fractionation and the complexities of quantifying proteins based on the abundances of their tryptic peptides. Here we report simple, semi-automated and time efficient (i.e., 3 h per sample) proteome profiling of skeletal muscle by 1-dimensional RPLC electrospray ionisation tandem MS. Solei were analysed from rats (n = 5, in each group) bred as either high- or low-capacity runners (HCR and LCR, respectively) that exhibited a 6.4-fold difference (1,625 ± 112 m vs. 252 ± 43 m, p ions, which spanned three orders of magnitude. In total, 207 proteins were analysed, which encompassed almost all enzymes of the major metabolic pathways in skeletal muscle. The most abundant protein detected was type I myosin heavy chain (RA = 5,843 ± 897) and the least abundant protein detected was heat shock 70 kDa protein (RA = 2 ± 0.5). Sixteen proteins were significantly (p ion (551.21 m/z) of the doubly-charged peptide SLGVGFATR (454.19 m/z) of residues 23-31 of FABPH. SRM was conducted on technical replicates of each biological sample and exhibited a coefficient of variation of 20%. The abundance of FABPH measured by SRM was 2.84-fold greater (p = 0.0095) in HCR muscle. In addition, SRM of FABPH was performed in vastus lateralis samples of young and elderly humans with different habitual activity levels (collected during a previous study) finding FABPH abundance was 2.23-fold greater (p = 0.0396) in endurance-trained individuals regardless of differences in age. In summary, our findings in HCR/LCR rats provide protein-level confirmation for earlier

  5. The Use of Platelet-Rich and Platelet-Poor Plasma to Enhance Differentiation of Skeletal Myoblasts: Implications for the Use of Autologous Blood Products for Muscle Regeneration.

    Science.gov (United States)

    Miroshnychenko, Olga; Chang, Wen-Teh; Dragoo, Jason L

    2017-03-01

    Platelet-rich plasma (PRP) has been used to augment tissue repair and regeneration after musculoskeletal injury. However, there is increasing clinical evidence that PRP does not show a consistent clinical effect. Purpose/Hypothesis: This study aimed to compare the effects of the following non-neutrophil-containing (leukocyte-poor) plasma fractions on human skeletal muscle myoblast (HSMM) differentiation: (1) PRP, (2) modified PRP (Mod-PRP), in which transforming growth factor β1 (TGF-β1) and myostatin (MSTN) were depleted, and (3) platelet-poor plasma (PPP). The hypothesis was that leukocyte-poor PRP would lead to myoblast proliferation (not differentiation), whereas certain modifications of PRP preparations would increase myoblast differentiation, which is necessary for skeletal muscle regeneration. Controlled laboratory study. Blood from 7 human donors was individually processed to simultaneously create leukocyte-poor fractions: PRP, Mod-PRP, PPP, and secondarily spun PRP and Mod-PRP (PRPss and Mod-PRPss, respectively). Mod-PRP was produced by removing TGF-β1 and MSTN from PRP using antibodies attached to sterile beads, while a second-stage centrifugal spin of PRP was performed to remove platelets. The biologics were individually added to cell culture groups. Analysis for induction into myoblast differentiation pathways included Western blot analysis, reverse-transcription polymerase chain reaction, and immunohistochemistry, as well as confocal microscopy to assess polynucleated myotubule formation. HSMMs cultured with PRP showed an increase in proliferation but no evidence of differentiation. Western blot analysis confirmed that MSTN and TGF-β1 could be decreased in Mod-PRP using antibody-coated beads, but this modification mildly improved myoblast differentiation. However, cell culture with PPP, PRPss, and Mod-PRPss led to a decreased proliferation rate but a significant induction of myoblast differentiation verified by increased multinucleated myotubule

  6. Skeletal muscle stem cells from animals I. Basic cell biology

    Science.gov (United States)

    Skeletal muscle stem cells from food-producing animals have been of interest to agricultural life scientists seeking to develop a better understanding of the molecular regulation of lean tissue (skeletal muscle protein hypertrophy) and intramuscular fat (marbling) development. Enhanced understanding...

  7. Large GLUT4 vesicles are stationary while locally and reversibly depleted during transient insulin stimulation of skeletal muscle of living mice: imaging analysis of GLUT4-enhanced green fluorescent protein vesicle dynamics

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M M; Galbo, Henrik; Brandauer, Josef

    2007-01-01

    OBJECTIVE: Insulin stimulates glucose transport in skeletal muscle by GLUT4 translocation from intracellular compartments to sarcolemma and t-tubules. We studied in living animals the recruitment of GLUT4 vesicles in more detail than previously done and, for the first time, analyzed the steady......-state recycling and subsequent re-internalization of GLUT4 on an insulin bolus. RESEARCH DESIGN AND METHODS: A confocal imaging technique was used in GLUT4-enhanced green fluorescent protein-transfected superficial muscle fibers in living mice. RESULTS: During the first 30 min of insulin stimulation, very few...... superficially or deeply located GLUT4 storage vesicles (>1 microm) moved in toto. Rather, big vesicles were stationary in their original position at sarcolemma or t-tubules and were locally depleted of GLUT4 by budding off of smaller vesicles. Photobleaching experiments revealed that during initial...

  8. β2-adrenergic stimulation enhances Ca2+ release and contractile properties of skeletal muscles, and counteracts exercise-induced reductions in Na+/K+-ATPase Vmax in trained men

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, A; Ortenblad, N

    2014-01-01

    The aim of the present study was to examine the effect of beta2-adrenergic stimulation on skeletal muscle contractile properties, sarcoplasmic reticulum (SR) rates of Ca(2+) release and uptake, and Na(+)/K(+)-ATPase-activity before and after fatiguing exercise in trained men. The study consisted......-fatigue, but terbutaline counteracted exercise-induced reductions in Vmax at time of fatigue. In conclusion, increased contractile force induced by beta2-adrenergic stimulation is associated with enhanced rate of Ca(2+) release in humans. While beta2-adrenergic stimulation elicits positive inotropic and lusitropic effects...... of two experiments (EXP1, n = 10 M, EXP2, n = 20 M), where beta2-adrenoceptor agonist (terbutaline) or placebo was randomly administered in double-blinded crossover designs. In EXP1, maximal voluntary isometric contraction of m.quadriceps (MVC) was measured, followed by exercise to fatigue at 120% of Vo2...

  9. The effects of ectopic UCP1 expression on gene expression in skeletal muscle [Mus Musculus

    NARCIS (Netherlands)

    Schothorst, van E.M.

    2015-01-01

    This SuperSeries is composed of the following subset Series: GSE45991: Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21 GSE45992: Transgenic overexpression of UCP1 in skeletal muscle in mice fed a HFD: signalling via FGF-21 Skeletal muscle FGF21 secretio

  10. The effects of ectopic UCP1 expression on gene expression in skeletal muscle [Mus Musculus

    NARCIS (Netherlands)

    Schothorst, van E.M.

    2015-01-01

    This SuperSeries is composed of the following subset Series: GSE45991: Amino acid deprivation due to overexpression of UCP1 in skeletal muscle: signalling via FGF-21 GSE45992: Transgenic overexpression of UCP1 in skeletal muscle in mice fed a HFD: signalling via FGF-21 Skeletal muscle FGF21

  11. Leg vascular and skeletal muscle mitochondrial adaptations to aerobic high-intensity exercise training are enhanced in the early postmenopausal phase

    DEFF Research Database (Denmark)

    Nyberg, Michael Permin; Egelund, Jon; Mandrup Jensen, Camilla Maria

    2017-01-01

    Exercise training leads to favourable adaptations within skeletal muscle; however, this effect of exercise training may be blunted in postmenopausal women due to the loss of oestrogens. Furthermore, postmenopausal women may have an impaired vascular response to acute exercise. We examined......) years of age were included. Before training, leg blood flow, O2 delivery, O2 uptake, and lactate release during knee-extensor exercise were similar in pre- and postmenopausal women. Exercise training reduced (P heart...... rate during the same absolute workloads in the postmenopausal women. These effects were not detected in the premenopausal women. Quadriceps muscle protein contents of mitochondrial complex II, III, and IV, endothelial nitric oxide synthase (eNOS), cyclooxygenase-1 (COX.1), COX-2, and oestrogen related...

  12. Enhancement of Esterification of Propionic Acid with Isopropyl Alcohol by Pervaporation Reactor

    Directory of Open Access Journals (Sweden)

    Ajit P. Rathod

    2014-01-01

    Full Text Available With increasing cost of raw materials and energy, there is an increasing inclination of chemical process industries toward new processes that result in lesser waste generation, greater efficiency, and substantial yield of the desired products. Esterification is a chemical reaction in which two reactants carboxylic acid and alcohol react to form an ester and water. This reaction is a reversible reaction and the equilibrium conversion can be altered by varying the process parameters. Pervaporation reactor can enhance the conversion by shifting the equilibrium of reversible esterification reactions. Polyvinyl alcohol-polyether sulfone composite hydrophilic membrane was used for pervaporation-assisted esterification of propionic acid with isopropyl alcohol. The experiments were carried out in the presence of sulphuric acid as a catalyst at 50°C to 80°C with various reactants ratios. The esterification was carried out for catalyst loadings of 0.089 kmol/m3 to 0.447 kmol/m3. The molar ratios of isopropyl to propionic acid used for the experiment were 1 to 1.5. Maximum conversion was obtained for the ratio of 1.4. Also effect of other parameters such as process temperature and catalyst concentration was discussed. It was found that the use of pervaporation reactor increased the conversion of the propionic acid considerably.

  13. Uteroplacental insufficiency down regulates insulin receptor and affects expression of key enzymes of long-chain fatty acid (LCFA metabolism in skeletal muscle at birth

    Directory of Open Access Journals (Sweden)

    Puglianiello Antonella

    2008-05-01

    Full Text Available Abstract Background Epidemiological studies have revealed a relationship between early growth restriction and the subsequent development of insulin resistance and type 2 diabetes. Ligation of the uterine arteries in rats mimics uteroplacental insufficiency and serves as a model of intrauterine growth restriction (IUGR and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia and adiposity in the offspring. The objective of this study was to investigate the effects of uterine artery ligation on the skeletal muscle expression of insulin receptor and key enzymes of LCFA metabolism. Methods Bilateral uterine artery ligation was performed on day 19 of gestation in Sprague-Dawley pregnant rats. Muscle of the posterior limb was dissected at birth and processed by real-time RT-PCR to analyze the expression of insulin receptor, ACCα, ACCβ (acetyl-CoA carboxylase alpha and beta subunits, ACS (acyl-CoA synthase, AMPK (AMP-activated protein kinase, alpha2 catalytic subunit, CPT1B (carnitine palmitoyltransferase-1 beta subunit, MCD (malonyl-CoA decarboxylase in 14 sham and 8 IUGR pups. Muscle tissue was treated with lysis buffer and Western immunoblotting was performed to assay the protein content of insulin receptor and ACC. Results A significant down regulation of insulin receptor protein (p Conclusion Our data suggest that uteroplacental insufficiency may affect skeletal muscle metabolism down regulating insulin receptor and reducing the expression of key enzymes involved in LCFA formation and oxidation.

  14. Combined humic acid adsorption and enhanced Fenton processes for the treatment of naphthalene dye intermediate wastewater.

    Science.gov (United States)

    Gu, Lin; Zhu, Nanwen; Wang, Liang; Bing, Xiaoxiao; Chen, Xiaoliang

    2011-12-30

    In this work, an humic acid adsorption with an enhanced Fenton oxidation was employed to treat the real effluent originating from the 1-diazo-2-naphthol-4-sulfonic acid (1,2,4-Acid) production plant. In a first step, humic acid with MgSO(4) was selected as adsorbent and precipitant for physicochemical pretreatment, the synergetic effect had led to 39% of COD removal and 89% of colour removal. A multi-staged Fenton oxidation process with inner circulation was introduced subsequently. The TOC, COD, 1,2,4-Acid, NH(4)(+)-N, SS and colour were reduced from 3024 mg/L, 12,780 mg/L, 9103 mg/L, 110 mg/L, 240 mg/L and 25,600 (multiple) to 46 mg/L, 210 mg/L, 21 mg/L, 16 mg/L, 3 mg/L and 25 through the combined process, respectively. Hydrogen peroxide consumed per kg COD had saved up to 36% when two-staged Fenton process with inner circulation (flow-back to influent ratio: 3) was applied. Influence of H(2)O(2) concentration, flow-back to influent ratio and staged Fenton mode were investigated in detail in order to find out the optimal operating parameters. The kinetics of 1,2,4-Acid degradation by two-staged Fenton process was investigated. The evolution of the main intermediates during the degradation process was conducted using the LC-(ESI)-TOF-MS technique, and the results showed a staged degradation pathway from the ring opening of naphthalene compounds to the formation of benzene compounds and carboxyl acids. The combined process had been proved effective in both technical and economic aspects.

  15. Comprehensive resource: Skeletal gene database.

    Science.gov (United States)

    Jia, L; Ho, N C; Park, S S; Powell, J; Francomano, C A

    2001-01-01

    The Skeletal Gene Database (SGD) is an integrated resource that provides comprehensive information about bone-related genes, mRNA, and proteins expressed in human and mouse, with rich links to numerous other electronic tools. SGD contains expressed sequence tag (EST) data from all the skeletal-related cDNA libraries that are available to the public. It supplies the query/data access analytic tools for users to search and compare each gene expressed in skeletal tissue(s). The results derived from EST tissue expression profiling will allow users to get the data on the mRNA copy numbers of each gene expressed in each tissue and its normalized value. From the SGD, researchers can obtain information regarding the name, symbol, size, exon/intron number, chromosomal location, LocusLink, and related disease (if any is known) of each gene. This electronic compendium also furnishes information on the protein of the corresponding gene including the protein size (amino acid number and molecular weight). It provides swift and ready access to other useful databases including OMIM, UniGene and PUBMED. The data will be updated regularly in step with current and future research, thereby providing what we hope will serve as a highly useful source of information and a powerful analytic tool to the scientific community.

  16. Phosphatidic acid enhances mTOR signaling and resistance exercise induced hypertrophy.

    Science.gov (United States)

    Joy, Jordan M; Gundermann, David M; Lowery, Ryan P; Jäger, Ralf; McCleary, Sean A; Purpura, Martin; Roberts, Michael D; Wilson, Stephanie Mc; Hornberger, Troy A; Wilson, Jacob M

    2014-01-01

    The lipid messenger phosphatidic acid (PA) plays a critical role in the stimulation of mTOR signaling. However, the mechanism by which PA stimulates mTOR is currently unknown. Therefore, the purpose of this study was to compare the effects of various PA precursors and phospholipids on their ability to stimulate mTOR signaling and its ability to augment resistance training-induced changes in body composition and performance. In phase one, C2C12 myoblasts cells were stimulated with different phospholipids and phospholipid precursors derived from soy and egg sources. The ratio of phosphorylated p70 (P-p70-389) to total p70 was then used as readout for mTOR signaling. In phase two, resistance trained subjects (n = 28, 21 ± 3 years, 77 ± 4 kg, 176 ± 9 cm) consumed either 750 mg PA daily or placebo and each took part in an 8 week periodized resistance training program. In phase one, soy-phosphatidylserine, soy-Lyso-PA, egg-PA, and soy-PA stimulated mTOR signaling, and the effects of soy-PA (+636%) were significantly greater than egg-PA (+221%). In phase two, PA significantly increased lean body mass (+2.4 kg), cross sectional area (+1.0 cm), and leg press strength (+51.9 kg) over placebo. PA significantly activates mTOR and significantly improved responses in skeletal muscle hypertrophy, lean body mass, and maximal strength to resistance exercise.

  17. Skeletal limb abnormalities

    Science.gov (United States)

    ... JA. Skeletal dysplasias. In: Herring JA, ed. Tachdjian's Pediatric Orthopaedics . 5th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 40. Moore KL, Persaud V, Torchia MG. Skeletal system. In: Moore KL, Persaud V, Torchia MG, eds. ... Assistant Professor of Pediatrics, University of Washington School of Medicine, Seattle, WA. ...

  18. Self-assembling micelle-like nanoparticles with detachable envelopes for enhanced delivery of nucleic acid therapeutics.

    Science.gov (United States)

    Battogtokh, Gantumur; Ko, Young Tag

    2014-03-01

    In spite of the great potential of nucleic acids as therapeutic agents, the clinical application of nucleic acid therapeutics requires the development of effective systemic delivery strategies. In an effort to develop effective nucleic acid delivery systems suitable for clinical application, we previously reported a self-assembling micelle-like nanoparticle that was based on phospholipid-polyethylenimine conjugates, i.e., "micelle-like nanoparticles" (MNPs). In this study, we aimed to improve the system by enhancing the efficiency of intracellular delivery of the payload via pH-responsive detachment of the monolayer envelope and release of the nucleic acid therapeutics upon reaching the target tissues with an acidic pH, e.g., tumors. The acid-cleavable phospholipid-polyethylenimine conjugate was synthesized via hydrazone bond, and acid-cleavable MNPs were then prepared and characterized as before. We evaluated the acid-cleavable MNP construct for in vitro and in vivo nucleic acid delivery efficiency using cultured tumor cells and tumor-bearing mice. The acid-cleavable nanocarrier showed an enhanced cellular delivery at pH 6.5 as compared to pH 7.4, whereas the noncleavable nanocarrier did not show any differences. Tail vein injections also led to enhanced intracellular uptake of the acid-cleavable nanocarrier compared to the noncleavable nanocarrier into tumor cells of tumor-bearing mice although no significant difference was observed in total tumor accumulation.

  19. β-cyclocitral upregulates salicylic acid signalling to enhance excess light acclimation in Arabidopsis.

    Science.gov (United States)

    Lv, Feifei; Zhou, Jun; Zeng, Lizhang; Xing, Da

    2015-08-01

    β-cyclocitral (β-CC), a volatile oxidized derivative of β-carotene, can upregulate the expression of defence genes to enhance excess light (EL) acclimation. However, the signalling cascades underlying this process remain unclear. In this study, salicylic acid (SA) is involved in alleviating damage to promote β-CC-enhanced EL acclimation. In early stages of EL illumination, β-CC pretreatment induced SA accumulation and impeded reactive oxygen species (ROS) production in the chloroplast. A comparative analysis of two SA synthesis pathways in Arabidopsis revealed that SA concentration mainly increased via the isochorismate synthase 1 (ICS1)-mediated isochorismate pathway, which depended on essential regulative function of enhanced disease susceptibility 1 (EDS1). Further results showed that, in the process of β-CC-enhanced EL acclimation, nuclear localization of nonexpressor of pathogenesis-related genes 1 (NPR1) was regulated by SA accumulation and NPR1 induced subsequent transcriptional reprogramming of gluthathione-S-transferase 5 (GST5) and GST13 implicated in detoxification. In summary, β-CC-induced SA synthesis contributes to EL acclimation response by decreasing ROS production in the chloroplast, promoting nuclear localization of NPR1, and upregulating GST transcriptional expression. This process is a possible molecular regulative mechanism of β-CC-enhanced EL acclimation.

  20. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence......, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle...

  1. Enhancement of solubility and mass transfer coefficient of salicylic acid through hydrotropy

    Institute of Scientific and Technical Information of China (English)

    S.THENESHKUMAR; D.GNANAPRAKASH; N.NAGENDRA GANDHI

    2009-01-01

    This study deals with the effect of hydrotropes on the solubility and mass transfer coefficient of salicylic acid.The solubility and mass transfer studies were performed using the hydrotropes,i.e.,sodium acetate,sodium salicylate,citric acid,and urea at concentrations of 0~3.0 mol/L and system temperatures of 303-333 K.It was found that the solubility and mass transfer coefficient of salicylic acid increases with increase in hydrotrope concentration and also with system temperature.All hydrotropes used in this work showed an enhancement in solubility and mass transfer coefficient to difierent degrees.The maximum enhancement factor values were determined for all hydrotropes used in this study.The highest value was 28.08 for solubility studies and 10.42 for mass trailsfer studies.The performance of hydrotropes Was measured in terms of the Setschenow constant(Ks).The highest value observed was 0.696.

  2. Biochar enhances Aspergillus niger rock phosphate solubilization by increasing organic acid production and alleviating fluoride toxicity.

    Science.gov (United States)

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo; Costa, Maurício Dutra

    2014-05-01

    During fungal rock phosphate (RP) solubilization, a significant quantity of fluoride (F(-)) is released together with phosphorus (P), strongly inhibiting the process. In the present study, the effect of two F(-) adsorbents [activated alumina (Al2O3) and biochar] on RP solubilization by Aspergillus niger was examined. Al2O3 adsorbed part of the F(-) released but also adsorbed soluble P, which makes it inappropriate for microbial RP solubilization systems. In contrast, biochar adsorbed only F(-) while enhancing phosphate solubilization 3-fold, leading to the accumulation of up to 160 mg of P per liter. By comparing the values of F(-) measured in solution at the end of incubation and those from a predictive model, it was estimated that up to 19 mg of F(-) per liter can be removed from solution by biochar when added at 3 g liter(-1) to the culture medium. Thus, biochar acted as an F(-) sink during RP solubilization and led to an F(-) concentration in solution that was less inhibitory to the process. In the presence of biochar, A. niger produced larger amounts of citric, gluconic, and oxalic acids, whether RP was present or not. Our results show that biochar enhances RP solubilization through two interrelated processes: partial removal of the released F(-) and increased organic acid production. Given the importance of organic acids for P solubilization and that most of the RPs contain high concentrations of F(-), the proposed solubilization system offers an important technological improvement for the microbial production of soluble P fertilizers from RP.

  3. Okadaic acid and trifluoperazine enhance Agrobacterium-mediated transformation in eastern white pine.

    Science.gov (United States)

    Tang, Wei; Lin, Jinxing; Newton, Ronald J

    2007-05-01

    Mature zygotic embryos of recalcitrant Christmas tree species eastern white pine (Pinus strobus L.) were used as explants for Agrobacterium tumefaciens strain GV3101-mediated transformation using the uidA (beta-Glucuronidase) gene as a reporter. Influence of the time of sonication and the concentrations of protein phosphatase inhibitor (okadaic acid) and kinase inhibitor (trifluoperazine) on Agrobacterium-mediated transformation have been evaluated. A high transformation frequency was obtained after embryos were sonicated for 45-50 s, or treated with 1.5-2.0 microM okadaic acid or treated with 100-200 microM trifluoperazine, respectively. Protein phosphatase and kinase inhibitors enhance Agrobacterium-mediated transformation in eastern white pine. A 2-3.5-fold higher rate of hygromycin-resistant callus was obtained with an addition of 2 microM okadaic acid or 150 microM trifluoperazine or sonicated embryos for 45 s. Stable integration of the uidA gene in the plant genome of eastern white pine was confirmed by polymerase chain reaction (PCR), Southern and northern blot analyses. These results demonstrated that a stable and enhanced transformation system has been established in eastern white pine and this system would provide an opportunity to transfer economically important genes into this Christmas tree species.

  4. Synergistic permeability enhancing effect of lysophospholipids and fatty acids on lipid membranes

    DEFF Research Database (Denmark)

    Davidsen, Jesper; Mouritsen, O.G.; Jørgensen, K.

    2002-01-01

    The permeability-enhancing effects of the two surfactants, 1-paltnitoyl-2-lyso-sn-gycero-3-pllosplloclloline (lysoPPC) and palmitic acid (PA), on lipid membranes that at physiological temperatures are in the gel, fluid, and liquid-ordered phases were determined using the concentration-dependent s......The permeability-enhancing effects of the two surfactants, 1-paltnitoyl-2-lyso-sn-gycero-3-pllosplloclloline (lysoPPC) and palmitic acid (PA), on lipid membranes that at physiological temperatures are in the gel, fluid, and liquid-ordered phases were determined using the concentration......-dependent self-quenching properties of the hydrophilic marker, calcein. Adding lysoPPC to lipid membranes in the gel-phase induced a time-dependent calcein release curve that can be described by the sum of two exponentials, whereas RA induces a considerably more complex release curve. However, when lyso......PPC and PA were added simultaneously in equimolar concentrations, a dramatic synergistic permeability-enhancing effect was observed. In contrast, when both lysoPPC and PA are added to liposomal membranes that are in the fluid or liquid-ordered phases, no effect on the transmembrane permeation of calcein...

  5. Abscisic Acid Regulation of Root Hydraulic Conductivity and Aquaporin Gene Expression Is Crucial to the Plant Shoot Growth Enhancement Caused by Rhizosphere Humic Acids.

    Science.gov (United States)

    Olaetxea, Maite; Mora, Verónica; Bacaicoa, Eva; Garnica, María; Fuentes, Marta; Casanova, Esther; Zamarreño, Angel M; Iriarte, Juan C; Etayo, David; Ederra, Iñigo; Gonzalo, Ramón; Baigorri, Roberto; García-Mina, Jose M

    2015-12-01

    The physiological and metabolic mechanisms behind the humic acid-mediated plant growth enhancement are discussed in detail. Experiments using cucumber (Cucumis sativus) plants show that the shoot growth enhancement caused by a structurally well-characterized humic acid with sedimentary origin is functionally associated with significant increases in abscisic acid (ABA) root concentration and root hydraulic conductivity. Complementary experiments involving a blocking agent of cell wall pores and water root transport (polyethylenglycol) show that increases in root hydraulic conductivity are essential in the shoot growth-promoting action of the model humic acid. Further experiments involving an inhibitor of ABA biosynthesis in root and shoot (fluridone) show that the humic acid-mediated enhancement of both root hydraulic conductivity and shoot growth depended on ABA signaling pathways. These experiments also show that a significant increase in the gene expression of the main root plasma membrane aquaporins is associated with the increase of root hydraulic conductivity caused by the model humic acid. Finally, experimental data suggest that all of these actions of model humic acid on root functionality, which are linked to its beneficial action on plant shoot growth, are likely related to the conformational structure of humic acid in solution and its interaction with the cell wall at the root surface.

  6. Enhancement and modeling of microparticle-added Rhizopus oryzae lactic acid production.

    Science.gov (United States)

    Coban, Hasan Bugra; Demirci, Ali

    2016-02-01

    Lactic acid has a wide industrial application area and can be produced by fungal strains. However, excessive bulk growth form of fungi during the fermentations is a major problem, which limits the fermentation performance. Microparticles are excellent tools to prevent bulk fungal growth and provide homogenized fermentation broth to increase uniformity and the prediction performance of the models. Therefore, in this study, addition of aluminum oxide and talcum microparticles into fermentations was evaluated to enhance the production of lactic acid by Rhizopus oryzae. The results showed that the bulk fungal growth was prevented and the lactic acid concentration increased from 6.02 to 13.88 and 24.01 g/L, when 15 g/L of aluminum oxide or 10 g/L of talcum was used, respectively, in the shake-flask fermentations. Additionally, substrate concentration, pH, and agitation were optimized in the bioreactors using response surface methodology, and optimum values were determined as 126 g/L of glucose, 6.22 pH, and 387 rpm, respectively. Under these conditions, lactic acid production further increased to 75.1 ± 1.5 g/L with 10 g/L of talcum addition. Also, lactic acid production and glucose consumption in the batch fermentation were successfully modeled with modified Gompertz model and modified logistic model. RMSE and MAE values for lactic acid production were calculated as 2.279 and 1.498 for the modified Gompertz model; 3.6 and 4.056 for the modified logistic model. Additionally, modified logistic model predicted glucose consumption with -2.088 MAE and 2.868 RMSE, whereas these values were calculated as 2.035 and 3.946 for the modified Gompertz model.

  7. Organic acids enhance bioavailability of tetracycline in water to Escherichia coli for uptake and expression of antibiotic resistance.

    Science.gov (United States)

    Zhang, Yingjie; Boyd, Stephen A; Teppen, Brian J; Tiedje, James M; Li, Hui

    2014-11-15

    Tetracyclines are a large class of antimicrobials used most extensively in livestock feeding operations. A large portion of tetracyclines administered to livestock is excreted in manure and urine which is collected in waste lagoons. Subsequent land application of these wastes introduces tetracyclines into the soil environment, where they could exert selective pressure for the development of antibiotic resistance genes in bacteria. Tetracyclines form metal-complexes in natural waters, which could reduce their bioavailability for bacterial uptake. We hypothesized that many naturally-occurring organic acids could effectively compete with tetracyclines as ligands for metal cations, hence altering the bioavailability of tetracyclines to bacteria in a manner that could enhance the selective pressure. In this study, we investigated the influence of acetic acid, succinic acid, malonic acid, oxalic acid and citric acid on tetracycline uptake from water by Escherichia coli bioreporter construct containing a tetracycline resistance gene which induces the emission of green fluorescence when activated. The presence of the added organic acid ligands altered tetracycline speciation in a manner that enhanced tetracycline uptake by E. coli. Increased bacterial uptake of tetracycline and concomitant enhanced antibiotic resistance response were quantified, and shown to be positively related to the degree of organic acid ligand complexation of metal cations in the order of citric acid > oxalic acid > malonic acid > succinic acid > acetic acid. The magnitude of the bioresponse increased with increasing aqueous organic acid concentration. Apparent positive relation between intracellular tetracycline concentration and zwitterionic tetracycline species in aqueous solution indicates that (net) neutral tetracycline is the species which most readily enters E. coli cells. Understanding how naturally-occurring organic acid ligands affect tetracycline speciation in solution, and how speciation

  8. Inhibition of oxidative phosphorylation for enhancing citric acid production by Aspergillus niger.

    Science.gov (United States)

    Wang, Lu; Zhang, Jianhua; Cao, Zhanglei; Wang, Yajun; Gao, Qiang; Zhang, Jian; Wang, Depei

    2015-01-16

    intracellular ATP can accelerate glycolysis and the TCA cycle to enhance citric acid yield.

  9. The uptake transporter OATP8 expression decreases during multistep hepatocarcinogenesis: correlation with gadoxetic acid enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Kitao, Azusa; Matsui, Osamu; Yoneda, Norihide; Kozaka, Kazuto; Shinmura, Rieko; Koda, Wataru; Kobayashi, Satoshi; Gabata, Toshifumi [Kanazawa University Graduate School of Medical Science, Department of Radiology, Kanazawa (Japan); Zen, Yoh [Kanazawa University Graduate School of Medical Science, Human Pathology, Kanazawa (Japan); King' s College Hospital, Institute of Liver Studies, London (United Kingdom); Yamashita, Tatsuya; Kaneko, Shuichi [Kanazawa University Graduate School of Medical Science, Gastroenterology, Kanazawa (Japan); Nakanuma, Yasuni [Kanazawa University Graduate School of Medical Science, Human Pathology, Kanazawa (Japan)

    2011-10-15

    To clarify the changes in organic anion-transporting polypeptide 8 (OATP8) expression and enhancement ratio on gadoxetic acid-enhanced MR imaging in hepatocellular nodules during multistep hepatocarcinogenesis. In imaging analysis, we focused on 71 surgically resected hepatocellular carcinomas (well, moderately and poorly differentiated HCCs) and 1 dysplastic nodule (DN). We examined the enhancement ratio in the hepatobiliary phase of gadoxetic acid enhanced MR imaging [(1/postcontrast T1 value-1/precontrast T1 value)/(1/precontrast T1 value)], then analysed the correlation among the enhancement ratio, tumour differentiation grade and intensity of immunohistochemical OATP8 expression. In pathological analysis, we focused on surgically resected 190 hepatocellular nodules: low-grade DNs, high-grade DNs, early HCCs, well-differentiated, moderately differentiated and poorly differentiated HCCs, including cases without gadoxetic acid-enhanced MR imaging. We evaluated the correlation between the immunohistochemical OATP8 expression and the tumour differentiation grade. The enhancement ratio of HCCs decreased in accordance with the decline in tumour differentiation (P < 0.0001, R = 0.28) and with the decline of OATP8 expression (P < 0.0001, R = 0.81). The immunohistochemical OATP8 expression decreased from low-grade DNs to poorly differentiated HCCs (P < 0.0001, R = 0.15). The immunohistochemical expression of OATP8 significantly decreases during multistep hepatocarcinogenesis, which may explain the decrease in enhancement ratio on gadoxetic acid-enhanced MR imaging. (orig.)

  10. Evaluation of hyper thermal acid hydrolysis of Kappaphycus alvarezii for enhanced bioethanol production.

    Science.gov (United States)

    Ra, Chae Hun; Nguyen, Trung Hau; Jeong, Gwi-Taek; Kim, Sung-Koo

    2016-06-01

    Hyper thermal (HT) acid hydrolysis of Kappaphycus alvarezii, a red seaweed, was optimized to 12% (w/v) seaweed slurry content, 180mM H2SO4 at 140°C for 5min. The maximum monosaccharide concentration of 38.3g/L and 66.7% conversion from total fermentable monosaccharides of 57.6g/L with 120gdw/L K. alvarezii slurry were obtained from HT acid hydrolysis and enzymatic saccharification. HT acid hydrolysis at a severity factor of 0.78 efficiently converted the carbohydrates of seaweed to monosaccharides and produced a low concentration of inhibitory compounds. The levels of ethanol production by separate hydrolysis and fermentation with non-adapted and adapted Kluyveromyces marxianus to high concentration of galactose were 6.1g/L with ethanol yield (YEtOH) of 0.19 at 84h and 16.0g/L with YEtOH of 0.42 at 72h, respectively. Development of the HT acid hydrolysis process and adapted yeast could enhance the overall ethanol fermentation yields of K. alvarezii seaweed.

  11. Photoassisted enhancement of the electrocatalytic oxidation of formic acid on platinized TiO₂ nanotubes.

    Science.gov (United States)

    Mojumder, Nazrul; Sarker, Swagotom; Abbas, Syed Arslan; Tian, Zong; Subramanian, Vaidyanathan Ravi

    2014-04-23

    A solvothermal method is used to deposit Pt nanoparticles on anodized TiO2 nanotubes (T_NT). Surface characterization using SEM, EDX, and XRD indicates the formation of polycrystalline TiO2 nanotubes of 110 ± 10 nm diameter with Pt nanoparticle islands. The application of the T_NT/Pt photoanode has been examined toward simultaneous electrooxidation and photo(electro)oxidation of formic acid (HCOOH). Upon UV-vis photoillumination, the T_NT/Pt photoelectrode generates a current density of 72 mA/cm(2), which is significantly higher (∼39-fold) than that of the T_NT electrode (1.85 mA/cm(2)). This boosting in the overall current is attributable to the enhanced oxidation of formic acid at the T_NT/Pt-electrolyte interface. Further, a series of cyclic voltammetric (CV) responses, of which each anodic scan is switched to photoillumination at a certain applied bias (i.e., 0.2 V, 0.4 V, etc.), is used to identify the role of T_NT/Pt as a promoter for the photoelectrooxidation of formic acid and understand a carbon monoxide (CO)-free pathway. Chronoamperometric (j/t) measurements demonstrate the evidence of an external bias dependent variation in the time lag during the current stabilization. An analysis of the CV plots and j/t profiles suggests the existence of both the charge-transfer controlled process and the diffusion-controlled process during formic acid photoelectrooxidation.

  12. Enhanced biodegradation of anthracene in acidic soil by inoculated Burkholderia sp. VUN10013.

    Science.gov (United States)

    Somtrakoon, Khanitta; Suanjit, Sudarat; Pokethitiyook, Prayad; Kruatrachue, Maleeya; Lee, Hung; Upatham, Suchart

    2008-08-01

    The ability of Burkholderia sp. VUN10013 to degrade anthracene in microcosms of two acidic Thai soils was studied. The addition of Burkholderia sp. VUN10013 (initial concentration of 10(5) cells g(-1) dry soil) to autoclaved soil collected from the Plew District, Chanthaburi Province, Thailand, supplemented with anthracene (50 mg kg(-1) dry soil) resulted in complete degradation of the added anthracene within 20 days. In contrast, under the same test conditions but using autoclaved soil collected from the Kitchagude District, Chanthaburi Province, Thailand, only approximately 46.3% of the added anthracene was degraded after 60 days of incubation. In nonautoclaved soils, without adding the VUN10013 inocula, 22.8 and 19.1% of the anthracene in Plew and Kitchagude soils, respectively, were degraded by indigenous bacteria after 60 days. In nonautoclaved soil inoculated with Burkholderia sp. VUN10013, the rate and extent of anthracene degradation were considerably better than those seen in autoclaved soils or in uninoculated nonautoclaved soils in that only 8.2 and 9.1% of anthracene remained in nonautoclaved Plew and Kitchagude soils, respectively, after 10 days of incubation. The results showed that the indigenous microorganisms in the pristine acidic soils have limited ability to degrade anthracene. Inoculation with the anthracene-degrading Burkholderia sp. VUN10013 significantly enhanced anthracene degradation in such acidic soils. The indigenous microorganisms greatly assisted the VUN10013 inoculum in anthracene degradation, especially in the more acidic Kitchagude soil.

  13. Enhancing the Acylation Activity of Acetic Acid by Formation of an Intermediate Aromatic Ester.

    Science.gov (United States)

    Duong, Nhung N; Wang, Bin; Sooknoi, Tawan; Crossley, Steven P; Resasco, Daniel E

    2017-07-10

    Acylation is an effective C-C bond-forming reaction to condense acetic acid and lignin-derived aromatic compounds into acetophenones, valuable precursors to fuels and chemicals. However, acetic acid is intrinsically an ineffective acylating agent. Here, we report that its acylation activity can be greatly enhanced by forming intermediate aromatic esters directly derived from acetic acid and phenolic compounds. Additionally, the acylation reaction was studied in the liquid phase over acid zeolites and was found to happen in two steps: 1) formation of an acylium ion and 2) C-C bond formation between the acylium ion and the aromatic substrate. Each of these steps may be rate-limiting, depending on the type of acylating agent and the aromatic substrate. Oxygen-containing substituents, such as -OH and -OCH3 , can activate aromatic substrates for step 2, with -OH> -OCH3 , whereas alkyl substituent -R cannot. At the same time, aromatic esters can rearrange to acetophenones by both an intramolecular pathway and, preferentially, an intermolecular one. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Gold Nanoparticles Enhance the Anticancer Activity of Gallic Acid against Cholangiocarcinoma Cell Lines.

    Science.gov (United States)

    Rattanata, Narintorn; Daduang, Sakda; Wongwattanakul, Molin; Leelayuwat, Chanvit; Limpaiboon, Temduang; Lekphrom, Ratsami; Sandee, Alisa; Boonsiri, Patcharee; Chio-Srichan, Sirinart; Daduang, Jureerut

    2015-01-01

    Gold nanoparticles (GNPs) were conjugated with gallic acid (GA) at various concentrations between 30 and 150 μM and characterized using transmission electron microscopy (TEM) and UV-Vis spectroscopy (UV-VIS). The anticancer activities of the gallic acid-stabilized gold nanoparticles against well-differentiated (M213) and moderately differentiated (M214) adenocarcinomas were then determined using a neutral red assay. The GA mechanism of action was evaluated using Fourier transform infrared (FTIR) microspectroscopy. Distinctive features of the FTIR spectra between the control and GA-treated cells were confirmed by principal component analysis (PCA). The surface plasmon resonance spectra of the GNPs had a maximum absorption at 520 nm, whereas GNPs-GA shifted the maximum absorption values. In an in vitro study, the complexed GNPs-GA had an increased ability to inhibit the proliferation of cancer cells that was statistically significant (Pacids, which may enhance the efficacy of this anticancer activity regarding apoptosis pathways.

  15. Scale-up cultivation enhanced arachidonic acid accumulation by red microalgae Porphyridium purpureum.

    Science.gov (United States)

    Chang, Jingyu; Le, Kai; Song, Xiaoqiang; Jiao, Kailin; Zeng, Xianhai; Ling, Xueping; Shi, Tuo; Tang, Xing; Sun, Yong; Lin, Lu

    2017-08-23

    The present study attempts to cultivate Porphyridium purpureum under different scale-up conditions for further development and commercialization of microalgae-derived PUFAs such as ARA and EPA. Different temperatures (25, 30, and 35 °C) and light intensities (70, 165, and 280 μmol/m(2)s) were applied to the 50 L pilot-scale cultivation of P. purpureum in ASW. The cultivation under the light intensity of 280 μmol/m(2)s at 35 °C obtained biomass concentration up to 9.52 g/L, total fatty acid content to 56.82 mg/g, and ARA content to 22.29 mg/g. While the maximum EPA content of 7.00 mg/g was achieved under the light intensity of 280 μmol/m(2)s at 25 °C and the highest ratio of UFAs to TFAs of 74.66% was also obtained in this trial. Both biomass concentration and TFAs content were improved by increasing light intensity and temperature. Moreover, the ratio of ARA to EPA was enhanced by increasing cultivation temperature under the light intensity of 280 μmol/m(2)s. In contrast with flask culture, the conversion of linoleic acid (C18:2) to ARA was enhanced in scale-up culture, leading to more ARA content. Phosphate limitation enhanced the synthesis of lipid and LPUFAs. Moreover, the biomass concentration and biosynthesis of palmitic acid were preferred by sufficient C (NaHCO3).

  16. Design and evaluation of Lumefantrine – Oleic Acid Self Nanoemulsifying Ionic Complex for Enhanced Dissolution

    Directory of Open Access Journals (Sweden)

    Pradeep Vavia

    2013-03-01

    Full Text Available Background:Lumefantrine, an antimalarial molecule has very low and variable bioavailability owing to its extremely poor solubility in water. It is recommended to be taken with milk to enhance its solubility and bioavailability. The aim of present study was to develop a Self Nanoemulsifying Delivery system (SNEDs of lumefantrine (LF to achieve rapid and complete dissolution independent of food-fat and surfactant in dissolution media.Methods:Solubility of LF in oil, co-solvent/co-surfactant and surfactant solution and emulsification efficiency of surfactant were analyzed to optimize the LF loaded self nanoemulsifying preconcentrate. Effect of LF-oleic acid complexation on emulsification, droplet size, zeta potential and dissolution were investigated. Effect of milk concentration and fat content on saturation solubility and dissolution of LF was investigated. Dissolution of marketed formulation and LF-SNEDs was carried out in pH 1.2 and pH 6.8 phosphate buffer.Results:LF exhibited very high solubility in oleic acid owing to complexation between tertiary amine of LF and carboxyl group of oleic acid (OA. Cremophore EL and medium chain monoglyceride were selected surfactant and co-surfactant, respectively. Significantly smaller droplet size (37 nm, shift in zeta potential from negative to positive value, very high drug loading in lipid based system (> 10%, no precipitation after dissolution are the major distinguish characteristics contributed by LF-OA complex in the SNED system. Saturation solubility and dissolution study in milk containing media pointed the significant increment in solubility of LF in the presence of milk-food fat. LF-SNEDs showed > 90% LF release within 30 min in pH 1.2 while marketed tablet showed almost 0% drug release.Conclusion:Self nanoemulsification promoting ionic complexation between basic drug and oleic acid hold great promise in enhancing solubility of hydrophobic drugs.

  17. SnO2 nanospheres supported Pd catalyst with enhanced performance for formic acid oxidation

    Science.gov (United States)

    Lu, Haiting; Fan, Yang; Huang, Ping; Xu, Dongli

    2012-10-01

    SnO2 nanospheres were employed as the support material for Pd catalyst. The as-prepared Pd/SnO2 catalyst exhibited remarkably improved electrocatalytic activity and stability towards formic acid oxidation, in comparison with that of the Vulcan XC-72 carbon black and the commercial SnO2 nanopowder supported Pd catalyst. The enhanced catalytic performance may arise from the unique structure and surface properties of the SnO2 nanospheres, which process extraordinary promotional effect on Pd catalyst.

  18. Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.

    Science.gov (United States)

    Lee, Hye-In; Kim, Young-Jin

    2016-06-01

    Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.

  19. Peracetic acid-ionic liquid pretreatment to enhance enzymatic saccharification of lignocellulosic biomass.

    Science.gov (United States)

    Uju; Abe, Kojiro; Uemura, Nobuyuki; Oshima, Toyoji; Goto, Masahiro; Kamiya, Noriho

    2013-06-01

    To enhance enzymatic saccharification of pine biomass, the pretreatment reagents peracetic acid (PAA) and ionic liquid (IL) were validated in single reagent pretreatments or combination pretreatments with different sequences. In a 1h saccharification, 5-25% cellulose conversion was obtained from the single pretreatment of PAA or IL. In contrast, a marked enhancement in conversion rates was achieved by PAA-IL combination pretreatments (45-70%). The PAA followed by IL (PAA+IL) pretreatment sequence was the most effective for preparing an enzymatic digestible regenerated biomass with 250-fold higher glucose formation rates than untreated biomass and 2- to 12-fold higher than single pretreatments with PAA or IL alone. Structural analysis confirmed that this pretreatment resulted in biomass with highly porous structural fibers associated with the reduction of lignin content and acetyl groups. Using the PAA+IL sequence, biomass loading in the pretreatment step can be increased from 5% to 15% without significant decrease in cellulose conversion.

  20. Alpha-lipoic acid inhibits mitochondrial oxidative stress in the rat skeletal muscle with chronic hypoxia exposure%α-硫辛酸抑制慢性低氧大鼠骨骼肌线粒体的氧化应激**

    Institute of Scientific and Technical Information of China (English)

    肖频; 庞奕辉; 彭朋; 薄海

    2013-01-01

    BACKGROUND: α-lipoic acid is named as “nature antioxidant” and “mitochondrial nutrition”. But it is unclear whether α-lipoic acid can be used to protect skeletal muscle with chronic hypoxia exposure, as wel as the relative mechanism. OBJECTIVE: To observe the effect of α-lipoic acid on the antioxidant enzymes and oxidative stress in rat skeletal muscle with chronic hypoxia exposure, and to investigate the relative signaling pathway of α-lipoic acid. METHODS: Thirty-six Sprague Dawley rats were randomly divided into three groups: normoxia control group, hypoxia control group, and hypoxia+α-lipoic acid group. Rats in the hypoxia control group were subjected to hypoxia exposure in normobaric hypoxic tent with 11.3% oxygen concentration. Rats in the hypoxia+α-lipoic acid group were induced by adding α-lipoic acid (0.25%) in the normal diet. Al the interventions were lasted for 4 weeks. RESULTS AND CONCLUSION: α-lipoic acid in hypoxia could markedly enhance the mitochondrial Sirtuin-3 expression, improve the mitochondrial adenosine triphosphate synthesis activity and membrane potential, up-regulate the mitochondrial state 3 respiratory rate, respiratory control ratio and ratio of phosphorus to oxygen, down-regulate the mitochondrial state 4 respiratory rate and promote and up-regulate the activity of mitochondrial antioxidant enzymes such as manganese superoxide dismutase, glutathione peroxidase and catalase, thus inhibiting mitochondrial H2O2 generation rate and reducing mitochondrial malondialdehyde level. The results indicated that α-lipoic acid could improve the efficiency of energy metabolism of chronic hypoxia skeletal muscle mitochondria and inhibit reactive oxygen generation, and it could inhibit the oxidative stress through improving antioxidant enzyme activity of mitochondria. The protection mechanism of α-lipoic acid on hypoxia skeletal muscle mitochondria may be related to the increasing of mitochondrial state 3 respiratory rate.%  背

  1. Enhanced absorption of anthocyanins after oral administration of phytic acid in rats and humans.

    Science.gov (United States)

    Matsumoto, Hitoshi; Ito, Kyoko; Yonekura, Kumiko; Tsuda, Takanori; Ichiyanagi, Takashi; Hirayama, Masao; Konishi, Tetsuya

    2007-03-21

    Many studies on the bioavailability of polyphenols have been reported. However, the relative urinary excretions of AC are also low, ranging from 0.004% to 0.1%. By contrast, other polyphenols show higher urinary excretion levels. Here, we studied the enhancing effects of phytic acid (IP6) on absorption of blackcurrant anthocyanins (BCAs) in rats and humans. In rats after oral administration of BCAs (as 241 mg of AC/kg body weight) in IP6 (0%, 0.25%, 0.5%, 1%, 2.5%) solution, the ACs recovery in urine was increased dependent on IP6 dose. These results suggest that the IP6 enhances gastrointestinal absorption of ACs. At the further analysis of IP6 enhancement effect in rat, whereas BCAs were normally passed through the stomach and duodenum within 2 h, in IP6 group, after 2-6 h post-administration, stomach and jejunum content's weights were specifically heavy, and large amounts of ACs were also detected in stomach, duodenum, and jejunum. These results suggested that the mixture of BCAs and IP6 reduced the gastrointestinal motility. Prolongation of ACs residue in gastrointestinal tract then caused the enhancing effects of IP6 on absorption of AC. In the human study, each subject was orally administrated a BCA beverage containing BCA concentrate (AC 4 mg/kg body weight), 1% of IP6, and 1% of sodium citrate as a pH stabilizer. Both the plasma level and the urinary excretion of AC were increased as compared to BCA administration without IP6. AC intake with IP6 may increase the bioavailability of AC to the comparative level as other polyphenols. Yet, phytic acid, being a strong chelator of important minerals, contributes to mineral deficiencies. An interference with iron uptake has been reported. Safety tests are therefore necessary before high dose IP6 can be used in foods.

  2. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging

    Science.gov (United States)

    Liopo, Anton; Su, Richard; Tsyboulski, Dmitri A.; Oraevsky, Alexander A.

    2016-08-01

    Enhanced delivery of optical clearing agents (OCA) through skin may improve sensitivity of optical and optoacoustic (OA) methods of imaging, sensing, and monitoring. This report describes a two-step method for enhancement of light penetration through skin. Here, we demonstrate that topical application of hyaluronic acid (HA) improves skin penetration of hydrophilic and lipophilic OCA and thus enhances their performance. We examined the OC effect of 100% polyethylene and polypropylene glycols (PPGs) and their mixture after pretreatment by HA, and demonstrated significant increase in efficiency of light penetration through skin. Increased light transmission resulted in a significant increase of OA image contrast in vitro. Topical pretreatment of skin for about 30 min with 0.5% HA in aqueous solution offers effective delivery of low molecular weight OCA such as a mixture of PPG-425 and polyethylene glycol (PEG)-400. The developed approach of pretreatment by HA prior to application of clearing agents (PEG and PPG) resulted in a ˜47-fold increase in transmission of red and near-infrared light and significantly enhanced contrast of OA images.

  3. Enhancement of the reductive transformation of pentachlorophenol by polycarboxylic acids at the iron oxide-water interface.

    Science.gov (United States)

    Li, Fangbai; Wang, Xugang; Li, Yongtao; Liu, Chengshuai; Zeng, Fang; Zhang, Lijia; Hao, Mingde; Ruan, Huada

    2008-05-15

    The enhancement effect of polycarboxylic acids on reductive dechlorination transformation of pentachlorophenol (PCP) reacting with iron oxides was studied in anoxic suspension. Batch experiments were performed with three species of iron oxides (goethite, lepidocrocite and hematite) and four species of polycarboxylic acids (oxalate, citrate, succinate, and tartrate) through anoxic abiotic reactors. The chemical analyses and morphological observation from scanning and transmission electron microscopy showed that different combinations between polycarboxylic acids and iron oxides produced distinct contents of Fe(II)-polycarboxylic ligand complexes, which significantly enhanced PCP transformation. Generation of the surface-bound Fe(II) depended on concentration of polycarboxylic acids. The optimal concentration for the enhancement was 2.0 mM oxalic acid. The dechlorination mechanism was further demonstrated by generation of chloride ions. The results suggest that surface-bound Fe(II) formed on the iron oxides surface appears to be a key factor in enhancing PCP transformation, and the mole ratio of oxalate to surface-bound Fe(II) (oxalate/Fe(II)) acted as an indicator of the enhancement effect. The enhancement mechanism attributes to strong nucleophilic ability and low reductive potential of the equivalent Fe(II)-polycarboxylate complexes. Therefore, the enhancement effects might be helpful for understanding the natural attenuation of reducible organic pollutants at the interface of contaminated soil in anoxic condition.

  4. Comparative proteomic analysis of differentially expressed proteins in β-aminobutyric acid enhanced Arabidopsis thaliana tolerance to simulated acid rain.

    Science.gov (United States)

    Liu, Tingwu; Jiang, Xinwu; Shi, Wuliang; Chen, Juan; Pei, Zhenming; Zheng, Hailei

    2011-05-01

    Acid rain is a worldwide environmental issue that has seriously destroyed forest ecosystems. As a highly effective and broad-spectrum plant resistance-inducing agent, β-aminobutyric acid could elevate the tolerance of Arabidopsis when subjected to simulated acid rain. Using comparative proteomic strategies, we analyzed 203 significantly varied proteins of which 175 proteins were identified responding to β-aminobutyric acid in the absence and presence of simulated acid rain. They could be divided into ten groups according to their biological functions. Among them, the majority was cell rescue, development and defense-related proteins, followed by transcription, protein synthesis, folding, modification and destination-associated proteins. Our conclusion is β-aminobutyric acid can lead to a large-scale primary metabolism change and simultaneously activate antioxidant system and salicylic acid, jasmonic acid, abscisic acid signaling pathways. In addition, β-aminobutyric acid can reinforce physical barriers to defend simulated acid rain stress.

  5. Metabolic engineering of Clostridium acetobutylicum for enhanced production of butyric acid.

    Science.gov (United States)

    Jang, Yu-Sin; Woo, Hee Moon; Im, Jung Ae; Kim, In Ho; Lee, Sang Yup

    2013-11-01

    Clostridium acetobutylicum has been considered as an attractive platform host for biorefinery due to its metabolic diversity. Considering its capability to overproduce butanol through butyrate, it was thought that butyric acid can also be efficiently produced by this bacterium through metabolic engineering. The pta-ctfB-deficient C. acetobutylicum CEKW, in which genes encoding phosphotransacetylase and CoA-transferase were knocked out, was assessed for its potential as a butyric acid producer in fermentations with four controlled pH values at 5.0, 5.5, 6.0, and 6.4. Butyric acid could be best produced by fermentation of the CEKW at pH 6.0, resulting in the highest titer of 26.6 g/l, which is 6.4 times higher than that obtained with the wild type. However, due to the remaining solventogenic ability of the CEKW, 3.6 g/l solvents were also produced. Thus, the CEKW was further engineered by knocking out the adhE1-encoding aldehyde/alcohol dehydrogenase to prevent solvent production. Batch fermentation of the resulting C. acetobutylicum HCEKW at pH 6.0 showed increased butyric acid production to 30.8 g/l with a ratio of butyric-to-acetic acid (BA/AA) of 6.6 g/g and a productivity of 0.72 g/l/h from 86.9 g/l glucose, while negligible solvent (0.8 g/l ethanol only) was produced. The butyric acid titer, BA/AA ratio, and productivity obtained in this study were the highest values reported for C. acetobutylicum, and the BA/AA ratio and productivity were also comparable to those of native butyric acid producer Clostridium tyrobutyricum. These results suggested that the simultaneous deletion of the pta-ctfB-adhE1 in C. acetobutylicum resulted in metabolic switch from biphasic to acidogenic fermentation, which enhanced butyric acid production.

  6. Proteomics of Skeletal Muscle

    DEFF Research Database (Denmark)

    Deshmukh, Atul

    2016-01-01

    Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability...... of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence...

  7. Using Laboratory Activities Enhanced with Concept Cartoons to Support Progression in Students' Understanding of Acid-Base Concepts

    Science.gov (United States)

    Ozmen, Haluk; Demircioglu, Gokhan; Burhan, Yasemin; Naseriazar, Akbar; Demircioglu, Hulya

    2012-01-01

    The aim of this study is to examine the effectiveness of an intervention based on a series of laboratory activities enhanced with concept cartoons. The purpose of the intervention was to enhance students' understanding of acid-base chemistry for eight grade students' from two classes in a Turkish primary school. A pretest-posttest non-equivalent…

  8. Using Laboratory Activities Enhanced with Concept Cartoons to Support Progression in Students' Understanding of Acid-Base Concepts

    Science.gov (United States)

    Ozmen, Haluk; Demircioglu, Gokhan; Burhan, Yasemin; Naseriazar, Akbar; Demircioglu, Hulya

    2012-01-01

    The aim of this study is to examine the effectiveness of an intervention based on a series of laboratory activities enhanced with concept cartoons. The purpose of the intervention was to enhance students' understanding of acid-base chemistry for eight grade students' from two classes in a Turkish primary school. A pretest-posttest non-equivalent…

  9. Engineering Yarrowia lipolytica for Enhanced Production of Lipid and Citric Acid

    Directory of Open Access Journals (Sweden)

    Ali Abghari

    2017-07-01

    Full Text Available Increasing demand for plant oil for food, feed, and fuel production has led to food-fuel competition, higher plant lipid cost, and more need for agricultural land. On the other hand, the growing global production of biodiesel has increased the production of glycerol as a by-product. Efficient utilization of this by-product can reduce biodiesel production costs. We engineered Yarrowia lipolytica (Y. lipolytica at various metabolic levels of lipid biosynthesis, degradation, and regulation for enhanced lipid and citric acid production. We used a one-step double gene knock-in and site-specific gene knock-out strategy. The resulting final strain combines the overexpression of homologous DGA1 and DGA2 in a POX-deleted background, and deletion of the SNF1 lipid regulator. This increased lipid and citric acid production in the strain under nitrogen-limiting conditions (C/N molar ratio of 60. The engineered strain constitutively accumulated lipid at a titer of more than 4.8 g/L with a lipid content of 53% of dry cell weight (DCW. The secreted citric acid reached a yield of 0.75 g/g (up to ~45 g/L from pure glycerol in 3 days of batch fermentation using a 1-L bioreactor. This yeast cell factory was capable of simultaneous lipid accumulation and citric acid secretion. It can be used in fed-batch or continuous bioprocessing for citric acid recovery from the supernatant, along with lipid extraction from the harvested biomass.

  10. Label-free direct surface-enhanced Raman scattering (SERS) of nucleic acids (Conference Presentation)

    Science.gov (United States)

    Guerrini, Luca; Morla-Folch, Judit; Gisbert-Quilis, Patricia; Xie, Hainan; Alvarez-Puebla, Ramon

    2016-03-01

    Recently, plasmonic-based biosensing has experienced an unprecedented level of attention, with a particular focus on the nucleic acid detection, offering efficient solutions to engineer simple, fast, highly sensitive sensing platforms while overcoming important limitations of PCR and microarray techniques. In the broad field of plasmonics, surface-enhanced Raman scattering (SERS) spectroscopy has arisen as a powerful analytical tool for detection and structural characterization of biomolecules. Today applications of SERS to nucleic acid analysis largely rely on indirect strategies, which have been demonstrated very effective for pure sensing purposes but completely dismiss the exquisite structural information provided by the direct acquisition of the biomolecular vibrational fingerprint. Contrarily, direct label-free SERS of nucleic acid shows an outstanding potential in terms of chemical-specific information which, however, remained largely unexpressed mainly because of the inherent poor spectral reproducibility and/or limited sensitivity. To address these limitations, we developed a fast and affordable high-throughput screening direct SERS method for gaining detailed genomic information on nucleic acids (DNA and RNA) and for the characterization and quantitative recognition of DNA interactions with exogenous agents. The simple strategy relies on the electrostatic adhesion of DNA/RNA onto positively-charged silver colloids that promotes the nanoparticle aggregation into stable clusters yielding intense and reproducible SERS spectra at picogram level (i.e. the analysis can be performed without the necessity of amplification steps thus providing realistic direct information of the nucleic acid in its native state). We anticipate this method to gain a vast impact and set of applications in different fields, including medical diagnostics, genomic screening, drug discovery, forensic science and even molecular electronics.

  11. Transcriptome analysis of acetic-acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance.

    Science.gov (United States)

    Lee, Yeji; Nasution, Olviyani; Choi, Eunyong; Choi, In-Geol; Kim, Wankee; Choi, Wonja

    2015-08-01

    Acetic acid inhibits the metabolic activities of Saccharomyces cerevisiae. Therefore, a better understanding of how S. cerevisiae cells acquire the tolerance to acetic acid is of importance to develop robust yeast strains to be used in industry. To do this, we examined the transcriptional changes that occur at 12 h post-exposure to acetic acid, revealing that 56 and 58 genes were upregulated and downregulated, respectively. Functional categorization of them revealed that 22 protein synthesis genes and 14 stress response genes constituted the largest portion of the upregulated and downregulated genes, respectively. To evaluate the association of the regulated genes with acetic acid tolerance, 3 upregulated genes (DBP2, ASC1, and GND1) were selected among 34 non-protein synthesis genes, and 54 viable mutants individually deleted for the downregulated genes were retrieved from the non-essential haploid deletion library. Strains overexpressing ASC1 and GND1 displayed enhanced tolerance to acetic acid, whereas a strain overexpressing DBP2 was sensitive. Fifty of 54 deletion mutants displayed enhanced acetic acid tolerance. Three chosen deletion mutants (hsps82Δ, ato2Δ, and ssa3Δ) were also tolerant to benzoic acid but not propionic and sorbic acids. Moreover, all those five (two overexpressing and three deleted) strains were more efficient in proton efflux and lower in membrane permeability and internal hydrogen peroxide content than controls. Individually or in combination, those physiological changes are likely to contribute at least in part to enhanced acetic acid tolerance. Overall, information of our transcriptional profile was very useful to identify molecular factors associated with acetic acid tolerance.

  12. Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition.

    Science.gov (United States)

    Wu, A; Ying, Z; Gomez-Pinilla, F

    2008-08-26

    Omega-3 fatty acids (i.e. docosahexaenoic acid; DHA), similar to exercise, improve cognitive function, promote neuroplasticity, and protect against neurological lesion. In this study, we investigated a possible synergistic action between DHA dietary supplementation and voluntary exercise on modulating synaptic plasticity and cognition. Rats received DHA dietary supplementation (1.25% DHA) with or without voluntary exercise for 12 days. We found that the DHA-enriched diet significantly increased spatial learning ability, and these effects were enhanced by exercise. The DHA-enriched diet increased levels of pro-brain-derived neurotrophic factor (BDNF) and mature BDNF, whereas the additional application of exercise boosted the levels of both. Furthermore, the levels of the activated forms of CREB and synapsin I were incremented by the DHA-enriched diet with greater elevation by the concurrent application of exercise. While the DHA diet reduced hippocampal oxidized protein levels, a combination of a DHA diet and exercise resulted in a greater reduction rate. The levels of activated forms of hippocampal Akt and CaMKII were increased by the DHA-enriched diet, and with even greater elevation by a combination of diet and exercise. Akt and CaMKII signaling are crucial step by which BDNF exerts its action on synaptic plasticity and learning and memory. These results indicate that the DHA diet enhanced the effects of exercise on cognition and BDNF-related synaptic plasticity, a capacity that may be used to promote mental health and reduce risk of neurological disorders.

  13. Enhanced esterification of oleic acid and methanol by deep eutectic solvent assisted Amberlyst heterogeneous catalyst.

    Science.gov (United States)

    Pan, Ying; Alam, Md Asraful; Wang, Zhongming; Wu, Jingcheng; Zhang, Yi; Yuan, Zhenhong

    2016-11-01

    In present study, esterification of oleic acid with methanol using deep eutectic solvent (DES) assisted Amberlyst heterogeneous catalyst was investigated to produce biodiesel. Results showed that esterification efficiency was enhanced by the DES. The combined effect of DES on Amberlyst BD20 (BD20) is better than Amberlyst 15 (A-15) due to different structure. The optimal reaction conditions were 12:1M ratio of methanol to oleic acid, 20%(wt/wt) catalyst (BD20-DES (2:8) and A-15-DES (8:2)) at 85°C for 100min with agitating at 200rpm. The mechanism involved in catalysis and their capacity to reuse were studied. We proposed, Choline chloride-glycerol (Chcl-gly) DES could enhance the Amberlyst function due to the hydrogen bond effect on both DES and water. BD20 has fewer pores than A-15, have desirable performance in decreasing the inhibition the water during esterification of high FFA content and provide better performance in reuse.

  14. Ultrasonic enhance acid hydrolysis selectivity of cellulose with HCl-FeCl3 as catalyst.

    Science.gov (United States)

    Li, Jinbao; Zhang, Xiangrong; Zhang, Meiyun; Xiu, Huijuan; He, Hang

    2015-03-06

    The effect of ultrasonic pretreatment coupled with HCl-FeCl3 catalyst was evaluated to hydrolyze cellulose amorphous regions. The ultrasonic pretreatment leads to cavitation that affects the morphology and microstructure of fibers, enhancing the accessibility of chemical reagent to the loosened amorphous regions of cellulose. In this work, Fourier transform infrared spectroscopy (FTIR) was used to identify characteristic absorption bands of the constituents and the crystallinity was evaluated by the X-ray diffraction (XRD) technique. The results indicated that appropriate ultrasonic pretreatment assisted with FeCl3 can enhance the acid hydrolysis of amorphous regions of cellulose, thus improving the crystallinity of the remaining hydrocellulose. It was observed that sonication samples that were pretreated for 300 W and 20 min followed by acid hydrolysis had maximum of 78.9% crystallinity. The crystallinity was 9.2% higher than samples that were not subjected to ultrasound. In addition, the average fines length decreased from 49 μm to 37 μm. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Hollow palladium nanospheres with porous shells supported on graphene as enhanced electrocatalysts for formic acid oxidation.

    Science.gov (United States)

    Wang, Bo; Yang, Jun; Wang, Lei; Wang, Ruihong; Tian, Chungui; Jiang, Baojiang; Tian, Mei; Fu, Honggang

    2013-11-28

    The hollow palladium nanospheres with the porous shell comprised of uniform 5 nm Pd nanoparticles (Pd NS-HP) have been synthesized successfully by employing a simple replacement process between PdCl4(2-) ions and Co with the assistance of a structure-directing agent, polyvinyl pyrrolidone (PVP). Then, the obtained Pd NS-HP is supported on graphene nanosheets (GN) to prepare Pd NS-HP/GN composites by a wet-impregnation method. As the catalyst towards formic acid electrooxidation, the Pd NS-HP/GN composite exhibits a larger electrochemically active surface area, better electrocatalytic activity and better stability compared with Pd nanoparticles/graphene (Pd NP/GN) and commercial Pd/C catalysts. The enhancement in electrocatalytic performance of Pd NS-HP/GN is attributed to the abundant connected pore channels in the inner and exterior surfaces of Pd nanospheres, which could provide a large contact surface for adsorption and transmission of reactants, facilitating the oxidation of formic acid molecules on its surface and also improving the utilization of Pd metal. Moreover, the support of graphene could enhance the stability of the catalyst.

  16. Detection of amino acid neurotransmitters by surface enhanced Raman scattering and hollow core photonic crystal fiber

    Science.gov (United States)

    Tiwari, Vidhu S.; Khetani, Altaf; Monfared, Ali Momenpour T.; Smith, Brett; Anis, Hanan; Trudeau, Vance L.

    2012-03-01

    The present work explores the feasibility of using surface enhanced Raman scattering (SERS) for detecting the neurotransmitters such as glutamate (GLU) and gamma-amino butyric acid (GABA). These amino acid neurotransmitters that respectively mediate fast excitatory and inhibitory neurotransmission in the brain, are important for neuroendocrine control, and upsets in their synthesis are also linked to epilepsy. Our SERS-based detection scheme enabled the detection of low amounts of GLU (10-7 M) and GABA (10-4 M). It may complement existing techniques for characterizing such kinds of neurotransmitters that include high-performance liquid chromatography (HPLC) or mass spectrography (MS). This is mainly because SERS has other advantages such as ease of sample preparation, molecular specificity and sensitivity, thus making it potentially applicable to characterization of experimental brain extracts or clinical diagnostic samples of cerebrospinal fluid and saliva. Using hollow core photonic crystal fiber (HC-PCF) further enhanced the Raman signal relative to that in a standard cuvette providing sensitive detection of GLU and GABA in micro-litre volume of aqueous solutions.

  17. Diet-induced weight loss and exercise alone and in combination enhance the expression of adiponectin receptors in adipose tissue and skeletal muscle, but only diet-induced weight loss enhanced circulating adiponectin

    DEFF Research Database (Denmark)

    Christiansen, Tore; Paulsen, Søren K; Bruun, Jens M

    2009-01-01

    and adiponectin receptors (AdipoR) in adipose tissue (AT) and skeletal muscle (SM). Design and Methods: Seventy-nine obese males and females were randomized into the following: 1) exercise only (12 wk of exercise without diet restriction); 2) hypocaloric diet [8 wk of very low energy diet (600 kcal/d) followed...... by 4 wk with a weight maintenance diet]; and 3) hypocaloric diet and exercise (DEX; 8 wk very low energy diet 800 kcal/d followed by 4 wk weight maintenance diet combined with exercise throughout the 12 wk). Blood samples and biopsies from sc abdominal AT and SM were collected at baseline and after 12...

  18. Skeletal muscle lipid metabolism in exercise and insulin resistance

    DEFF Research Database (Denmark)

    Kiens, Bente

    2006-01-01

    Lipids as fuel for energy provision originate from different sources: albumin-bound long-chain fatty acids (LCFA) in the blood plasma, circulating very-low-density lipoproteins-triacylglycerols (VLDL-TG), fatty acids from triacylglycerol located in the muscle cell (IMTG), and possibly fatty acids...... of insulin resistance in skeletal muscle, including possible molecular mechanisms involved, is discussed....

  19. Acidity enhancement of unsaturated bases of group 15 by association with borane and beryllium dihydride. Unexpected boron and beryllium Brønsted acids.

    Science.gov (United States)

    Martín-Sómer, Ana; Mó, Otilia; Yáñez, Manuel; Guillemin, Jean-Claude

    2015-01-21

    The intrinsic acidity of CH2[double bond, length as m-dash]CHXH2, HC[triple bond, length as m-dash]CXH2 (X = N, P, As, Sb) derivatives and of their complexes with BeH2 and BH3 has been investigated by means of high-level density functional theory and molecular orbital ab initio calculations, using as a reference the ethyl saturated analogues. The acidity of the free systems steadily increases down the group for the three series of derivatives, ethyl, vinyl and ethynyl. The association with both beryllium dihydride and borane leads to a very significant acidity enhancement, being larger for BeH2 than for BH3 complexes. This acidity enhancement, for the unsaturated compounds, is accompanied by a change in the acidity trends down the group, which do not steadily decrease but present a minimum value for both the vinyl- and the ethynyl-phosphine. When the molecule acting as the Lewis acid is beryllium dihydride, the π-type complexes in which the BeH2 molecules interact with the double or triple bond are found, in some cases, to be more stable, in terms of free energies, than the conventional complexes in which the attachment takes place at the heteroatom, X. The most important finding, however, is that P, As, and Sb ethynyl complexes with BeH2 do not behave as P, As, or Sb Brønsted acids, but unexpectedly as Be acids.

  20. The effects of orbital spaceflight on bone histomorphometry and messenger ribonucleic acid levels for bone matrix proteins and skeletal signaling peptides in ovariectomized growing rats

    Science.gov (United States)

    Cavolina, J. M.; Evans, G. L.; Harris, S. A.; Zhang, M.; Westerlind, K. C.; Turner, R. T.

    1997-01-01

    bone loss in the unloaded limb in excess of that induced by gonadal hormone deficiency. This additional bone loss was arrested by estrogen replacement. We conclude from these studies that estrogen alters the expression of signaling peptides believed to mediate skeletal adaptation to changes in mechanical usage and likewise modifies the skeletal response to mechanical unloading.

  1. Cariporide Enhances the DNA Damage and Apoptosis in Acid-tolerable Malignant Mesothelioma H-2452 Cells.

    Science.gov (United States)

    Lee, Yoon-Jin; Bae, Jin-Ho; Kim, Soo-A; Kim, Sung-Ho; Woo, Kee-Min; Nam, Hae-Seon; Cho, Moon-Kyun; Lee, Sang-Han

    2017-08-01

    The Na(+)/H(+) exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular Na(+) and the extrusion of intracellular H(+). The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent Na(+)/H(+)-exchange inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a sub-G0/G1 peak, and a G2/M phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, p-ATM(Ser1981), p-ATR(Ser428), p-CHK1(Ser345), and p-CHK2(Thr68), as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acid-tolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.

  2. Up-Regulation of Toll-Like Receptor 4/Nuclear Factor-κB Signaling Is Associated with Enhanced Adipogenesis and Insulin Resistance in Fetal Skeletal Muscle of Obese Sheep at Late Gestation

    National Research Council Canada - National Science Library

    Yan, Xu; Zhu, Mei J; Xu, Wei; Tong, Jun F; Ford, Stephen P; Nathanielsz, Peter W; Du, Min

    2010-01-01

    .... The objective of this study was to evaluate effects of maternal obesity on adipogenesis, inflammatory signaling, and insulin pathways at late gestation when ovine fetal skeletal muscle matures...

  3. Skeletal muscle tissue engineering

    National Research Council Canada - National Science Library

    Bach, A. D; Beier, J. P; Stern‐Staeter, J; Horch, R. E

    2004-01-01

    The reconstruction of skeletal muscle tissue either lost by traumatic injury or tumor ablation or functional damage due to myopathies is hampered by the lack of availability of functional substitution...

  4. Ursolic Acid Mediates Hepatic Protection through Enhancing of anti-aging Biomarkers.

    Science.gov (United States)

    Gharibi, Shadi; Bakhtiari, Nuredin; Jalalvand, Elham-Moslemee

    2017-05-30

    Age-associated loss of liver function has been recognized for decades. But, the mechanism driving liver regeneration and its decline with age remains elusive. Hence, to support of our previous studies about anti-aging effects of Ursolic Acid (UA), a compound which extensively present in apple peels. The aim of this study is to address whether UA might alter sensors of the cell metabolic state such as SIRT1, SIRT6, PGC-1β and Klotho proteins. To evaluate the effect of UA on hepatic indicated proteins, mice were administrated with UA twice daily for 7 days. The involvements of these proteins in the UA-mediated effect harmony hepatic protection were investigated by immunofluorescence microscopy technique. Our findings clearly illustrated that UA enhanced SIRT1 (~ 5 ± 0.2 folds) and SIRT6 (~ 8 ± 0.5 folds) proteins levels in hepatic, p<0.001. In addition, the data showed that UA increased PGC-1β (~ 7 ± 0.4 folds) protein overexpression, p<0.001. Moreover, we showed that UA up-regulated Klotho (~ 3.5 ± 0.2 folds) protein in order to improve hepatic performance, p<0.01. Our results suggest that UA through increasing of SIRT1 up-regulation ameliorate reverse cholesterol transport, fatty acid use and oxidative stress defense. In addition, it seems that UA by enhancing of SIRT6 expression promotes cholesterol homeostasis through repressing of SREBP1 and SREBP2. Reciprocally, UA might be involved in VLDL synthesis and exportation through PGC-1β up-regulation. Finally, UA might be as key regulators of mineral homeostasis and bile acid/cholesterol metabolism, by inducing of Klotho overexpression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. [Enhanced phytoextraction of heavy metal contaminated soil by chelating agents and auxin indole-3-acetic acid].

    Science.gov (United States)

    Zhou, Jian-min; Dang, Zhi; Chen, Neng-chang; Xu, Sheng-guang; Xie, Zhi-yi

    2007-09-01

    The environmental risk of chelating agents such as EDTA application to the heavy metals polluted soils and the stress on plant roots due to the abrupt increase metals concentration limit the wide commercial use of chelate-induced phytoextraction. Chelating agent ethylenediaminetetraacetic acid (EDTA) and nitrilotriacetic acid (NTA) and auxin indole-3-acetic acid (IAA) were used for enhancing heavy metals uptake from soils by Zea mays L. (corn) in pot experiments. The metals content in plant tissues was quantified using an inductively coupled plasma mass spectrometer (ICP-MS). The results showed that the combination of IAA and EDTA increased the biomass by about 40.0% and the contents of Cu, Zn, Cd and Pb in corn shoots by 27.0%, 26.8%, 27.5% and 32.8% respectively, as compared to those in EDTA treatment. While NTA&IAA treatment increased the biomass by about 29.9% and the contents of Cu, Zn, Cd and Pb in corn shoots by 31.8%, 27.6%, 17.0% and 26.9% respectively, as compared to those in NTA treatment. These results indicated that corn growth was promoted, and the biomass and the accumulation of heavy metals in plant shoots were increased significantly with the addition of IAA, which probably helps to change the cell membrane properties and the biomass distribution, resulting in the alleviation of the phytotoxicity of metals and the chelating agents.

  6. Freezing-Enhanced Dissolution of Iron Oxides: Effects of Inorganic Acid Anions.

    Science.gov (United States)

    Jeong, Daun; Kim, Kitae; Min, Dae Wi; Choi, Wonyong

    2015-11-03

    Dissolution of iron from mineral dust particles greatly depends upon the type and amount of copresent inorganic anions. In this study, we investigated the roles of sulfate, chloride, nitrate, and perchlorate on the dissolution of maghemite and lepidocrocite in ice under both dark and UV irradiation and compared the results with those of their aqueous counterparts. After 96 h of reaction, the total dissolved iron in ice (pH 3 before freezing) was higher than that in the aqueous phase (pH 3) by 6-28 times and 10-20 times under dark and UV irradiation, respectively. Sulfuric acid was the most efficient in producing labile iron under dark condition, whereas hydrochloric acid induced the most dissolution of the total and ferrous iron in the presence of light. This ice-induced dissolution result was also confirmed with Arizona Test Dust (AZTD). In the freeze-thaw cycling test, the iron oxide samples containing chloride, nitrate, or perchlorate showed a similar extent of total dissolved iron after each cycling while the sulfate-containing sample rapidly lost its dissolution activity with repeating the cycle. This unique phenomenon observed in ice might be related to the freeze concentration of protons, iron oxides, and inorganic anions in the liquid-like ice grain boundary region. These results suggest that the ice-enhanced dissolution of iron oxides can be a potential source of bioavailable iron, and the acid anions critically influence this process.

  7. Enhanced Blood Compatibility of Metallocene Polyethylene Subjected to Hydrochloric Acid Treatment for Cardiovascular Implants

    Directory of Open Access Journals (Sweden)

    Saravana Kumar Jaganathan

    2014-01-01

    Full Text Available Blood compatibility of metallocene polyethylene (mPE was investigated after modifying the surface using hydrochloric acid. Contact angle of the mPE exposed to HCl poses a decrease in its value which indicates increasing wettability and better blood compatibility. Surface of mPE analyzed by using FTIR revealed no significant changes in its functional groups after treatment. Furthermore, scanning electron microscope images supported the increasing wettability through the modifications like pit formations and etching on the acid rendered surface. To evaluate the effect of acid treatment on the coagulation cascade, prothrombin time (PT and activated partial thromboplastin time (APTT were measured. Both PT and APTT were delayed significantly (P<0.05 after 60 min exposure implying improved blood compatibility of the surfaces. Hemolysis assay of the treated surface showed a remarkable decrease in the percentage of lysis of red blood cells when compared with untreated surface. Moreover, platelet adhesion assay demonstrated that HCl exposed surfaces deter the attachment of platelets and thereby reduce the chances of activation of blood coagulation cascade. These results confirmed the enhanced blood compatibility of mPE after HCl exposure which can be utilized for cardiovascular implants like artificial vascular prostheses, implants, and various blood contacting devices.

  8. Gadoxetate Acid-Enhanced MR Imaging for HCC: A Review for Clinicians

    Directory of Open Access Journals (Sweden)

    Jendana Chanyaputhipong

    2011-01-01

    Full Text Available Hepatocellular carcinoma (HCC is increasingly being detected at an earlier stage, owing to the screening programs and regular imaging follow-up in high-risk populations. Small HCCs still pose diagnostic challenges on imaging due to decreased sensitivity and increased frequency of atypical features. Differentiating early HCC from premalignant or benign nodules is important as management differs and has implications on both the quality of life and the overall survival for the patients. Gadoxetate acid (Gd-EOB-DTPA, Primovist®, Bayer Schering Pharma is a relatively new, safe and well-tolerated liver-specific contrast agent for magnetic resonance (MR imaging of the liver that has combined perfusion- and hepatocyte-specific properties, allowing for the acquisition of both dynamic and hepatobiliary phase images. Its high biliary uptake and excretion improves lesion detection and characterization by increasing liver-to-lesion conspicuity in the added hepatobiliary phase imaging. To date, gadoxetate acid-enhanced MRI has been mostly shown to be superior to unenhanced MRI, computed tomography, and other types of contrast agents in the detection and characterization of liver lesions. This review article focuses on the evolving role of gadoxetate acid in the characterization of HCC, differentiating it from other mimickers of HCC.

  9. Acid and alkaline treatments for enhancing the growth of rhizobia in sludge

    Energy Technology Data Exchange (ETDEWEB)

    Rebah, F. B.; Tyagi, R. D. [Quebec Univ., Institut national de la recherche scientifique, Sainte Foy, PQ (Canada); Prevost, D. [Agriculture and Agri-Food Canada, Centre de recherche et de developpement sur les sols et les grandes cultures, Sainte Foy, PQ (Canada)

    2001-06-01

    Wastewater treatment processes produce large amounts of sludge. The application of sludge to agricultural soils improves the soil's physical and biological properties because it contains organic matter and plant nutrients. Wastewater sludge has been used for producing certain bacteria. It has also been proposed as an effective method for the production of rhizobia. Although the amount of sludge required for the production of bacterial inoculum is low, this new application constitutes an additional and suitable alternative for wastewater sludge recycling. The purpose of this study was to determine the potential of using acid or alkaline pre-treatments in sludges having different solid concentrations, to increase the biodegradability of organic material, thereby to enhance the growth of rhizobia, while using sludge as a culture medium. Results of the experiment show that both acid and alkaline treatments improved the rhizobial cell count and reduced mean generation time in primary and secondary sludges, but the efficiency of the treatment was also dependent on the total suspended solids (TSS) concentration. The highest cell count was obtained with primary sludge at 0.65 per cent TSS under alkaline treatment. For secondary sludge, the highest cell count was reached under acid hydrolysis. The mean generation time was reduced by both pre-treatments, with best values obtained for alkaline treatment in primary sludge. 31 refs., 6 tabs.

  10. Facile plasma-enhanced deposition of ultrathin crosslinked amino acid films for conformal biometallization.

    Science.gov (United States)

    Anderson, Kyle D; Slocik, Joseph M; McConney, Michael E; Enlow, Jesse O; Jakubiak, Rachel; Bunning, Timothy J; Naik, Rajesh R; Tsukruk, Vladimir V

    2009-03-01

    A novel method for the facile fabrication of conformal, ultrathin, and uniform synthetic amino acid coatings on a variety of practical surfaces by plasma-enhanced chemical vapor deposition is introduced. Tyrosine, which is utilized as an agent to reduce gold nanoparticles from solution, is sublimed into the plasma field and directly deposited on a variety of substrates to form a homogeneous, conformal, and robust polyamino acid coating in a one-step, solvent-free process. This approach is applicable to many practical surfaces and allows surface-induced biometallization while avoiding multiple wet-chemistry treatments that can damage many soft materials. Moreover, by placing a mask over the substrate during deposition, the tyrosine coating can be micropatterned. Upon its exposure to a solution of gold chloride, a network of gold nanoparticles forms on the surface, replicating the initial micropattern. This method of templated biometallization is adaptable to a variety of practical inorganic and organic substrates, such as silicon, glass, nitrocellulose, polystyrene, polydimethylsiloxane, polytetrafluoroethylene, polyethylene, and woven silk fibers. No special pretreatment is necessary, and the technique results in a rapid, conformal amino acid coating that can be utilized for further biometallization.

  11. Aliphatic carboxylic acids and alcohols as efficiency and elution strength enhancers in micellar liquid chromatography.

    Science.gov (United States)

    Boichenko, Alexander P; Berthod, Alain

    2010-09-03

    Micellar liquid chromatography (MLC) uses surfactant solutions as mobile phases with added organic additives to enhance both the elution strength and the chromatographic efficiency. Two aliphatic carboxylic acids (1-butanoic and 1-pentanoic) were used as MLC additives and compared with the two corresponding alcohols (1-butanol, 1-pentanol) in terms of elution strength, efficiency and selectivity. A set of 11 phenol derivatives was used as probe compounds. All micellar mobile phases were prepared with sodium dodecylsulfate (SDS) with concentration ranging from 0.05 to 0.15M and the modifier content within 1.0 and 5.0% (v/v). The elution strength of different mobile phases containing a constant amount of SDS and different amounts of modifiers; and mobile phases containing a constant amount of modifier and different SDS concentration were determined and discussed. The effect of the acid modifiers on efficiency was studied constructing van Deemter plots that showed no minimum within the 0.01-0.7mL/min flow rate range studied. Temperature effects were also studied constructing the classical van't Hoff plots. The slight curvature of the plots in the 25-70 degrees C range may indicate some modification of the surfactant-bonded moiety layer on the stationary phase surface. Since no definitive advantage of the use of aliphatic acids were established compared to their alcohol counterpart, their terrible smell will probably preclude their use as MLC organic modifiers.

  12. Enhanced biofilm production by a toluene-degrading Rhodococcus observed after exposure to perfluoroalkyl acids.

    Science.gov (United States)

    Weathers, Tess S; Higgins, Christopher P; Sharp, Jonathan O

    2015-05-05

    This study focuses on interactions between aerobic soil-derived hydrocarbon degrading bacteria and a suite of perfluorocarboxylic acids and perfluoroalkylsulfonates that are found in aqueous film-forming foams used for fire suppression. No effect on toluene degradation rate or induction time was observed when active cells of Rhodococcus jostii strain RHA1 were exposed to toluene and a mixture of perfluoroalkyl acids (PFAAs) including perfluorooctanoic acid (PFOA) and perfluorooctanesulfonate (PFOS) at concentrations near the upper bounds of groundwater relevance (11 PFAAs at 10 mg/L each). However, exposure to aqueous PFAA concentrations above 2 mg/L (each) was associated with enhanced aggregation of bacterial cells and significant increases in extracellular polymeric substance production. Flocculation was only observed during exponential growth and not elicited when PFAAs were added to resting incubations; analogous flocculation was also observed in soil enrichments. Aggregation was accompanied by 2- to 3-fold upregulation of stress-associated genes, sigF3 and prmA, during growth of this Rhodococcus in the presence of PFAAs. These results suggest that biological responses, such as microbial stress and biofilm formation, could be more prominent than suppression of co-contaminant biodegradation in subsurface locations where poly- and perfluoroalkyl substances occur with hydrocarbon fuels.

  13. Folic acid-polydopamine nanofibers show enhanced ordered-stacking via π-π interactions.

    Science.gov (United States)

    Fan, Hailong; Yu, Xiang; Liu, Yang; Shi, Zujin; Liu, Huihui; Nie, Zongxiu; Wu, Decheng; Jin, Zhaoxia

    2015-06-21

    Recent research has indicated that polydopamine and synthetic eumelanins are optoelectronic biomaterials in which one-dimensional aggregates composed of ordered-stacking oligomers have been proposed as unique organic semiconductors. However, improving the ordered-stacking of oligomers in polydopamine nanostructures is a big challenge. Herein, we first demonstrate how folic acid molecules influence the morphology and nanostructure of polydopamine via tuning the π-π interactions of oligomers. MALDI-TOF mass spectrometry reveals that porphyrin-like tetramers are characteristic of folic acid-polydopamine (FA-PDA) nanofibers. X-ray diffraction combined with simulation studies indicate that these oligomers favour aggregation into graphite-like ordered nanostructures via strong π-π interactions. High-resolution TEM characterization of carbonized FA-PDA hybrids show that in FA-PDA nanofibers the size of the graphite-like domains is over 100 nm. The addition of folic acid in polydopamine enhances the ordered stacking of oligomers in its nanostructure. Our study steps forward to discover the mystery of the structure-property relationship of FA-PDA hybrids. It paves a way to optimize the properties of PDA through the design and selection of oligomer structures.

  14. Acid-etched microtexture for enhancement of bone growth into porous-coated implants.

    Science.gov (United States)

    Hacking, S A; Harvey, E J; Tanzer, M; Krygier, J J; Bobyn, J D

    2003-11-01

    We designed an in vivo study to determine if the superimposition of a microtexture on the surface of sintered titanium beads affected the extent of bone ingrowth. Cylindrical titanium intramedullary implants were coated with titanium beads to form a porous finish using commercial sintering techniques. A control group of implants was left in the as-sintered condition. The test group was etched in a boiling acidic solution to create an irregular surface over the entire porous coating. Six experimental dogs underwent simultaneous bilateral femoral intramedullary implantation of a control implant and an acid etched implant. At 12 weeks, the implants were harvested in situ and the femora processed for undecalcified, histological examination. Eight transverse serial sections for each implant were analysed by backscattered electron microscopy and the extent of bone ingrowth was quantified by computer-aided image analysis. The extent of bone ingrowth into the control implants was 15.8% while the extent of bone ingrowth into the etched implants was 25.3%, a difference of 60% that was statistically significant. These results are consistent with other research that documents the positive effect of microtextured surfaces on bone formation at an implant surface. The acid etching process developed for this study represents a simple method for enhancing the potential of commonly available porous coatings for biological fixation.

  15. Studying Pellet Formation of a Filamentous Fungus Rhizopus oryzae to Enhance Organic Acid Production

    Science.gov (United States)

    Liao, Wei; Liu, Yan; Chen, Shulin

    Using pelletized fungal biomass can effectively improve the fermentation performance for most of fugal strains. This article studied the effects of inoculum and medium compositions such as potato dextrose broth (PDB) as carbon source, soybean peptone, calcium carbonate, and metal ions on pellet formation of Rhizopus oryzae. It has been found that metal ions had significantly negative effects on pellet formation whereas soybean peptone had positive effects. In addition PDB and calcium carbonate were beneficial to R. oryzae for growing small smooth pellets during the culture. The study also demonstrated that an inoculum size of less than 1.5×109 spores/L had no significant influence on pellet formation. Thus, a new approach to form pellets has been developed using only PDB, soybean peptone, and calcium carbonate. Meanwhile, palletized fungal fermentation significantly enhanced organic acid production. Lactic acid concentration reached 65.0 g/L in 30 h using pelletized R. oryzae NRRL 395, and fumeric acid concentration reached 31.0 g/L in 96 h using pelletized R. oryzae ATCC 20344.

  16. Flow-injection chemiluminescence determination of acetylsalicylic acid based on its enhancing effect on the lucigenin–hydrogen peroxide system.

    Science.gov (United States)

    Wabaidur, S M; Alam, S M; Alothmana, Z A; Eldesokya, Gaber

    2014-09-01

    A sensitive flow-injection chemiluminescence method for the determination of acetylsalicylic acid is described. It is based on the enhanced chemiluminescent emission of the alkaline lucigenin–H2O2 system by acetylsalicylic acid. The difference in chemiluminescent intensity of alkaline lucigenin–H2O2 in the presence of acetylsalicylic acid from that in the absence of acetylsalicylic acid was linear at acetylsalicylic acid concentrations in the range of 0.0029–47.37 μg/mL, with detection and quantification limits of 0.0011 and 0.0029 μg/mL, respectively. The correlation coefficient of the working curve was 0.9983. The relative standard deviation (n = 10) for 25 μg/mL acetylsalicylic acid is 1.95%. All experimental parameters were optimized. The method was successfully applied to the determination of acetylsalicylic acid in pharmaceutical preparations. The recovery results obtained by the method were satisfactory.

  17. Identification of amino acids associated with skeletal muscle growth in late gestation and at weaning in lambs of well-nourished sheep.

    Science.gov (United States)

    Sales, F A; Pacheco, D; Blair, H T; Kenyon, P R; Nicholas, G; Senna Salerno, M; McCoard, S A

    2014-11-01

    The objective of this study was to determine the association between intracellular free AA (FAA) profiles in skeletal muscle with muscle growth in twin and singleton fetuses in late pregnancy and at weaning, under an ad libitum feeding regime of the dam. Plasma from singleton- (n = 9) and twin-bearing (n = 10) ewes at d 140 of pregnancy and FAA in the semitendinosus muscle (STM) from the corresponding fetuses were studied. At weaning, intracellular STM FAA concentrations were compared between twins at the same age as singletons (Twin(age); n = 17) and at the same weight as singletons (Twin(wt); n = 17) to that of singletons (n = 20). Twin fetuses were 15% lighter (P = 0.03) with a 20% lighter STM (P = 0.02) compared to singletons. Maternal plasma FAA were similar (P ≥ 0.17) between singleton- and twin-bearing ewes. Twin fetuses had greater (P muscle concentration and STM weight at weaning. Males differed from females in intracellular FAA both in late pregnancy and at weaning. Twins had reduced RNA content during pregnancy and at weaning, suggesting a lower capacity for protein accretion. These data suggest that specific FAA concentrations are associated with differences in muscle growth during late pregnancy, notably arginine and glutamine, and reduced protein synthesis capacity. However, the relevance of specific FAA varies according to stage of development and sex of the lamb.

  18. Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis.

    Science.gov (United States)

    Fang, Linchuan; Su, Lingye; Sun, Xiaoming; Li, Xinbo; Sun, Mengxiang; Karungo, Sospeter Karanja; Fang, Shuang; Chu, Jinfang; Li, Shaohua; Xin, Haiping

    2016-04-01

    The growth and fruit quality of grapevines are widely affected by abnormal climatic conditions such as water deficits, but many of the precise mechanisms by which grapevines respond to drought stress are still largely unknown. Here, we report that VaNAC26, a member of the NAC transcription factor family, was upregulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardy wild Vitis species. Heterologous overexpression of VaNAC26 enhanced drought and salt tolerance in transgenic Arabidopsis. Higher activities of antioxidant enzymes and lower concentrations of H2O2 and O2 (-) were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicated that scavenging by reactive oxygen species (ROS) was enhanced by VaNAC26 in transgenic lines. Microarray-based transcriptome analysis revealed that genes related to jasmonic acid (JA) synthesis and signaling were upregulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on the NAC recognition sequence (NACRS) motif, which broadly exists in the promoter regions of upregulated genes in transgenic lines. Endogenous JA content significantly increased in the VaNAC26-OE lines 2 and 3. Our data suggest that VaNAC26 responds to abiotic stresses and may enhance drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis.

  19. Expression of Vitis amurensis NAC26 in Arabidopsis enhances drought tolerance by modulating jasmonic acid synthesis

    Science.gov (United States)

    Fang, Linchuan; Su, Lingye; Sun, Xiaoming; Li, Xinbo; Sun, Mengxiang; Karungo, Sospeter Karanja; Fang, Shuang; Chu, Jinfang; Li, Shaohua; Xin, Haiping

    2016-01-01

    The growth and fruit quality of grapevines are widely affected by abnormal climatic conditions such as water deficits, but many of the precise mechanisms by which grapevines respond to drought stress are still largely unknown. Here, we report that VaNAC26, a member of the NAC transcription factor family, was upregulated dramatically during cold, drought and salinity treatments in Vitis amurensis, a cold and drought-hardy wild Vitis species. Heterologous overexpression of VaNAC26 enhanced drought and salt tolerance in transgenic Arabidopsis. Higher activities of antioxidant enzymes and lower concentrations of H2O2 and O2 − were found in VaNAC26-OE lines than in wild type plants under drought stress. These results indicated that scavenging by reactive oxygen species (ROS) was enhanced by VaNAC26 in transgenic lines. Microarray-based transcriptome analysis revealed that genes related to jasmonic acid (JA) synthesis and signaling were upregulated in VaNAC26-OE lines under both normal and drought conditions. VaNAC26 showed a specific binding ability on the NAC recognition sequence (NACRS) motif, which broadly exists in the promoter regions of upregulated genes in transgenic lines. Endogenous JA content significantly increased in the VaNAC26-OE lines 2 and 3. Our data suggest that VaNAC26 responds to abiotic stresses and may enhance drought tolerance by transcriptional regulation of JA synthesis in Arabidopsis. PMID:27162276

  20. Production of Polyamines Is Enhanced by Endogenous Abscisic Acid in Maize Seedlings Subjected to Salt Stress

    Institute of Scientific and Technical Information of China (English)

    Jun LIU; Ming-Yi JIANG; Yi-Feng ZHOU; You-Liang LIU

    2005-01-01

    It is known that salt stress and exogenously applied abscisic acid (ABA) can enhance the polyamine content in plants and that salt stress itself can lead to an increase in endogenous ABA production.In the present study, the relationships between salt-induced ABA and polyamine accumulation were investigated using ABA-deficient mutant (vp5/vp5) maize (Zea mays L.) seedlings and ABA and polyamine :biosynthesis inhibitors. The results show that reduced endogenous ABA levels, as a result of either the mutation or by using a chemical inhibitor (sodium tungstate), also reduced the accumulation of polyamines in salt-stressed leaves of maize seedlings. The polyamine synthesis inhibitors D-arginine and αdifluoromethylornithine also reduced the polyamine content of the leaves of maize seedling under salt stress. Both ABA and polyamine enhanced the dry weight accumulation of salt-stressed seedlings and also increased the activities of the two dominant tonoplast membrane enzymes, H+-ATPase and H+-PPase, when plants were under salt stress. The results suggest that salt stress induces an increase in endogenous ABA levels, which then enhances polyamine synthesis. Such responses may increase a plant's tolerance to salt.

  1. Chromate enhanced visible light driven TiO₂ photocatalytic mechanism on Acid Orange 7 photodegradation.

    Science.gov (United States)

    Wang, Yeoung-Sheng; Shen, Jyun-Hong; Horng, Jao-Jia

    2014-06-15

    When hexavalent chromium (Cr(VI)) is added to a TiO2 photocatalytic reaction, the decolorization and mineralization efficiencies of azo dyes Acid Orange 7 (AO7) are enhanced even though the mechanism is unclear. This study used 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) as the scavenger and the analysis of Electron Spin Resonance (ESR) to investigate this enhancement effect by observing the hydroxyl radical (OH) generation of the Cr(VI)/TiO2 system under UV and visible light (Vis) irradiation. With Cr(VI), the decolorization efficiencies were approximately 95% and 62% under UV and Vis, and those efficiencies were 25% less in the absence of Cr(VI). The phenomena of the DMPO-OH signals during the ESR analysis under Vis 405 and 550 nm irradiation were obviously the enhancement effects of Cr(VI) in aerobic conditions. In anoxic conditions, the catalytic effects of Cr(VI) could not be achieved due to the lack of a redox reaction between Cr(VI) and the adsorbed oxygen at the oxygen vacancy sites on the TiO2 surfaces. The results suggest that by introducing the agents of redox reactions such as chromate ions, we could lower the photoenergy of TiO2 needed and allow Vis irradiation to activate photocatalysis.

  2. Enhancing post anaerobic digestion of full-scale anaerobically digested sludge using free nitrous acid treatment.

    Science.gov (United States)

    Zhang, Tingting; Wang, Qilin; Ye, Liu; Yuan, Zhiguo

    2016-05-01

    In some wastewater treatment plants (WWTPs), the ever increasing production of sludge with the expanding population overloaded the anaerobic digestion which compromises the sludge reduction efficiency. Post anaerobic digestion of anaerobically digested sludge (ADS) has been applied to enhance sludge reduction, however, to a very limited extent. This study verified the effectiveness of free nitrous acid (FNA i.e. HNO2) pre-treatment on enhancing full-scale ADS degradation in post anaerobic digestion. The ADS collected from a full-scale WWTP was subject to FNA treatment at concentrations of 0.77, 1.54, 2.31, 3.08, and 3.85 mg N/L for 24 h followed by biochemical methane potential tests. The FNA treatment at all concentrations resulted in an increase (from 1.5-3.1 % compared to the control) in sludge reduction with the highest improvement achieved at 0.77 mg HNO2-N/L. The FNA treatment at this concentration also resulted in the highest increase in methane production (40 %) compared to the control. The economic analysis indicates that FNA treatment is economically attractive for enhancing post anaerobic digestion of full-scale ADS.

  3. Improved focal liver lesion detection by increasing flip angle during gadoxetic acid-enhancement in MRI

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Jy [Dept. of Medical science Graduate school, Chonnam National University, Kwangju (Korea, Republic of); Kim, Young Keun [Dept. of Radiotechnology, Gwang-ju Health university, Gwangju (Korea, Republic of)

    2015-06-15

    To study the differences of focal liver lesion image detection at 3 minute, 10 minute and 15 minute time points on gadoxetic acid (GA)’s enhanced MR imaging with a flip angle (FA) of 30° compared with a 11°. The subjects were 69 patients evaluated with GA enhanced MR imaging with 3.0T MR scanner. The patients are total 35(23 men and 7 women at the mean age of 60.4 years), hepatocellular carcinoma(23) and metastsis(12) except for normal, cyst and hemangioma. After GA was injected, FA 11° and 30° images were obtained at 3 minute, 10 minute and 15 minute time points respectively. After quantitative and qualitative assessment of each image was done, statistical analysis was performed by using the independent sample T-test. From both quantitative and qualitative assessment of 3 minute and 10 minute MR images after the injection of GA, FA 30° images was found to be superior than FA 11°, but there were no statistical significance. However, at 15 minute time point, Statistically significant FA 30° image(p<0.05) was better than FA 11° therefore, the FA 30° improves the focal liver lesion detection. FA 30° of MR image can detect liver lesion more sensitively than the existing FA11° image after GA contrast enhancement at 15 minute time point.

  4. Retinoic acid enhances lactoferrin-induced IgA responses by increasing betaglycan expression.

    Science.gov (United States)

    Lee, Jeong-Min; Jang, Young-Saeng; Jin, Bo-Ra; Kim, Sun-Jin; Kim, Hyeon-Jin; Kwon, Bo-Eun; Ko, Hyun-Jeong; Yoon, Sung-Il; Lee, Geun-Shik; Kim, Woan-Sub; Seo, Goo-Young; Kim, Pyeung-Hyeun

    2016-11-01

    Lactoferrin (LF) and retinoic acid (RA) are enriched in colostrum, milk, and mucosal tissues. We recently showed that LF-induced IgA class switching through binding to betaglycan (transforming growth factor-beta receptor III, TβRIII) and activation of canonical TGF-β signaling. We investigated the combined effect of LF and RA on the overall IgA response. An increase in IgA production by LF was further augmented by RA. This combination effect was also evident in Ig germ-line α (GLα) transcription and GLα promoter activity, indicating that LF in cooperation with RA increased IgA isotype switching. We subsequently found that RA enhanced TβRIII expression and that this increase contributed to LF-stimulated IgA production. In addition to the IgA response, LF and RA in combination also enhanced the expression of the gut-homing molecules C-C chemokine receptor 9 (CCR9) and α4β7 on B cells. Finally, peroral administration of LF and RA enhanced the frequency of CCR9(+)IgA(+) plasma cells in the lamina propria. Taken together, these results suggest that LF in cooperation with RA can contribute to the establishment of gut IgA responses.

  5. Genetic engineering for skeletal regenerative medicine.

    Science.gov (United States)

    Gersbach, Charles A; Phillips, Jennifer E; García, Andrés J

    2007-01-01

    The clinical challenges of skeletal regenerative medicine have motivated significant advances in cellular and tissue engineering in recent years. In particular, advances in molecular biology have provided the tools necessary for the design of gene-based strategies for skeletal tissue repair. Consequently, genetic engineering has emerged as a promising method to address the need for sustained and robust cellular differentiation and extracellular matrix production. As a result, gene therapy has been established as a conventional approach to enhance cellular activities for skeletal tissue repair. Recent literature clearly demonstrates that genetic engineering is a principal factor in constructing effective methods for tissue engineering approaches to bone, cartilage, and connective tissue regeneration. This review highlights this literature, including advances in the development of efficacious gene carriers, novel cell sources, successful delivery strategies, and optimal target genes. The current status of the field and the challenges impeding the clinical realization of these approaches are also discussed.

  6. Raman and surface-enhanced Raman spectroscopy of amino acids and nucleotide bases for target bacterial vibrational mode identification

    Science.gov (United States)

    Guicheteau, Jason; Argue, Leanne; Hyre, Aaron; Jacobson, Michele; Christesen, Steven D.

    2006-05-01

    Raman and surface-enhanced Raman spectroscopy (SERS) studies of bacteria have reported a wide range of vibrational mode assignments associated with biological material. We present Raman and SER spectra of the amino acids phenylalanine, tyrosine, tryptophan, glutamine, cysteine, alanine, proline, methionine, asparagine, threonine, valine, glycine, serine, leucine, isoleucine, aspartic acid and glutamic acid and the nucleic acid bases adenosine, guanosine, thymidine, and uridine to better characterize biological vibrational mode assignments for bacterial target identification. We also report spectra of the bacteria Bacillus globigii, Pantoea agglomerans, and Yersinia rhodei along with band assignments determined from the reference spectra obtained.

  7. Systems-based Discovery of Tomatidine as a Natural Small Molecule Inhibitor of Skeletal Muscle Atrophy*

    Science.gov (United States)

    Dyle, Michael C.; Ebert, Scott M.; Cook, Daniel P.; Kunkel, Steven D.; Fox, Daniel K.; Bongers, Kale S.; Bullard, Steven A.; Dierdorff, Jason M.; Adams, Christopher M.

    2014-01-01

    Skeletal muscle atrophy is a common and debilitating condition that lacks an effective therapy. To address this problem, we used a systems-based discovery strategy to search for a small molecule whose mRNA expression signature negatively correlates to mRNA expression signatures of human skeletal muscle atrophy. This strategy identified a natural small molecule from tomato plants, tomatidine. Using cultured skeletal myotubes from both humans and mice, we found that tomatidine stimulated mTORC1 signaling and anabolism, leading to accumulation of protein and mitochondria, and ultimately, cell growth. Furthermore, in mice, tomatidine increased skeletal muscle mTORC1 signaling, reduced skeletal muscle atrophy, enhanced recovery from skeletal muscle atrophy, stimulated skeletal muscle hypertrophy, and increased strength and exercise capacity. Collectively, these results identify tomatidine as a novel small molecule inhibitor of muscle atrophy. Tomatidine may have utility as a therapeutic agent or lead compound for skeletal muscle atrophy. PMID:24719321

  8. Passive leg movement enhances interstitial VEGF protein, endothelial cell proliferation, and eNOS mRNA content in human skeletal muscle

    DEFF Research Database (Denmark)

    Hellsten, Ylva; Rufener, Nora; Nielsen, Jens J

    2008-01-01

    were analyzed for mRNA content of VEGF, endothelial nitric oxide synthase (eNOS), and matrix metalloproteinase-2 (MMP-2). The passive leg movement caused an increase (P dialysate...... to cultured endothelial cells revealed that dialysate obtained during leg movement induced a 3.2-fold higher proliferation rate (P dialysate obtained at rest. Passive movement also enhanced (P

  9. Lewis Acids as Activators in CBS-Catalysed Diels-Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4.

    Science.gov (United States)

    Nödling, Alexander R; Möckel, Robert; Tonner, Ralf; Hilt, Gerhard

    2016-09-05

    The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While (2) H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT-IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ((2) H) values and rate constants kDA , which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid-CBS complexes. Unexpectedly, a significant deviation was found for SnCl4 as Lewis acid. The SnCl4 -CBS adduct was much more reactive than the Δδ((2) H) values predicted and gave similar reaction rates to those observed for the prominent AlBr3 -CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid-CBS-naphthoquinone adducts and kDA could be found. For the SnCl4 -CBS-naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA-NOCV) calculations revealed the relevant interactions and activation mode of SnCl4 as Lewis acid in Diels-Alder reactions. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Ion pair formation as a possible mechanism for the enhancement effect of lauric acid on the transdermal permeation of ondansetron.

    Science.gov (United States)

    Dimas, Dimitrios A; Dallas, Paraskevas P; Rekkas, Dimitrios M

    2004-08-01

    Transdermal application can be an alternative drug delivery route for ondansetron, an antiemetic drug. Previous studies found that fatty acids, namely oleic and lauric, were the most effective penetration enhancers. The aim of this study was to investigate the formation of an ion pair between ondansetron and lauric acid as a possible mechanism of its enhancing action. Several techniques were used to reveal the formation of an ion pair complex. Partitioning experiments, where the n-octanol/water coefficient was measured, showed an increase in the distribution coefficient in the presence of the acid, possibly as a result of the formation of more lipophilic ion pairs between the charged molecules of ondansetron and lauric acid. Further evidence of complex formation between ondansetron and lauric acid, was gained from the 13C-nuclear magnetic resonance (13C-NMR) spectra of ondansetron, lauric acid, and their mixture (molar ratio 1:1). The NMR spectra revealed alterations to the magnetic environment of the carbon atoms adjacent to the ionized group, which are the carbonyl group of the acid and the nitrogen of the imidazole ring of ondansetron. This evidence substantiates the theory of ion pair formation. Finally, thermal analysis of the binary mixtures of ondansetron and lauric acid revealed the formation of an additional compound, with different melting point from pure ondansetron and lauric acid, which is thermodynamically favored.

  11. Endoplasmic reticulum-located PDAT1-2 from castor bean enhances hydroxy fatty acid accumulation in transgenic plants.

    Science.gov (United States)

    Kim, Hyun Uk; Lee, Kyeong-Ryeol; Go, Young Sam; Jung, Jin Hee; Suh, Mi-Chung; Kim, Jong Bum

    2011-06-01

    Ricinoleic acid (12-hydroxy-octadeca-9-enoic acid) is a major unusual fatty acid in castor oil. This hydroxy fatty acid is useful in industrial materials. This unusual fatty acid accumulates in triacylglycerol (TAG) in the seeds of the castor bean (Ricinus communis L.), even though it is synthesized in phospholipids, which indicates that the castor plant has an editing enzyme, which functions as a phospholipid:diacylglycerol acyltransferase (PDAT) that is specific to ricinoleic acid. Transgenic plants containing fatty acid Δ12-hydroxylase encoded by the castor bean FAH12 gene produce a limited amount of hydroxy fatty acid, a maximum of around 17% of TAGs present in Arabidopsis seeds, and this unusual fatty acid remains in phospholipids of cell membranes in seeds. Identification of ricinoleate-specific PDAT from castor bean and manipulation of the phospholipid editing system in transgenic plants will enhance accumulation of the hydroxy fatty acid in transgenic seeds. The castor plant has three PDAT genes; PDAT1-1 and PDAT2 are homologs of PDAT, which are commonly found in plants; however, PDAT1-2 is newly grouped as a castor bean-specific gene. PDAT1-2 is expressed in developing seeds and localized in the endoplasmic reticulum, similar to FAH12, indicating its involvement in conversion of ricinoleic acid into TAG. PDAT1-2 significantly enhances accumulation of total hydroxy fatty acid up to 25%, with a significant increase in castor-like oil, 2-OH TAG, in seeds of transgenic Arabidopsis, which is an identification of the key gene for oilseed engineering in production of unusual fatty acids.

  12. Enhanced optoelectronic quality of perovskite thin films with hypophosphorous acid for planar heterojunction solar cells.

    Science.gov (United States)

    Zhang, Wei; Pathak, Sandeep; Sakai, Nobuya; Stergiopoulos, Thomas; Nayak, Pabitra K; Noel, Nakita K; Haghighirad, Amir A; Burlakov, Victor M; deQuilettes, Dane W; Sadhanala, Aditya; Li, Wenzhe; Wang, Liduo; Ginger, David S; Friend, Richard H; Snaith, Henry J

    2015-11-30

    Solution-processed metal halide perovskite semiconductors, such as CH3NH3PbI3, have exhibited remarkable performance in solar cells, despite having non-negligible density of defect states. A likely candidate is halide vacancies within the perovskite crystals, or the presence of metallic lead, both generated due to the imbalanced I/Pb stoichiometry which could evolve during crystallization. Herein, we show that the addition of hypophosphorous acid (HPA) in the precursor solution can significantly improve the film quality, both electronically and topologically, and enhance the photoluminescence intensity, which leads to more efficient and reproducible photovoltaic devices. We demonstrate that the HPA can reduce the oxidized I2 back into I(-), and our results indicate that this facilitates an improved stoichiometry in the perovskite crystal and a reduced density of metallic lead.

  13. Conjugation of curcumin onto hyaluronic acid enhances its aqueous solubility and stability.

    Science.gov (United States)

    Manju, S; Sreenivasan, K

    2011-07-01

    Polymer-drug conjugates have gained much attention largely to circumvent lower drug solubility and to enhance drug stability. Curcumin is widely known for its medicinal properties including its anticancer efficacy. One of the serious drawbacks of curcumin is its poor water solubility which leads to reduced bioavailability. With a view to address these issues, we synthesized hyaluronic acid-curcumin (HA-Cur) conjugate. The drug conjugate was characterized using FT-IR, NMR, Dynamic light scattering and TEM techniques. The conjugates, interestingly found to assembles as micelles in aqueous phase. The formation of micelles seems to improve the stability of the drug in physiological pH. We also assessed cytotoxicity of the conjugate using L929 fibroblast cells and quantified by MTT assay. Copyright © 2011 Elsevier Inc. All rights reserved.