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Sample records for acids increased significantly

  1. Down-regulation of crambe fatty acid desaturase and elongase in Arabidopsis and crambe resulted in significantly increased oleic acid content in seed oil.

    PubMed

    Li, Xueyuan; Mei, Desheng; Liu, Qing; Fan, Jing; Singh, Surinder; Green, Allan; Zhou, Xue-Rong; Zhu, Li-Hua

    2016-01-01

    High oleic oil is an important industrial feedstock that has been one of the main targets for oil improvement in a number of oil crops. Crambe (Crambe abyssinica) is a dedicated oilseed crop, suitable for industrial oil production. In this study, we down-regulated the crambe fatty acid desaturase (FAD) and fatty acid elongase (FAE) genes for creating high oleic seed oil. We first cloned the crambe CaFAD2, CaFAD3 and CaFAE1 genes. Multiple copies of each of these genes were isolated, and the highly homologous sequences were used to make RNAi constructs. These constructs were first tested in Arabidopsis, which led to the elevated oleic or linoleic levels depending on the genes targeted, indicating that the RNAi constructs were effective in regulating the expression of the target genes in nonidentical but closely related species. Furthermore, down-regulation of CaFAD2 and CaFAE1 in crambe with the FAD2-FAE1 RNAi vector resulted in even more significant increase in oleic acid level in the seed oil with up to 80% compared to 13% for wild type. The high oleic trait has been stable in subsequent five generations and the GM line grew normally in greenhouse. This work has demonstrated the great potential of producing high oleic oil in crambe, thus contributing to its development into an oil crop platform for industrial oil production. PMID:25998013

  2. A Naturally Occurring Single Amino Acid Replacement in Multiple Gene Regulator of Group A Streptococcus Significantly Increases Virulence

    PubMed Central

    Sanson, Misu; O'Neill, Brian E.; Kachroo, Priyanka; Anderson, Jeff R.; Flores, Anthony R.; Valson, Chandni; Cantu, Concepcion C.; Makthal, Nishanth; Karmonik, Christof; Fittipaldi, Nahuel; Kumaraswami, Muthiah; Musser, James M.; Olsen, Randall J.

    2016-01-01

    Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype–patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes. PMID:25476528

  3. A naturally occurring single amino acid replacement in multiple gene regulator of group A Streptococcus significantly increases virulence.

    PubMed

    Sanson, Misu; O'Neill, Brian E; Kachroo, Priyanka; Anderson, Jeff R; Flores, Anthony R; Valson, Chandni; Cantu, Concepcion C; Makthal, Nishanth; Karmonik, Christof; Fittipaldi, Nahuel; Kumaraswami, Muthiah; Musser, James M; Olsen, Randall J

    2015-02-01

    Single-nucleotide polymorphisms (SNPs) are the most common source of genetic variation within a species; however, few investigations demonstrate how naturally occurring SNPs may increase strain virulence. We recently used group A Streptococcus as a model pathogen to study bacteria strain genotype-patient disease phenotype relationships. Whole-genome sequencing of approximately 800 serotype M59 group A Streptococcus strains, recovered during an outbreak of severe invasive infections across North America, identified a disproportionate number of SNPs in the gene encoding multiple gene regulator of group A Streptococcus (mga). Herein, we report results of studies designed to test the hypothesis that the most commonly occurring SNP, encoding a replacement of arginine for histidine at codon 201 of Mga (H201R), significantly increases virulence. Whole transcriptome analysis revealed that the H201R replacement significantly increased expression of mga and 54 other genes, including many proven virulence factors. Compared to the wild-type strain, a H201R isogenic mutant strain caused significantly larger skin lesions in mice. Serial quantitative bacterial culture and noninvasive magnetic resonance imaging also demonstrated that the isogenic H201R strain was significantly more virulent in a nonhuman primate model of joint infection. These findings show that the H201R replacement in Mga increases the virulence of M59 group A Streptococcus and provide new insight to how a naturally occurring SNP in bacteria contributes to human disease phenotypes. PMID:25476528

  4. Addition of an N-terminal epitope tag significantly increases the activity of plant fatty acid desaturases expressed in yeast cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saccharomyces cerevisiae shows great potential for development of bioreactor systems geared towards the production of high-value lipids such as polyunsaturated omega-3 fatty acids, the yields of which are largely dependent on the activity of ectopically-expressed enzymes. Here we show that the addit...

  5. Increase of α1-acid glycoprotein after treatment with amitriptyline

    PubMed Central

    Baumann, P.; Tinguely, D.; Schöpf, J.

    1982-01-01

    Sixteen primary depressive patients were treated for 3 weeks with amitriptyline 150 mg daily. In thirteen patients the plasma level of α1-acid glycoprotein (AAG) significantly increased after the treatment but the albumin levels did not change. PMID:7104160

  6. A single amino acid change (Y318F) in the L-arabitol dehydrogenase (LadA) from Aspergillus niger results in a significant increase in affinity for D-sorbitol

    PubMed Central

    2009-01-01

    Background L-arabitol dehydrogenase (LAD) and xylitol dehydrogenase (XDH) are involved in the degradation of L-arabinose and D-xylose, which are among the most abundant monosaccharides on earth. Previous data demonstrated that LAD and XDH not only differ in the activity on their biological substrate, but also that only XDH has significant activity on D-sorbitol and may therefore be more closely related to D-sorbitol dehydrogenases (SDH). In this study we aimed to identify residues involved in the difference in substrate specificity. Results Phylogenetic analysis demonstrated that LAD, XDH and SDH form 3 distinct groups of the family of dehydrogenases containing an Alcohol dehydrogenase GroES-like domain (pfam08240) and likely have evolved from a common ancestor. Modelling of LadA and XdhA of the saprobic fungus Aspergillus niger on human SDH identified two residues in LadA (M70 and Y318), that may explain the absence of activity on D-sorbitol. While introduction of the mutation M70F in LadA of A. niger resulted in a nearly complete enzyme inactivation, the Y318F resulted in increased activity for L-arabitol and xylitol. Moreover, the affinity for D-sorbitol was increased in this mutant. Conclusion These data demonstrates that Y318 of LadA contributes significantly to the substrate specificity difference between LAD and XDH/SDH. PMID:19674460

  7. Significant increase in travel-associated dengue fever in Germany.

    PubMed

    Allwinn, Regina

    2011-08-01

    Increasing numbers of dengue fever (DF) cases reflect the increasing travel mobility together with the expanding geographical distribution of the vector Aedes aegypti. Compared with earlier surveys in Germany, higher incidences occur and correlate well with ongoing outbreaks. Therefore, we investigated 767 serum samples from 594 returning travellers with suspected DF between 2005 and 2010, which where sent from different hospitals in the drainage area Frankfurt/Main. Established diagnostic assays were ELISA, immunofluorescence and chromatographic tests. We obtained 112 dengue-seropositive serum samples from totally 60 patients: the detection rate was 10.1% (60 out of 594). A significant increase was found in 2010. Most patients were aged between 40 and 49, and indirect immunofluorescence technique indicated mainly DF serotype 2. Actual data reveal a significant rise in imported DF cases in 2010 according to an increasing risk to acquire DF virus infection. Nevertheless, dengue haemorrhagic fever and dengue shock syndrome are still rare in travellers, but those with a history of dengue should be tested for DF serotypes and advised to protect themselves well from mosquitoes when travelling to endemic areas. PMID:21311908

  8. Sixteen-Day Bedrest Significantly Increases Plasma Colloid Osmotic Pressure

    NASA Technical Reports Server (NTRS)

    Hargens, Alan R.; Hsieh, S. T.; Murthy, G.; Ballard, R. E.; Convertino, V. A.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    Upon exposure to microgravity, astronauts lose up to 10% of their total plasma volume, which may contribute to orthostatic intolerance after space flight. Because plasma colloid osmotic pressure (COP) is a primary factor maintaining plasma volume, our objective was to measure time course changes in COP during microgravity simulated by 6 deg. head-down tilt (HDT). Seven healthy male subjects (30-55 years of age) were placed in HDT for 16 days. For the purpose of another study, three of the seven subjects were chosen to exercise on a cycle ergometer on day 16. Blood samples were drawn immediately before bedrest on day 14 of bedrest, 18-24 hours following exercise while all subjects were still in HDT and 1 hour following bedrest termination. Plasma COP was measured in all 20 microliter EDTA-treated samples using an osmometer fitted with a PM 30 membrane. Data were analyzed with paired and unpaired t-tests. Plasma COP on day 14 of bedrest (29.9 +/- 0.69 mmHg) was significantly higher (p less than 0.005) than the control, pre-bedrest value (23.1 +/- 0.76 mmHg). At one hour of upright recovery after HDT, plasma COP remained significantly elevated (exercise: 26.9 +/- 0.87 mmHg; no exercise: 26.3 +/- 0.85 mmHg). Additionally, exercise had no significant effect on plasma COP 18-24 hours following exercise (exercise: 27.8 +/- 1.09 mmHg; no exercise: 27.1 +/- 0.78 mmHg). Our results demonstrate that plasma COP increases significantly with microgravity simulated by HDT. However, preliminary results indicate exercise during HDT does not significantly affect plasma COP.

  9. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity.

    PubMed

    Simopoulos, Artemis P

    2016-01-01

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

  10. An Increase in the Omega-6/Omega-3 Fatty Acid Ratio Increases the Risk for Obesity

    PubMed Central

    Simopoulos, Artemis P.

    2016-01-01

    In the past three decades, total fat and saturated fat intake as a percentage of total calories has continuously decreased in Western diets, while the intake of omega-6 fatty acid increased and the omega-3 fatty acid decreased, resulting in a large increase in the omega-6/omega-3 ratio from 1:1 during evolution to 20:1 today or even higher. This change in the composition of fatty acids parallels a significant increase in the prevalence of overweight and obesity. Experimental studies have suggested that omega-6 and omega-3 fatty acids elicit divergent effects on body fat gain through mechanisms of adipogenesis, browning of adipose tissue, lipid homeostasis, brain-gut-adipose tissue axis, and most importantly systemic inflammation. Prospective studies clearly show an increase in the risk of obesity as the level of omega-6 fatty acids and the omega-6/omega-3 ratio increase in red blood cell (RBC) membrane phospholipids, whereas high omega-3 RBC membrane phospholipids decrease the risk of obesity. Recent studies in humans show that in addition to absolute amounts of omega-6 and omega-3 fatty acid intake, the omega-6/omega-3 ratio plays an important role in increasing the development of obesity via both AA eicosanoid metabolites and hyperactivity of the cannabinoid system, which can be reversed with increased intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A balanced omega-6/omega-3 ratio is important for health and in the prevention and management of obesity. PMID:26950145

  11. Increased diffuse radiation fraction does not significantly accelerate plant growth

    NASA Astrophysics Data System (ADS)

    Angert, Alon; Krakauer, Nir

    2010-05-01

    ), will result in a measurable decrease (~0.6ppm) in the seasonal CO2 minimum. This holds regardless of whether the sink is the result of 1) An increase in NPP, or 2) The combined effect of a temperature-driven decrease in heterotrophic respiration (Rh) and no change in NPP. This is since both NPP and Rh peak in summer. By contrast, observations from the NOAA global CO2 monitoring network show the opposite change in the seasonal minimum in 1992 and 1993 (~0.2ppm increase) both at Mauna Loa, and in the Marine Boundary Layer mean (>20° N), which is hard to reconcile with increased NPP in northern summer. Another indicator of annual NPP is tree wood increment. Previous work (Krakauer et al., 2003) showed that the average response in tree ring series after past Pinatubo-size volcanic eruptions implied lower NPP north of 45° N, presumably as a result of shorter growing season and lower total irradiance induced by scattering aerosols, and no significant change in NPP at lower latitudes. Here we show that In 1992, after the Pinatubo eruption, ring width in the 25° N-45° N band was 99.3±2.9% of average (n=351 sites), similar to the average of 100.4±2.2% over past eruptions (n=15 eruptions) (Uncertainty is given as 2 SE.). These results are also inconsistent with substantial NPP enhancement, although a limitation of the tree-ring approach is that available measurements do not uniformly sample the latitude band. The combined evidence of tree rings and the CO2 seasonal cycle shows that the enhancement of NPP by scattering aerosols on annual timescales is weak. This result suggests that reducing aerosols through stricter pollution controls may strengthen the land carbon sink, while geo-engineering schemes which aim to mitigate global warming by spreading scattering aerosols in the stratosphere may weaken it.

  12. Increased isoprostane levels in oleic acid-induced lung injury

    SciTech Connect

    Ono, Koichi; Koizumi, Tomonobu; Tsushima, Kenji; Yoshikawa, Sumiko; Yokoyama, Toshiki; Nakagawa, Rikimaru; Obata, Toru

    2009-10-16

    The present study was performed to examine a role of oxidative stress in oleic acid-induced lung injury model. Fifteen anesthetized sheep were ventilated and instrumented with a lung lymph fistula and vascular catheters for blood gas analysis and measurement of isoprostanes (8-epi prostaglandin F2{alpha}). Following stable baseline measurements, oleic acid (0.08 ml/kg) was administered and observed 4 h. Isoprostane was measured by gas chromatography mass spectrometry with the isotope dilution method. Isoprostane levels in plasma and lung lymph were significantly increased 2 h after oleic acid administration and then decreased at 4 h. The percent increases in isoprostane levels in plasma and lung lymph at 2 h were significantly correlated with deteriorated oxygenation at the same time point, respectively. These findings suggest that oxidative stress is involved in the pathogenesis of the pulmonary fat embolism-induced acute lung injury model in sheep and that the increase relates with the deteriorated oxygenation.

  13. Significance of increased `splenic uptake' on liver scintiscanning

    PubMed Central

    Eddleston, A. L. W. F.; Blendis, L. M.; Osborn, S. B.; Williams, Roger

    1969-01-01

    Peak activity over the spleen as a percentage of peak activity over the liver was measured in 265 99mTechnetium sulphur colloid liver scintiscans. The value exceeded 70% in 50 cases. In 32 of these cirrhosis was present; the other 18 scans were from patients with a wide variety of conditions, including secondary deposits, hepatitis, and diseases involving the reticuloendothelial system. A measure of the total activity in the spleen was derived from the peak activity and the length of the spleen. In cirrhosis this was closely related to the finding of oesophageal varices thus showing the importance of a collateral circulation (which allows colloid to bypass the liver) in the increased uptake of colloid by the spleen. In eight patients with hepatosplenomegaly due to blood dyscrasia or disease involving the reticuloendothelial system, total activities in the liver and spleen were estimated from the anteroposterior colour dot scan, and both liver and spleen blood flow were measured by methods independent of reticuloendothelial cell function. The results showed that the main factor causing increased uptake of colloid by the spleen in these diseases was an increased blood flow in the spleen relative to that in the liver. ImagesFIG. 1FIG. 5 PMID:5386628

  14. Increased expression of β-glucosidase A in Clostridium thermocellum 27405 significantly increases cellulase activity

    PubMed Central

    Maki, Miranda L.; Armstrong, Lachlan; Leung, Kam Tin; Qin, Wensheng

    2013-01-01

    β-glucosidase A (bglA) in Clostridium thermocellum 27405 was increased by expression from shuttle vector pIBglA in attempts to increase cellulase activity and ethanol titer by lowering the end product inhibition of cellulase. Through a modified electrotransformation protocol C. thermocellum transformant (+MCbglA) harbouring pIBglA was produced. The β-glucosidase activity of +MCbglA was 2.3- and 1.6-fold greater than wild-type (WT) during late log and stationary phases of growth. Similarly, total cellulase activity of +MCbglA was shown to be 1.7-, 2.3- and 1.6-fold greater than WT during, log, late log and stationary phases of growth. However, there was no significant correlation found between increased cellulase activity and increased ethanol titers for +MCbglA compared with the WT. C. thermocellum has industrial potential for consolidated bioprocessing (CBP) to make a more cost effective production of biofuels; however, the hydrolysis rate of the strain is still hindered by end product inhibition. We successfully increased total cellulase activity by increased expression of bglA and thereby increased the productivity of C. thermocellum during the hydrolysis stage in CBP. Our work also lends insights into the complex metabolism of C. thermocellum for future improvement of this strain. PMID:22922214

  15. Heterogeneity of aquatic sediment significantly increases nitrogen removal

    NASA Astrophysics Data System (ADS)

    Sawyer, A. H.

    2014-12-01

    In recent decades, nitrate loads to rivers and coasts have increased dramatically and contributed to eutrophication and hypoxia in coastal waters. A major sink for nitrate in the environment is denitrification in aquatic sediments. Here, I show that nitrate removal rates are as much as 100 times more efficient in heterogeneous than equivalent homogeneous aquatic sediments. Numerical experiments quantify nitrate removal from groundwater discharging through shallow columns of heterogeneous aquatic sediment. The steady groundwater flow equation was coupled to the advection-dispersion-reaction equations for dissolved oxygen, nitrate, and dissolved organic carbon (DOC). Bimodal sediments composed of sand and clay were simulated using TPROGS for a wide range of clay fractions. Small (centimeter-scale) sedimentary structures were intended to represent infilled burrows or clay rip-up clasts. Clay structures were assigned a relatively high organic carbon content (2%). The local source of DOC fuels oxygen consumption in clay structures and promotes restricted zones of denitrification in otherwise aerobic sediments. As a result, redox transformations do not strictly depend on residence times but rather on distributions of organic carbon in aquatic sediments. Furthermore, bimodal sand and clay deposits are more efficient than either clean sand or homogeneous sandy-clay at removing nitrate. These results help explain observations of efficient nitrate removal in relatively sandy, oxygenated aquatic sediments when small organic-rich structures are present. The results also suggest that models of reactive transport in homogeneous sediment underestimate biogeochemical transformation rates relative to heterogeneous sediment. Similarly, laboratory-derived denitrification rates on homogenized cores are likely underestimated relative to intact cores.

  16. Phytohormone supplementation significantly increases growth of Chlamydomonas reinhardtii cultivated for biodiesel production.

    PubMed

    Park, Won-Kun; Yoo, Gursong; Moon, Myounghoon; Kim, Chul Woong; Choi, Yoon-E; Yang, Ji-Won

    2013-11-01

    Cultivation is the most expensive step in the production of biodiesel from microalgae, and substantial research has been devoted to developing more cost-effective cultivation methods. Plant hormones (phytohormones) are chemical messengers that regulate various aspects of growth and development and are typically active at very low concentrations. In this study, we investigated the effect of different phytohormones on microalgal growth and biodiesel production in Chlamydomonas reinhardtii and their potential to lower the overall cost of commercial biofuel production. The results indicated that all five of the tested phytohormones (indole-3-acetic acid, gibberellic acid, kinetin, 1-triacontanol, and abscisic acid) promoted microalgal growth. In particular, hormone treatment increased biomass production by 54 to 69 % relative to the control growth medium (Tris-acetate-phosphate, TAP). Phytohormone treatments also affected microalgal cell morphology but had no effect on the yields of fatty acid methyl esters (FAMEs) as a percent of biomass. We also tested the effect of these phytohormones on microalgal growth in nitrogen-limited media by supplementation in the early stationary phase. Maximum cell densities after addition of phytohormones were higher than in TAP medium, even when the nitrogen source was reduced to 40 % of that in TAP medium. Taken together, our results indicate that phytohormones significantly increased microalgal growth, particularly in nitrogen-limited media, and have potential for use in the development of efficient microalgal cultivation for biofuel production. PMID:23881782

  17. Increased formation of ursodeoxycholic acid in patients treated with chenodeoxycholic acid.

    PubMed Central

    Salen, G; Tint, G S; Eliav, B; Deering, N; Mosbach, E H

    1974-01-01

    The formation of ursodeoxycholic acid, the 7 beta-hydroxy epimer of chenodeoxycholic acid, was investigated in three subjects with cerebrotendinous xanthomatosis and in four subjects with gallstones. Total biliary bile acid composition was analyzed by gas-liquid chromatography before and after 4 months of treatment with 0.75 g/day of chenodeoxycholic acid. Individual bile acids were identified by mass spectrometry. Before treatment, bile from cerebrotendinous xanthomatosis (CTX) subjects contained cholic acid, 85%; chenodeoxycholic acid, 7%; deoxycholic acid, 3%; allocholic acid, 3%; and unidentified steroids, 2%; while bile from gallstone subjects contained cholic acid, 45%; chenodeoxycholic acid, 43%; deoxycholic acid, 11%, and lithocholic acid, 1%. In all subjects, 4 months of chenodeoxycholic acid therapy increased the proportion of this bile acid to approximately 80% and decreased cholic acid to 3% of the total biliary bile acids, the remaining 17% of bile acids were identified as ursodeoxycholic acid. After the intravenous injection of [3H]chenodeoxycholic acid, the specific activity of biliary ursodeoxycholic acid exceeded the specific activity of chenodeoxycholic acid, and the resulting specific activity decay curves suggested precursor-product relationships. When [3H]7-ketolithocholic acid was administrated to another patient treated with chenodeoxycholic acid, radioactivity was detected in both the ursodeoxycholic acid and chenodeoxycholic acid fractions. These results indicate that substantial amounts of ursodeoxycholic acid are formed in patients treated with chenodeoxycholic acid. The ursodeoxycholic acid was synthesized from chenodeoxycholic acid presumably via 7-ketolithocholic acid. Images PMID:11344576

  18. The significance of plasma phytanic acid levels in adults.

    PubMed Central

    Britton, T C; Gibberd, F B; Clemens, M E; Billimoria, J D; Sidey, M C

    1989-01-01

    The presence of phytanic acid in tissues and plasma has been considered diagnostic of heredopathia atactica polyneuritiformis (Refsum's disease), but recently slightly raised plasma phytanic acid levels have been reported in other conditions. Forty two normal people were found to have a phytanic acid level of 0-33 mumol/l. Fourteen patients with heredopathia atactica polyneuritiformis had a plasma phytanic acid level before treatment of 992-6400 mumol/l. Five patients with retinitis pigmentosa but not heredopathia atactica polyneuritiformis had plasma levels of 38-192 mumol/l. It was concluded that some patients with retinitis pigmentosa without heredopathia atactica polyneuritiformis but a raised plasma phytanic acid may represent a group of patients with a disease or diseases as yet uncharacterised apart from the retinal condition. PMID:2475586

  19. Significant association between parathyroid hormone and uric acid level in men

    PubMed Central

    Chin, Kok-Yong; Ima Nirwana, Soelaiman; Wan Ngah, Wan Zurinah

    2015-01-01

    Background Previous reports of patients undergoing parathyroidectomy and of patients receiving teriparatide as antiosteoporotic treatment have suggested a plausible relationship between parathyroid hormone (PTH) and uric acid. However, similar data at population level were lacking. The current study aimed to determine the relationship between PTH and uric acid in a group of apparently healthy Malaysian men. Methods A cross-sectional study was conducted among 380 Malay and Chinese men aged 20 years and above, residing in the Klang Valley, Malaysia. Their body anthropometry was measured, and their fasting blood samples were collected for biochemical analysis. The relationship between PTH and uric acid was analyzed using regression analysis. Results Increased serum PTH level was significantly associated with increased serum uric acid level (β=0.165; P=0.001). Increased PTH level was also significantly associated with the condition of hyperuricemia in the study population (odds ratio [OR], 1.045; 95% confidence interval [CI], 1.017–1.075; P=0.002). All analyses were adjusted for age, body mass index, vitamin D, total calcium, inorganic phosphate, blood urea nitrogen and creatinine levels. Conclusion There is a significant positive relationship between PTH level and uric acid level in Malaysian men. This relationship and its clinical significance should be further investigated in a larger longitudinal study. PMID:26346636

  20. Molecular mechanism and functional significance of acid generation in the Drosophila midgut

    PubMed Central

    Overend, Gayle; Luo, Yuan; Henderson, Louise; Douglas, Angela E.; Davies, Shireen A.; Dow, Julian A. T.

    2016-01-01

    The gut of Drosophila melanogaster includes a proximal acidic region (~pH 2), however the genome lacks the H+/K+ ATPase characteristic of the mammalian gastric parietal cell, and the molecular mechanisms of acid generation are poorly understood. Here, we show that maintenance of the low pH of the acidic region is dependent on H+ V-ATPase, together with carbonic anhydrase and five further transporters or channels that mediate K+, Cl− and HCO3− transport. Abrogation of the low pH did not influence larval survival under standard laboratory conditions, but was deleterious for insects subjected to high Na+ or K+ load. Insects with elevated pH in the acidic region displayed increased susceptibility to Pseudomonas pathogens and increased abundance of key members of the gut microbiota (Acetobacter and Lactobacillus), suggesting that the acidic region has bacteriostatic or bacteriocidal activity. Conversely, the pH of the acidic region was significantly reduced in germ-free Drosophila, indicative of a role of the gut bacteria in shaping the pH conditions of the gut. These results demonstrate that the acidic gut region protects the insect and gut microbiome from pathological disruption, and shed light on the mechanisms by which low pH can be maintained in the absence of H+, K+ ATPase. PMID:27250760

  1. Molecular mechanism and functional significance of acid generation in the Drosophila midgut.

    PubMed

    Overend, Gayle; Luo, Yuan; Henderson, Louise; Douglas, Angela E; Davies, Shireen A; Dow, Julian A T

    2016-01-01

    The gut of Drosophila melanogaster includes a proximal acidic region (~pH 2), however the genome lacks the H(+)/K(+) ATPase characteristic of the mammalian gastric parietal cell, and the molecular mechanisms of acid generation are poorly understood. Here, we show that maintenance of the low pH of the acidic region is dependent on H(+) V-ATPase, together with carbonic anhydrase and five further transporters or channels that mediate K(+), Cl(-) and HCO3(-) transport. Abrogation of the low pH did not influence larval survival under standard laboratory conditions, but was deleterious for insects subjected to high Na(+) or K(+) load. Insects with elevated pH in the acidic region displayed increased susceptibility to Pseudomonas pathogens and increased abundance of key members of the gut microbiota (Acetobacter and Lactobacillus), suggesting that the acidic region has bacteriostatic or bacteriocidal activity. Conversely, the pH of the acidic region was significantly reduced in germ-free Drosophila, indicative of a role of the gut bacteria in shaping the pH conditions of the gut. These results demonstrate that the acidic gut region protects the insect and gut microbiome from pathological disruption, and shed light on the mechanisms by which low pH can be maintained in the absence of H(+), K(+) ATPase. PMID:27250760

  2. Method of increasing conversion of a fatty acid to its corresponding dicarboxylic acid

    DOEpatents

    Craft, David L.; Wilson, C. Ron; Eirich, Dudley; Zhang, Yeyan

    2004-09-14

    A nucleic acid sequence including a CYP promoter operably linked to nucleic acid encoding a heterologous protein is provided to increase transcription of the nucleic acid. Expression vectors and host cells containing the nucleic acid sequence are also provided. The methods and compositions described herein are especially useful in the production of polycarboxylic acids by yeast cells.

  3. Transcript and metabolite alterations increase ganoderic acid content in Ganoderma lucidum using acetic acid as an inducer.

    PubMed

    Ren, Ang; Li, Xiong-Biao; Miao, Zhi-Gang; Shi, Liang; Jaing, Ai-Liang; Zhao, Ming-Wen

    2014-12-01

    Acetic acid at 5-8 mM increased ganoderic acid (GA) accumulation in Ganoderma lucidum. After optimization by the response surface methodology, the GA content reached 5.5/100 mg dry weight, an increase of 105% compared with the control. The intermediate metabolites of GA biosynthesis, lanosterol and squalene also increased to 47 and 15.8 μg/g dry weight, respectively, in response to acetic acid. Acetic acid significantly induced transcription levels of sqs, lano, hmgs and cyp51 in the GA biosynthesis pathway. An acetic acid-unregulated acetyl coenzyme A synthase (acs) gene was selected from ten candidate homologous acs genes. The results indicate that acetic acid alters the expression of genes related to acetic acid assimilation and increases GA biosynthesis and the metabolic levels of lanosterol, squalene and GA-a, thereby resulting in GA accumulation. PMID:25216642

  4. Breeding Vegetables with Increased Content in Bioactive Phenolic Acids.

    PubMed

    Kaushik, Prashant; Andújar, Isabel; Vilanova, Santiago; Plazas, Mariola; Gramazio, Pietro; Herraiz, Francisco Javier; Brar, Navjot Singh; Prohens, Jaime

    2015-01-01

    Vegetables represent a major source of phenolic acids, powerful antioxidants characterized by an organic carboxylic acid function and which present multiple properties beneficial for human health. In consequence, developing new varieties with enhanced content in phenolic acids is an increasingly important breeding objective. Major phenolic acids present in vegetables are derivatives of cinnamic acid and to a lesser extent of benzoic acid. A large diversity in phenolic acids content has been found among cultivars and wild relatives of many vegetable crops. Identification of sources of variation for phenolic acids content can be accomplished by screening germplasm collections, but also through morphological characteristics and origin, as well as by evaluating mutations in key genes. Gene action estimates together with relatively high values for heritability indicate that selection for enhanced phenolic acids content will be efficient. Modern genomics and biotechnological strategies, such as QTL detection, candidate genes approaches and genetic transformation, are powerful tools for identification of genomic regions and genes with a key role in accumulation of phenolic acids in vegetables. However, genetically increasing the content in phenolic acids may also affect other traits important for the success of a variety. We anticipate that the combination of conventional and modern strategies will facilitate the development of a new generation of vegetable varieties with enhanced content in phenolic acids. PMID:26473812

  5. Dietary arachidonic acid dose-dependently increases the arachidonic acid concentration in human milk.

    PubMed

    Weseler, Antje R; Dirix, Chantal E H; Bruins, Maaike J; Hornstra, Gerard

    2008-11-01

    Lactation hampers normalization of the maternal arachidonic acid (AA) status, which is reduced after pregnancy and can further decline by the presently recommended increased consumption of (n-3) long-chain PUFA [(n-3) LCPUFA]. This may be unfavorable for breast-fed infants, because they also require an optimum supply of (n-6) LCPUFA. We therefore investigated the LCPUFA responses in nursing mothers upon increased consumption of AA and (n-3) LCPUFA. In a parallel, double-blind, controlled trial, lactating women received for 8 wk no extra LCPUFA (control group, n = 8), 200 (low AA group, n = 9), or 400 (high AA group, n = 8) mg/d AA in combination with (n-3) LCPUFA [320 mg/d docosahexaenoic acid (DHA), 80 mg/d eicosapentaenoic acid, and 80 mg/d other (n-3) fatty acids], or this dose of (n-3) LCPUFA alone [DHA + eicosapentaenoic acid group, n = 8]. Relative concentrations of AA, DHA, and sums of (n-6) and (n-3) LCPUFA were measured in milk total lipids (TL) and erythrocyte phospholipids (PL) after 2 and 8 wk and changes were compared by ANCOVA. The combined consumption of AA and (n-3) LCPUFA caused dose-dependent elevations of AA and total (n-6) LCPUFA concentrations in milk TL and did not significantly affect the DHA and total (n-3) LCPUFA increases caused by (n-3) LCPUFA supplementation only. This latter treatment did not significantly affect breast milk AA and total (n-6) LCPUFA concentrations. AA and DHA concentrations in milk TL and their changes were strongly and positively correlated with their corresponding values in erythrocyte PL (r(2) = 0.27-0.50; P increased the AA concentration of their milk TL. PMID:18936218

  6. Significance of long-chain polyunsaturated fatty acids (PUFAs) for the development and behaviour of children.

    PubMed

    Schuchardt, Jan Philipp; Huss, Michael; Stauss-Grabo, Manuela; Hahn, Andreas

    2010-02-01

    omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) play a central role in the normal development and functioning of the brain and central nervous system. Long-chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA, C20:5omega-3), docosahexaenoic acid (DHA, C22:6omega-3) and arachidonic acid (AA, C20:4omega-6), in particular, are involved in numerous neuronal processes, ranging from effects on membrane fluidity to gene expression regulation. Deficiencies and imbalances of these nutrients, not only during the developmental phase but throughout the whole life span, have significant effects on brain function. Numerous observational studies have shown a link between childhood developmental disorders and omega-6:omega-3 fatty acid imbalances. For instance, neurocognitive disorders such as attention-deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia and autism spectrum disorders are often associated with a relative lack of omega-3 fatty acids. In addition to a high omega-6 fatty acid intake and, in many cases, an insufficient supply of omega-3 fatty acids among the population, evidence is increasing to suggest that PUFA metabolism can be impaired in individuals with ADHD. In this context, PUFA imbalances are being discussed as potential risk factors for neurodevelopmental disorders. Another focus is whether the nutritive PUFA requirements-especially long-chain omega-3 fatty acid requirements-are higher among some individuals. Meanwhile, several controlled studies investigated the clinical benefits of LC-PUFA supplementation in affected children and adolescents, with occasionally conflicting results. PMID:19672626

  7. Intravenous lipid and amino acids briskly increase plasma glucose concentrations in small premature infants.

    PubMed

    Savich, R D; Finley, S L; Ogata, E S

    1988-07-01

    We determined the glycemic response to intravenous lipid infusion alone, lipid with amino acids, or amino acids alone in 15 very small premature infants receiving constant glucose infusion during early life. Infants who received lipid or lipid and amino acids demonstrated significant increases in glucose compared with infants who received amino acids. The combination of lipid and amino acids resulted in an earlier increase than lipid alone. Although plasma insulin did not change in all three groups, infants who received amino acids alone demonstrated an appropriate increase in glucagon. These data suggest that lipid infusion, a commonly used means of providing nutrition to premature infants, may cause significant disturbances in glucoregulation, particularly when administered with amino acids. PMID:3132930

  8. Increasing the Oleic Acid in Soybean Oil with Plant Breeding

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing the oleic acid content along with decrease in linolenic acid can improve the oxidative stability of soybean oil. Genetic changes in soybean using standard plant breeding practices has resulted in a publicly released a mid-oleic breeding line, N98-4445A, with oil that averages 57% oleic ac...

  9. Prognostic Significance of Uric Acid Levels in Ischemic Stroke Patients.

    PubMed

    Zhang, Xia; Huang, Zhi-Chao; Lu, Tao-Sheng; You, Shou-Jiang; Cao, Yong-Jun; Liu, Chun-Feng

    2016-01-01

    The importance and function of serum uric acid (UA) levels in patients with cardiovascular disease or stroke are unclear. We sought to evaluate the appropriate UA levels for stroke patients and the association between endogenous UA levels and clinical outcomes in acute ischemic stroke (AIS) patients, particularly regarding the possible interaction between gender and UA levels with respect to AIS prognosis. We examined 303 patients who had an onset of ischemic stroke within 48 h. Of those, 101 patients received thrombolytic treatment. Serum UA (μmol/L) levels were measured the second morning after admission. Patient prognosis was evaluated 90 days after clinical onset by modified Rankin Scale. Patients were divided into four groups according to serum UA quartiles. A binary multivariate logistic regression model was used to assess clinical relevance in regard to functional outcome and endogenous UA levels. Analysis of subgroups by gender and normal glomerular filtration rate were also been done. Poor functional outcome was associated with older age, history of atrial fibrillation, or higher baseline National Institutes of Health Stroke Scale scores. After adjustment for potential confounders, patients with higher UA levels (>380 μmol/L) or lower UA levels (≤250 μmol/L) were 2-3 times more likely to have a poor outcome (OR 2.95, 95% CI 1.14-7.61; OR 2.78, 95% CI 1.02-7.58, respectively) compared to the baseline group (UA level 316-380 μmol/L). The same results were observed in thrombolyzed patients. Patients with high and low UA levels were 9-18 times more likely to having poor outcomes compared to the baseline group (UA level: 316-380 μmol/L; OR 18.50, 95% CI: 2.041-167.67; OR 9.66, 95% CI 1.42-65.88, respectively). In men, patients with high UA levels were 6 times more likely to have poor outcomes compared to the baseline group (UA level: 279-334 μmol/L; OR 6.10, 95% CI 1.62-22.93). However, female patients with UA level 271-337 μmol/L were seven times more

  10. Increased Rat Placental Fatty Acid, but Decreased Amino Acid and Glucose Transporters Potentially Modify Intrauterine Programming.

    PubMed

    Nüsken, Eva; Gellhaus, Alexandra; Kühnel, Elisabeth; Swoboda, Isabelle; Wohlfarth, Maria; Vohlen, Christina; Schneider, Holm; Dötsch, Jörg; Nüsken, Kai-Dietrich

    2016-07-01

    Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc. PMID:26590355

  11. Uric acid excretion predicts increased aggression in urban adolescents.

    PubMed

    Mrug, Sylvie; Mrug, Michal

    2016-09-01

    Elevated levels of uric acid have been linked with impulsive and disinhibited behavior in clinical and community populations of adults, but no studies have examined uric acid in relation to adolescent aggression. This study examined the prospective role of uric acid in aggressive behavior among urban, low income adolescents, and whether this relationship varies by gender. A total of 84 adolescents (M age 13.36years; 50% male; 95% African American) self-reported on their physical aggression at baseline and 1.5years later. At baseline, the youth also completed a 12-h (overnight) urine collection at home which was used to measure uric acid excretion. After adjusting for baseline aggression and age, greater uric acid excretion predicted more frequent aggressive behavior at follow up, with no significant gender differences. The results suggest that lowering uric acid levels may help reduce youth aggression. PMID:27180134

  12. Increase in the permeability of tonoplast of garlic (Allium sativum) by monocarboxylic acids.

    PubMed

    Bai, Bing; Li, Lei; Hu, Xiaosong; Wang, Zhengfu; Zhao, Guanghua

    2006-10-18

    Immersion of intact aged garlic (Allium sativum) cloves in a series of 5% weak organic monocarboxylate solutions (pH 2.0) resulted in green color formation. No color was formed upon treatment with other weak organic acids, such as citric and malic acids, and the inorganic hydrochloric acid under the same conditions. To understand the significance of monocarboxylic acids and their differing function from that of other acids, acetic acid was compared with organic acids citric and malic and the inorganic hydrochloric acid. The effects of these acids on the permeability of plasma and intracellular membrane of garlic cells were measured by conductivity, light microscopy, and transmission electron microscopy. Except for hydrochloric acid, treatment of garlic with all three organic acids greatly increased the relative conductivity of their respective pickling solutions, indicating that all tested organic acids increased the permeability of plasma membrane. Moreover, a pickling solution containing acetic acid exhibited 1.5-fold higher relative conductivity (approximately 90%) as compared to those (approximately 60%) of both citric and malic acids, implying that exposure of garlic cloves to acetic acid not only changed the permeability of the plasma membrane but also increased the permeability of intracellular membrane. Exposure of garlic to acetic acid led to the production of precipitate along the tonoplast, but no precipitate was formed by citric and malic acids. This indicates that the structure of the tonoplast was damaged by this treatment. Further support for this conclusion comes from results showing that the concentration of thiosulfinates [which are produced only by catalytic conversion of S-alk(en)yl-l-cysteine sulfoxides in cytosol by alliinase located in the vacuole] in the acetic acid pickling solution is 1.3 mg/mL, but almost no thiosulfinates were detected in the pickling solution of citric and malic acids. Thus, all present results suggest that damage of

  13. Acid mine drainage and subsidence: effects of increased coal utilization.

    PubMed Central

    Hill, R D; Bates, E R

    1979-01-01

    The increases above 1975 levels for acid mine drainage and subsidence for the years 1985 and 2000 based on projections of current mining trends and the National Energy Plan are presented. No increases are projected for acid mine drainage from surface mines or waste since enforcement under present laws should control this problem. The increase in acid mine drainage from underground mines is projected to be 16 percent by 1985 and 10 percent by 2000. The smaller increase in 2000 over 1985 reflects the impact of the PL 95-87 abandoned mine program. Mine subsidence is projected to increase by 34 and 115 percent respectively for 1985 and 2000. This estimate assumes that subsidence will parallel the rate of underground coal production and that no new subsidence control measures are adopted to mitigate subsidence occurrence. PMID:540617

  14. Cinnamic acid increases lignin production and inhibits soybean root growth.

    PubMed

    Salvador, Victor Hugo; Lima, Rogério Barbosa; dos Santos, Wanderley Dantas; Soares, Anderson Ricardo; Böhm, Paulo Alfredo Feitoza; Marchiosi, Rogério; Ferrarese, Maria de Lourdes Lucio; Ferrarese-Filho, Osvaldo

    2013-01-01

    Cinnamic acid is a known allelochemical that affects seed germination and plant root growth and therefore influences several metabolic processes. In the present work, we evaluated its effects on growth, indole-3-acetic acid (IAA) oxidase and cinnamate 4-hydroxylase (C4H) activities and lignin monomer composition in soybean (Glycine max) roots. The results revealed that exogenously applied cinnamic acid inhibited root growth and increased IAA oxidase and C4H activities. The allelochemical increased the total lignin content, thus altering the sum and ratios of the p-hydroxyphenyl (H), guaiacyl (G), and syringyl (S) lignin monomers. When applied alone or with cinnamic acid, piperonylic acid (PIP, a quasi-irreversible inhibitor of C4H) reduced C4H activity, lignin and the H, G, S monomer content compared to the cinnamic acid treatment. Taken together, these results indicate that exogenously applied cinnamic acid can be channeled into the phenylpropanoid pathway via the C4H reaction, resulting in an increase in H lignin. In conjunction with enhanced IAA oxidase activity, these metabolic responses lead to the stiffening of the cell wall and are followed by a reduction in soybean root growth. PMID:23922685

  15. Increased mutagenicity of chromium compounds by nitrilotriacetic acid

    SciTech Connect

    Loprieno, N.; Boncristiani, G.; Venier, P.; Montaldi, A.; Majone, F.; Bianchi, V.; Paglialunga, S.; Levis, A.G.

    1985-01-01

    Nitrilotriacetic acid trisodium salt (NTA), which is a substitute for polyphosphates in household laundry detergents, and N-nitrosoiminodiacetic acid (NIDA), a derivative of NTA produced by metabolism of soil microorganisms, were tested for in vitro mutagenicity in bacteria and yeasts. No gene reversions in five strains of Salmonella typhimurium (TA1535, TA1537, TA1538, TA98, and TA100), no forward gene mutations in Schizosaccharomyces pombe P1, and no mitotic gene conversions at two loci in Saccharomyces cerevisiae D4 were induced by NTA and NIDA independently of the presence of rat liver metabolic activation. The influence of NTA on the mutagenic and clastogenic activity of several chromium compounds was examined in the Salmonella/microsome assay and in the sister chromatid exchange (SCE) assay in mammalian cell cultures (Chinese hamster ovary (CHO) line). NTA does not affect the genetic inactivity of water-soluble Cr(III) (Cr/sub 2/(SO/sub 4/)/sub 3/) and the direct mutagenicity of soluble Cr(VI) (Na/sub 2/CrO/sub 4/, K/sub 2/Cr/sub 2/O/sub 7/) compounds. The very insoluble Cr(VI) compounds PbCrO/sub 4/ and PbCrO/sub 4/ x PbO are instead clearly mutagenic in the Salmonella/microsome assay (TA100 strain) only in the presence of NTA or NaOH. The chromosome-damaging activity of PbCrO/sub 4/ is significantly increased by NTA but not by NaOH.

  16. Acid-activated biochar increased sulfamethazine retention in soils.

    PubMed

    Vithanage, Meththika; Rajapaksha, Anushka Upamali; Zhang, Ming; Thiele-Bruhn, Sören; Lee, Sang Soo; Ok, Yong Sik

    2015-02-01

    Sulfamethazine (SMZ) is an ionizable and highly mobile antibiotic which is frequently found in soil and water environments. We investigated the sorption of SMZ onto soils amended with biochars (BCs) at varying pH and contact time. Invasive plants were pyrolyzed at 700 °C and were further activated with 30 % sulfuric (SBBC) and oxalic (OBBC) acids. The sorption rate of SMZ onto SBBC and OBBC was pronouncedly pH dependent and was decreased significantly when the values of soil pH increased from 3 to 5. Modeled effective sorption coefficients (K D,eff) values indicated excellent sorption on SBBC-treated loamy sand and sandy loam soils for 229 and 183 L/kg, respectively. On the other hand, the low sorption values were determined for OBBC- and BBC700-treated loamy sand and sandy loam soils. Kinetic modeling demonstrated that the pseudo second order model was the best followed by intra-particle diffusion and the Elovich model, indicating that multiple processes govern SMZ sorption. These findings were also supported by sorption edge experiments based on BC characteristics. Chemisorption onto protonated and ligand containing functional groups of the BC surface, and diffusion in macro-, meso-, and micro-pores of the acid-activated BCs are the proposed mechanisms of SMZ retention in soils. Calculated and experimental q e (amount adsorbed per kg of the adsorbent at equilibrium) values were well fitted to the pseudo second order model, and the predicted maximum equilibrium concentration of SBBC for loamy sand soils was 182 mg/kg. Overall, SBBC represents a suitable soil amendment because of its high sorption rate of SMZ in soils. PMID:25172460

  17. No significant increase in long-term CH4 emissions on North Slope of Alaska despite significant increase in air temperature

    NASA Astrophysics Data System (ADS)

    Sweeney, Colm; Dlugokencky, Edward; Miller, Charles E.; Wofsy, Steven; Karion, Anna; Dinardo, Steve; Chang, Rachel Y.-W.; Miller, John B.; Bruhwiler, Lori; Crotwell, Andrew M.; Newberger, Tim; McKain, Kathryn; Stone, Robert S.; Wolter, Sonja E.; Lang, Patricia E.; Tans, Pieter

    2016-06-01

    Continuous measurements of atmospheric methane (CH4) mole fractions measured by NOAA's Global Greenhouse Gas Reference Network in Barrow, AK (BRW), show strong enhancements above background values when winds come from the land sector from July to December from 1986 to 2015, indicating that emissions from arctic tundra continue through autumn and into early winter. Twenty-nine years of measurements show little change in seasonal mean land sector CH4 enhancements, despite an increase in annual mean temperatures of 1.2 ± 0.8°C/decade (2σ). The record does reveal small increases in CH4 enhancements in November and December after 2010 due to increased late-season emissions. The lack of significant long-term trends suggests that more complex biogeochemical processes are counteracting the observed short-term (monthly) temperature sensitivity of 5.0 ± 3.6 ppb CH4/°C. Our results suggest that even the observed short-term temperature sensitivity from the Arctic will have little impact on the global atmospheric CH4 budget in the long term if future trajectories evolve with the same temperature sensitivity.

  18. Chlorogenic acid increased 5-hydroxymethylfurfural formation when heating fructose alone or with aspartic acid at two pH levels.

    PubMed

    Zhang, Zhenhua; Zou, Yueyu; Wu, Taigang; Huang, Caihuan; Pei, Kehan; Zhang, Guangwen; Lin, Xiaohua; Bai, Weibin; Ou, Shiyi

    2016-01-01

    Chlorogenic acid (CGA) is a phenolic acid that ubiquitously exists in fruits. This work aims to investigate whether and how CGA influences HMF formation during heating fructose alone, or with an amino acid. The results showed that that CGA increased 5-hydroxymethylfurfural (HMF) formation. At pH 5.5 and 7.0, the addition of 5.0 μmol/ml CGA increased HMF formation by 49.4% and 25.2%, respectively when heating fructose alone, and by 9.0% and 16.7%, respectively when heating fructose with aspartic acid. CGA significantly increased HMF formation by promoting 3-deoxosone formation, and its conversion to HMF by inhibiting HMF elimination, especially in the Maillard reaction system. A comparison of the catalytic capacity of CGA with its six analogous compounds showed that both its di-hydroxyphenyl and carboxyl groups function in increasing HMF formation. PMID:26213045

  19. An Increase Incidence in Uric Acid Nephrolithiasis: Changing Patterns

    PubMed Central

    Kumari, Asha; Mittal, Pawan; Kumar, Rajender; Goel, Richa; Bansal, Piyush; Kumar, Himanshu Devender; Bhutani, Jaikrit

    2016-01-01

    Introduction Nephrolithiasis is a complex disease affecting all age groups globally. As the causative factors for nephrolithiasis rises significantly, its incidence, prevalence and recurrence continues to baffle clinicians and patients. Aim To study the prevalence of different types of renal stones extracted by Percutaneous Nephrolithotomy (PCNL) and open surgical procedures. Materials and Methods Renal stones from 50 patients were retrieved by Percutaneous Nephrolithotomy (PCNL), Ureterorenoscopy (URS) and open surgical techniques for qualitative tests for detection of calcium, oxalate, uric acid, phosphate, ammonium ion, carbonate, cystine and xanthine. Results Three patients had stone removed by open surgery and rest had undergone PCNL. Nine of the stones were pure of calcium oxalate, 9 were of pure uric acid and 32 were mixed stones. Forty one stones had calcium. Among the mixed stones, oxalate was present in 25 samples (39 of total), uric acid was seen in 17 (25 of total stones), phosphate was present in 23 (23 of total) and carbonate was present in 4 stones (4 of total). Only 1 patient had triple phosphate stone. 12 were of staghorn appearance of which 6 were of struvite type, 6 were pure uric acid and remaining were mixed oxalate-phosphate stones. Conclusion Our study, though in a small number of hospital based patients, found much higher prevalence of uric acid stones and mixed stones than reported by previous hospital based studies in north India (oxalate stones~90%, uric acid~1% and mixed stones~3%). Biochemical analysis of renal stones is warranted in all cases.

  20. Significance of Increasing n-3 PUFA Content in Pork on Human Health.

    PubMed

    Ma, Xianyong; Jiang, Zongyong; Lai, Chaoqiang

    2016-04-01

    Evidence for the health-promoting effects of food rich in n-3 polyunsaturated fatty acids (n-3 PUFA) is reviewed. Pork is an important meat source for humans. According to a report by the US Department of Agriculture ( http://www.ers.usda.gov/topics ), the pork consumption worldwide in 2011 was about 79.3 million tons, much higher than that of beef (48.2 million tons). Pork also contains high levels of unsaturated fatty acids relative to ruminant meats (Enser, M., Hallett, K., Hewett, B., Fursey, G. A. J. and Wood, J. D. (1996) . Fatty acid content and composition of English beef, lamb, and pork at retail. Meat Sci. 44:443-458). The available literature indicates that the levels of eicosatetraenoic and docosahexaenoic in pork may be increased by fish-derived or linseed products, the extent of which being dependent on the nature of the supplementation. Transgenic pigs and plants show promise with high content of n-3 PUFA and low ratio of n-6/n-3 fatty acids in their tissues. The approaches mentioned for decreasing n-6/n-3 ratios have both advantages and disadvantages. Selected articles are critically reviewed and summarized. PMID:26237277

  1. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2002-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  2. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, M.; Millard, C.S.; Stols, L.

    1998-06-23

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria. 2 figs.

  3. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    1998-01-01

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which as been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  4. Mutant E. coli strain with increased succinic acid production

    DOEpatents

    Donnelly, Mark; Millard, Cynthia S.; Stols, Lucy

    2001-09-25

    A method for isolating succinic acid producing bacteria is provided comprising increasing the biomass of an organism which lacks the ability to catabolize pyruvate, and then subjecting the biomass to glucose-rich medium in an anaerobic environment to enable pyruvate-catabolizing mutants to grow. The invention also provides for a mutant that produces high amounts of succinic acid, which has been derived from a parent which lacked the genes for pyruvate formate lyase and lactate dehydrogenase, and which belongs to the E.coli Group of Bacteria.

  5. Hippuric Acid as a Significant Regulator of Supersaturation in Calcium Oxalate Lithiasis: The Physiological Evidence

    PubMed Central

    Atanassova, Stoyanka S.; Gutzow, Ivan S.

    2013-01-01

    At present, the clinical significance of existing physicochemical and biological evidence and especially the results we have obtained from our previous in vitro experiments have been analyzed, and we have come to the conclusion that hippuric acid (C6H5CONHCH2COOH) is a very active solvent of Calcium Oxalate (CaOX) in physiological solutions. Two types of experiments have been discussed: clinical laboratory analysis on the urine excretion of hippuric acid (HA) in patients with CaOX lithiasis and detailed measurements of the kinetics of the dissolution of CaOX calculi in artificial urine, containing various concentrations of HA. It turns out that the most probable value of the HA concentration in the control group is approximately ten times higher than the corresponding value in the group of the stone-formers. Our in vitro analytical measurements demonstrate even a possibility to dissolve CaOX stones in human urine, in which increased concentration of HA have been established. A conclusion can be that drowning out HA is a significant regulator of CaOX supersaturation and thus a regulation of CaOX stone formation in human urine. Discussions have arisen to use increased concentration of HA in urine both as a solubilizator of CaOX stones in the urinary tract and on the purpose of a prolonged metaphylactic treatment. PMID:24307993

  6. Studies of the prevalence and significance of radiolabeled bile acid malabsorption in a group of patients with idiopathic chronic diarrhea

    SciTech Connect

    Schiller, L.R.; Hogan, R.B.; Morawski, S.G.; Santa Ana, C.A.; Bern, M.J.; Norgaard, R.P.; Bo-Linn, G.W.; Fordtran, J.S.

    1987-01-01

    We studied radiolabeled fecal bile acid excretion in 11 normal subjects and 17 patients with idiopathic chronic diarrhea for three major purposes: to establish normal values for this test in the presence of increased stool volumes (induced in normal subjects by ingestion of poorly absorbable solutions); to test for bile acid malabsorption in the patients and to correlate this with an independent test of ileal function, the Schilling test; and to compare the results of the bile acid excretion test with the subsequent effect of a bile acid binding agent (cholestyramine) on stool weight. In normal subjects fecal excretion of the radiolabel was increased with increasing stool volumes. As a group, patients with idiopathic chronic diarrhea excreted radiolabeled bile acid more rapidly than normal subjects with induced diarrhea (t1/2 56 +/- 8 vs. 236 +/- 60 h, respectively, p less than 0.005). There was a statistically significant positive correlation between t1/2 of radiolabeled bile acid and Schilling test results in these patients. Although 14 of 17 patients absorbed labeled taurocholic acid less well than any of the normal subjects with comparable volumes of induced diarrhea, cholestyramine had no statistically significant effect on stool weight in the patient group, and in none of the patients was stool weight reduced to within the normal range. In summary, most patients with idiopathic chronic diarrhea have bile acid malabsorption (as measured by fecal excretion of labeled bile acid), but they do not respond to cholestyramine therapy with a significant reduction in stool weight. Although the significance of these findings was not clearly established, the most likely interpretation is that bile acid malabsorption is a manifestation of an underlying intestinal motility or absorptive defect rather than the primary cause of diarrhea.

  7. Increased acyclovir oral bioavailability via a bile acid conjugate.

    PubMed

    Tolle-Sander, Sanna; Lentz, Kimberley A; Maeda, Dean Y; Coop, Andrew; Polli, James E

    2004-01-12

    The objective of this work was to design an acyclovir prodrug that would utilize the human apical sodium-dependent bile acid transporter (hASBT) and enhance acyclovir oral bioavailability. Using each chenodeoxycholate, deoxycholate, cholate, and ursodeoxycholate, four bile acid prodrugs of acyclovir were synthesized, where acyclovir was conjugated to a bile acid via a valine linker. The affinity of the prodrug for hASBT was determined through inhibition of taurocholate uptake by COS-7 cells transfected with hASBT (hASBT-COS). The prodrug with the highest inhibitory affinity was further evaluated in vitro and in vivo. The prodrug acyclovir valylchenodeoxycholate yielded the highest affinity for hASBT (Ki = 35 microM), showing that chenodeoxycholate is the free bile acid with the greatest affinity for hASBT. Acyclovir valylchenodeoxycholate's affinity was similar to that of cholic acid (Ki = 25 microM). Further characterization showed that acyclovir was catalytically liberated from acyclovir valylchenode-oxycholate by esterase. Relative to cellular uptake studies of acyclovir alone, the cellular uptake from the prodrug resulted in a 16-fold greater acyclovir accumulation within hASBT-COS cells, indicating enhanced permeation properties of the prodrug. Enhanced permeability was due to hASBT-mediated uptake and increased passive permeability. The extent of acyclovir uptake in the presence of sodium was 1.4-fold greater than the extent of passive prodrug uptake in the absence of sodium (p = 0.02), indicating translocation of the prodrug by hASBT. The prodrug also exhibited an almost 12-fold enhanced passive permeability, relative to acyclovir's passive permeability. Oral administration of acyclovir valylchenodeoxycholate to rats resulted in a 2-fold increase in the bioavailability of acyclovir, compared to the bioavailability after administration of acyclovir alone. Results indicate that a bile acid prodrug strategy may be useful in improving the oral bioavailability of

  8. The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity.

    PubMed

    Broeders, Evie P M; Nascimento, Emmani B M; Havekes, Bas; Brans, Boudewijn; Roumans, Kay H M; Tailleux, Anne; Schaart, Gert; Kouach, Mostafa; Charton, Julie; Deprez, Benoit; Bouvy, Nicole D; Mottaghy, Felix; Staels, Bart; van Marken Lichtenbelt, Wouter D; Schrauwen, Patrick

    2015-09-01

    The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans. PMID:26235421

  9. Exogenous fatty acids affect CDP-choline pathway to increase phosphatidylcholine synthesis in granular pneumocytes

    SciTech Connect

    Chander, A.; Gullo, J.; Reicherter, J.; Fisher, A.

    1987-05-01

    Regulation of phosphatidylcholine (PC) synthesis in rat granular pneumocytes isolated by tryptic digestion of lungs and maintained in primary culture for 24 h was investigated by following effects of exogenous fatty acids on (/sup 3/H-methyl)choline incorporation into PC and disaturated PC (DSPC). At 0.1 mM choline, the rate of choline incorporation into PC and DSPC was 440 +/- and 380 +/- 50 pmol/h/ug Pi (mean +/- SE, n=3-5), respectively, and was linear for up to 3 h. PC synthesis was significantly increased by 0.1 mM each of palmitic, oleic, linoleic, or linolenic acid. However, synthesis of DSPC was increased only by palmitic acid and this increase was prevented by addition of oleic acid suggesting lack of effect on the remodeling pathway. Pulse-chase experiments with choline in absence or presence of palmitic or oleic acid showed that the label declined in choline phosphate and increased in PC more rapidly in presence of either of the fatty acids, suggesting rapid conversion of choline phosphate to PC. Microsomal choline phosphate cytidyltransferase activity in cells preincubated without or with palmitic acid for 3 h was 0.81 +/- 0.07 and 1.81 +/- 0.09 nmol choline phosphate converted/min/mg protein (n=4). These results suggest that in granular pneumocytes, exogenous fatty acids modulate PC synthesis by increasing choline phosphate cytidyltransferase activity.

  10. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    SciTech Connect

    Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

    2012-08-15

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

  11. The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: characterization and significance.

    PubMed Central

    Zeldin, D C; Plitman, J D; Kobayashi, J; Miller, R F; Snapper, J R; Falck, J R; Szarek, J L; Philpot, R M; Capdevila, J H

    1995-01-01

    Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney. Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoic acids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in the presence of NADPH-cytochrome P450 reductase and cytochrome b5, metabolized arachidonic acid, producing primarily EETs. EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid. Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, 11(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid. At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung. Images PMID:7738183

  12. Notalgia paresthetica with a significant increase in the number of intradermal nerves.

    PubMed

    Inaloz, H Serhat; Kirtak, Necmettin; Erguven, H Gulcin; Karakok, Metin; Inaloz, Serap S

    2002-11-01

    Notalgia paresthetica is an isolated mononeuropathy involving the skin over or near the scapula. The cause remains unknown. We histologically observed a significant increase in the number of dermal nerves in a case of notalgia paresthetica. Immunohistochemical examination using a neural marker, S-100, positively stained the nerves. Interestingly, a biopsy from perilesional skin also showed an abnormal nerve proliferation. PMID:12484438

  13. Prednisone lowers serum uric acid levels in patients with decompensated heart failure by increasing renal uric acid clearance.

    PubMed

    Liu, Chao; Zhen, Yuzhi; Zhao, Qingzhen; Zhai, Jian-Long; Liu, Kunshen; Zhang, Jian-Xin

    2016-07-01

    Clinical studies have shown that large doses of prednisone could lower serum uric acid (SUA) in patients with decompensated heart failure (HF); however, the optimal dose of prednisone and underlying mechanisms are unknown. Thirty-eight patients with decompensated HF were randomized to receive standard HF care alone (n = 10) or with low-dose (15 mg/day, n = 8), medium-dose (30 mg/day, n = 10), or high-dose prednisone (60 mg/day, n = 10), for 10 days. At the end of the study, only high-dose prednisone significantly reduced SUA, whereas low- and medium-dose prednisone and standard HF care had no effect on SUA. The reduction in SUA in high-dose prednisone groups was associated with a significant increase in renal uric acid clearance. In conclusion, prednisone can reduce SUA levels by increasing renal uric acid clearance in patients with decompensated HF. PMID:27144905

  14. Increased brain uptake of gamma-aminobutyric acid in a rabbit model of hepatic encephalopathy

    SciTech Connect

    Bassett, M.L.; Mullen, K.D.; Scholz, B.; Fenstermacher, J.D.; Jones, E.A. )

    1990-03-01

    Transfer of the inhibitory neurotransmitter gamma-aminobutyric acid across the normal blood-brain barrier is minimal. One prerequisite for gamma-aminobutyric acid in plasma contributing to the neural inhibition of hepatic encephalopathy would be that increased transfer of gamma-aminobutyric acid across the blood-brain barrier occurs in liver failure. The aim of the present study was to determine if brain gamma-aminobutyric acid uptake is increased in rabbits with stage II-III (precoma) hepatic encephalopathy due to galactosamine-induced fulminant hepatic failure. A modification of the Oldendorf intracarotid artery-injection technique was applied. (3H) gamma-aminobutyric acid, (14C) butanol, and 113mIn-labeled serum protein (transferrin) were injected simultaneously 4 s before decapitation. The ipsilateral brain uptake index of gamma-aminobutyric acid was determined from measurements of the 3 isotopes in 5 brain regions. Uncorrected or simple brain uptake indices of (3H) gamma-aminobutyric acid and (113mIn) transferrin were calculated using (14C) butanol as the highly extracted reference compound. The (113mIn) transferrin data were also used to correct the brain uptake index of (3H) gamma-aminobutyric acid for intravascular retention of (3H) gamma-aminobutyric acid. The methodology adopted minimized problems attributable to rapid (3H) gamma-aminobutyric acid metabolism, and slow brain washout and recirculation of the radiolabeled tracers. Both the uncorrected and corrected brain uptake indices of gamma-aminobutyric acid as well as the simple brain uptake index of transferrin were significantly increased in both stage II and III hepatic encephalopathy in all brain regions studied. Moreover, these brain uptake indices were significantly greater in stage III hepatic encephalopathy than in stage II hepatic encephalopathy.

  15. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    PubMed

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume. PMID:20929114

  16. Tassel Removal Positively Affects Biomass Production Coupled with Significantly Increasing Stem Digestibility in Switchgrass

    PubMed Central

    Zhao, Chunqiao; Fan, Xifeng; Hou, Xincun; Zhu, Yi; Yue, Yuesen; Zhang, Shuang; Wu, Juying

    2015-01-01

    In this study, tassels of Cave-in-Rock (upland) and Alamo (lowland) were removed at or near tassel emergence to explore its effects on biomass production and quality. Tassel-removed (TR) Cave-in-Rock and Alamo both exhibited a significant (P<0.05) increase in plant heights (not including tassel length), tiller number, and aboveground biomass dry weight (10% and 12%, 30% and 13%, 13% and 18%, respectively by variety) compared to a control (CK) treatment. Notably, total sugar yields of TR Cave-in-Rock and Alamo stems increased significantly (P<0.05 or 0.01) by 19% and 19%, 21% and 14%, 52% and 18%, respectively by variety, compared to those of control switchgrass under 3 treatments by direct enzymatic hydrolysis (DEH), enzymatic hydrolysis after 1% NaOH pretreatment (EHAL) and enzymatic hydrolysis after 1% H2SO4 pretreatment (EHAC). These differences were mainly due to significantly (P<0.05 or 0.01) higher cellulose content, lower cellulose crystallinity indexes (CrI) caused by higher arabinose (Ara) substitution in xylans, and lower S/G ratio in lignin. However, the increases of nitrogen (N) and sulphur (S) concentration negatively affects the combustion quality of switchgrass aboveground biomass. This work provides information for increasing biomass production and quality in switchgrass and also facilitates the inhibition of gene dispersal of switchgrass in China. PMID:25849123

  17. Why does precipitation in northwest China show a significant increasing trend from 1960 to 2010?

    NASA Astrophysics Data System (ADS)

    Li, Baofu; Chen, Yaning; Chen, Zhongsheng; Xiong, Heigang; Lian, Lishu

    2016-01-01

    Based on monthly precipitation data from 74 weather stations in the arid region of northwest China, we employed statistical methods to analyse the characteristics of precipitation and investigated the relationships between precipitation and 11 atmospheric circulations. The results showed that the precipitation in northwest China had a significantly increasing trend (P < 0.01), at a rate of 0.61 mm/year, which is higher than the average rate of China (- 0.16 mm/year) for the same period. Annual precipitation increased markedly after 1987, but the increase in precipitation gradually declined from north to south and from west to east. We found that the precipitation variation in spring, summer, autumn, and winter plays an important role in the yearly change, accounting for 21.6%, 42.4%, 18.4%, and 17.6%, respectively. The correlation analysis indicated that the annual precipitation revealed strong and significant associations with the West Pacific Subtropical High (WPSH, R = 0.60, P < 0.001) and the North America Subtropical High (NASH, R = 0.57, P < 0.001) from 1960 to 2010. We therefore suggest that the strengthening of the WPSH and NASH after the mid-1980s is probably the main cause for the significant increasing trend of precipitation in northwest China.

  18. Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences

    PubMed Central

    Derr, Julien; Manapat, Michael L.; Rajamani, Sudha; Leu, Kevin; Xulvi-Brunet, Ramon; Joseph, Isaac; Nowak, Martin A.; Chen, Irene A.

    2012-01-01

    During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life. PMID:22319215

  19. The Expression and Prognostic Significance of Retinoic Acid Metabolising Enzymes in Colorectal Cancer

    PubMed Central

    Brown, Gordon T.; Cash, Beatriz Gimenez; Blihoghe, Daniela; Johansson, Petronella; Alnabulsi, Ayham; Murray, Graeme I.

    2014-01-01

    Colorectal cancer is one of the most common types of cancer with over fifty percent of patients presenting at an advanced stage. Retinoic acid is a metabolite of vitamin A and is essential for normal cell growth and aberrant retinoic acid metabolism is implicated in tumourigenesis. This study has profiled the expression of retinoic acid metabolising enzymes using a well characterised colorectal cancer tissue microarray containing 650 primary colorectal cancers, 285 lymph node metastasis and 50 normal colonic mucosal samples. Immunohistochemistry was performed on the tissue microarray using monoclonal antibodies which we have developed to the retinoic acid metabolising enzymes CYP26A1, CYP26B1, CYP26C1 and lecithin retinol acyl transferase (LRAT) using a semi-quantitative scoring scheme to assess expression. Moderate or strong expression of CYP26A1was observed in 32.5% of cancers compared to 10% of normal colonic epithelium samples (p<0.001). CYP26B1 was moderately or strongly expressed in 25.2% of tumours and was significantly less expressed in normal colonic epithelium (p<0.001). CYP26C1 was not expressed in any sample. LRAT also showed significantly increased expression in primary colorectal cancers compared with normal colonic epithelium (p<0.001). Strong CYP26B1 expression was significantly associated with poor prognosis (HR = 1.239, 95%CI = 1.104–1.390, χ2 = 15.063, p = 0.002). Strong LRAT was also associated with poorer outcome (HR = 1.321, 95%CI = 1.034–1.688, χ2 = 5.039, p = 0.025). In mismatch repair proficient tumours strong CYP26B1 (HR = 1.330, 95%CI = 1.173–1.509, χ2 = 21.493, p<0.001) and strong LRAT (HR = 1.464, 95%CI = 1.110–1.930, χ2 = 7.425, p = 0.006) were also associated with poorer prognosis. This study has shown that the retinoic acid metabolising enzymes CYP26A1, CYP26B1 and LRAT are significantly overexpressed in colorectal cancer and that CYP26B1 and LRAT are

  20. Endogenous flow of amino acids in the avian ileum as influenced by increasing dietary peptide concentrations.

    PubMed

    Ravindran, Velmurugu; Morel, Patrick C H; Rutherfurd, Shane M; Thomas, Donald V

    2009-03-01

    The aim of the present study was to establish whether feeding broiler chickens with diets containing increasing dietary peptide concentrations would cause increases in ileal endogenous amino acid flow. The flow of N and most amino acids increased quadratically (P < 0.05 to 0.001) with increasing dietary concentrations of peptides. The exceptions were the flow of threonine, serine, glycine, tyrosine and cystine, which increased linearly (P < 0.001) with dietary peptide levels. Another notable exception to the general trend was the flow of proline, which was significantly higher (P < 0.01) in birds fed the protein-free diet. The amino acid profile of endogenous protein, expressed as proportion of crude protein, indicated that the ratios of threonine, glutamic acid, proline, glycine, leucine, histidine, arginine and cystine were influenced (P < 0.05) with increasing dietary peptide concentrations. In general, compared with the protein-free diet, the ratios of threonine and arginine in endogenous protein were lower (P < 0.05) and those of glutamic acid, glycine and histidine were greater (P < 0.05) in diets with high concentrations of peptides. The ratio of proline was found to decrease (P < 0.05) with increasing dietary peptide concentrations. These changes in the amino acid profile of endogenous protein are probably reflective of changes in the output of one or more of the components of endogenous protein. Overall, the present results demonstrated that increasing dietary peptide concentrations increased the flow of endogenous amino acid flow at the terminal ileum of broiler chickens in a dose-dependent manner and also caused changes in the composition of endogenous protein. The observed changes in endogenous amino flow will influence the maintenance requirements for amino acids and also have implications for the calculation of true digestibility coefficient of feedstuffs. PMID:18662428

  1. Acetic acid suppresses the increase in disaccharidase activity that occurs during culture of caco-2 cells.

    PubMed

    Ogawa, N; Satsu, H; Watanabe, H; Fukaya, M; Tsukamoto, Y; Miyamoto, Y; Shimizu, M

    2000-03-01

    To understand how blood glucose level is lowered by oral administration of vinegar, we examined effects of acetic acid on glucose transport and disaccharidase activity in Caco-2 cells. Cells were cultured for 15 d in a medium containing 5 mmol/L of acetic acid. This chronic treatment did not affect cell growth or viability, and furthermore, apoptotic cell death was not observed. Glucose transport, evaluated with a nonmetabolizable substrate, 3-O-methyl glucose, also was not affected. However, the increase of sucrase activity observed in control cells (no acetic acid) was significantly suppressed by acetic acid (P < 0.01). Acetic acid suppressed sucrase activity in concentration- and time-dependent manners. Similar treatments (5 mmol/L and 15 d) with other organic acids such as citric, succinic, L-maric, L-lactic, L-tartaric and itaconic acids, did not suppress the increase in sucrase activity. Acetic acid treatment (5 mmol/L and 15 d) significantly decreased the activities of disaccharidases (sucrase, maltase, trehalase and lactase) and angiotensin-I-converting enzyme, whereas the activities of other hydrolases (alkaline phosphatase, aminopeptidase-N, dipeptidylpeptidase-IV and gamma-glutamyltranspeptidase) were not affected. To understand mechanisms underlying the suppression of disaccharidase activity by acetic acid, Northern and Western analyses of the sucrase-isomaltase complex were performed. Acetic acid did not affect the de novo synthesis of this complex at either the transcriptional or translational levels. The antihyperglycemic effect of acetic acid may be partially due to the suppression of disaccharidase activity. This suppression seems to occur during the post-translational processing. PMID:10702577

  2. An innovative thermal system approach significantly increases system reliability and power and packaging densities

    SciTech Connect

    Burns, K.K.; Alexander, R.; Burns, J.R.

    1996-12-31

    An innovative self-contained active cooling system for electronic products, which increases power and packaging densities and improves reliability, was investigated. The cooling technology uses low cost, readily available, and reliable components. While this thermal control method can be applied to many applications, a simple power system cooling application will be demonstrated. The application demonstrates increased power density of a common 48 Vdc to 5Vdc high density DC-DC power converter module having standard dimensions of 2.4in.x4.6in.x0.5in. An increase in power density from 50W/in{sup 3} to over 80W/in{sup 3} was realized. In addition, significantly high calculated MTBF, from 300K hours to greater than 3M hours, was realized with low temperature operation.

  3. Increased frequency of monoclonal gammopathy of undetermined significance in patients with nonimmune chronic idiopathic neutropenia syndrome.

    PubMed

    Papadaki, H A; Eliopoulos, D G; Ponticoglou, C; Eliopoulos, G D

    2001-04-01

    This study describes the frequency of monoclonal gammopathy of undetermined significance (MGUS) and the changes in some inflammation-related serum proteins in 157 patients with nonimmune chronic idiopathic neutropenia syndrome (NI-CINS). Of these patients, 42 had pronounced neutropenia with neutrophil counts < 1500/microL, and 115 had mild neutropenia with neutrophil counts ranging from 1500 to 2499/microL. Sixty-six volunteers served as healthy control subjects and 157 age- and sex-matched patients hospitalized for nonmalignant diseases served as patient control subjects. We found that 28.6% of patients with pronounced neutropenia and 14.8% of patients with mild neutropenia had increased serum gamma globulins (above the 95% confidence limit of values of the control subjects). In the group of patients with pronounced neutropenia, 30.9% had increased immunoglobulin (Ig)G values and 23.8% had increased IgA values. In the group of patients with mild neutropenia, 17.4% had increased IgG values and 21.7% had increased IgA values. IgG and IgA values strongly correlated with the neutrophil count. No changes in serum IgM were found. Three of 42 patients with pronounced neutropenia (7.14%) and 3 of 115 patients with mild neutropenia (2.61%) had serum immunofixation tests which showed a small monoclonal spike--4 were IgG-kappa type, 1 was IgG-lambda type, and 1 was IgA-kappa type. None of the healthy or patient control subjects had any evidence of MGUS. No significant changes in the amount of monoclonal spikes were documented during an 18- to 143-month follow-up (median, 58 months). Except for significantly increased alpha1-antitrypsin levels, there were no significant differences in the levels of acute-phase proteins studied between the study patients and the control subjects. These findings are consistent with our previous report suggesting the possible existence of an unrecognized low-grade chronic inflammation in patients with NI-CINS, which may be involved in the

  4. Fatty acids and glucose increase neutral endopeptidase activity in human microvascular endothelial cells.

    PubMed

    Muangman, Pornprom; Spenny, Michelle L; Tamura, Richard N; Gibran, Nicole S

    2003-06-01

    Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and endothelin may regulate response to injury. We have previously demonstrated increased NEP localization and enzyme activity in diabetic wounds and skin compared with normal controls. We hypothesized that hyperlipidemia and hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP activity and thereby diminish normal response to injury. Human microvascular endothelial cells were treated with five different fatty acids (40 microM) with varying degrees of saturation, including oleic acid, linoleic acid, palmitic acid, stearic acid, and linolenic acid and/or glucose (40 mM) for 48 h. The effect of the antioxidative agents vitamin E and C on NEP enzyme activation was determined by treating the cultured cells with alpha-tocopherol succinate and/or L-ascorbic acid. Cell membrane preparations were assayed for NEP activity by incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a fluorescent degradation product methoxy 2 naphthylamine. High glucose or fatty acid concentration upregulated NEP activity. The highest NEP activity was observed with combined elevated glucose, linoleic acid, and oleic acid (P < 0.05). Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P < 0.05). Thus, hyperglycemia and hyperlipidemia associated with type 2 diabetes mellitus may increase endothelial cell NEP activity and thereby decrease early pro-inflammatory responses. The modulator effect of vitamin E and C on NEP membrane enzyme activity after exposure to fatty acid stimulation suggests that lipid oxidation may activate NEP. PMID:12785004

  5. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    PubMed Central

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  6. Exam anxiety induces significant blood pressure and heart rate increase in college students.

    PubMed

    Zhang, Zhihong; Su, Hai; Peng, Qiang; Yang, Qing; Cheng, Xiaoshu

    2011-01-01

    To investigate the relationship between the anxiety and blood pressure (BP) and heart rate (HR) increase in peri-exam period. Sixty-four college students(20.0 ± 0.1 year old) were included in this study. The BP and HR were measured in the morning and in the evening for 3 days during the prereview (ba), review, and exam periods. The BP and HR increase amplitudes (HRIA) of review and exam periods were from the difference of corresponding values and basic values, and the BPIA/baBP and HRIA/baHR were calculated. All of the students completed the Self-Rating Anxiety score (SAS) questionnaire the first day of the exam period. Scores over 50 points were used as the standard for anxiety. From the prereview to exam periods, the BP and HR increased gradually. The exam SBPIA (4.3 ± 1.3 vs. 0.3 ± 0.5 mmHg, P < 0.05) and DBPIA (4.4 ± 1.5 vs. 1.0 ± 0.5 mmHg, P < 0.05) were significantly higher in the anxiety group than in the no-anxiety group. The SBPIA/DBPIA and HRIA showed a similar profile also(9.7 ± 2.1 vs. 1.9 ± 0.9 bpm, P < 0.05). Strong positive correlations were found between the SAS score and BPIA and HRIA both in the review and exam period. The smoking group and family hypertension group had higher anxiety score; meanwhile, their exam BPIAs and HRIAs were significantly higher than their corresponding group. The BP and HR increase in the review and exam period, anxiety is an important factor of BP and HR increase. PMID:21787237

  7. Significantly Increasing the Ductility of High Performance Polymer Semiconductors through Polymer Blending.

    PubMed

    Scott, Joshua I; Xue, Xiao; Wang, Ming; Kline, R Joseph; Hoffman, Benjamin C; Dougherty, Daniel; Zhou, Chuanzhen; Bazan, Guillermo; O'Connor, Brendan T

    2016-06-01

    Polymer semiconductors based on donor-acceptor monomers have recently resulted in significant gains in field effect mobility in organic thin film transistors (OTFTs). These polymers incorporate fused aromatic rings and have been designed to have stiff planar backbones, resulting in strong intermolecular interactions, which subsequently result in stiff and brittle films. The complex synthesis typically required for these materials may also result in increased production costs. Thus, the development of methods to improve mechanical plasticity while lowering material consumption during fabrication will significantly improve opportunities for adoption in flexible and stretchable electronics. To achieve these goals, we consider blending a brittle donor-acceptor polymer, poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiadiazolo[3,4-c]pyridine] (PCDTPT), with ductile poly(3-hexylthiophene). We found that the ductility of the blend films is significantly improved compared to that of neat PCDTPT films, and when the blend film is employed in an OTFT, the performance is largely maintained. The ability to maintain charge transport character is due to vertical segregation within the blend, while the improved ductility is due to intermixing of the polymers throughout the film thickness. Importantly, the application of large strains to the ductile films is shown to orient both polymers, which further increases charge carrier mobility. These results highlight a processing approach to achieve high performance polymer OTFTs that are electrically and mechanically optimized. PMID:27200458

  8. Chemical Changes Associated with Increased Acid Resistance of Er:YAG Laser Irradiated Enamel

    PubMed Central

    Olea-Mejía, Oscar Fernando; García-Fabila, María Magdalena; Rodríguez-Vilchis, Laura Emma; Sánchez-Flores, Ignacio; Centeno-Pedraza, Claudia

    2014-01-01

    Background. An increase in the acid resistance of dental enamel, as well as morphological and structural changes produced by Er:YAG laser irradiation, has been reported. Purpose. To evaluate the chemical changes associated with acid resistance of enamel treated with Er:YAG laser. Methods. Forty-eight enamel samples were divided into 4 groups (n = 12). Group I (control); Groups II, III, and IV were irradiated with Er:YAG at 100 mJ (12.7 J/cm2), 200 mJ (25.5 J/cm2), and 300 mJ (38.2 J/cm2), respectively. Results. There were significant differences in composition of irradiated groups (with the exception of chlorine) and in the amount of calcium released. Conclusions. Chemical changes associated with an increase in acid resistance of enamel treated with Er:YAG laser showed a clear postirradiation pattern characterized by a decrease in C at.% and an increase in O, P, and Ca at.% and no changes in Cl at.%. An increased Ca/P ratio after Er:YAG laser irradiation was associated with the use of higher laser energy densities. Chemical changes produced by acid dissolution showed a similar trend among experimental groups. Stable or increased Ca/P ratio after acid dissolution was observed in the irradiated groups, with reduction of Ca released into the acid solution. PMID:24600327

  9. Significant increase of surface ozone at a rural site, north of eastern China

    NASA Astrophysics Data System (ADS)

    Ma, Zhiqiang; Xu, Jing; Quan, Weijun; Zhang, Ziyin; Lin, Weili; Xu, Xiaobin

    2016-03-01

    Ozone pollution in eastern China has become one of the top environmental issues. Quantifying the temporal trend of surface ozone helps to assess the impacts of the anthropogenic precursor reductions and the likely effects of emission control strategies implemented. In this paper, ozone data collected at the Shangdianzi (SDZ) regional atmospheric background station from 2003 to 2015 are presented and analyzed to obtain the variation in the trend of surface ozone in the most polluted region of China, north of eastern China or the North China Plain. A modified Kolmogorov-Zurbenko (KZ) filter method was performed on the maximum daily average 8 h (MDA8) concentrations of ozone to separate the contributions of different factors from the variation of surface ozone and remove the influence of meteorological fluctuations on surface ozone. Results reveal that the short-term, seasonal and long-term components of ozone account for 36.4, 57.6 and 2.2 % of the total variance, respectively. The long-term trend indicates that the MDA8 has undergone a significant increase in the period of 2003-2015, with an average rate of 1.13 ± 0.01 ppb year-1 (R2 = 0.92). It is found that meteorological factors did not significantly influence the long-term variation of ozone and the increase may be completely attributed to changes in emissions. Furthermore, there is no significant correlation between the long-term O3 and NO2 trends. This study suggests that emission changes in VOCs might have played a more important role in the observed increase of surface ozone at SDZ.

  10. Proposed U.S. Geological Survey Budget Would Provide "Significant" Increase

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2013-04-01

    The White House's proposed budget for the U.S. Geological Survey (USGS) for fiscal year (FY) 2014, which the administration submitted to Congress on 10 April, would provide the agency with 1.17 billion, an increase of 98.02 million, 9.17% more than the FY 2012 enacted budget of $1.07 billion (see Table 1). The proposed budget is a "significant" increase and "makes a statement about the USGS's relevance in the federal research community," USGS acting director Suzette Kimball said at the agency's briefing. Because Congress approved the FY 2013 budget just a few weeks prior to the release of the Obama administration's proposal, the FY 2014 budget is compared with the FY 2012 enacted budget here.

  11. The APC I1307K allele conveys a significant increased risk for cancer.

    PubMed

    Leshno, Ari; Shapira, Shiran; Liberman, Eliezer; Kraus, Sarah; Sror, Miri; Harlap-Gat, Amira; Avivi, Doran; Galazan, Lior; David, Maayan; Maharshak, Nitsan; Moanis, Serhan; Arber, Nadir; Moshkowitz, Menachem

    2016-03-15

    This study is the first attempt to evaluate the association between the APC I1307K variant and overall cancer risk. It is unique in both its large sample size and in the reliability of data in the control group. The findings described in this article have major implications in terms of identifying asymptomatic individuals who are at increased risk to harbor cancer and therefore targeted to be enrolled in specific early detection and prevention programs. The prevalence of the APC I1307K missense mutation among Ashkenazi Jews is ∼ 6%. Carriers are at an increased risk for colorectal neoplasia. In this study, we examined the association of this variant with non-colorectal cancers. Consecutive 13,013 healthy subjects who underwent screening at the Integrated Cancer Prevention Center between 2006 and 2014 were enrolled. This population was supplemented with 1,611 cancer patients from the same institution. Demographics, medical history, and pathological data were recorded. Mortality data were obtained from the Ministry of Health's registry. The prevalence of APC I1307K in cancer patients and healthy subjects was compared. The APC I1307K variant was detected in 189 (11.8%) cancer patients compared to 614 (4.7%) healthy subjects, reflecting an adjusted age and sex odds ratio (OR) of 2.53 (p < 0.0001). History of two or more cancer types was associated with a positive carrier prevalence (OR = 4.38 p < 0.0001). Males had significantly increased carrier prevalence in lung, urologic, pancreatic, and skin cancers. The carrier prevalence among females was significantly higher only in breast and skin cancers. Female carriers developed cancer at a significantly older age compared to non-carriers (average 62.7 years vs. 57.8, respectively, p = 0.027), had better survival rates (HR = 0.58, p = 0.022) and overall increased longevity (average age of death 78.8 vs. 70.4 years, respectively, p = 0.003). In conclusion, the APC I1307K variant is a reliable marker for overall cancer risk

  12. Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling

    PubMed Central

    Alrob, Osama Abo; Sankaralingam, Sowndramalingam; Ma, Cary; Wagg, Cory S.; Fillmore, Natasha; Jaswal, Jagdip S.; Sack, Michael N.; Lehner, Richard; Gupta, Mahesh P.; Michelakis, Evangelos D.; Padwal, Raj S.; Johnstone, David E.; Sharma, Arya M.; Lopaschuk, Gary D.

    2014-01-01

    Aims Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. Methods and results C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and β-hydroxyacyl-CoA dehydrogenase (β-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and β-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and β-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. Conclusion We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial β-oxidation enzymes. PMID:24966184

  13. [A significant increase in intraoperative flash visual evoked potential amplitude during craniopharyngioma surgery-case report].

    PubMed

    Kawaguchi, Tomohiro; Ogawa, Yoshikazu; Fujiwara, Satoru; Tominaga, Teiji

    2015-04-01

    The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction. PMID:25838303

  14. Sleep restriction increases free fatty acids in healthy men

    PubMed Central

    Broussard, Josiane L.; Chapotot, Florian; Abraham, Varghese; Day, Andrew; Delebecque, Fanny; Whitmore, Harry R.; Tasali, Esra

    2015-01-01

    Aims/hypothesis Sleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels. Methods We studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test. Results Sleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels. Conclusions/interpretation Sleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss. PMID:25702040

  15. Significant Increase in Ecosystem C Can Be Achieved with Sustainable Forest Management in Subtropical Plantation Forests

    PubMed Central

    Wei, Xiaohua; Blanco, Juan A.

    2014-01-01

    Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500–2500 trees ha−1. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata) plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir – Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr−1, offsetting 1.9% of China’s annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production of timber

  16. Anti-PD-1 antibody significantly increases therapeutic efficacy of Listeria monocytogenes (Lm)-LLO immunotherapy

    PubMed Central

    2013-01-01

    Background One of the significant tumor immune escape mechanisms and substantial barrier for successful immunotherapy is tumor-mediated inhibition of immune response through cell-to-cell or receptor/ligand interactions. Programmed death receptor-1 (PD-1) interaction with its ligands, PD-L1 and PD-L2, is one of the important strategies that many tumors employ to escape immune surveillance. Upon PD-Ls binding to PD-1, T cell receptor (TCR) signaling is dampened, causing inhibition of proliferation, decreased cytokine production, anergy and/or apoptosis. Thus PD-Ls expression by tumor cells serves as a protective mechanism, leading to suppression of tumor-infiltrating lymphocytes in the tumor microenvironment. Lm-LLO immunotherapies have been shown to be therapeutically effective due to their ability to induce potent antigen-specific immune responses. However, it has been demonstrated that infection with Lm leads to up-regulation of PD-L1 on mouse immune cells that can inhibit effector T cells through PD-1/PD-L1 pathway. Methods Therapeutic and immune efficacy of Listeria-based vaccine (Lm-LLO-E7) in combination with anti-PD-1 antibody was tested in E7 antigen expressing TC-1 mouse tumor model. Tumor growth, survival, as well as peripheral and tumor-infiltrating immune cell profiles after immunotherapy were assessed. Results Here we demonstrate that the combination of an Lm-LLO immunotherapy with anti-PD-1 antibody that blocks PD-1/PD-L1 interaction, significantly improves immune and therapeutic efficacy of treatment in TC-1 mouse tumor model. Importantly, we show that in addition to significant reduction of regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) in both spleen and tumor microenvironment that are mediated solely by the Lm-LLO immunotherapy, the addition of anti-PD-1 antibody to the treatment results in significant increase of antigen-specific immune responses in periphery and CD8 T cell infiltration into the tumor. As a result, this

  17. Significantly Increased Medical Expenditure on Breast Cancer Failing to Bring Down Its Mortality and Incidence Rate

    PubMed Central

    Ho, Ming-Lin; Liaw, Yung-Po; Lai, Chien-Hsu; Chen, Yen-Yu; Tsai, Horng-Der; Chou, Ming-Chih; Hsiao, Yi-Hsuan

    2013-01-01

    Background: The direct impact of medical expenses on breast cancer incidence and mortality rate has not been sufficiently addressed. The purpose of this study is to investigate the potential correlation between the incidence and mortality rate of breast cancer and the medical expenses in Taiwan. Materials and Methods: Breast cancer cases were identified from the National Health Insurance Research Database (NHIRD) with corresponding to International Classification of Diseases, and the Ninth Revision (ICD-9) code 174, 1740-1749, 175, 1750 and 1759 from January 1999 to December 2006. Age-specific incidences were estimated by population data obtained from the Department of Statistics, Ministry of the Interior. Medical expenses, including outpatient and inpatient services, were also retrieved from the NHIRD. Results: The incidence increased from 20.06 per 100,000 in 1999 to 30.34 per 100,000 in 2006; the total expenses increased from 1,449,333,521 in 1999 to 4,350,400,592 Taiwan dollars in 2006. The age-standardized mortality rate for female breast cancer remained essentially unchanged, while the age-standardized incidence increased steadily (except 2002-2003). Among the top 20 coexisting ICD-9 codes for expenses, four are directly on cancers, while 16 are on other diseases or symptoms, which are not necessarily caused by breast cancer. Conclusions: Significantly increased medical expenditure on breast cancer failed to bring down its mortality and incidence rate. The finding has implications for healthcare policy planners in proposing strategies for breast cancer control and allocating the resources. PMID:23983817

  18. Ascorbic Acid may Exacerbate Aspirin-Induced Increase in Intestinal Permeability.

    PubMed

    Sequeira, Ivana R; Kruger, Marlena C; Hurst, Roger D; Lentle, Roger G

    2015-09-01

    Ascorbic acid in combination with aspirin has been used to prevent aspirin-induced oxidative GI damage. We aimed to determine whether ascorbic acid reduces or prevents aspirin-induced changes in intestinal permeability over a 6-hr period using saccharidic probes mannitol and lactulose. The effects of administration of 600 mg aspirin alone, 500 mg ascorbic acid alone and simultaneous dosage of both agents were compared in a cross-over study in 28 healthy female volunteers. These effects were also compared with that of a placebo. The ability of ascorbic acid to mitigate the effects of aspirin when administered either half an hour before or after dosage with aspirin was also assessed in 19 healthy female volunteers. The excretion of lactulose over the 6-hr period was augmented after consumption of either aspirin or ascorbic acid compared with that after consumption of placebo. Dosage with ascorbic acid alone augmented the excretion of lactulose more than did aspirin alone. Simultaneous dosage with both agents augmented the excretion of lactulose in an additive manner. The timing of dosage with ascorbic acid in relation to that with aspirin had no significant effect on the excretion of the two sugars. These findings indicate that ascorbic acid does not prevent aspirin-induced increase in gut permeability rather that both agents augment it to a similar extent. The additive effect on simultaneous dosage with both agents in augmenting the absorption of lactulose suggests that each influences paracellular permeability by different pathways. PMID:25641731

  19. Increased acid responsiveness in vagal sensory neurons in a guinea pig model of eosinophilic esophagitis

    PubMed Central

    Hu, Youtian; Liu, Zhenyu; Yu, Xiaoyun; Pasricha, Pankaj J.; Undem, Bradley J.

    2014-01-01

    Eosinophilic esophagitis (EoE) is characterized with eosinophils and mast cells predominated allergic inflammation in the esophagus and present with esophageal dysfunctions such as dysphagia, food impaction, and heartburn. However, the underlying mechanism of esophageal dysfunctions is unclear. This study aims to determine whether neurons in the vagal sensory ganglia are modulated in a guinea pig model of EoE. Animals were actively sensitized by ovalbumin (OVA) and then challenged with aerosol OVA inhalation for 2 wk. This results in a mild esophagitis with increases in mast cells and eosinophils in the esophageal wall. Vagal nodose and jugular neurons were disassociated, and their responses to acid, capsaicin, and transient receptor potential vanilloid type 1 (TRPV1) antagonist AMG-9810 were studied by calcium imaging and whole cell patch-clamp recording. Compared with naïve animals, antigen challenge significantly increased acid responsiveness in both nodose and jugular neurons. Their responses to capsaicin were also increased after antigen challenge. AMG-9810, at a concentration that blocked capsaicin-evoked calcium influx, abolished the increase in acid-induced activation in both nodose and jugular neurons. Vagotomy strongly attenuated those increased responses of nodose and jugular neurons to both acid and capsaicin induced by antigen challenge. These data for the first time demonstrated that prolonged antigen challenge significantly increases acid responsiveness in vagal nodose and jugular ganglia neurons. This sensitization effect is mediated largely through TRPV1 and initiated at sensory nerve endings in the peripheral tissues. Allergen-induced enhancement of responsiveness to noxious stimulation by acid in sensory nerve may contribute to the development of esophageal dysfunctions such as heartburn in EoE. PMID:24875100

  20. Significant increase of Curie temperature in nano-scale BaTiO{sub 3}

    SciTech Connect

    Li, Yueliang; Liao, Zhenyu; Fang, Fang; Zhu, Jing; Wang, Xiaohui; Li, Longtu

    2014-11-03

    The low Curie temperature (T{sub c} = 130 °C) of bulk BaTiO{sub 3} greatly limits its applications. In this work, the phase structures of BaTiO{sub 3} nanoparticles with sizes ranging from 2.5 nm to 10 nm were studied at various temperatures by using aberration-corrected transmission electron microscopy (TEM) equipped with an in-situ heating holder. The results implied that each BaTiO{sub 3} nanoparticle was composed of different phases, and the ferroelectric ones were observed in the shells due to the complicated surface structure. The ferroelectric phases in BaTiO{sub 3} nanoparticles remained at 600 °C, suggesting a significant increase of T{sub c}. Based on the in-situ TEM results and the data reported by others, temperature-size phase diagrams for BaTiO{sub 3} particles and ceramics were proposed, showing that the phase transition became diffused and the T{sub c} obviously increased with decreasing size. The present work sheds light on the design and fabrication of advanced devices for high temperature applications.

  1. Significant increasing of onset temperature of FM transition in LSMO thin films

    NASA Astrophysics Data System (ADS)

    Chromik, Štefan; Štrbík, Vladimír; Dobročka, Edmund; Dujavová, Agáta; Reiffers, Marián; Liday, Jozef; Španková, Marianna

    2013-03-01

    La0.67Sr0.33MnO3 (LSMO) thin films with a significant increased onset temperature of ferromagnetic transition were prepared using an on-axis dc magnetron sputtering from a stoichiometric ceramic target onto one-side polished MgO (0 0 1). The highest temperature of insulator-metal transition was observed at TP = 416 K. Magnetization hysteresis curves taken at T = 398 K indicate the beginning of the ferromagnetic transition above 400 K. The negative magnetoresistance reaches 15% at a temperature of 400 K. We show that the LSMO thin films with increased temperature values of resistance peak TP and Curie temperature TC are characteristic by a proper microstructure with distorted orthorhombic unit cells. This microstructure is developed during the layer growth, it is not caused by the underlying substrate and it is linked with an appropriate pseudocubic out-of-plane lattice parameter ac⊥, splitted Bragg reflections in rocking curves and as well as in reciprocal space maps.

  2. Deletion of the DNA Ligase IV Gene in Candida glabrata Significantly Increases Gene-Targeting Efficiency

    PubMed Central

    Cen, Yuke; Fiori, Alessandro

    2015-01-01

    Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in the United States. Over the last decades, its incidence increased, whereas that of Candida albicans decreased slightly. One of the main reasons for this shift is attributed to the inherent tolerance of C. glabrata toward the commonly used azole antifungal drugs. Despite a close phylogenetic distance to Saccharomyces cerevisiae, homologous recombination works with poor efficiency in C. glabrata compared to baker's yeast, in fact limiting targeted genetic alterations of the pathogen's genome. It has been shown that nonhomologous DNA end joining is dominant over specific gene targeting in C. glabrata. To improve the homologous recombination efficiency, we have generated a strain in which the LIG4 gene has been deleted, which resulted in a significant increase in correct gene targeting. The very specific function of Lig4 in mediating nonhomologous end joining is the reason for the absence of clear side effects, some of which affect the ku80 mutant, another mutant with reduced nonhomologous end joining. We also generated a LIG4 reintegration cassette. Our results show that the lig4 mutant strain may be a valuable tool for the C. glabrata research community. PMID:26048009

  3. HBV Outreach Programs Significantly Increase Knowledge and Vaccination Rates Among Asian Pacific Islanders.

    PubMed

    Zacharias, Tresa; Wang, Winnie; Dao, Doan; Wojciechowski, Helena; Lee, William M; Do, Son; Singal, Amit G

    2015-08-01

    Hepatitis B virus (HBV) testing and vaccination rates remain low among Asian-American/Pacific Islanders (APIs) despite high rates of HBV infection. The aim of our study was to assess the effectiveness of an outreach campaign to increase HBV knowledge, testing, and vaccination among a cohort of APIs. Vietnamese Americans were invited to participate in a free HBV screening and vaccination outreach program though pubic service announcements. Attendees completed a survey to assess barriers to vaccination and HBV-related knowledge before and after a 30-min education session by a bilingual board-certified gastroenterologist. Among 98 participants, 100% (22/22) of HBV naïve patients were provided a HBV vaccination series at no cost and over 75% (14/18) of HBV-infected patients were connected to further medical care. Notable reported barriers to prior testing and/or vaccination were cost of the vaccine, concern about missing work for evaluation, and lack of provider recommendation. Knowledge levels about HBV risk factors, potential consequences, and treatment options were poor at baseline but significantly increased after the education session (49 vs. 64%, p < 0.001). Outreach campaigns linked with education can successfully address several barriers to HBV testing and offer an approach to improve HBV awareness and prevention among difficult-to-reach populations. PMID:25476035

  4. Concomitant Sleep Disorders Significantly Increase the Risk of Cardiovascular Disease in Patients with Psoriasis

    PubMed Central

    Chiang, Yi-Ting; Tsai, Yi-Wen; Huang, Weng-Foung; Li, Cheng-Yuan; Wang, Ting-Shun; Tsai, Tsen-Fang

    2016-01-01

    Background The increased rates of cardiovascular morbidity and mortality in patients with psoriasis are not adequately explained by traditional risk factors. Whether concomitant sleep disorders (SDs) modify the risk of cardiovascular disease (CVD) in patients with psoriasis remains unknown. Methods Using the Taiwan National Health Insurance Research Database (NHIRD), we conducted a cohort study to investigate the association between concomitant SDs and CVD risk in patients with psoriasis. Data from 99,628 adults who received a psoriasis diagnosis during the period from 2004 to 2010 were analyzed. Cox proportional hazards regression analysis models were used to compare the risks of ischemic heart disease (IHD) and stroke between patients with and without SDs. Results Psoriasis patients with a concomitant SD had significantly higher risks of IHD (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 1.22–1.28) and stroke (aHR, 1.24; 95% CI, 1.16–1.33) as compared with psoriasis patients without SDs. All psoriasis patient subgroups, including those with mild and severe psoriasis and those with and without arthritis, had increased HRs for IHD and stroke. The increases in IHD and stroke risks conferred by SDs were proportional to the dose of hypnotics used. The effect of SDs on the risks of IHD and stroke was greater in young adults than in middle-aged and older adults. Conclusions The risks of IHD and stroke were higher for psoriasis patients with SDs than for those without SDs. Clinicians should carefully evaluate CVD risk, particularly in young patients with psoriasis. PMID:26745869

  5. Ocean acidification increases fatty acids levels of larval fish.

    PubMed

    Díaz-Gil, Carlos; Catalán, Ignacio A; Palmer, Miquel; Faulk, Cynthia K; Fuiman, Lee A

    2015-07-01

    Rising levels of anthropogenic carbon dioxide in the atmosphere are acidifying the oceans and producing diverse and important effects on marine ecosystems, including the production of fatty acids (FAs) by primary producers and their transfer through food webs. FAs, particularly essential FAs, are necessary for normal structure and function in animals and influence composition and trophic structure of marine food webs. To test the effect of ocean acidification (OA) on the FA composition of fish, we conducted a replicated experiment in which larvae of the marine fish red drum (Sciaenops ocellatus) were reared under a climate change scenario of elevated CO2 levels (2100 µatm) and under current control levels (400 µatm). We found significantly higher whole-body levels of FAs, including nine of the 11 essential FAs, and altered relative proportions of FAs in the larvae reared under higher levels of CO2. Consequences of this effect of OA could include alterations in performance and survival of fish larvae and transfer of FAs through food webs. PMID:26179801

  6. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V.

    2012-02-21

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  7. Recombinant microorganisms for increased production of organic acids

    DOEpatents

    Yi, Jian; Kleff, Susanne; Guettler, Michael V

    2013-04-30

    Disclosed are recombinant microorganisms for producing organic acids. The recombinant microorganisms express a polypeptide that has the enzymatic activity of an enzyme that is utilized in the pentose phosphate cycle. The recombinant microorganism may include recombinant Actinobacillus succinogenes that has been transformed to express a Zwischenferment (Zwf) gene. The recombinant microorganisms may be useful in fermentation processes for producing organic acids such as succinic acid and lactic acid. Also disclosed are novel plasmids that are useful for transforming microorganisms to produce recombinant microorganisms that express enzymes such as Zwf.

  8. Improved bowel preparation increases polyp detection and unmasks significant polyp miss rate

    PubMed Central

    Papanikolaou, Ioannis S; Sioulas, Athanasios D; Magdalinos, Nektarios; Beintaris, Iosif; Lazaridis, Lazaros-Dimitrios; Polymeros, Dimitrios; Malli, Chrysoula; Dimitriadis, George D; Triantafyllou, Konstantinos

    2015-01-01

    AIM: To retrospectively compare previous-day vs split-dose preparation in terms of bowel cleanliness and polyp detection in patients referred for polypectomy. METHODS: Fifty patients underwent two colonoscopies: one diagnostic in a private clinic and a second for polypectomy in a University Hospital. The latter procedures were performed within 12 wk of the index ones. Examinations were accomplished by two experienced endoscopists, different in each facility. Twenty-seven patients underwent screening/surveillance colonoscopy, while the rest were symptomatic. Previous day bowel preparation was utilized initially and split-dose for polypectomy. Colon cleansing was evaluated using the Aronchick scale. We measured the number of detected polyps, and the polyp miss rates per-polyp. RESULTS: Excellent/good preparation was reported in 38 cases with previous-day preparation (76%) vs 46 with split-dose (92%), respectively (P = 0.03). One hundred and twenty-six polyps were detected initially and 169 subsequently (P < 0.0001); 88 vs 126 polyps were diminutive (P < 0.0001), 25 vs 29 small (P = 0.048) and 13 vs 14 equal or larger than 10 mm. The miss rates for total, diminutive, small and large polyps were 25.4%, 30.1%, 13.7% and 6.6%, respectively. Multivariate analysis revealed that split-dose preparation was significantly associated (OR, P) with increased number of polyps detected overall (0.869, P < 0.001), in the right (0.418, P = 0.008) and in the left colon (0.452, P = 0.02). CONCLUSION: Split-dose preparation improved colon cleansing, enhanced polyp detection and unmasked significant polyp miss rates. PMID:26488024

  9. Salicylic Acid Treatment Increases the Levels of Triterpene Glycosides in Black Cohosh (Actaea Racemosa) Rhizomes.

    PubMed

    De Capite, Annette; Lancaster, Tyler; Puthoff, David

    2016-01-01

    Black cohosh (Actaea racemosa) serves as the host plant for the Appalachian azure butterfly, Celastrina neglectamajor. Overharvesting of Black cohosh for the dietary supplement industry may result in its extirpation, and may also cause the elimination of the dependent butterfly. One way to increase or maintain the number of host plants in forested environments would be to reduce the number harvested, for example by increasing the levels of the desired metabolites in Black cohosh rhizomes. The secondary metabolites actein and deoxyactein are triterpene glycosides and are among the compounds associated with the putative activity of Black cohosh extracts. Acetein and deoxyacetein are used to standardize Black cohosh supplements. To gain an understanding of mechanisms that may control actein and deoxyactein accumulation, Black cohosh rhizomes were treated with exogenous salicylic acid, jasmonic acid, or ethylene, or were mechanically wounded. Salicylic acid treatment significantly increased the levels of actein and deoxyactein in the rhizome of Black cohosh, suggesting that the synthesis of triterpene glycosides is controlled in part by salicylic acid. Using salicylic acid or related chemicals to increase the levels of actein and deoxyactein in rhizomes may help supply the supplement industry and, simultaneously, help conserve Black cohosh and species dependent upon it. PMID:26634573

  10. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    SciTech Connect

    Hsieh, Yi-Chen; Lien, Li-Ming; Chung, Wen-Ting; Hsieh, Fang-I; Hsieh, Pei-Fan; Wu, Meei-Maan; Tseng, Hung-Pin; Chiou, Hung-Yi; Chen, Chien-Jen

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  11. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

    PubMed

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  12. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance

    PubMed Central

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-01-01

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80–11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density. PMID:26314987

  13. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils.

    PubMed

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-01-01

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg(-1)) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica. PMID:25394572

  14. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    NASA Astrophysics Data System (ADS)

    Kucharski, Timothy J.; Ferralis, Nicola; Kolpak, Alexie M.; Zheng, Jennie O.; Nocera, Daniel G.; Grossman, Jeffrey C.

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol-1, and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  15. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

    PubMed

    Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain. PMID:24755597

  16. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    SciTech Connect

    Kucharski, TJ; Ferralis, N; Kolpak, AM; Zheng, JO; Nocera, DG; Grossman, JC

    2014-04-13

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  17. Increased Mortality in Diabetic Foot Ulcer Patients: The Significance of Ulcer Type

    PubMed Central

    Chammas, N. K.; Hill, R. L. R.; Edmonds, M. E.

    2016-01-01

    Diabetic foot ulcer (DFU) patients have a greater than twofold increase in mortality compared with nonulcerated diabetic patients. We investigated (a) cause of death in DFU patients, (b) age at death, and (c) relationship between cause of death and ulcer type. This was an eleven-year retrospective study on DFU patients who attended King's College Hospital Foot Clinic and subsequently died. A control group of nonulcerated diabetic patients was matched for age and type of diabetes mellitus. The cause of death was identified from death certificates (DC) and postmortem (PM) examinations. There were 243 DFU patient deaths during this period. Ischaemic heart disease (IHD) was the major cause of death in 62.5% on PM compared to 45.7% on DC. Mean age at death from IHD on PM was 5 years lower in DFU patients compared to controls (68.2 ± 8.7 years versus 73.1 ± 8.0 years, P = 0.015). IHD as a cause of death at PM was significantly linked to neuropathic foot ulcers (OR 3.064, 95% CI 1.003–9.366, and P = 0.049). Conclusions. IHD is the major cause of premature mortality in DFU patients with the neuropathic foot ulcer patients being at a greater risk. PMID:27213157

  18. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils

    PubMed Central

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-01-01

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg−1) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica. PMID:25394572

  19. Incorporation of Farnesol Significantly Increases the Efficacy of Liposomal Ciprofloxacin against Pseudomonas aeruginosa Biofilms in Vitro.

    PubMed

    Bandara, H M H N; Herpin, M J; Kolacny, D; Harb, A; Romanovicz, D; Smyth, H D C

    2016-08-01

    The challenge of eliminating Pseudomonas aeruginosa infections, such as in cystic fibrosis lungs, remains unchanged due to the rapid development of antibiotic resistance. Poor drug penetration into dense P. aeruginosa biofilms plays a vital role in ineffective clearance of the infection. Thus, the current antibiotic therapy against P. aeruginosa biofilms need to be revisited and alternative antibiofilm strategies need to be invented. Fungal quorum sensing molecule (QSM), farnesol, appears to have detrimental effects on P. aeruginosa. Thus, this study aimed to codeliver naturally occurring QSM farnesol, with the antibiotic ciprofloxacin as a liposomal formulation to eradicate P. aeruginosa biofilms. Four different liposomes (with ciprofloxacin and farnesol, Lcip+far; with ciprofloxacin, Lcip; with farnesol, Lfar; control, Lcon) were prepared using dehydration-rehydration method and characterized. Drug entrapment and release were evaluated by spectrometry and high performance liquid chromatography (HPLC). The efficacy of liposomes was assessed using standard biofilm assay. Liposome-treated 24 h P. aeruginosa biofilms were quantitatively assessed by XTT reduction assay and crystal violet assay, and qualitatively by confocal laser scanning microscopy (CLSM) and transmission electron microscopy (TEM). Ciprofloxacin release from liposomes was higher when encapsulated with farnesol (Lcip+far) compared to Lcip (3.06% vs 1.48%), whereas farnesol release was lower when encapsulated with ciprofloxacin (Lcip+far) compared to Lfar (1.81% vs 4.75%). The biofilm metabolism was significantly lower when treated with Lcip+far or Lcip compared to free ciprofloxacin (XTT, P < 0.05). When administered as Lcip+far, the ciprofloxacin concentration required to achieve similar biofilm inhibition was 125-fold or 10-fold lower compared to free ciprofloxacin or Lcip, respectively (P < 0.05). CLSM and TEM confirmed predominant biofilm disruption, greater dead cell ratio, and increased depth of

  20. Increased significance of food wastes: selective recovery of added-value compounds.

    PubMed

    Reis, Igor A O; Santos, Samuel B; Santos, Ludmila A; Oliveira, Naiana; Freire, Mara G; Pereira, Jorge F B; Ventura, Sónia P M; Coutinho, João A P; Soares, Cleide M F; Lima, Álvaro S

    2012-12-15

    A single-step selective separation of two food additives was investigated using alcohol-salt aqueous two-phase systems (ATPS). The selective partitioning of two of the most used additives from a processed food waste material, vanillin and l-ascorbic acid, was successfully accomplished. The results obtained prove that alcohol-salt ATPS can be easily applied as cheaper processes for the selective recovery of valuable chemical products from food wastes and other sources. As a first approach, the phase diagrams of ATPS composed of different alcohol+inorganic salt+water were determined at 298 (± 1)K and atmospheric pressure. The influence of methanol, ethanol, 1-propanol, and 2-propanol and K(3)PO(4), K(2)HPO(4) or KH(2)PO(4)/K(2)HPO(4) in the design of the phase diagrams was addressed. After the evaluation of the phase diagrams behaviour, the influence of the phase forming constituents was assessed towards the partition coefficients and recovery percentages of vanillin and l-ascorbic acid among the coexisting phases. Both model systems and real processed food waste materials were employed. Using these ATPS as partitioning systems it is possible to recover and separate vanillin, which migrates for the alcohol-rich phase, from l-ascorbic acid, which preferentially partitions for the salt-rich phase. PMID:22980828

  1. Constrained parameterisation of photosynthetic capacity causes significant increase of modelled tropical vegetation surface temperature

    NASA Astrophysics Data System (ADS)

    Kattge, J.; Knorr, W.; Raddatz, T.; Wirth, C.

    2009-04-01

    Photosynthetic capacity is one of the most sensitive parameters of terrestrial biosphere models whose representation in global scale simulations has been severely hampered by a lack of systematic analyses using a sufficiently broad database. Due to its coupling to stomatal conductance changes in the parameterisation of photosynthetic capacity may potentially influence transpiration rates and vegetation surface temperature. Here, we provide a constrained parameterisation of photosynthetic capacity for different plant functional types in the context of the photosynthesis model proposed by Farquhar et al. (1980), based on a comprehensive compilation of leaf photosynthesis rates and leaf nitrogen content. Mean values of photosynthetic capacity were implemented into the coupled climate-vegetation model ECHAM5/JSBACH and modelled gross primary production (GPP) is compared to a compilation of independent observations on stand scale. Compared to the current standard parameterisation the root-mean-squared difference between modelled and observed GPP is substantially reduced for almost all PFTs by the new parameterisation of photosynthetic capacity. We find a systematic depression of NUE (photosynthetic capacity divided by leaf nitrogen content) on certain tropical soils that are known to be deficient in phosphorus. Photosynthetic capacity of tropical trees derived by this study is substantially lower than standard estimates currently used in terrestrial biosphere models. This causes a decrease of modelled GPP while it significantly increases modelled tropical vegetation surface temperatures, up to 0.8°C. These results emphasise the importance of a constrained parameterisation of photosynthetic capacity not only for the carbon cycle, but also for the climate system.

  2. Identification of significant medium components that affect docosahexaenoic acid production by Schizochytrium sp. SW1

    NASA Astrophysics Data System (ADS)

    Manikan, Vidyah; Hamid, Aidil A.

    2013-11-01

    Central composite design (CCD) was employed to investigate the significance of glucose, yeast extract, MSG and sea salt in affecting the amount of docosahexaenoic acid (DHA) accumulated by a locally isolated strain of Schizochytrium. Design Expert software was used to construct a set of experiments where each medium component mentioned above was varied over three levels. Cultivation was carried out in 250mL flasks containing 50mL of medium, incubated at 30°C with 200 rpm agitation for 96 hours. ANOVA was conducted to identify the influential factors and the level of their significance where factors that scored a probability value of less than 0.05 were considered significant. The level of influence for each independent variable was also interpreted using perturbation whereas pattern of interaction between the factors were interpreted using interaction plots. This experiment revealed that yeast extract and monosodium glutamate have significant influence on DHA accumulation process by Schizochytrium sp. SW1.

  3. Uric acid or 1-methyl uric acid in the urinary bladder increases serum glucose, insulin, true triglyceride, and total cholesterol levels in Wistar rats.

    PubMed

    Balasubramanian, T

    2003-10-01

    In animals deprived of food for a long period, a drop in the fat mass below 5% of the total body mass results in an increase in blood glucocorticoids and uric acid levels, followed by foraging activity. Since the glucocorticoids increase the uric acid excretion, an increase in the level of uric acid in the bladder urine could be the signal for this feeding behaviour and subsequent fat storage. Accumulation of fat is associated with hyperglycaemia, hyperinsulinaemia, hyperlipidaemia, and hypercholesterolaemia as seen in the metabolic syndrome or hibernation. It is hypothesized that uric acid or its structurally related compound, 1-methyl uric acid (one of the metabolites of the methyl xanthines namely caffeine, theophylline, and theobromine present in coffee, tea, cocoa, and some drugs), can act on the urinary bladder mucosa and increases the blood glucose, insulin, triglyceride, and cholesterol levels. In rats, perfusion of the urinary bladder with saturated aqueous solution of uric acid or 1-methyl uric acid results in a significant increase in the serum levels of glucose, insulin, true triglyceride, and total cholesterol in comparison with perfusion of the bladder with distilled water at 20, 40, and 80 min. The uric acid or the 1-methyl uric acid acts on the urinary bladder mucosa and increases the serum glucose, insulin, true triglyceride, and total cholesterol levels. PMID:15241498

  4. Soy-Based Multiple Amino Acid Oral Supplementation Increases the Anti-Sarcoma Effect of Cyclophosphamide

    PubMed Central

    Yao, Chien-An; Chen, Chin-Chu; Wang, Nai-Phog; Chien, Chiang-Ting

    2016-01-01

    The use of a mixture of amino acids caused a selective apoptosis induction against a variety of tumor cell lines, reduced the adverse effects of anti-cancer drugs and increased the sensitivity of tumor cells to chemotherapeutic agents. We evaluated the effects and underlying mechanisms of soy-derived multiple amino acids’ oral supplementation on the therapeutic efficacy of low-dose cyclophosphamide (CTX) and on tumor growth, apoptosis, and autophagy in severe combined immunodeficiency (SCID) mice that were injected with sarcoma-180 (S-180) cells. 3-methyladenine or siRNA knockdown of Atg5 was used to evaluate its effect on sarcoma growth. A comparison of mice with implanted sarcoma cells, CTX, and oral saline and mice with implanted sarcoma cells, CTX, and an oral soy-derived multiple amino acid supplement indicated that the soy-derived multiple amino acid supplement significantly decreased overall sarcoma growth, increased the Bax/Bcl-2 ratio, caspase 3 expression, and apoptosis, and depressed LC3 II-mediated autophagy. Treatment with 3-methyladenine or Atg5 siRNA elicited similar responses as CTX plus soy-derived multiple amino acid in downregulating autophagy and upregulating apoptosis. A low dose of CTX combined with an oral soy-derived multiple amino acid supplement had a potent anti-tumor effect mediated through downregulation of autophagy and upregulation of apoptosis. PMID:27043621

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

    SciTech Connect

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

    2013-02-01

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

  6. Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids.

    PubMed

    Yang, Li; Li, Bosheng; Zheng, Xiao-yu; Li, Jigang; Yang, Mei; Dong, Xinnian; He, Guangming; An, Chengcai; Deng, Xing Wang

    2015-01-01

    Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits in Arabidopsis thaliana, but its effect on defence remains largely unexplored. Here, we show that hybrids between some A. thaliana accessions show increased resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Comparisons of transcriptomes between these hybrids and their parents after inoculation reveal that several key salicylic acid (SA) biosynthesis genes are significantly upregulated in hybrids. Moreover, SA levels are higher in hybrids than in either parent. Increased resistance to Pst DC3000 is significantly compromised in hybrids of pad4 mutants in which the SA biosynthesis pathway is blocked. Finally, increased histone H3 acetylation of key SA biosynthesis genes correlates with their upregulation in infected hybrids. Our data demonstrate that enhanced activation of SA biosynthesis in A. thaliana hybrids may contribute to their increased resistance to a biotrophic bacterial pathogen. PMID:26065719

  7. Salicylic acid biosynthesis is enhanced and contributes to increased biotrophic pathogen resistance in Arabidopsis hybrids

    PubMed Central

    Yang, Li; Li, Bosheng; Zheng, Xiao-yu; Li, Jigang; Yang, Mei; Dong, Xinnian; He, Guangming; An, Chengcai; Deng, Xing Wang

    2015-01-01

    Heterosis, the phenotypic superiority of a hybrid over its parents, has been demonstrated for many traits in Arabidopsis thaliana, but its effect on defence remains largely unexplored. Here, we show that hybrids between some A. thaliana accessions show increased resistance to the biotrophic bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000. Comparisons of transcriptomes between these hybrids and their parents after inoculation reveal that several key salicylic acid (SA) biosynthesis genes are significantly upregulated in hybrids. Moreover, SA levels are higher in hybrids than in either parent. Increased resistance to Pst DC3000 is significantly compromised in hybrids of pad4 mutants in which the SA biosynthesis pathway is blocked. Finally, increased histone H3 acetylation of key SA biosynthesis genes correlates with their upregulation in infected hybrids. Our data demonstrate that enhanced activation of SA biosynthesis in A. thaliana hybrids may contribute to their increased resistance to a biotrophic bacterial pathogen. PMID:26065719

  8. Engineering Porous Organic Cage Crystals with Increased Acid Gas Resistance.

    PubMed

    Zhu, Guanghui; Hoffman, Christopher D; Liu, Yang; Bhattacharyya, Souryadeep; Tumuluri, Uma; Jue, Melinda L; Wu, Zili; Sholl, David S; Nair, Sankar; Jones, Christopher W; Lively, Ryan P

    2016-07-25

    Both known and new CC3-based porous organic cages are prepared and exposed to acidic SO2 in vapor and liquid conditions. Distinct differences in the stability of the CC3 cages exist depending on the chirality of the diamine linkers used. The acid catalyzed CC3 degradation mechanism is probed via in situ IR and a degradation pathway is proposed and supported with computational results. CC3 crystals synthesized with racemic mixtures of diaminocyclohexane exhibited enhanced stability compared to CC3-R and CC3-S. Confocal fluorescent microscope images reveal that the stability difference in CC3 species originates from an abundance of mesoporous grain boundaries in CC3-R and CC3-S, allowing facile access of aqueous SO2 throughout the crystal, promoting decomposition. These grain boundaries are absent from CC3 crystals made with racemic linkers. PMID:27253350

  9. Leatherback nests increasing significantly in Florida, USA; trends assessed over 30 years using multilevel modeling.

    PubMed

    Stewart, Kelly; Sims, Michelle; Meylan, Anne; Witherington, Blair; Brost, Beth; Crowder, Larry B

    2011-01-01

    Understanding population status for endangered species is critical to developing and evaluating recovery plans mandated by the Endangered Species Act. For sea turtles, changes in abundance are difficult to detect because most life stages occur in the water. Currently, nest counts are the most reliable way of assessing trends. We determined the rate of growth for leatherback turtle (Dermochelys coriacea) nest numbers in Florida (USA) using a multilevel Poisson regression. We modeled nest counts from 68 beaches over 30 years and, using beach-level covariates (including latitude), we allowed for partial pooling of information between neighboring beaches. This modeling approach is ideal for nest count data because it recognizes the hierarchical structure of the data while incorporating variables related to survey effort. Nesting has increased at all 68 beaches in Florida, with trends ranging from 3.1% to 16.3% per year. Overall, across the state, the number of nests has been increasing by 10.2% per year since 1979. Despite being a small population (probably < 1000 individuals), this nesting population may help achieve objectives in the federal recovery plan. This exponential growth rate mirrors trends observed for other Atlantic populations and may be driven partially by improved protection of nesting beaches. However, nesting is increasing even where beach protection has not been enhanced. Climate variability and associated marine food web dynamics, which could enhance productivity and reduce predators, may be driving this trend. PMID:21516903

  10. The organic geochemistry of black sedimentary barite: significance and implications of trapped fatty acids

    USGS Publications Warehouse

    Miller, R.E.; Brobst, D.A.; Beck, P.C.

    1977-01-01

    Fatty acids isolated in sedimentary black barite (BaSO4) from Arkansas and Nevada were identified by gas chromatography-mass spectroscopy. The dominant or major fatty acids found in these beds of barite are C16:0, C18:0, and C18:1. The occurrence and distribution of these acids in this type of rock may serve as "molecular fingerprints" of microbial biogeochemical processes. The organic matter and associated microorganisms are shown to be trapped within the finely crystalline barite, thus forming a closed system for microbial diagenesis. Important differences that occur in the distribution of the lesser or minor fatty acids probably result from: (1) the nature of the progenitor organic detritus in the environment of barite deposition: and (2) the subsequent degree of microbiological alteration of the parent organic debris swept into and trapped in the depositional environment. Three general models of sedimentary environments are proposed in which anoxic conditions may prevail and where barium sulfate (BaSO4) may precipitate: (1) in a silled basin with semi-restricted circulation; (2) on an outer continental shelf where the slope is encroached upon by water of the oxygen minimum layer; (3) on a low-energy, inner shelf or semi-restricted embayment impinged by a wedge of anoxic water. The major geochemical and geological parameters which are believed to be the significant factors controlling the formation and high grade of these organic-rich, black bedded barites are: (1) a unique source of barium-rich fluid that only contains trace amounts of other elements; (2) the presence of an anoxic bottom environment within the depositional basin; (3) a reflux source of sulfate ion; (4) an adequate source of organic matter. The results of this study may serve as guidelines for future exploration in similar, untested sedimentary basins, especially those with rocks of middle Paleozoic age. ?? 1977.

  11. Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein

    PubMed Central

    Gupta, Aditi; Adami, Christoph

    2016-01-01

    Epistatic interactions between residues determine a protein’s adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1) using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient) condition that detects epistasis in most cases. We analyze the “fossils” of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing environment. PMID

  12. Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

    PubMed

    Gupta, Aditi; Adami, Christoph

    2016-03-01

    Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1) using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient) condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing environment. PMID

  13. Big data integration shows Australian bush-fire frequency is increasing significantly.

    PubMed

    Dutta, Ritaban; Das, Aruneema; Aryal, Jagannath

    2016-02-01

    Increasing Australian bush-fire frequencies over the last decade has indicated a major climatic change in coming future. Understanding such climatic change for Australian bush-fire is limited and there is an urgent need of scientific research, which is capable enough to contribute to Australian society. Frequency of bush-fire carries information on spatial, temporal and climatic aspects of bush-fire events and provides contextual information to model various climate data for accurately predicting future bush-fire hot spots. In this study, we develop an ensemble method based on a two-layered machine learning model to establish relationship between fire incidence and climatic data. In a 336 week data trial, we demonstrate that the model provides highly accurate bush-fire incidence hot-spot estimation (91% global accuracy) from the weekly climatic surfaces. Our analysis also indicates that Australian weekly bush-fire frequencies increased by 40% over the last 5 years, particularly during summer months, implicating a serious climatic shift. PMID:26998312

  14. Big data integration shows Australian bush-fire frequency is increasing significantly

    PubMed Central

    Dutta, Ritaban; Das, Aruneema; Aryal, Jagannath

    2016-01-01

    Increasing Australian bush-fire frequencies over the last decade has indicated a major climatic change in coming future. Understanding such climatic change for Australian bush-fire is limited and there is an urgent need of scientific research, which is capable enough to contribute to Australian society. Frequency of bush-fire carries information on spatial, temporal and climatic aspects of bush-fire events and provides contextual information to model various climate data for accurately predicting future bush-fire hot spots. In this study, we develop an ensemble method based on a two-layered machine learning model to establish relationship between fire incidence and climatic data. In a 336 week data trial, we demonstrate that the model provides highly accurate bush-fire incidence hot-spot estimation (91% global accuracy) from the weekly climatic surfaces. Our analysis also indicates that Australian weekly bush-fire frequencies increased by 40% over the last 5 years, particularly during summer months, implicating a serious climatic shift. PMID:26998312

  15. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    PubMed

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL. PMID:26101530

  16. Modern Environmental Health Hazards: A Public Health Issue of Increasing Significance in Africa

    PubMed Central

    Nweke, Onyemaechi C.; Sanders III, William H.

    2009-01-01

    Objectives Traditional hazards such as poor sanitation currently account for most of Africa’s environmentally related disease burden. However, with rapid development absent appropriate safeguards for environment and health, modern environmental health hazards (MEHHs) may emerge as critical contributors to the continent’s disease burden. We review recent evidence of human exposure to and health effects from MEHHs, and their occurrence in environmental media and consumer products. Our purpose is to highlight the growing significance of these hazards as African countries experience urbanization, industrial growth, and development. Data sources We reviewed published epidemiologic, exposure, and environmental studies of chemical agents such as heavy metals and pesticides. Data synthesis The body of evidence demonstrates ongoing environmental releases of MEHHs and human exposures sometimes at toxicologically relevant levels. Several sources of MEHHs in environmental media have been identified, including natural resource mining and processing and automobile exhaust. Biomonitoring studies provided direct evidence of human exposure to metals such as mercury and lead and pesticides such as p,p′-dichlorodiphenyltrichloroethane (DDT) and organophosphates. Land and water resource pollution and industrial air toxics are areas of significant data gaps, notwithstanding the presence of several emitting sources. Conclusion Unmitigated MEHH releases and human exposure have implications for Africa’s disease burden. For Africans encumbered by conditions such as malnutrition that impair resilience to toxicologic challenges, the burden may be higher. A shift in public health policy toward accommodating the emerging diversity in Africa’s environmental health issues is necessary to successfully alleviate the burden of avoidable ill health and premature death for all its communities now and in the future. PMID:19590675

  17. Acid-base titrations for polyacids: Significance of the pK sub a and parameters in the Kern equation

    NASA Technical Reports Server (NTRS)

    Meites, L.

    1978-01-01

    A new method is suggested for calculating the dissociation constants of polyvalent acids, especially polymeric acids. In qualitative form the most significant characteristics of the titration curves are demonstrated and identified which are obtained when titrating the solutions of such acids with a standard base potentiometrically.

  18. [West Nile virus--causative agent of a zoonosis with increasing significance?].

    PubMed

    Müller, H; Johne, R; Schusser, G; Giese, M; Linke, S; Pauli, G

    2006-12-01

    The epidemic West Nile Virus (WNV) infections observed in the last years, particularly those in the USA in 1999 and the following years, have led to an increasing interest in this zoonotic infection. Here, the most prominent aspects of WNV biology and epidemiology are presented. Clinical signs observed in men and horses are described, as well as the current state of diagnostics and immunoprophylaxis. Preliminary results of investigations on the prevalence of WNV in Germany show that migrating birds have been in contact with WNV; there is however no indication for the presence of this virus. While WNV is endemic in many parts of the "Old World", thus inducing "natural immunity" in (migrating) birds and vertebrates, a susceptible bird population with no existing immunity against this virus was exposed in the "New World". PMID:17233278

  19. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin

    PubMed Central

    de Bruijn, Henriëtte S.; Brooks, Sander; van der Ploeg-van den Heuvel, Angélique; ten Hagen, Timo L. M.; de Haas, Ellen R. M.; Robinson, Dominic J.

    2016-01-01

    Background Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models. Results In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination. Discussion The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy. PMID:26872051

  20. Increased fracture penetration and productivity using xanthan gelled acid in massive carbonate formations

    SciTech Connect

    Molon, J.P.; Fox, K.B.

    1983-03-01

    A measurable improvement in productivity can be achieved using xanthan gelled acid to stimulate carbonate formations. Well productivity results were compared to conventional acid fracture treatments. The significant improvements over classical acid fracturing techniques are due to the improved control of acid leakoff rates, retarded reaction rate and improved fracture width maintenance. The difficulties involved in acid fracturing massive Middle East carbonate formations are discussed and solutions are proposed using gelled acid technology. Some limitations in computer predictions of acid fracturing results are also discussed.

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

    SciTech Connect

    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.

  2. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses

    PubMed Central

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G.

    2016-01-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  3. TNFRSF14 aberrations in follicular lymphoma increase clinically significant allogeneic T-cell responses.

    PubMed

    Kotsiou, Eleni; Okosun, Jessica; Besley, Caroline; Iqbal, Sameena; Matthews, Janet; Fitzgibbon, Jude; Gribben, John G; Davies, Jeffrey K

    2016-07-01

    Donor T-cell immune responses can eradicate lymphomas after allogeneic hematopoietic stem cell transplantation (AHSCT), but can also damage healthy tissues resulting in harmful graft-versus-host disease (GVHD). Next-generation sequencing has recently identified many new genetic lesions in follicular lymphoma (FL). One such gene, tumor necrosis factor receptor superfamily 14 (TNFRSF14), abnormal in 40% of FL patients, encodes the herpes virus entry mediator (HVEM) which limits T-cell activation via ligation of the B- and T-lymphocyte attenuator. As lymphoma B cells can act as antigen-presenting cells, we hypothesized that TNFRSF14 aberrations that reduce HVEM expression could alter the capacity of FL B cells to stimulate allogeneic T-cell responses and impact the outcome of AHSCT. In an in vitro model of alloreactivity, human lymphoma B cells with TNFRSF14 aberrations had reduced HVEM expression and greater alloantigen-presenting capacity than wild-type lymphoma B cells. The increased immune-stimulatory capacity of lymphoma B cells with TNFRSF14 aberrations had clinical relevance, associating with higher incidence of acute GVHD in patients undergoing AHSCT. FL patients with TNFRSF14 aberrations may benefit from more aggressive immunosuppression to reduce harmful GVHD after transplantation. Importantly, this study is the first to demonstrate the impact of an acquired genetic lesion on the capacity of tumor cells to stimulate allogeneic T-cell immune responses which may have wider consequences for adoptive immunotherapy strategies. PMID:27103745

  4. 100-years of Australian bushfire property losses: is the risk significant and is it increasing?

    PubMed

    McAneney, John; Chen, Keping; Pitman, Andy

    2009-06-01

    This study examines the bushfire (wildland fire) risk to the built environment in Australia. The most salient result is that the annual probability of building destruction has remained almost constant over the last century despite large demographic and social changes as well as improvements in fire fighting technique and resources. Most historical losses have taken place in a few extreme fires which if repeated are likely to overwhelm even the most professional of fire services. We also calculate the average annual probability of a random home on the urban-bushland interface being destroyed by a bushfire to be of the order of 1 in 6500, a factor 6.5 times lower than the ignition probability of a structural house fire. Thus on average and if this risk was perceived rationally, the incentive for individual homeowners to mitigate and reduce the bushfire danger even further is low. This being the case and despite predictions of an increasing likelihood of conditions favouring bushfires under global climate change, we suspect that building losses due to bushfires are unlikely to alter materially in the near future. PMID:19410362

  5. Increased tachykinin levels in induced sputum from asthmatic and cough patients with acid reflux

    PubMed Central

    Patterson, Robert N; Johnston, Brian T; Ardill, Joy E S; Heaney, Liam G; McGarvey, Lorcan P A

    2007-01-01

    Background Acid reflux may aggravate airway disease including asthma and chronic cough. One postulated mechanism concerns a vagally‐mediated oesophageal‐tracheobronchial reflex with airway sensory nerve activation and tachykinin release. Aim To test the hypothesis that patients with airways disease and reflux have higher airway tachykinin levels than those without reflux. Methods Thirty‐two patients with airways disease (16 with mild asthma and 16 non‐asthmatic subjects with chronic cough) underwent 24 h oesophageal pH monitoring. Acid reflux was defined as increased total oesophageal acid exposure (% total time pH <4 of >4.9% at the distal probe). All subjects underwent sputum induction. Differential cell counts and concentrations of substance P (SP), neurokinin A (NKA), albumin and α2‐macroglobulin were determined. Results SP and NKA levels were significantly higher in patients with reflux than in those without (SP: 1434 (680) pg/ml vs 906 (593) pg/ml, p = 0.026; NKA: 81 (33) pg/ml vs 52 (36) pg/ml, p = 0.03). Significantly higher tachykinin levels were also found in asthmatic patients with reflux than in asthmatic patients without reflux (SP: 1508 (781) pg/ml vs 737 (512) pg/ml, p = 0.035; NKA: median (interquartile range 108 (85–120) pg/ml vs 75 (2–98) pg/ml, p = 0.02). In patients with asthma there was a significant positive correlation between distal oesophageal acid exposure and SP levels (r = 0.59, p = 0.01) and NKA levels (r = 0.56, p = 0.02). Non‐significant increases in SP and NKA were measured in patients with cough with reflux (SP: 1534.71 (711) pg/ml vs 1089 (606) pg/ml, p = 0.20; NKA: 56 (43) pg/ml vs 49 (17) pg/ml, p = 0.71). No significant difference in differential cell counts or any other biochemical parameter was noted between study groups. Conclusion This study demonstrates increased airway tachykinin levels in patients with asthma and cough patients with

  6. Marine animals significantly increase tundra N2O and CH4 emissions in maritime Antarctica

    NASA Astrophysics Data System (ADS)

    Zhu, Renbin; Liu, Yashu; Xu, Hua; Ma, Dawei; Jiang, Shan

    2013-12-01

    studies on greenhouse gas emissions from animals concentrated on domestic animals, with limited data available from wild animals. The number of marine animals is potentially large in coastal Antarctica. In this paper, N2O and CH4 emissions were investigated from a penguin colony, a seal colony, a skua colony, the adjacent animal-lacking tundra, and background tundra sites to test the effects of marine animals on their fluxes in maritime Antarctica. Extremely high N2O emissions occurred in the penguin puddles (mean 392 µg N2O m-2 h-1) and seal wallows (mean 579 µg N2O m-2 h-1). The N2O emissions from animal colony tundra (13-57 µg N2O m-2 h-1) are much higher than those from the animal-lacking tundra, whereas the background tundra showed negligible N2O fluxes. Penguin puddles and seal wallows were stronger CH4 emitters than animal colony tundra soils, while animal-lacking tundra soils were strong CH4 sinks. Overall high N2O and CH4 emissions were modulated by soil physical and chemical processes associated with marine animal activities: sufficient supply of the nutrients NH4+-N and NO3--N, total nitrogen, and total organic carbon from marine animal excreta, animal tramp, and high soil water-filled pore space. Laboratory incubation experiments further confirmed that penguin and seal colony soils produced much higher N2O and CH4 emissions than animal-lacking tundra soils. Our results indicate that marine animal colonies are the hot spots for N2O and CH4 emissions in maritime Antarctica, and even at the global scale, and current climate warming will further increase their emissions.

  7. Steam cooking significantly improves in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage.

    PubMed

    Kahlon, Talwinder Singh; Chiu, Mei-Chen M; Chapman, Mary H

    2008-06-01

    Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowered recirculation of bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increased risk of cancer. Bile acid binding potential has been related to lowering the risk of heart disease and that of cancer. Previously, we have reported bile acid binding by several uncooked vegetables. However, most vegetables are consumed after cooking. How cooking would influence in vitro bile acid binding of various vegetables was investigated using a mixture of bile acids secreted in human bile under physiological conditions. Eight replicate incubations were conducted for each treatment simulating gastric and intestinal digestion, which included a substrate only, a bile acid mixture only, and 6 with substrate and bile acid mixture. Cholestyramine (a cholesterol-lowering, bile acid binding drug) was the positive control treatment and cellulose was the negative control. Relative to cholestyramine, in vitro bile acid binding on dry matter basis was for the collard greens, kale, and mustard greens, 13%; broccoli, 10%; Brussels sprouts and spinach, 8%; green bell pepper, 7%; and cabbage, 5%. These results point to the significantly different (P < or = .05) health-promoting potential of collard greens = kale = mustard greens > broccoli > Brussels sprouts = spinach = green bell pepper > cabbage as indicated by their bile acid binding on dry matter basis. Steam cooking significantly improved the in vitro bile acid binding of collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage compared with previously observed bile acid binding values for these vegetables raw (uncooked). Inclusion of steam-cooked collard greens, kale, mustard greens, broccoli, green bell pepper, and cabbage in our daily diet as health-promoting vegetables should be emphasized. These green

  8. Effects of increasing docosahexaenoic acid intake in human healthy volunteers on lymphocyte activation and monocyte apoptosis

    PubMed Central

    Mebarek, Saïda; Ermak, Natalia; Benzaria, Amal; Vicca, Stéphanie; Dubois, Madeleine; Némoz, Georges; Laville, Martine; Lacour, Bernard; Véricel, Evelyne; Lagarde, Michel; Prigent, Annie-France

    2009-01-01

    Dietary intake of long-chain n-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to decrease several markers of lymphocyte activation and modulate monocyte susceptibility to apoptosis. However most human studies examined the combined effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) using relatively high daily amounts of n-3 PUFA. The present study investigated the effects of increasing doses of DHA added to the regular diet of human healthy volunteers on lymphocyte response to tetradecanoylphorbol acetate (TPA) plus ionomycin activation, and on monocyte apoptosis induced by oxidized LDL (oxLDL). Eight subjects were supplemented with increasing daily doses of DHA (200, 400, 800 and 1600mg) in a triacylglycerol form containing DHA as the only PUFA, for two weeks each dose. DHA intake dose-dependently increased the proportion of DHA in mononuclear cell phospholipids, the augmentation being significant after 400mg DHA/day. The TPA plus ionomycin-stimulated IL-2 mRNA level started to increase after ingestion of 400mg DHA/day, with a maximum after 800mg intake, and was positively correlated (P<0.003) with DHA enrichment in cell phospholipids. The treatment of monocytes by oxLDL before DHA supplementation drastically reduced mitochondrial membrane potential as compared with native LDL treatment. OxLDL apoptotic effect was significantly attenuated after 400mg DHA/day and the protective effect was maintained throughout the experiment, although to a lesser extent at higher doses. The present results show that supplementation of the human diet with low DHA dosages improves lymphocyte activability. It also increases monocyte resistance to oxLDL-induced apoptosis, which may be beneficial in the prevention of atherosclerosis. PMID:18710607

  9. Increased Bile Acid Synthesis and Deconjugation After Biliopancreatic Diversion.

    PubMed

    Ferrannini, Ele; Camastra, Stefania; Astiarraga, Brenno; Nannipieri, Monica; Castro-Perez, Jose; Xie, Dan; Wang, Liangsu; Chakravarthy, Manu; Haeusler, Rebecca A

    2015-10-01

    Biliopancreatic diversion (BPD) improves insulin sensitivity and decreases serum cholesterol out of proportion with weight loss. Mechanisms of these effects are unknown. One set of proposed contributors to metabolic improvements after bariatric surgeries is bile acids (BAs). We investigated the early and late effects of BPD on plasma BA levels, composition, and markers of BA synthesis in 15 patients with type 2 diabetes (T2D). We compared these to the early and late effects of Roux-en-Y gastric bypass (RYGB) in 22 patients with T2D and 16 with normal glucose tolerance. Seven weeks after BPD, insulin sensitivity had doubled and serum cholesterol had halved. At this time, BA synthesis markers and total plasma BAs, particularly unconjugated BAs, had markedly risen; this effect could not be entirely explained by low FGF19. In contrast, after RYGB, insulin sensitivity improved gradually with weight loss and cholesterol levels declined marginally; BA synthesis markers were decreased at an early time point (2 weeks) after surgery and returned to the normal range 1 year later. These findings indicate that BA synthesis contributes to the decreased serum cholesterol after BPD. Moreover, they suggest a potential role for altered enterohepatic circulation of BAs in improving insulin sensitivity and cholesterol metabolism after BPD. PMID:26015549

  10. Humic substances increase survival of freshwater shrimp Caridina sp. D to acid mine drainage.

    PubMed

    Holland, Aleicia; Duivenvoorden, Leo J; Kinnear, Susan H W

    2013-02-01

    Humic substances (HS) are known to decrease the toxicity of heavy metals to aquatic organisms, and it has been suggested that they can provide buffering protection in low pH conditions. Despite this, little is known about the ability for HS to increase survival to acid mine drainage (AMD). In this study, the ability of HS to increase survival of the freshwater shrimp (Caridina sp. D sensu Page et al. in Biol Lett 1:139-142, 2005) to acid mine drainage was investigated using test waters collected from the Mount Morgan open pit in Central Queensland with the addition of Aldrich humic acid (AHA). The AMD water from the Mount Morgan open pit is highly acidic (pH 2.67) as well as contaminated with heavy metals (1780 mg/L aluminum, 101 mg/L copper [Cu], 173 mg/L manganese, 51.8 mg/L zinc [Zn], and 51.8 mg/L iron). Freshwater shrimp were exposed to dilutions in the range of 0.5 % to 5 % AMD water with and without the addition of 10 or 20 mg/L AHA. In the absence of HS, all shrimp died in the 2.5 % AMD treatment. In contrast, addition of HS increased survival in the 2.5 % AMD treatment by ≤66 % as well as significantly decreased the concentration of dissolved Cu, cobalt, cadmium, and Zn. The decreased toxicity of AMD in the presence of HS is likely to be due to complexation and precipitation of heavy metals with the HS; it is also possible that HS caused changes to the physiological condition of the shrimp, thus increasing their survival. These results are valuable in contributing to an improved understanding of potential role of HS in ameliorating the toxicity of AMD environments. PMID:23135152

  11. Significantly enhancing supercapacitive performance of nitrogen-doped graphene nanosheet electrodes by phosphoric acid activation.

    PubMed

    Wang, Ping; He, Haili; Xu, Xiaolong; Jin, Yongdong

    2014-02-12

    In this work, we present a new method to synthesize the phosphorus, nitrogen contained graphene nanosheets, which uses dicyandiamide to prevent the aggregation of graphene oxide and act as the nitrogen precursor, and phosphoric acid (H3PO4) as the activation reagent. We have found that through the H3PO4 activation, the samples exhibit the remarkably enhanced supercapacitive performance, and depending on the amount of H3PO4 introduced, the specific capacitance of the samples is gradually increased from 7.6 to 244.6 F g(-1). Meanwhile, the samples also exhibit the good rate capability and excellent stability (up to 10 000 cycles). Through the transmission electron microscopy, high-resolution transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Brunauer-Emmett-Teller analyses, H3PO4 treatment induced large pore volume and phosphorus related function groups in the product are assumed to response for the enhancement. PMID:24456232

  12. 17β-estradiol increases liver and serum docosahexaenoic acid in mice fed varying levels of α-linolenic acid.

    PubMed

    Mason, Julie K; Kharotia, Shikhil; Wiggins, Ashleigh K A; Kitson, Alex P; Chen, Jianmin; Bazinet, Richard P; Thompson, Lilian U

    2014-08-01

    Docosahexaenoic acid (DHA) is considered to be important for cardiac and brain function, and 17β-estradiol (E2) appears to increase the conversion of α-linolenic acid (ALA) into DHA. However, the effect of varying ALA intake on the positive effect of E2 on DHA synthesis is not known. Therefore, the objective of this study was to investigate the effects of E2 supplementation on tissue and serum fatty acids in mice fed a low-ALA corn oil-based diet (CO, providing 0.6 % fatty acids as ALA) or a high ALA flaxseed meal-based diet (FS, providing 11.2 % ALA). Ovariectomized mice were implanted with a slow-release E2 pellet at 3 weeks of age and half the mice had the pellet removed at 7 weeks of age. Mice were then randomized onto either the CO or FS diet. After 4 weeks, the DHA concentration was measured in serum, liver and brain. A significant main effect of E2 was found for liver and serum DHA, corresponding to 25 and 15 % higher DHA in livers of CO and FS rats, respectively, and 19 and 13 % in serum of CO and FS rats, respectively, compared to unsupplemented mice. There was no effect of E2 on brain DHA. E2 results in higher DHA in serum and liver, at both levels of dietary ALA investigated presently, suggesting that higher ALA intake may result in higher DHA in individuals with higher E2 status. PMID:24913495

  13. Hyaluronic acid is increased in the skin and urine in patients with amyotrophic lateral sclerosis

    NASA Technical Reports Server (NTRS)

    Ono, S.; Imai, T.; Yamauchi, M.; Nagao, K.

    1996-01-01

    We performed morphological studies of skin and measured glycosaminoglycans in the urine from patients with sporadic amyotrophic lateral sclerosis (ALS) and control subjects. The wide spaces separating collagen bundles reacted strongly with alcian blue stain in ALS patients and stained more markedly as ALS progressed. Staining with alcian blue was virtually eliminated by Streptomyces hyaluronidase. The urinary excretion of hyaluronic acid (HA) (mg/day) was significantly increased (P < 0.01) in ALS patients compared with that of control subjects, and there was a significant positive correlation between the excreted amount of HA and the duration of illness in advanced ALS patients with a duration of more than 2 years from clinical onset (r = 0.72, P < 0.02). We suggest that sporadic ALS includes a metabolic disorder of HA in which an accumulation of HA in the skin is linked to an increased urinary excretion of HA.

  14. Increasing dietary palmitic acid decreases fat oxidation and daily energy expenditure123

    PubMed Central

    Bunn, Janice Y; Ugrasbul, Figen

    2005-01-01

    Background Oleic acid (OA) is oxidized more rapidly than is palmitic acid (PA). Objective We hypothesized that changing the dietary intakes of PA and OA would affect fatty acid oxidation and energy expenditure. Design A double-masked trial was conducted in 43 healthy young adults, who, after a 28-d, baseline, solid-food diet (41% of energy as fat, 8.4% as PA, and 13.1% as OA), were randomly assigned to one of two 28-d formula diets: high PA (40% of energy as fat, 16.8% as PA, and 16.4% as OA; n = 21) or high OA (40% of energy as fat, 1.7% as PA, and 31.4% as OA; n = 22). Differences in the change from baseline were evaluated by analysis of covariance. Results In the fed state, the respiratory quotient was lower (P = 0.01) with the high OA (0.86 ± 0.01) than with the high-PA (0.89 ± 0.01) diet, and the rate of fat oxidation was higher (P = 0.03) with the high-OA (0.0008 ± 0.0001) than with the high-PA (0.0005 ± 0.0001 mg · kg fat-free mass−1 · min−1) diet. Resting energy expenditure in the fed and fasting states was not significantly different between groups. Change in daily energy expenditure in the high-OA group (9 ± 60 kcal/d) was significantly different from that in the high-PA group (−214 ±69 kcal/d; P = 0.02 or 0.04 when expressed per fat-free mass). Conclusions Increases in dietary PA decrease fat oxidation and daily energy expenditure, whereas decreases in PA and increases in OA had the opposite effect. Increases in dietary PA may increase the risk of obesity and insulin resistance. PMID:16087974

  15. Increased serum bile acid concentration following low-dose chronic administration of thioacetamide in rats, as evidenced by metabolomic analysis.

    PubMed

    Jeong, Eun Sook; Kim, Gabin; Shin, Ho Jung; Park, Se-Myo; Oh, Jung-Hwa; Kim, Yong-Bum; Moon, Kyoung-Sik; Choi, Hyung-Kyoon; Jeong, Jayoung; Shin, Jae-Gook; Kim, Dong Hyun

    2015-10-15

    A liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS)-based metabolomics approach was employed to identify endogenous metabolites as potential biomarkers for thioacetamide (TAA)-induced liver injury. TAA (10 and 30mg/kg), a well-known hepatotoxic agent, was administered daily to male Sprague-Dawley (SD) rats for 28days. We then conducted untargeted analyses of endogenous serum and liver metabolites. Partial least squares discriminant analysis (PLS-DA) was performed on serum and liver samples to evaluate metabolites associated with TAA-induced perturbation. TAA administration resulted in altered levels of bile acids, acyl carnitines, and phospholipids in serum and in the liver. We subsequently demonstrated and confirmed the occurrence of compromised bile acid homeostasis. TAA treatment significantly increased serum levels of conjugated bile acids in a dose-dependent manner, which correlated well with toxicity. However, hepatic levels of these metabolites were not substantially changed. Gene expression profiling showed that the hepatic mRNA levels of Ntcp, Bsep, and Oatp1b2 were significantly suppressed, whereas those of basolateral Mrp3 and Mrp4 were increased. Decreased levels of Ntcp, Oatp1b2, and Ostα proteins in the liver were confirmed by western blot analysis. These results suggest that serum bile acids might be increased due to the inhibition of bile acid enterohepatic circulation rather than increased endogenous bile acid synthesis. Moreover, serum bile acids are a good indicator of TAA-induced hepatotoxicity. PMID:26222700

  16. Coffee polyphenol caffeic acid but not chlorogenic acid increases 5'AMP-activated protein kinase and insulin-independent glucose transport in rat skeletal muscle.

    PubMed

    Tsuda, Satoshi; Egawa, Tatsuro; Ma, Xiao; Oshima, Rieko; Kurogi, Eriko; Hayashi, Tatsuya

    2012-11-01

    Chlorogenic acid is an ester of caffeic and quinic acids, and is one of the most widely consumed polyphenols because it is abundant in foods, especially coffee. We explored whether chlorogenic acid and its metabolite, caffeic acid, act directly on skeletal muscle to stimulate 5'-adenosine monophosphate-activated protein kinase (AMPK). Incubation of rat epitrochlearis muscles with Krebs buffer containing caffeic acid (≥0.1 mM, ≥30 min) but not chlorogenic acid increased the phosphorylation of AMPKα Thr(172), an essential step for kinase activation, and acetyl CoA carboxylase Ser(79), a downstream target of AMPK, in a dose- and time-dependent manner. Analysis of isoform-specific AMPK activity revealed that AMPKα2 activity increased significantly, whereas AMPKα1 activity did not change. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeic acid but not chlorogenic acid acutely stimulates skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status. PMID:22227267

  17. Increased universality of Lepidopteran elicitor compounds across insects: Identification of fatty acid amino acid conjugates (FACs)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fatty acid amino acid conjugates (FACs) are known elicitors of induced release of volatile compounds in plants that, in turn, attract foraging parasitoids. Since the discovery of volicitin [N-(17-hydroxylinolenoyl)-L-glutamine] in the regurgitant of larval Spodoptera exigua1, a series of related FAC...

  18. Prognostic significance of periodic acid-Schiff-positive patterns in primary cutaneous melanoma.

    PubMed

    Warso, M A; Maniotis, A J; Chen, X; Majumdar, D; Patel, M K; Shilkaitis, A; Gupta, T K; Folberg, R

    2001-03-01

    The patterns of periodic acid-Schiff (PAS) staining of extracellular matrix in histological sections of certain melanomas may be predictive of outcome. Recent in vitro and molecular genetic data suggest that the appearance of these patterns in both uveal and cutaneous melanoma is a function of aggressive tumor cells. We studied 96 patients with primary cutaneous melanomas treated at the University of Illinois at Chicago who were monitored for disease-free survival. Survival probabilities were determined by Kaplan-Meier estimates, and prognostic factors were evaluated by multivariate analysis. By univariate analysis, there was a significant decrease in disease-free survival among patients whose tumors contained parallel with cross-linking or network patterns (PXNs; P = 0.0070). Stepwise regression with Cox models that included the combinations of the PAS-positive patterns, tumor thickness, female gender, ulceration, and age yielded a model with thickness and the PAS-positive parallel with cross-linking or networks. Despite the relatively small sample size in this study, the detection of the PAS-positive parallel with cross-linking or networking in cutaneous melanoma was associated with a decrease in disease-free outcome. Additional studies of the prognostic significance of these patterns is warranted on larger data sets. PMID:11297236

  19. Overexpression of acetyl-CoA synthetase in Saccharomyces cerevisiae increases acetic acid tolerance

    PubMed Central

    Ding, Jun; Holzwarth, Garrett; Penner, Michael H.; Patton-Vogt, Jana; Bakalinsky, Alan T.

    2015-01-01

    Acetic acid-mediated inhibition of the fermentation of lignocellulose-derived sugars impedes development of plant biomass as a source of renewable ethanol. In order to overcome this inhibition, the capacity of Saccharomyces cerevisiae to synthesize acetyl-CoA from acetic acid was increased by overexpressing ACS2 encoding acetyl-coenzyme A synthetase. Overexpression of ACS2 resulted in higher resistance to acetic acid as measured by an increased growth rate and shorter lag phase relative to a wild-type control strain, suggesting that Acs2-mediated consumption of acetic acid during fermentation contributes to acetic acid detoxification. PMID:25673654

  20. Increase of betulinic acid production in Saccharomyces cerevisiae by balancing fatty acids and betulinic acid forming pathways.

    PubMed

    Li, Jing; Zhang, Yansheng

    2014-04-01

    Betulinic acid is a plant-based triterpenoid that has been recognized for its antitumor and anti-HIV activities. The level of betulinic acid in its natural hosts is extremely low. In the present study, we constructed betulinic acid biosynthetic pathway in Saccharomyces cerevisiae by metabolic engineering. Given the betulinic acid forming pathways sharing the common substrate acetyl-CoA with fatty acid synthesis, the metabolic fluxes between the two pathways were varied by changing gene expressions, and their effects on betulinic acid production were investigated. We constructed nine S. cerevisiae strains representing nine combinations of the flux distributions between betulinic acid and fatty acid pathways. Our results demonstrated that it was possible to improve the betulinic acid production in S. cerevisiae while keeping a desirable growth phenotype by optimally balancing the carbon fluxes of the two pathways. Through modulating the expressions of the key genes on betulinic acid and fatty acid pathways, the difference in betulinic acid yield varied largely in the range of 0.01-1.92 mg L(-1) OD(-1). The metabolic engineering approach used in this study could be extended for synthesizing other triterpenoids in S. cerevisiae. PMID:24389702

  1. Exogenous abscisic acid significantly affects proteome in tea plant (Camellia sinensis) exposed to drought stress

    PubMed Central

    Zhou, Lin; Xu, Hui; Mischke, Sue; Meinhardt, Lyndel W; Zhang, Dapeng; Zhu, Xujun; Li, Xinghui; Fang, Wanping

    2014-01-01

    Tea [Camellia sinensis (L.) O. Kuntze] is an important economic crop, and drought is the most important abiotic stress affecting yield and quality. Abscisic acid (ABA) is an important phytohormone responsible for activating drought resistance. Increased understanding of ABA effects on tea plant under drought stress is essential to develop drought-tolerant tea genotypes, along with crop management practices that can mitigate drought stress. The objective of the present investigation is evaluation of effects of exogenous ABA on the leaf proteome in tea plant exposed to drought stress. Leaf protein patterns of tea plants under simulated drought stress [(polyethylene glycol (PEG)-treated] and exogenous ABA treatment were analyzed in a time-course experiment using two-dimensional electrophoresis (2-DE), followed by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). Among the 72 protein spots identified by MALDI-TOF MS, 16 proteins were downregulated and two were upregulated by exogenous ABA. The upregulated proteins have roles in glycolysis and photosystem II stabilization. Twenty-one protein spots were responsive to drought stress and most participate in carbohydrate and nitrogen metabolism, control of reactive oxygen species (ROS), defense, signaling or nucleic acid metabolism. The combined treatments of exogenous ABA and drought showed upregulation of 10 protein spots at 12 h and upregulation of 11 proteins at 72 h after initiation of drought stress. The results support the importance of the role that ABA plays in the tea plant during drought stress, by improving protein transport, carbon metabolism and expression of resistance proteins. PMID:27076915

  2. Directed evolution increases desaturation of a cyanobacterial fatty acid desaturase in eukaryotic expression systems.

    PubMed

    Bai, Shuangyi; Wallis, James G; Denolf, Peter; Browse, John

    2016-07-01

    Directed evolution of a cyanobacterial Δ9 fatty acid desaturase (DSG) from Synechococcus elongatus, PCC6301 created new, more productive desaturases and revealed the importance of certain amino acid residues to increased desaturation. A codon-optimized DSG open reading frame with an endoplasmic-reticulum retention/retrieval signal appended was used as template for random mutagenesis. Increased desaturation was detected using a novel screen based on complementation of the unsaturated fatty acid auxotrophy of Saccharomyces cerevisiae mutant ole1Δ. Amino acid residues whose importance was discovered by the random processes were further examined by saturation mutation to determine the best amino acid at each identified location in the peptide chain and by combinatorial analysis. One frequently-detected single amino acid change, Q240R, yielded a nearly 25-fold increase in total desaturation in S. cerevisiae. Several other variants of the protein sequence with multiple amino acid changes increased total desaturation more than 60-fold. Many changes leading to increased desaturation were in the vicinity of the canonical histidine-rich regions known to be critical for electron transfer mediated by these di-iron proteins. Expression of these evolved proteins in the seed of Arabidopsis thaliana altered the fatty acid composition, increasing monounsaturated fatty acids and decreasing the level of saturated fatty acid, suggesting a potential application of these desaturases in oilseed crops. Biotechnol. Bioeng. 2016;113: 1522-1530. © 2016 Wiley Periodicals, Inc. PMID:26724425

  3. Inhibition of endocannabinoid-degrading enzyme fatty acid amide hydrolase increases atherosclerotic plaque vulnerability in mice.

    PubMed

    Hoyer, Friedrich Felix; Khoury, Mona; Slomka, Heike; Kebschull, Moritz; Lerner, Raissa; Lutz, Beat; Schott, Hans; Lütjohann, Dieter; Wojtalla, Alexandra; Becker, Astrid; Zimmer, Andreas; Nickenig, Georg

    2014-01-01

    The role of endocannabinoids such as anandamide during atherogenesis remains largely unknown. Fatty acid amide hydrolase (FAAH) represents the key enzyme in anandamide degradation, and its inhibition is associated with subsequent higher levels of anandamide. Here, we tested whether selective inhibition of FAAH influences the progression of atherosclerosis in mice. Selective inhibition of FAAH using URB597 resulted in significantly increased plasma levels of anandamide compared to control, as assessed by mass spectrometry experiments in mice. Apolipoprotein E-deficient (ApoE(-/-)) mice were fed a high-fat, cholesterol-rich diet to induce atherosclerotic conditions. Simultaneously, mice received either the pharmacological FAAH inhibitor URB597 1mg/kg body weight (n=28) or vehicle (n=25) via intraperitoneal injection three times a week. After eight weeks, mice were sacrificed, and experiments were performed. Vascular superoxide generation did not differ between both groups, as measured by L012 assay. To determine whether selective inhibition of FAAH affects atherosclerotic plaque inflammation, immunohistochemical staining of the aortic root was performed. Atherosclerotic plaque formation, vascular macrophage accumulation, as well as vascular T cell infiltration did not differ between both groups. Interestingly, neutrophil cell accumulation was significantly increased in mice receiving URB597 compared to control. Vascular collagen structures in atherosclerotic plaques were significantly diminished in mice treated with URB597 compared to control, as assessed by picro-sirius-red staining. This was accompanied by an increased aortic expression of matrix metalloproteinase-9, as determined by quantitative RT-PCR and western blot analysis. Inhibition of fatty acid amide hydrolase does not influence plaque size but increases plaque vulnerability in mice. PMID:24286707

  4. Optical clearing of skin enhanced with hyaluronic acid for increased contrast of optoacoustic imaging.

    PubMed

    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. PMID:27232721

  5. Phosphorus limitation strategy to increase propionic acid flux towards 3-hydroxyvaleric acid monomers in Cupriavidus necator.

    PubMed

    Grousseau, Estelle; Blanchet, Elise; Déléris, Stéphane; Albuquerque, Maria G E; Paul, Etienne; Uribelarrea, Jean-Louis

    2014-02-01

    Properties of polyhydroxybutyrate-co-hydroxyvalerate (P(3HB-co-3HV)) depend on their 3HV content. 3HV can be produced by Cupriavidus necator from propionic acid. Few studies explored carbon distribution and dynamics of 3HV and 3HB monomers production, and none of them have been done with phosphorus as limiting nutrient. In this study, fed-batch cultures of C. necator with propionic acid, as sole carbon source or mixed with butyric acid, were performed. Phosphorus deficiency allowed sustaining 3HV production rate and decreasing 3HB production rate, leading to an instant production of up to 100% of 3HV. When a residual growth is sustained by a phosphorus feeding, the maximum 3HV percentage produced from propionic acid is limited to 33% (Mole.Mole(-1)). The association of a second carbon source like butyric acid lead to higher conversion of propionic acid into 3HV. This study showed the importance of the limiting nutrient and of the culture strategy to get the appropriate product. PMID:24365742

  6. Gamma-irradiation of malic acid in aqueous solutions. [prebiotic significance

    NASA Technical Reports Server (NTRS)

    Negron-Mendoza, A.; Graff, R. L.; Ponnamperuma, C.

    1980-01-01

    The gamma-irradiation of malic acid in aqueous solutions was studied under initially oxygenated and oxygen-free conditions in an attempt to determine the possible interconversion of malic acid into other carboxylic acids, specifically those associated with Krebs cycle. The effect of dose on product formation of the system was investigated. Gas-liquid chromatography combined with mass spectrometry was used as the principal means of identification of the nonvolatile products. Thin layer chromatography and direct probe mass spectroscopy were also employed. The findings show that a variety of carboxylic acids are formed, with malonic and succinic acids in greatest abundance. These products have all been identified as being formed in the gamma-irradiation of acetic acid, suggesting a common intermediary. Since these molecules fit into a metabolic cycle, it is strongly suggestive that prebiotic pathways provided the basis for biological systems.

  7. Significant effect of Ca2+ on improving the heat resistance of lactic acid bacteria.

    PubMed

    Huang, Song; Chen, Xiao Dong

    2013-07-01

    The heat resistance of lactic acid bacteria (LAB) has been extensively investigated due to its highly practical significance. Reconstituted skim milk (RSM) has been found to be one of the most effective protectant wall materials for microencapsulating microorganisms during convective drying, such as spray drying. In addition to proteins and carbohydrate, RSM is rich in calcium. It is not clear which component is critical in the RSM protection mechanism. This study investigated the independent effect of calcium. Ca(2+) was added to lactose solution to examine its influence on the heat resistance of Lactobacillus rhamnosus ZY, Lactobacillus casei Zhang, Lactobacillus plantarum P8 and Streptococcus thermophilus ND03. The results showed that certain Ca(2+) concentrations enhanced the heat resistance of the LAB strains to different extents, that is produced higher survival and shorter regrowth lag times of the bacterial cells. In some cases, the improvements were dramatic. More scientifically insightful and more intensive instrumental study of the Ca(2+) behavior around and in the cells should be carried out in the near future. In the meantime, this work may lead to the development of more cost-effective wall materials with Ca(2+) added as a prime factor. PMID:23617813

  8. Effect of increased protein intake on renal acid load and renal hemodynamic responses.

    PubMed

    Teunissen-Beekman, Karianna F M; Dopheide, Janneke; Geleijnse, Johanna M; Bakker, Stephan J L; Brink, Elizabeth J; de Leeuw, Peter W; van Baak, Marleen A

    2016-03-01

    Increased protein intake versus maltodextrin intake for 4 weeks lowers blood pressure. Concerns exist that high-protein diets reduce renal function. Effects of acute and 4-week protein intake versus maltodextrin intake on renal acid load, glomerular filtration rate and related parameters were compared in this study. Seventy-nine overweight individuals with untreated elevated blood pressure and normal kidney function were randomized to consume a mix of protein isolates (60 g/day) or maltodextrin (60 g/day) for 4 weeks in energy balance. Twenty-four-hour urinary potential renal acid load (uPRAL) was compared between groups. A subgroup (maltodextrin N = 27, protein mix N = 25) participated in extra test days investigating fasting levels and postprandial effects of meals supplemented with a moderate protein- or maltodextrin-load on glomerular filtration rate, effective renal plasma flow, plasma renin, aldosterone, pH, and bicarbonate. uPRAL was significantly higher in the protein group after 4 weeks (P ≤ 0.001). Postprandial filtration fraction decreased further after the protein-supplemented breakfast than after the maltodextrin-supplemented breakfast after 4 weeks of supplementation (P ≤ 0.001). Fasting and postprandial levels of glomerular filtration rate, effective renal plasma flow, renin, aldosterone, angiotensin-converting enzyme, pH and bicarbonate did not differ between groups. In conclusion, 4 weeks on an increased protein diet (25% of energy intake) increased renal acid load, but did not affect renal function. Postprandial changes, except for filtration fraction, also did not differ between groups. These data suggest that a moderate increase in protein intake by consumption of a protein mix for 4 weeks causes no (undesirable) effects on kidney function in overweight and obese individuals with normal kidney function. PMID:26997623

  9. Abiogenic Syntheses of Lipoamino Acids and Lipopeptides and their Prebiotic Significance.

    PubMed

    Sproul, Gordon

    2015-12-01

    Researchers have formed peptide bonds under a variety of presumed prebiotic conditions. Here it is proposed that these same conditions would have also formed amide bonds between fatty acids and amino acids, producing phosphate-free amphipathic lipoamino acids and lipopeptides. These compounds are known to form vesicles and are ubiquitous in living organisms. They could represent molecules that provided protection by membranes as well as possibilities for proto-life metabolism . It is here demonstrated that when a fatty acid is heated with various amino acids, optimally in the presence of suitable salts or minerals, lipoamino acids are formed. Magnesium and potassium carbonates as well as iron (II) sulfide are found to be particularly useful in these reactions. In this manner N-lauroylglycine, N-lauroylalanine, N-stearoylalanine and several other lipoamino acids have been synthesized. Similarly, when glycylglycine was heated with lauric acid in the presence of magnesium carbonate, the lipopeptide N-lauroylglycylglycine was formed. Such compounds are proposed to have been critical precursors to the development of life. PMID:26248658

  10. Abiogenic Syntheses of Lipoamino Acids and Lipopeptides and their Prebiotic Significance

    NASA Astrophysics Data System (ADS)

    Sproul, Gordon

    2015-12-01

    Researchers have formed peptide bonds under a variety of presumed prebiotic conditions. Here it is proposed that these same conditions would have also formed amide bonds between fatty acids and amino acids, producing phosphate-free amphipathic lipoamino acids and lipopeptides. These compounds are known to form vesicles and are ubiquitous in living organisms. They could represent molecules that provided protection by membranes as well as possibilities for proto-life metabolism . It is here demonstrated that when a fatty acid is heated with various amino acids, optimally in the presence of suitable salts or minerals, lipoamino acids are formed. Magnesium and potassium carbonates as well as iron (II) sulfide are found to be particularly useful in these reactions. In this manner N-lauroylglycine, N-lauroylalanine, N-stearoylalanine and several other lipoamino acids have been synthesized. Similarly, when glycylglycine was heated with lauric acid in the presence of magnesium carbonate, the lipopeptide N-lauroylglycylglycine was formed. Such compounds are proposed to have been critical precursors to the development of life.

  11. Nicotinic acid increases the lipid content of rat brain synaptosomes. [Ethanol effects

    SciTech Connect

    Basilio, C.; Flores, M.

    1989-02-09

    Chronic administration of nicotinic acid (NA) increase hepatic lipids and potentiates a similar effect induced by ethanol. The amethystic properties of NA promoted us to study its effects on the lipid content of brain synaptosomes of native and ethanol treated rats. Groups of 10 Sprague-Dawley female rats received i.p. either saline, ethanol (4g/kg), NA (50mg/kg), or a mixture of both compounds once a week during 3 weeks. The sleeping time (ST) of the animals receiving ethanol was recorded, brain synaptosomes of all groups were prepared and total lipids (TL) and cholesterol (Chol) content were determined. NA, ethanol and ethanol + NA markedly increased both TL and Chol of synaptosomes. Animals treated with ethanol or ethanol + NA developed tolerance. The group treated with ethanol-NA showed the highest Chol content and slept significantly less than the one treated with ethanol alone indicating that the changes induced by NA favored the appearance of tolerance.

  12. High levels of retinal membrane docosahexaenoic acid increase susceptibility to stress-induced degeneration.

    PubMed

    Tanito, Masaki; Brush, Richard S; Elliott, Michael H; Wicker, Lea D; Henry, Kimberly R; Anderson, Robert E

    2009-05-01

    The fat-1 gene cloned from C. elegans encodes an n-3 fatty acid desaturase that converts n-6 to n-3 PUFA. Mice carrying the fat-1 transgene and wild-type controls were fed an n-3-deficient/n-6-enriched diet [fat-1- safflower oil (SFO) and wt-SFO, respectively]. Fatty acid profiles of rod outer segments (ROS), cerebellum, plasma, and liver demonstrated significantly lower n-6/n-3 ratios and higher docosahexaenoic acid (DHA) levels in fat-1-SFO compared with wt-SFO. When mice were exposed to light stress: 1) the outer nuclear layer (ONL) thickness was reduced; 2) amplitudes of the electroretinogram (ERG) were lower; 3) the number of apoptotic photoreceptor cells was greater; and 4) modification of retinal proteins by 4-hydroxyhexenal (4-HHE), an end-product of n-3 PUFA oxidation was increased in both fat-1-SFO and wt mice fed a regular lab chow diet compared with wt-SFO. The results indicate a positive correlation between the level of DHA, the degree of n-3 PUFA lipid peroxidation, and the vulnerability of the retina to photooxidative stress. In mice not exposed to intense light, the reduction in DHA resulted in reduced efficacy in phototransduction gain steps, while no differences in the retinal morphology or retinal biochemistry. These results highlight the dual roles of DHA in cellular physiology and pathology. PMID:19023138

  13. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    PubMed

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease. PMID:25616451

  14. Increased Biomass Yield of Lactococcus lactis by Reduced Overconsumption of Amino Acids and Increased Catalytic Activities of Enzymes

    PubMed Central

    Adamberg, Kaarel; Seiman, Andrus; Vilu, Raivo

    2012-01-01

    Steady state cultivation and multidimensional data analysis (metabolic fluxes, absolute proteome, and transcriptome) are used to identify parameters that control the increase in biomass yield of Lactococcus lactis from 0.10 to 0.12 C-mol C-mol−1 with an increase in specific growth rate by 5 times from 0.1 to 0.5 h−1. Reorganization of amino acid consumption was expressed by the inactivation of the arginine deiminase pathway at a specific growth rate of 0.35 h−1 followed by reduced over-consumption of pyruvate directed amino acids (asparagine, serine, threonine, alanine and cysteine) until almost all consumed amino acids were used only for protein synthesis at maximal specific growth rate. This balanced growth was characterized by a high glycolytic flux carrying up to 87% of the carbon flow and only amino acids that relate to nucleotide synthesis (glutamine, serine and asparagine) were consumed in higher amounts than required for cellular protein synthesis. Changes in the proteome were minor (mainly increase in the translation apparatus). Instead, the apparent catalytic activities of enzymes and ribosomes increased by 3.5 times (0.1 vs 0.5 h−1). The apparent catalytic activities of glycolytic enzymes and ribosomal proteins were seen to follow this regulation pattern while those of enzymes involved in nucleotide metabolism increased more than the specific growth rate (over 5.5 times). Nucleotide synthesis formed the most abundant biomonomer synthetic pathway in the cells with an expenditure of 6% from the total ATP required for biosynthesis. Due to the increase in apparent catalytic activity, ribosome translation was more efficient at higher growth rates as evidenced by a decrease of protein to mRNA ratios. All these effects resulted in a 30% decrease of calculated ATP spilling (0.1 vs 0.5 h−1). Our results show that bioprocesses can be made more efficient (using a balanced metabolism) by varying the growth conditions. PMID:23133574

  15. Increased expression of sialic acid in cervical biopsies with squamous intraepithelial lesions

    PubMed Central

    2010-01-01

    Background Altered sialylation has been observed during oncogenic transformation. Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumor progression and metastases. In the cervical cancer high levels of sialic acid have been reported in the patients serum, and an increased of total sialic acid concentration has been reported for the cervical neoplasia and cervical cancer. This study investigates the changes in expression and distribution of α2,3-linked sialic acid and α2,6- linked sialic acid in low and high squamous intraepithelial lesions and in normal tissue. Methods Lectin histochemistry was used to examine the expression and distribution of sialic acid in different grades of cervical neoplasia. We applied Maackia amurensis lectin, which interacts with α2,3-linked sialic acid and Sambucus nigra lectin specific for α2,6-linked sialic acid. Results The histochemical analysis showed that α2,3-linked sialic acid and α2,6- linked sialic acid increased in intensity and distribution in concordance with the grade of squamous intraepithelial lesion (SIL). These results are in concordance with a previous study that reports increased RNAm levels of three sialyltransferases. Conclusions These results show that the change in sialylation occurs before cancer development and may play an important role in cellular transformation. These findings provide the basis for more detailed studies of the possible role of cell surface glycoconjugates bearing sialic acid in the cellular cervix transformation. PMID:21092209

  16. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy.

    PubMed

    Viswanathan, V; Sivakumar, S; Sekar, V; Umapathy, D; Kumpatla, S

    2015-01-01

    This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio) at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM). A total of 65 (M: F; 42:23) T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10) nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22), microalbuminuric (n = 22) and macroalbuminuric (n = 21). Estimated glomerular filtration rate (eGFR) was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval) for normoalbuminuria was 0.65 (0.47-0.97), microalbuminuria was 0.99 (0.55-1.97) and macroalbuminuria was 5.16 (1.8-14.5), (P = 0.005). In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects. PMID:26628791

  17. Clinical significance of urinary liver-type fatty acid binding protein at various stages of nephropathy

    PubMed Central

    Viswanathan, V.; Sivakumar, S.; Sekar, V.; Umapathy, D.; Kumpatla, S.

    2015-01-01

    This cross-sectional study was to evaluate the levels of urinary liver-type fatty acid binding protein (u-LFABP pg/mg urine creatinine ratio) at different stages of diabetic nephropathy and to see its correlation with other clinical parameters in South Indian patients with type 2 diabetes mellitus (T2DM). A total of 65 (M: F; 42:23) T2DM subjects were divided into three groups, and were compared with 13 (M: F; 3:10) nondiabetic controls. The study groups were as follows: normoalbuminuric (n = 22), microalbuminuric (n = 22) and macroalbuminuric (n = 21). Estimated glomerular filtration rate (eGFR) was calculated using Cockcroft and Gault formula. u-LFABP levels in spot urine samples were measured with a solid phase enzyme linked immunosorbent assay. This study showed that u-LFABP levels were undetectable in healthy controls and was very low in the normoalbuminuric subjects. Elevated levels of u-LFABP are evident from the microalbuminuric stage indicating tubular damage. The levels of u-LFABP increased gradually with declining renal function. Geometric mean (95% confidence interval) for normoalbuminuria was 0.65 (0.47–0.97), microalbuminuria was 0.99 (0.55–1.97) and macroalbuminuria was 5.16 (1.8–14.5), (P = 0.005). In conclusion, u-LFABP levels were elevated in patients with reduced eGFR and showed a positive correlation with systolic blood pressure and protein to creatinine ratio in the total study subjects. PMID:26628791

  18. Ferulic acid prevents liver injury and increases the anti-tumor effect of diosbulbin B in vivo *

    PubMed Central

    Wang, Jun-ming; Sheng, Yu-chen; Ji, Li-li; Wang, Zheng-tao

    2014-01-01

    The present study is designed to investigate the protection by ferulic acid against the hepatotoxicity induced by diosbulbin B and its possible mechanism, and further observe whether ferulic acid augments diosbulbin B-induced anti-tumor activity. The results show that ferulic acid decreases diosbulbin B-increased serum alanine transaminase/aspartate transaminase (ALT/AST) levels. Ferulic acid also decreases lipid peroxide (LPO) levels which are elevated in diosbulbin B-treated mice. Histological evaluation of the liver demonstrates hydropic degeneration in diosbulbin B-treated mice, while ferulic acid reverses this injury. Moreover, the activities of copper- and zinc-containing superoxide dismutase (CuZn-SOD) and catalase (CAT) are decreased in the livers of diosbulbin B-treated mice, while ferulic acid reverses these decreases. Further results demonstrate that the mRNA expressions of CuZn-SOD and CAT in diosbulbin B-treated mouse liver are significantly decreased, while ferulic acid prevents this decrease. In addition, ferulic acid also augments diosbulbin B-induced tumor growth inhibition compared with diosbulbin B alone. Taken together, the present study shows that ferulic acid prevents diosbulbin B-induced liver injury via ameliorating diosbulbin B-induced liver oxidative stress injury and augments diosbulbin B-induced anti-tumor activity. PMID:24903991

  19. Occurrence of 3-hydroxy acids in microalgae and cyanobacteria and their geochemical significance

    NASA Astrophysics Data System (ADS)

    Matsumoto, Genki I.; Nagashima, Hideyuki

    1984-08-01

    3-Hydroxy acids were detected in pure cultured microalgae: Chlorophyta— Chlamydomonas reinhardtii and Chlorella pyrenoidosa and Rhodophyta— Cyanidium caldarium (two strains), and cyanobacteria (Cyanophyta)— Anacystis nidulans, Phormidium foveolarum, Anabaena variabilis and Oscillatoria sp. Normal and branched (iso and anteiso) 3-hydroxy acids in the ranges of C 8-C 26 were found in all the samples studied at concentrations ranging from 0.036 to 2.3 and 0.000 to 0.12 mg g -1 of dry sample, respectively. The major constituents were generally even-carbon numbered normal acids with carbon chain lengths below C 20. Microalgae and cyanobacteria may be the important sources of 3-hydroxy acids in natural environments.

  20. Omega-3 fatty acids protect renal functions by increasing docosahexaenoic acid-derived metabolite levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Katakura, Masanori; Hashimoto, Michio; Inoue, Takayuki; Al Mamun, Abdullah; Tanabe, Yoko; Iwamoto, Ryo; Arita, Makoto; Tsuchikura, Satoru; Shido, Osamu

    2014-01-01

    The omega-3 polyunsaturated fatty acids (ω-3 PUFAs) docosahexaenoic acid (DHA) and/or eicosapentaenoic acid (EPA) protect against diabetic nephropathy by inhibiting inflammation. The aim of this study was to assess the effects of highly purified DHA and EPA or EPA only administration on renal function and renal eicosanoid and docosanoid levels in an animal model of metabolic syndrome, SHR.Cg-Lepr(cp)/NDmcr (SHRcp) rats. Male SHRcp rats were divided into 3 groups. Control (5% arabic gum), TAK-085 (300 mg/kg/day, containing 467 mg/g EPA and 365 mg/g DHA), or EPA (300 mg/kg/day) was orally administered for 20 weeks. The urinary albumin to creatinine ratio in the TAK-085-administered group was significantly lower than that in other groups. The glomerular sclerosis score in the TAK-085-administered group was significantly lower than that in the other groups. Although DHA levels were increased in total kidney fatty acids, the levels of nonesterified DHA were not significantly different among the 3 groups, whereas the levels of protectin D1, resolvin D1, and resolvin D2 were significantly increased in the TAK-085-administered group. The results show that the use of combination therapy with DHA and EPA in SHRcp rats improved or prevented renal failure associate with metabolic syndrome with decreasing triglyceride levels and increasing ω-3 PUFA lipid mediators. PMID:24642910

  1. Dietary Conjugated Linoleic Acid (CLA) increases milk yield without losing body weight in lactating sows.

    PubMed

    Lee, Sung-Hoon; Joo, Young-Kuk; Lee, Jin-Woo; Ha, Young-Joo; Yeo, Joon-Mo; Kim, Wan-Young

    2014-01-01

    This study was conducted to evaluate the effects of dietary conjugated linoleic acid (CLA) on the performance of lactating sows and piglets as well as the immunity of piglets suckling from sows fed CLA. Eighteen multiparous Duroc sows with an average body weight (BW) of 232.0 ± 6.38 kg were randomly selected and assigned to two dietary treatments (n = 9 for each treatment), control (no CLA addition) and 1% CLA supplementation. For the control diet, CLA was replaced with soybean oil. Experimental diets were fed to sows during a 28-day lactation period. Litter size for each sow was standardized to nine piglets by cross-fostering within 24 hours after birth. Sow milk and blood samples were taken from sows and piglets after 21 and 27 days of lactation, respectively. Loss of BW was significantly (p < 0.05) higher in sows fed control diet compared to sows fed CLA diet. Piglet weights at weaning and weight gain during suckling were significantly (p < 0.05) higher in sows fed CLA compared to sows fed control diet. Serum non-esterified fatty acid (NEFA) and urea nitrogen concentrations were significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. IgG concentrations of the groups supplemented with CLA increased by 49% in sow serum (p < 0.0001), 23% in milk (p < 0.05), and 35% in piglet serum (p < 0.05) compared with the control group. Sows fed CLA showed an increase of 10% in milk yield compared with sows fed soybean oil (p < 0.05), even though there was no difference in daily feed intake between the treatments. Milk fat content was significantly (p < 0.05) lower in sows fed CLA than in sows fed soybean oil. Solid-not-fat yield was significantly (p < 0.05) higher in sows supplemented with CLA than in sows fed control diet and also protein-to-fat ratio in milk was significantly (p < 0.05) higher in sows fed CLA compared with the control group. The results show that CLA supplementation to sows increased milk yield without losing BW during

  2. Clinical significance of elevated serum A-FABP and free fatty acid in neonates with hypoxic ischemic brain damage

    PubMed Central

    Li, Mei; Jiang, Lian; Zhang, Huifen; Wang, Dandan; Zhang, Min; Zhang, Lianshan

    2016-01-01

    The main function of adipocyte fatty acid-binding protein (A-FABP) is to regulate fatty acid metabolism as its molecular chaperone. The clinical significance of A-FABP in hypoxic-ischemic brain damage (HIBD) neonates is not yet clear. Free fatty acid (FFA) in cerebral cortex increases along with hypoxia ischemia degree. Thus, we aimed to investigate whether FFA can induce A-FABP expression and elevate the serum A-FABP level in HIBD neonates. In the present study, 42 HIBD neonates were selected including 11 cases as mild, 16 cases as moderate and 15 cases as severe. The serum was collected from peripheral vein at 72 h after the first visit (acute stage) and 7 days after birth (recovery stage), and the serum from 10 normal neonates was used as the control. The serum level of A-FABP and FFA in 42 neonates with acute phase and recovery phase HIBD were detected using ELISA and copper colorimetric method. The overall serum A-FABP content in HIBD neonates at the acute stage was significantly higher compared to the normal neonates (P<0.05). The serum A-FABP level in severe HIBD neonates was significantly higher than that in mild HIBD, moderate HIBD and normal neonates (P<0.05). The serum FFA level in HIBD neonates at the acute stage was 1,521.57±605.63 µmol/l, which was significantly higher than that in the normal neonates 838.24±294.22 µmol/l. The serum FFA levels in mild, moderate and severe HIBD neonates were significantly higher than those in the normal neonates. The overall A-FABP level in HIBD neonates at the recovery stage was significantly lower compared to the acute stage, which was significant in severe HIBD neonates. A-FABP levels in mild and moderate HIBD neonates at recovery stage were decreased compared with the acute stage, although there was no statistical difference. There was a positive correlation between serum A-FABP and FFA in HIBD neonates at acute stage (r=0.369, P<0.05). In conclusion, serum A-FABP and FFA levels were signifcantly increased in

  3. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline. PMID:25450447

  4. Dephytinisation with Intrinsic Wheat Phytase and Iron Fortification Significantly Increase Iron Absorption from Fonio (Digitaria exilis) Meals in West African Women

    PubMed Central

    Moretti, Diego; Schuth, Stephan; Egli, Ines; Zimmermann, Michael B.; Brouwer, Inge D.

    2013-01-01

    Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16), using non-dephytinised fonio porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each fortified with 57Fe or 58Fe labeled FeSO4. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio) to 2.9±1.3 phytase unit (PU) per g (whole wheat). Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C). Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly increased from 2.6% (0.8–7.8) in FFP to 8.3% (3.8–17.9) in FWFP (P<0.0001). Dephytinisation of fonio porridge with intrinsic wheat phytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges. PMID:24124445

  5. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice.

    PubMed

    Fu, Zidong Donna; Klaassen, Curtis D

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a "dose-response" model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR "dose-dependently" increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. PMID:24183703

  6. Uric acid secretion from adipose tissue and its increase in obesity.

    PubMed

    Tsushima, Yu; Nishizawa, Hitoshi; Tochino, Yoshihiro; Nakatsuji, Hideaki; Sekimoto, Ryohei; Nagao, Hirofumi; Shirakura, Takashi; Kato, Kenta; Imaizumi, Keiichiro; Takahashi, Hiroyuki; Tamura, Mizuho; Maeda, Norikazu; Funahashi, Tohru; Shimomura, Iichiro

    2013-09-20

    Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity. PMID:23913681

  7. Dietary oleic acid increases M2 macrophages in the mesenteric adipose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Several studies have implicated fatty-acids as inflammatory regulators, suggesting that there may be a direct role for common dietary fatty-acids in regulating innate immune cells. In humans, a single high-fat meal increases systemic cytokines and leukocytes. In mice, short term high-fat feeding in...

  8. Camelina meal increases egg n-3 fatty acid content without altering quality or production in laying hens.

    PubMed

    Kakani, Radhika; Fowler, Justin; Haq, Akram-Ul; Murphy, Eric J; Rosenberger, Thad A; Berhow, Mark; Bailey, Christopher A

    2012-05-01

    Camelina sativa is an oilseed plant rich in n-3 and n-6 fatty acids and extruding the seeds results in high protein meal (*40%) containing high levels of n-3 fatty acids. In this study, we examined the effects of feeding extruded defatted camelina meal to commercial laying hens, measuring egg production, quality, and fatty acid composition. Lohmann White Leghorn hens (29 weeks old) were randomly allocated to three dietary treatment groups (n = 25 per group) and data was collected over a 12 week production period. All the treatment groups were fed a corn soy based experimental diet containing 0% (control), 5, or 10% extruded camelina meal. We found no significant differences in percent hen-day egg production and feed consumed per dozen eggs. Egg shell strength was significantly higher in both camelina groups compared to the controls. Egg total n-3 fatty acid content increased 1.9- and 2.7-fold in 5 and 10% camelina groups respectively relative to the control. A similar increase in DHA content also occurred. Further camelina meal did not alter glucosinolate levels and no detectable glucosinolates or metabolic product isothiocyanates were found in the eggs from either the 5 or 10% camelina groups. These results indicate that camelina meal is a viable dietary source of n-3 fatty acids for poultry and its dietary inclusion results in eggs enriched with n-3 fatty acids. PMID:22302480

  9. A Significant Increase in the Incidence of Central Precocious Puberty among Korean Girls from 2004 to 2010

    PubMed Central

    Kim, Shin Hye; Huh, Kyoung; Won, Sungho; Lee, Kuk-Wha; Park, Mi-Jung

    2015-01-01

    Background Few studies have explored the trends in central precocious puberty (CPP) in Asian populations. This study assessed the prevalence and annual incidence of CPP among Korean children. Methods Using data from the Korean Health Insurance Review Agency from 2004 to 2010, we reviewed the records of 21,351 children, including those registered with a diagnosis of CPP for the first time and those diagnosed with CPP who were treated with gonadotropin-releasing hormone analogs. Results The prevalence of CPP was 55.9 per 100,000 girls and 1.7 per 100,000 boys, respectively. The overall incidence of CPP was 15.3 per 100,000 girls, and 0.6 per 100,000 boys. The annual incidence of CPP in girls significantly increased from 3.3 to 50.4 per 100,000 girls; whereas in boys, it gradually increased from 0.3 to 1.2 per 100,000 boys. The annual incidence of CPP in girls consistently increased at all ages year by year, with greater increases at older ages (≥6 years of age), and smaller increases in girls aged < 6 years. In contrast, the annual incidence remained relatively constant in boys aged < 8 years, while a small increase was observed only in boys aged 8 years. The increase of annual incidence showed significant differences depending on age and gender (P <0.0001). Conclusions The annual incidence of CPP has substantially increased among Korean girls over the past 7 years. Continued monitoring of CPP trends among Korean children will be informative. PMID:26539988

  10. Public health significance of supplementation or fortification of grain products with folic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The need for supplemental folate can be traced to the initial phase of the discovery of this vitamin as a micronutrient for the prevention of pregnancy related anemia. In the post discovery era, folic acid was used primarily to prevent deficiency as manifested by low blood folate levels and megalob...

  11. Increase in adipose tissue linoleic acid of US adults in the last half century.

    PubMed

    Guyenet, Stephan J; Carlson, Susan E

    2015-11-01

    Linoleic acid (LA) is a bioactive fatty acid with diverse effects on human physiology and pathophysiology. LA is a major dietary fatty acid, and also one of the most abundant fatty acids in adipose tissue, where its concentration reflects dietary intake. Over the last half century in the United States, dietary LA intake has greatly increased as dietary fat sources have shifted toward polyunsaturated seed oils such as soybean oil. We have conducted a systematic literature review of studies reporting the concentration of LA in subcutaneous adipose tissue of US cohorts. Our results indicate that adipose tissue LA has increased by 136% over the last half century and that this increase is highly correlated with an increase in dietary LA intake over the same period of time. PMID:26567191

  12. The Significance of Acid Alteration in the Los Humeros High-Temperature Geothermal Field, Puebla, Mexico.

    NASA Astrophysics Data System (ADS)

    Elders, W. A.; Izquierdo, G.

    2014-12-01

    The Los Humeros geothermal field is a high-enthalpy hydrothermal system with more than 40 drilled deep wells, mostly producing high steam fractions at > 300oC. However, although it has a large resource potential, low permeability and corrosive acid fluids have hampered development so that it currently has an installed electrical generating capacity of only 40 MWe. The widespread production of low pH fluids from the reservoir is inconsistent with the marked absence in the reservoir rocks of hydrothermal minerals typical of acid alteration. Instead the hydrothermal alteration observed is typical of that due to neutral to alkaline pH waters reacting with the volcanic rocks of the production zones. Thus it appears that since the reservoir has recently suffered a marked drop in fluid pressure and is in process of transitioning from being water-dominated to being vapor-dominated. However sparse examples of acid leaching are observed locally at depths of about 2 km in the form of bleached, intensely silicified zones, in low permeability and very hot (>350oC) parts of reservoir. Although these leached rocks retain their primary volcanic and pyroclastic textures, they are altered almost entirely to microcrystalline quartz, with some relict pseudomorphs of plagioclase phenocrysts and traces of earlier-formed hydrothermal chlorite and pyrite. These acid-altered zones are usually only some tens of meters thick and deeper rocks lack such silicification. The acid fluids responsible for their formation could either be magmatic volatiles, or could be formed during production (e.g. reaction of water and salts forming hydrogen chloride by hydrolysis at high temperatures). The very high boron content of the fluids produced by the Los Humeros wells suggests that their ultimate source is most likely magmatic gases. However, these acid gases did not react widely with the rocks. We suggest that the silicified zones are forming locally where colder descending waters are encountering

  13. Dihydrolipoic acid activates oligomycin-sensitive thiol groups and increases ATP synthesis in mitochondria.

    PubMed

    Zimmer, G; Mainka, L; Krüger, E

    1991-08-01

    Investigations with dihydrolipoic acid in rat heart mitochondria and mitoplasts reveal an activation of ATP-synthase up to 45%, whereas ATPase activities decrease by 36%. In parallel with an increase in ATP synthesis oligomycin-sensitive mitochondrial -SH groups are activated at 2-4 nmol dihydrolipoic acid/mg protein. ATPase activation by the uncouplers carbonylcyanide-p-trifluoromethoxyphenylhydrazone and oleate is diminished by dihydrolipoic acid, and ATP synthesis depressed by oleate is partially restored. No such efficiency of dihydrolipoic acid is seen with palmitate-induced ATPase activation or decrease of ATP synthesis. This indicates different interference of oleate and palmitate with mitochondria. In addition to its known coenzymatic properties dihydrolipoic acid may act as a substitute for coenzyme A, thereby diminishing the uncoupling efficiency of oleate. Furthermore, dihydrolipoic acid is a very potent antioxidant, shifting the -SH-S-S- equilibrium in mitochondria to the reduced state and improving the energetic state of cells. PMID:1832845

  14. Regulation of carnitine palmitoyltransferase (CPT) I during fasting in rainbow trout (Oncorhynchus mykiss) promotes increased mitochondrial fatty acid oxidation.

    PubMed

    Morash, Andrea J; McClelland, Grant B

    2011-01-01

    Periods of fasting, in most animals, are fueled principally by fatty acids, and changes in the regulation of fatty acid oxidation must exist to meet this change in metabolic substrate use. We examined the regulation of carnitine palmitoyltransferase (CPT) I, to help explain changes in mitochondrial fatty acid oxidation with fasting. After fasting rainbow trout (Oncorhynchus mykiss) for 5 wk, the mitochondria were isolated from red muscle and liver to determine (1) mitochondrial fatty acid oxidation rate, (2) CPT I activity and the concentration of malonyl-CoA needed to inhibit this activity by 50% (IC(50)), (3) mitochondrial membrane fluidity, and (4) CPT I (all five known isoforms) and peroxisome proliferator-activated receptor (PPARα and PPARβ) mRNA levels. Fatty acid oxidation in isolated mitochondria increased during fasting by 2.5- and 1.75-fold in liver and red muscle, respectively. Fasting also decreased sensitivity of CPT I to malonyl-CoA (increased IC(50)), by two and eight times in red muscle and liver, respectively, suggesting it facilitates the rate of fatty acid oxidation. In the liver, there was also a significant increase CPT I activity per milligram mitochondrial protein and in whole-tissue PPARα and PPARβ mRNA levels. However, there were no changes in mitochondrial membrane fluidity in either tissue, indicating that the decrease in CPT I sensitivity to malonyl-CoA is not due to bulk fluidity changes in the membrane. However, there were significant differences in CPT I mRNA levels during fasting. Overall, these data indicate some important changes in the regulation of CPT I that promote the increased mitochondrial fatty acid oxidation that occurs during fasting in trout. PMID:22030855

  15. Skeletal muscle amino acid transporter expression is increased in young and older adults following resistance exercise

    PubMed Central

    Fry, Christopher S.; Glynn, Erin L.; Timmerman, Kyle L.; Dickinson, Jared M.; Walker, Dillon K.; Gundermann, David M.; Volpi, Elena; Rasmussen, Blake B.

    2011-01-01

    Amino acid transporters and mammalian target of rapamycin complex 1 (mTORC1) signaling are important contributors to muscle protein anabolism. Aging is associated with reduced mTORC1 signaling following resistance exercise, but the role of amino acid transporters is unknown. Young (n = 13; 28 ± 2 yr) and older (n = 13; 68 ± 2 yr) subjects performed a bout of resistance exercise. Skeletal muscle biopsies (vastus lateralis) were obtained at basal and 3, 6, and 24 h postexercise and were analyzed for amino acid transporter mRNA and protein expression and regulators of amino acid transporter transcription utilizing real-time PCR and Western blotting. We found that basal amino acid transporter expression was similar in young and older adults (P > 0.05). Exercise increased L-type amino acid transporter 1/solute-linked carrier (SLC) 7A5, CD98/SLC3A2, sodium-coupled neutral amino acid transporter 2/SLC38A2, proton-assisted amino acid transporter 1/SLC36A1, and cationic amino acid transporter 1/SLC7A1 mRNA expression in both young and older adults (P < 0.05). L-type amino acid transporter 1 and CD98 protein increased only in younger adults (P < 0.05). eukaryotic initiation factor 2 α-subunit (S52) increased similarly in young and older adults postexercise (P < 0.05). Ribosomal protein S6 (S240/244) and activating transcription factor 4 nuclear protein expression tended to be higher in the young, while nuclear signal transducer and activator of transcription 3 (STAT3) (Y705) was higher in the older subjects postexercise (P < 0.05). These results suggest that the rapid upregulation of amino acid transporter expression following resistance exercise may be regulated differently between the age groups, but involves a combination of mTORC1, activating transcription factor 4, eukaryotic initiation factor 2 α-subunit, and STAT3. We propose an increase in amino acid transporter expression may contribute to enhanced amino acid sensitivity following exercise in young and older

  16. Placement in an acidic environment increase the solubility of white mineral trioxide aggregate

    PubMed Central

    Yavari, Hamid Reza; Borna, Zahra; Rahimi, Saeed; Shahi, Shahriar; Valizadeh, Hadi; Ghojazadeh, Morteza

    2013-01-01

    Aims: The aim of the present study was to evaluate solubility of white mineral trioxide aggregate (WMTA) in an acidic environment. Materials and Methods: Twenty-four metal rings were prepared, filled with WMTA and randomly divided into two groups. The samples in groups 1 and 2 were set in synthetic tissue fluid with pH values of 7.4 and 4.4, respectively and then were transferred to beakers containing synthetic tissue fluid with pH values of 7.7 and 4.4. Solubility of WMTA samples were calculated at the 9 experimental intervals. Data was analyzed with two-factor ANOVA and Bonferroni test (P < 0.03). Results: The total solubility of WMTA in groups 1 and 2 were −9.1796 ± 1.9158% and −1.1192 ± 2.6236%, (P = 0.028) with weight changes of 9.1574 ± 2.1432% and 7.3276 ± 1.5823%, respectively (P = 0.002). Statistical analysis revealed significant differences between the two groups. Conclusions: It was concluded that solubility of WMTA increases in acidic environments and additional therapeutic precautions should be taken to decrease inflammation in endodontic treatment. PMID:23833462

  17. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli.

    PubMed

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M; Baerga-Ortiz, Abel

    2014-02-01

    Increasing the production of fatty acids by microbial fermentation remains an important step toward the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations toward accessible biodiesel precursors. PMID:24411456

  18. Expression of dehydratase domains from a polyunsaturated fatty acid synthase increases the production of fatty acids in Escherichia coli

    PubMed Central

    Oyola-Robles, Delise; Rullán-Lind, Carlos; Carballeira, Néstor M.; Baerga-Ortiz, Abel

    2014-01-01

    Increasing the production of fatty acids by microbial fermentation remains an important step towards the generation of biodiesel and other portable liquid fuels. In this work, we report an Escherichia coli strain engineered to overexpress a fragment consisting of four dehydratase domains from the polyunsaturated fatty acid (PUFA) synthase enzyme complex from the deep-sea bacterium, Photobacterium profundum. The DH1-DH2-UMA enzyme fragment was excised from its natural context within a multi-enzyme PKS and expressed as a stand-alone protein. Fatty acids were extracted from the cell pellet, esterified with methanol and quantified by GC-MS analysis. Results show that the E. coli strain expressing the DH tetradomain fragment was capable of producing up to a 5-fold increase (80.31 mg total FA/L culture) in total fatty acids over the negative control strain lacking the recombinant enzyme. The enhancement in production was observed across the board for all the fatty acids that are typically made by E. coli. The overexpression of the DH tetradomain did not affect E. coli cell growth, thus showing that the observed enhancement in fatty acid production was not a result of effects associated with cell density. The observed enhancement was more pronounced at lower temperatures (3.8-fold at 16 °C, 3.5-fold at 22 °C and 1.5-fold at 30 °C) and supplementation of the media with 0.4% glycerol did not result in an increase in fatty acid production. All these results taken together suggest that either the dehydration of fatty acid intermediates are a limiting step in the E. coli fatty acid biosynthesis machinery, or that the recombinant dehydratase domains used in this study are also capable of catalyzing thioester hydrolysis of the final products. The enzyme in this report is a new tool which could be incorporated into other existing strategies aimed at improving fatty acid production in bacterial fermentations towards accessible biodiesel precursors. PMID:24411456

  19. An evaluation of the significance of mouth and hand contamination for lead absorption in lead-acid battery workers.

    PubMed

    Far, H S; Pin, N T; Kong, C Y; Fong, K S; Kian, C W; Yan, C K

    1993-01-01

    The present study was conducted to evaluate the role of ingestion through hand and mouth contamination in the absorption of lead in 25 lead-acid battery workers. Levels of personal exposure to airborne lead ranged from 0.004 to 2.58 mg/m3 [geometric mean 0.098, with 25% of samples exceeding threshold limit values (ACGIH) of 0.15 mg/m3]; the mean (SD) blood lead level was 48.9 (10.8) micrograms/dl. Mean hand lead contents increased 33-fold from preshift levels on Monday mornings (33.5 micrograms/500 ml) to midshift levels on Thursday afternoons (1121 micrograms/500 ml). Mouth lead contents increased 16-fold from 0.021 micrograms/50 ml on Mondays to 0.345 micrograms/50 ml on Thursdays. The typical Malay racial habit of feeding with bare hands and fingers without utensils (closely associated with mouth and hand lead levels on Mondays) explained the bulk of the variance in blood lead levels (40%), with mouth lead on Thursdays (closely associated with poor personal hygiene) explaining a further 10%. Air lead was not a significant explanatory variable. The implementation of a programme of reinforcing hand-washing and mouth-rinsing practices resulted in a reduction of the blood lead level by 11.5% 6 months later. These results indicate that parenteral intake from hand and mouth contamination is an important cause of lead absorption in lead-exposed workers. PMID:8458660

  20. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production.

    PubMed

    Hellmann, Jason; Zhang, Michael J; Tang, Yunan; Rane, Madhavi; Bhatnagar, Aruni; Spite, Matthew

    2013-08-01

    Extensive evidence indicates that nutrient excess associated with obesity and type 2 diabetes activates innate immune responses that lead to chronic, sterile low-grade inflammation, and obese and diabetic humans also have deficits in wound healing and increased susceptibility to infections. Nevertheless, the mechanisms that sustain unresolved inflammation during obesity remain unclear. In this study, we report that saturated free fatty acids that are elevated in obesity alter resolution of acute sterile inflammation by promoting neutrophil survival and decreasing macrophage phagocytosis. Using a targeted mass spectrometry-based lipidomics approach, we found that in db/db mice, PGE2/D2 levels were elevated in inflammatory exudates during the development of acute peritonitis. Moreover, in isolated macrophages, palmitic acid stimulated cyclooxygenase-2 induction and prostanoid production. Defects in macrophage phagocytosis induced by palmitic acid were mimicked by PGE2 and PGD2 and were reversed by cyclooxygenase inhibition or prostanoid receptor antagonism. Macrophages isolated from obese-diabetic mice expressed prostanoid receptors, EP2 and DP1, and contained significantly higher levels of downstream effector, cAMP, compared with wild-type mice. Therapeutic administration of EP2/DP1 dual receptor antagonist, AH6809, decreased neutrophil accumulation in the peritoneum of db/db mice, as well as the accumulation of apoptotic cells in the thymus. Taken together, these studies provide new insights into the mechanisms underlying altered innate immune responses in obesity and suggest that targeting specific prostanoid receptors may represent a novel strategy for resolving inflammation and restoring phagocyte defects in obese and diabetic individuals. PMID:23785121

  1. Biochar enhances Aspergillus niger rock phosphate solubilization by increasing organic acid production and alleviating fluoride toxicity.

    PubMed

    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. PMID:24610849

  2. Biochar Enhances Aspergillus niger Rock Phosphate Solubilization by Increasing Organic Acid Production and Alleviating Fluoride Toxicity

    PubMed Central

    Mendes, Gilberto de Oliveira; Zafra, David Lopez; Vassilev, Nikolay Bojkov; Silva, Ivo Ribeiro; Ribeiro, José Ivo

    2014-01-01

    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. PMID:24610849

  3. Ecophysiological Significance of CO2-Recycling via Crassulacean Acid Metabolism in Talinum calycinum Engelm. (Portulacaceae) 1

    PubMed Central

    Martin, Craig E.; Higley, Michael; Wang, Wei-Zhong

    1988-01-01

    High levels of variability in gas exchange characteristics and degree of CAM-cycling were found in the same and different individuals of Talinum calycinum Engelm. collected from rock outcrops in Missouri. Differences in CO2 assimilation were mostly correlated with differences in shoot conductance to CO2 not shoot internal CO2 concentration. As found previously, CAM acid fluctuations were evident in well-watered plants exhibiting C3 gas exchange patterns (CAM-cycling) and also in drought-stressed plants with stomata closed, or nearly so, day and night (CAM-idling). Drought stress also resulted in rapid stomatal closure, conserving water during droughts. Maximal CO2 uptake rates occurred below 35°C; higher temperatures induced decreases in CO2 assimilation and conductance while shoot internal CO2 concentrations remained similar. Plant water-use-efficiency was severely curtailed at temperatures above 30°C. Tissue acid fluctuations were the result of changes in malic acid concentrations. Calculations of the amount of water potentially conserved by CAM-cycling yielded values of approximately 5 to 44% of daytime water loss. Thus, CAM-cycling may be an important adaptation minimizing water loss by perennial succulents growing in shallow soil on rock outcrops. PMID:16665946

  4. Dietary alpha-linolenic acid increases brain but not heart and liver docosahexaenoic acid levels.

    PubMed

    Barceló-Coblijn, Gwendolyn; Collison, Lauren W; Jolly, Christopher A; Murphy, Eric J

    2005-08-01

    Fish oil-enriched diets increase n-3 FA in tissue phospholipids; however, a similar effect by plant-derived n-3 FA is poorly defined. To address this question, we determined mass changes in phospholipid FA, individual phospholipid classes, and cholesterol in the liver, heart, and brain of rats fed diets enriched in flax oil (rich in 18:3n-3), fish oil (rich in 22:6n-3 and 20:5n-3), or safflower oil (rich in 18:2n-6) for 8 wk. In the heart and liver phospholipids, 22:6n-3 levels increased only in the fish oil group, although rats fed flax oil accumulated 20:5n-3 and 22:5n-3. However, in the brain, the flax and fish oil diets increased the phospholipid 22:6n-3 mass. In all tissues, these diets decreased the 20:4n-6 mass, although the effect was more marked in the fish oil than in the flax oil group. Although these data do not provide direct evidence for 18:3n-3 elongation and desaturation by the brain, they demonstrate that 18:3n-3-enriched diets reduced tissue 20:4n-6 levels and increased cellular n-3 levels in a tissue-dependent manner. We hypothesize, based on the lack of increased 22:6n-3 but increased 18:3n-3 in the liver and heart, that the flax oil diet increased circulating 18:3n-3, thereby presenting tissue with this EFA for further elongation and desaturation. PMID:16296397

  5. Increased bile acids in enterohepatic circulation by short-term calorie restriction in male mice

    SciTech Connect

    Fu, Zidong Donna; Klaassen, Curtis D.

    2013-12-15

    Previous studies showed glucose and insulin signaling can regulate bile acid (BA) metabolism during fasting or feeding. However, limited knowledge is available on the effect of calorie restriction (CR), a well-known anti-aging intervention, on BA homeostasis. To address this, the present study utilized a “dose–response” model of CR, where male C57BL/6 mice were fed 0, 15, 30, or 40% CR diets for one month, followed by BA profiling in various compartments of the enterohepatic circulation by UPLC-MS/MS technique. This study showed that 40% CR increased the BA pool size (162%) as well as total BAs in serum, gallbladder, and small intestinal contents. In addition, CR “dose-dependently” increased the concentrations of tauro-cholic acid (TCA) and many secondary BAs (produced by intestinal bacteria) in serum, such as tauro-deoxycholic acid (TDCA), DCA, lithocholic acid, ω-muricholic acid (ωMCA), and hyodeoxycholic acid. Notably, 40% CR increased TDCA by over 1000% (serum, liver, and gallbladder). Interestingly, 40% CR increased the proportion of 12α-hydroxylated BAs (CA and DCA), which correlated with improved glucose tolerance and lipid parameters. The CR-induced increase in BAs correlated with increased expression of BA-synthetic (Cyp7a1) and conjugating enzymes (BAL), and the ileal BA-binding protein (Ibabp). These results suggest that CR increases BAs in male mice possibly through orchestrated increases in BA synthesis and conjugation in liver as well as intracellular transport in ileum. - Highlights: • Dose response effects of short-term CR on BA homeostasis in male mice. • CR increased the BA pool size and many individual BAs. • CR altered BA composition (increased proportion of 12α-hydroxylated BAs). • Increased mRNAs of BA enzymes in liver (Cyp7a1 and BAL) and ileal BA binding protein.

  6. Organic Acid Excretion in Penicillium ochrochloron Increases with Ambient pH

    PubMed Central

    Vrabl, Pamela; Fuchs, Viktoria; Pichler, Barbara; Schinagl, Christoph W.; Burgstaller, Wolfgang

    2012-01-01

    Despite being of high biotechnological relevance, many aspects of organic acid excretion in filamentous fungi like the influence of ambient pH are still insufficiently understood. While the excretion of an individual organic acid may peak at a certain pH value, the few available studies investigating a broader range of organic acids indicate that total organic acid excretion rises with increasing external pH. We hypothesized that this phenomenon might be a general response of filamentous fungi to increased ambient pH. If this is the case, the observation should be widely independent of the organism, growth conditions, or experimental design and might therefore be a crucial key point in understanding the function and mechanisms of organic acid excretion in filamentous fungi. In this study we explored this hypothesis using ammonium-limited chemostat cultivations (pH 2–7), and ammonium or phosphate-limited bioreactor batch cultivations (pH 5 and 7). Two strains of Penicillium ochrochloron were investigated differing in the spectrum of excreted organic acids. Confirming our hypothesis, the main result demonstrated that organic acid excretion in P. ochrochloron was enhanced at high external pH levels compared to low pH levels independent of the tested strain, nutrient limitation, and cultivation method. We discuss these findings against the background of three hypotheses explaining organic acid excretion in filamentous fungi, i.e., overflow metabolism, charge balance, and aggressive acidification hypothesis. PMID:22493592

  7. Conjugated linoleic acid supplementation for twelve weeks increases lean body mass in obese humans.

    PubMed

    Steck, Susan E; Chalecki, Allison M; Miller, Paul; Conway, Jason; Austin, Gregory L; Hardin, James W; Albright, Craig D; Thuillier, Philippe

    2007-05-01

    Conjugated linoleic acid (CLA) alters body composition in animal models, but few studies have examined the effects of CLA supplementation on body composition and clinical safety measures in obese humans. In the present study, we performed a randomized, double-blind, placebo-controlled trial to examine the changes in body composition and clinical laboratory values following CLA (50:50 ratio of cis-9, trans-11 and trans-10, cis-12 isomers) supplementation for 12 wk in otherwise healthy obese humans. Forty-eight participants (13 males and 35 females) were randomized to receive placebo (8 g safflower oil/d), 3.2 g/d CLA, or 6.4 g/d CLA for 12 wk. Changes in body fat mass and lean body mass were determined by dual-energy X-ray absorptiometry. Resting energy expenditure was assessed by indirect calorimetry. Clinical laboratory values and adverse-event reporting were used to monitor safety. Lean body mass increased by 0.64 kg in the 6.4 g/d CLA group (P < 0.05) after 12 wk of intervention. Significant decreases in serum HDL-cholesterol and sodium, hemoglobin, and hematocrit, and significant increases in serum alkaline phosphatase, C-reactive protein, and IL-6, and white blood cells occurred in the 6.4 g/d CLA group, although all values remained within normal limits. The intervention was well tolerated and no severe adverse events were reported, although mild gastrointestinal adverse events were reported in all treatment groups. In conclusion, whereas CLA may increase lean body mass in obese humans, it may also increase markers of inflammation in the short term. PMID:17449580

  8. High hydrostatic pressure increases amino acid requirements in the piezo-hyperthermophilic archaeon Thermococcus barophilus.

    PubMed

    Cario, Anaïs; Lormières, Florence; Xiang, Xiao; Oger, Philippe

    2015-11-01

    We have established a defined growth medium for the piezophilic hyperthermophilic archaeon Thermococcus barophilus, which allows growth yields of ca. 10(8) cells/ml under both atmospheric and high hydrostatic pressure. Our results demonstrate a major impact of hydrostatic pressure on amino acid metabolism, with increases from 3 amino acids required at atmospheric pressure to 17 at 40 MPa. We observe in T. barophilus and other Thermococcales a similar discrepancy between the presence/absence of amino acid synthesis pathways and amino acid requirements, which supports the existence of alternate, but yet unknown, amino acid synthesis pathways, and may explain the low number of essential amino acids observed in T. barophilus and other Thermococcales. T. barophilus displays a strong metabolic preference for organic polymers such as polypeptides and chitin, which may constitute a more readily available resource of carbon and energy in situ in deep-sea hydrothermal vents. We hypothesize that the low energy yields of fermentation of organic polymers, together with energetic constraints imposed by high hydrostatic pressure, may render de novo synthesis of amino acids ecologically unfavorable. Induction of this metabolic switch to amino acid recycling can explain the requirement for non-essential amino acids by Thermococcales for efficient growth in defined medium. PMID:26226334

  9. Electric field increases the phase transition temperature in the bilayer membrane of phosphatidic acid.

    PubMed

    Antonov, V F; Smirnova EYu; Shevchenko, E V

    1990-02-01

    The effect of the electric field on the phase transition temperature (Tc) of acidic 1,2-dipalmitoyl-sn-glycero-3-phosphate (DPPA) and 1,2-dipalmitoyl-sn-glycero-3-thionphosphate (thion-DPPA) and zwitterion, i.e. 1,2-dipalmitoyl-rac-3-phosphocholine and 1,2-distearoyl-rac-glycero-3-phosphocholine (DPPC and DSPC), lipids has been investigated. The phase transition was detected using the jump-like increase effect in the conductance of the planar bilayer membrane. A voltage increase to 150 mV has been shown to increase the phase transition temperature in a bilayer lipid membrane (BLM) of phosphatidic acids (DPPA and thion-DPPA) by 8-12 degrees C while the transition temperature in the bilayer of zwitterion lipids (DPPC and DSPC) increases insignificantly. The increasing of Tt in BLM of acidic lipids is attributed to the voltage-induced changes in the molecule packing density. PMID:2340602

  10. Effects of nanomaterials on luciferase with significant protection and increased enzyme activity observed for zinc oxide nanomaterials.

    PubMed

    Barber, S; Abdelhakiem, M; Ghosh, K; Mitchell, L; Spidle, R; Jacobs, B; Washington, L; Li, J; Wanekaya, A; Glaspell, G; DeLong, R K

    2011-12-01

    This principle goal of this research was to examine the effects of various nanomaterials on the activity and behavior of the firefly enzyme luciferase. Nanomaterials have been found to stabilize, and in some instances, shown to increase the activity of enzymes. In this study gold, manganese oxide (MnO), and zinc oxide (ZnO) nanomaterials were utilized in order to test their effects on enzyme activity. Luciferase was used because its activity is easy to analyze, as it typically produces a large amount of bioluminescence easily detected by a Microtiter plate reader. Following incubation with the various nanomaterials, luciferase was subjected to degradation by several protein denaturing agents, such as heat, SDS, urea, ethanol, protease, hydrogen peroxide, and pH changes. Results indicated that luciferase activity is indeed affected when combined with nanomaterials, accompanied by both increases and decreases in enzyme activity depending on the type of nanomaterial and denaturing agent used. In most of the experiments, when incubated with ZnO nanomaterials, luciferase depicted significant increases in activity and bioluminescence. Additional experiments, in which human A375 cells were treated with luciferase-nanomaterial mixtures, also depicted increased enzyme activity and bioluminescence for luciferase incubated with ZnO nanomaterials. Ultimately, our findings indicated that when luciferase was subjected to multiple types of denaturation, zinc oxide nanomaterials dramatically preserved and increased enzyme activity and bioluminescence. PMID:22408903

  11. Effects of Step-Wise Increases in Dietary Carbohydrate on Circulating Saturated Fatty Acids and Palmitoleic Acid in Adults with Metabolic Syndrome

    PubMed Central

    Volk, Brittanie M.; Kunces, Laura J.; Freidenreich, Daniel J.; Kupchak, Brian R.; Saenz, Catherine; Artistizabal, Juan C.; Fernandez, Maria Luz; Bruno, Richard S.; Maresh, Carl M.; Kraemer, William J.; Phinney, Stephen D.; Volek, Jeff S.

    2014-01-01

    Recent meta-analyses have found no association between heart disease and dietary saturated fat; however, higher proportions of plasma saturated fatty acids (SFA) predict greater risk for developing type-2 diabetes and heart disease. These observations suggest a disconnect between dietary saturated fat and plasma SFA, but few controlled feeding studies have specifically examined how varying saturated fat intake across a broad range affects circulating SFA levels. Sixteen adults with metabolic syndrome (age 44.9±9.9 yr, BMI 37.9±6.3 kg/m2) were fed six 3-wk diets that progressively increased carbohydrate (from 47 to 346 g/day) with concomitant decreases in total and saturated fat. Despite a distinct increase in saturated fat intake from baseline to the low-carbohydrate diet (46 to 84 g/day), and then a gradual decrease in saturated fat to 32 g/day at the highest carbohydrate phase, there were no significant changes in the proportion of total SFA in any plasma lipid fractions. Whereas plasma saturated fat remained relatively stable, the proportion of palmitoleic acid in plasma triglyceride and cholesteryl ester was significantly and uniformly reduced as carbohydrate intake decreased, and then gradually increased as dietary carbohydrate was re-introduced. The results show that dietary and plasma saturated fat are not related, and that increasing dietary carbohydrate across a range of intakes promotes incremental increases in plasma palmitoleic acid, a biomarker consistently associated with adverse health outcomes. PMID:25415333

  12. Nordihydroguaiaretic acid and aspirin increase lifespan of genetically heterogeneous male mice.

    PubMed

    Strong, Randy; Miller, Richard A; Astle, Clinton M; Floyd, Robert A; Flurkey, Kevin; Hensley, Kenneth L; Javors, Martin A; Leeuwenburgh, Christiaan; Nelson, James F; Ongini, Ennio; Nadon, Nancy L; Warner, Huber R; Harrison, David E

    2008-10-01

    The National Institute on Aging's Interventions Testing Program was established to evaluate agents that are purported to increase lifespan and delay the appearance of age-related disease in genetically heterogeneous mice. Up to five compounds are added to the study each year and each compound is tested at three test sites (The Jackson Laboratory, University of Michigan, and University of Texas Health Science Center at San Antonio). Mice in the first cohort were exposed to one of four agents: aspirin, nitroflurbiprofen, 4-OH-alpha-phenyl-N-tert-butyl nitrone, or nordihydroguaiaretic acid (NDGA). Sample size was sufficient to detect a 10% difference in lifespan in either sex,with 80% power, using data from two of the three sites. Pooling data from all three sites, a log-rank test showed that both NDGA (p=0.0006) and aspirin (p=0.01) led to increased lifespan of male mice. Comparison of the proportion of live mice at the age of 90% mortality was used as a surrogate for measurement of maximum lifespan;neither NDGA (p=0.12) nor aspirin (p=0.16) had a significant effect in this test. Measures of blood levels of NDGA or aspirin and its salicylic acid metabolite suggest that the observed lack of effects of NDGA or aspirin on life span in females could be related to gender differences in drug disposition or metabolism. Further studies are warranted to find whether NDGA or aspirin, over a range of doses,might prove to postpone death and various age-related outcomes reproducibly in mice. PMID:18631321

  13. Amylases without known homologues discovered in an acid mine drainage: significance and impact

    PubMed Central

    Delavat, François; Phalip, Vincent; Forster, Anne; Plewniak, Frédéric; Lett, Marie-Claire; Lièvremont, Didier

    2012-01-01

    Acid Mine Drainages (AMDs) are extreme environments characterized by acidic and oligotrophic conditions and by metal contaminations. A function-based screening of an AMD-derived metagenomic library led to the discovery and partial characterization of two non-homologous endo-acting amylases sharing no sequence similarity with any known amylase nor glycosidase. None carried known amylolytic domains, nor could be assigned to any GH-family. One amylase displayed no similarity with any known protein, whereas the second one was similar to TraC proteins involved in the bacterial type IV secretion system. According to the scarce similarities with known proteins, 3D-structure modelling using I-TASSER was unsuccessful. This study underlined the utility of a function-driven metagenomic approach to obtain a clearer image of the bacterial community enzymatic landscape. More generally, this work points out that screening for microorganisms or biomolecules in a priori incongruous environments could provide unconventional and new exciting ways for bioprospecting. PMID:22482035

  14. Intranasal administration of glial-derived neurotrophic factor (GDNF) rapidly and significantly increases whole-brain GDNF level in rats.

    PubMed

    Bender, T S; Migliore, M M; Campbell, R B; John Gatley, S; Waszczak, B L

    2015-09-10

    Previous studies have shown that glial cell line-derived neurotrophic factor (GDNF) exerts significant neuroprotective effects on substantia nigra (SN) neurons in the rat 6-hydroxydopamine (6-OHDA) model of Parkinson's disease (PD). In this study we used enzyme-linked immunosorbent assay (ELISA) to determine GDNF brain levels and distribution to target regions (i.e. striatum and SN) following intranasal administration of GDNF at different time points after administration. Brain levels increased significantly within 1h following a single 50-μg dose of GDNF in a liposomal formulation, returning to baseline by 24h. In a second study, different doses of GDNF (10-150 μg) in phosphate-buffered saline (PBS) were studied at the 1-h time point. Dose-dependent increases in brain GDNF levels were observed with apparent saturation of uptake at doses above 100 μg. Liposomes delivered 10-fold more GDNF to brain than PBS despite yielding similar neuroprotective efficacy in the 6-OHDA model, suggesting incomplete release of GDNF from liposomes in tissue. In a third study, autoradiography was performed on brain sections taken 1h after intranasal (125)I-labeled GDNF. Radioactivity was detected throughout the brain along the rostral-to-caudal axis, indicating that nasally administered GDNF can reach target areas. Collectively, these results demonstrate that intranasal administration of GDNF in liposomes or PBS achieves significant increases in GDNF in target brain areas, supporting use of intranasal administration as a non-invasive means of delivering GDNF to the brain to protect dopamine neurons and arrest disease progression in PD. PMID:26166725

  15. A critical combination of operating parameters can significantly increase the electrotransformation efficiency of a gram-positive Dietzia strain.

    PubMed

    Lu, Shelian; Nie, Yong; Tang, Yue-Qin; Xiong, Guangming; Wu, Xiao-Lei

    2014-08-01

    Dietzia spp. have broad potential applications in industries. However, genetic manipulation of these species is obstructed by their low transformation efficiency, which is in the range of 10(4)colony-forming units (CFU)μg(-1) exogenous DNA. In this study, both single-factor and orthogonal experiments were conducted to test the effects of competent cell concentration (parameter A), electroporation time (B), and field strength (C), as well as the concentrations of glycine (D), isonicotinic acid hydrazide (INH, E), Tween 80 (F), and penicillin G (G) on the electrotransformation efficiency of Dietzia sp. DQ12-45-1b. The order in which the parameters contributed to electrotransformation efficiency was C>D>F>G>B>A>E, suggesting that field strength, glycine, and Tween 80 each had a greater capability to increase electrotransformation efficiency than the other parameters tested. Using the optimized protocol deduced from the results of the orthogonal experiments, the electrotransformation efficiency of Dietzia sp. DQ12-45-1b reached 2.51×10(7)CFUμg(-1) plasmid. To the best of our knowledge, this is the highest transformation efficiency that has been reported for Dietzia bacteria to date. Thus, we present a method that combines the transformation factors to obtain the optimal transformation efficiency for a target bacterium. PMID:24892513

  16. Plasma Circulating Nucleic Acids Levels Increase According to the Morbidity of Plasmodium vivax Malaria

    PubMed Central

    Franklin, Bernardo S.; Vitorino, Barbara L. F.; Coelho, Helena C.; Menezes-Neto, Armando; Santos, Marina L. S.; Campos, Fernanda M. F.; Brito, Cristiana F.; Fontes, Cor J.; Lacerda, Marcus V.; Carvalho, Luzia H.

    2011-01-01

    Background Given the increasing evidence of Plasmodium vivax infections associated with severe and fatal disease, the identification of sensitive and reliable markers for vivax severity is crucial to improve patient care. Circulating nucleic acids (CNAs) have been increasingly recognized as powerful diagnostic and prognostic tools for various inflammatory diseases and tumors as their plasma concentrations increase according to malignancy. Given the marked inflammatory status of P. vivax infection, we investigated here the usefulness of CNAs as biomarkers for malaria morbidity. Methods and Findings CNAs levels in plasma from twenty-one acute P. vivax malaria patients from the Brazilian Amazon and 14 malaria non-exposed healthy donors were quantified by two different methodologies: amplification of the human telomerase reverse transcriptase (hTERT) genomic sequence by quantitative real time PCR (qPCR), and the fluorometric dsDNA quantification by Pico Green. CNAs levels were significantly increased in plasma from P. vivax patients as compared to healthy donors (p<0.0001). Importantly, plasma CNAs levels were strongly associated with vivax morbidity (p<0.0001), including a drop in platelet counts (p = 0.0021). These findings were further sustained when we assessed CNAS levels in plasma samples from 14 additional P. vivax patients of a different endemic area in Brazil, in which CNAS levels strongly correlated with thrombocytopenia (p = 0.0072). We further show that plasma CNAs levels decrease and reach physiological levels after antimalarial treatment. Although we found both host and parasite specific genomic sequences circulating in plasma, only host CNAs clearly reflected the clinical spectrum of P. vivax malaria. Conclusions Here, we provide the first evidence of increased plasma CNAs levels in malaria patients and reveal their potential as sensitive biomarkers for vivax malaria morbidity. PMID:21611202

  17. Retinoic Acid-Treated Pluripotent Stem Cells Undergoing Neurogenesis Present Increased Aneuploidy and Micronuclei Formation

    PubMed Central

    Sartore, Rafaela C.; Campos, Priscila B.; Trujillo, Cleber A.; Ramalho, Bia L.; Negraes, Priscilla D.; Paulsen, Bruna S.; Meletti, Tamara; Costa, Elaine S.; Chicaybam, Leonardo; Bonamino, Martin H.; Ulrich, Henning; Rehen, Stevens K.

    2011-01-01

    The existence of loss and gain of chromosomes, known as aneuploidy, has been previously described within the central nervous system. During development, at least one-third of neural progenitor cells (NPCs) are aneuploid. Notably, aneuploid NPCs may survive and functionally integrate into the mature neural circuitry. Given the unanswered significance of this phenomenon, we tested the hypothesis that neural differentiation induced by all-trans retinoic acid (RA) in pluripotent stem cells is accompanied by increased levels of aneuploidy, as previously described for cortical NPCs in vivo. In this work we used embryonal carcinoma (EC) cells, embryonic stem (ES) cells and induced pluripotent stem (iPS) cells undergoing differentiation into NPCs. Ploidy analysis revealed a 2-fold increase in the rate of aneuploidy, with the prevalence of chromosome loss in RA primed stem cells when compared to naïve cells. In an attempt to understand the basis of neurogenic aneuploidy, micronuclei formation and survivin expression was assessed in pluripotent stem cells exposed to RA. RA increased micronuclei occurrence by almost 2-fold while decreased survivin expression by 50%, indicating possible mechanisms by which stem cells lose their chromosomes during neural differentiation. DNA fragmentation analysis demonstrated no increase in apoptosis on embryoid bodies treated with RA, indicating that cell death is not the mandatory fate of aneuploid NPCs derived from pluripotent cells. In order to exclude that the increase in aneuploidy was a spurious consequence of RA treatment, not related to neurogenesis, mouse embryonic fibroblasts were treated with RA under the same conditions and no alterations in chromosome gain or loss were observed. These findings indicate a correlation amongst neural differentiation, aneuploidy, micronuclei formation and survivin downregulation in pluripotent stem cells exposed to RA, providing evidence that somatically generated chromosomal variation accompanies

  18. Analysis of a large dataset of mycorrhiza inoculation field trials on potato shows highly significant increases in yield.

    PubMed

    Hijri, Mohamed

    2016-04-01

    An increasing human population requires more food production in nutrient-efficient systems in order to simultaneously meet global food needs while reducing the environmental footprint of agriculture. Arbuscular mycorrhizal fungi (AMF) have the potential to enhance crop yield, but their efficiency has yet to be demonstrated in large-scale crop production systems. This study reports an analysis of a dataset consisting of 231 field trials in which the same AMF inoculant (Rhizophagus irregularis DAOM 197198) was applied to potato over a 4-year period in North America and Europe under authentic field conditions. The inoculation was performed using a liquid suspension of AMF spores that was sprayed onto potato seed pieces, yielding a calculated 71 spores per seed piece. Statistical analysis showed a highly significant increase in marketable potato yield (ANOVA, P < 0.0001) for inoculated fields (42.2 tons/ha) compared with non-inoculated controls (38.3 tons/ha), irrespective of trial year. The average yield increase was 3.9 tons/ha, representing 9.5 % of total crop yield. Inoculation was profitable with a 0.67-tons/ha increase in yield, a threshold reached in almost 79 % of all trials. This finding clearly demonstrates the benefits of mycorrhizal-based inoculation on crop yield, using potato as a case study. Further improvements of these beneficial inoculants will help compensate for crop production deficits, both now and in the future. PMID:26403242

  19. Significance of pH on the Cytotoxic Potential of the Water Disinfection By-Product Iodoacetic Acid

    EPA Science Inventory

    Significance of pH on the Cytotoxic Potential of the Water Disinfection By-Product Iodoacetic Acid Vicki Richardson1, Susan D. Richardson2, Mary Moyer3, Jane Ellen Simmons1, and Anthony DeAngelo1, 1U.S. Environmental Protection Agency, Research Triangle Park, NC, 2University of...

  20. CONCENTRATION OF GLIAL FIBRILLARY ACIDIC PROTEIN INCREASES WITH AGE IN THE MOUSE AND RAT BRAIN

    EPA Science Inventory

    The role of aging in the expression of the astrocyte protein, glial fibrillary acidic protein (GFAP), was examined. n both mice and rats the concentration of GFAP increased throughout the brain as a function of aging. he largest increase (2-fold) was observed in striatum for both...

  1. Dietary conjugated linoleic acids increase intramuscular fat deposition and decrease subcutaneous fat deposition in Yellow Breed × Simmental cattle.

    PubMed

    Zhang, Haibo; Dong, Xianwen; Wang, Zhisheng; Zhou, Aiming; Peng, Quanhui; Zou, Huawei; Xue, Bai; Wang, Lizhi

    2016-04-01

    This study was conducted to estimate the effect of dietary conjugated linoleic acids (CLA) on intramuscular and subcutaneous fat deposition in Yellow Breed × Simmental cattle. The experiment was conducted for 60 days. The results showed that the average backfat thickness, (testicles + kidney + pelvic) fat percentage and subcutaneous fat percentage in dietary CLA were significantly lower than in the control group, while intramuscular the fat percentage was significantly higher. Compared to the control group, the Longissimus muscle enzyme activities of lipoprotein lipase (LPL), fatty acid synthase (FAS) and acetyl-coenzyme A carboxylase (ACC) in dietary CLA and the subcutaneous fat enzyme activities of LPL, hormone-sensitive lipase (HSL) and carnitine palmitoyltransferase-1 (CPT-1) were significantly increased. Similarly, compared to the control group, the Longissimus muscle sterol regulatory element binding protein 1 (SREBP-1), FAS, stearoyl-coenzyme A desaturase (SCD), ACC, peroxisome proliferator-activated receptor γ (PPARγ), heart fatty-acid binding protein (H-FABP) and LPL gene expression in dietary CLA were significant increased, as were the subcutaneous fat of PPARγ, H-FABP, LPL, CPT-1 and HSL in dietary CLA. These results indicated that dietary CLA increases IMF deposition mainly by the up-regulation of lipogenic gene expression, while decreasing subcutaneous fat deposition mainly by the up-regulation of lipolytic gene expression. PMID:26582037

  2. Structural stability and prebiotic properties of resistant starch type 3 increase bile acid turnover and lower secondary bile acid formation.

    PubMed

    Dongowski, Gerhard; Jacobasch, Gisela; Schmiedl, Detlef

    2005-11-16

    Microbial metabolism is essential in maintaining a healthy mucosa in the large bowel, preferentially through butyrate specific mechanisms. This system depends on starch supply. Two structurally different resistant starches type 3 (RS3) have been investigated with respect to their resistance to digestion, fermentability, and their effects on the composition and turnover of bile acids in rats. RSA (a mixture of retrograded maltodextrins and branched high molecular weight polymers), which is more resistant than RSB (a retrograded potato starch), increased the rate of fermentation accompanied by a decrease of pH in cecum, colon, and feces. Because they were bound to RS3, less bile acids were reabsorbed, resulting in a higher turnover through the large bowel. Because of the rise of volume, the bile acid level was unchanged and the formation of secondary bile acids was partly suppressed. The results proved a strong relation between RS3, short chain fatty acid production, and microflora. However, butyrate specific benefits are only achieved by an intake of RS3 that result in good fermentation properties, which depend on the kind of the resistant starch structures. PMID:16277431

  3. Strain-induced significant increase in metal-insulator transition temperature in oxygen-deficient Fe oxide epitaxial thin films

    NASA Astrophysics Data System (ADS)

    Hirai, Kei; Kan, Daisuke; Ichikawa, Noriya; Mibu, Ko; Yoda, Yoshitaka; Andreeva, Marina; Shimakawa, Yuichi

    2015-01-01

    Oxygen coordination of transition metals is a key for functional properties of transition-metal oxides, because hybridization of transition-metal d and oxygen p orbitals determines correlations between charges, spins and lattices. Strain often modifies the oxygen coordination environment and affects such correlations in the oxides, resulting in the emergence of unusual properties and, in some cases, fascinating behaviors. While these strain effects have been studied in many of the fully-oxygenated oxides, such as ABO3 perovskites, those in oxygen-deficient oxides consisting of various oxygen coordination environments like tetrahedra and pyramids as well as octahedra remain unexplored. Here we report on the discovery of a strain-induced significant increase, by 550 K, in the metal-insulator transition temperature of an oxygen-deficient Fe oxide epitaxial thin film. The observed transition at 620 K is ascribed to charge disproportionation of Fe3.66+ into Fe4+ and Fe3+, associated with oxygen-vacancy ordering. The significant increase in the metal-insulator transition temperature, from 70 K in the bulk material, demonstrates that epitaxial growth of oxygen-deficient oxides under substrate-induced strain is a promising route for exploring novel functionality.

  4. Strain-induced significant increase in metal-insulator transition temperature in oxygen-deficient Fe oxide epitaxial thin films

    PubMed Central

    Hirai, Kei; Kan, Daisuke; Ichikawa, Noriya; Mibu, Ko; Yoda, Yoshitaka; Andreeva, Marina; Shimakawa, Yuichi

    2015-01-01

    Oxygen coordination of transition metals is a key for functional properties of transition-metal oxides, because hybridization of transition-metal d and oxygen p orbitals determines correlations between charges, spins and lattices. Strain often modifies the oxygen coordination environment and affects such correlations in the oxides, resulting in the emergence of unusual properties and, in some cases, fascinating behaviors. While these strain effects have been studied in many of the fully-oxygenated oxides, such as ABO3 perovskites, those in oxygen-deficient oxides consisting of various oxygen coordination environments like tetrahedra and pyramids as well as octahedra remain unexplored. Here we report on the discovery of a strain-induced significant increase, by 550 K, in the metal-insulator transition temperature of an oxygen-deficient Fe oxide epitaxial thin film. The observed transition at 620 K is ascribed to charge disproportionation of Fe3.66+ into Fe4+ and Fe3+, associated with oxygen-vacancy ordering. The significant increase in the metal-insulator transition temperature, from 70 K in the bulk material, demonstrates that epitaxial growth of oxygen-deficient oxides under substrate-induced strain is a promising route for exploring novel functionality. PMID:25600001

  5. Three conazoles increase hepatic microsomal retinoic acid metabolism and decrease mouse hepatic retinoic acid levels in vivo

    SciTech Connect

    Chen, P.-J.; Padgett, William T.; Moore, Tanya; Winnik, Witold; Lambert, Guy R.; Thai, Sheau-Fung; Hester, Susan D.; Nesnow, Stephen

    2009-01-15

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with cancer-preventative properties (Ward et al., Toxicol. Pathol. 2006; 34:863-78). The goals of this study were to examine effects of propiconazole, triadimefon, and myclobutanil, three triazole-containing conazoles, on the microsomal metabolism of atRA, the associated hepatic cytochrome P450 (P450) enzyme(s) involved in atRA metabolism, and their effects on hepatic atRA levels in vivo. The in vitro metabolism of atRA was quantitatively measured in liver microsomes from male CD-1 mice following four daily intraperitoneal injections of propiconazole (210 mg/kg/d), triadimefon (257 mg/kg/d) or myclobutanil (270 mg/kg/d). The formation of both 4-hydroxy-atRA and 4-oxo-atRA were significantly increased by all three conazoles. Propiconazole-induced microsomes possessed slightly greater metabolizing activities compared to myclobutanil-induced microsomes. Both propiconazole and triadimefon treatment induced greater formation of 4-hydroxy-atRA compared to myclobutanil treatment. Chemical and immuno-inhibition metabolism studies suggested that Cyp26a1, Cyp2b, and Cyp3a, but not Cyp1a1 proteins were involved in atRA metabolism. Cyp2b10/20 and Cyp3a11 genes were significantly over-expressed in the livers of both triadimefon- and propiconazole-treated mice while Cyp26a1, Cyp2c65 and Cyp1a2 genes were over-expressed in the livers of either triadimefon- or propiconazole-treated mice, and Cyp2b10/20 and Cyp3a13 genes were over-expressed in the livers of myclobutanil-treated mice. Western blot analyses indicated conazole induced-increases in Cyp2b and Cyp3a proteins. All three conazoles decreased hepatic atRA tissue levels ranging from 45-67%. The possible implications of these changes in hepatic atRA levels

  6. Oleic, Linoleic and Linolenic Acids Increase ROS Production by Fibroblasts via NADPH Oxidase Activation

    PubMed Central

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47phox phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47phox mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  7. Oleic, linoleic and linolenic acids increase ros production by fibroblasts via NADPH oxidase activation.

    PubMed

    Hatanaka, Elaine; Dermargos, Alexandre; Hirata, Aparecida Emiko; Vinolo, Marco Aurélio Ramirez; Carpinelli, Angelo Rafael; Newsholme, Philip; Armelin, Hugo Aguirre; Curi, Rui

    2013-01-01

    The effect of oleic, linoleic and γ-linolenic acids on ROS production by 3T3 Swiss and Rat 1 fibroblasts was investigated. Using lucigenin-amplified chemiluminescence, a dose-dependent increase in extracellular superoxide levels was observed during the treatment of fibroblasts with oleic, linoleic and γ-linolenic acids. ROS production was dependent on the addition of β-NADH or NADPH to the medium. Diphenyleneiodonium inhibited the effect of oleic, linoleic and γ-linolenic acids on fibroblast superoxide release by 79%, 92% and 82%, respectively. Increased levels of p47 (phox) phosphorylation due to fatty acid treatment were detected by Western blotting analyses of fibroblast proteins. Increased p47 (phox) mRNA expression was observed using real-time PCR. The rank order for the fatty acid stimulation of the fibroblast oxidative burst was as follows: γ-linolenic > linoleic > oleic. In conclusion, oleic, linoleic and γ-linolenic acids stimulated ROS production via activation of the NADPH oxidase enzyme complex in fibroblasts. PMID:23579616

  8. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    SciTech Connect

    Hamrick, Mark W.; Herberg, Samuel; Arounleut, Phonepasong; He, Hong-Zhi; Shiver, Austin; Qi, Rui-Qun; Zhou, Li; Isales, Carlos M.; and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  9. Significance and prognostic value of increased serum direct bilirubin level for lymph node metastasis in Chinese rectal cancer patients

    PubMed Central

    Gao, Chun; Fang, Long; Li, Jing-Tao; Zhao, Hong-Chuan

    2016-01-01

    AIM: To determine the significance of increased serum direct bilirubin level for lymph node metastasis (LNM) in Chinese rectal cancer patients, after those with known hepatobiliary and pancreatic diseases were excluded. METHODS: A cohort of 469 patients, who were treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period from January 2003 to June 2011, and with a pathological diagnosis of rectal adenocarcinoma, were recruited. They included 231 patients with LNM (49.3%) and 238 patients without LNM. Follow-up for these patients was taken through to December 31, 2012. RESULTS: The baseline serum direct bilirubin concentration was (median/inter-quartile range) 2.30/1.60-3.42 μmol/L. Univariate analysis showed that compared with patients without LNM, the patients with LNM had an increased level of direct bilirubin (2.50/1.70-3.42 vs 2.10/1.40-3.42, P = 0.025). Multivariate analysis showed that direct bilirubin was independently associated with LNM (OR = 1.602; 95%CI: 1.098-2.338, P = 0.015). Moreover, we found that: (1) serum direct bilirubin differs between male and female patients; a higher concentration was associated with poor tumor classification; (2) as the baseline serum direct bilirubin concentration increased, the percentage of patients with LNM increased; and (3) serum direct bilirubin was associated with the prognosis of rectal cancer patients and higher values indicated poor prognosis. CONCLUSION: Higher serum direct bilirubin concentration was associated with the increased risk of LNM and poor prognosis in our rectal cancers. PMID:26937145

  10. Engineered antibody domains with significantly increased transcytosis and half-life in macaques mediated by FcRn

    PubMed Central

    Ying, Tianlei; Wang, Yanping; Feng, Yang; Prabakaran, Ponraj; Gong, Rui; Wang, Lili; Crowder, Karalyne; Dimitrov, Dimiter S

    2015-01-01

    Engineered antibody domains (eAds) are promising candidate therapeutics but their half-life is relatively short partly due to weak or absent binding to the neonatal Fc receptor (FcRn). We developed a novel approach to increase the eAd binding to FcRn based on a combination of structure-based design, computational modeling and phage display methodologies. By using this approach, we identified 2 IgG1 CH2-derived eAds fused to a short FcRn-binding motif derived from IgG1 CH3 that exhibited greatly enhanced FcRn binding with strict pH dependency. Importantly, the increased affinity resulted in significantly enhanced FcRn-mediated epithelial transcytosis and prolonged elimination half-life (mean 44.1 hours) in cynomolgus macaques. These results demonstrate for the first time that the half-life of isolated eAds can be prolonged (optimized) by increasing their binding to FcRn while maintaining their small size, which has important implications for development of therapeutics, including eAd-drug conjugates with enhanced penetration in solid tissues. PMID:26179052

  11. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields

    NASA Astrophysics Data System (ADS)

    Koppes, Abigail N.; Seggio, Angela M.; Thompson, Deanna M.

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm-1). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm-1, and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm-1 electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm-1 dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  12. Awareness of folic acid use increases its consumption, and reduces the risk of spina bifida.

    PubMed

    Kondo, Atsuo; Morota, Nobuhito; Date, Hiroaki; Yoshifuji, Kazuhisa; Morishima, Toshibumi; Miyazato, Minoru; Shirane, Reizo; Sakai, Hideki; Pooh, Kyong Hon; Watanabe, Tomoyuki

    2015-07-14

    The majority of neural tube defects were believed to be folic acid (FA)-preventable in the 1990s. The Japanese government recommended women planning pregnancy to take FA supplements of 400 μg/d in 2000, but the incidence of spina bifida has not decreased. We aimed to evaluate the OR of having an infant with spina bifida for women who periconceptionally took FA supplements and the association between an increase in supplement use and possible promoters for the increase. This is a case-control study which used 360 case women who gave birth to newborns afflicted with spina bifida, and 2333 control women who gave birth to healthy newborns during the first 12 years of this century. They were divided into two 6-year periods; from 2001 to 2006 and from 2007 to 2012. Logistic regression analyses were conducted to compute OR between cases and controls. The adjusted OR of having an infant with spina bifida for supplement users was 0.48 in the first period, and 0.53 in the second period. The proportion of women who periconceptionally consumed supplements significantly increased from 10 % in the first period to 30 % in the second period. Awareness of the preventive role of FA was a promoter for an increase in supplement use, and thus an FA campaign in high school seems rational and effective. The failure of the current public health policy is responsible for an epidemic of spina bifida. Mandatory food fortification with FA is urgent and long overdue in Japan. PMID:25999131

  13. Increased physical activity decreases hepatic free fatty acid uptake: a study in human monozygotic twins.

    PubMed

    Hannukainen, Jarna C; Nuutila, Pirjo; Borra, Ronald; Ronald, Borra; Kaprio, Jaakko; Kujala, Urho M; Janatuinen, Tuula; Heinonen, Olli J; Kapanen, Jukka; Viljanen, Tapio; Haaparanta, Merja; Rönnemaa, Tapani; Parkkola, Riitta; Knuuti, Juhani; Kalliokoski, Kari K

    2007-01-01

    Exercise is considered to be beneficial for free fatty acid (FFA) metabolism, although reports of the effects of increased physical activity on FFA uptake and oxidation in different tissues in vivo in humans have been inconsistent. To investigate the heredity-independent effects of physical activity and fitness on FFA uptake in skeletal muscle, the myocardium, and liver we used positron emission tomography (PET) in nine healthy young male monozygotic twin pairs discordant for physical activity and fitness. The cotwins with higher physical activity constituting the more active group had a similar body mass index but less body fat and 18 +/- 10% higher (P < 0.001) compared to the less active brothers with lower physical activity. Low-intensity knee-extension exercise increased skeletal muscle FFA and oxygen uptake six to 10 times compared to resting values but no differences were observed between the groups at rest or during exercise. At rest the more active group had lower hepatic FFA uptake compared to the less active group (5.5 +/- 4.3 versus 9.0 +/- 6.1 micromol (100 ml)(-1) min(-1), P = 0.04). Hepatic FFA uptake associated significantly with body fat percentage (P = 0.05). Myocardial FFA uptake was similar between the groups. In conclusion, in the absence of the confounding effects of genetic factors, moderately increased physical activity and aerobic fitness decrease body adiposity even in normal-weighted healthy young adult men. Further, increased physical activity together with decreased intra-abdominal adiposity seems to decrease hepatic FFA uptake but has no effects on skeletal muscle or myocardial FFA uptake. PMID:17053033

  14. Biological Significance of Urolithins, the Gut Microbial Ellagic Acid-Derived Metabolites: The Evidence So Far

    PubMed Central

    Espín, Juan Carlos; Larrosa, Mar; García-Conesa, María Teresa; Tomás-Barberán, Francisco

    2013-01-01

    The health benefits attributed to pomegranate have been associated with its high content in polyphenols, particularly ellagitannins. This is also the case for other ellagitannin-containing fruits and nuts including strawberry, raspberry, blackberry, walnuts, and muscadine grapes. The bioavailability of ellagitannins and ellagic acid is however very low. These molecules suffer extensive metabolism by the gut microbiota to produce urolithins that are much better absorbed. Urolithins circulate in plasma as glucuronide and sulfate conjugates at concentrations in the range of 0.2–20 μM. It is therefore conceivable that the health effects of ellagitannin-containing products can be associated with these gut-produced urolithins, and thus the evaluation of the biological effects of these metabolites is essential. Recent research, mostly based on in vitro testing, has shown preliminary evidence of the anti-inflammatory, anticarcinogenic, antiglycative, antioxidant, and antimicrobial effects of urolithins, supporting their potential contribution to the health effects attributed to pomegranate and ellagitannin-rich foods. The number of in vivo studies is still limited, but they show preventive effects of urolithins on gut and systemic inflammation that encourage further research. Both in vivo and mechanistic studies are necessary to clarify the health effects of these metabolites. Attention should be paid when designing these mechanistic studies in order to use the physiologically relevant metabolites (urolithins in gut models and their conjugated derivatives in systemic models) at concentrations that can be reached in vivo. PMID:23781257

  15. High surface-area amidoxime-based polymer fibers co-grafted with various acid monomers yielding increased adsorption capacity for the extraction of uranium from seawater.

    PubMed

    Oyola, Yatsandra; Dai, Sheng

    2016-06-01

    Uranium is dissolved in the ocean at a uniform concentration of 3.34 ppb, which translates to approximately 4-5 billion tons of uranium. The development of adsorbents that can extract uranium from seawater has been a long term goal, but the extremely dilute uranium concentration along with the competition of other metal salts (which are at higher concentrations) has hindered the development of an economical adsorption process. Several acid monomers were co-grafted with acrylonitrile (AN) to help increase the hydrophilicity of the adsorbent to improve access to the metal adsorption sites. Grafting various acid monomers on PE fibers was found to significantly affect the uranium adsorption in simulated seawater in the following order: acrylic acid (AA) < vinyl sulfonic acid (VSA) < methacrylic acid (MAA) < itaconic acid (ITA) < vinyl phosphonic acid (VPA). Interestingly, the uranium adsorption capacity significantly increased when Mohr's salt was added with acrylic acid, most likely due to the reduction of co-polymerization of the monomers. When testing under more realistic conditions, the acid-grafted PE fiber adsorbents were exposed to natural seawater (more dilute uranium), the uranium adsorption capacity increased in the following order: MAA < AA (Mohr's salt) < VSA < ITA (Mohr's salt) < ITA < VPA, which agreed well with the simulated seawater results. Characterization of the adsorbents indicated that the increase in uranium adsorption capacity with each acid monomer was related to higher grafting of AN and therefore a higher conversion to amidoxime (AO). PMID:27145863

  16. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage.

    PubMed

    Shearn, Colin T; Orlicky, David J; McCullough, Rebecca L; Jiang, Hua; Maclean, Kenneth N; Mercer, Kelly E; Stiles, Bangyan L; Saba, Laura M; Ronis, Martin J; Petersen, Dennis R

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  17. Liver-Specific Deletion of Phosphatase and Tensin Homolog Deleted on Chromosome 10 Significantly Ameliorates Chronic EtOH-Induced Increases in Hepatocellular Damage

    PubMed Central

    Orlicky, David J.; McCullough, Rebecca L.; Jiang, Hua; Maclean, Kenneth N.; Mercer, Kelly E.; Stiles, Bangyan L.; Saba, Laura M.; Ronis, Martin J.; Petersen, Dennis R.

    2016-01-01

    Alcoholic liver disease is a significant contributor to global liver failure. In murine models, chronic ethanol consumption dysregulates PTEN/Akt signaling. Hepatospecific deletion of phosphatase and tensin homolog deleted on chromosome 10 (PTENLKO) mice possess constitutive activation of Akt(s) and increased de novo lipogenesis resulting in increased hepatocellular steatosis. This makes PTENLKO a viable model to examine the effects of ethanol in an environment of preexisting steatosis. The aim of this study was to determine the impact of chronic ethanol consumption and the absence of PTEN (PTENLKO) compared to Alb-Cre control mice (PTENf/f) on hepatocellular damage as evidenced by changes in lipid accumulation, protein carbonylation and alanine amino transferase (ALT). In the control PTENf/f animals, ethanol significantly increased ALT, liver triglycerides and steatosis. In contrast, chronic ethanol consumption in PTENLKO mice decreased hepatocellular damage when compared to PTENLKO pair-fed controls. Consumption of ethanol elevated protein carbonylation in PTENf/f animals but had no effect in PTENLKO animals. In PTENLKO mice, overall hepatic mRNA expression of genes that contribute to GSH homeostasis as well as reduced glutathione (GSH) and oxidized glutathione (GSSG) concentrations were significantly elevated compared to respective PTENf/f counterparts. These data indicate that during conditions of constitutive Akt activation and steatosis, increased GSH homeostasis assists in mitigation of ethanol-dependent induction of oxidative stress and hepatocellular damage. Furthermore, data herein suggest a divergence in EtOH-induced hepatocellular damage and increases in steatosis due to polyunsaturated fatty acids downstream of PTEN. PMID:27124661

  18. Ligand-directed stearic acid grafted chitosan micelles to increase therapeutic efficacy in hepatic cancer.

    PubMed

    Yang, Yuan; Yuan, Sheng-Xian; Zhao, Ling-Hao; Wang, Chao; Ni, Jun-Sheng; Wang, Zhen-Guang; Lin, Chuan; Wu, Meng-Chao; Zhou, Wei-Ping

    2015-02-01

    Targeted delivery system would be an interesting platform to enhance the therapeutic effect and to reduce the side effects of anticancer drugs. In this study, we have developed lactobionic acid (LA)-modified chitosan-stearic acid (CS-SA) (CSS-LA) to deliver doxorubicin (DOX) to hepatic cancer cells. The average particle size of CSS-LA/DOX was ∼100 nm with a high entrapment efficiency of >95%. Drug release studies showed that DOX release from pH-sensitive micelles is significantly faster at pH 5.0 than at pH 7.4. The LA conjugated micelles showed enhanced cellular uptake in HepG2 and BEL-7402 liver cancer cells than free drug and unconjugated micelles. Consistently, CSS-LA/DOX showed enhanced cell cytotoxicity in these two cell lines. Annexin-V/FITC and PI based apoptosis assay showed that the number of living cells greatly reduced in this group with marked presence of necrotic and apoptotic cells. LA-conjugated carrier induced typical chromatic condensation of cells; membrane blebbing and apoptotic bodies began to appear. In vivo, CSS-LA/DOX showed an excellent tumor regression profile with no toxic side effects. The active targeting moiety, long circulation profile, and EPR effect contributed to its superior anticancer effect in HepG2 based tumor. Our results showed that polymeric micelles conjugated with LA increased the therapeutic availability of DOX in the liver cancer cell based solid tumor without any toxic side effects. The active targeting ligand conjugated nanoparticulate system could be a promising therapeutic strategy in the treatment of hepatic cancers. PMID:25495890

  19. HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation

    PubMed Central

    Henrick, Bethany M.; Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2015-01-01

    Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development. PMID:26347747

  20. High glucose levels reduce fatty acid oxidation and increase triglyceride accumulation in human placenta.

    PubMed

    Visiedo, Francisco; Bugatto, Fernando; Sánchez, Viviana; Cózar-Castellano, Irene; Bartha, Jose L; Perdomo, Germán

    2013-07-15

    Placentas of women with gestational diabetes mellitus (GDM) exhibit an altered lipid metabolism. The mechanism by which GDM is linked to alterations in placental lipid metabolism remains obscure. We hypothesized that high glucose levels reduce mitochondrial fatty acid oxidation (FAO) and increase triglyceride accumulation in human placenta. To test this hypothesis, we measured FAO, fatty acid esterification, de novo fatty acid synthesis, triglyceride levels, and carnitine palmitoyltransferase activities (CPT) in placental explants of women with GDM or no pregnancy complication. In women with GDM, FAO was reduced by ~30% without change in mitochondrial content, and triglyceride content was threefold higher than in the control group. Likewise, in placental explants of women with no complications, high glucose levels reduced FAO by ~20%, and esterification increased linearly with increasing fatty acid concentrations. However, de novo fatty acid synthesis remained unchanged between high and low glucose levels. In addition, high glucose levels increased triglyceride content approximately twofold compared with low glucose levels. Furthermore, etomoxir-mediated inhibition of FAO enhanced esterification capacity by ~40% and elevated triglyceride content 1.5-fold in placental explants of women, with no complications. Finally, high glucose levels reduced CPT I activity by ~70% and phosphorylation levels of acetyl-CoA carboxylase by ~25% in placental explants of women, with no complications. We reveal an unrecognized regulatory mechanism on placental fatty acid metabolism by which high glucose levels reduce mitochondrial FAO through inhibition of CPT I, shifting flux of fatty acids away from oxidation toward the esterification pathway, leading to accumulation of placental triglycerides. PMID:23673156

  1. Increase of electrodermal activity of heart meridian during physical exercise: the significance of electrical values in acupuncture and diagnostic importance.

    PubMed

    Pontarollo, Francesco; Rapacioli, Giuliana; Bellavite, Paolo

    2010-08-01

    Electric field measurements of skin potential and electrical currents are physiological indicators of electrodermal activity (EDA) and have been associated with a variety of sensory, cognitive and emotional stimuli. The aim of this study was to investigate the EDA at some hand acupoints before, during and after a physical exercise. EDA of eight points located at the corner of fingernails of hands was measured in 10 healthy young volunteers before, during and after a 14-min acute exercise in a bicycle ergometer. In pre-exercise resting state the parameters were stable and similar between the 8 different tested points, while during exercise a significant increase of current (from 1000-2000 to 4000-8000 nA) was observed, with the maximal values related to the point located on the ulnar side of the little finger, at the base of the nail, corresponding to the Shao chong (HT9) of heart meridian. PMID:20621275

  2. Production of siderophores increases resistance to fusaric acid in Pseudomonas protegens Pf-5.

    PubMed

    Ruiz, Jimena A; Bernar, Evangelina M; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  3. Production of Siderophores Increases Resistance to Fusaric Acid in Pseudomonas protegens Pf-5

    PubMed Central

    Ruiz, Jimena A.; Bernar, Evangelina M.; Jung, Kirsten

    2015-01-01

    Fusaric acid is produced by pathogenic fungi of the genus Fusarium, and is toxic to plants and rhizobacteria. Many fluorescent pseudomonads can prevent wilt diseases caused by these fungi. This study was undertaken to evaluate the effect of fusaric acid on P. protegens Pf-5 and elucidate the mechanisms that enable the bacterium to survive in the presence of the mycotoxin. The results confirm that fusaric acid negatively affects growth and motility of P. protegens. Moreover, a notable increase in secretion of the siderophore pyoverdine was observed when P. protegens was grown in the presence of fusaric acid. Concomitantly, levels of enzymes involved in the biosynthesis of pyoverdine and enantio-pyochelin, the second siderophore encoded by P. protegens, increased markedly. Moreover, while similar levels of resistance to fusaric acid were observed for P. protegens mutants unable to synthesize either pyoverdine or enanto-pyochelin and the wild type strain, a double mutant unable to synthesize both kinds of siderophores showed a dramatically reduced resistance to this compound. This reduced resistance was not observed when this mutant was grown under conditions of iron excess. Spectrophotometric titrations revealed that fusaric acid binds not only Fe2+ and Fe3+, but also Zn2+, Mn2+ and Cu2+, with high affinity. Our results demonstrate that iron sequestration accounts at least in part for the deleterious effect of the mycotoxin on P. protegens. PMID:25569682

  4. Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes

    PubMed Central

    Crown, Scott B.; Marze, Nicholas; Antoniewicz, Maciek R.

    2015-01-01

    The branched chain amino acids (BCAA) valine, leucine and isoleucine have been implicated in a number of diseases including obesity, insulin resistance, and type 2 diabetes mellitus, although the mechanisms are still poorly understood. Adipose tissue plays an important role in BCAA homeostasis by actively metabolizing circulating BCAA. In this work, we have investigated the link between BCAA catabolism and fatty acid synthesis in 3T3-L1 adipocytes using parallel 13C-labeling experiments, mass spectrometry and model-based isotopomer data analysis. Specifically, we performed parallel labeling experiments with four fully 13C-labeled tracers, [U-13C]valine, [U-13C]leucine, [U-13C]isoleucine and [U-13C]glutamine. We measured mass isotopomer distributions of fatty acids and intracellular metabolites by GC-MS and analyzed the data using the isotopomer spectral analysis (ISA) framework. We demonstrate that 3T3-L1 adipocytes accumulate significant amounts of even chain length (C14:0, C16:0 and C18:0) and odd chain length (C15:0 and C17:0) fatty acids under standard cell culture conditions. Using a novel GC-MS method, we demonstrate that propionyl-CoA acts as the primer on fatty acid synthase for the production of odd chain fatty acids. BCAA contributed significantly to the production of all fatty acids. Leucine and isoleucine contributed at least 25% to lipogenic acetyl-CoA pool, and valine and isoleucine contributed 100% to lipogenic propionyl-CoA pool. Our results further suggest that low activity of methylmalonyl-CoA mutase and mass action kinetics of propionyl-CoA on fatty acid synthase result in high rates of odd chain fatty acid synthesis in 3T3-L1 cells. Overall, this work provides important new insights into the connection between BCAA catabolism and fatty acid synthesis in adipocytes and underscores the high capacity of adipocytes for metabolizing BCAA. PMID:26710334

  5. Linoleic acid supplementation results in increased arachidonic acid and eicosanoid production in CF airway cells and in cftr−/− transgenic mice

    PubMed Central

    Zaman, Munir M.; Martin, Camilia R.; Andersson, Charlotte; Bhutta, Abdul Q.; Cluette-Brown, Joanne E.; Laposata, Michael

    2010-01-01

    Cystic fibrosis (CF) patients display a fatty acid imbalance characterized by low linoleic acid levels and variable changes in arachidonic acid. This led to the recommendation that CF patients consume a high-fat diet containing >6% linoleic acid. We hypothesized that increased conversion of linoleic acid to arachidonic acid in CF leads to increased levels of arachidonate-derived proinflammatory metabolites and that this process is exacerbated by increasing linoleic acid levels in the diet. To test this hypothesis, we determined the effect of linoleic acid supplementation on downstream proinflammatory biomarkers in two CF models: 1) in vitro cell culture model using 16HBE14o− sense [wild-type (WT)] and antisense (CF) human airway epithelial cells; and 2) in an in vivo model using cftr−/− transgenic mice. Fatty acids were analyzed by gas chromatography-mass spectrometry (GC/MS), and IL-8 and eicosanoids were measured by ELISA. Neutrophils were quantified in bronchoalveolar lavage fluid from knockout mice following linoleic acid supplementation and exposure to aerosolized Pseudomonas LPS. Linoleic acid supplementation increased arachidonic acid levels in CF but not WT cells. IL-8, PGE2, and PGF2α secretion were increased in CF compared with WT cells, with a further increase following linoleic acid supplementation. cftr−/− Mice supplemented with 100 mg of linoleic acid had increased arachidonic acid levels in lung tissue associated with increased neutrophil infiltration into the airway compared with control mice. These findings support the hypothesis that increasing linoleic acid levels in the setting of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function leads to increased arachidonic acid levels and proinflammatory mediators. PMID:20656894

  6. Increased production of omega-3 fatty acids protects retinal ganglion cells after optic nerve injury in mice.

    PubMed

    Peng, Shanshan; Shi, Zhe; Su, Huanxing; So, Kwok-Fai; Cui, Qi

    2016-07-01

    Injury to the central nervous system causes progressive degeneration of injured axons, leading to loss of the neuronal bodies. Neuronal survival after injury is a prerequisite for successful regeneration of injured axons. In this study, we investigated the effects of increased production of omega-3 fatty acids and elevation of cAMP on retinal ganglion cell (RGC) survival and axonal regeneration after optic nerve (ON) crush injury in adult mice. We found that increased production of omega-3 fatty acids in mice enhanced RGC survival, but not axonal regeneration, over a period of 3 weeks after ON injury. cAMP elevation promoted RGC survival in wild type mice, but no significant difference in cell survival was seen in mice over-producing omega-3 fatty acids and receiving intravitreal injections of CPT-cAMP, suggesting that cAMP elevation protects RGCs after injury but does not potentiate the actions of the omega-3 fatty acids. The observed omega-3 fatty acid-mediated neuroprotection is likely achieved partially through ERK1/2 signaling as inhibition of this pathway by PD98059 hindered, but did not completely block, RGC protection. Our study thus enhances our current understanding of neural repair after CNS injury, including the visual system. PMID:27264241

  7. The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients.

    PubMed

    Morel, Agnieszka; Miller, Elzbieta; Bijak, Michal; Saluk, Joanna

    2016-09-01

    Platelet activation is increasingly postulated as a possible component of the pathogenesis of multiple sclerosis (MS), especially due to the increased risk of cardiovascular events in MS. Arachidonic acid cascade metabolized by cyclooxygenase (COX) is a key pathway of platelet activation. The aim of our study was to investigate the COX-dependent arachidonic acid metabolic pathway in blood platelets from secondary progressive multiple sclerosis (SP MS) patients. The blood samples were obtained from 50 patients (man n = 22; female n = 28), suffering from SP MS, diagnosed according to the revised McDonald criteria. Platelet aggregation was measured in platelet-rich plasma after arachidonic acid stimulation. The level of COX activity and thromboxane B2 concentration were determined by ELISA method. Lipid peroxidation was assessed by measuring the level of malondialdehyde. The results were compared with a control group of healthy volunteers. We found that blood platelets obtained from SP MS patients were more sensitive to arachidonic acid and their response measured as platelet aggregation was stronger (about 14 %) relative to control. We also observed a significantly increased activity of COX (about 40 %) and synthesis of thromboxane B2 (about 113 %). The generation of malondialdehyde as a marker of lipid peroxidation was about 10 % higher in SP MS than in control. Cyclooxygenase-dependent arachidonic acid metabolism is significantly increased in blood platelets of patients with SP MS. Future clinical studies are required to recommend the use of low-dose aspirin, and possibly other COX inhibitors in the prevention of cardiovascular risk in MS. PMID:27507559

  8. A Prolonged Time Interval Between Trauma and Prophylactic Radiation Therapy Significantly Increases the Risk of Heterotopic Ossification

    SciTech Connect

    Mourad, Waleed F.; Packianathan, Satyaseelan; Shourbaji, Rania A.; Zhang Zhen; Graves, Mathew; Khan, Majid A.; Baird, Michael C.; Russell, George; Vijayakumar, Srinivasan

    2012-03-01

    Purpose: To ascertain whether the time from injury to prophylactic radiation therapy (RT) influences the rate of heterotopic ossification (HO) after operative treatment of displaced acetabular fractures. Methods and Materials: This is a single-institution, retrospective analysis of patients referred for RT for the prevention of HO. Between January 2000 and January 2009, 585 patients with displaced acetabular fractures were treated surgically followed by RT for HO prevention. We analyzed the effect of time from injury on prevention of HO by RT. In all patients, 700 cGy was prescribed in a single fraction and delivered within 72 hours postsurgery. The patients were stratified into five groups according to time interval (in days) from the date of their accident to the date of RT: Groups A {<=}3, B {<=}7, C {<=}14, D {<=}21, and E >21days. Results: Of the 585 patients with displaced acetabular fractures treated with RT, (18%) 106 patients developed HO within the irradiated field. The risk of HO after RT increased from 10% for RT delivered {<=}3 days to 92% for treatment delivered >21 days after the initial injury. Wilcoxon test showed a significant correlation between the risk of HO and the length of time from injury to RT (p < 0.0001). Chi-square test and multiple logistic regression analysis showed no significant association between all other factors and the risk of HO (race, gender, cause and type of fracture, surgical approach, or the use of indomethacin). Conclusions: Our data suggest that there is higher incidence and risk of HO if prophylactic RT is significantly delayed after a displaced acetabular fracture. Thus, RT should be administered as early as clinically possible after the trauma. Patients undergoing RT >3 weeks from their displaced acetabular fracture should be informed of the higher risk (>90%) of developing HO despite prophylaxis.

  9. Tumorigenic lung tumorospheres exhibit stem-like features with significantly increased expression of CD133 and ABCG2.

    PubMed

    Zhao, Wensi; Luo, Yi; Li, Boyi; Zhang, Tao

    2016-09-01

    Accumulating evidence supports the existence of cancer stem cells (CSCs) in human tumors, and the successful certification of CSCs may lead to the identification of therapeutic targets, which are more effective for the treatment of cancer. The use of spherical cancer models has increased in popularity in cancer stem cell investigations. Tumorospheres, which are used as a model of CSCs and are established in serum‑free medium supplemented with growth factors under non‑adherent conditions, are one of the most commonly used cancer spherical models and are a valuable method for enriching the CSC fraction. To investigate whether this model is applicable in lung cancer (LC), the identification of lung CSCs and their capacities is essential. In the present study, lung CSCs were enriched by sphere-forming culturing and their stem‑like properties were assessed. The results indicated that the lung tumorospheres had enhanced proliferation, clonality, invasion and cisplatin‑resistance, and showed significantly increased expression levels of CD133 and breast cancer resistance protein (ABCG2). These results, together with findings previously reported in literature, indicated that the sphere‑forming culturing of LC cells induced the enrichment of CSCs and that the tumorospheres exhibited stem cell characteristics. In addition, the higher expression levels of CD133 and ABCG2 in the tumorospheres may provide a rationale for therapeutic targets for LC. PMID:27432082

  10. Tumorigenic lung tumorospheres exhibit stem-like features with significantly increased expression of CD133 and ABCG2

    PubMed Central

    Zhao, Wensi; Luo, Yi; Li, Boyi; Zhang, Tao

    2016-01-01

    Accumulating evidence supports the existence of cancer stem cells (CSCs) in human tumors, and the successful certification of CSCs may lead to the identification of therapeutic targets, which are more effective for the treatment of cancer. The use of spherical cancer models has increased in popularity in cancer stem cell investigations. Tumorospheres, which are used as a model of CSCs and are established in serum-free medium supplemented with growth factors under non-adherent conditions, are one of the most commonly used cancer spherical models and are a valuable method for enriching the CSC fraction. To investigate whether this model is applicable in lung cancer (LC), the identification of lung CSCs and their capacities is essential. In the present study, lung CSCs were enriched by sphere-forming culturing and their stem-like properties were assessed. The results indicated that the lung tumorospheres had enhanced proliferation, clonality, invasion and cisplatin-resistance, and showed significantly increased expression levels of CD133 and breast cancer resistance protein (ABCG2). These results, together with findings previously reported in literature, indicated that the sphere-forming culturing of LC cells induced the enrichment of CSCs and that the tumorospheres exhibited stem cell characteristics. In addition, the higher expression levels of CD133 and ABCG2 in the tumorospheres may provide a rationale for therapeutic targets for LC. PMID:27432082

  11. Increased hepatic Fatty Acid uptake and esterification contribute to tetracycline-induced steatosis in mice.

    PubMed

    Choi, You-Jin; Lee, Chae-Hyeon; Lee, Kang-Yo; Jung, Seung-Hwan; Lee, Byung-Hoon

    2015-06-01

    Tetracycline induces microvesicular steatosis, which has a poor long-term prognosis and a higher risk of steatohepatitis development compared with macrovesicular steatosis. Recent gene expression studies indicated that tetracycline treatment affects the expression of many genes associated with fatty acid transport and esterification. In this study, we investigated the role of fatty acid transport and esterification in tetracycline-induced steatosis. Intracellular lipid accumulation and the protein expression of fatty acid translocase (FAT or CD36) and diacylglycerol acyltransferase (DGAT) 2 were increased in both mouse liver and HepG2 cells treated with tetracycline at 50 mg/kg (intraperitoneal injection, i.p.) and 100 μM, respectively. Tetracycline increased the cellular uptake of boron-dipyrromethene-labeled C16 fatty acid, which was abolished by CD36 RNA interference. Oleate-induced cellular lipid accumulation was further enhanced by co-incubation with tetracycline. Tetracycline downregulated extracellular signal-regulated kinase (ERK) phosphorylation, which negatively regulated DGAT2 expression. U0126, a specific ERK inhibitor, also increased DGAT2 expression and cellular lipid accumulation. DGAT1 and 2 knock-down with specific small interfering (si)-RNA completely abrogated the steatogenic effect of tetracycline in HepG2 cells. Taken together, our data showed that tetracycline induces lipid accumulation by facilitating fatty acid transport and triglyceride esterification by upregulating CD36 and DGAT2, respectively. PMID:25745068

  12. Unequivocal detection of ozone recovery in the Antarctic Ozone Hole through significant increases in atmospheric layers with minimum ozone

    NASA Astrophysics Data System (ADS)

    de Laat, Jos; van Weele, Michiel; van der A, Ronald

    2015-04-01

    An important new landmark in present day ozone research is presented through MLS satellite observations of significant ozone increases during the ozone hole season that are attributed unequivocally to declining ozone depleting substances. For many decades the Antarctic ozone hole has been the prime example of both the detrimental effects of human activities on our environment as well as how to construct effective and successful environmental policies. Nowadays atmospheric concentrations of ozone depleting substances are on the decline and first signs of recovery of stratospheric ozone and ozone in the Antarctic ozone hole have been observed. The claimed detection of significant recovery, however, is still subject of debate. In this talk we will discuss first current uncertainties in the assessment of ozone recovery in the Antarctic ozone hole by using multi-variate regression methods, and, secondly present an alternative approach to identify ozone hole recovery unequivocally. Even though multi-variate regression methods help to reduce uncertainties in estimates of ozone recovery, great care has to be taken in their application due to the existence of uncertainties and degrees of freedom in the choice of independent variables. We show that taking all uncertainties into account in the regressions the formal recovery of ozone in the Antarctic ozone hole cannot be established yet, though is likely before the end of the decade (before 2020). Rather than focusing on time and area averages of total ozone columns or ozone profiles, we argue that the time evolution of the probability distribution of vertically resolved ozone in the Antarctic ozone hole contains a better fingerprint for the detection of ozone recovery in the Antarctic ozone hole. The advantages of this method over more tradition methods of trend analyses based on spatio-temporal average ozone are discussed. The 10-year record of MLS satellite measurements of ozone in the Antarctic ozone hole shows a

  13. Beef tallow increases the potency of conjugated linoleic acid in the reduction of mouse mammary tumor metastasis.

    PubMed

    Hubbard, Neil E; Lim, Debora; Erickson, Kent L

    2006-01-01

    Animal studies consistently show that dietary conjugated linoleic acid (CLA) reduces mammary tumorigenesis including metastasis. Relatively low concentrations of CLA are required for those effects, and a threshold level exists above which there is no added reduction. We reasoned that the concentration of CLA required to effectively alter mammary tumor metastasis may be dependent on the type of dietary fat because select fatty acids can enhance or suppress normal or malignant cell growth and metastasis. For this study, the diets (a total of 12 different groups) differed in fatty acid composition but not in energy from fat (40%). In experiments involving spontaneous metastasis, mice were fed for 11 wk; in experiments in which mice were injected i.v. with tumor cells, they were fed for 7 wk. Mice were then assessed for the effect of CLA concentration on mammary tumorigenesis. Mammary tumor growth was not altered, but metastasis was significantly decreased when beef tallow (BT) replaced half of a defined vegetable fat blend (VFB). That blend reflects the typical fat content of a Western diet. In addition, that same VFB:BT diet lowered the concentration of CLA required to significantly decrease mammary tumor metastasis from 0.1% of the diet to 0.05%. A diet in which corn oil replaced half of the VFB did not lower the threshold from 0.1 to 0.05%. In vitro, the main fatty acid in vegetable oil, linoleic acid, reduced the efficacy of CLA toxicity on mammary tumor cells in culture. Alternatively, fatty acids normally found in BT, such as oleic, stearic, and palmitic acids, either did not change or enhanced the cytolytic effects of CLA isomers on mouse mammary tumor cells in culture. These data provide evidence that dietary BT, itself with negligible levels of CLA, may increase the efficacy of dietary CLA in reducing mammary tumorigenesis. PMID:16365064

  14. Increased production of apolipoprotein B and its lipoproteins by oleic acid in Caco-2 cells.

    PubMed

    Dashti, N; Smith, E A; Alaupovic, P

    1990-01-01

    The production of lipids, apolipoproteins (apo), and lipoproteins induced by oleic acid has been examined in Caco-2 cells. The rates of accumulation in the control medium of 15-day-old Caco-2 cells of triglycerides, unesterified cholesterol, and cholesteryl esters were 102 +/- 8, 73 +/- 5, and 11 +/- 1 ng/mg cell protein/h, respectively; the accumulation rates for apolipoproteins A-I, B, C-III, and E were 111 +/- 9, 53 +/- 4, 13 +/- 1, and 63 +/- 4 ng/mg cell protein/h, respectively. Whereas apolipoproteins A-IV and C-II were detected by immunoblotting, apoA-II was absent in most culture media. In contrast to an early production of apolipoproteins A-I and E occurring 2 days after plating, the apoB expression appeared to be differentiation-dependent and was not measurable in the medium until the sixth day post-confluency. In the control medium, very low density lipoproteins (VLDL), low density lipoproteins (LDL), high density lipoproteins (HDL), and lipid-poor very high density lipoproteins (VHDL) accounted for 12%, 46%, 18%, and 24% of the total lipid and apolipoprotein contents, respectively. The triglyceride-rich VLDL contained mainly apoE (75%) and apoB (23%), while the protein moiety of LDL was composed of apoB (59%), apoE (20%), apoA-I (15%), and apoC-III (6%). The cholesterol-rich HDL contained mainly apoA-I (69%) and apoE (27%). In the control medium, major portions of apolipoproteins B and C-III (93-97%) were present in LDL, whereas the main parts of apoA-I (92%) and apoE (76%) were associated with HDL and VHDL. Oleate increased the production of triglycerides 10-fold, cholesteryl esters 7-fold, and apoB 2- to 4-fold. There was also a moderate increase (39%) in the production of apoC-III but no significant changes in those of apolipoproteins A-I and E. These increases were reflected mainly in a 55-fold elevation in the concentration of VLDL, and a 2-fold increase in the level of LDL; there were no significant changes in HDL and VHDL. VLDL contained the

  15. A high linoleic acid diet increases oxidative stress in vivo and affects nitric oxide metabolism in humans.

    PubMed

    Turpeinen, A M; Basu, S; Mutanen, M

    1998-09-01

    Evidence from in vitro studies shows that increased intake of polyunsaturated fatty acids leads to increased oxidative stress, which may be associated with endothelial damage. We measured the urinary levels of 8-iso-PGF2alpha and nitric oxide metabolites as well as plasma sICAM-1 levels from healthy subjects after strictly controlled diets rich in either linoleic acid (LA, C18:2 n-6) or oleic acid (OA, C18:1 n-9). Thirty-eight volunteers (20 women and 18 men, mean age 27 years) consumed a baseline diet rich in saturated fatty acids (SFA) for 4 weeks and were then switched to either a high LA diet (11.5 en%) or a high OA diet (18.0 en%) also for 4 weeks. During the LA and OA diets, nearly all food was provided for the whole day. A control group of 13 subjects consumed their habitual diet throughout the study. Urinary excretion of 8-iso-PGF2alpha was significantly increased after the LA diet (170 vs 241 ng/mmol creatinine, P=0.04), whereas the urinary concentration of nitric oxide metabolites decreased (4.2 vs 2.6 mg/mmol creatinine, P=0.03). No significant changes were seen in the OA group. Significant differences between the LA and control group were found for both 8-oxo-PGF2alpha (P=0.03) and NO (P=0.02), whereas the OA and LA groups did not differ with respect to any parameter. Also plasma sICAM-1 remained unchanged in both groups throughout the study. In conclusion, the high-LA diet increased oxidative stress and affected endothelial function in a way which may in the long-term predispose to endothelial dysfunction. PMID:9844997

  16. Ascorbic acid recycling by cultured beta cells: effects of increased glucose metabolism.

    PubMed

    Steffner, Robert J; Wu, Lan; Powers, Alvin C; May, James M

    2004-11-15

    Ascorbic acid is necessary for optimal insulin secretion from pancreatic islets. We evaluated ascorbate recycling and whether it is impaired by increased glucose metabolism in the rat beta-cell line INS-1. INS-1 cells, engineered with the potential for overexpression of glucokinase under the control of a tetracycline-inducible gene expression system, took up and reduced dehydroascorbic acid to ascorbate in a concentration-dependent manner that was optimal in the presence of physiologic D-glucose concentrations. Ascorbate uptake did not affect intracellular GSH concentrations. Whereas depletion of GSH in culture to levels about 25% of normal also did not affect the ability of the cells to reduce dehydroascorbic acid, more severe acute GSH depletion to less than 10% of normal levels did impair dehydroascorbic acid reduction. Culture of inducible cells in 11.8 mM D-glucose and doxycycline for 48 h enhanced glucokinase activity, increased glucose utilization, abolished D-glucose-dependent insulin secretion, and increased generation of reactive oxygen species. The latter may have contributed to subsequent decreases in the ability of the cells both to maintain intracellular ascorbate and to recycle it from dehydroascorbic acid. Cultured beta cells have a high capacity to recycle ascorbate, but this is sensitive to oxidant stress generated by increased glucose metabolism due to culture in high glucose concentrations and increased glucokinase expression. Impaired ascorbate recycling as a result of increased glucose metabolism may have implications for the role of ascorbate in insulin secretion in diabetes mellitus and may partially explain glucose toxicity in beta cells. PMID:15477012

  17. INCREASE IN GLIAL FIBRILLARY ACIDIC PROTEIN FOLLOWS BRAIN HYPERTHERMIA IN RATS

    EPA Science Inventory

    Previously, the authors have demonstrated that an increase in the astrocyte-associated protein, glial fibrillary acidic protein (GFAP), accompanies brain injury induced by a variety of chemical insults. In the present study the authors examined the effects of microwave-induced hy...

  18. Polyunsaturated fatty acid content is increased in the milk of women with pregnancy associated breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Pregnancy associated breast cancer (PABC) is aggressive and difficult to diagnose. High intake of most types of dietary fat is thought to increase breast cancer risk, however results in humans supporting this premise remain equivocal. Fatty acid (FA) concentrations in the body comprise b...

  19. Brain microsomal fatty acid elongation is increased in abcd1-deficient mouse during active myelination phase.

    PubMed

    Morita, Masashi; Kawamichi, Misato; Shimura, Yusuke; Kawaguchi, Kosuke; Watanabe, Shiro; Imanaka, Tsuneo

    2015-12-01

    The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fatty acid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fatty acid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fatty acid elongation activity in the microsomal fraction was measured by the incorporation of [2-(14)C]malonyl-CoA into fatty acids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fatty acid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fatty acid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fatty acid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin. PMID:26108493

  20. Nod2 deficiency protects mice from cholestatic liver disease by increasing renal excretion of bile acids

    PubMed Central

    Wang, Lirui; Hartmann, Phillipp; Haimerl, Michael; Bathena, Sai P.; Sjöwall, Christopher; Almer, Sven; Alnouti, Yazen; Hofmann, Alan F.; Schnabl, Bernd

    2014-01-01

    Background & aims Chronic liver disease is characterized by fibrosis that may progress to cirrhosis. Nucleotide oligomerization domain 2 (Nod2), a member of the Nod-like receptor (NLR) family of intracellular immune receptors, plays an important role in the defense against bacterial infection through binding to the ligand muramyl dipeptide (MDP). Here, we investigated the role of Nod2 in the development of liver fibrosis. Methods We studied experimental cholestatic liver disease induced by bile duct ligation or toxic liver disease induced by carbon tetrachloride in wild type and Nod2−/− mice. Results Nod2 deficiency protected mice from cholestatic but not toxin-induced liver injury and fibrosis. Most notably, the hepatic bile acid concentration was lower in Nod2−/− mice than wild type mice following bile duct ligation for 3 weeks. In contrast to wild type mice, Nod2−/− mice had increased urinary excretion of bile acids, including sulfated bile acids, and an upregulation of the bile acid efflux transporters MRP2 and MRP4 in tubular epithelial cells of the kidney. MRP2 and MRP4 were downregulated by IL-1β in a Nod2 dependent fashion. Conclusions Our findings indicate that Nod2 deficiency protects mice from cholestatic liver injury and fibrosis through enhancing renal excretion of bile acids that in turn contributes to decreased concentration of bile acids in the hepatocyte. PMID:24560660

  1. Combination of BMP2 and MSCs Significantly Increases Bone Formation in the Rat Arterio-Venous Loop Model

    PubMed Central

    Buehrer, Gregor; Balzer, Amelie; Arnold, Isabel; Beier, Justus P.; Koerner, Carolin; Bleiziffer, Oliver; Brandl, Andreas; Weis, Christian; Horch, Raymund E.; Kneser, Ulrich

    2015-01-01

    Introduction: In this study the induction of bone formation in an axially vascularized bone matrix using mesenchymal stem cells (MSCs) and application of bone morphogenetic protein 2 (BMP2) was analyzed in the arteriovenous loop (AVL) model. Materials and Methods: An AVL was created in the medial thigh of 42 rats and placed in a porous titanium chamber filled with a particulated porous hydroxyapatite and beta-tricalcium phosphate matrix and fibrin. In group A the fibrin was loaded with 5×106 DiI-stained fibrin gel-immobilized primary MSCs from syngenic Lewis rats, in group B the matrix was loaded with 60 μg/mL BMP2 and in group C both, BMP2 and MSCs were applied at implantation time point. After 6 and 12 weeks, specimens were investigated by means of histological, morphometrical, and micro-computed tomography analysis. Results: After implantation of an AVL a dense vascular network was visible in all groups. In group A, newly generated bone islands were detected in the periphery of the main vascular axis. Using BMP2 alone (group B), small islands of newly formed bone were visible evenly distributed in all parts of the constructs. In group C nearly the whole matrix was interspersed with bone formations. In all groups there was an increase of bone formation between the 6 and 12 weeks explantation time points. Conclusions: This study demonstrates for the first time the successful generation of axially vascularized bone substitutes using MSCs and BMP2 in the AVL rat model using a one step procedure. Using the combination of BMP2 and MSCs there was a significant increase of bone formations detectable compared to the BMP2 or MSCs alone groups. PMID:25135080

  2. Increased muscle fatty acid oxidation in dairy cows with intensive body fat mobilization during early lactation.

    PubMed

    Schäff, C; Börner, S; Hacke, S; Kautzsch, U; Sauerwein, H; Spachmann, S K; Schweigel-Röntgen, M; Hammon, H M; Kuhla, B

    2013-10-01

    The beginning of lactation requires huge metabolic adaptations to meet increased energy demands for milk production of dairy cows. One of the adaptations is the mobilization of body reserves mainly from adipose tissue as reflected by increased plasma nonesterified fatty acid (NEFA) concentrations. The capacity of the liver for complete oxidation of NEFA is limited, leading to an increased formation of ketone bodies, reesterification, and accumulation of triglycerides in the liver. As the skeletal muscle also may oxidize fatty acids, it may help to decrease the fatty acid load on the liver. To test this hypothesis, 19 German Holstein cows were weekly blood sampled from 7 wk before until 5 wk after parturition to analyze plasma NEFA concentrations. Liver biopsies were obtained at d 3, 18, and 30 after parturition and, based on the mean liver fat content, cows were grouped to the 10 highest (HI) and 9 lowest (LO). In addition, muscle biopsies were obtained at d -17, 3, and 30 relative to parturition and used to quantify mRNA abundance of genes involved in fatty acid degradation. Plasma NEFA concentrations peaked after parturition and were 1.5-fold higher in HI than LO cows. Muscle carnitine palmitoyltransferase 1α and β mRNA was upregulated in early lactation. The mRNA abundance of muscle peroxisome proliferator-activated receptor γ (PPARG) increased in early lactation and was higher in HI than in LO cows, whereas the abundance of PPARA continuously decreased after parturition. The mRNA abundance of muscle PPARD, uncoupling protein 3, and the β-oxidative enzymes 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase, very long-chain acyl-CoA dehydrogenase, and 3-ketoacyl-CoA was greatest at d 3 after parturition, whereas the abundance of PPARγ coactivator 1α decreased after parturition. Our results indicate that around parturition, oxidation of fatty acids in skeletal muscle is highly activated, which may contribute to diminish the fatty acid load on the liver. The

  3. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    SciTech Connect

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. )

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  4. Preharvest application of oxalic acid increased fruit size, bioactive compounds, and antioxidant capacity in sweet cherry cultivars (Prunus avium L.).

    PubMed

    Martínez-Esplá, Alejandra; Zapata, Pedro Javier; Valero, Daniel; García-Viguera, Cristina; Castillo, Salvador; Serrano, María

    2014-04-16

    Trees of 'Sweet Heart' and 'Sweet Late' sweet cherry cultivars (Prunus avium L.) were treated with oxalic acid (OA) at 0.5, 1.0, and 2.0 mM at 98, 112, and 126 days after full blossom. Results showed that all treatments increased fruit size at harvest, manifested by higher fruit volume and weight in cherries from treated trees than from controls, the higher effect being found with 2.0 mM OA (18 and 30% higher weight for 'Sweet Heart' and 'Sweet Late', respectively). Other quality parameters, such as color and firmness, were also increased by OA treatments, although no significant differences were found in total soluble solids or total acidity, showing that OA treatments did not affect the on-tree ripening process of sweet cherry. However, the increases in total anthocyanins, total phenolics, and antioxidant activity associated with the ripening process were higher in treated than in control cherries, leading to fruit with high bioactive compounds and antioxidant potential at commercial harvest (≅45% more anthocyanins and ≅20% more total phenolics). In addition, individual anthocyanins, flavonols, and chlorogenic acid derivatives were also increased by OA treatment. Thus, OA preharvest treatments could be an efficient and natural way to increase the quality and functional properties of sweet cherries. PMID:24684635

  5. Steam Cooking Significantly Improves In Vitro Bile Acid Binding of Collard Greens, Kale, Mustard Greens, Broccoli, Green Bell Pepper and Cabbage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bile acid binding capacity has been related to the cholesterol-lowering potential of foods and food fractions. Lowering recirculating bile acids results in utilization of cholesterol to synthesize bile acid and reduced fat absorption. Secondary bile acids have been associated with increasing the r...

  6. Altered myocardial metabolic adaptation to increased fatty acid availability in cardiomyocyte-specific CLOCK mutant mice.

    PubMed

    Peliciari-Garcia, Rodrigo A; Goel, Mehak; Aristorenas, Jonathan A; Shah, Krishna; He, Lan; Yang, Qinglin; Shalev, Anath; Bailey, Shannon M; Prabhu, Sumanth D; Chatham, John C; Gamble, Karen L; Young, Martin E

    2016-10-01

    A mismatch between fatty acid availability and utilization leads to cellular/organ dysfunction during cardiometabolic disease states (e.g., obesity, diabetes mellitus). This can precipitate cardiac dysfunction. The heart adapts to increased fatty acid availability at transcriptional, translational, post-translational and metabolic levels, thereby attenuating cardiomyopathy development. We have previously reported that the cardiomyocyte circadian clock regulates transcriptional responsiveness of the heart to acute increases in fatty acid availability (e.g., short-term fasting). The purpose of the present study was to investigate whether the cardiomyocyte circadian clock plays a role in adaptation of the heart to chronic elevations in fatty acid availability. Fatty acid availability was increased in cardiomyocyte-specific CLOCK mutant (CCM) and wild-type (WT) littermate mice for 9weeks in time-of-day-independent (streptozotocin (STZ) induced diabetes) and dependent (high fat diet meal feeding) manners. Indices of myocardial metabolic adaptation (e.g., substrate reliance perturbations) to STZ-induced diabetes and high fat meal feeding were found to be dependent on genotype. Various transcriptional and post-translational mechanisms were investigated, revealing that Cte1 mRNA induction in the heart during STZ-induced diabetes is attenuated in CCM hearts. At the functional level, time-of-day-dependent high fat meal feeding tended to influence cardiac function to a greater extent in WT versus CCM mice. Collectively, these data suggest that CLOCK (a circadian clock component) is important for metabolic adaption of the heart to prolonged elevations in fatty acid availability. This article is part of a Special Issue entitled: Heart Lipid Metabolism edited by G.D. Lopaschuk. PMID:26721420

  7. Homologous electron transport components fail to increase fatty acid hydroxylation in transgenic Arabidopsis thaliana

    PubMed Central

    Wayne, Laura L.; Browse, John

    2013-01-01

    Ricinoleic acid, a hydroxylated fatty acid (HFA) present in castor ( Ricinus communis) seeds, is an important industrial commodity used in products ranging from inks and paints to polymers and fuels. However, due to the deadly toxin ricin and allergens also present in castor, it would be advantageous to produce ricinoleic acid in a different agricultural crop. Unfortunately, repeated efforts at heterologous expression of the castor fatty acid hydroxylase (RcFAH12) in the model plant Arabidopsis thaliana have produced only 17-19% HFA in the seed triacylglycerols (TAG), whereas castor seeds accumulate up to 90% ricinoleic acid in the endosperm TAG. RcFAH12 requires an electron supply from NADH:cytochrome b5 reductase (CBR1) and cytochrome b5 (Cb5) to synthesize ricinoleic acid. Previously, our laboratory found a mutation in the Arabidopsis CBR1 gene, cbr1-1, that caused an 85% decrease in HFA levels in the RcFAH12 Arabidopsis line. These results raise the possibility that electron supply to the heterologous RcFAH12 may limit the production of HFA. Therefore, we hypothesized that by heterologously expressing RcCb5, the reductant supply to RcFAH12 would be improved and lead to increased HFA accumulation in Arabidopsis seeds. Contrary to this proposal, heterologous expression of the top three RcCb5 candidates did not increase HFA accumulation. Furthermore, coexpression of RcCBR1 and RcCb5 in RcFAH12 Arabidopsis also did not increase in HFA levels compared to the parental lines. These results demonstrate that the Arabidopsis electron transfer system is supplying sufficient reductant to RcFAH12 and that there must be other bottlenecks limiting the accumulation of HFA. PMID:24555099

  8. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats.

    PubMed

    Takahashi, Kei; Fukuwatari, Tsutomu; Shibata, Katsumi

    2015-01-01

    It is thought that both exercise and dietary composition increase the utilization of, and thus the requirement for, certain water-soluble vitamins. However, there have been no studies evaluating the combined impacts of exercise and dietary composition on vitamin utilization. In this experiment, rats were fed a pantothenic acid (PaA)-restricted (0.004 g PaA-Ca/kg diet) diet containing 5% (ordinary amount of dietary fat) or 20% fat (high fat), and were forced to swim until exhaustion every other day for 22 d. PaA status was assessed by urinary excretion, which reflects body stores of water-soluble vitamins. The urinary excretion of PaA in rats fed a 5% fat diet was not affected by swimming (5% fat + non-swimming vs. 5% fat + swim; p>0.05). Excretion of PaA was decreased by the high-fat diet (5% fat + non-swim vs. 20% fat + non-swim; p<0.05) and synergistically decreased by exercise (20% fat + non-swim vs. 20% fat + swim; p<0.05). There was a significant interaction between exercise and a high-fat diet. Plasma PaA concentrations showed changes similar to those seen for urinary excretion. The experiment was then repeated using rats fed a PaA-sufficient (0.016 g PaA-Ca/kg diet) diet, and PaA excretion was again synergistically decreased by the combination of exercise and a high-fat diet (p<0.05). These results suggest that the combination of exercise and a high-fat diet synergistically increases the requirement for PaA. PMID:26226957

  9. Tracking and Increasing Viability of Topically Injected Fibroblasts Suspended in Hyaluronic Acid Filler.

    PubMed

    You, Hi-Jin; Namgoong, Sik; Rhee, Sung-Mi; Han, Seung-Kyu

    2016-03-01

    A new injectable tissue-engineered soft tissue consisting of a mixture of hyaluronic acid (HA) filler and cultured human fibroblasts have been developed by the authors. To establish this method as a standard treatment, a further study was required to determine whether the injected fibroblasts could stay at the injected place or move to other sites. In addition, effective strategies were needed to increase viability of the injected fibroblasts. The purpose of this study was to track the injected fibroblasts and to determine the effect of adding prostaglandin E1 (PGE1) or vitamin C on the viability of fibroblasts.Human fibroblasts labeled with fluorescence dye were suspended in HA filler and injected into 4 sites on the back of nude mice. The injected bioimplants consisted of one of the 4 followings: HA filler without cells (HA group), fibroblasts suspended in HA filler (HA + FB group), PGE1-supplemented fibroblasts in HA filler (HA + FB + PGE1 group), and vitamin C-supplemented fibroblasts in HA filler (HA + FB + VC group). At 4 weeks after injection, locations and intensities of the fluorescence signals were evaluated using a live imaging system.The fluorescence signals of the fibroblast-containing groups were visible only at the injected sites without dispersing to other sites. The HA +FB + PGE1 group showed a significantly higher fluorescence signal than the HA + FB and the HA + FB +VC groups (P < 0.05, each). There was no statistical difference between the HA + FB and HA + FB +VC groups (P = 0.69).The results of the current study collectively suggest that injected fibroblasts suspended in HA filler stay at the injected place without moving to other sites. In addition, PGE1 treatment may increase the remaining rhodamine B isothiocynanate dye at the injected site of the human dermal fibroblasts. PMID:26854786

  10. Six Year Refractive Change among White Children and Young Adults: Evidence for Significant Increase in Myopia among White UK Children

    PubMed Central

    2016-01-01

    Objective To determine six-year spherical refractive error change among white children and young adults in the UK and evaluate differences in refractive profiles between contemporary Australian children and historical UK data. Design Population-based prospective study. Participants The Northern Ireland Childhood Errors of Refraction (NICER) study Phase 1 examined 1068 children in two cohorts aged 6–7 years and 12–13 years. Prospective data for six-year follow-up (Phase 3) are available for 212 12–13 year olds and 226 18–20 year olds in each cohort respectively. Methods Cycloplegic refractive error was determined using binocular open-field autorefraction (Shin-Nippon NVision-K 5001, cyclopentolate 1%). Participants were defined by spherical equivalent refraction (SER) as myopic SER ≤-0.50D, emmetropic -0.50Dsignificantly increased between 6–7 years (1.9%) and 12–13 years (14.6%) (p<0.001) but not between 12–13 and 18–20 years (16.4% to 18.6%, p = 0.51). The estimated annual incidence of myopia was 2.2% and 0.7% for the younger and older cohorts respectively. There were significantly more myopic children in the UK at age 12–13 years in the NICER study (16.4%) than reported in Australia (4.4%) (p<0.001). However by 17 years the proportion of myopia neared equivalence in the two populations (NICER 18.6%, Australia 17.7%, p = 0.75). The proportion of myopic children aged 12–13 years in the present study (2006–2008) was 16.4%, significantly greater than that reported for children aged 10–16 years in the 1960’s (7.2%, p = 0.01). The proportion of hyperopes in the younger NICER cohort decreased significantly over the six year period (from 21.7% to 14.2%, p = 0.04). Hyperopes with SER ≥+3.50D in both NICER age cohorts demonstrated persistent hyperopia. Conclusions The incidence and proportion of myopia are relatively

  11. 4-O-Acetyl-sialic acid (Neu4,5Ac2) in acidic milk oligosaccharides of the platypus (Ornithorhynchus anatinus) and its evolutionary significance.

    PubMed

    Urashima, Tadasu; Inamori, Hiroaki; Fukuda, Kenji; Saito, Tadao; Messer, Michael; Oftedal, Olav T

    2015-06-01

    Monotremes (echidnas and platypus) retain an ancestral form of reproduction: egg-laying followed by secretion of milk onto skin and hair in a mammary patch, in the absence of nipples. Offspring are highly immature at hatching and depend on oligosaccharide-rich milk for many months. The primary saccharide in long-beaked echidna milk is an acidic trisaccharide Neu4,5Ac2(α2-3)Gal(β1-4)Glc (4-O-acetyl 3'-sialyllactose), but acidic oligosaccharides have not been characterized in platypus milk. In this study, acidic oligosaccharides purified from the carbohydrate fraction of platypus milk were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. All identified structures, except Neu5Ac(α2-3)Gal(β1-4)Glc (3'-sialyllactose) contained Neu4,5Ac2 (4-O-acetyl-sialic acid). These include the trisaccharide 4-O-acetyl 3'-sialyllactose, the pentasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-tetraose d) and the hexasaccharide Neu4,5Ac2(α2-3)Gal(β1-4)[Fuc(α1-3)]GlcNAc(β1-3)Gal(β1-4)Glc (4-O-acetyl-3'-sialyllacto-N-fucopentaose III). At least seven different octa- to deca-oligosaccharides each contained a lacto-N-neohexaose core (LNnH) and one or two Neu4,5Ac2 and one to three fucose residues. We conclude that platypus milk contains a diverse (≥ 20) array of neutral and acidic oligosaccharides based primarily on lactose, lacto-N-neotetraose (LNnT) and LNnH structural cores and shares with echidna milk the unique feature that all identified acidic oligosaccharides (other than 3'-sialyllactose) contain the 4-O-acetyl-sialic acid moiety. We propose that 4-O-acetylation of sialic acid moieties protects acidic milk oligosaccharides secreted onto integumental surfaces from bacterial hydrolysis via steric interference with bacterial sialidases. This may be of evolutionary significance since taxa ancestral to monotremes and other mammals are

  12. Boric acid increases the expression levels of human anion exchanger genes SLC4A2 and SLC4A3.

    PubMed

    Akbas, F; Aydin, Z

    2012-01-01

    Boron is an important micronutrient in plants and animals. The role of boron in living systems includes coordinated regulation of gene expression, growth and proliferation of higher plants and animals. There are several well-defined genes associated with boron transportation and tolerance in plants and these genes show close homology with human anion exchanger genes. Mutation of these genes also characterizes some genetic disorders. We investigated the toxic effects of boric acid on HEK293 cells and mRNA expression of anion exchanger (SLC4A1, SLC4A2 and SLC4A3) genes. Cytotoxicity of boric acid at different concentrations was tested by using the methylthiazolyldiphenyl-tetrazolium bromide assay. Gene expression profiles were examined using quantitative real-time PCR. In the HEK293 cells, the nontoxic upper concentration of boric acid was 250 μM; more than 500 μM caused cytotoxicity. The 250 μM boric acid concentration increased gene expression level of SLC4A2 up to 8.6-fold and SLC4A3 up to 2.6-fold, after 36-h incubation. There was no significant effect of boric acid on SLC4A1 mRNA expression levels. PMID:22576912

  13. Combination of PLR, MLR, MWR, and Tumor Size Could Significantly Increase the Prognostic Value for Gastrointestinal Stromal Tumors.

    PubMed

    Feng, Fan; Tian, Yangzi; Liu, Shushang; Zheng, Gaozan; Liu, Zhen; Xu, Guanghui; Guo, Man; Lian, Xiao; Fan, Daiming; Zhang, Hongwei

    2016-04-01

    Systemic inflammation and immune response were associated with prognosis of tumors. However, data was limited due to the relatively low incidence of gastrointestinal stromal tumors (GISTs). The aim of the present study was to investigate the predictive value of preoperative peripheral blood cells in prognosis of GISTs.From September 2008 to July 2015, a total of 274 GIST patients in our department were enrolled in the present study. Clinicopathological features of GISTs were recorded. The association between preoperative peripheral blood cells and prognosis of GISTs were analyzed.Tumor location, tumor size, mitotic index, intratumoral necrosis, and National Institutes of Health (NIH) risk category were associated with prognosis of GISTs. High neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-white blood cell ratio (NWR), monocyte-to-white blood cell ratio (MWR) and low lymphocyte-to-white blood cell ratio (LWR) was associated with poor prognosis of GISTs (76.2% vs 83.7%, P = 0.010. 70.5% vs 98.7%, P = 0.000. 65.7% vs 96.4%, P = 0.004. 78.5% vs 82.5%, P = 0.044. 73.5% vs 97.8%, P = 0.004. 76.6% vs 83.6%, P = 0.012, respectively). However, tumor size was the only independent risk factor for prognosis according to multivariate analysis (P = 0.006). Tumor location, tumor size, mitotic index, and NIH risk category were significantly correlated with the above-mentioned parameters (all P < 0.05). The prognosis of GISTs with tumor size >5 cm, high MLR, high PLR, and high MWR was significantly lower than the remnant patients (P = 0.010).The peripheral blood routine test is convenient, reproducible, and inexpensive. High NLR, MLR, PLR, NWR, MWR, and low LWR were associated with poor prognosis of GISTs. The association between the above parameters and prognosis of GISTs may be attributed to their correlation with tumor size, mitotic index, and NIH risk category. The

  14. Organic reactions increasing the absorption index of atmospheric sulfuric acid aerosols

    NASA Astrophysics Data System (ADS)

    Nozière, B.; Esteve, W.

    2005-02-01

    Unlike most environments present at Earth's surface atmospheric aerosols can be favorable to organic reactions. Among them, the acid-catalyzed aldol condensation of aldehydes and ketones produces light-absorbing compounds. In this work the increase of the absorption index of sulfuric acid solutions 50-96 wt. % resulting from the uptake of gas-phase acetaldehyde, acetone, and 2-butanone (methyl ethyl ketone), has been measured in the near UV and visible range. Our results indicate that the absorption index between 200 and 500 nm for stratospheric sulfuric aerosols exposed to 100 pptV of acetaldehyde (1 pptV = 10-12 v/v) would increase by four orders of magnitude over a two-year lifetime. Rough estimates based on previous radiative calculations suggest that this reaction could result in an increase of the radiative forcing of sulfate aerosols of the order of 0.01 W m-2, and that these processes are worth further investigation.

  15. Significance of amino acid variation at human immunodeficiency virus type 1 reverse transcriptase residue 210 for zidovudine susceptibility.

    PubMed Central

    Harrigan, P R; Kinghorn, I; Bloor, S; Kemp, S D; Nájera, I; Kohli, A; Larder, B A

    1996-01-01

    Amino acid variation at reverse transcriptase (RT) codon 210 (generally Leu-210 to Trp [L210W], TTG-->TGG) is occasionally detected after the initiation of azidothymidine (AZT) therapy. The impact of this variation on AZT resistance and viral replication was addressed by four different approaches. The frequency and genetic background of the L210W mutation in vivo were assessed by analyzing sera of AZT-naive and AZT-experienced patients by RT-PCR and DNA sequencing. The degree of AZT resistance (50% infective concentration [IC50]) of recombinant viruses constructed by using the RT of 21 clinical isolates was stratified by the presence or absence of the 210 mutation. The AZT IC50S of a panel of mutant viruses (with or without W-210) constructed by site-directed mutagenesis in an HXB2 background were assayed by using a HeLa CD4 plaque reduction assay. Finally, the effect of the 210 mutation on viral replication was assessed by replication competition of an AZT-resistant virus, RTMN (L-41/Y-215), and RTMN with the W-210 mutation in the presence and in the absence of AZT. In AZT-naive patients, tryptophan at RT residue 210 was rare. After AZT exposure, W-210 appeared in a minority of those patients, most commonly in association with L-41 and Y-215. The presence of W-210 increased the AZTIC50 by two- to fourfold, as determined by both the recombinant virus assay and site-directed mutagenesis. A significant replication advantage in favor of the wild-type L-210 over W-210 was observed, although the selection against the 210 mutant was two- to threefold lower when the viruses were grown in the presence of 5 microM AZT. In summary, the L210W mutation appears to be of marginal significance, conferring approximately two- to fourfold-reduced sensitivity to AZT compared with similar AZT-resistant genomes with L-210. The selection pressure against W-210 may account for the modest proportion of patients in which W-210 appears in vivo. PMID:8709214

  16. THYROID HORMONE REVERSES AGING-INDUCED MYOCARDIAL FATTY ACID OXIDATION DEFECTS AND IMPROVES THE RESPONSE TO ACUTELY INCREASED AFTERLOAD

    SciTech Connect

    Ledee, Dolena; Portman, Michael A.; Kajimoto, Masaki; Isern, Nancy G.; Olson, Aaron

    2013-06-07

    Background: Subclinical hypothyroidism occurs during aging in humans and mice and may contribute to development of heart failure. Aging also impairs myocardial fatty acid oxidation, causing increased reliance on flux through pyruvate dehydrogenase (PDH) to maintain function. We hypothesize that the metabolic changes in aged hearts make them less tolerant to acutely increased work and that thyroid hormone reverses these defects. Methods: Studies were performed on young (Young, 4-6 months) and aged (Old, 22-24 months) C57/BL6 mice at standard (50 mmHg) and high afterload (80 mmHg). Another aged group received thyroid hormone for 3 weeks (Old-TH, high afterload only). Function was measured in isolated working hearts along with substrate fractional contributions (Fc) to the citric acid cycle (CAC) using perfusate with 13C labeled lactate, pyruvate, glucose and unlabeled palmitate and insulin. Results: Cardiac function was similar between Young and Old mice at standard afterload. Palmitate Fc was reduced but no individual carbohydrate contributions differed. CAC and individual substrate fluxes decreased in aged. At high afterload, -dP/dT was decreased in Old versus Young. Similar to low afterload, palmitate Fc was decreased in Old. Thyroid hormone reversed aging-induced changes in palmitate Fc and flux while significantly improving cardiac function. Conclusion: The aged heart shows diminished ability to increase cardiac work due to substrate limitations, primarily impaired fatty acid oxidation. The heart accommodates slightly by increasing efficiency through oxidation of carbohydrate substrates. Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation.

  17. Climate change and increased zinc concentrations in a Rocky Mountain acid rock drainage stream

    NASA Astrophysics Data System (ADS)

    Crouch, C. M.; Todd, A. S.; McKnight, D. M.

    2009-12-01

    The Snake River Watershed in Colorado is impacted by acid rock drainage (ARD) originating from both natural sources and sources associated with the historic mining in the watershed. Downstream of mines, the high metal ion concentrations, low pH, and metal oxide deposition cause contamination which disrupts ecosystem functions, impairs biological diversity, and contaminates surface and groundwater drinking supplies. One obvious measure of the severity of this contamination is that the self-sustaining trout populations in the watershed are quite sparse. While elevated concentrations of numerous trace metals are present, dissolved zinc is used as an indicator of trout habitat water quality because the fish are so impacted by its presence. Water quality was monitored along the Snake River from 1980 to 1990 and since then less frequent sampling was conducted as part of research studies and efforts to designate portions of the watershed for mitigation. Metals concentrations during the seasonal low flows of September and October have been observed to increase significantly over that time. In particular, at a site in the headwaters well above the historic mining impacts, zinc concentrations, which were measured between 0.3 and 0.4 mg/L through the 1980s, have now exceeded 1.2 mg/L in the past several years. This four-fold increase in zinc concentrations is associated with an increase in sulfate concentrations, which indicates that these water quality changes are driven primarily by accelerated natural weathering of pyrite in the watershed. The observed increase in natural ARD - possibly the result of climate change - may have implications for mitigation. Currently, these trends are being evaluated by reanalyzing the archived samples to delineate the spatial and temporal changes in contamination. Processes which may be driving the accelerated natural weathering include the earlier occurrence of peak snowmelt due to climate change which causes lower stream flows and drier

  18. High-fat Diet-induced Intestinal Hyperpermeability is Associated with Increased Bile Acids in the Large Intestine of Mice.

    PubMed

    Murakami, Yuki; Tanabe, Soichi; Suzuki, Takuya

    2016-01-01

    Metabolic syndrome is characterized by low-grade chronic systemic inflammation, which is associated with intestinal hyperpermeability. This study examined the effects of 3 high-fat diets (HFDs) composed of different fat sources (soybean oil and lard) on the intestinal permeability, tight junction (TJ) protein expression, and cecal bile acid (BA) concentrations in mice, and then analyzed their interrelations. C57/BL6 mice were fed the control diet, HFD (soybean oil), HFD (lard), and HFD (mix; containing equal concentrations of soybean oil and lard) for 8 wk. Glucose tolerance, intestinal permeability, TJ protein expression, and cecal BA concentration were evaluated. Feeding with the 3 HDFs similarly increased body weight, liver weight, and fat pad weight, and induced glucose intolerance and intestinal hyperpermeability. The expression of TJ proteins, zonula occludens-2 and junctional adhesion molecule-A, were lower in the colons of the 3 HFD groups than in the control group (P < 0.05), and these changes appeared to be related to intestinal hyperpermeability. Feeding with HFDs increased total secondary BA (SBA) and total BA concentrations along with increases in some individual BAs in the cecum. Significant positive correlations between intestinal permeability and the concentrations of most SBAs, such as deoxycholic acid and ω-muricholic acids, were detected (P < 0.05). These results suggest that the HFD-induced intestinal hyperpermeability is associated with increased BA secretion. The abundance of SBAs in the large intestine may be responsible for the hyperpermeability. PMID:26595891

  19. Conjugated linoleic acid increases in milk from cows fed condensed corn distillers solubles and fish oil.

    PubMed

    Bharathan, M; Schingoethe, D J; Hippen, A R; Kalscheur, K F; Gibson, M L; Karges, K

    2008-07-01

    Twelve lactating Holstein cows were randomly assigned to 1 of 4 experimental diets in a replicated 4 x 4 Latin square design with 4-wk periods to ascertain the lactational response to feeding fish oil (FO), condensed corn distillers solubles (CDS) as a source of extra linoleic acid, or both. Diets contained either no FO or 0.5% FO and either no CDS or 10% CDS in a 2 x 2 factorial arrangement of treatments. Diets were fed as total mixed rations for ad libitum consumption. The forage to concentrate ratio was 55:45 on a dry matter basis for all diets and the diets contained 16.2% crude protein. The ether extract concentrations were 2.86, 3.22, 4.77, and 5.02% for control, FO, CDS, and FOCDS diets, respectively. Inclusion of FO or CDS or both had no effect on dry matter intake, feed efficiency, body weight, and body condition scores compared with diets without FO and CDS, respectively. Yields of milk (33.3 kg/d), energy-corrected milk, protein, lactose, and milk urea N were similar for all diets. Feeding FO and CDS decreased milk fat percentages (3.85, 3.39, 3.33, and 3.12%) and yields compared with diets without FO and CDS. Proportions of trans-11 C18:1 (vaccenic acid), cis-9 trans-11 conjugated linoleic acid (CLA; 0.52, 0.90, 1.11, and 1.52 g/100 g of fatty acids), and trans-10 cis-12 CLA (0.07, 0.14, 0.13, and 0.16 g/100 g of fatty acids) in milk fat were increased by FO and CDS. No interactions were observed between FO and CDS on cis-9 trans-11 CLA although vaccenic acid tended to be higher with the interaction. The addition of CDS to diets increased trans-10 C18:1. Greater ratios of vaccenic acid to cis-9 trans-11 CLA in plasma than in milk fat indicate tissue synthesis of cis-9 trans-11 CLA in the mammary gland from vaccenic acid in cows fed FO or CDS. Feeding fish oil at 0.5% of diet dry matter with a C18:2 n-6 rich source such as CDS increased the milk CLA content but decreased milk fat percentages. PMID:18565937

  20. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

    PubMed

    D'Aniello, Enrico; Rydeen, Ariel B; Anderson, Jane L; Mandal, Amrita; Waxman, Joshua S

    2013-01-01

    Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA) signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1), a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM) specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA. PMID:23990796

  1. Increased Serum Uric Acid Levels Blunt the Antihypertensive Efficacy of Lifestyle Modifications in Children at Cardiovascular Risk.

    PubMed

    Viazzi, Francesca; Rebora, Paola; Giussani, Marco; Orlando, Antonina; Stella, Andrea; Antolini, Laura; Valsecchi, Maria Grazia; Pontremoli, Roberto; Genovesi, Simonetta

    2016-05-01

    Primary hypertension is a growing concern in children because of the obesity epidemic largely attributable to western lifestyles. Serum uric acid is known to be influenced by dietary habits, correlates with obesity, and could represent a risk factor for hypertension. Preliminary studies in children highlighted uric acid as a potentially modifiable risk factor for the prevention and treatment of hypertension. The effect of lifestyle changes (increase of physical activity and dietary modifications) on blood pressure values, weight status, and serum uric acid levels in a cohort of 248 children referred for cardiovascular risk assessment were evaluated over a mean 1.5-year follow-up. At baseline, 48% of children were obese and 50% showed blood pressure values >90th percentile. At follow-up, a significant improvement in weight class (24% obese;P<0.0001) and blood pressure category (22% >90th percentile;P<0.0001) was found. Systolic blood pressure z-score (P<0.0001), uric acid value (P=0.0056), and puberty at baseline (P=0.0048) were independently associated with higher systolic blood pressure z-score at follow-up, whereas a negative association was observed with body mass index z-score decrease during follow-up (P=0.0033). The risk of hypertension at follow-up was associated with body mass index (P=0.0025) and systolic blood pressure (P<0.0001) z-score at baseline and inversely related to delta body mass index (P=0.0002), whereas the risk of showing hypertension ≥99th percentile was more than doubled for each baseline 1 mg/dL increase of serum uric acid (P=0.0130). Uric acid is a powerful determinant of blood pressure over time, independent of lifestyle modifications. PMID:27021006

  2. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed

    Jung, R T; Shetty, P S; James, W P

    1980-05-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  3. Heparin, free fatty acids and an increased metabolic demand for oxygen.

    PubMed Central

    Jung, R. T.; Shetty, P. S.; James, W. P.

    1980-01-01

    Obese and lean subjects were given heparin with or without Intralipid in order to assess the effect of heparin on plasma concentration of free fatty acids (FFA) and oxidative metabolism. The FFA response depended on the triglyceride concentration and was associated with a prompt rise in oxygen consumption. Plasma catecholamines did not alter after heparin and the increase in oxygen uptake was proportional to the rise in FFA. The use of heparin, therefore, has metabolic disadvantages which may outweigh the potential benefits, for example in the management of myocardial infarction where heparin may increase the metabolic demand on the heart by increasing FFA levels. PMID:7443592

  4. Metabolic engineering of Aspergillus oryzae NRRL 3488 for increased production of L-malic acid.

    PubMed

    Brown, Stephen H; Bashkirova, Lena; Berka, Randy; Chandler, Tyler; Doty, Tammy; McCall, Keith; McCulloch, Michael; McFarland, Sarah; Thompson, Sheryl; Yaver, Debbie; Berry, Alan

    2013-10-01

    Malic acid, a petroleum-derived C4-dicarboxylic acid that is used in the food and beverage industries, is also produced by a number of microorganisms that follow a variety of metabolic routes. Several members of the genus Aspergillus utilize a two-step cytosolic pathway from pyruvate to malate known as the reductive tricarboxylic acid (rTCA) pathway. This simple and efficient pathway has a maximum theoretical yield of 2 mol malate/mol glucose when the starting pyruvate originates from glycolysis. Production of malic acid by Aspergillus oryzae NRRL 3488 was first improved by overexpression of a native C4-dicarboxylate transporter, leading to a greater than twofold increase in the rate of malate production. Overexpression of the native cytosolic alleles of pyruvate carboxylase and malate dehydrogenase, comprising the rTCA pathway, in conjunction with the transporter resulted in an additional 27 % increase in malate production rate. A strain overexpressing all three genes achieved a malate titer of 154 g/L in 164 h, corresponding to a production rate of 0.94 g/L/h, with an associated yield on glucose of 1.38 mol/mol (69 % of the theoretical maximum). This rate of malate production is the highest reported for any microbial system. PMID:23925533

  5. Chlorogenic acid ameliorates intestinal mitochondrial injury by increasing antioxidant effects and activity of respiratory complexes.

    PubMed

    Zhou, Yan; Zhou, Lili; Ruan, Zheng; Mi, Shumei; Jiang, Min; Li, Xiaolan; Wu, Xin; Deng, Zeyuan; Yin, Yulong

    2016-05-01

    Dietary polyphenols are thought to be beneficial for human health by acting as antioxidants. Chlorogenic acid (CGA) is abundant in plant-based foods as an ester of caffeic acid and quinic acid. In this study, we investigated the effects of CGA on mitochondrial protection. Our results demonstrated that pretreatment with CGA ameliorated the intestinal mitochondrial injury induced by H2O2; membrane potential was increased, mitochondrial swelling, levels of reactive oxygen species, contents of 8-hydroxy-2-deoxyguanosine, and cytochrome c released were decreased. The beneficial effects of CGA were accompanied by an increase in antioxidant and respiratory-chain complex I, IV, and V activities. In trinitrobenzene-sulfonic acid-induced colitic rats indicated that CGA supplementation improved mitochondria ultrastructure and decreased mitochondrial injury. Our results suggest a promising role for CGA as a mitochondria-targeted antioxidant in combating intestinal oxidative injury. Daily intake of diets containing CGA, such as coffee and honeysuckle, may be useful for prevention of intestinal diseases. PMID:26824685

  6. Long-Term Ritonavir Exposure Increases Fatty Acid and Glycerol Recycling in 3T3-L1 Adipocytes as Compensatory Mechanisms for Increased Triacylglycerol Hydrolysis

    PubMed Central

    Adler-Wailes, Diane C.; Guiney, Evan L.; Wolins, Nathan E.; Yanovski, Jack A.

    2010-01-01

    Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P < 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P < 0.05) and protein (P < 0.05). Ritonavir increased glycerol (P < 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P < 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P < 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thus increasing FA efflux, and leads to compensatory increases in FA reesterification with glycerol and acylglycerols. These changes in FA metabolism may, in part, explain the increased FA efflux observed in ritonavir-associated lipodystrophy. PMID:20228169

  7. Acidic pH increases airway surface liquid viscosity in cystic fibrosis.

    PubMed

    Tang, Xiao Xiao; Ostedgaard, Lynda S; Hoegger, Mark J; Moninger, Thomas O; Karp, Philip H; McMenimen, James D; Choudhury, Biswa; Varki, Ajit; Stoltz, David A; Welsh, Michael J

    2016-03-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3- concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator-dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  8. Acidic pH increases airway surface liquid viscosity in cystic fibrosis

    PubMed Central

    Tang, Xiao Xiao; Ostedgaard, Lynda S.; Hoegger, Mark J.; Moninger, Thomas O.; Karp, Philip H.; McMenimen, James D.; Choudhury, Biswa; Varki, Ajit; Stoltz, David A.; Welsh, Michael J.

    2016-01-01

    Cystic fibrosis (CF) disrupts respiratory host defenses, allowing bacterial infection, inflammation, and mucus accumulation to progressively destroy the lungs. Our previous studies revealed that mucus with abnormal behavior impaired mucociliary transport in newborn CF piglets prior to the onset of secondary manifestations. To further investigate mucus abnormalities, here we studied airway surface liquid (ASL) collected from newborn piglets and ASL on cultured airway epithelia. Fluorescence recovery after photobleaching revealed that the viscosity of CF ASL was increased relative to that of non-CF ASL. CF ASL had a reduced pH, which was necessary and sufficient for genotype-dependent viscosity differences. The increased viscosity of CF ASL was not explained by pH-independent changes in HCO3– concentration, altered glycosylation, additional pH-induced disulfide bond formation, increased percentage of nonvolatile material, or increased sulfation. Treating acidic ASL with hypertonic saline or heparin largely reversed the increased viscosity, suggesting that acidic pH influences mucin electrostatic interactions. These findings link loss of cystic fibrosis transmembrane conductance regulator–dependent alkalinization to abnormal CF ASL. In addition, we found that increasing Ca2+ concentrations elevated ASL viscosity, in part, independently of pH. The results suggest that increasing pH, reducing Ca2+ concentration, and/or altering electrostatic interactions in ASL might benefit early CF. PMID:26808501

  9. The significant increasing of atmospheric bi-weekly disturbances over Northeast Asia during the global-warming hiatus

    NASA Astrophysics Data System (ADS)

    Li, S.; Gong, D.

    2015-12-01

    Based on daily 500 hPa heights from ERA-Interim reanalysis, this study analyzed the day-to-day circulation variance in cold season (October-March) during the global-warming hiatus by employing composite and correlation analysis. Two same-length time periods, i.e., the hiatus period (1999-2013) and the rapid warming period (1984-1998), are compared. Spectral analysis reveals that over the mid-high latitude northern hemisphere the most outstanding peak in the daily 500hPa height variance is of quasi bi-weekly (QBW) time scale (about 10-20d), which accounts for about 32% of the total variance. During the global-warming hiatus, the QBW disturbances have changed remarkably in Northeast Asia. On average in the domain of 128°E-142°E, 42°N-50°N the QBW variance has changed from 1860m2 in the rapid warming period to 2475m2 in the hiatus, increasing by about 33% and being statistically significant at the 95% level. The time-lag analysis shows that the QBW signal could be traced back to about 14 days ago with a origin around Ural Mountains, then the signals developed and moved southeastward, its location about 10 days ago was located in West Siberia, about 6 days ago located in Mongolian Plat. at finally move to Northeast Asia. Compared the propagation process between the two periods, we found that the path was basically the same, but there are evident difference in their signal intensity along its eastward propagation. Comparing with the rapid warm period, the QBW during the hiatus got much intensive as the signal move across the West Siberia. And the enhanced signal keeps its intensity till to Northeast Asia. The intensification of QBW may be related to the changes in the background circulation. During the hiatus period, there are anomalous large-scale changes in 500hPa heights, with a strengthened Ural ridge and a westward East Asia trough. Accordingly, there is a stronger east-west pressure gradient in western Siberia, being a condition beneficial to strengthen the

  10. Increase in fatty acid oxidation in calvaria cells cultured with diphosphonates.

    PubMed Central

    Felix, R; Fleisch, H

    1981-01-01

    1. Cultured calvaria cells oxidized palmitate and octanoate to CO2 and water-soluble products. 2. When these cells were treated for 6 days with 0.025 and 0.25 mM-dichloromethanediphosphonate, oxidation of palmitate was increased, whereas that of octanoate was influenced less. 3. When the rate of oxidation was raised by increasing the palmitate concentration in the medium, the effect of the diphosphonate was decreased and finally disappeared. 4. 1-Hydroxyethane-1,1-diphosphonate had only minor effects. 5. The increase in palmitate oxidation appeared 2 days after the addition of dichloromethanediphosphonate, simultaneously with a fall in lactate production. (Inhibition of glycolysis by diphosphonates has already been shown.) 6. Cycloheximide, an inhibitor of protein synthesis, did not influence the effect of dichloromethanediphosphonate on the oxidation of palmitate and the production of lactate. 7. Cells cultured with dichloromethanediphosphonate showed a faster uptake of palmitic acid than did control cells. However, this observation did not explain the increased palmitate oxidation, since uptake was much faster than oxidation, and was therefore not the rate-limiting step. 8. 2-Bromopalmitate, an inhibitor of fatty acid oxidation, did not influence the inhibition of glycolysis by the diphosphonates. This inhibition, therefore, did not result from the increased oxidation of palmitate. It is also unlikely that the increased oxidation of palmitate is connected with the inhibition of glycolysis. PMID:6458286

  11. Increasing Fatty Acid Oxidation Remodels the Hypothalamic Neurometabolome to Mitigate Stress and Inflammation

    PubMed Central

    McFadden, Joseph W.; Aja, Susan; Li, Qun; Bandaru, Veera V. R.; Kim, Eun-Kyoung; Haughey, Norman J.; Kuhajda, Francis P.; Ronnett, Gabriele V.

    2014-01-01

    Modification of hypothalamic fatty acid (FA) metabolism can improve energy homeostasis and prevent hyperphagia and excessive weight gain in diet-induced obesity (DIO) from a diet high in saturated fatty acids. We have shown previously that C75, a stimulator of carnitine palmitoyl transferase-1 (CPT-1) and fatty acid oxidation (FAOx), exerts at least some of its hypophagic effects via neuronal mechanisms in the hypothalamus. In the present work, we characterized the effects of C75 and another anorexigenic compound, the glycerol-3-phosphate acyltransferase (GPAT) inhibitor FSG67, on FA metabolism, metabolomics profiles, and metabolic stress responses in cultured hypothalamic neurons and hypothalamic neuronal cell lines during lipid excess with palmitate. Both compounds enhanced palmitate oxidation, increased ATP, and inactivated AMP-activated protein kinase (AMPK) in hypothalamic neurons in vitro. Lipidomics and untargeted metabolomics revealed that enhanced catabolism of FA decreased palmitate availability and prevented the production of fatty acylglycerols, ceramides, and cholesterol esters, lipids that are associated with lipotoxicity-provoked metabolic stress. This improved metabolic signature was accompanied by increased levels of reactive oxygen species (ROS), and yet favorable changes in oxidative stress, overt ER stress, and inflammation. We propose that enhancing FAOx in hypothalamic neurons exposed to excess lipids promotes metabolic remodeling that reduces local inflammatory and cell stress responses. This shift would restore mitochondrial function such that increased FAOx can produce hypothalamic neuronal ATP and lead to decreased food intake and body weight to improve systemic metabolism. PMID:25541737

  12. Decrease in erythrocyte glycophorin sialic acid content is associated with increased erythrocyte aggregation in human diabetes.

    PubMed

    Rogers, M E; Williams, D T; Niththyananthan, R; Rampling, M W; Heslop, K E; Johnston, D G

    1992-03-01

    1. Sialic acid moieties of erythrocyte membrane glycoproteins are the principal determinants of the negative charge on the cell surface. The resultant electrostatic repulsion between the cells reduces erythrocyte aggregation and hence the low shear rate viscosity and yield stress of blood. 2. Using g.c.-m.s., a decrease in sialic acid content has been observed in the major erythrocyte membrane glycoprotein, glycophorin A, obtained from nine diabetic patients compared with that from seven normal control subjects [median (range): 3.30 (0.01-11.90) versus 18.60 (3.20-32.60) micrograms/100 micrograms of protein, P less than 0.02]. 3. Erythrocyte aggregation, measured by viscometry as the ratio of suspension viscosity to supernatant viscosity (LS/S) in fibrinogen solution, was increased in ten diabetic patients compared with ten normal control subjects (mean +/- SEM, 37.6 +/- 1.3 versus 33.8 +/- 0.6, P less than 0.02). 4. In the patients in whom both viscometry and carbohydrate analysis were performed, the decrease in erythrocyte glycophorin sialylation and the increase in erythrocyte aggregation in fibrinogen solution were related statistically (LS/S correlated negatively with glycophorin sialic acid content, r = 0.73, P less than 0.05). 5. Decreased glycophorin sialylation provides an explanation at the molecular level for increased erythrocyte aggregation and it may be important in the pathogenesis of vascular disease in diabetes. PMID:1312416

  13. Dietary Crude Lecithin Increases Systemic Availability of Dietary Docosahexaenoic Acid with Combined Intake in Rats.

    PubMed

    van Wijk, Nick; Balvers, Martin; Cansev, Mehmet; Maher, Timothy J; Sijben, John W C; Broersen, Laus M

    2016-07-01

    Crude lecithin, a mixture of mainly phospholipids, potentially helps to increase the systemic availability of dietary omega-3 polyunsaturated fatty acids (n-3 PUFA), such as docosahexaenoic acid (DHA). Nevertheless, no clear data exist on the effects of prolonged combined dietary supplementation of DHA and lecithin on RBC and plasma PUFA levels. In the current experiments, levels of DHA and choline, two dietary ingredients that enhance neuronal membrane formation and function, were determined in plasma and red blood cells (RBC) from rats after dietary supplementation of DHA-containing oils with and without concomitant dietary supplementation of crude lecithin for 2-3 weeks. The aim was to provide experimental evidence for the hypothesized additive effects of dietary lecithin (not containing any DHA) on top of dietary DHA on PUFA levels in plasma and RBC. Dietary supplementation of DHA-containing oils, either as vegetable algae oil or as fish oil, increased DHA, eicosapentaenoic acid (EPA), and total n-3 PUFA, and decreased total omega-6 PUFA levels in plasma and RBC, while dietary lecithin supplementation alone did not affect these levels. However, combined dietary supplementation of DHA and lecithin increased the changes induced by DHA supplementation alone. Animals receiving a lecithin-containing diet also had a higher plasma free choline concentration as compared to controls. In conclusion, dietary DHA-containing oils and crude lecithin have synergistic effects on increasing plasma and RBC n-3 PUFA levels, including DHA and EPA. By increasing the systemic availability of dietary DHA, dietary lecithin may increase the efficacy of DHA supplementation when their intake is combined. PMID:27038174

  14. Investigating the significance of zero-point motion in small molecular clusters of sulphuric acid and water

    SciTech Connect

    Stinson, Jake L. Ford, Ian J.; Kathmann, Shawn M.

    2014-01-14

    The nucleation of particles from trace gases in the atmosphere is an important source of cloud condensation nuclei, and these are vital for the formation of clouds in view of the high supersaturations required for homogeneous water droplet nucleation. The methods of quantum chemistry have increasingly been employed to model nucleation due to their high accuracy and efficiency in calculating configurational energies; and nucleation rates can be obtained from the associated free energies of particle formation. However, even in such advanced approaches, it is typically assumed that the nuclei have a classical nature, which is questionable for some systems. The importance of zero-point motion (also known as quantum nuclear dynamics) in modelling small clusters of sulphuric acid and water is tested here using the path integral molecular dynamics method at the density functional level of theory. The general effect of zero-point motion is to distort the mean structure slightly, and to promote the extent of proton transfer with respect to classical behaviour. In a particular configuration of one sulphuric acid molecule with three waters, the range of positions explored by a proton between a sulphuric acid and a water molecule at 300 K (a broad range in contrast to the confinement suggested by geometry optimisation at 0 K) is clearly affected by the inclusion of zero point motion, and similar effects are observed for other configurations.

  15. Note: Significant increase to the temporal resolution of 2D X-ray detectors using a novel beam chopper system

    SciTech Connect

    Küchemann, Stefan; Mahn, Carsten; Samwer, Konrad

    2014-01-15

    The investigation of short time dynamics using X-ray scattering techniques is commonly limited either by the read out frequency of the detector or by a low intensity. In this paper, we present a chopper system, which can increase the temporal resolution of 2D X-ray detectors by a factor of 13. This technique only applies to amorphous or polycrystalline samples due to their circular diffraction patterns. Using the chopper, we successfully increased the temporal resolution up to 5.1 ms during synchrotron experiments. For the construction, we provide a mathematical formalism, which, in principle, allows an even higher increase of the temporal resolution.

  16. Synergism of α-linolenic acid, conjugated linoleic acid and calcium in decreasing adipocyte and increasing osteoblast cell growth.

    PubMed

    Kim, Youjin; Kelly, Owen J; Ilich, Jasminka Z

    2013-08-01

    Whole fat milk and dairy products (although providing more energy compared to low- or non-fat products), are good sources of α-linolenic acid (ALA), conjugated linoleic acid (CLA) and calcium, which may be favorable in modulating bone and adipose tissue metabolism. We examined individual and/or synergistic effects of ALA, CLA and calcium (at levels similar to those in whole milk/dairy products) in regulating bone and adipose cell growth. ST2 stromal, MC3T3-L1 adipocyte-like and MC3T3-E1 osteoblast-like cells were treated with: (a) linoleic acid (LNA):ALA ratios = 1-5:1; (b) individual/combined 80-90 % c9, t11 (9,11) and 5-10 % t10, c12 (10,12) CLA isomers; (c) 0.5-3.0 mM calcium; (d) combinations of (a), (b), (c); and (e) control. Local mediators, including eicosanoids and growth factors, were measured. (a) The optimal effect was found at the 4:1 LNA:ALA ratio where insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) production was the lowest in MC3T3-L1 cells. (b) All CLA isomer blends decreased MC3T3-L1 and increased MC3T3-E1 cell differentiation. (c) 1.5-2.5 mM calcium increased ST2 and MC3T3-E1, and decreased MC3T3-L1 cell proliferation. (d) Combination of 4:1 LNA:ALA + 90:10 % CLA + 2.0 mM calcium lowered MC3T3-L1 and increased MC3T3-E1 cell differentiation. Overall, the optimal LNA:ALA ratio to enhance osteoblastogenesis and inhibit adipogenesis was 4:1. This effect was enhanced by 90:10 % CLA + 2.0 mM calcium, indicating possible synergism of these dietary factors in promoting osteoblast and inhibiting adipocyte differentiation in cell cultures. PMID:23757205

  17. The Fatty Acid Signaling Molecule cis-2-Decenoic Acid Increases Metabolic Activity and Reverts Persister Cells to an Antimicrobial-Susceptible State

    PubMed Central

    Morozov, Aleksey; Planzos, Penny; Zelaya, Hector M.

    2014-01-01

    Persister cells, which are tolerant to antimicrobials, contribute to biofilm recalcitrance to therapeutic agents. In turn, the ability to kill persister cells is believed to significantly improve efforts in eradicating biofilm-related, chronic infections. While much research has focused on elucidating the mechanism(s) by which persister cells form, little is known about the mechanism or factors that enable persister cells to revert to an active and susceptible state. Here, we demonstrate that cis-2-decenoic acid (cis-DA), a fatty acid signaling molecule, is able to change the status of Pseudomonas aeruginosa and Escherichia coli persister cells from a dormant to a metabolically active state without an increase in cell number. This cell awakening is supported by an increase of the persister cells' respiratory activity together with changes in protein abundance and increases of the transcript expression levels of several metabolic markers, including acpP, 16S rRNA, atpH, and ppx. Given that most antimicrobials target actively growing cells, we also explored the effect of cis-DA on enhancing antibiotic efficacy in killing persister cells due to their inability to keep a persister cell state. Compared to antimicrobial treatment alone, combinational treatments of persister cell subpopulations with antimicrobials and cis-DA resulted in a significantly greater decrease in cell viability. In addition, the presence of cis-DA led to a decrease in the number of persister cells isolated. We thus demonstrate the ability of a fatty acid signaling molecule to revert bacterial cells from a tolerant phenotype to a metabolically active, antimicrobial-sensitive state. PMID:25192989

  18. Butyric acid increases transepithelial transport of ferulic acid through upregulation of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4).

    PubMed

    Ziegler, Kerstin; Kerimi, Asimina; Poquet, Laure; Williamson, Gary

    2016-06-01

    Ferulic acid is released by microbial hydrolysis in the colon, where butyric acid, a major by-product of fermentation, constitutes the main energy source for colonic enterocytes. We investigated how varying concentrations of this short chain fatty acid may influence the absorption of the phenolic acid. Chronic treatment of Caco-2 cells with butyric acid resulted in increased mRNA and protein abundance of the monocarboxylate transporters SLC16A1 (MCT1) and SLC16A3 (MCT4), previously proposed to facilitate ferulic acid absorption in addition to passive diffusion. Short term incubation with butyric acid only led to upregulation of MCT4 while both conditions increased transepithelial transport of ferulic acid in the apical to basolateral, but not basolateral to apical, direction. Chronic treatment also elevated intracellular concentrations of ferulic acid, which in turn gave rise to increased concentrations of ferulic acid metabolites. Immunofluorescence staining of cells revealed uniform distribution of MCT1 protein in the cell membrane, whereas MCT4 was only detected in the lateral plasma membrane sections of Caco-2 cells. We therefore propose that MCT1 may be acting as an uptake transporter and MCT4 as an efflux system across the basolateral membrane for ferulic acid, and that this process is stimulated by butyric acid. PMID:26854723

  19. De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection

    PubMed Central

    Greseth, Matthew D.; Traktman, Paula

    2014-01-01

    The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in

  20. De novo fatty acid biosynthesis contributes significantly to establishment of a bioenergetically favorable environment for vaccinia virus infection.

    PubMed

    Greseth, Matthew D; Traktman, Paula

    2014-03-01

    The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in

  1. [The noninvasive evaluation of degree of expression of fibrosis of liver and significance of polymorphism of gene of hyaluronic acid under chronic hepatitis C].

    PubMed

    Bulatova, I A; Schekotova, A P; Krivtsov, A V; Schekotov, V V; Pavlov, A I

    2015-03-01

    The study was carries out to evaluate degree of expression of fibrosis, reparation processes in liver and value of polymorphism of gene of hyaluronic acid HASI (rs11084111) in progression of affection of liver in patients with chronic hepatitis C. The sampling included 100 patients with chronic hepatitis C. The control group included 83 healthy donors. The blood serum was tested to detect concentration of hyaluronic acid and alpha-fetoprotein. The stage of liver fibrosis (F) was evaluated by using ultrasound fibroflexography The polymorphism of gene (rs11084111) was analysed by polymerase chain reaction technique. In the group of patients with F1 the average concentration of hyaluronic acid in blood serum in 1.8 times surpassed this indicator in group with F0. The concentration of hyaluronic acid was almost 2 times higher under F3 as compared with F1-F2. This indicator permitted differentiating F3 and F4 which followed by activation of cytolysis and cholestasis in F1 and F3 and by increasing of level of alpha-fetoprotein at stages F1 and F4. The study detected no statistically significant difference between rates of genotypes and alleles of gene HASI (rs11084111) in groups of healthy patients and patients with chronic hepatitis C. The direct relationships are established between hyaluronic acid and markers of cytolysis, cholestasis, alpha-fetoprotein (p = 0.001), viral load (p = 0.003) liver elasticity index according fibroflexography data (p < 0.001) and fibrosis index (p < 0.001). The established relationships indicate association of hepatofibrosis with cytolysis, cholestasis, hepatocytes regeneration and virus activity. The hyaluronic acid permits to stratify minimal expressed fibrosis and also the transition of disease to the stage of cirrhosis. PMID:26031159

  2. Increased betulinic acid induced cytotoxicity and radiosensitivity in glioma cells under hypoxic conditions

    PubMed Central

    2011-01-01

    Background Betulinic acid (BA) is a novel antineoplastic agent under evaluation for tumor therapy. Because of the selective cytotoxic effects of BA in tumor cells (including gliomas), the combination of this agent with conservative therapies (such as radiotherapy and chemotherapy) may be useful. Previously, the combination of BA with irradiation under hypoxic conditions had never been studied. Methods In this study, the effects of 3 to 30 μM BA on cytotoxicity, migration, the protein expression of PARP, survivin and HIF-1α, as well as radiosensitivity under normoxic and hypoxic conditions were analyzed in the human malignant glioma cell lines U251MG and U343MG. Cytotoxicity and radiosensitivity were analyzed with clonogenic survival assays, migration was analyzed with Boyden chamber assays (or scratch assays) and protein expression was examined with Western blot analyses. Results Under normoxic conditions, a half maximal inhibitory concentration (IC50) of 23 μM was observed in U251MG cells and 24 μM was observed in U343MG cells. Under hypoxic conditions, 10 μM or 15 μM of BA showed a significantly increased cytotoxicity in U251MG cells (p = 0.004 and p = 0.01, respectively) and U343MG cells (p < 0.05 and p = 0.01, respectively). The combination of BA with radiotherapy resulted in an additive effect in the U343MG cell line under normoxic and hypoxic conditions. Weak radiation enhancement was observed in U251MG cell line after treatment with BA under normoxic conditions. Furthermore, under hypoxic conditions, the incubation with BA resulted in increased radiation enhancement. The enhancement factor, at an irradiation dose of 15 Gy after treatment with 10 or 15 μM BA, was 2.20 (p = 0.02) and 4.50 (p = 0.03), respectively. Incubation with BA led to decreased cell migration, cleavage of PARP and decreased expression levels of survivin in both cell lines. Additionally, BA treatment resulted in a reduction of HIF-1α protein under hypoxic conditions. Conclusion Our

  3. Multifold Increases in Turing Pattern Wavelength in the Chlorine Dioxide-Iodine-Malonic Acid Reaction-Diffusion System

    NASA Astrophysics Data System (ADS)

    Gaskins, Delora K.; Pruc, Emily E.; Epstein, Irving R.; Dolnik, Milos

    2016-07-01

    Turing patterns in the chlorine dioxide-iodine-malonic acid reaction were modified through additions of sodium halide salt solutions. The range of wavelengths obtained is several times larger than in the previously reported literature. Pattern wavelength was observed to significantly increase with sodium bromide or sodium chloride. A transition to a uniform state was found at high halide concentrations. The observed experimental results are qualitatively well reproduced in numerical simulations with the Lengyel-Epstein model with an additional chemically realistic kinetic term to account for the added halide and an adjustment of the activator diffusion rate to allow for interhalogen formation.

  4. Multifold Increases in Turing Pattern Wavelength in the Chlorine Dioxide-Iodine-Malonic Acid Reaction-Diffusion System.

    PubMed

    Gaskins, Delora K; Pruc, Emily E; Epstein, Irving R; Dolnik, Milos

    2016-07-29

    Turing patterns in the chlorine dioxide-iodine-malonic acid reaction were modified through additions of sodium halide salt solutions. The range of wavelengths obtained is several times larger than in the previously reported literature. Pattern wavelength was observed to significantly increase with sodium bromide or sodium chloride. A transition to a uniform state was found at high halide concentrations. The observed experimental results are qualitatively well reproduced in numerical simulations with the Lengyel-Epstein model with an additional chemically realistic kinetic term to account for the added halide and an adjustment of the activator diffusion rate to allow for interhalogen formation. PMID:27517779

  5. Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans.

    PubMed

    Schlittler, Maja; Goiny, Michel; Agudelo, Leandro Z; Venckunas, Tomas; Brazaitis, Marius; Skurvydas, Albertas; Kamandulis, Sigitas; Ruas, Jorge L; Erhardt, Sophie; Westerblad, Håkan; Andersson, Daniel C

    2016-05-15

    Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder. PMID:27030575

  6. Chronic xerostomia increases esophageal acid exposure and is associated with esophageal injury

    SciTech Connect

    Korsten, M.A.; Rosman, A.S.; Fishbein, S.; Shlein, R.D.; Goldberg, H.E.; Biener, A. )

    1991-06-01

    OBJECTIVES: To assess the effects of chronic xerostomia on parameters of gastroesophageal reflux and esophagitis. DESIGN: Observational study of a cohort of male patients with xerostomia and age-matched control subjects. SETTING: Tertiary-care Veterans Affairs Medical Center. SUBJECTS: Sixteen male patients with chronic xerostomia secondary to radiation for head and neck cancers or medications. Nineteen age-matched male control subjects with comparable alcohol and smoking histories. MEASUREMENTS AND MAIN RESULTS: Esophageal motility was similar in patients with xerostomia and controls. Clearance of acid from the esophagus and 24-hour intraesophageal pH were markedly abnormal in patients with xerostomia. Symptoms and signs of esophagitis were significantly more frequent in subjects with xerostomia. CONCLUSIONS: Chronic xerostomia may predispose to esophageal injury, at least in part, by decreasing the clearance of acid from the esophagus and altering 24-hour intraesophageal pH. Esophageal injury is a previously unreported complication of long-term salivary deficiency.

  7. Increased microcirculation detected by dynamic contrast-enhanced magnetic resonance imaging is of prognostic significance in asymptomatic myeloma.

    PubMed

    Hillengass, Jens; Ritsch, Judith; Merz, Maximilian; Wagner, Barbara; Kunz, Christina; Hielscher, Thomas; Laue, Hendrik; Bäuerle, Tobias; Zechmann, Christian M; Ho, Anthony D; Schlemmer, Heinz-Peter; Goldschmidt, Hartmut; Moehler, Thomas M; Delorme, Stefan

    2016-07-01

    This prospective study aimed to investigate the prognostic significance of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) as a non-invasive imaging technique delivering the quantitative parameters amplitude A (reflecting blood volume) and exchange rate constant kep (reflecting vascular permeability) in patients with asymptomatic monoclonal plasma cell diseases. We analysed DCE-MRI parameters in 33 healthy controls and 148 patients with monoclonal gammopathy of undetermined significance (MGUS) or smouldering multiple myeloma (SMM) according to the 2003 IMWG guidelines. All individuals underwent standardized DCE-MRI of the lumbar spine. Regions of interest were drawn manually on T1-weighted images encompassing the bone marrow of each of the 5 lumbar vertebrae sparing the vertebral vessel. Prognostic significance for median of amplitude A (univariate: P < 0·001, hazard ratio (HR) 2·42, multivariate P = 0·02, HR 2·7) and exchange rate constant kep (univariate P = 0·03, HR 1·92, multivariate P = 0·46, HR 1·5) for time to progression of 79 patients with SMM was found. Patients with amplitude A above the optimal cut-off point of 0·89 arbitrary units had a 2-year progression rate into symptomatic disease of 80%. In conclusion, DCE-MRI parameters are of prognostic significance for time to progression in patients with SMM but not in individuals with MGUS. PMID:26991959

  8. Adipose tissue fatty acid chain length and mono-unsaturation increases with obesity and insulin resistance

    PubMed Central

    Yew Tan, Chong; Virtue, Samuel; Murfitt, Steven; Robert, Lee D.; Phua, Yi Hui; Dale, Martin; Griffin, Julian L.; Tinahones, Francisco; Scherer, Philipp E.; Vidal-Puig, Antonio

    2015-01-01

    The non-essential fatty acids, C18:1n9, C16:0, C16:1n7, C18:0 and C18:1n7 account for over 75% of fatty acids in white adipose (WAT) triacylglycerol (TAG). The relative composition of these fatty acids (FA) is influenced by the desaturases, SCD1-4 and the elongase, ELOVL6. In knock-out models, loss of SCD1 or ELOVL6 results in reduced Δ9 desaturated and reduced 18-carbon non-essential FA respectively. Both Elovl6 KO and SCD1 KO mice exhibit improved insulin sensitivity. Here we describe the relationship between WAT TAG composition in obese mouse models and obese humans stratified for insulin resistance. In mouse models with increasing obesity and insulin resistance, there was an increase in scWAT Δ9 desaturated FAs (SCD ratio) and FAs with 18-carbons (Elovl6 ratio) in mice. Data from mouse models discordant for obesity and insulin resistance (AKT2 KO, Adiponectin aP2-transgenic), suggested that scWAT TAG Elovl6 ratio was associated with insulin sensitivity, whereas SCD1 ratio was associated with fat mass. In humans, a greater SCD1 and Elovl6 ratio was found in metabolically more harmful visceral adipose tissue when compared to subcutaneous adipose tissue. PMID:26679101

  9. Human Insulin Resistance Is Associated With Increased Plasma Levels of 12α-Hydroxylated Bile Acids

    PubMed Central

    Haeusler, Rebecca A.; Astiarraga, Brenno; Camastra, Stefania; Accili, Domenico; Ferrannini, Ele

    2013-01-01

    Bile acids (BAs) exert pleiotropic metabolic effects, and physicochemical properties of different BAs affect their function. In rodents, insulin regulates BA composition, in part by regulating the BA 12α-hydroxylase CYP8B1. However, it is unclear whether a similar effect occurs in humans. To address this question, we examined the relationship between clamp-measured insulin sensitivity and plasma BA composition in a cohort of 200 healthy subjects and 35 type 2 diabetic (T2D) patients. In healthy subjects, insulin resistance (IR) was associated with increased 12α-hydroxylated BAs (cholic acid, deoxycholic acid, and their conjugated forms). Furthermore, ratios of 12α-hydroxylated/non–12α-hydroxylated BAs were associated with key features of IR, including higher insulin, proinsulin, glucose, glucagon, and triglyceride (TG) levels and lower HDL cholesterol. In T2D patients, BAs were nearly twofold elevated, and more hydrophobic, compared with healthy subjects, although we did not observe disproportionate increases in 12α-hydroxylated BAs. In multivariate analysis of the whole dataset, controlling for sex, age, BMI, and glucose tolerance status, higher 12α-hydroxy/non–12α-hydroxy BA ratios were associated with lower insulin sensitivity and higher plasma TGs. These findings suggest a role for 12α-hydroxylated BAs in metabolic abnormalities in the natural history of T2D and raise the possibility of developing insulin-sensitizing therapeutics based on manipulations of BA composition. PMID:23884887

  10. Dietary histidine increases mouse skin urocanic acid levels and enhances UVB-induced immune suppression of contact hypersensitivity.

    PubMed

    Reilly, S K; De Fabo, E C

    1991-04-01

    Urocanic Acid (UCA) exists in mammalian skin primarily as the trans isomer and is photoisomerized to cis UCA upon UVB absorption. Our previous studies indicated that the photoisomerization of UCA is the initiating event in UBV-induced suppression of cell-mediated immunity (tUCA----cUCA----immune suppression). The purpose of this study was to verify the role of UCA in UV-induced immune suppression of contact hypersensitivity (CHS) in BALB/c mice. Since UCA is a metabolite of the amino acid L-histidine, we reasoned that increased dietary levels of histidine should raise skin tUCA levels. If skin tUCA is the UVB photoreceptor for immune suppression, this increase should enhance UV-induced suppression of CHS. HPLC analysis of skin from BALB/c mice given a histidine-rich diet (10%) showed that the total amount of UCA is significantly higher in these animals than in mice fed a normal diet. Further, levels of suppression of CHS of 3% and 49% in control fed mice, induced by 4.8 and 7.2 kJ/m2 UVB were significantly increased to 21% and 71% respectively in histidine-fed animals at these same UVB doses. These findings provide additional support for the UCA model for immune suppression, and provide the first evidence that UV-induced immune suppression can be enhanced by a dietary component, L-histidine. PMID:1857737

  11. Elevated dietary linoleic acid increases gastric carcinoma cell invasion and metastasis in mice

    PubMed Central

    Matsuoka, T; Adair, J E; Lih, F B; Hsi, L C; Rubino, M; Eling, T E; Tomer, K B; Yashiro, M; Hirakawa, K; Olden, K; Roberts, J D

    2010-01-01

    Background: Dietary (n-6)-polyunsaturated fatty acids influence cancer development, but the mechanisms have not been well characterised in gastric carcinoma. Methods: We used two in vivo models to investigate the effects of these common dietary components on tumour metastasis. In a model of experimental metastasis, immunocompromised mice were fed diets containing linoleic acid (LA) at 2% (LLA), 8% (HLA) or 12% (VHLA) by weight and inoculated intraperitoneally (i.p.) with human gastric carcinoma cells (OCUM-2MD3). To model spontaneous metastasis, OCUM-2MD3 tumours were grafted onto the stomach walls of mice fed with the different diets. In in vitro assays, we investigated invasion and ERK phosphorylation of OCUM-2MD3 cells in the presence or absence of LA. Finally, we tested whether a cyclooxygenase (COX) inhibitor, indomethacin, could block peritoneal metastasis in vivo. Results: Both the HLA and VHLA groups showed increased incidence of tumour nodules (LA: 53% HLA: 89% VHLA: 100% P<0.03); the VHLA group also displayed increased numbers of tumour nodules and higher total volume relative to LLA group in experimental metastasis model. Both liver invasion (78%) and metastasis to the peritoneal cavity (67%) were more frequent in VHLA group compared with the LLA group (22% and 11%, respectively; P<0.03) in spontaneous metastasis model. We also found that the invasive ability of these cells is greatly enhanced when exposed to LA in vitro. Linoleic acid also increased invasion of other scirrhous gastric carcinoma cells, OCUM-12, NUGC3 and MKN-45. Linoleic acid effect on OCUM-2MD3 cells seems to be dependent on phosphorylation of ERK. The data suggest that invasion and phosphorylation of ERK were dependent on COX. Indomethacin decreased the number of tumours and total tumour volume in both LLA and VHLA groups. Finally, COX-1, which is known to be an important enzyme in the generation of bioactive metabolites from dietary fatty acids, appears to be responsible for the

  12. Twice-weekly consumption of farmed Atlantic salmon increases plasma content of phospholipid n-3 fatty acids

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Elevated intake of the n-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), is related to risk reduction of cardiovascular and other diseases. Increased consumption of seafood such as farmed Atlantic salmon is an effective way to consume n-3 but there is a paucity of data as ...

  13. Increased glutamate and homocysteine and decreased glutamine levels in autism: a review and strategies for future studies of amino acids in autism.

    PubMed

    Ghanizadeh, Ahmad

    2013-01-01

    There are many reports about the significant roles of some amino acids in neurobiology and treatment of autism. This is a critical review of amino acids levels in autism. No published review article about the level of amino acids in autism was found. The levels of glutamate and homocystein are increased in autism while the levels of glutamine and tryptophan are decreased. Findings regarding the plasma levels of taurine and lysine are controversial. The urinary levels of homocysteine and essential amino acids in both the untreated and treated autistic children are significantly less than those in the controls. The current literature suffers from many methodological shortcomings which needed to be considered in future studies. Some of them are age, gender, developmental level, autism symptoms severity, type of autism spectrum disorders, medical comorbidities, intelligent quotient, diet, concomitant medications, body mass index, and technical method of assessment of amino acids. PMID:24167375

  14. Omega-3 fatty acid docosahexaenoic acid increases SorLA/LR11, a sorting protein with reduced expression in sporadic Alzheimer's disease (AD): relevance to AD prevention.

    PubMed

    Ma, Qiu-Lan; Teter, Bruce; Ubeda, Oliver J; Morihara, Takashi; Dhoot, Dilsher; Nyby, Michael D; Tuck, Michael L; Frautschy, Sally A; Cole, Greg M

    2007-12-26

    Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential omega-3 fatty acid related to reduced AD risk and reduced Abeta accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Abeta production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD. PMID:18160637

  15. Reducing Isozyme Competition Increases Target Fatty Acid Accumulation in Seed Triacylglycerols of Transgenic Arabidopsis1[OPEN

    PubMed Central

    van Erp, Harrie; Shockey, Jay; Zhang, Meng; Adhikari, Neil D.; Browse, John

    2015-01-01

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on hydroxy fatty acids (HFAs) and conjugated polyenoic FAs (α-eleostearic acids [ESAs]) using Arabidopsis (Arabidopsis thaliana) as a model. These FAs are found naturally in seed oils of castor (Ricinus communis) and tung tree (Vernicia fordii), respectively, and used for the production of lubricants, nylon, and paints. Transgenic oils typically contain less target FA than that produced in the source species. We hypothesized that competition between endogenous and transgenic isozymes for substrates limits accumulation of unique FAs in Arabidopsis seeds. This hypothesis was tested by introducing a mutation in Arabidopsis diacylglycerol acyltransferase1 (AtDGAT1) in a line expressing castor FA hydroxylase and acyl-Coenzyme A:RcDGAT2 in its seeds. This led to a 17% increase in the proportion of HFA in seed oil. Expression of castor phospholipid:diacylglycerol acyltransferase 1A in this line increased the proportion of HFA by an additional 12%. To determine if our observations are more widely applicable, we investigated if isozyme competition influenced production of ESA. Expression of tung tree FA conjugase/desaturase in Arabidopsis produced approximately 7.5% ESA in seed lipids. Coexpression of VfDGAT2 increased ESA levels to approximately 11%. Overexpression of VfDGAT2 combined with suppression of AtDGAT1 increased ESA accumulation to 14% to 15%. Our results indicate that isozyme competition is a limiting factor in the engineering of unusual FAs in heterologous plant systems and that reduction of competition through mutation and RNA suppression may be a useful component of seed metabolic engineering strategies. PMID:25739701

  16. Acute Administration of Branched-Chain Amino Acids Increases the Pro-BDNF/Total-BDNF Ratio in the Rat Brain.

    PubMed

    Scaini, Giselli; Morais, Meline O S; Furlanetto, Camila B; Kist, Luiza W; Pereira, Talita C B; Schuck, Patrícia F; Ferreira, Gustavo C; Pasquali, Matheus A B; Gelain, Daniel P; Moreira, José Cláudio F; Bogo, Maurício R; Streck, Emilio L

    2015-05-01

    Maple syrup urine disease (MSUD) is caused by an inborn error in metabolism resulting from a deficiency in the branched-chain α-keto acid dehydrogenase complex activity. This blockage leads to accumulation of the branched-chain amino acids (BCAA) leucine, isoleucine and valine, as well as their corresponding α-keto acids and α-hydroxy acids. High levels of BCAAs are associated with neurological dysfunction and the role of pro- and mature brain-derived neurotrophic factor (BDNF) in the neurological dysfunction of MSUD is still unclear. Thus, in the present study we investigated the effect of an acute BCAA pool administration on BDNF levels and on the pro-BDNF cleavage-related proteins S100A10 and tissue plasminogen activator (tPA) in rat brains. Our results demonstrated that acute Hyper-BCAA (H-BCAA) exposure during the early postnatal period increases pro-BDNF and total-BDNF levels in the hippocampus and striatum. Moreover, tPA levels were significantly decreased, without modifications in the tPA transcript levels in the hippocampus and striatum. On the other hand, the S100A10 mRNA and S100A10 protein levels were not changed in the hippocampus and striatum. In the 30-day-old rats, we observed increased pro-BDNF, total-BDNF and tPA levels only in the striatum, whereas the tPA and S100A10 mRNA expression and the immunocontent of S100A10 were not altered. In conclusion, we demonstrated that acute H-BCAA administration increases the pro-BDNF/total-BDNF ratio and decreases the tPA levels in animals, suggesting that the BCAA effect may depend, at least in part, on changes in BDNF post-translational processing. PMID:25681161

  17. Increase of Unsaturated Fatty Acids (Low Melting Point) of Broiler Fatty Waste Obtained Through Staphylococcus xylosus Fermentation.

    PubMed

    Marques, Roger V; Duval, Eduarda H; Corrêa, Luciara B; Corrêa, Érico K

    2015-11-01

    The increasing rise in the production of meat around the world causes a significant generation of agro-industrial waste--most of it with a low value added. Fatty wastes have the potential of being converted into biodiesel, given the overcome of technological and economical barriers, as well as its presentation in solid form. Therefore, the aim of this work was to investigate the capacity of Staphylococcus xylosus strains to modify the chemical structure of chicken fatty wastes intending to reduce the melting points of the wastes to mild temperatures, thereby breaking new ground in the production of biodiesel from these sources in an economically attractive and sustainable manner. The effects in time of fermentation and concentration of the fat in the medium were investigated, assessing the melting point and profile of fatty acids. The melting temperature showed a decrease of approximately 22 °C in the best operational conditions, due to reduction in the content of saturated fatty acids (high melting point) and increase of unsaturated fatty acids (low melting point). PMID:26289722

  18. Organic amendments increase soil solution phosphate concentrations in an acid soil: A controlled environment study

    SciTech Connect

    Schefe, C.R.; Patti, A.F.; Clune, T.S.; Jackson, R.

    2008-04-15

    Soil acidification affects at least 4 million hectares of agricultural land in Victoria, Australia. Low soil pH can inhibit plant growth through increased soluble aluminum (Al) concentrations and decreased available phosphorus (P). The addition of organic amendments may increase P availability through competition for P binding sites, solubilization of poorly soluble P pools, and increased solution pH. The effect of two organic amendments (lignite and compost) on P solubility in an acid soil was determined through controlled environment (incubation) studies. Three days after the addition of lignite and compost, both treatments increased orthophosphate and total P measured in soil solution, with the compost treatments having the greatest positive effect. Increased incubation time (26 days) increased soil solution P concentrations in both untreated and amended soils, with the greatest effect seen in total P concentrations. The measured differences in solution P concentrations between the lignite- and compost-amended treatments were likely caused by differences in solution chemistry, predominantly solution pH and cation dynamics. Soil amendment with lignite or compost also increased microbial activity in the incubation systems, as measured by carbon dioxide respiration. Based on the results presented, it is proposed that the measured increase in soil solution P with amendment addition was likely caused by both chemical and biological processes, including biotic and abiotic P solubilization reactions, and the formation of soluble organic-metal complexes.

  19. Inhibiting the platelet derived growth factor receptor increases signs of retinoic acid syndrome in myeloid differentiated HL- 60 cells

    PubMed Central

    Reiterer, Gudrun; Bunaciu, Rodica P.; Smith, James L.; Yen, Andrew

    2008-01-01

    PDGFR inhibitors are successfully used in a number of cancer treatments. The standard treatment for acute promyelocytic leukemia (APL) involves differentiation therapy with retinoic acid (RA). However, the relapse rates are significant. In the present work we evaluated the effects of RA therapy in the presence of PDGFR inhibitor, AG1296. Adding AG1296 with RA increased secretion of TNF-α, IL-8, and MMP-9 expression. This treatment induced higher levels of ICAM-1 endothelial cell expression, and increased cellular mobility. Inhibiting PDGFR enhanced RA-induced expression of integrin. Integrin ligand increased differentiation markers CD11b, inducible oxidative metabolism and PDGFR-â phosphorylation. While the neutrophil- endothelial cell interactions are strengthened by the combined treatment, the endotheliumsubstratum interactions are weakened, a situation common in RAS. PMID:18571505

  20. Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

    PubMed

    Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

    2015-05-01

    Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others. PMID:25584779

  1. Significant increase in trisomy 21 in Berlin nine months after the Chernobyl reactor accident: temporal correlation or causal relation?

    PubMed Central

    Sperling, K.; Pelz, J.; Wegner, R. D.; Dörries, A.; Grüters, A.; Mikkelsen, M.

    1994-01-01

    OBJECTIVE--To assess whether the increased prevalence of trisomy 21 in West Berlin in January 1987 might have been causally related to exposure to ionising radiation as a result of the Chernobyl reactor accident or was merely a chance event. DESIGN--Analysis of monthly prevalence of trisomy 21 in West Berlin from January 1980 to December 1989. SETTING--Confines of West Berlin. RESULTS--Owing to the former "island" situation of West Berlin and its well organised health services, ascertainment of trisomy 21 was thought to be almost complete. A cluster of 12 cases occurred in January 1987 as compared with two or three expected. After exclusion of factors that might have explained the increase, including maternal age distribution, only exposure to radiation as a result of the Chernobyl reactor accident remained. In six of seven cases that could be studied cytogenetically the extra chromosome was of maternal origin, confirming that nondisjunction had occurred at about the time of conception. CONCLUSION--On the basis of two assumptions--(a) that maternal meiosis is an error prone process susceptible to exogenous factors at the time of conception; (b) that owing to the high prevalence of iodine deficiency in Berlin a large amount of iodine-131 would have been accumulated over a short period--it is concluded that the increased prevalence of trisomy 21 in West Berlin in January 1987 was causally related to a short period of exposure to ionising radiation as a result of the Chernobyl reactor accident. PMID:8044094

  2. Serum Sialic Acid Level Is Significantly Associated with Nonalcoholic Fatty Liver Disease in a Nonobese Chinese Population: A Cross-Sectional Study

    PubMed Central

    Lu, Zhenya; Ma, Han; Xu, Chengfu; Shao, Zhou; Cen, Chao; Li, Youming

    2016-01-01

    Background/Aim. To investigate the association between serum sialic acid (SA) levels and nonalcoholic fatty liver disease (NAFLD) in a nonobese Chinese population. Methods. A cross-sectional study was performed among the 5916 adults who took their annual health examinations at International Health Care Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, from December 2013 to November 2014. Results. A total of 693 (11.71%) subjects fulfilled the diagnostic criteria of NAFLD, and NAFLD patients had significantly higher serum SA levels than controls (P < 0.001). The prevalence of NAFLD was positively associated with serum SA levels (P for trend <0.001). Serum sialic acid levels are significantly associated with features of metabolic syndrome (Ps < 0.01). Multivariate logistic regression analysis showed that serum SA level was significantly associated with risk for NAFLD (odds ratio: 1.018, 95%; confidence interval: 1.007–1.030; P = 0.002). Conclusions. Our results suggest for the first time that NAFLD patients had higher serum SA level than controls, and increased serum SA level is significantly associated with risk for NAFLD in a large nonobese Chinese population. PMID:27042666

  3. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.

    PubMed

    Kottyan, Leah C; Collier, Ann R; Cao, Khanh H; Niese, Kathryn A; Hedgebeth, Megan; Radu, Caius G; Witte, Owen N; Khurana Hershey, Gurjit K; Rothenberg, Marc E; Zimmermann, Nives

    2009-09-24

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5'-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase-dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  4. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner

    PubMed Central

    Kottyan, Leah C.; Collier, Ann R.; Cao, Khanh H.; Niese, Kathryn A.; Hedgebeth, Megan; Radu, Caius G.; Witte, Owen N.; Khurana Hershey, Gurjit K.; Rothenberg, Marc E.

    2009-01-01

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5′-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase–dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65−/− mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  5. AMP kinase activation with AICAR further increases fatty acid oxidation and blunts triacylglycerol hydrolysis in contracting rat soleus muscle

    PubMed Central

    Smith, Angela C; Bruce, Clinton R; Dyck, David J

    2005-01-01

    Muscle contraction increases glucose uptake and fatty acid (FA) metabolism in isolated rat skeletal muscle, due at least in part to an increase in AMP-activated kinase activity (AMPK). However, the extent to which AMPK plays a role in the regulation of substrate utilization during contraction is not fully understood. We examined the acute effects of 5-aminoimidazole-4-carboxamide riboside (AICAR; 2 mm), a pharmacological activator of AMPK, on FA metabolism and glucose oxidation during high intensity tetanic contraction in isolated rat soleus muscle strips. Muscle strips were exposed to two different FA concentrations (low fatty acid, LFA, 0.2 mm; high fatty acid, HFA, 1 mm) to examine the role that FA availability may play in both exogenous and endogenous FA metabolism with contraction and AICAR. Synergistic increases in AMPK α2 activity (+45%; P < 0.05) were observed after 30 min of contraction with AICAR, which further increased exogenous FA oxidation (LFA: +71%, P < 0.05; HFA: +46%, P < 0.05) regardless of FA availability. While there were no changes in triacylglycerol (TAG) esterification, AICAR did increase the ratio of FA partitioned to oxidation relative to TAG esterification (LFA: +65%, P < 0.05). AICAR significantly blunted endogenous TAG hydrolysis (LFA: −294%, P < 0.001; HFA: −117%, P < 0.05), but had no effect on endogenous oxidation rates, suggesting a better matching between TAG hydrolysis and subsequent oxidative needs of the muscle. There was no effect of AICAR on the already elevated rates of glucose oxidation during contraction. These results suggest that FA metabolism is very sensitive to AMPK α2 stimulation during contraction. PMID:15774529

  6. Peanut consumption increases levels of plasma very long chain fatty acids in humans.

    PubMed

    Lam, Christina; Wong, Derek; Cederbaum, Stephen; Lim, Bennie; Qu, Yong

    2012-11-01

    Peanut consumption has been suspected of raising plasma very long chain fatty acid (VLCFA) levels in humans. The effect of peanut consumption on VLCFAs was studied in six human subjects. After 3 to 4h of peanut butter ingestion, plasma C26:0 and C26:0/C22:0 were found to be significantly elevated to levels seen in patients with peroxisomal disorders. These levels returned to normal within 12h. Peanut consumption needs to be accounted for when interpreting VLCFAs. PMID:22864056

  7. Aspartame and sucrose produce a similar increase in the plasma phenylalanine to large neutral amino acid ratio in healthy subjects.

    PubMed

    Burns, T S; Stargel, W W; Tschanz, C; Kotsonis, F N; Hurwitz, A

    1991-01-01

    Aspartame (L-aspartyl-L-phenylalanine methyl ester) consumption has been postulated to increase brain phenylalanine levels by increasing the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids (Phe/LNAA). Dietary manipulations with carbohydrate or protein can also produce changes in the Phe/LNAA value. To compare the effects of aspartame and carbohydrate on Phe/LNAA, beverages sweetened with aspartame, sucrose, and aspartame plus sucrose, and unsweetened beverage were ingested by 8 healthy, fasted subjects in a randomized, four-way crossover design. The beverages were sweetened with an amount of aspartame (500 mg) and/or sucrose (100 g) approximately equivalent to that used to sweeten 1 liter of soft drink. The baseline-corrected plasma Phe/LNAA values did not differ significantly following ingestion of aspartame or sucrose. Following aspartame alone, the high mean ratio increased 26% over baseline 1 h after ingestion. Following sucrose alone, the high mean ratio increased 19% at 2.5 h. Sucrose increased the Phe/LNAA value due to an insulin-mediated decrease in the plasma LNAA, while aspartame increased the ratio by increasing the plasma Phe concentration. These findings indicate that similar increases in plasma Phe/LNAA occur when healthy, fasting subjects ingest amounts of equivalent sweetness of sucrose or aspartame. PMID:1771173

  8. Acidic Residues in the Hfq Chaperone Increase the Selectivity of sRNA Binding and Annealing.

    PubMed

    Panja, Subrata; Santiago-Frangos, Andrew; Schu, Daniel J; Gottesman, Susan; Woodson, Sarah A

    2015-11-01

    Hfq facilitates gene regulation by small non-coding RNAs (sRNAs), thereby affecting bacterial attributes such as biofilm formation and virulence. Escherichia coli Hfq recognizes specific U-rich and AAN motifs in sRNAs and target mRNAs, after which an arginine patch on the rim promotes base pairing between their complementary sequences. In the cell, Hfq must discriminate between many similar RNAs. Here, we report that acidic amino acids lining the sRNA binding channel between the inner pore and rim of the Hfq hexamer contribute to the selectivity of Hfq's chaperone activity. RNase footprinting, in vitro binding and stopped-flow fluorescence annealing assays showed that alanine substitution of D9, E18 or E37 strengthened RNA interactions with the rim of Hfq and increased annealing of non-specific or U-tailed RNA oligomers. Although the mutants were less able than wild-type Hfq to anneal sRNAs with wild-type rpoS mRNA, the D9A mutation bypassed recruitment of Hfq to an (AAN)4 motif in rpoS, both in vitro and in vivo. These results suggest that acidic residues normally modulate access of RNAs to the arginine patch. We propose that this selectivity limits indiscriminate target selection by E. coli Hfq and enforces binding modes that favor genuine sRNA and mRNA pairs. PMID:26196441

  9. Hematological Indices in Malian Children Change Significantly During a Malaria Season and with Increasing Age: Implications for Malaria Epidemiological Studies.

    PubMed

    Diakite, Mahamadou; Miura, Kazutoyo; Diouf, Ababacar; Konate, Drissa; Keita, Abdoul S; Doumbia, Saibou; Diakite, Seidina; Traore, Karim; Doumbouya, Mory; Anderson, Jennifer M; Fairhurst, Rick M; Long, Carole A

    2016-08-01

    Standard hematological indices are commonly used in malaria epidemiological studies to measure anemia prevalence and calculate blood parasite densities. In Africa, few studies have investigated how these indices change during a malaria transmission season and with increasing age. To address these knowledge gaps, we collected blood from 169 healthy Malian children aged 3-12 years before (May 2010) and after (January 2011) a transmission season. Red blood cell (RBC) count, hemoglobin (Hb) level, hematocrit (Ht), white blood cell (WBC) count, and WBC subsets were measured in paired blood samples, and the data were stratified by month (May, January) and age group (3-5, 6-8, and 9-12 years). From May to January, RBC count (4.53-4.70 × 10(6)/μL; P < 0.0001), Hb level (11.5-11.9 g/dL; P < 0.0001), and Ht (37.1-39.2%; P < 0.0001) increased, and WBC count (6.46-5.96 × 10(3)/μL; P = 0.0006) decreased. From May to January, the prevalence of WBC subsets also changed: 35-43% neutrophils, 6.5-7.6% monocytes, and 53-45% lymphocytes (P < 0.001). These seasonal changes were not associated with the number of malaria episodes experienced in the interim or the presence of RBC polymorphisms. In May, Hb (11.2, 11.4, and 11.8 g/dL; P = 0.0013) and Ht (36.5%, 36.7%, and 38.1%; P = 0.0154) increased and WBC count (8.04, 6.43, and 5.76 × 10(3)/μL; P < 0.0001) decreased with age group; similar differences were observed in January. These data suggest that season- and age-based reference values for hematological indices are needed to better estimate anemia prevalence and parasite density in malaria epidemiological studies. PMID:27296389

  10. Antiangiogenic agents significantly improve survival in tumor-bearing mice by increasing tolerance to chemotherapy-induced toxicity

    PubMed Central

    Zhang, Danfang; Hedlund, Eva-Maria E.; Lim, Sharon; Chen, Fang; Zhang, Yin; Sun, Baocun; Cao, Yihai

    2011-01-01

    Chemotherapy-induced broad toxicities are the leading cause of the drug-induced mortality in cancer patients. Antiangiogenic drugs (ADs) in combination with chemotherapy are widely used as front-line therapy for the treatment of various human cancers. However, the beneficial mechanisms underlying combination therapy are poorly understood. Here we show that, in several murine tumor models, administration of sunitinib markedly reduced chemotherapy-induced bone marrow toxicity. Intriguingly, in a sequential treatment regimen, delivery of ADs followed by chemotherapy demonstrated superior survival benefits compared with simultaneous administration of two drugs. In murine tumor models, we show that VEGF increased chemotoxicity by synergistically suppressing bone marrow hematopoiesis with cytostatic drugs. These findings shed light on molecular mechanisms by which ADs in combination with chemotherapy produce survival benefits in cancer patients and provide conceptual information guiding future designs of clinical trials, current practice, and optimization of ADs for the treatment of cancer. PMID:21367692

  11. Experimentally caused proliferation of lysosomes in cultured BHK cells involving an increase of biphosphatidic acids and triglycerides.

    PubMed

    Brotherus, J; Niinioja, T; Sandelin, K; Renkonen, O

    1977-05-01

    When cultured hamster fibroblasts (BHK 21 cells) were incubated in a synthetic serum-free medium up to 4 days, they developed signs of a progressive proliferation of lysosomes. The cells became filled with vacuoles that contained polymorphic debris and showed acid phosphatase activity. The specific activities of acid protease and acid phosphatase in the cell cultures increased three- to fourfold. The process was accompanied by a marked decrease in the contents of protein, deoxyribonucleic acid, and total phospholipids of the cultures. The concentration of lysobisphosphatidic acid increased during the incubation from about 1.5% to 3-6% of the cellular phospholipids. The concentrations of two related lipids, bisphosphatidic acid and semilysobisphosphatidic acid also increased substantially. The triglyceride content of the cells increased several fold, whereas the concentration of phosphatidylcholine decreased markedly. Lysobisphosphatidic acid did not increase upon induction of vacuolization by exogenous sucrose, nor when there was an accumulation of triglyceride due to addition of oleic acid to the growth medium. These findings suggest that the formation of the bisphosphatidic acids may be specifically linked to the autolysis of the phospholipids of the cellular membranes and the formation of triglycerides associated with this process. PMID:864326

  12. Significant increase in Young's modulus of ATDC5 cells during chondrogenic differentiation induced by PAMPS/PDMAAm double-network gel: comparison with induction by insulin.

    PubMed

    Maeda, Eijiro; Tsutsumi, Takehiro; Kitamura, Nobuto; Kurokawa, Takayuki; Ping Gong, Jian; Yasuda, Kazunori; Ohashi, Toshiro

    2014-10-17

    A double-network (DN) gel, which was composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated the biomechanical and biological responses of chondrogenic progenitor ATDC5 cells cultured on the DN gel. ATDC5 cells were cultured on a polystyrene surface without insulin (Culture 1) and with insulin (Culture 2), and on the DN gel without insulin (Culture 3). The cultured cells were evaluated using micropipette aspiration for cell Young's modulus and qPCR for gene expression of chondrogenic and actin organization markers on days 3, 7 and 14. On day 3, the cells in Culture 3 formed nodules, in which the cells exhibited an actin cortical layer inside them, and gene expression of type-II collagen, aggrecan, and SOX9 was significantly higher in Culture 3 than Cultures 1 and 2 (p<0.05). Young's modulus in Culture 3 was significantly higher than that in Culture 1 throughout the testing period (p<0.05) and that in Culture 2 on day 14 (p<0.01). There was continuous expression of actin organization markers in Culture 3. This study highlights that the cells on the DN gel increased the modulus and mRNA expression of chondrogenic markers at an earlier time point with a greater magnitude compared to those on the polystyrene surface with insulin. This study also demonstrates a possible strong interrelation among alteration of cell mechanical properties, changes in actin organization and the induction of chondrogenic differentiation. PMID:25110167

  13. Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit

    PubMed Central

    2014-01-01

    Background Children with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial. Objective The objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies. Results Eighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females. In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known. The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty. Conclusion Our experience was quite positive with normalization of

  14. Adverse effects of free fatty acid associated with increased oxidative stress in postischemic isolated rat hearts.

    PubMed

    Gambert, Ségolène; Vergely, Catherine; Filomenko, Rodolphe; Moreau, Daniel; Bettaieb, Ali; Opie, Lionel H; Rochette, Luc

    2006-02-01

    The mechanisms of the adverse effects of free fatty acids on the ischemic-reperfused myocardium are not fully understood. Long-chain fatty acids, including palmitate, uncouple oxidative phosphorylation and should therefore promote the formation of oxygen-derived free radicals, with consequent adverse effects. Conversely, the antianginal agent trimetazidine (TMZ), known to inhibit cardiac fatty acid oxidation, could hypothetically lessen the formation of reactive oxygen species (ROS) and thus improve reperfusion mechanical function. Isolated perfused rat hearts underwent 30 min of total global ischemia followed by 30 min of reperfusion. Hearts were perfused with glucose 5.5 mmol/l or palmitate 1.5 mmol/l with or without TMZ (100 micromol/l). Ascorbyl free radical (AFR) release during perfusion periods was measured by electron spin resonance as a marker of oxidative stress. Post-ischemic recovery in the palmitate group of heart was lower than in the glucose group with a marked rise in diastolic tension and reduction in left ventricular developed pressure (Glucose: 85 +/- 11 mmHg; Palmitate: 10 +/- 6 mmHg; p < 0.001). TMZ decreased diastolic tension in both glucose- and in palmitate-perfused hearts. Release of AFR within the first minute of reperfusion was greater in palmitate-perfused hearts and in hearts perfused with either substrate, this marker of oxidative stress was decreased by TMZ (expressed in arbitrary units/ml; respectively: 8.49 +/- 1.24 vs. 1.06 +/- 0.70 p < 0.05; 12.47 +/- 2.49 vs. 3.37 +/- 1.29 p < 0.05). Palmitate increased the formation of ROS and reperfusion contracture. TMZ, a potential inhibitor of palmitate-induced mitochondrial uncoupling, decreased the formation of free radicals and improved postischemic mechanical dysfunction. The novel conclusion is that adverse effects of fatty acids on ischemic-reperfusion injury may be mediated, at least in part, by oxygen-derived free radicals. PMID:16444597

  15. N- and C-terminal truncations of a GH10 xylanase significantly increase its activity and thermostability but decrease its SDS resistance.

    PubMed

    Zheng, Fei; Huang, Jingxuan; Liu, Xingchen; Hu, Hang; Long, Liangkun; Chen, Kaixiang; Ding, Shaojun

    2016-04-01

    XynII from Volvariella volvacea has high sodium dodecyl sulfate (SDS) resistance, with the potential for industrial applications under harsh conditions. It consists of a single glycoside hydrolase family 10 (GH10) catalytic domain but contains an additional unique 10 and 4 amino acid residues at the N- and C-terminus, respectively. In this study, five XynII derivatives with N- and/or C-terminus deletions were constructed to determine the effects of these regions on enzyme activity, substrate specificity, thermostability, and SDS resistance. Our results revealed that N- and/or C-terminal truncations significantly increased enzyme activity and thermostability, but reduced SDS resistance. Specifically, the XynIIΔNC4 mutant had 2.53-fold more catalytic efficiency (k cat/K m) towards beechwood xylan than wild-type and 3.0-fold more thermostability (t 1/2 [55°C]). XynIIΔNC4 displayed 3.33-, 4.38-, 1.37-, and 1.98-fold more activity against xylotriose, xylotetraose, xylopentaose, and xylohexaose, respectively, than XynII did. However, its half-life (t 1/2) in 4 % SDS was only 1.72 h, while that of XynII was 4.65 h. Circular dichroism analysis revealed that deletion of N- and C-terminal segments caused minor changes in secondary structure. Our observations suggest that the extra N- and C-terminal segments in wild-type XynII evolved to strengthen the interaction between these regions of the protein, making the local structure more rigid and reducing structural flexibility. In this way, N- and C-terminal truncations increased the thermostability and activity of XynII on different xylans and linear xylooligosaccharides, but reduced its resistance to SDS. PMID:26621803

  16. Irrigation Is Significantly Associated with an Increased Prevalence of Listeria monocytogenes in Produce Production Environments in New York State.

    PubMed

    Weller, Daniel; Wiedmann, Martin; Strawn, Laura K

    2015-06-01

    Environmental (i.e., meteorological and landscape) factors and management practices can affect the prevalence of foodborne pathogens in produce production environments. This study was conducted to determine the prevalence of Listeria monocytogenes, Listeria species (including L. monocytogenes), Salmonella, and Shiga toxin-producing Escherichia coli (STEC) in produce production environments and to identify environmental factors and management practices associated with their isolation. Ten produce farms in New York State were sampled during a 6-week period in 2010, and 124 georeferenced samples (80 terrestrial, 33 water, and 11 fecal) were collected. L. monocytogenes, Listeria spp., Salmonella, and STEC were detected in 16, 44, 4, and 5% of terrestrial samples, 30, 58, 12, and 3% of water samples, and 45, 45, 27, and 9% of fecal samples, respectively. Environmental factors and management practices were evaluated for their association with terrestrial samples positive for L. monocytogenes or other Listeria species by univariate logistic regression; analysis was not conducted for Salmonella or STEC because the number of samples positive for these pathogens was low. Although univariate analysis identified associations between isolation of L. monocytogenes or Listeria spp. from terrestrial samples and various water-related factors (e.g., proximity to wetlands and precipitation), multivariate analysis revealed that only irrigation within 3 days of sample collection was significantly associated with isolation of L. monocytogenes (odds ratio = 39) and Listeria spp. (odds ratio = 5) from terrestrial samples. These findings suggest that intervention at the irrigation level may reduce the risk of produce contamination. PMID:26038903

  17. Periplasmic Acid Stress Increases Cell Division Asymmetry (Polar Aging) of Escherichia coli

    PubMed Central

    Clark, Michelle W.; Yie, Anna M.; Eder, Elizabeth K.; Dennis, Richard G.; Basting, Preston J.; Martinez, Keith A.; Jones, Brian D.; Slonczewski, Joan L.

    2015-01-01

    Under certain kinds of cytoplasmic stress, Escherichia coli selectively reproduce by distributing the newer cytoplasmic components to new-pole cells while sequestering older, damaged components in cells inheriting the old pole. This phenomenon is termed polar aging or cell division asymmetry. It is unknown whether cell division asymmetry can arise from a periplasmic stress, such as the stress of extracellular acid, which is mediated by the periplasm. We tested the effect of periplasmic acid stress on growth and division of adherent single cells. We tracked individual cell lineages over five or more generations, using fluorescence microscopy with ratiometric pHluorin to measure cytoplasmic pH. Adherent colonies were perfused continually with LBK medium buffered at pH 6.00 or at pH 7.50; the external pH determines periplasmic pH. In each experiment, cell lineages were mapped to correlate division time, pole age and cell generation number. In colonies perfused at pH 6.0, the cells inheriting the oldest pole divided significantly more slowly than the cells inheriting the newest pole. In colonies perfused at pH 7.50 (near or above cytoplasmic pH), no significant cell division asymmetry was observed. Under both conditions (periplasmic pH 6.0 or pH 7.5) the cells maintained cytoplasmic pH values at 7.2–7.3. No evidence of cytoplasmic protein aggregation was seen. Thus, periplasmic acid stress leads to cell division asymmetry with minimal cytoplasmic stress. PMID:26713733

  18. Abscisic acid deficiency increases defence responses against Myzus persicae in Arabidopsis.

    PubMed

    Hillwig, Melissa S; Chiozza, Mariana; Casteel, Clare L; Lau, Siau Ting; Hohenstein, Jessica; Hernández, Enrique; Jander, Georg; MacIntosh, Gustavo C

    2016-02-01

    Comparison of Arabidopsis thaliana (Arabidopsis) gene expression induced by Myzus persicae (green peach aphid) feeding, aphid saliva infiltration and abscisic acid (ABA) treatment showed a significant positive correlation. In particular, ABA-regulated genes are over-represented among genes that are induced by M. persicae saliva infiltration into Arabidopsis leaves. This suggests that the induction of ABA-related gene expression could be an important component of the Arabidopsis-aphid interaction. Consistent with this hypothesis, M. persicae populations induced ABA production in wild-type plants. Furthermore, aphid populations were smaller on Arabidopsis aba1-1 mutants, which cannot synthesize ABA, and showed a significant preference for wild-type plants compared with the mutant. Total free amino acids, which play an important role in aphid nutrition, were not altered in the aba1-1 mutant line, but the levels of isoleucine (Ile) and tryptophan (Trp) were differentially affected by aphids in wild-type and mutant plants. Recently, indole glucosinolates have been shown to promote aphid resistance in Arabidopsis. In this study, 4-methoxyindol-3-ylmethylglucosinolate was more abundant in the aba1-1 mutant than in wild-type Arabidopsis, suggesting that the induction of ABA signals that decrease the accumulation of defence compounds may be beneficial for aphids. PMID:25943308

  19. Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.

    PubMed

    Poreba, Marcin; Mihelic, Marko; Krai, Priscilla; Rajkovic, Jelena; Krezel, Artur; Pawelczak, Malgorzata; Klemba, Michael; Turk, Dusan; Turk, Boris; Latajka, Rafal; Drag, Marcin

    2014-04-01

    Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad range of unnatural amino acids. Our approach identified very efficiently hydrolyzed substrates containing unnatural amino acids, which resulted in the design of significantly better substrates than those previously known. Additionally, in this study significant differences in terms of the structures of optimal substrates for human and malarial orthologs are important from the therapeutic point of view. These data can be also used for the design of specific inhibitors or activity-based probes. PMID:24381006

  20. Hesperetin Modifies the Composition of Fecal Microbiota and Increases Cecal Levels of Short-Chain Fatty Acids in Rats.

    PubMed

    Unno, Tomonori; Hisada, Takayoshi; Takahashi, Shunsuke

    2015-09-16

    There has been particular interest in the prebiotic-like effects of commonly consumed polyphenols. This study aimed to evaluate the effects of hesperidin (HD) and its aglycone hesperetin (HT), major flavonoids in citrus fruits, on the structure and activity of gut microbiota in rats. Rats ingested an assigned diet (a control diet, a 0.5% HT diet, or a 1.0% HD diet) for 3 weeks. Terminal restriction fragment length polymorphism analysis revealed that the proportion of Clostridium subcluster XIVa in the feces collected at the third week of feeding was significantly reduced by the HT diet: 19.8 ± 4.3% for the control diet versus 5.3 ± 1.5% for the HT diet (P < 0.01). There was a significant difference in the cecal pool of short-chain fatty acids (SCFA), the sum of acetic, propionic, and butyric acids, between the control diet (212 ± 71 μmol) and the HT diet (310 ± 51 μmol) (P < 0.05), whereas the HD diet exhibited no effects (245 ± 51 μmol). Interestingly, dietary HT resulted in a significant increase in the excretion of starch in the feces. HT, but not HD, might reduce starch digestion, and parts of undigested starch were utilized to produce SCFA by microbial fermentation in the large intestine. PMID:26306898

  1. Resistance of essential fatty acid-deficient rats to endotoxin-induced increases in vascular permeability

    SciTech Connect

    Li, E.J.; Cook, J.A.; Spicer, K.M.; Wise, W.C.; Rokach, J.; Halushka, P.V. )

    1990-06-01

    Resistance to endotoxin in essential fatty acid-deficient (EFAD) rats is associated with reduced synthesis of certain arachidonic acid metabolites. It was hypothesized that EFAD rats would manifest decreased vascular permeability changes during endotoxemia as a consequence of reduced arachidonic acid metabolism. To test this hypothesis, changes in hematocrit (HCT) and mesenteric localization rate of technetium-labeled human serum albumin (99mTc-HSA) and red blood cells (99mTc-RBC) were assessed in EFAD and normal rats using gamma-camera imaging. Thirty minutes after Salmonella enteritidis endotoxin, EFAD rats exhibited less hemoconcentration as determined by % HCT than normal rats. Endotoxin caused a less severe change in permeability index in the splanchnic region in EFAD rats than in normal rats (1.2 +/- 0.6 x 10(-3)min-1 vs. 4.9 +/- 1.7 x 10(-3)min-1 respectively, P less than 0.05). In contrast to 99mTc-HSA, mesenteric localization of 99mTc-RBC was not changed by endotoxin in control or EFAD rats. Supplementation with ethyl-arachidonic acid did not enhance susceptibility of EFAD rats to endotoxin-induced splanchnic permeability to 99mTc-HSA. Leukotrienes have been implicated as mediators of increased vascular permeability in endotoxin shock. Since LTC3 formation has been reported to be increased in EFA deficiency, we hypothesized that LTC3 may be less potent than LTC4. Thus the effect of LTC3 on mean arterial pressure and permeability was compared to LTC4 in normal rats. LTC3-induced increases in peak mean arterial pressure were less than LTC4 at 10 micrograms/kg (39 +/- 5 mm Hg vs. 58 +/- 4 mm Hg respectively, P less than 0.05) and at 20 micrograms/kg (56 +/- 4 mm Hg vs. 75 +/- 2 mm Hg respectively, P less than 0.05). LY171883 (30 mg/kg), an LTD4/E4 receptor antagonist, attenuated the pressor effect of LTC4, LTD4, and LTC3.

  2. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort

    PubMed Central

    Clarke, Alan T.; Johnson, Paul C. D.; Hall, Gillian C.; Ford, Ian; Mills, Peter R.

    2016-01-01

    Background & Aims Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment. Methods The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions. Results Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4–2.6]. High dose was classified as 40–80mg daily and low dose 10–20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2–12.7] for HDA, 1.4 [0.9–2.0] for LDA and 1.5 [1.0–2.2] for HDS. Conclusions The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small. PMID:26983033

  3. Metabolic profiling of plasma amino acids shows that histidine increases following the consumption of pork

    PubMed Central

    Samman, Samir; Crossett, Ben; Somers, Miles; Bell, Kirstine J; Lai, Nicole T; Sullivan, David R; Petocz, Peter

    2014-01-01

    Amino acid (AA) status is determined by factors including nutrition, metabolic rate, and interactions between the metabolism of AA, carbohydrates, and lipids. Analysis of the plasma AA profile, together with markers of glucose and lipid metabolism, will shed light on metabolic regulation. The objectives of this study were to investigate the acute responses to the consumption of meals containing either pork (PM) or chicken (CM), and to identify relationships between plasma AA and markers of glycemic and lipemic control. A secondary aim was to explore AA predictors of plasma zinc concentrations. Ten healthy adults participated in a postprandial study on two separate occasions. In a randomized cross-over design, participants consumed PM or CM. The concentrations of 21 AA, glucose, insulin, triglycerides, nonesterified fatty acids, and zinc were determined over 5 hours postprandially. The meal composition did not influence glucose, insulin, triglyceride, nonesterified fatty acid, or zinc concentrations. Plasma histidine was higher following the consumption of PM (P=0.014), with consistently higher changes observed after 60 minutes (P<0.001). Greater percentage increases were noted at limited time points for valine and leucine + isoleucine in those who consumed CM compared to PM. In linear regression, some AAs emerged as predictors of the metabolic responses, irrespective of the meal that was consumed. The present study demonstrates that a single meal of PM or CM produces a differential profile of AA in the postprandial state. The sustained increase in histidine following the consumption of a PM is consistent with the reported effects of lean pork on cardiometabolic risk factors. PMID:24971025

  4. Increased Missense Mutation Burden of Fatty Acid Metabolism Related Genes in Nunavik Inuit Population

    PubMed Central

    Zhou, Sirui; Xiong, Lan; Xie, Pingxing; Ambalavanan, Amirthagowri; Bourassa, Cynthia V.; Dionne-Laporte, Alexandre; Spiegelman, Dan; Turcotte Gauthier, Maude; Henrion, Edouard; Diallo, Ousmane; Dion, Patrick A.; Rouleau, Guy A.

    2015-01-01

    Background Nunavik Inuit (northern Quebec, Canada) reside along the arctic coastline where for generations their daily energy intake has mainly been derived from animal fat. Given this particular diet it has been hypothesized that natural selection would lead to population specific allele frequency differences and unique variants in genes related to fatty acid metabolism. A group of genes, namely CPT1A, CPT1B, CPT1C, CPT2, CRAT and CROT, encode for three carnitine acyltransferases that are important for the oxidation of fatty acids, a critical step in their metabolism. Methods Exome sequencing and SNP array genotyping were used to examine the genetic variations in the six genes encoding for the carnitine acyltransferases in 113 Nunavik Inuit individuals. Results Altogether ten missense variants were found in genes CPT1A, CPT1B, CPT1C, CPT2 and CRAT, including three novel variants and one Inuit specific variant CPT1A p.P479L (rs80356779). The latter has the highest frequency (0.955) compared to other Inuit populations. We found that by comparison to Asians or Europeans, the Nunavik Inuit have an increased mutation burden in CPT1A, CPT2 and CRAT; there is also a high level of population differentiation based on carnitine acyltransferase gene variations between Nunavik Inuit and Asians. Conclusion The increased number and frequency of deleterious variants in these fatty acid metabolism genes in Nunavik Inuit may be the result of genetic adaptation to their diet and/or the extremely cold climate. In addition, the identification of these variants may help to understand some of the specific health risks of Nunavik Inuit. PMID:26010953

  5. AMPK activation promotes lipid droplet dispersion on detyrosinated microtubules to increase mitochondrial fatty acid oxidation

    PubMed Central

    Herms, Albert; Bosch, Marta; Reddy, Babu J.N.; Schieber, Nicole L.; Fajardo, Alba; Rupérez, Celia; Fernández-Vidal, Andrea; Ferguson, Charles; Rentero, Carles; Tebar, Francesc; Enrich, Carlos; Parton, Robert G.; Gross, Steven P.; Pol, Albert

    2015-01-01

    Lipid droplets (LDs) are intracellular organelles that provide fatty acids (FAs) to cellular processes including synthesis of membranes and production of metabolic energy. While known to move bidirectionally along microtubules (MTs), the role of LD motion and whether it facilitates interaction with other organelles are unclear. Here we show that during nutrient starvation, LDs and mitochondria relocate on detyrosinated MT from the cell centre to adopt a dispersed distribution. In the cell periphery, LD–mitochondria interactions increase and LDs efficiently supply FAs for mitochondrial beta-oxidation. This cellular adaptation requires the activation of the energy sensor AMPK, which in response to starvation simultaneously increases LD motion, reorganizes the network of detyrosinated MTs and activates mitochondria. In conclusion, we describe the existence of a specialized cellular network connecting the cellular energetic status and MT dynamics to coordinate the functioning of LDs and mitochondria during nutrient scarcity. PMID:26013497

  6. IDH1 Mutations Alter Citric Acid Cycle Metabolism and Increase Dependence on Oxidative Mitochondrial Metabolism

    PubMed Central

    Grassian, Alexandra R.; Parker, Seth J.; Davidson, Shawn M.; Divakarun, Ajit S.; Green, Courtney R.; Zhang, Xiamei; Slocum, Kelly L.; Pu, Minying; Lin, Fallon; Vickers, Chad; Joud-Caldwell, Carol; Chung, Franklin; Yin, Hong; Handly, Erika D.; Straub, Christopher; Growney, Joseph D.; Vander Heiden, Matthew G.; Murphy, Anne N.; Pagliarini, Raymond; Metallo, Christian M.

    2016-01-01

    Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed 13C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. PMID:24755473

  7. Phosphatidic acid osmotically destabilizes lysosomes through increased permeability to K+ and H+.

    PubMed

    Yi, Y-P; Wang, X; Zhang, G; Fu, T-S; Zhang, G-J

    2006-06-01

    Lysosomal destabilization is a critical event not only for the organelle but also for living cells. However, what factors can affect lysosomal stability is not fully studied. In this work, the effects of phosphatidic acid (PA) on the lysosomal integrity were investigated. Through the measurements of lysosomal beta-hexosaminidase free activity, intralysosomal pH, leakage of lysosomal protons and lysosomal latency loss in hypotonic sucrose medium, we established that PA could increase the lysosomal permeability to K+ and H+, and enhance the lysosomal osmotic sensitivity. Treatment of lysosomes with PA promoted entry of K+ into the organelle via K+/H+ exchange, which could produce osmotic stresses and osmotically destabilize the lysosomes. In addition, PA-induced increase in the lysosomal osmotic sensitivity caused the lysosomes to become more liable to destabilization in osmotic shocks. The results suggest that PA may play a role in the lysosomal destabilization. PMID:16917129

  8. Zoledronic acid in vivo increases in vitro proliferation of rat mesenchymal stromal cells.

    PubMed

    Heino, Terhi J; Alm, Jessica J; Halkosaari, Heikki J; Välimäki, Ville-Valtteri

    2016-08-01

    Background and purpose - Bisphosphonates are widely used in the treatment of bone loss, but they might also have positive effects on osteoblastic cells and bone formation. We evaluated the effect of in vivo zoledronic acid (ZA) treatment and possible concomitant effects of ZA and fracture on the ex vivo osteogenic capacity of rat mesenchymal stromal cells (MSCs). Methods - A closed femoral fracture model was used in adult female rats and ZA was administered as a single bolus or as weekly doses up to 8 weeks. Bone marrow MSCs were isolated and cultured for in vitro analyses. Fracture healing was evaluated by radiography, micro-computed tomography (μCT), and histology. Results - Both bolus and weekly ZA increased fracture-site bone mineral content and volume. MSCs from weekly ZA-treated animals showed increased ex vivo proliferative capacity, while no substantial effect on osteoblastic differentiation was observed. Fracture itself did not have any substantial effect on cell proliferation or differentiation at 8 weeks. Serum biochemical markers showed higher levels of bone formation in animals with fracture than in intact animals, while no difference in bone resorption was observed. Interestingly, ex vivo osteoblastic differentiation of MSCs was found to correlate with in vivo serum bone markers. Interpretation - Our data show that in vivo zoledronic acid treatment can influence ex vivo proliferation of MSCs, indicating that bisphosphonates can have sustainable effects on cells of the osteoblastic lineage. Further research is needed to investigate the mechanisms. PMID:27196705

  9. Effects of increasing acidity on metal(loid) bioprecipitation in groundwater: column studies.

    PubMed

    Davis, Alexander C; Patterson, Bradley M; Grassi, Michelle E; Robertson, Blair S; Prommer, Henning; McKinley, Allan J

    2007-10-15

    Large-scale column experiments were carried out over a period of 545 days to assess the effect of increasing acidity on bacterial denitrification, sulfate reduction, and metal(loid) bioprecipitation in groundwater affected by acid mine drainage. At a groundwater pH of 5.5, denitrification and Cu2+ removal, probably via malachite (Cu2(OH)2CO3) precipitation, were observed in the ethanol-amended column. Sulfate reduction, sulfide production, and Zn2+ removal were also observed, with Zn2+ removal observed in the zone of sulfate reduction, indicating likely precipitation as sphalerite (ZnS). Se6+ removal was also observed in the sulfate reducing zone, probably as direct bioreduction to elemental selenium via ethanol/acetate oxidation or sulfide oxidation precipitating elemental sulfur. A step decrease in groundwater pH from 5.5 to 4.25 resulted in increased denitrification and sulfate reduction half-lives, migration of both these redox zones along the ethanol-amended column, and the formation of an elevated Cu2+ plume. Additionally, an elevated Zn2+ plume formed in the previous sulfate reducing zone of the ethanol-amended column, suggesting dissolution of precipitated sphalerite as a result of the reduction in groundwater pH. As Cu2+ passed through the zone of sphalerite dissolution, SEM imaging and EDS detection suggested that Cu2+ removal had occurred via chalcocite (Cu2S) or covellite (CuS) precipitation. PMID:17993159

  10. Lipoteichoic Acid Isolated from Weissella cibaria Increases Cytokine Production in Human Monocyte-Like THP-1 Cells and Mouse Splenocytes.

    PubMed

    Hong, Yi-Fan; Lee, Yoon-Doo; Park, Jae-Yeon; Kim, Seongjae; Lee, Youn-Woo; Jeon, Boram; Jagdish, Deepa; Kim, Hangeun; Chung, Dae Kyun

    2016-07-28

    Lactic acid bacteria (LAB) have beneficial effects on intestinal health and skin diseases. Lipoteichoic acid (LTA), a cell wall component of gram-positive bacteria, is known to induce the production of several cytokines such as TNF-α, IL-1β, and IL-8 and affect the intestinal microflora, anti-aging, sepsis, and cholesterol level. In this study, Weissella cibaria was isolated from Indian dairy products, and we examined its immune-enhancing effects. Live and heatkilled W. cibaria did not induce the secretion of immune-related cytokines, whereas LTA isolated from W. cibaria (cLTA) significantly increased the secretion of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. cLTA increased the phosphorylation of nuclear factor kappalight-chain-enhancer of activated B cells, p38 mitogen-activated protein kinases, and c-Jun N-terminal kinases in THP-1 cells. The secretion of TNF-α and IL-6 was also increased in the cLTA-treated mouse splenocytes. These results suggest that cLTA, but not W. cibaria whole cells, has immune-boosting potential and can be used to treat immunosuppression diseases. PMID:27012236

  11. Increasing bioavailability of (R)-alpha-lipoic acid to boost antioxidant activity in the treatment of neuropathic pain.

    PubMed

    Maglione, Emilia; Marrese, Cinzia; Migliaro, Elisa; Marcuccio, Fortuna; Panico, Claudia; Salvati, Carmine; Citro, Giuseppe; Quercio, Marco; Roncagliolo, Federico; Torello, Carlo; Brufani, Mario

    2015-01-01

    a-lipoic acid (a-LA) is a potent natural antioxidant because it has a broad spectrum of action towards a great many free radical species and boosts the endogenous antioxidant systems.Although it is a multi-functional molecule, its pharmacokinetic characteristics pose restrictions to its use in the treatment of oxidative stress-dependent illnesses. Formulations that increase the bioavailability of a-LA have a better potential efficacy as adjuvants for the treatment of these conditions.This objective was achieved with a liquid formulation for oral use containing only R-aLA, the natural enantiomeric and most active form of a-lipoic acid.For the first time, the effects of this formulation were evaluated on neuropathic pain, a symptom caused by an increase in oxidative stress, regardless of the underlying cause. Neuropathic patients who have used this dietary supplement noticed an improvement in their quality of life and a significant reduction was observed in a number of certain descriptive pain parameters (intensity, burning, unpleasantness, superficial pain).Undoubtedly further, more in-depth, studies need to be conducted; however, this first investigation confirms the role of R-aLA as an anti-oxidant for the aetiological treatment of peripheral neuropathy. Increasing its plasma bioavailability even after a non-invasive administration through the oral route is a good starting point for proposing a valid adjuvant for the treatment of pain symptoms. PMID:26694149

  12. Increasing the oscillation frequency of strong magnetic fields above 101 kHz significantly raises peripheral nerve excitation thresholds

    PubMed Central

    Weinberg, Irving N.; Stepanov, Pavel Y.; Fricke, Stanley T.; Probst, Roland; Urdaneta, Mario; Warnow, Daniel; Sanders, Howard; Glidden, Steven C.; McMillan, Alan; Starewicz, Piotr M.; Reilly, J. Patrick

    2012-01-01

    subjects. Results: For 0.4 T pulses at 2, 25, 59, 101, and 183 kHz, stimulation was reported by 22 (84.6%), 24 (92.3%), 15 (57.7%), 2 (7.7%), and 1 (3.8%) subjects, respectively. Conclusions: The probability of PNS due to brief biphasic time-varying sinusoidal magnetic fields with magnetic excursions up to 0.4 T is shown to decrease significantly at and above 101 kHz. This phenomenon may have particular uses in dynamic scenarios (e.g., cardiac imaging) and in studying processes with short decay times (e.g., electron paramagnetic resonance imaging, bone and solids imaging). The study suggests the possibility of new designs for human and preclinical MRI systems that may be useful in clinical practice and scientific research. PMID:22559628

  13. Krill oil supplementation increases plasma concentrations of eicosapentaenoic and docosahexaenoic acids in overweight and obese men and women.

    PubMed

    Maki, Kevin C; Reeves, Mathew S; Farmer, Mildred; Griinari, Mikko; Berge, Kjetil; Vik, Hogne; Hubacher, Rachel; Rains, Tia M

    2009-09-01

    Antarctic krill, also known as Euphausia superba, is a marine crustacean rich in both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We tested the hypothesis that krill oil would increase plasma concentrations of EPA and DHA without adversely affecting indicators of safety, tolerability, or selected metabolic parameters. In this randomized, double-blind parallel arm trial, overweight and obese men and women (N = 76) were randomly assigned to receive double-blind capsules containing 2 g/d of krill oil, menhaden oil, or control (olive) oil for 4 weeks. Results showed that plasma EPA and DHA concentrations increased significantly more (P < .001) in the krill oil (178.4 +/- 38.7 and 90.2 +/- 40.3 micromol/L, respectively) and menhaden oil (131.8 +/- 28.0 and 149.9 +/- 30.4 micromol/L, respectively) groups than in the control group (2.9 +/- 13.8 and -1.1 +/- 32.4 micromol/L, respectively). Systolic blood pressure declined significantly more (P < .05) in the menhaden oil (-2.2 +/- 2.0 mm Hg) group than in the control group (3.3 +/- 1.5 mm Hg), and the response in the krill oil group (-0.8 +/- 1.4 mm Hg) did not differ from the other 2 treatments. Blood urea nitrogen declined in the krill oil group as compared with the menhaden oil group (P < .006). No significant differences for other safety variables were noted, including adverse events. In conclusion, 4 weeks of krill oil supplementation increased plasma EPA and DHA and was well tolerated, with no indication of adverse effects on safety parameters. PMID:19854375

  14. Reducing isozyme competition increases target fatty acid accumulation in seed triacylglycerols of transgenic Arabidopsis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One goal of green chemistry is the production of industrially useful fatty acids (FAs) in crop plants. We focus on the engineering of industrial FAs, specifically hydroxy fatty acids (HFA) and conjugated polyenoic fatty acids (a-eleostearic acid, ESA), using Arabidopsis (Arabidopsis thaliana) as a m...

  15. Raised dietary n-6 polyunsaturated fatty acid intake increases 2-series prostaglandin production during labour in the ewe

    PubMed Central

    Elmes, M; Green, LR; Poore, K; Newman, J; Burrage, D; Abayasekara, DRE; Cheng, Z; Hanson, MA; Wathes, DC

    2005-01-01

    Preterm labour is the major cause of perinatal morbidity and mortality in humans. The incidence is around 10% and the causes are often unknown. Consumption of dietary n-6 polyunsaturated fatty acids (PUFAs) in western societies is increasing. These are metabolized to arachidonic acid, the precursor for 2-series prostaglandins (PGs), major signalling molecules during labour. This study investigated the effect of dietary supplementation with linoleic acid (LA, 18 : 2, n-6) on parturition. Ewes were fed a control or LA-supplemented diet from 100 days gestation. Labour was induced using a standardized glucocorticoid challenge (dexamethasone, Dex) to the fetus, starting on day 139. Electromyographic (EMG) activity and fetal and maternal circulating PG concentrations were monitored. One third of LA-fed ewes delivered early (pre-Dex) although basal uterine EMG activity preceding Dex was higher in control ewes (P < 0.05). A steep increase in EMG activity occurred 18–38 h after the start of Dex infusion. Twice basal EMG activity (defined as established labour) occurred on average 7 h earlier in the LA-supplemented ewes (P < 0.05). The basal concentrations of maternal and fetal PGFM and fetal PGE2 were approximately doubled in LA-supplemented ewes before the start of Dex infusion (P < 0.01). The rise in fetal PGE2 and maternal oestradiol concentrations post-Dex occurred earlier in the LA-supplemented ewes. All PG measurements remained significantly higher in the LA-supplemented ewes during labour onset. This study suggests that consumption of a high LA diet in late pregnancy can enhance placental PG production and may thus increase the risk of preterm labour. PMID:15513945

  16. Haplotypes of the D-Amino Acid Oxidase Gene Are Significantly Associated with Schizophrenia and Its Neurocognitive Deficits

    PubMed Central

    Hwu, Hai-Gwo; Fann, Cathy Shen-Jang; Yang, Ueng-Cheng; Yang, Wei-Chih; Hsu, Pei-Chun; Chang, Chien-Ching; Wen, Chun-Chiang; Tsai-Wu, Jyy-Jih; Hwang, Tzung-Jeng; Hsieh, Ming H.; Liu, Chen-Chung; Chien, Yi-Ling; Fang, Chiu-Ping; Faraone, Stephen V.; Tsuang, Ming T.; Chen, Wei J.; Liu, Chih-Min

    2016-01-01

    D-amino acid oxidase (DAO) has been reported to be associated with schizophrenia. This study aimed to search for genetic variants associated with this gene. The genomic regions of all exons, highly conserved regions of introns, and promoters of this gene were sequenced. Potentially meaningful single-nucleotide polymorphisms (SNPs) obtained from direct sequencing were selected for genotyping in 600 controls and 912 patients with schizophrenia and in a replicated sample consisting of 388 patients with schizophrenia. Genetic associations were examined using single-locus and haplotype association analyses. In single-locus analyses, the frequency of the C allele of a novel SNP rs55944529 located at intron 8 was found to be significantly higher in the original large patient sample (p = 0.016). This allele was associated with a higher level of DAO mRNA expression in the Epstein-Barr virus-transformed lymphocytes. The haplotype distribution of a haplotype block composed of rs11114083-rs2070586-rs2070587-rs55944529 across intron 1 and intron 8 was significantly different between the patients and controls and the haplotype frequencies of AAGC were significantly higher in patients, in both the original (corrected p < 0.0001) and replicated samples (corrected p = 0.0003). The CGTC haplotype was specifically associated with the subgroup with deficits in sustained attention and executive function and the AAGC haplotype was associated with the subgroup without such deficits. The DAO gene was a susceptibility gene for schizophrenia and the genomic region between intron 1 and intron 8 may harbor functional genetic variants, which may influence the mRNA expression of DAO and neurocognitive functions in schizophrenia. PMID:26986737

  17. Adaptation of in vivo amino acid kinetics facilitates increased amino acid availability for fetal growth in adolescent and adult pregnancies alike

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During pregnancy, adult women with a normal BMI synthesize extra amino acids after an overnight fast by increasing body protein breakdown and decreasing amino acid oxidation. It is not known whether adolescent girls can make these adaptations during pregnancy. The present study aimed to measure and ...

  18. Uric acid is released in the brain during seizure activity and increases severity of seizures in a mouse model for acute limbic seizures.

    PubMed

    Thyrion, Lisa; Raedt, Robrecht; Portelli, Jeanelle; Van Loo, Pieter; Wadman, Wytse J; Glorieux, Griet; Lambrecht, Bart N; Janssens, Sophie; Vonck, Kristl; Boon, Paul

    2016-03-01

    Recent evidence points at an important role of endogenous cell-damage induced pro-inflammatory molecules in the generation of epileptic seizures. Uric acid, under the form of monosodium urate crystals, has shown to have pro-inflammatory properties in the body, but less is known about its role in seizure generation. This study aimed to unravel the contribution of uric acid to seizure generation in a mouse model for acute limbic seizures. We measured extracellular levels of uric acid in the brain and modulated them using complementary pharmacological and genetic tools. Local extracellular uric acid levels increased three to four times during acute limbic seizures and peaked between 50 and 100 min after kainic acid infusion. Manipulating uric acid levels through administration of allopurinol or knock-out of urate oxidase significantly altered the number of generalized seizures, decreasing and increasing them by a twofold respectively. Taken together, our results consistently show that uric acid is released during limbic seizures and suggest that uric acid facilitates seizure generalization. PMID:26774005

  19. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids.

    PubMed

    Lachmandas, Ekta; van den Heuvel, Corina N A M; Damen, Michelle S M A; Cleophas, Maartje C P; Netea, Mihai G; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis. PMID:27057552

  20. Diabetes Mellitus and Increased Tuberculosis Susceptibility: The Role of Short-Chain Fatty Acids

    PubMed Central

    Lachmandas, Ekta; van den Heuvel, Corina N. A. M.; Damen, Michelle S. M. A.; Cleophas, Maartje C. P.; Netea, Mihai G.; van Crevel, Reinout

    2016-01-01

    Type 2 diabetes mellitus confers a threefold increased risk for tuberculosis, but the underlying immunological mechanisms are still largely unknown. Possible mediators of this increased susceptibility are short-chain fatty acids, levels of which have been shown to be altered in individuals with diabetes. We examined the influence of physiological concentrations of butyrate on cytokine responses to Mycobacterium tuberculosis (Mtb) in human peripheral blood mononuclear cells (PBMCs). Butyrate decreased Mtb-induced proinflammatory cytokine responses, while it increased production of IL-10. This anti-inflammatory effect was independent of butyrate's well-characterised inhibition of HDAC activity and was not accompanied by changes in Toll-like receptor signalling pathways, the eicosanoid pathway, or cellular metabolism. In contrast blocking IL-10 activity reversed the effects of butyrate on Mtb-induced inflammation. Alteration of the gut microbiota, thereby increasing butyrate concentrations, can reduce insulin resistance and obesity, but further studies are needed to determine how this affects susceptibility to tuberculosis. PMID:27057552

  1. Proteins implicated in the increase of adhesivity induced by suberoylanilide hydroxamic acid in leukemic cells.

    PubMed

    Grebeňová, D; Röselová, P; Pluskalová, M; Halada, P; Rösel, D; Suttnar, J; Brodská, B; Otevřelová, P; Kuželová, K

    2012-12-21

    We have previously shown that suberoylanilide hydroxamic acid (SAHA) treatment increases the adhesivity of leukemic cells to fibronectin at clinically relevant concentrations. Now, we present the results of the proteomic analysis of SAHA effects on leukemic cell lines using 2-DE and ProteomLab PF2D system. Histone acetylation at all studied acetylation sites reached the maximal level after 5 to 10 h of SAHA treatment. No difference in histone acetylation between subtoxic and toxic SAHA doses was observed. SAHA treatment induced cofilin phosphorylation at Ser3, an increase in vimentin and paxillin expression and a decrease in stathmin expression as confirmed by western-blotting and immunofluorescence microscopy. The interaction of cofilin with 14-3-3 epsilon was documented using both Duolink system and coimmunoprecipitation. However, this interaction was independent of cofilin Ser3 phosphorylation and the amount of 14-3-3-ε-bound cofilin did not rise following SAHA treatment. SAHA-induced increase in the cell adhesivity was associated with an increase in PAK phosphorylation in CML-T1 cells and was abrogated by simultaneous treatment with IPA-3, a PAK inhibitor. The effects of SAHA on JURL-MK1 cells were similar to those of other histone deacetylase inhibitors, tubastatin A and sodium butyrate. The proteome analysis also revealed several potential non-histone targets of histone deacetylases. PMID:23022583

  2. Discrete carbon nanotubes increase lead acid battery charge acceptance and performance

    NASA Astrophysics Data System (ADS)

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

    2014-09-01

    Performance demands placed upon lead acid batteries have outgrown the technology's ability to deliver. These demands, typically leading to Negative Active Material (NAM) failure, include: short, high-current surges; prolonged, minimal, overvoltage charging; repeated, Ah deficit charging; and frequent deep discharges. Research shows these failure mechanisms are attenuated by inclusion of carbon allotropes into the NAM. Addition of significant quantities of carbon, however, produces detrimental changes in paste rheology, leading to lowered industrial throughput. Additionally, capacity, cold-cranking performance, and other battery metrics are negatively affected at high carbon loads. Presented here is Molecular Rebar® Lead Negative, a new battery additive comprising discrete carbon nanotubes (dCNT) which uniformly disperse within battery pastes during mixing. NS40ZL batteries containing dCNT show enhanced charge acceptance, reserve capacity, and cold-cranking performance, decreased risk of polarization, and no detrimental changes to paste properties, when compared to dCNT-free controls. This work focuses on the dCNT as NAM additives only, but early-stage research is underway to test their functionality as a PAM additive. Batteries infused with Molecular Rebar® Lead Negative address the needs of modern lead acid battery applications, produce none of the detrimental side effects associated with carbon additives, and require no change to existing production lines.

  3. Increased palmitoyl-myristoyl-phosphatidylcholine in neonatal rat surfactant is lung specific and correlates with oral myristic acid supply.

    PubMed

    Bernhard, Wolfgang; Raith, Marco; Pynn, Christopher J; Gille, Christian; Stichtenoth, Guido; Stoll, Dieter; Schleicher, Erwin; Poets, Christian F

    2011-08-01

    Surfactant predominantly comprises phosphatidylcholine (PC) species, together with phosphatidylglycerols, phosphatidylinositols, neutral lipids, and surfactant proteins-A to -D. Together, dipalmitoyl-PC (PC16:0/16:0), palmitoyl-myristoyl-PC (PC16:0/14:0), and palmitoyl-palmitoleoyl-PC (PC16:0/16:1) make up 75-80% of mammalian surfactant PC, the proportions of which vary during development and in chronic lung diseases. PC16:0/14:0, which exerts specific effects on macrophage differentiation in vitro, increases in surfactant during alveolarization (at the expense of PC16:0/16:0), a prenatal event in humans but postnatal in rats. The mechanisms responsible and the significance of this reversible increase are, however, not understood. We hypothesized that, in rats, myristic acid (C14:0) enriched milk is key to lung-specific PC16:0/14:0 increases in surfactant. We found that surfactant PC16:0/14:0 in suckling rats correlates with C14:0 concentration in plasma chylomicrons and lung tissue triglycerides, and that PC16:0/14:0 fractions reflect exogenous C14:0 supply. Significantly, C14:0 was increased neither in plasma PC, nor in liver triglycerides, free fatty acids, or PC. Lauric acid was also abundant in triglycerides, but was not incorporated into surfactant PC. Comparing a C14:0-rich milk diet with a C14:0-poor carbohydrate diet revealed increased C14:0 and decreased C16:0 in plasma and lung triglycerides, respectively. PC16:0/14:0 enrichment at the expense of PC16:0/16:0 did not impair surfactant surface tension function. However, the PC profile of the alveolar macrophages from the milk-fed animals changed from PC16:0/16:0 rich to PC16:0/14:0 rich. This was accompanied by reduced reactive oxygen species production. We propose that nutritional supply with C14:0 and its lung-specific enrichment may contribute to decreased reactive oxygen species production during alveolarization. PMID:21636561

  4. Increase of eicosapentaenoic acid in thraustochytrids through thraustochytrid ubiquitin promoter-driven expression of a fatty acid {delta}5 desaturase gene.

    PubMed

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-06-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C(16:0)), n - 6 docosapentaenoic acid (DPA) (C(22:5)(n) (- 6)), and docosahexaenoic acid (DHA) (C(22:6)(n) (- 3)), with eicosapentaenoic acid (EPA) (C(20:5)(n) (- 3)) and arachidonic acid (AA) (C(20:4)(n) (- 6)) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C(20:4)(n) (- 3)) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C(20:3)(n) (- 6)) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  5. Increase of Eicosapentaenoic Acid in Thraustochytrids through Thraustochytrid Ubiquitin Promoter-Driven Expression of a Fatty Acid Δ5 Desaturase Gene▿†

    PubMed Central

    Kobayashi, Takumi; Sakaguchi, Keishi; Matsuda, Takanori; Abe, Eriko; Hama, Yoichiro; Hayashi, Masahiro; Honda, Daiske; Okita, Yuji; Sugimoto, Shinichi; Okino, Nozomu; Ito, Makoto

    2011-01-01

    Thraustochytrids, marine protists known to accumulate polyunsaturated fatty acids (PUFAs) in lipid droplets, are considered an alternative to fish oils as a source of PUFAs. The major fatty acids produced in thraustochytrids are palmitic acid (C16:0), n − 6 docosapentaenoic acid (DPA) (C22:5n − 6), and docosahexaenoic acid (DHA) (C22:6n − 3), with eicosapentaenoic acid (EPA) (C20:5n − 3) and arachidonic acid (AA) (C20:4n − 6) as minor constituents. We attempted here to alter the fatty acid composition of thraustochytrids through the expression of a fatty acid Δ5 desaturase gene driven by the thraustochytrid ubiquitin promoter. The gene was functionally expressed in Aurantiochytrium limacinum mh0186, increasing the amount of EPA converted from eicosatetraenoic acid (ETA) (C20:4n − 3) by the Δ5 desaturase. The levels of EPA and AA were also increased by 4.6- and 13.2-fold in the transgenic thraustochytrids compared to levels in the mock transfectants when ETA and dihomo-γ-linolenic acid (DGLA) (C20:3n − 6) were added to the culture at 0.1 mM. Interestingly, the amount of EPA in the transgenic thraustochytrids increased in proportion to the amount of ETA added to the culture up to 0.4 mM. The rates of conversion and accumulation of EPA were much higher in the thraustochytrids than in baker's yeasts when the desaturase gene was expressed with the respective promoters. This report describes for the first time the finding that an increase of EPA could be accomplished by introducing the Δ5 desaturase gene into thraustochytrids and indicates that molecular breeding of thraustochytrids is a promising strategy for generating beneficial PUFAs. PMID:21478316

  6. Elaidate, an 18-Carbon Trans-monoenoic Fatty Acid, but not Physiological Fatty Acids Increases Intracellular Zn2+ in Human Macrophages

    PubMed Central

    Zacherl, Janelle R.; Tourkova, Irina; St Croix, Claudette M.; Robinson, Lisa J.; Peck Palmer, Octavia M.; Mihalik, Stephanie J.; Blair, Harry C.

    2015-01-01

    Artificial trans fatty acids promote atherosclerosis by blocking macrophage clearance of cell debris. Classical fatty-acid response mechanisms include TLR4-NF-κB activation, and Erk1/2 phosphorylation, but these may not indicate long-term mechanisms. Indeed, nuclear NF-κB was increased by 60 minute treatment by 30 μM of the 18 carbon trans unsaturated fatty acid elaidic acid (elaidate), the physiological cis-unsaturated fatty acid oleic acid (oleate), and the 18 or 16 carbon saturated fatty acids stearic and palmitic acid (stearate or palmitate). However, except for stearate, effects on related pathways were minimal at 44 hours. To determine longer term effects of trans fatty acids, we compared whole exome mRNA expression of (trans) elaidate to (cis) oleate, 30 μM, at 44 hours in human macrophages. We found that elaidate changed Zn2+-homeostasis gene mRNAs markedly. This might be important because Zn2+ is a major regulator of macrophage activity. Messenger RNAs of seven Zn2+-binding metallothioneins decreased 2–4 fold; the zinc importer SLC39A10 increased 2-fold, in elaidate relative to oleate-treated cells. Results were followed by quantitative PCR comparing cis, trans, and saturated fatty acid effects on Zn2+-homeostasis gene mRNAs. This confirmed that elaidate uniquely decreased metallothionein expression and increased SLC39A10 at 44 hours. Further, intracellular Zn2+ was measured using N-(carboxymethyl)-N-[2-[2-[2(carboxymethyl)amino]-5-(2,7,-difluoro-6-hydroxy-3-oxo-3H-xanthen-9-yl)-phenoxy]-ethoxy]-4-methoxyphenyl]glycine, acetoxymethyl ester (FluoZin-3-AM). This showed that, at 44 hours, only cells treated with elaidate had increased Zn2+. The durable effect of elaidate on Zn2+ activation is a novel and specific effect of trans fatty acids on peripheral macrophage metabolism. PMID:25358453

  7. Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes.

    PubMed

    Lee, Bonggi; Kwon, Misung; Choi, Jae Sue; Jeong, Hyoung Oh; Chung, Hae Young; Kim, Hyeung-Rak

    2015-12-01

    Stamens of Nelumbo nucifera Gaertn have been used as a Chinese medicine due to its antioxidant, hypoglycemic, and antiatherogenic activity. However, the effects of kaempferol, a main component of N. nucifera, on obesity are not fully understood. We examined the effect of kaempferol on adipogenesis and fatty acid oxidation signaling pathways in 3T3-L1 adipocytes. Kaempferol reduced cytoplasmic triglyceride (TG) accumulation in dose and time-dependent manners during adipocyte differentiation. Accumulation of TG was rapidly reversed by retrieving kaempferol treatment. Kaempferol broadly decreased mRNA or protein levels of adipogenic transcription factors and their target genes related to lipid accumulation. Kaempferol also suppressed glucose uptake and glucose transporter GLUT4 mRNA expression in adipocytes. Furthermore, protein docking simulation suggests that Kaempferol can directly bind to and activate peroxisome proliferator-activated receptor (PPAR)-α by forming hydrophobic interactions with VAL324, THR279, and LEU321 residues of PPARα. The binding affinity was higher than a well-known PPARα agonist fenofibrate. Consistently, mRNA expression levels of PPARα target genes were increased. Our study indicates while kaempferol inhibits lipogenic transcription factors and lipid accumulation, it may bind to PPARα and stimulate fatty acid oxidation signaling in adipocytes. PMID:26280739

  8. Select microtubule inhibitors increase lysosome acidity and promote lysosomal disruption in acute myeloid leukemia (AML) cells.

    PubMed

    Bernard, Dannie; Gebbia, Marinella; Prabha, Swayam; Gronda, Marcela; MacLean, Neil; Wang, Xiaoming; Hurren, Rose; Sukhai, Mahadeo A; Cho, Eunice E; Manolson, Morris F; Datti, Alessandro; Wrana, Jeffrey; Minden, Mark D; Al-Awar, Rima; Aman, Ahmed; Nislow, Corey; Giaever, Guri; Schimmer, Aaron D

    2015-07-01

    To identify new biological vulnerabilities in acute myeloid leukemia, we screened a library of natural products for compounds cytotoxic to TEX leukemia cells. This screen identified the novel small molecule Deoxysappanone B 7,4' dimethyl ether (Deox B 7,4), which possessed nanomolar anti-leukemic activity. To determine the anti-leukemic mechanism of action of Deox B 7,4, we conducted a genome-wide screen in Saccharomyces cerevisiae and identified enrichment of genes related to mitotic cell cycle as well as vacuolar acidification, therefore pointing to microtubules and vacuolar (V)-ATPase as potential drug targets. Further investigations into the mechanisms of action of Deox B 7,4 and a related analogue revealed that these compounds were reversible microtubule inhibitors that bound near the colchicine site. In addition, Deox B 7,4 and its analogue increased lysosomal V-ATPase activity and lysosome acidity. The effects on microtubules and lysosomes were functionally important for the anti-leukemic effects of these drugs. The lysosomal effects were characteristic of select microtubule inhibitors as only the Deox compounds and nocodazole, but not colchicine, vinca alkaloids or paclitaxel, altered lysosome acidity and induced lysosomal disruption. Thus, our data highlight a new mechanism of action of select microtubule inhibitors on lysosomal function. PMID:25832785

  9. Azetidine-2-carboxylic acid resistant mutants of Arabidopsis thaliana with increased salt tolerance

    SciTech Connect

    Lehle, F.R.; Murphy, M.A.; Khan, R.A. )

    1989-04-01

    Nineteen mutant Arabidopsis families resistant to the proline analog azetidine-2-carboxylic acid (ACA) were characterized in terms of NaCl tolerance and proline content. Mutants were selected from about 64,000 progeny of about 16,000 self-pollinated Columbia parents which had been mutated with ethyl methane sulfonate during seed imbibition. Selections were performed during seed germination on aseptic agar medium containing 0.2 to 0.25 mM ACA. Nineteen mutant families, 12 clearly independent, retained resistance to ACA in the M{sub 4} generation. Based on germination on 150 mM NaCl, 13 of the mutant families were more tolerant than the wild type. Two mutants of intermediate resistance to ACA were markedly more salt tolerant than the others. Four mutant families appeared to overproduce proline. Of these, only 3 showed slight increases in salt tolerance.

  10. Evidence that nitric acid increases relative humidity in low-temperature cirrus clouds.

    PubMed

    Gao, R S; Popp, P J; Fahey, D W; Marcy, T P; Herman, R L; Weinstock, E M; Baumgardner, D G; Garrett, T J; Rosenlof, K H; Thompson, T L; Bui, P T; Ridley, B A; Wofsy, S C; Toon, O B; Tolbert, M A; Kärcher, B; Peter, Th; Hudson, P K; Weinheimer, A J; Heymsfield, A J

    2004-01-23

    In situ measurements of the relative humidity with respect to ice (RHi) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RHi values show a sharp increase to average values of over 130% in both cloud types. These enhanced RHi values are attributed to the presence of a new class of HNO3-containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor. PMID:14739457

  11. Evidence That Nitric Acid Increases Relative Humidity in Low-Temperature Cirrus Clouds

    NASA Technical Reports Server (NTRS)

    Gao, R. S.; Popp, P. J.; Fahey, D. W.; Marcy, T. P.; Herman, R. L.; Weinstock, E. M.; Baumgardner, D. G.; Garrett, T. J.; Rosenlof, K. H.; Thompson, T. L.

    2004-01-01

    In situ measurements of the relative humidity with respect to ice (RH(sub(i)) and of nitric acid (HNO3) were made in both natural and contrail cirrus clouds in the upper troposphere. At temperatures lower than 202 kelvin, RH(sub i) values show a sharp increase to average values of over 130% in both cloud types. These enhanced RH(sub i) values are attributed to the presence of a new class of NHO3- containing ice particles (Delta-ice). We propose that surface HNO3 molecules prevent the ice/vapor system from reaching equilibrium by a mechanism similar to that of freezing point depression by antifreeze proteins. Delta-ice represents a new link between global climate and natural and anthropogenic nitrogen oxide emissions. Including Delta-ice in climate models will alter simulated cirrus properties and the distribution of upper tropospheric water vapor.

  12. Bioinspired syntheses of dimeric hydroxycinnamic acids (lignans) and hybrids, using phenol oxidative coupling as key reaction, and medicinal significance thereof.

    PubMed

    Magoulas, George E; Papaioannou, Dionissios

    2014-01-01

    Lignans are mainly dimers of 4-hydroxycinnamic acids (HCAs) and reduced analogs thereof which are produced in Nature through phenol oxidative coupling (POC) as the primary C-C or C-O bond-forming reaction under the action of the enzymes peroxidases and laccases. They present a large structural variety and particularly interesting biological activities, therefore, significant efforts has been devoted to the development of efficient methodologies for the synthesis of lignans isolated from natural sources, analogs and hybrids with other biologically interesting small molecules. We summarize in the present review those methods which mimic Nature for the assembly of the most common lignan skeleta by using either enzymes or one-electron inorganic oxidants to effect POC of HCAs and derivatives, such as esters and amides, or cross-POC of pairs of HCAs or HCAs with 4-hydrocycinnamyl alcohols. We, furthermore, provide outlines of mechanistic schemes accounting for the formation of the coupled products and, where applicable, indicate their potential application in medicine. PMID:25460307

  13. Increasing or stabilizing renal epoxyeicosatrienoic acid production attenuates abnormal renal function and hypertension in obese rats.

    PubMed

    Huang, Hui; Morisseau, Christophe; Wang, JingFeng; Yang, Tianxin; Falck, John R; Hammock, Bruce D; Wang, Mong-Heng

    2007-07-01

    Since epoxyeicosatrienoic acids (EETs) affect sodium reabsorption in renal tubules and dilate the renal vasculature, we have examined their effects on renal hemodynamics and sodium balance in male rats fed a high-fat (HF) diet by fenofibrate, a peroxisome proliferator-activated receptor-alpha (PPAR-alpha) agonist and an inducer of cytochrome P-450 (CYP) epoxygenases; by N-methanesulfonyl-6-(2-proparyloxyphenyl)hexanamide (MSPPOH), a selective EET biosynthesis inhibitor; and by 12-(3-adamantane-1-yl-ureido)dodecanoic acid (AUDA), a selective inhibitor of soluble epoxide hydrolase. In rats treated with fenofibrate (30 mg.kg(-1).day(-1) ig) or AUDA (50 mg/l in drinking water) for 2 wk, mean arterial pressure, renal vascular resistance, and glomerular filtration rate were lower but renal blood flow was higher than in vehicle-treated control rats. In addition, fenofibrate and AUDA decreased cumulative sodium balance in the HF rats. Treatment with MSPPOH (20 mg.kg(-1).day(-1) iv) + fenofibrate for 2 wk reversed renal hemodynamics and sodium balance to the levels in control HF rats. Moreover, fenofibrate caused a threefold increase in renal cortical CYP epoxygenase activity, whereas the fenofibrate-induced elevation of this activity was attenuated by MSPPOH. Western blot analysis showed that fenofibrate induced the expression of CYP epoxygenases in renal cortex and microvessels and that the induction effect of fenofibrate was blocked by MSPPOH. These results demonstrate that the fenofibrate-induced increase of CYP epoxygenase expression and the AUDA-induced stabilization of EET production in the kidneys cause renal vascular dilation and reduce sodium retention, contributing to the improvement of abnormal renal hemodynamics and hypertension in HF rats. PMID:17442729

  14. Effects of increasing acidity on metal(loid) bioprecipitation in groundwater: column studies

    SciTech Connect

    Alexander C. Davis; Bradley M. Patterson; Michelle E. Grassi; Blair S. Robertson; Henning Prommer; Allan J. McKinley

    2007-10-15

    Large-scale column experiments were carried out over a period of 545 days to assess the effect of increasing acidity on bacterial denitrification, sulfate reduction, and metal(loid) bioprecipitation in groundwater affected by acid mine drainage. At a groundwater pH of 5.5, denitrification and Cu{sup 2+} removal, probably via malachite (Cu{sub 2}(OH){sub 2}CO{sub 3}) precipitation, were observed in the ethanol-amended column. Sulfate reduction, sulfide production, and Zn{sup 2+} removal were also observed, with Zn{sup 2+} removal observed in the zone of sulfate reduction, indicating likely precipitation as sphalerite (ZnS). Se{sup 6+} removal was also observed in the sulfate reducing zone, probably as direct bioreduction to elemental selenium via ethanol/acetate oxidation or sulfide oxidation precipitating elemental sulfur. A step decrease in groundwater pH from 5.5 to 4.25 resulted in increased denitrification and sulfate reduction half-lives, migration of both these redox zones along the ethanol-amended column, and the formation of an elevated Cu{sup 2+} plume. Additionally, an elevated Zn{sup 2+} plume formed in the previous sulfate reducing zone of the ethanol-amended column, suggesting dissolution of precipitated sphalerite as a result of the reduction in groundwater pH. As Cu{sup 2+} passed through the zone of sphalerite dissolution, SEM imaging and EDS detection suggested that Cu{sup 2+} removal had occurred via chalcocite (Cu{sub 2}S) or covellite (CuS) precipitation. 23 refs., 8 figs.

  15. Mice Deficient in Transmembrane Prostatic Acid Phosphatase Display Increased GABAergic Transmission and Neurological Alterations

    PubMed Central

    Myöhänen, Timo T.; Voikar, Vootele; Mijatovic, Jelena; Segerstråle, Mikael; Herrala, Annakaisa M.; Kulesskaya, Natalia; Pulkka, Anitta E.; Kivinummi, Tanja; Abo-Ramadan, Usama; Taira, Tomi; Piepponen, T. Petteri; Rauvala, Heikki; Vihko, Pirkko

    2014-01-01

    Prostatic acid phosphatase (PAP), the first diagnostic marker and present therapeutic target for prostate cancer, modulates nociception at the dorsal root ganglia (DRG), but its function in the central nervous system has remained unknown. We studied expression and function of TMPAP (the transmembrane isoform of PAP) in the brain by utilizing mice deficient in TMPAP (PAP−/− mice). Here we report that TMPAP is expressed in a subpopulation of cerebral GABAergic neurons, and mice deficient in TMPAP show multiple behavioral and neurochemical features linked to hyperdopaminergic dysregulation and altered GABAergic transmission. In addition to increased anxiety, disturbed prepulse inhibition, increased synthesis of striatal dopamine, and augmented response to amphetamine, PAP-deficient mice have enlarged lateral ventricles, reduced diazepam-induced loss of righting reflex, and increased GABAergic tone in the hippocampus. TMPAP in the mouse brain is localized presynaptically, and colocalized with SNARE-associated protein snapin, a protein involved in synaptic vesicle docking and fusion, and PAP-deficient mice display altered subcellular distribution of snapin. We have previously shown TMPAP to reside in prostatic exosomes and we propose that TMPAP is involved in the control of GABAergic tone in the brain also through exocytosis, and that PAP deficiency produces a distinct neurological phenotype. PMID:24846136

  16. Suberoylanilide hydroxamic acid (SAHA) at subtoxic concentrations increases the adhesivity of human leukemic cells to fibronectin.

    PubMed

    Kuzelová, Katerina; Pluskalová, Michaela; Brodská, Barbora; Otevrelová, Petra; Elknerová, Klára; Grebenová, Dana; Hrkal, Zbynek

    2010-01-01

    Suberoylanilide hydroxamic acid (SAHA) is an inhibitor of histone deacetylases (HDACs) which is being introduced into clinic for the treatment of hematological diseases. We studied the effect of this compound on six human hematopoietic cell lines (JURL-MK1, K562, CML-T1, Karpas-299, HL-60, and ML-2) as well as on normal human lymphocytes and on leukemic primary cells. SAHA induced dose-dependent and cell type-dependent cell death which displayed apoptotic features (caspase-3 activation and apoptotic DNA fragmentation) in most cell types including the normal lymphocytes. At subtoxic concentrations (0.5-1 microM), SAHA increased the cell adhesivity to fibronectin (FN) in all leukemia/lymphoma-derived cell lines but not in normal lymphocytes. This increase was accompanied by an enhanced expression of integrin beta1 and paxillin, an essential constituent of focal adhesion complexes, both at the protein and mRNA level. On the other hand, the inhibition of ROCK protein, an important regulator of cytoskeleton structure, had no consistent effect on SAHA-induced increase in the cell adhesivity. The promotion of cell adhesivity to FN seems to be specific for SAHA as we observed no such effects with other HDAC inhibitors (trichostatin A and sodium butyrate). PMID:19911379

  17. Increased Cortical Gamma-Aminobutyric Acid Precedes Incomplete Extinction of Conditioned Fear and Increased Hippocampal Excitatory Tone in a Mouse Model of Mild Traumatic Brain Injury.

    PubMed

    Schneider, Brandy L; Ghoddoussi, Farhad; Charlton, Jennifer L; Kohler, Robert J; Galloway, Matthew P; Perrine, Shane A; Conti, Alana C

    2016-09-01

    Mild traumatic brain injury (mTBI) contributes to development of affective disorders, including post-traumatic stress disorder (PTSD). Psychiatric symptoms typically emerge in a tardive fashion post-TBI, with negative effects on recovery. Patients with PTSD, as well as rodent models of PTSD, demonstrate structural and functional changes in brain regions mediating fear learning, including prefrontal cortex (PFC), amygdala (AMYG), and hippocampus (HC). These changes may reflect loss of top-down control by which PFC normally exhibits inhibitory influence over AMYG reactivity to fearful stimuli, with HC contribution. Considering the susceptibility of these regions to injury, we examined fear conditioning (FC) in the delayed post-injury period, using a mouse model of mTBI. Mice with mTBI displayed enhanced acquisition and delayed extinction of FC. Using proton magnetic resonance spectroscopy ex vivo, we examined PFC, AMYG, and HC levels of gamma-aminobutyric acid (GABA) and glutamate as surrogate measures of inhibitory and excitatory neurotransmission, respectively. Eight days post-injury, GABA was increased in PFC, with no significant changes in AMYG. In animals receiving FC and mTBI, glutamate trended toward an increase and the GABA/glutamate ratio decreased in ventral HC at 25 days post-injury, whereas GABA decreased and GABA/glutamate decreased in dorsal HC. These neurochemical changes are consistent with early TBI-induced PFC hypoactivation facilitating the fear learning circuit and exacerbating behavioral fear responses. The latent emergence of overall increased excitatory tone in the HC, despite distinct plasticity in dorsal and ventral HC fields, may be associated with disordered memory function, manifested as incomplete extinction and enhanced FC recall. PMID:26529240

  18. Increased fatty acid unsaturation and production of arachidonic acid by homologous over-expression of the mitochondrial malic enzyme in Mortierella alpina

    PubMed Central

    Hao, Guangfei; Du, Kai; Huang, Xiaoyun; Song, Yuanda; Gu, Zhennan; Wang, Lei; Zhang, Hao; Chen, Wei; Chen, Yong Q.

    2015-01-01

    Malic enzyme (ME) catalyses the oxidative decarboxylation of L-malate to pyruvate and provides NADPH for intracellular metabolism, such as fatty acid synthesis. Here, the mitochondrial ME (mME) gene from Mortierella alpina was homologously over-expressed. Compared with controls, fungal arachidonic acid (ARA; 20:4 n-6) content increased by 60 % without affecting the total fatty acid content. Our results suggest that enhancing mME activity may be an effective mean to increase industrial production of ARA in M. alpina. PMID:24863290

  19. A thraustochytrid diacylglycerol acyltransferase 2 with broad substrate specificity strongly increases oleic acid content in engineered Arabidopsis thaliana seeds

    PubMed Central

    Zhang, Chunyu; Iskandarov, Umidjon; Cahoon, Edgar B.

    2013-01-01

    Diacylglycerol acyltransferase (DGAT) catalyses the last step in acyl-CoA-dependent triacylglycerol (TAG) biosynthesis and is an important determinant of cellular oil content and quality. In this study, a gene, designated TaDGAT2, encoding a type 2 DGAT (DGAT2)-related enzyme was identified from the oleaginous marine protist Thraustochytrium aureum. The deduced TaDGAT2 sequence contains a ~460 amino acid domain most closely related to DGAT2s from Dictyostelium sp. (45–50% identity). Recombinant TaDGAT2 restored TAG biosynthesis to the Saccharomyces cerevisiae H1246 TAG-deficient mutant, and microsomes from the complemented mutant displayed DGAT activity with C16 and C18 saturated and unsaturated fatty acyl-CoA and diacylglycerol substrates. To examine its biotechnological potential, TaDGAT2 was expressed under control of a strong seed-specific promoter in wild-type Arabidopsis thaliana and the high linoleic acid fad3fae1 mutant. In both backgrounds, little change was detected in seed oil content, but a striking increase in oleic acid content of seeds was observed. This increase was greatest in fad3fae1 seeds, where relative amounts of oleic acid increased nearly 2-fold to >50% of total fatty acids. In addition, >2-fold increase in oleic acid levels was detected in the triacylglycerol sn-2 position and in the major seed phospholipid phosphatidylcholine. These results suggest that increased seed oleic acid content mediated by TaDGAT2 is influenced in part by the fatty acid composition of host cells and occurs not by enhancing oleic acid content at the TAG sn-3 position directly but by increasing total oleic acid levels in seeds, presumably by limiting flux through phosphatidylcholine-based desaturation reactions. PMID:23814277

  20. Steam Cooking Significantly Improves in Vitro Bile Acid Binding of Beets, Eggplant, Asparagus, Carrots, Green Beans and Cauliflower

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The relative healthful potential of cooked beets, okra, eggplant, asparagus, carrots, green beans, cauliflower and turnips was evaluated by determining their in vitro bile acid binding using a mixture of bile acids secreted in human bile at a duodenal physiological pH of 6.3. Six treatments and two...

  1. The retinoic acid receptor agonist Am80 increases hippocampal ADAM10 in aged SAMP8 mice.

    PubMed

    Kitaoka, Kazuyoshi; Shimizu, Noriyuki; Ono, Koji; Chikahisa, Sachiko; Nakagomi, Madoka; Shudo, Koichi; Ishimura, Kazunori; Séi, Hiroyoshi; Yoshizaki, Kazuo

    2013-09-01

    The retinoic acid (RA, a vitamin A metabolite) receptor (RAR) is a transcription factor. Vitamin A/RA administration improves the Alzheimer's disease (AD)- and age-related attenuation of memory/learning in mouse models. Recently, a disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was identified as a key molecule in RA-mediated anti-AD mechanisms. We investigated the effect of chronic administration of the RAR agonist Am80 (tamibarotene) on ADAM10 expression in senescence-accelerated mice (SAMP8). Moreover, we estimated changes in the expression of the amyloid precursor protein (APP), amyloid beta (Aβ), and hairy/enhancer of split (Hes), which are mediated by ADAM10. Spatial working memory and the levels of a hippocampal proliferation marker (Ki67) were also assessed in these mice. ADAM10 mRNA and protein expression was significantly reduced in the hippocampus of 13-month-old SAMP8 mice; their expression improved significantly after Am80 administration. Further, after Am80 administration, the expression levels of Hes5 and Ki67 were restored and the deterioration of working memory was suppressed, whereas APP and Aβ levels remained unchanged. Our results suggest that Am80 administration effectively improves dementia by activating the hippocampal ADAM10-Notch-Hes5 proliferative pathway. PMID:23624141

  2. Method for construction of bacterial strains with increased succinic acid production

    DOEpatents

    Donnelly, Mark I.; Sanville-Millard, Cynthia; Chatterjee, Ranjini

    2000-01-01

    A fermentation process for producing succinic acid is provided comprising selecting a bacterial strain that does not produce succinic acid in high yield, disrupting the normal regulation of sugar metabolism of said bacterial strain, and combining the mutant bacterial strain and selected sugar in anaerobic conditions to facilitate production of succinic acid. Also provided is a method for changing low yield succinic acid producing bacteria to high yield succinic acid producing bacteria comprising selecting a bacterial strain having a phosphotransferase system and altering the phosphotransferase system so as to allow the bacterial strain to simultaneously metabolize different sugars.

  3. Activation of glucosidase via stress-induced polymerization rapidly increases active pools of abscisic acid.

    PubMed

    Lee, Kwang Hee; Piao, Hai Lan; Kim, Ho-Youn; Choi, Sang Mi; Jiang, Fan; Hartung, Wolfram; Hwang, Ildoo; Kwak, June M; Lee, In-Jung; Hwang, Inhwan

    2006-09-22

    Abscisic acid (ABA) is a phytohormone critical for plant growth, development, and adaptation to various stress conditions. Plants have to adjust ABA levels constantly to respond to changing physiological and environmental conditions. To date, the mechanisms for fine-tuning ABA levels remain elusive. Here we report that AtBG1, a beta-glucosidase, hydrolyzes glucose-conjugated, biologically inactive ABA to produce active ABA. Loss of AtBG1 causes defective stomatal movement, early germination, abiotic stress-sensitive phenotypes, and lower ABA levels, whereas plants with ectopic AtBG1 accumulate higher ABA levels and display enhanced tolerance to abiotic stress. Dehydration rapidly induces polymerization of AtBG1, resulting in a 4-fold increase in enzymatic activity. Furthermore, diurnal increases in ABA levels are attributable to polymerization-mediated AtBG1 activation. We propose that the activation of inactive ABA pools by polymerized AtBG1 is a mechanism by which plants rapidly adjust ABA levels and respond to changing environmental cues. PMID:16990135

  4. Suppression of Adult Neurogenesis Increases the Acute Effects of Kainic Acid

    PubMed Central

    Iyengar, Sloka S.; LaFrancois, John J.; Friedman, Daniel; Drew, Liam J.; Denny, Christine A.; Burghardt, Nesha S.; Wu, Melody V.; Hsieh, Jenny; Hen, René; Scharfman, Helen E.

    2016-01-01

    Adult neurogenesis, the generation of new neurons in the adult brain, occurs in the hippocampal dentate gyrus (DG) and the olfactory bulb (OB) of all mammals, but the functions of these new neurons are not entirely clear. Originally, adult-born neurons were considered to have excitatory effects on the DG network, but recent studies suggest a net inhibitory effect. Therefore, we hypothesized that selective removal of newborn neurons would lead to increased susceptibility to the effects of a convulsant. This hypothesis was tested by evaluating the response to the chemoconvulsant kainic acid (KA) in mice with reduced adult neurogenesis, produced either by focal X-irradiation of the DG, or by pharmacogenetic deletion of dividing radial glial precursors. In the first 4 hrs after KA administration, when mice have the most robust seizures, mice with reduced adult neurogenesis had more severe convulsive seizures, exhibited either as a decreased latency to the first convulsive seizure, greater number of convulsive seizures, or longer convulsive seizures. Nonconvulsive seizures did not appear to change or they decreased. Four-21 hrs after KA injection, mice with reduced adult neurogenesis showed more interictal spikes (IIS) and delayed seizures than controls. Effects were greater when the anticonvulsant ethosuximide was injected 30 min prior to KA administration; ethosuximide allows forebrain seizure activity to be more easily examined in mice by suppressing seizures dominated by the brainstem. These data support the hypothesis that reduction of adult-born neurons increases the susceptibility of the brain to effects of KA. PMID:25476494

  5. A geographic cline in leaf salicylic acid with increasing elevation in Arabidopsis thaliana.

    PubMed

    Zhang, Nana; Tonsor, Stephen J; Traw, M Brian

    2015-01-01

    Salicylic acid (SA) occupies a key role as a hormone central to both plant resistance to bacterial pathogens and tolerance of abiotic stresses. Plants at high elevation experience colder temperatures and elevated UV levels. While it has been predicted that SA concentrations will be higher in plants from high elevation populations, few studies have addressed this question. Here, we asked how concentrations of SA vary in natural populations of Arabidopsis thaliana collected across an elevational gradient on the Iberian Peninsula. In a series of common garden experiments, we found that constitutive SA concentrations were highest in genotypes from the low elevation populations. This result was in the opposite direction from our prediction and is an exception to the general finding that phenolic compounds increase with increasing elevation. These data suggest that high constitutive SA is not associated with resistance to cold temperatures in these plants. Furthermore, we also found that leaf constitutive camalexin concentrations, an important defense against some bacterial and fungal enemies, were highest in the low elevation populations, suggesting that pathogen pressures may be important. Further examination of this elevational cline will likely provide additional insights into the interplay between phenolic compounds and biotic and abiotic stress. PMID:25875692

  6. A geographic cline in leaf salicylic acid with increasing elevation in Arabidopsis thaliana

    PubMed Central

    Zhang, Nana; Tonsor, Stephen J; Traw, M Brian

    2015-01-01

    Salicylic acid (SA) occupies a key role as a hormone central to both plant resistance to bacterial pathogens and tolerance of abiotic stresses. Plants at high elevation experience colder temperatures and elevated UV levels. While it has been predicted that SA concentrations will be higher in plants from high elevation populations, few studies have addressed this question. Here, we asked how concentrations of SA vary in natural populations of Arabidopsis thaliana collected across an elevational gradient on the Iberian Peninsula. In a series of common garden experiments, we found that constitutive SA concentrations were highest in genotypes from the low elevation populations. This result was in the opposite direction from our prediction and is an exception to the general finding that phenolic compounds increase with increasing elevation. These data suggest that high constitutive SA is not associated with resistance to cold temperatures in these plants. Furthermore, we also found that leaf constitutive camalexin concentrations, an important defense against some bacterial and fungal enemies, were highest in the low elevation populations, suggesting that pathogen pressures may be important. Further examination of this elevational cline will likely provide additional insights into the interplay between phenolic compounds and biotic and abiotic stress. PMID:25875692

  7. A Chronological Increase in Gastric Acid Secretion from 1995 to 2014 in Young Japanese Healthy Volunteers under the Age of 40 Years Old.

    PubMed

    Iijima, Katsunori; Koike, Tomoyuki; Abe, Yasuhiko; Ohara, Shuichi; Shimosegawa, Tooru

    2016-01-01

    Gastric acid secretion levels are an important determinant of the manifestation of acid-related upper GI diseases such as gastroesophageal reflux disease. We recently reported that gastric acid secretion levels did not change from the 1990s to 2010s in H. pylori-negative asymptomatic Japanese outpatients with a mean age of 63 years old. However, because young people have a quite different lifestyle, including dietary pattern, from elderly people in Japan, it is worth investigating any chronologic changes in gastric acid secretion in younger generations. The aim of this analysis is to investigate the potential changes in gastric acid secretion from 1995 to 2014 in young Japanese healthy volunteers. Eighty-eight young Japanese healthy volunteers under the age of 40 with a mean age of 26 were extracted from a database accumulated from 1995 to 2014 for the present analysis. Their gastrin-stimulated gastric acid level was determined with the endoscopic gastrin test. In 76 H. pylori-negative subjects, gastric acid secretion levels showed a significant positive correlation with the calendar year when the test was performed (r = 0.27, p < 0.01). A similar trend was observed in 12 H. pylori-positive subjects. A chronological 5-year time period showed a significant positive association with gastric acid secretion in univariate and multivariate analyses (p < 0.01 and p = 0.01, respectively). Gastric acid secretion levels have been increasing in young Japanese healthy volunteers during the last 20 years. We need to monitor future trends in the prevalence of acid-related diseases such as gastro-esophageal reflux disease in Japan. PMID:27440759

  8. [THE DETECTION OF CONTENT OF DIAGNOSTICALLY SIGNIFICANT FATTY ACIDS AND INDIVIDUAL TRIGLYCERIDES IN BIOLOGICAL MEDIUMS BASED ON INFRARED SPECTROMETRY].

    PubMed

    Kalinin, A V; Krasheninnikov, V N; Sviridov, A P; Titov, V N

    2015-11-01

    The content of clinically important fatty acids and individual triglycerides in food and biological mediums are traditionally detected by gas and fluid chromatography in various methodical modifications. The techniques are hard-to-get in laboratories of clinical biochemistry. The study was carried out to develop procedures and equipment for operative quantitative detection of concentration of fatty acids, primarily palmitic saturated fatty acid and oleic mono unsaturated fatty acid. Also detection was applied to sums ofpolyenoic (eicosapentaenoic and docosahexaenoic acid) fatty acids in biological mediums (cod-liver oil, tissues, blood plasma) using spectrometers of short-range infrared band of different types: with Fourier transform, diffraction and combined scattering. The evidences of reliable and reproducible quantitative detection offatty acids were received on the basis of technique of calibration (regression) by projection on latent structures using standard samples of mixtures of oils and fats. The evaluation is implemented concerning possibility of separate detection of content of palmitic and oleic triglycerides in mediums with presence of water The choice of technical conditions and mode of application of certain types of infrared spectrometers and techniques of their calibration is substantiated PMID:26999859

  9. Increase in the Bmax of gamma-aminobutyric acid-A recognition sites in brain regions of mice receiving diazepam.

    PubMed Central

    Ferrero, P; Guidotti, A; Costa, E

    1984-01-01

    gamma-Aminobutyric acid (GABA) receptors were characterized in vivo by studying ex vivo the binding of [3H]muscimol to cerebellum, cortex, hippocampus, and corpus striatum of mice receiving intravenous injections of tracer doses of high-specific-activity (approximately equal to 30 Ci/mmol) [3H]muscimol. This ligand binds with high affinity (apparent Kd, 2-3 X 10(-9) M) to a single population of binding sites (apparent Bmax, 250-180 fmol per 10 mg of protein). Pharmacological studies using drugs that selectively bind to GABAA or GABAB receptors suggest that [3H]muscimol specifically labels a GABAA recognition site. Moreover, diazepam (1.5 mumol/kg, i.p.) increases the Bmax but fails to change the affinity of [3H]muscimol binding to different brain areas. This diazepam-elicited increase in Bmax is blocked in mice receiving the diazepam antagonist Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5a]-[1,4] benzodiazepine-3-carboxylate). Since the diazepam-induced increase of [3H]muscimol binding is paralleled by a significant potentiation of the inhibitory effect of muscimol on locomotor activity, it is proposed that the facilitatory action on GABAergic transmission elicited in vivo by diazepam is mediated by an increase in the Bmax of the binding sites of GABAA receptors. Images PMID:6326115

  10. Three Conazoles Increase Hepatic Microsomal Retinoic Acid Metabolism and Decrease Mouse Hepatic Retinoic Acid Levels In Vivo

    EPA Science Inventory

    Conazoles are fungicides used in agriculture and as pharmaceuticals. In a previous toxicogenomic study of triazole-containing conazoles we found gene expression changes consistent with the alteration of the metabolism of all trans-retinoic acid (atRA), a vitamin A metabolite with...

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

    NASA Astrophysics Data System (ADS)

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

    1983-11-01

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

  12. Amaranth oil increased fecal excretion of bile Acid but had no effect in reducing plasma cholesterol in hamsters.

    PubMed

    de Castro, Luíla Ivini Andrade; Soares, Rosana Aparecida Manólio; Saldiva, Paulo H N; Ferrari, Roseli A; Miguel, Ana M R O; Almeida, Claudia A S; Arêas, José Alfredo Gomes

    2013-06-01

    Hamsters were fed for 4 weeks on four different diets: control (C) (balanced diet containing 20 % corn oil as the lipid source), hypercholesterolemic (H) (identical to C but containing 12 % coconut oil, 8 % corn oil and 0.1 % cholesterol as the lipid source), amaranth oil (A) (identical to H without corn oil but with amaranth oil), and squalene (S) (identical to H but admixed with squalene in the ratio found in amaranth oil). There were no significant differences in lipid profile, and in the cholesterol excreted in the animals' feces from amaranth oil (A) and squalene (S) groups. Fecal excretion of bile acids was greater in the amaranth oil (A) and squalene groups (S) as compared to the other groups. The scores of steatosis and parenchymal inflammation observed in the amaranth oil (A) and squalene groups (S) were superior to the ones observed in the other groups. Our findings demonstrated that amaranth oil, and its component squalene, increased the excretion of bile acids but did not have a hypocholesterolemic effect in hamsters fed on a diet containing high amounts of saturated fat and cholesterol. PMID:23456975

  13. Life at acidic pH imposes an increased energetic cost for a eukaryotic acidophile.

    PubMed

    Messerli, Mark A; Amaral-Zettler, Linda A; Zettler, Erik; Jung, Sung-Kwon; Smith, Peter J S; Sogin, Mitchell L

    2005-07-01

    Organisms growing in acidic environments, pH<3, would be expected to possess fundamentally different molecular structures and physiological controls in comparison with similar species restricted to neutral pH. We begin to investigate this premise by determining the magnitude of the transmembrane electrochemical H+ gradient in an acidophilic Chlamydomonas sp. (ATCC PRA-125) isolated from the Rio Tinto, a heavy metal laden, acidic river (pH 1.7-2.5). This acidophile grows most rapidly at pH 2 but is capable of growth over a wide pH range (1.5-7.0), while Chlamydomonas reinhardtii is restricted to growth at pH>or=3 with optimal growth between pH 5.5 and 8.5. With the fluorescent H+ indicator, 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein (BCECF), we show that the acidophilic Chlamydomonas maintains an average cytosolic pH of 6.6 in culture medium at both pH 2 and pH 7 while Chlamydomonas reinhardtii maintains an average cytosolic pH of 7.1 in pH 7 culture medium. The transmembrane electric potential difference of Chlamydomonas sp., measured using intracellular electrodes at both pH 2 and 7, is close to 0 mV, a rare value for plants, animals and protists. The 40,000-fold difference in [H+] could be the result of either active or passive mechanisms. Evidence for active maintenance was detected by monitoring the rate of ATP consumption. At the peak, cells consume about 7% more ATP per second in medium at pH 2 than at pH 7. This increased rate of consumption is sufficient to account for removal of H+ entering the cytosol across a membrane with relatively high permeability to H+ (7x10(-8) cm s-1). Our results indicate that the small increase in the rate of ATP consumption can account for maintenance of the transmembrane H+ gradient without the imposition of cell surface H+ barriers. PMID:15961743

  14. Increase on the Initial Soluble Heme Levels in Acidic Conditions Is an Important Mechanism for Spontaneous Heme Crystallization In Vitro

    PubMed Central

    Egan, Timothy J.; Wright, David W.; Oliveira, Marcus F.

    2010-01-01

    Background Hemozoin (Hz) is a heme crystal that represents a vital pathway for heme disposal in several blood-feeding organisms. Recent evidence demonstrated that β-hematin (βH) (the synthetic counterpart of Hz) formation occurs under physiological conditions near synthetic or biological hydrophilic-hydrophobic interfaces. This seems to require a heme dimer acting as a precursor of Hz crystals that would be formed spontaneously in the absence of the competing water molecules bound to the heme iron. Here, we aimed to investigate the role of medium polarity on spontaneous βH formation in vitro. Methodology/Principal Findings We assessed the effect of water content on spontaneous βH formation by using the aprotic solvent dimethylsulfoxide (DMSO) and a series of polyethyleneglycols (PEGs). We observed that both DMSO and PEGs (3.350, 6.000, 8.000, and 22.000) increased the levels of soluble heme under acidic conditions. These compounds were able to stimulate the production of βH crystals in the absence of any biological sample. Interestingly, the effects of DMSO and PEGs on βH formation were positively correlated with their capacity to promote previous heme solubilization in acidic conditions. Curiously, a short chain polyethyleneglycol (PEG 300) caused a significant reduction in both soluble heme levels and βH formation. Finally, both heme solubilization and βH formation strongly correlated with reduced medium water activity provided by increased DMSO concentrations. Conclusions The data presented here support the notion that reduction of the water activity is an important mechanism to support spontaneous heme crystallization, which depends on the previous increase of soluble heme levels. PMID:20856937

  15. Ocean acidification increases copper toxicity differentially in two key marine invertebrates with distinct acid-base responses.

    PubMed

    Lewis, Ceri; Ellis, Robert P; Vernon, Emily; Elliot, Katie; Newbatt, Sam; Wilson, Rod W

    2016-01-01

    Ocean acidification (OA) is expected to indirectly impact biota living in contaminated coastal environments by altering the bioavailability and potentially toxicity of many pH-sensitive metals. Here, we show that OA (pH 7.71; pCO2 1480 μatm) significantly increases the toxicity responses to a global coastal contaminant (copper ~0.1 μM) in two keystone benthic species; mussels (Mytilus edulis) and purple sea urchins (Paracentrotus lividus). Mussels showed an extracellular acidosis in response to OA and copper individually which was enhanced during combined exposure. In contrast, urchins maintained extracellular fluid pH under OA by accumulating bicarbonate but exhibited a slight alkalosis in response to copper either alone or with OA. Importantly, copper-induced damage to DNA and lipids was significantly greater under OA compared to control conditions (pH 8.14; pCO2 470 μatm) for both species. However, this increase in DNA-damage was four times lower in urchins than mussels, suggesting that internal acid-base regulation in urchins may substantially moderate the magnitude of this OA-induced copper toxicity effect. Thus, changes in metal toxicity under OA may not purely be driven by metal speciation in seawater and may be far more diverse than either single-stressor or single-species studies indicate. This has important implications for future environmental management strategies. PMID:26899803

  16. Ocean acidification increases copper toxicity differentially in two key marine invertebrates with distinct acid-base responses

    PubMed Central

    Lewis, Ceri; Ellis, Robert P.; Vernon, Emily; Elliot, Katie; Newbatt, Sam; Wilson, Rod W.

    2016-01-01

    Ocean acidification (OA) is expected to indirectly impact biota living in contaminated coastal environments by altering the bioavailability and potentially toxicity of many pH-sensitive metals. Here, we show that OA (pH 7.71; pCO2 1480 μatm) significantly increases the toxicity responses to a global coastal contaminant (copper ~0.1 μM) in two keystone benthic species; mussels (Mytilus edulis) and purple sea urchins (Paracentrotus lividus). Mussels showed an extracellular acidosis in response to OA and copper individually which was enhanced during combined exposure. In contrast, urchins maintained extracellular fluid pH under OA by accumulating bicarbonate but exhibited a slight alkalosis in response to copper either alone or with OA. Importantly, copper-induced damage to DNA and lipids was significantly greater under OA compared to control conditions (pH 8.14; pCO2 470 μatm) for both species. However, this increase in DNA-damage was four times lower in urchins than mussels, suggesting that internal acid-base regulation in urchins may substantially moderate the magnitude of this OA-induced copper toxicity effect. Thus, changes in metal toxicity under OA may not purely be driven by metal speciation in seawater and may be far more diverse than either single-stressor or single-species studies indicate. This has important implications for future environmental management strategies. PMID:26899803

  17. Increased Serum Level of Cyclopropaneoctanoic Acid 2-Hexyl in Patients with Hypertriglyceridemia-Related Disorders.

    PubMed

    Mika, Adriana; Stepnowski, Piotr; Chmielewski, Michal; Malgorzewicz, Sylwia; Kaska, Lukasz; Proczko, Monika; Ratnicki-Sklucki, Krzysztof; Sledzinski, Maciej; Sledzinski, Tomasz

    2016-07-01

    We recently reported the presence of various cyclopropane fatty acids-among them, cyclopropaneoctanoic acid 2-hexyl-in the adipose tissue of obese women. The aim of this study was to verify whether the presence of cyclopropaneoctanoic acid 2-hexyl in human serum was associated with obesity or chronic kidney disease (both being related to dyslipidemia), and to find potential associations between the serum level of this compound and specific markers of the these conditions. The serum concentration of cyclopropaneoctanoic acid 2-hexyl was determined by gas chromatography-mass spectrometry (GC-MS) in non-obese controls, obese patients, obese patients after a 3-month low-calorie diet, and individuals with chronic kidney disease. Obese patients and those with chronic kidney disease presented with higher serum levels of cyclopropaneoctanoic acid 2-hexyl than controls. Switching obese individuals to a low-calorie (low-lipid) diet resulted in a reduction in this fatty acid concentration to the level observed in controls. Cyclopropaneoctanoic acid 2-hexyl was also found in foods derived from animal fat. Serum concentrations of triacylglycerols in the analyzed groups followed a pattern similar to that for serum cyclopropaneoctanoic acid 2-hexyl, and these variables were positively correlated with each other among the studied groups. Patients with hypertriglyceridemia-related conditions presented with elevated serum levels of cyclopropaneoctanoic acid 2-hexyl. Our findings suggest that its high serum level is related to high serum triacylglycerol concentrations rather than to body mass or BMI. PMID:27003900

  18. Experimental fertilization increases amino acid content in floral nectar, fruit set and degree of selfing in the orchid Gymnadenia conopsea.

    PubMed

    Gijbels, Pieter; Ceulemans, Tobias; Van den Ende, Wim; Honnay, Olivier

    2015-11-01

    Floral traits have evolved to maximize reproductive success by attracting pollinators and facilitating pollination. Highly attractive floral traits may, however, also increase the degree of self-pollination, which could become detrimental for plant fitness through inbreeding depression. Floral nectar is a trait that is known to strongly mediate pollinator attraction and plant reproductive success, but the particular role of the nectar amino acid (AA) composition is poorly understood. Therefore, we experimentally manipulated the nectar AA composition and abundance of the Lepidoptera-pollinated orchid Gymnadenia conopsea through soil fertilization, and we quantified AA content and AA composition through high performance anion exchange chromatography with pulsed amperometric detection. Mixed models were then used to evaluate differences in pollinia removal, fruit set, seed set and degree of selfing between fertilized and control individuals. Selfing rates were estimated using microsatellite markers. We found that fertilized individuals had a significantly higher nectar AA content and an altered AA composition, whereas plant height, number of flowers, nectar volume and sugar concentration remained unchanged. Fertilized individuals also had significantly more pollinia removed and a higher fruit set, whereas control plants that did not receive the fertilization treatment had significantly fewer selfed seeds, and more viable seeds. Although we cannot exclude a role of changes in floral scent following the fertilization treatment, our results strongly suggest a relation among nectar AA composition, fruiting success and selfing rates. Our results also indicate potential consequences of nutrient pollution for plant reproductive success, through the induced changes in nectar AA composition. PMID:26149746

  19. Commercial Phaseolus vulgaris extract (starch stopper) increases ileal endogenous amino acid and crude protein losses in the growing rat.

    PubMed

    Deglaire, A; Moughan, P J; Bos, C; Tome, D

    2006-07-12

    The effect of a commercial Phaseolus vulgaris extract (PVE, starch stopper) on ileal and fecal endogenous protein losses was studied. Growing rats were fed for 14 days a protein-free diet containing PVE at a nutritional concentration of 0% (PF1), 0.4% (PF2), or 1.1% PVE (PF3) or 1.1% autoclaved PVE (PF4). An indigestible marker (TiO(2)) was included in each diet. Ileal endogenous amino acid (AA) losses were significantly higher (P < 0.05) in PF3 (20% higher than in PF1), except for Pro, Gly, Ala, and His. Endogenous ileal N losses were 22% higher in PF3 than in PF1. Endogenous fecal AA and N losses were all significantly higher (P < 0.05) in PF3. Starch digestibility ( approximately 100%), food intake (single daily meal, d10-23), and body weight loss were not significantly different among the groups. PVE, at 1.1% of the diet, not only was ineffective in reducing starch digestibility but also led to increased ileal endogenous N losses, possibly due to the antinutritional factors (trypsin inhibitor, lectin) present in the PVE. PMID:16819935

  20. Acid-Sensitive Sheddable PEGylated PLGA Nanoparticles Increase the Delivery of TNF-α siRNA in Chronic Inflammation Sites.

    PubMed

    Aldayel, Abdulaziz M; Naguib, Youssef W; O'Mary, Hannah L; Li, Xu; Niu, Mengmeng; Ruwona, Tinashe B; Cui, Zhengrong

    2016-01-01

    There has been growing interest in utilizing small interfering RNA (siRNA) specific to pro-inflammatory cytokines, such as tumor necrosis factor-α ( TNF-α), in chronic inflammation therapy. However, delivery systems that can increase the distribution of the siRNA in chronic inflammation sites after intravenous administration are needed. Herein we report that innovative functionalization of the surface of siRNA-incorporated poly (lactic-co-glycolic) acid (PLGA) nanoparticles significantly increases the delivery of the siRNA in the chronic inflammation sites in a mouse model. The TNF-α siRNA incorporated PLGA nanoparticles were prepared by the standard double emulsion method, but using stearoyl-hydrazone-polyethylene glycol 2000, a unique acid-sensitive surface active agent, as the emulsifying agent, which renders (i) the nanoparticles PEGylated and (ii) the PEGylation sheddable in low pH environment such as that in chronic inflammation sites. In a mouse model of lipopolysaccharide-induced chronic inflammation, the acid-sensitive sheddable PEGylated PLGA nanoparticles showed significantly higher accumulation or distribution in chronic inflammation sites than PLGA nanoparticles prepared with an acid-insensitive emulsifying agent (i.e., stearoyl-amide-polyethylene glycol 2000) and significantly increased the distribution of the TNF-α siRNA incorporated into the nanoparticles in inflamed mouse foot. PMID:27434685

  1. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition.

    PubMed

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-04-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. PMID:26951372

  2. Increasing abscisic acid levels by immunomodulation in barley grains induces precocious maturation without changing grain composition

    PubMed Central

    Staroske, Nicole; Conrad, Udo; Kumlehn, Jochen; Hensel, Götz; Radchuk, Ruslana; Erban, Alexander; Kopka, Joachim; Weschke, Winfriede; Weber, Hans

    2016-01-01

    Abscisic acid (ABA) accumulates in seeds during the transition to the seed filling phase. ABA triggers seed maturation, storage activity, and stress signalling and tolerance. Immunomodulation was used to alter the ABA status in barley grains, with the resulting transgenic caryopses responding to the anti-ABA antibody gene expression with increased accumulation of ABA. Calculation of free versus antibody-bound ABA reveals large excess of free ABA, increasing signficantly in caryopses from 10 days after fertilization. Metabolite and transcript profiling in anti-ABA grains expose triggered and enhanced ABA-functions such as transcriptional up-regulation of sucrose-to-starch metabolism, storage protein synthesis and ABA-related signal transduction. Thus, enhanced ABA during transition phases induces precocious maturation but negatively interferes with growth and development. Anti-ABA grains display broad constitutive gene induction related to biotic and abiotic stresses. Most of these genes are ABA- and/or stress-inducible, including alcohol and aldehyde dehydrogenases, peroxidases, chaperones, glutathione-S-transferase, drought- and salt-inducible proteins. Conclusively, ABA immunomodulation results in precocious ABA accumulation that generates an integrated response of stress and maturation. Repression of ABA signalling, occurring in anti-ABA grains, potentially antagonizes effects caused by overshooting production. Finally, mature grain weight and composition are unchanged in anti-ABA plants, although germination is somewhat delayed. This indicates that anti-ABA caryopses induce specific mechanisms to desensitize ABA signalling efficiently, which finally yields mature grains with nearly unchanged dry weight and composition. Such compensation implicates the enormous physiological and metabolic flexibilities of barley grains to adjust effects of unnaturally high ABA amounts in order to ensure and maintain proper grain development. PMID:26951372

  3. Medium-chain triglycerides and conjugated linoleic acids in beverage form increase satiety and reduce food intake in humans.

    PubMed

    Coleman, Hannah; Quinn, Paul; Clegg, Miriam E

    2016-06-01

    Both developed and developing countries are seeing increasing trends of obesity in people young and old. It is thought that satiety may play a role in the prevention of obesity by increasing satiety and reducing energy intake. We hypothesized that medium-chain triglycerides (MCT) would increase satiety and decrease food intake compared with conjugated linoleic acid (CLA) and a control oil. Nineteen healthy participants were tested on 3 separate occasions, where they consumed a beverage test breakfast containing (1) vegetable oil (control), (2) CLA, or (3) MCT. Participants self-requested an ad libitum sandwich buffet lunch. Time between meals, satiety from visual analog scales, energy intake at lunch, and intake for the rest of the day using weighed food diaries were measured. The results indicated that the time until a meal request was significantly different between the 3 meals (P=.016); however, there were no differences in intakes at the ad libitum lunch (P>.05). The CLA breakfast generated the greatest delay in meal time request. There was a difference between the control lipid compared with both the CLA and MCT for energy intake over the remainder of the test day and for total energy intake on the test day (P<.001 for both), with the CLA and MCT resulting in a lower intake than the control throughout the day. There were no significant differences in satiety from visual analog scale scores (P>.05). Both CLA and MCT increased satiety and reduced energy intake, indicating a potential role in aiding the maintenance of energy balance. PMID:27188898

  4. Autolysis of Lactococcus lactis Is Increased upon d-Alanine Depletion of Peptidoglycan and Lipoteichoic Acids

    PubMed Central

    Steen, Anton; Palumbo, Emmanuelle; Deghorain, Marie; Cocconcelli, Pier Sandro; Delcour, Jean; Kuipers, Oscar P.; Kok, Jan; Buist, Girbe; Hols, Pascal

    2005-01-01

    Mutations in the genes encoding enzymes responsible for the incorporation of d-Ala into the cell wall of Lactococcus lactis affect autolysis. An L. lactis alanine racemase (alr) mutant is strictly dependent on an external supply of d-Ala to be able to synthesize peptidoglycan and to incorporate d-Ala in the lipoteichoic acids (LTA). The mutant lyses rapidly when d-Ala is removed at mid-exponential growth. AcmA, the major lactococcal autolysin, is partially involved in the increased lysis since an alr acmA double mutant still lyses, albeit to a lesser extent. To investigate the role of d-Ala on LTA in the increased cell lysis, a dltD mutant of L. lactis was investigated, since this mutant is only affected in the d-alanylation of LTA and not the synthesis of peptidoglycan. Mutation of dltD results in increased lysis, showing that d-alanylation of LTA also influences autolysis. Since a dltD acmA double mutant does not lyse, the lysis of the dltD mutant is totally AcmA dependent. Zymographic analysis shows that no degradation of AcmA takes place in the dltD mutant, whereas AcmA is degraded by the extracellular protease HtrA in the wild-type strain. In L. lactis, LTA has been shown to be involved in controlled (directed) binding of AcmA. LTA lacking d-Ala has been reported in other bacterial species to have an improved capacity for autolysin binding. Mutation of dltD in L. lactis, however, does not affect peptidoglycan binding of AcmA; neither the amount of AcmA binding to the cells nor the binding to specific loci is altered. In conclusion, d-Ala depletion of the cell wall causes lysis by two distinct mechanisms. First, it results in an altered peptidoglycan that is more susceptible to lysis by AcmA and also by other factors, e.g., one or more of the other (putative) cell wall hydrolases expressed by L. lactis. Second, reduced amounts of d-Ala on LTA result in decreased degradation of AcmA by HtrA, which results in increased lytic activity. PMID:15601695

  5. Minodronic acid ameliorates vertebral bone strength by increasing bone mineral density in 9-month treatment of ovariectomized cynomolgus monkeys.

    PubMed

    Tanaka, Makoto; Mori, Hiroshi; Kawabata, Kazuhito; Mashiba, Tasuku

    2016-07-01

    The effect of treatment for 9months with minodronic acid, a nitrogen-containing bisphosphonate, on vertebral mechanical strength was examined in ovariectomized (OVX) cynomolgus monkeys. Forty skeletally mature female monkeys were randomized into four OVX groups and one sham group (n=8) based on lumbar bone mineral density (BMD). OVX animals were treated orally with 15 and 150μg/kg QD of minodronic acid or 500μg/kg QD alendronate as a reference drug. Measurements of bone turnover markers and lumbar BMD were conducted at 0, 4 and 8months. Measurements of bone mechanical strength and minodronic acid concentration in vertebral bodies were also performed. OVX resulted in a decrease in lumbar BMD and an increase in bone turnover markers at 4 and 8months, compared to the sham group, and the ultimate load on the lumbar vertebra was decreased in OVX animals. Minodronic acid and alendronate prevented the OVX-induced increase in bone turnover markers and decrease in lumbar BMD. Minodronic acid at 150μg/kg increased the ultimate load on lumbar vertebra compared to untreated OVX animals. Regression analysis revealed that the ultimate load was correlated with lumbar BMD and bone mineral content (BMC), and most strongly with the increase in lumbar BMD and BMC over 8months. In a separate analysis within the sham-OVX controls and minodronic acid and alendronate treatment groups, the ultimate loads were also correlated with BMD and BMC. The load-BMD (BMC) correlation in the minodronic acid group showed a trend for a shift to a higher load from the basal relationship in the sham-OVX controls. These results indicate that treatment with minodronic acid for 9months increases vertebral mechanical strength in OVX monkeys, mainly by increasing BMD and BMC. PMID:27155564

  6. Oxidized and nitrated oleic acid in biological systems: analysis by GC-MS/MS and LC-MS/MS, and biological significance.

    PubMed

    Tsikas, Dimitrios; Zoerner, Alexander A; Jordan, Jens

    2011-11-01

    Compared to the arachidonic acid (C20:4) cascade, the oleic acid (C18:1) family comprises a handful known metabolites. The pathophysiology of oleic acid and its oxidized and nitrated metabolites, i.e., cis-9,10-epoxyoctadecanoic acid (cis-EpOA) and the two vinylic nitro-oleic acids cis-9-nitro-oleic acid (9-NO(2)-OA) and cis-10-nitro-oleic acid (10-NO(2)-OA), is only little investigated and little understood. cis-EpOA, 9-NO(2)-OA and 10-NO(2)-OA have been detected in plasma of healthy and ill human subjects by means of gas chromatography-tandem mass spectrometry (GC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) techniques in their acid and esterified forms. cis-EpOA is formed from oleic acid by the catalytic action of various cytochrome P450 isozymes. In end-stage liver disease, cis-EpOA plasma concentration is lower than in healthy subjects suggesting liver as the main organ responsible for cis-EpOA synthesis. The origin of 9-NO(2)-OA and 10-NO(2)-OA and of other nitrated oleic acid metabolites is unknown. In vitro models, nitro-oleic acid species can be formed non-enzymatically from oleic acid and nitrogen dioxide. Thus, endogenous nitro-oleic acids could serve as biomarkers of fatty acid nitration by reactive nitrogen species. Synthetic 9-NO(2)-OA and 10-NO(2)-OA at concentrations of three orders of magnitude higher than their endogenous counterparts have interesting pharmacological features and are currently intensely investigated. The present article reviews and discusses currently available analytical methods for the quantitative determination of cis-EpOA, 9-NO(2)-OA and 10-NO(2)-OA in biological samples, notably in human plasma, and the potential biological significance of these oleic acid metabolites. Special emphasis is given to GC-MS/MS and LC-MS/MS methods utilizing the stable-isotope dilution technique. The sensitivity and specificity of the MS/MS approach make electron-capture negative ion chemical ionization (ECNICI) GC

  7. Investigating the significance of zero-point motion in small molecular clusters of sulphuric acid and water

    SciTech Connect

    Stinson, Jake L.; Kathmann, Shawn M.; Ford, Ian J.

    2014-01-14

    The nucleation of particles from trace gases in the atmosphere is an important source of cloud condensation nuclei (CCN), and these are vital for the formation of clouds in view of the high supersaturations required for homogeneous water droplet nucleation. The methods of quantum chemistry have increasingly been employed to model nucleation due to their high accuracy and efficiency in calculating configurational energies; and nucleation rates can be obtained from the associated free energies of particle formation. However, even in such advanced approaches, it is typically assumed that the nuclei have a classical nature, which is questionable for some systems. The importance of zero-point motion (also known as quantum nuclear dynamics) in modelling small clusters of sulphuric acid and water is tested here using the path integral molecular dynamics (PIMD) method at the density functional theory (DFT) level of theory. We observe a small zero-point effect on the the equilibrium structures of certain clusters. One configuration is found to display a bimodal behaviour at 300 K in contrast to the stable ionised state suggested from a zero temperature classical geometry optimisation. The general effect of zero-point motion is to promote the extent of proton transfer with respect to classical behaviour. We thank Prof. Angelos Michaelides and his group in University College London (UCL) for practical advice and helpful discussions. This work benefited from interactions with the Thomas Young Centre through seminar and discussions involving the PIMD method. SMK was supported by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. JLS and IJF were supported by the IMPACT scheme at UCL and by the U.S. Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences, and Biosciences. We are grateful for use of the UCL Legion High Performance Computing Facility and the

  8. The rolC gene increases caffeoylquinic acid production in transformed artichoke cells.

    PubMed

    Vereshchagina, Y V; Bulgakov, V P; Grigorchuk, V P; Rybin, V G; Veremeichik, G N; Tchernoded, G K; Gorpenchenko, T Y; Koren, O G; Phan, N H T; Minh, N T; Chau, L T; Zhuravlev, Y N

    2014-09-01

    Caffeoylquinic acids are found in artichokes, and they are currently considered important therapeutic or preventive agents for treating Alzheimer's disease and diabetes. We transformed artichoke [the cultivated cardoon or Cynara cardunculus var. altilis DC (Asteraceae)] with the rolC gene, which is a known inducer of secondary metabolism. High-performance liquid chromatography with UV and high-resolution mass spectrometry (HPLC-UV-HRMS) revealed that the predominant metabolites synthesized in the transgenic calli were 1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, and chlorogenic acid. The rolC-transformed calli contained 1.5% caffeoylquinic acids by dry weight. The overall production of these metabolites was three times higher than that of the corresponding control calli. The enhancing effect of rolC remained stable over long-term cultivation. PMID:24938208

  9. A solid acid esterification catalyst which reduces waste and increases yields

    SciTech Connect

    Lundquist, E.G.

    1993-12-31

    Recent research on polymeric catalysts has led to the development of a new solid acid esterification catalyst which is highly active for the esterification of fatty acids and maleic anhydride at elevated temperatures. The use of this catalyst eliminates the need for a final neutralization step which is required when using traditional homogenous acid (H{sub 2}SO{sub 4} and HCl) catalysts. This neutralization step generates large amounts of waste salts and hurts efficiency since unconsumed organic acid reactants are also neutralized. In the high temperature esterification reactions studied here, the production of dialkyl ether by-products from the acid catalyzed self-condensation of alcohol is also greatly reduced allowing for both high activity and selectivity.

  10. Warming decreased and grazing increased plant uptake of amino acids in an alpine meadow.

    PubMed

    Ma, Shuang; Zhu, Xiaoxue; Zhang, Jing; Zhang, Lirong; Che, Rongxiao; Wang, Fang; Liu, Hanke; Niu, Haishan; Wang, Shiping; Cui, Xiaoyong

    2015-09-01

    Organic nitrogen (N) uptake by plants has been recognized as a significant component of terrestrial N cycle. Several studies indicated that plants have the ability to switch their preference between inorganic and organic forms of N in diverse environments; however, research on plant community response in organic nitrogen uptake to warming and grazing is scarce. Here, we demonstrated that organic N uptake by an alpine plant community decreased under warming with (13)C-(15)N-enriched glycine addition method. After 6 years of treatment, warming decreased plant organic N uptake by 37% as compared to control treatment. Under the condition of grazing, warming reduced plant organic N uptake by 44%. Grazing alone significantly increased organic N absorption by 15%, whereas under warming condition grazing did not affect organic N uptake by the Kobresia humilis community on Tibetan Plateau. Besides, soil NO 3-N content explained more than 70% of the variability observed in glycine uptake, and C:N ratio in soil dissolved organic matter remarkably increased under warming treatment. These results suggested warming promoted soil microbial activity and dissolved organic N mineralization. Grazing stimulated organic N uptake by plants, which counteracted the effect of warming. PMID:26442646

  11. Intake of n-3 Polyunsaturated Fatty Acids Increases Omega-3 Index in Aged Male and Female Spontaneously Hypertensive Rats

    PubMed Central

    Bačová, Barbara; Seč, Peter; Čertik, Milan

    2013-01-01

    The purpose of this study was to examine whether n-3 PUFA intake affects n-3 and n-6 FA levels in plasma and red blood cells as well as omega-3 index in old male and female spontaneously hypertensive (SHR) and healthy rats. Plasma linoleic acid and eicosapentaenoic acid increased due to n-3 PUFA intake in SHR and healthy rats. Comparing to healthy rats the levels of PUFA in red blood cells of SHR were lower in males and higher in females with exception of arachidonic acid, which was high in males and low in females. Feeding of rats with n-3 PUFA resulted in increase of red blood cells levels of eicosapentaenoic acid and/or docosahexaenoic acid in a sex- and strain-dependent manner. Moreover, n-3 PUFA intake decreased arachidonic acid in healthy female rats but increased it in SHR and did not affect it in males. Omega-3 index was lower in SHR comparing to healthy rats and it increased due to the consumption of n-3 PUFA. Results point out sex- and strain-related differences in red blood cells levels of n-3 and n-6 PUFA in basal conditions as well as in response to n-3 PUFA intake. PMID:24967252

  12. Sulfur mustard-induced increase in intracellular free calcium level and arachidonic acid release from cell membrane

    SciTech Connect

    Ray, R.; Legere, R.H.; Majerus, B.J.; Petrali, J.P.

    1995-12-31

    The mechanism of action of the alkylating agent bis-(2-chloroethyl)sulfide (sulfur mustard, SM) was studied using the in thai vitro mouse neuroblastoma-rat glioma hybrid NG 108-1 S clonal p cell line model. Following 0.3 mM SM exposure, cell viability remained high (>80% of untreated control) up to 9 hr and then declined steadily to about 40% of control after 20-24 hr. During the early period of SM exposure, when there was no significant cell viability loss, the following effects were observed. The cellular glutathione level decreased 20% after 1 hr and 34% after 6 hr. Between 2 and 6 hr, there was a time-dependent increase (about 10 to 30%) in intracellular free calcium (Ca2+), which was localized to the limiting membrane of swollen endoplasmic reticula and mitochondria, to euchromatin areas of the nucleus, and to areas of the cytosol and plasma membrane. Moreover,there was also a time-dependent increase in the release of isotopically labeled arachidonic acid ((3H)AA) from cellular membranes. Increase in (3H)AA release was 28% at 3 hr and about 60-80% between 6 and 9 hr. This increase in I3HIAA release was inhibited by quinacrine (20 uM), which is a phospholipase (PLA2) inhibitor. At 16 hr after SM exposure, there was a large increase (about 200% of control) in I3HIAA release, which was coincident with a 50% loss of cell viability. These results suggest a Ca2+-mediated toxic mechanism of SM via PLA2 activation and arachidonate release.

  13. Increased Flow of Fatty Acids toward β-Oxidation in Developing Seeds of Arabidopsis Deficient in Diacylglycerol Acyltransferase Activity or Synthesizing Medium-Chain-Length Fatty Acids1

    PubMed Central

    Poirier, Yves; Ventre, Giovanni; Caldelari, Daniela

    1999-01-01

    Synthesis of polyhydroxyalkanoates (PHAs) from intermediates of fatty acid β-oxidation was used as a tool to study fatty acid degradation in developing seeds of Arabidopsis. Transgenic plants expressing a peroxisomal PHA synthase under the control of a napin promoter accumulated PHA in developing seeds to a final level of 0.06 mg g−1 dry weight. In plants co-expressing a plastidial acyl-acyl carrier protein thioesterase from Cuphea lanceolata and a peroxisomal PHA synthase, approximately 18-fold more PHA accumulated in developing seeds. The proportion of 3-hydroxydecanoic acid monomer in the PHA was strongly increased, indicating a large flow of capric acid toward β-oxidation. Furthermore, expression of the peroxisomal PHA synthase in an Arabidopsis mutant deficient in the enzyme diacylglycerol acyltransferase resulted in a 10-fold increase in PHA accumulation in developing seeds. These data indicate that plants can respond to the inadequate incorporation of fatty acids into triacylglycerides by recycling the fatty acids via β-oxidation and that a considerable flow toward β-oxidation can occur even in a plant tissue primarily devoted to the accumulation of storage lipids. PMID:10594123

  14. Fed levels of amino acids are required for the somatotropin-induced increase in muscle protein synthesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chronic somatotropin (pST) treatment in pigs increases muscle protein synthesis and circulating insulin, a known promoter of protein synthesis. Previously, we showed that the pST-mediated rise in insulin could not account for the pST-induced increase in muscle protein synthesis when amino acids were...

  15. Potassium increases the antitumor effects of ascorbic acid in breast cancer cell lines in vitro

    PubMed Central

    FRAJESE, GIOVANNI VANNI; BENVENUTO, MONICA; FANTINI, MASSIMO; AMBROSIN, ELENA; SACCHETTI, PAMELA; MASUELLI, LAURA; GIGANTI, MARIA GABRIELLA; MODESTI, ANDREA; BEI, ROBERTO

    2016-01-01

    Ascorbic acid (A) has been demonstrated to exhibit anti-cancer activity in association with chemotherapeutic agents. Potassium (K) is a regulator of cellular proliferation. In the present study, the biological effects of A and K bicarbonate, alone or in combination (A+K), on breast cancer cell lines were evaluated. The survival of cancer cells was determined by sulforhodamine B cell proliferation assay, while analysis of the cell cycle distribution was conducted via fluorescence-activated cell sorting. In addition, the expression of signaling proteins was analyzed upon treatment. The results indicated that there was a heterogeneous response of the different cell lines to A and K, and the best effects were achieved by A+K and A treatment. The interaction between A+K indicated an additive or synergistic effect. In addition, A+K increased the percentage of cells in the sub-G1 phase of the cell cycle, and was the most effective treatment in activating the degradation of poly(adenosine diphosphate-ribose) polymerase-1. In the breast cancer cell line MCF-7, A+K induced the appearance of the 18 kDa isoform of B-cell lymphoma-2-associated X protein (Bax), which is a more potent inducer of apoptosis than the full-length Bax-p21. The effects of A and K on the phosphorylation of extracellular signal-regulated kinase (ERK)1 and ERK2 were heterogeneous. In addition, treatment with K, A and A+K inhibited the expression of nuclear factor-κB. Overall, the results of the present study indicated that K potentiated the anti-tumoral effects of A in breast cancer cells in vitro. PMID:27313770

  16. Calyculin and okadaic acid promote perilipin phosphorylation and increase lipolysis in primary rat adipocytes.

    PubMed

    He, Jinhan; Jiang, Hongfeng; Tansey, John T; Tang, Chaoshu; Pu, Shenshen; Xu, Guoheng

    2006-02-01

    Lipolysis is primarily regulated by protein kinase A (PKA), which phosphorylates perilipin and hormone-sensitive lipase (HSL), and causes translocation of HSL from cytosol to lipid droplets in adipocytes. Perilipin coats lipid droplet surface and assumes to prevent lipase access to triacylglycerols, thus inhibiting basal lipolysis; phosphorylated perilipin facilitates lipolysis on PKA activation. Here, we induced lipolysis in primary rat adipocytes by inhibiting protein serine/threonine phosphatase with specific inhibitors, okadaic acid and calyculin. The incubation with calyculin promotes incorporation of 32Pi into perilipins, thus, confirming that perilipin is hyperphosphorylated. The lipolysis response to calyculin is gradually accompanied by increased accumulation of phosphorylated perilipin A in a concentration- and time-responsive manner. When perilipin phosphorylation is abrogated by the addition of N-ethylmaleimide, lipolysis ceases. Different from a considerable translocation of HSL upon PKA activation with isoproterenol, calyculin does not alter HSL redistribution in primary or differentiated adipocytes, as confirmed by both immunostaining and immunoblotting. Thus, we suggest that inhibition of the phosphatase by calyculin activates lipolysis via promoting perilipin phosphorylation rather than eliciting HSL translocation in adipocytes. Further, we show that when the endogenous phosphatase is inhibited by calyculin, simultaneous PKA activation with isoproterenol converts most of the perilipin to the hyperphosphorylated species, and induces enhanced lipolysis. Apparently, as PKA phosphorylates perilipin and stimulates lipolysis, the phosphatase acts to dephosphorylate perilipin and attenuate lipolysis. This suggests a two-step strategy governed by a kinase and a phosphatase to modulate the steady state of perilipin phosphorylation and hence the lipolysis response to hormonal stimulation. PMID:16545598

  17. Significant enhancement of photoreactivity of graphitic carbon nitride catalysts under acidic conditions and the underlying H(+)-mediated mechanism.

    PubMed

    Zhang, Xue-Song; Tian, Ke; Hu, Jian-Yang; Jiang, Hong

    2015-12-01

    Graphitic carbon nitride (g-C3N4) is an emerging photocatalyst for organic pollutants degradation owing to its excellent stability and metal-free property. In this study, the photocatalytic activity of acidified g-C3N4 (ag-C3N4) was systematically investigated using rhodamine B (rhB) as a model organic pollutant. The results showed the photoreactivity of ag-C3N4 is significantly enhanced with the decrease of pH values. The apparent rate constant (kapp) of rhB degradation over ag-C3N4 is 11.59×10(-3)min(-1) at pH7.0 and it increases to 103.50×10(-3)min(-1) at pH3.0 under visible light. A series of analyses demonstrate that the photodegradation mechanism is a combination of a H(+)-promoted generation of OH and elevation of the redox potential of conduct band of C3N4. The change of surface properties of C3N4 caused by pH variation also affects the degradation of some zwitterionic compounds by changing the adsorption orientation of pollutants. The revealed mechanism of visible light-C3N4-rhB system is meaningful to broaden the usage of C3N4 to the photodegradation of other organic pollutants. PMID:26172516

  18. Valproic Acid Increases CD133 Positive Cells that Show Low Sensitivity to Cytostatics in Neuroblastoma.

    PubMed

    Khalil, Mohamed Ashraf; Hraběta, Jan; Groh, Tomáš; Procházka, Pavel; Doktorová, Helena; Eckschlager, Tomáš

    2016-01-01

    Valproic acid (VPA) is a well-known antiepileptic drug that exhibits antitumor activities through its action as a histone deacetylase inhibitor. CD133 is considered to be a cancer stem cell marker in several tumors including neuroblastoma. CD133 transcription is strictly regulated by epigenetic modifications. We evaluated the epigenetic effects of treatment with 1mM VPA and its influence on the expression of CD133 in four human neuroblastoma cell lines. Chemoresistance and cell cycle of CD133+ and CD133- populations were examined by flow cytometry. We performed bisulfite conversion followed by methylation-sensitive high resolution melting analysis to assess the methylation status of CD133 promoters P1 and P3. Our results revealed that VPA induced CD133 expression that was associated with increased acetylation of histones H3 and H4. On treatment with VPA and cytostatics, CD133+ cells were mainly detected in the S and G2/M phases of the cell cycle and they showed less activated caspase-3 compared to CD133- cells. UKF-NB-3 neuroblastoma cells which express CD133 displayed higher colony and neurosphere formation capacities when treated with VPA, unlike IMR-32 which lacks for CD133 protein. Induction of CD133 in UKF-NB-3 was associated with increased expression of phosphorylated Akt and pluripotency transcription factors Nanog, Oct-4 and Sox2. VPA did not induce CD133 expression in cell lines with methylated P1 and P3 promoters, where the CD133 protein was not detected. Applying the demethylating agent 5-aza-2'-deoxycytidine to the cell lines with methylated promoters resulted in CD133 re-expression that was associated with a drop in P1 and P3 methylation level. In conclusion, CD133 expression in neuroblastoma can be regulated by histone acetylation and/or methylation of its CpG promoters. VPA can induce CD133+ cells which display high proliferation potential and low sensitivity to cytostatics in neuroblastoma. These results give new insight into the possible

  19. Rosiglitazone increases fatty acid oxidation and fatty acid translocase (FAT/CD36) but not carnitine palmitoyltransferase I in rat muscle mitochondria

    PubMed Central

    Benton, Carley R; Holloway, Graham P; Campbell, S E; Yoshida, Yuko; Tandon, Narendra N; Glatz, Jan F C; Luiken, Joost J J F P; Spriet, Lawrence L; Bonen, Arend

    2008-01-01

    Peroxisome proliferator-activated receptors (PPARs) alter the expression of genes involved in regulating lipid metabolism. Rosiglitazone, a PPARγ agonist, induces tissue-specific effects on lipid metabolism; however, its mode of action in skeletal muscle remains unclear. Since fatty acid translocase (FAT/CD36) was recently identified as a possible regulator of skeletal muscle fatty acid transport and mitochondrial fatty acid oxidation, we examined in this tissue the effects of rosiglitazone infusion (7 days, 1 mg day−1) on FAT/CD36 mRNA and protein, its plasmalemmal content and fatty acid transport. In addition, in isolated subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria we examined rates of fatty acid oxidation, FAT/CD36 and carnitine palmitoyltransferase I (CPTI) protein, and CPTI and β-hydroxyacyl CoA dehydrogenase (β-HAD) activities. Rosiglitazone did not alter FAT/CD36 mRNA or protein expression, FAT/CD36 plasmalemmal content, or the rate of fatty acid transport into muscle (P > 0.05). In contrast, rosiglitazone increased the rates of fatty acid oxidation in both SS (+21%) and IMF mitochondria (+36%). This was accompanied by concomitant increases in FAT/CD36 in subsarcolemmal (SS) (+43%) and intermyofibrillar (IMF) mitochondria (+46%), while SS and IMF CPTI protein content, and CPTI submaximal and maximal activities (P > 0.05) were not altered. Similarly, citrate synthase (CS) and β-HAD activities were also not altered by rosiglitazone in SS and IMF mitochondria (P > 0.05). These studies provide another example whereby changes in mitochondrial fatty oxidation are associated with concomitant changes in mitochondrial FAT/CD36 independent of any changes in CPTI. Moreover, these studies identify for the first time a mechanism by which rosiglitazone stimulates fatty acid oxidation in skeletal muscle, namely the chronic, subcellular relocation of FAT/CD36 to mitochondria. PMID:18238811

  20. A 24.7-kDa copper-containing oxidase, secreted by Thermobifida fusca, significantly increasing the xylanase/cellulase-catalyzed hydrolysis of sugarcane bagasse.

    PubMed

    Chen, Cheng-Yu; Hsieh, Zhi-Shen; Cheepudom, Jatuporn; Yang, Chao-Hsun; Meng, Menghsiao

    2013-10-01

    Thermobifida fusca is a moderately thermophilic soil bacterium belonging to Actinobacteria. It has been known for its capability to degrade plant cell wall polymers except lignin and pectin. To know whether it can produce enzymes to facilitate lignin degradation, the extracellular proteins bound to sugarcane bagasse were harvested and identified by liquid chromatography tandem mass spectrometry. Among the identified proteins, a putative copper-containing polyphenol oxidase of 241 amino acids, encoded by the locus Tfu_1114, was thought to presumably play a role in lignin degradation. This protein (Tfu1114) was thus expressed in E. coli and characterized. Similarly to common laccases, Tfu1114 is able to catalyze the oxidation reaction of phenolic and nonphenolic lignin related compounds such as 2,6-dimethoxyphenol and veratryl alcohol. More interestingly, it can significantly enhance the enzymatic hydrolysis of bagasse by xylanase and cellulase. Tfu1114 is stable against heat, with a half-life of 4.7 h at 90 °C, and organic solvents. It is sensitive to ethylenediaminetetraacetic acid and reducing agents but resistant to sodium azide, a potent inhibitor of laccases. Atomic absorption spectroscopy indicated that the ratio of copper to the protein monomer is 1, instead of 4, a feature of classical laccases. All these data suggest that Tfu1114 is a novel oxidase with laccase-like activity, potentially useful in biotechnology application. PMID:23377789

  1. Fibers from fruit by-products enhance probiotic viability and fatty acid profile and increase CLA content in yoghurts.

    PubMed

    do Espírito Santo, Ana Paula; Cartolano, Nathalie S; Silva, Thaiane F; Soares, Fabiana A S M; Gioielli, Luiz A; Perego, Patrizia; Converti, Attilio; Oliveira, Maricê N

    2012-03-15

    This study evaluated the effect of the supplementation of total dietary fiber from apple, banana or passion fruit processing by-products on the post-acidification, total titratable acidity, bacteria counts and fatty acid profiles in skim milk yoghurts co-fermented by four different probiotics strains: Lactobacillus acidophilus L10 and Bifidobacterium animalis subsp. lactis BL04, HN019 and B94. Apple and banana fibers increased the probiotic viability during shelf-life. All the fibers were able to increase the short chain and polyunsaturated fatty acid contents of yoghurts compared to their respective controls. A synergistic effect between the type of fiber and the probiotic strain on the conjugated linoleic acid content was observed, and the amount of α-linolenic acid was increased by banana fiber. The results of this study demonstrate, for the first time, that fruit fibers can improve the fatty acid profile of probiotic yoghurts and point out the suitability of using fibers from fruit processing the by-products to develop new high value-added fermented dairy products. PMID:22264421

  2. Uric acid is a danger signal of increasing risk for osteoarthritis through inflammasome activation

    PubMed Central

    Denoble, Anna E.; Huffman, Kim M.; Stabler, Thomas V.; Kelly, Susan J.; Hershfield, Michael S.; McDaniel, Gary E.; Coleman, R. Edward; Kraus, Virginia B.

    2011-01-01

    Uric acid (UA) is known to activate the NLRP3 (Nacht, leucine-rich repeat and pyrin domain containing protein 3) inflammasome. When activated, the NLRP3 (also known as NALP3) inflammasome leads to the production of IL-18 and IL-1β. In this cohort of subjects with knee osteoarthritis (OA), synovial fluid uric acid was strongly correlated with synovial fluid IL-18 and IL-1β. Synovial fluid uric acid and IL-18 were strongly and positively associated with OA severity as measured by both radiograph and bone scintigraphy, and synovial fluid IL-1β was associated with OA severity but only by radiograph. Furthermore, synovial fluid IL-18 was associated with a 3-y change in OA severity, on the basis of the radiograph. We conclude that synovial fluid uric acid is a marker of knee OA severity. The correlation of synovial fluid uric acid with the two cytokines (IL-18 and IL-1β) known to be produced by uric acid-activated inflammasomes and the association of synovial fluid IL-18 with OA progression, lend strong support to the potential involvement of the innate immune system in OA pathology and OA progression. PMID:21245324

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

    PubMed

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

    2016-10-01

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

  4. Cis-urocanic acid increases immunotoxicity and lethality of dermally administered permethrin in C57BL/6N mice.

    PubMed

    Prater, M R; Gogal, R M; Blaylock, B L; Holladay, S D

    2003-01-01

    Immunomodulatory effects of a single topical permethrin exposure, 5-day exposure to cis-urocanic acid (cUCA), or a combination of the two chemicals were evaluated in 4- to 5-week-old female C57BL/6N mice. Permethrin alone decreased thymic weight and cellularity. Although cUCA alone did not affect thymic end points, coexposure to topical permethrin and cUCA exacerbated the thymolytic effects of permethrin. The single topical dose of permethrin also depressed several immune responses in isolated splenic leukocytes. This included splenic T-cell proliferative response to mitogen, splenic macrophage hydrogen peroxide production, and splenic B lymphocyte-specific antibody production. Unlike the effect of coexposure to these agents on thymic end points, cUCA did not exacerbate permethrin's adverse effect on any of the splenic end points examined. These results appear to suggest divergent mechanisms by which these compounds affect precursor and functionally mature T cells. At the doses used in this study, permethrin caused neurotoxic effects, including lethality, in a portion of the mice. For undetermined reasons, cUCA significantly increased the rate of lethality caused by permethrin. Although the permethrin doses used in this study exceed that typically used in human medicine, these results raise some concerns about the possibility that sunlight, via cUCA, may increase the risk of adverse central nervous system and immune effects caused by permethrin alone. PMID:12573947

  5. Maternal obesity upregulates fatty acid and glucose transporters and increases expression of enzymes mediating fatty acid biosynthesis in fetal adipose tissue depots.

    PubMed

    Long, N M; Rule, D C; Zhu, M J; Nathanielsz, P W; Ford, S P

    2012-07-01

    Maternal nutrient restriction leads to alteration in fetal adipose tissue, and offspring from obese mothers have an increased risk of developing obesity. We hypothesized that maternal obesity increases fetal adipogenesis. Multiparous ewes (Columbia/Rambouillet cross 3 to 5 yr of age) carrying twins were assigned to a diet of 100% (Control; CON; n = 4) or 150% (Obese; OB, n = 7) of NRC maintenance requirements from 60 d before conception until necropsy on d 135 of gestation. Maternal and fetal plasma were collected and stored at -80°C for glucose and hormone analyses. Fetal measurements were made at necropsy, and perirenal, pericardial, and subcutaneous adipose tissues were collected from 7 male twin fetuses per group and snap frozen at -80°C. Protein and mRNA expression of fatty acid translocase [cluster of differentiation (CD) 36], fatty acid transport proteins (FATP) 1 and 4, insulin-sensitive glucose transporter (GLUT-4), fatty acid synthase (FASN), and acetyl-coA carboxylase (ACC) was evaluated. Fetal weight was similar, but fetal carcass weight (FCW) was reduced (P < 0.05) in OB versus CON fetuses. Pericardial and perirenal adipose tissue weights were increased (P < 0.05) as a percentage of FCW in OB versus CON fetuses, as was subcutaneous fat thickness (P < 0.001). Average adipocyte diameter was greater (P < 0.01) in the perirenal fat and the pericardial fat (P = 0.06) in OB fetuses compared with CON fetuses. Maternal plasma showed no difference (P > 0.05) in glucose or other hormones, fetal plasma glucose was similar (P = 0.42), and cortisol, IGF-1, and thyroxine were reduced (P ≤ 0.05) in OB fetuses compared with CON fetuses. Protein and mRNA expression of CD 36, FATP 1 and 4, and GLUT-4 were increased (P ≤ 0.05) in all fetal adipose depots in OB versus CON fetuses. The mRNA expression of FASN and ACC was increased (P < 0.05) in OB vs. CON fetuses in all 3 fetal adipose tissue depots. Fatty acid concentrations were increased (P = 0.01) in the

  6. Reduced gastric acid production in burn shock period and its significance in the prevention and treatment of acute gastric mucosal lesions.

    PubMed

    Zhu, Li; Yang, Zhong-Cheng; Li, Ao; Cheng, De-Chang

    2000-02-01

    AIM:To investigate the changes of gastric acid production and its mechanism in shock period of severe burn in rats.METHODS:A rat model with 30% TBSA full thickness burn injury was employed and the gastric acid production,together with gastric mucosal blood flow (GMBF) and energy charge (EC) were measured serially within 48h postburn.RESULTS:The gastric acid production in the acute shock period was markedly inhibited after severe burn injury.At the 3rd h postburn,the gastric juice volume, total acidity and acid output were already significantly decreased (P < 0.01 =, and reached the lowest point, 0.63mL/L ± 0.20mL/L, 10.81mmol/L ± 2.58mmol/L and 2.23mmol/h ± 0.73mmol/h respectively, at the 12th h postburn. Although restored to some degree 24h after thermal injury, the variables above were still statistically lower, compared with those of control animals at the 48th h postburn. The GMBF and EC were also significantly reduced after severe burns, consistent with the trend of gastric acid production changes.CONCLUSION:Gastric acid production, as well as GMBF and EC was predominantly decreased in the early postburn stage, suggesting that gastric mucosal ischemia and hypoxia with resultant disturbance in energy metabolism, but not gastric acid proper, might be the decisive factor in the pathogenesis of AGML after thermal injury, and that the preventive use of anti-acid drugs during burn shock period was unreasonable in some respects. Therefore, taking effective measures to improve gastric mucosal blood perfusion as early as possible postburn might be more preferable for the AGML prevention and treatment. PMID:11819529

  7. COX-2, aspirin and metabolism of arachidonic, eicosapentaenoic and docosahexaenoic acids and their physiological and clinical significance.

    PubMed

    Poorani, R; Bhatt, Anant N; Dwarakanath, B S; Das, Undurti N

    2016-08-15

    Polyunsaturated fatty acids (PUFAs) are vital for normal growth and development and physiological function of various tissues in humans. PUFAs have immunomodulatory actions in addition to their ability to modulate inflammation, vascular reactivity, neurotransmission and stem cell biology. PUFAs and their metabolites possess both pro- and anti-inflammatory properties that underlie their actions and involvement in several diseases. Aspirin, a non-steroidal anti-inflammatory drug (NSAID), possesses both cyclo-oxygenase (COX) and lipoxygenase (LOX) inhibitory action and enhances the production of anti-inflammatory lipoxin A4 {(called as epi-lipoxin A4, aspirin-triggered lipoxins (ATLs))}. In addition, at low doses aspirin may not interfere with the production of prostacyclin (PGI2). Both lipoxin A4 and PGI2 have vasodilator, platelet anti-aggregator and anti-inflammatory actions that may underlie the beneficial actions of aspirin. Paradoxically, other NSAIDs may not have the same actions as that of aspirin on PUFA metabolism. Similar anti-inflammatory compounds are formed from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) by the action of aspirin termed as resolvins (from EPA and DHA) and protectins and maresins from DHA. PUFAs: arachidonic acid (AA), EPA and DHA and their various products modulate not only inflammation and immune response but also possess actions on various genes, nuclear factors, cyclic AMP and GMP, G-protein coupled receptors (GPRs), hypothalamic neurotransmitters, hormones, cytokines and enzymes, and interact with nitric oxide, carbon monoxide, and hydrogen sulfide to regulate their formation and action and to form new compounds that have several biological actions. These pleiotropic actions of PUFAs and their metabolites may explain their ability to play a role in several physiological actions and diseases. The big challenge is to harness these actions to prevent and manage clinical conditions. PMID:26335394

  8. Estimates of Soil Bacterial Ribosome Content and Diversity Are Significantly Affected by the Nucleic Acid Extraction Method Employed.

    PubMed

    Wüst, Pia K; Nacke, Heiko; Kaiser, Kristin; Marhan, Sven; Sikorski, Johannes; Kandeler, Ellen; Daniel, Rolf; Overmann, Jörg

    2016-05-01

    Modern sequencing technologies allow high-resolution analyses of total and potentially active soil microbial communities based on their DNA and RNA, respectively. In the present study, quantitative PCR and 454 pyrosequencing were used to evaluate the effects of different extraction methods on the abundance and diversity of 16S rRNA genes and transcripts recovered from three different types of soils (leptosol, stagnosol, and gleysol). The quality and yield of nucleic acids varied considerably with respect to both the applied extraction method and the analyzed type of soil. The bacterial ribosome content (calculated as the ratio of 16S rRNA transcripts to 16S rRNA genes) can serve as an indicator of the potential activity of bacterial cells and differed by 2 orders of magnitude between nucleic acid extracts obtained by the various extraction methods. Depending on the extraction method, the relative abundances of dominant soil taxa, in particularActinobacteriaandProteobacteria, varied by a factor of up to 10. Through this systematic approach, the present study allows guidelines to be deduced for the selection of the appropriate extraction protocol according to the specific soil properties, the nucleic acid of interest, and the target organisms. PMID:26896137

  9. Exposure to Kynurenic Acid during Adolescence Increases Sign-Tracking and Impairs Long-Term Potentiation in Adulthood

    PubMed Central

    DeAngeli, Nicole E.; Todd, Travis P.; Chang, Stephen E.; Yeh, Hermes H.; Yeh, Pamela W.; Bucci, David J.

    2015-01-01

    Changes in brain reward systems are thought to contribute significantly to the cognitive and behavioral impairments of schizophrenia, as well as the propensity to develop co-occurring substance abuse disorders. Presently, there are few treatments for persons with a dual diagnosis and little is known about the neural substrates that underlie co-occurring schizophrenia and substance abuse. One goal of the present study was to determine if a change in the concentration of kynurenic acid (KYNA), a tryptophan metabolite that is increased in the brains of people with schizophrenia, affects reward-related behavior. KYNA is an endogenous antagonist of NMDA glutamate receptors and α7 nicotinic acetylcholine receptors, both of which are critically involved in neurodevelopment, plasticity, and behavior. In Experiment 1, rats were treated throughout adolescence with L-kynurenine (L-KYN), the precursor of KYNA. As adults, the rats were tested drug-free in an autoshaping procedure in which a lever was paired with food. Rats treated with L-KYN during adolescence exhibited increased sign-tracking behavior (lever pressing) when they were tested as adults. Sign-tracking is thought to reflect the lever acquiring incentive salience (motivational value) as a result of its pairing with reward. Thus, KYNA exposure may increase the incentive salience of cues associated with reward, perhaps contributing to an increase in sensitivity to drug-related cues in persons with schizophrenia. In Experiment 2, we tested the effects of exposure to KYNA during adolescence on hippocampal long-term potentiation (LTP). Rats treated with L-KYN exhibited no LTP after a burst of high-frequency stimulation that was sufficient to produce robust LTP in vehicle-treated rats. This finding represents the first demonstrated consequence of elevated KYNA concentration during development and provides insight into the basis for cognitive and behavioral deficits that result from exposure to KYNA during adolescence

  10. Increased expression of retinoic acid-induced gene 1 in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression

    PubMed Central

    Haybaeck, Johannes; Postruznik, Magdalena; Miller, Christine L; Dulay, Jeannette R; Llenos, Ida C; Weis, Serge

    2015-01-01

    Background Retinoids regulate gene expression in different cells and tissues at the transcriptional level. Retinoic acid transcriptionally regulates downstream regulatory molecules, including enzymes, transcription factors, cytokines, and cytokine receptors. Animal models indicate an involvement of retinoid signaling pathways in the regulation of synaptic plasticity and learning, especially in the hippocampus. Retinoic acid-inducible or induced gene 1 (RAI-1) is induced during neuronal differentiation, and was associated with the severity of the phenotype and response to medication in schizophrenic patients. Methods In the present study, we used immunohistochemistry to investigate the expression of RAI-1 in 60 brains from the Stanley Neuropathology Consortium (15 cases each from controls and from patients with schizophrenia, bipolar disorder, and major depression). Rating scores for density and intensity were determined in the dorsolateral prefrontal cortex. Results All four groups showed high interindividual variation. RAI-1-positive cells were identified as neurons and astrocytes. Significantly increased intensities in cortical neurons were noted in all three major psychiatric groups compared with controls. The density of RAI-1-positive neurons was increased (P=0.06) in schizophrenia and bipolar disorder. In bipolar disorder, RAI-1-positive astrocytes in gray matter showed a significantly increased intensity and compound value. Thus, a significant increase in the parameters measured was found in schizophrenia, bipolar disorder, and major depression. Conclusion Our study shows a significant increase in expression of RAI-1 in the brains from patients with schizophrenia, bipolar disorder, or major depression. The increased expression might reflect altered signaling pathways, like that for retinoic acid. The underlying mechanisms leading to the increased expression and its functional consequences are so far unknown, and remain to be investigated in future studies

  11. Pre-harvest application of oxalic acid increases quality and resistance to Penicillium expansum in kiwifruit during postharvest storage.

    PubMed

    Zhu, Yuyan; Yu, Jie; Brecht, Jeffrey K; Jiang, Tianjia; Zheng, Xiaolin

    2016-01-01

    Kiwifruit (Actinidia deliciosa cv. Bruno) fruits were sprayed with 5mM oxalic acid (OA) at 130, 137, and 144 days after full blossom, and then harvested at commercial maturity [soluble solid content (SSC) around 10.0%] and stored at room temperature (20 ± 1 °C). Pre-harvest application of OA led to fruit with higher ascorbic acid content at harvest, slowed the decreases in fruit firmness and ascorbic acid content and increase in SSC during storage, and also decreased the natural disease incidence, lesion diameter, and patulin accumulation in fruit inoculated with Penicillium expansum, indicating that the OA treatment increased quality and induced disease resistance in kiwifruit. It was suggested that the increase in activities of defense-related enzymes and in levels of substances related to disease resistance might collectively contribute to resistance in kiwifruit against fungi such as P. expansum in storage. PMID:26213007

  12. Carica papaya Leaves Juice Significantly Accelerates the Rate of Increase in Platelet Count among Patients with Dengue Fever and Dengue Haemorrhagic Fever.

    PubMed

    Subenthiran, Soobitha; Choon, Tan Chwee; Cheong, Kee Chee; Thayan, Ravindran; Teck, Mok Boon; Muniandy, Prem Kumar; Afzan, Adlin; Abdullah, Noor Rain; Ismail, Zakiah

    2013-01-01

    The study was conducted to investigate the platelet increasing property of Carica papaya leaves juice (CPLJ) in patients with dengue fever (DF). An open labeled randomized controlled trial was carried out on 228 patients with DF and dengue haemorrhagic fever (DHF). Approximately half the patients received the juice, for 3 consecutive days while the others remained as controls and received the standard management. Their full blood count was monitored 8 hours for 48 hours. Gene expression studies were conducted on the ALOX 12 and PTAFR genes. The mean increase in platelet counts were compared in both groups using repeated measure ANCOVA. There was a significant increase in mean platelet count observed in the intervention group (P < 0.001) but not in the control group 40 hours since the first dose of CPLJ. Comparison of mean platelet count between intervention and control group showed that mean platelet count in intervention group was significantly higher than control group after 40 and 48 hours of admission (P < 0.01). The ALOX 12 (FC  =  15.00) and PTAFR (FC  =  13.42) genes were highly expressed among those on the juice. It was concluded that CPLJ does significantly increase the platelet count in patients with DF and DHF. PMID:23662145

  13. Responses to increasing amounts of high-oleic sunflower fatty acids infused into the abomasum of lactating dairy cows.

    PubMed

    Drackley, J K; Overton, T R; Ortiz-Gonzalez, G; Beaulieu, A D; Barbano, D M; Lynch, J M; Perkins, E G

    2007-11-01

    Increasing the oleic acid (18:1 cis-9) content of milk fat might be desirable to meet consumer concerns about dietary healthfulness and for certain manufacturing applications. The extent to which milk fat could be enriched with oleic acid is not known. Increasing the intestinal supply of polyunsaturated fatty acids decreases dry matter intake (DMI) in cows, but the effects of oleic acid have not been quantified. In a crossover design, 4 multiparous Holstein cows were abomasally infused with increasing amounts (0, 250, 500, 750, or 1,000 g/d) of free fatty acids from high-oleic sunflower oil (HOSFA) or with carrier alone. Continuous infusions (20 to 22 h/d) were for 7 d at each amount. Infusions were homogenates of HOSFA with 240 g/d of meat solubles and 11.2 g/d of Tween 80; controls received carrier only. The HOSFA contained (by wt) 2.4% 16:0, 1.8% 18:0, 91.4% 18:1 cis-9, and 2.4% 18:2. The DMI decreased linearly (range 22.0 to 5.8 kg/d) as the infused amount of HOSFA increased. Apparent total tract digestibilities of dry matter, organic matter, neutral detergent fiber, and energy decreased as the infusion increased to 750 g/d and then increased when 1,000 g/d was infused. Digestibility of total fatty acids increased linearly as infused fatty acids increased. Yields of milk, fat, true protein, casein, and total solids decreased quadratically as infused amounts increased; decreases were greatest when 750 or 1,000 g/d of HOSFA were infused. Concentrations of fat and total solids increased at the higher amounts of HOSFA. The volume mean diameter of milk fat droplets and the diameter below which 90% of the volume of milk fat is contained both increased as HOSFA infusion increased. Concentrations of short-chain fatty acids, 12:0, 14:0, and 16:0 in milk fat decreased linearly as HOSFA increased. The concentration of 18:1 cis-9 (19.4 to 57.4% of total fatty acids) increased linearly as HOSFA infusion increased. Concentrations of 18:1 cis-9 in blood triglyceride

  14. Treatment of flaxseed to reduce biohydrogenation of a-linolenic acid by ruminal microbes in sheep and cattle and increase n-3 fatty acid concentrations in red meat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our study determined if flaxseed treated with a formaldehyde-free process increased n-3 fatty acid (FA) levels in ruminant muscle. Twenty-four lambs (initial BW 43.8 ± 4.4 kg) were randomly divided into 4 groups for a 90-d trial. One treatment group (FLX) was fed 136 g/d of non-treated ground flaxse...

  15. Role of a single amino acid substitution of VP3 H142D for increased acid resistance of foot-and-mouth disease virus serotype A.

    PubMed

    Biswal, Jitendra K; Das, Biswajit; Sharma, Gaurav K; Khulape, Sagar A; Pattnaik, Bramhadev

    2016-04-01

    Foot-and-mouth disease virus (FMDV) particles lose infectivity due to their dissociation into pentamers at pH value below 6.5. After the uptake of FMDV by receptor-mediated endocytosis, the acid-dependent dissociation process is required for the release of FMDV genome inside endosomes. Nevertheless, dissociation of FMDV particles in mildly acidic conditions renders the inactivated FMD vaccine less effective. To improve the acid stability of inactivated FMD vaccine during the manufacturing process, a serotype A IND 40/2000 (in-use vaccine strain) mutant with increased resistance to acid inactivation was generated through reverse genetics approach. Based upon the earlier reports, the crucial amino acid residue, H142 of VP3 capsid protein was substituted separately to various amino acid residues Arg (R), Phe (F), Ala (A), and Asp (D) on the full-genome length cDNA clone. While the H142 → R or H142 → F or H142 → A substitutions resulted in non-infectious FMDV, H142 → D mutation on VP3 protein (H3142D) resulted in the generation of mutant virus with enhanced resistance to acid-induced inactivation. In addition, H3142D substitution did not alter the replication ability and antigenicity of mutant as compared to the parental virus. However, the virus competition experiments revealed that the H3142D substitution conferred a loss of fitness for the mutant virus. Results from this study demonstrate that the H3142D substitution is the molecular determinant of acid-resistant phenotype in FMDV serotype A. PMID:26873406

  16. Increased fatty acid synthesis inhibits nitrogen starvation-induced autophagy in lipid droplet-deficient yeast.

    PubMed

    Régnacq, Matthieu; Voisin, Pierre; Sere, Yves Y; Wan, Bin; Soeroso, Venty M S; Bernard, Marianne; Camougrand, Nadine; Bernard, François-Xavier; Barrault, Christine; Bergès, Thierry

    2016-08-12

    Macroautophagy is a degradative pathway whereby cells encapsulate and degrade cytoplasmic material within endogenously-built membranes. Previous studies have suggested that autophagosome membranes originate from lipid droplets. However, it was recently shown that rapamycin could induce autophagy in cells lacking these organelles. Here we show that lipid droplet-deprived cells are unable to perform autophagy in response to nitrogen-starvation because of an accelerated lipid synthesis that is not observed with rapamycin. Using cerulenin, a potent inhibitor of fatty acid synthase, and exogenous addition of palmitic acid we could restore nitrogen-starvation induced autophagy in the absence of lipid droplets. PMID:27270031

  17. Maternal Obesity in Sheep Increases Fatty Acid Synthesis, Upregulates Nutrient Transporters, and Increases Adiposity in Adult Male Offspring after a Feeding Challenge

    PubMed Central

    Long, Nathan M.; Rule, Daniel C.; Tuersunjiang, Nuermaimaiti; Nathanielsz, Peter W.; Ford, Stephen P.

    2015-01-01

    Maternal obesity in women is increasing worldwide. The objective of this study was to evaluate differences in adipose tissue metabolism and function in adult male offspring from obese and control fed mothers subjected to an ad libitum feeding challenge. We developed a model in which obese ewes were fed 150% of feed provided for controls from 60 days before mating to term. All ewes were fed to requirements during lactation. After weaning, F1 male offspring were fed only to maintenance requirements until adulthood (control = 7, obese = 6), when they were fed ad libitum for 12 weeks with intake monitored. At the end of the feeding challenge offspring were given an intravenous glucose tolerance test (IVGTT), necropsied, and adipose tissue collected. During the feeding trial F1obese males consumed more (P < 0.01), gained more weight (P < 0.01) and became heavier (P < 0.05) than F1control males. During IVGTT, Obese F1 offspring were hyperglycemic and hypoinsulinemic (P < 0.01) compared to F1 control F1. At necropsy perirenal and omental adipose depots weights were 47% and 58% greater respectively and subcutaneous fat thickness 41% greater in F1obese vs F1control males (P < 0.05). Adipocyte diameters were greater (P ≤ 0.04) in perirenal, omental and subcutaneous adipose depots in F1obese males (11, 8 and 7% increase vs. control, respectively). When adipose tissue was incubated for 2 hrs with C-14 labeled acetate, subcutaneous, perirenal, and omental adipose tissue of F1 obese males exhibited greater incorporation (290, 83, and 90% increase vs. control, respectively P < 0.05) of acetate into lipids. Expression of fatty acid transporting, binding, and syntheses mRNA and protein was increased (P < 0.05) compared to F1 control offspring. Maternal obesity increased appetite and adiposity associated with increased adipocyte diameters and increased fatty acid synthesis in over-nourished adult male offspring. PMID:25875659

  18. Significant Increase in Hydrogen Photoproduction Rates and Yields by Wild-Type Algae is Detected at High Photobioreactor Gas Phase Volume (Fact Sheet)

    SciTech Connect

    Not Available

    2012-07-01

    This NREL Hydrogen and Fuel Cell Technical Highlight describes how hydrogen photoproduction activity in algal cultures can be improved dramatically by increasing the gas-phase to liquid-phase volume ratio of the photobioreactor. NREL, in partnership with subcontractors from the Institute of Basic Biological Problems in Pushchino, Russia, demonstrated that the hydrogen photoproduction rate in algal cultures always decreases exponentially with increasing hydrogen partial pressure above the culture. The inhibitory effect of high hydrogen concentrations in the photobioreactor gas phase on hydrogen photoproduction by algae is significant and comparable to the effect observed with some anaerobic bacteria.

  19. Hepatitis C Virus Increases Free Fatty Acids Absorption and Promotes its Replication Via Down-Regulating GADD45α Expression

    PubMed Central

    Chen, Wei; Li, Xiao-ming; Li, An-ling; Yang, Gui; Hu, Han-ning

    2016-01-01

    Background Hepatitis C virus (HCV) infection, as a major cause of chronic hepatic diseases, is always accompanied with an abnormality of lipid metabolism. The aim of this study was to investigate the pathogenic role of free fatty acids (FFA) in human HCV infection. Material/Methods Peripheral blood lipid indexes among HCV patients with different viral loads (199 samples) and healthy donors (80 samples) were detected by clinical biochemistry tests. HCV replication and the expression of growth arrest and DNA-damage-inducible gene 45-α (GADD45α) in Huh7 cells and clinical samples were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. Lipid accumulation in Huh7 cells was detected by immunofluorescence. Results In this study, we found that FFA showed a significant positive correlation with viral load in peripheral blood of HCV patients, but not total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), or low-density lipoprotein cholesterol (LDL-C). GADD45α expression in HCV patients dramatically decreased with the increase of viral load. In Huh7 cells, FFA treatment significantly enhanced HCV replication. HCV infection inhibited GADD45α expression, and this effect was further enhanced with the presence of FFA treatment. Ectopic expression of GADD45α in HCV-infected Huh7 cells markedly inhibited the absorption of FFA and HCV replication. However, FFA significantly elevated GADD45α expression without HCV infection. Conclusions These results demonstrated that HCV down-regulates GADD45α expression to enhance FFA absorption and thus facilitate its replication. GADD45α is an essential mediator for the pathogenesis of HCV infection. Thus, our study provides potential clues in the search for novel therapeutics and fatty lipid control options for HCV patients. PMID:27381636

  20. The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase

    PubMed Central

    Patel, Sachin; Wohlfeil, Eric R; Rademacher, David J; Carrier, Erica J; Perry, LaToya J; Kundu, Abhijit; Falck, J R; Nithipatikom, Kasem; Campbell, William B; Hillard, Cecilia J

    2003-01-01

    Propofol (2,6-diisopropylphenol) is widely used as a general anesthetic and for the maintenance of long-term sedation. We have tested the hypothesis that propofol alters endocannabinoid brain content and that this effect contributes to its sedative properties. A sedating dose of propofol in mice produced a significant increase in the whole-brain content of the endocannabinoid, N-arachidonylethanolamine (anandamide), when administered intraperitoneally in either Intralipid or emulphor-ethanol vehicles. In vitro, propofol is a competitive inhibitor (IC50 52 μM; 95% confidence interval 31, 87) of fatty acid amide hydrolase (FAAH), which catalyzes the degradation of anandamide. Within a series of propofol analogs, the critical structural determinants of FAAH inhibition and sedation were found to overlap. Other intravenous general anesthetics, including midazolam, ketamine, etomidate, and thiopental, do not affect FAAH activity at sedative-relevant concentrations. Thiopental, however, is a noncompetitive inhibitor of FAAH at a concentration of 2 mM. Pretreatment of mice with the CB1 receptor antagonist SR141716 (1 mg kg−1, i.p.) significantly reduced the number of mice that lost their righting reflex in response to propofol. Pretreatment of mice with the CB1 receptor agonist, Win 55212-2 (1 mg kg−1, i.p.), significantly potentiated the loss of righting reflex produced by propofol. These data indicate that CB1 receptor activity contributes to the sedative properties of propofol. These data suggest that propofol activation of the endocannabinoid system, possibly via inhibition of anandamide catabolism, contributes to the sedative properties of propofol and that FAAH could be a novel target for anesthetic development. PMID:12839875

  1. Acetylsalicylic Acid Reduces the Severity of Dextran Sodium Sulfate-Induced Colitis and Increases the Formation of Anti-Inflammatory Lipid Mediators

    PubMed Central

    Köhnke, Thomas; Bilal, Süleyman; Zhou, Xiangzhi; Rothe, Michael; Baumgart, Daniel C.; Weylandt, Karsten H.

    2013-01-01

    The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation. PMID:24083240

  2. Acetylsalicylic Acid reduces the severity of dextran sodium sulfate-induced colitis and increases the formation of anti-inflammatory lipid mediators.

    PubMed

    Köhnke, Thomas; Gomolka, Beate; Bilal, Süleyman; Zhou, Xiangzhi; Sun, Yanping; Rothe, Michael; Baumgart, Daniel C; Weylandt, Karsten H

    2013-01-01

    The role of non-steroidal anti-inflammatory drugs in inflammatory bowel disease is controversial, as they have been implicated in disease aggravation. Different from other cyclooxygenase inhibitors, acetylsalicylic acid (ASA) enhances the formation of anti-inflammatory and proresolution lipoxins derived from arachidonic acid as well as resolvins from omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA). In this study, we examined the effect of ASA on murine dextran sodium sulfate colitis. A mouse magnetic resonance imaging (MRI) protocol and post mortem assessment were used to assess disease severity, and lipid metabolites were measured using liquid chromatography-coupled tandem mass spectrometry. Decreased colitis activity was demonstrated by phenotype and MRI assessment in mice treated with ASA, and confirmed in postmortem analysis. Analysis of lipid mediators showed sustained formation of lipoxin A4 and an increase of DHA-derived 17-hydroxydocosahexaenoic acid (17-HDHA) after treatment with ASA. Furthermore, in vitro experiments in RAW264.7 murine macrophages demonstrated significantly increased phagocytosis activity after incubation with 17-HDHA, supporting its proresolution effect. These results show a protective effect of ASA in a murine colitis model and could give a rationale for a careful reassessment of ASA therapy in patients with inflammatory bowel disease and particularly ulcerative colitis, possibly combined with DHA supplementation. PMID:24083240

  3. Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

    PubMed Central

    Schuchardt, Jan Philipp; Schneider, Inga; Willenberg, Ina; Yang, Jun; Hammock, Bruce D.; Hahn, Andreas; Schebb, Nils Helge

    2014-01-01

    Introduction Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. Subjects and methods In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48 h of fish oil (1008 mg EPA and 672 mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC–MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. Results All EPA-derived oxylipin levels were significantly increased 6 h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48 h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Discussion and conclusions Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation. PMID:24667634

  4. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    PubMed

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions. PMID:22041135

  5. On the Nutritive Significance of Dissolved Free Amino Acid Uptake for the Cosmopolitan Oligochaete Nais elinguisMüller (Naididae)

    NASA Astrophysics Data System (ADS)

    Petersen, S.; Arlt, G.; Faubel, A.; Carman, K. R.

    1998-01-01

    Uptake of dissolved free amino acids (DFAA) byNais elinguisMüller from a brackish water lagoon has been confirmed by autoradiographic studies, liquid scintillation counting of animals incubated with labelled DFAA, and by HPLC analysis of the incubation water. Net uptake was shown to occur at ambient DFAA concentrations. The results indicate that most of the absorbed DFAA were respired, and only a minor portion was incorporated into proteins. Parallel determination of respiration and DFAA uptake in a flow-through system allowed a calculation of the contribution of uptake to the maintainance metabolism ofN. elinguis. The average weight-specific uptake rate of mixed DFAA was 1·4 μmol g-1h-1at a salinity of 6 and 4·1 μmol g-1h-1at a salinity of 12 (temperature 20 °C). Assuming that 10 μmol of mixed amino acids (average mol wt. 100) require 44·64 μmol O2for complete oxidation, the nutritional profit of DFAA absorption at a salinity of 6 accounted for 7% of the total oxidative needs and for 24% at a salinity of 12. The results demonstrate that DFAA uptake can provide an important nutritional input.

  6. Solution structure of gamma-bungarotoxin: the functional significance of amino acid residues flanking the RGD motif in integrin binding.

    PubMed

    Shiu, Jia-Hau; Chen, Chiu-Yueh; Chang, Long-Sen; Chen, Yi-Chun; Chen, Yen-Chin; Lo, Yu-Hui; Liu, Yu-Chen; Chuang, Woei-Jer

    2004-12-01

    Gamma-bungarotoxin, a snake venom protein isolated from Bungarus multicinctus, contains 68 amino acids, including 10 cysteine residues and a TAVRGDGP sequence at positions 30-37. The solution structure of gamma-bungarotoxin has been determined by nuclear magnetic resonance (NMR) spectroscopy. The structure is similar to that of the short-chain neurotoxins that contain three loops extending from a disulfide-bridged core. The tripeptide Arg-Gly-Asp (RGD) sequence is located at the apex of the flexible loop and is similar to that of other RGD-containing proteins. However, gamma-bungarotoxin only inhibits platelet aggregations with an IC50 of 34 microM. To understand its weak activity in inhibiting platelet aggregation, we mutated the RGD loop sequences of rhodostomin, a potent platelet aggregation inhibitor, from RIPRGDMP to TAVRGDGP, resulting in a 196-fold decrease in activity. In addition, the average Calpha-to-Calpha distance between R33 and G36 of gamma-bungarotoxin is 6.02 A, i.e., shorter than that of other RGD-containing proteins that range from 6.55 to 7.46 A. These results suggested that the amino acid residues flanking the RGD motif might control the width of the RGD loop. This structural difference may be responsible for its decrease in platelet aggregation inhibition compared with other RGD-containing proteins. PMID:15390258

  7. Surface functionalization of bioactive glasses with natural molecules of biological significance, Part I: Gallic acid as model molecule

    NASA Astrophysics Data System (ADS)

    Zhang, Xin; Ferraris, Sara; Prenesti, Enrico; Verné, Enrica

    2013-12-01

    Gallic acid (3,4,5-trihydroxybenzoic acid, GA) and its derivatives are a group of biomolecules (polyphenols) obtained from plants. They have effects which are potentially beneficial to heath, for example they are antioxidant, anticarcinogenic and antibacterial, as recently investigated in many fields such as medicine, food and plant sciences. The main drawbacks of these molecules are both low stability and bioavailability. In this research work the opportunity to graft GA to bioactive glasses is investigated, in order to deliver the undamaged biological molecule into the body, using the biomaterial surfaces as a localized carrier. GA was considered for functionalization since it is a good model molecule for polyphenols and presents several interesting biological activities, like antibacterial, antioxidant and anticarcinogenic properties. Two different silica based bioactive glasses (SCNA and CEL2), with different reactivity, were employed as substrates. UV photometry combined with the Folin&Ciocalteu reagent was adopted to test the concentration of GA in uptake solution after functionalization. This test verified how much GA consumption occurred with surface modification and it was also used on solid samples to test the presence of GA on functionalized glasses. XPS and SEM-EDS techniques were employed to characterize the modification of material surface properties and functional group composition before and after functionalization.

  8. Reducing dietary intake of linoleic acid of mouse dams during lactation increases offspring brain n-3 LCPUFA content.

    PubMed

    Schipper, L; Oosting, A; Scheurink, A J W; van Dijk, G; van der Beek, E M

    2016-07-01

    Omega (n-)3 and n-6 long chain polyunsaturated fatty acids (LCPUFA) accumulation in the infant brain after birth is strongly driven by dietary supply of n-3 and n-6 LCPUFAs and their C18 precursors through breast milk or infant formula. n-3 LCPUFA accretion is associated with positive effects on neurodevelopmental outcome whereas high n-6 LCPUFA accumulation is considered disadvantageous. Maternal diet is crucial for breast milk fatty acid composition. Unfortunately, global increases in linoleic acid (C18:2n-6; LA) intake have dramatically increased n-6 LCPUFA and reduced n-3 LCPUFA availability for breastfed infants. We investigated the effects of reducing maternal dietary LA, or increasing n-3 LCPUFA, during lactation on milk and offspring brain fatty acids in mice. Offspring brain n-3 LCPUFA was higher following both interventions, although effects were mediated by different mechanisms. Because of competitive interactions between n-3 and n-6 fatty acids, lowering maternal LA intake may support neurodevelopment in breastfed infants. PMID:27255638

  9. Oleanolic Acid Prevents Increase in Blood Pressure and Nephrotoxicity in Nitric Oxide Dependent Type of Hypertension in Rats

    PubMed Central

    Bachhav, Sagar S.; Bhutada, Mukesh S.; Patil, Sachin P.; Sharma, Kinjal S.; Patil, Savita D.

    2015-01-01

    Background: Recently, we have reported antihypertensive activity of oleanolic acid (OA) in glucocorticoid-induced hypertension with restoration of nitric oxide (NO) level. However, the involvement of NO-releasing action of OA was unclear. Objective: To explore antihypertensive activity of OA in Nω-nitro-L-arginine methyl ester (L-NAME) hypertensive rats wherein NO is completely blocked, which would allow exploring the possibility of involvement of NO-releasing action of OA. Materials and Methods: Five groups of rats were investigated as normal control, L-NAME (40 mg/kg/day), L-NAME + enalapril (15 mg/kg/day), L-NAME + l-arginine (100 mg/kg/day), and L-NAME + OA (60 mg/kg/day) for 4 weeks. The systolic blood pressure, body weight, and heart rate were measured weekly for 4 weeks. Serum nitrate/nitrite (NOx) level, urine electrolytes concentration, cardiac mass index, and serum creatinine level were determined followed by organ histopathology. Results: OA and enalapril delayed the rise in blood pleasure following L-NAME administration. Decreased serum NOx level was not significantly increased with any of the treatment. OA produced a small, though nonsignificant, increase in the NOx level. L-NAME administration did not affect cardiac mass index. There was an increase in serum creatinine upon L-NAME administration which was prevented by OA. Decreased urine volume, urine sodium and potassium were reversed by OA. Conclusion: These results suggest that the antihypertensive effect of OA in L-NAME hypertension is due to diuresis and nephroprotection. However, OA has nonsignificantly affected the NO levels. PMID:26692754

  10. Retinoic acid imprints a mucosal-like phenotype on dendritic cells with an increased ability to fuel HIV-1 infection.

    PubMed

    Guerra-Pérez, Natalia; Frank, Ines; Veglia, Filippo; Aravantinou, Meropi; Goode, Diana; Blanchard, James L; Gettie, Agegnehu; Robbiani, Melissa; Martinelli, Elena

    2015-03-01

    The tissue microenvironment shapes the characteristics and functions of dendritic cells (DCs), which are important players in HIV infection and dissemination. Notably, DCs in the gut have the daunting task of orchestrating the balance between immune response and tolerance. They produce retinoic acid (RA), which imprints a gut-homing phenotype and influences surrounding DCs. To investigate how the gut microenvironment impacts the ability of DCs to drive HIV infection, we conditioned human immature monocyte-derived DCs (moDCs) with RA (RA-DCs), before pulsing them with HIV and mixing them with autologous T cells. RA-DCs showed a semimature, mucosal-like phenotype and released higher amounts of TGF-β1 and CCL2. Using flow cytometry, Western blot, and microscopy, we determined that moDCs express the cell adhesion molecule mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) and that RA increases its expression. MAdCAM-1 was also detected on a small population of DCs in rhesus macaque (Macaca mulata) mesenteric lymph node. RA-DCs formed more DC-T cell conjugates and promoted significantly higher HIV replication in DC-T cell mixtures compared with moDCs. This correlated with the increase in MAdCAM-1 expression. Blocking MAdCAM-1 partially inhibited the enhanced HIV replication. In summary, RA influences DC phenotype, increasing their ability to exacerbate HIV infection. We describe a previously unknown mechanism that may contribute to rapid HIV spread in the gut, a major site of HIV replication after mucosal exposure. PMID:25624458

  11. Adaptation and Transcriptome Analysis of Aureobasidium pullulans in Corncob Hydrolysate for Increased Inhibitor Tolerance to Malic Acid Production

    PubMed Central

    Zou, Xiang; Wang, Yongkang; Tu, Guangwei; Zan, Zhanquan; Wu, Xiaoyan

    2015-01-01

    Malic acid is a dicarboxylic acid widely used in the food industry, and is also a potential C4 platform chemical. Corncob is a low-cost renewable feedstock from agricultural industry. However, side-reaction products (furfural, 5-hydroxymethylfurfural (HMF), formic acid, and acetic acid) that severely hinder fermentation are formed during corncob pretreatment. The process for producing malic acid from a hydrolysate of corncob was investigated with a polymalic acid (PMA)-producing Aureobasidium pullulans strain. Under the optimal hydrolysate sugar concentration 110 g/L, A. pullulans was further adapted in an aerobic fibrous bed bioreactor (AFBB) by gradually increasing the sugar concentration of hydrolysate. After nine batches of fermentation, the production and productivity of malic acid reached 38.6 g/L and 0.4 g/L h, respectively, which was higher than that in the first batch (27.6 g/L and 0.29 g/L h, respectively). The adapted strain could grow under the stress of 0.5 g/L furfural, 3 g/L HMF, 2g/L acetic acid, and 0.5 g/L formic acid, whereas the wild type did not. Transcriptome analysis revealed that the differentially expressed genes were related to carbohydrate transport and metabolism, lipid transport and metabolism, signal transduction mechanism, redox metabolism, and energy production and conversion under 0.5 g/L furfural and 3 g/L HMF stress conditions. In total, 42 genes in the adapted strain were upregulated by 15-fold or more, and qRT-PCR also confirmed that the expression levels of key genes (i.e. SIR, GSS, CYS, and GSR) involved in sulfur assimilation pathway were upregulated by over 10-fold in adapted strain for cellular protection against oxidative stress. PMID:25793624

  12. RESPONSE OF LOW SEED PHYTIC ACID SOYBEANS TO INCREASES IN EXTERNAL P SUPPLY

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Commercial development of soybean (Glycine max L. Merr.) varieties with low seed phytic acid concentrations will depend on both the stability of the trait when grown in soils with a wide range of phosphorus (P) availabilities, and on the impact of genetically altered P composition on protein and oil...

  13. Increased amoxicillin-clavulanic acid resistance in Escherichia coli blood isolates, Spain.

    PubMed

    Oteo, Jesús; Campos, José; Lázaro, Edurne; Cuevas, Oscar; García-Cobos, Silvia; Pérez-Vázquez, María; de Abajo, F J

    2008-08-01

    To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006. PMID:18680650

  14. Pros and cons of increasing folic acid and vitamin B12 intake by fortification

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is no doubt that folic acid fortification can be effective for reducing the incidence of neural tube defects (NTDs). The degree of efficacy depends on both the level of folate depletion and other, yet to be fully characterized, genetic and/or environmental factors. This article summarizes brie...

  15. 5,7-DIHYDROXYTRYPTAMINE INJECTIONS INCREASE GLIAL FIBRILLARY ACIDIC PROTEIN IN THE HYPOTHALAMUS OF ADULT RATS

    EPA Science Inventory

    The distribution and level of glial fibrillary acidic protein (GFAP) were determined in the adult rat hypothalamus following axotomy of serotonin (5-HT) neurons. even days after unilateral intrahypothalamic injection of the 5-HT neurotoxic, 5,7- dihydroxytryptamine, there gas a m...

  16. Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth.

    PubMed

    Yamashita, Aki; Kawana, Kei; Tomio, Kensuke; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Masuda, Koji; Furuya, Hitomi; Nagamatsu, Takeshi; Nagasaka, Kazunori; Arimoto, Takahide; Oda, Katsutoshi; Wada-Hiraike, Osamu; Yamashita, Takahiro; Taketani, Yuji; Kang, Jing X; Kozuma, Shiro; Arai, Hiroyuki; Arita, Makoto; Osuga, Yutaka; Fujii, Tomoyuki

    2013-01-01

    Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth. PMID:24177907

  17. Increased tissue levels of omega-3 polyunsaturated fatty acids prevents pathological preterm birth

    PubMed Central

    Yamashita, Aki; Kawana, Kei; Tomio, Kensuke; Taguchi, Ayumi; Isobe, Yosuke; Iwamoto, Ryo; Masuda, Koji; Furuya, Hitomi; Nagamatsu, Takeshi; Nagasaka, Kazunori; Arimoto, Takahide; Oda, Katsutoshi; Wada-Hiraike, Osamu; Yamashita, Takahiro; Taketani, Yuji; Kang, Jing X.; Kozuma, Shiro; Arai, Hiroyuki; Arita, Makoto; Osuga, Yutaka; Fujii, Tomoyuki

    2013-01-01

    Omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) have anti-inflammatory effects. Preterm birth is an important problem in modern obstetrics and one of the main causes is an inflammation. We here showed that abundance of omega-3 fatty acids reduced the incidence of preterm birth induced by LPS with fat-1 mice, capable of converting omega-6 to omega-3 fatty acids. We also indicated that the gene expression of IL-6 and IL-1β in uteruses and the number of cervical infiltrating macrophages were reduced in fat-1 mice. The analyses of lipid metabolomics showed the high level of 18-hydroxyeicosapentaenoate in fat-1 mice, which was derived from EPA and was metabolized to anti-inflammatory product named resolvin E3 (RvE3). We finally showed that the administration of RvE3 to LPS-exposed pregnant wild type mice lowered the incidence of preterm birth. Our data suggest that RvE3 could be a potential new therapeutic for the prevention of preterm birth. PMID:24177907

  18. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

    PubMed Central

    Schwieler, Lilly; Larsson, Markus K.; Skogh, Elisabeth; Kegel, Magdalena E.; Orhan, Funda; Abdelmoaty, Sally; Finn, Anja; Bhat, Maria; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schuppe-Koistinen, Ina; Svensson, Camilla I.; Erhardt, Sophie; Engberg, Göran

    2015-01-01

    Background Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia. PMID:25455350

  19. Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring

    PubMed Central

    Kuizon, Salomon; Buenaventura, Diego; Stapley, Nathan W.; Ruocco, Felicia; Begum, Umme; Guariglia, Sara R.; Brown, W. Ted; Junaid, Mohammed A.

    2014-01-01

    Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the

  20. Potential for increased photosynthetic performance and crop productivity in response to climate change: role of CBFs and gibberellic acid

    PubMed Central

    Hüner, Norman P. A.; Dahal, Keshav; Kurepin, Leonid V.; Savitch, Leonid; Singh, Jas; Ivanov, Alexander G.; Kane, Khalil; Sarhan, Fathey

    2014-01-01

    We propose that targeting the enhanced photosynthetic performance associated with the cold acclimation of winter cultivars of rye (Secale cereale L.), wheat (Triticum aestivum L.), and Brassica napus L. may provide a novel approach to improve crop productivity under abiotic as well as biotic stress conditions. In support of this hypothesis, we provide the physiological, biochemical, and molecular evidence that the dwarf phenotype induced by cold acclimation is coupled to significant enhancement in photosynthetic performance, resistance to photoinhibition, and a decreased dependence on photoprotection through non-photochemical quenching which result in enhanced biomass production and ultimately increased seed yield. These system-wide changes at the levels of phenotype, physiology, and biochemistry appear to be governed by the family of C-repeat/dehydration-responsive family of transcription factors (CBF/DREB1). We relate this phenomenon to the semi-dwarf, gibberellic acid insensitive (GAI), cereal varieties developed during the “green revolution” of the early 1960s and 1970s. We suggest that genetic manipulation of the family of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) may provide a novel approach for the maintenance and perhaps even the enhancement of plant productivity under conditions of sub-optimal growth conditions predicted for our future climate. PMID:24860799

  1. Potential for Increased Photosynthetic Performance and Crop Productivity in Response to Climate Change: role of CBFs and Gibberellic Acid

    NASA Astrophysics Data System (ADS)

    Huner, Norman; Dahal, Keshav; Kurepin, Leonid; Savitch, Leonid; Singh, Jas; Ivanov, Alexander; Kane, Khalil; Sarhan, Fathey

    2014-04-01

    We propose that targeting the dwarf phenotype, enhanced photosynthetic performance typically associated with the cold acclimation of winter cultivars of rye (Secale cereale L.), wheat (Triticum aestivum L.) and Brassica napus L. may provide a novel approach to improve crop yield and productivity under abiotic as well as biotic stress conditions. In support of this hypothesis, we provide the physiological, biochemical and molecular evidence that the dwarf phenotype induced by cold acclimation is coupled to significant enhancement in photosynthetic performance, resistance to photoinhibition and a decreased dependence on photoprotection through nonphotochemical quenching which result in enhanced biomass production and ultimately increased seed yield. These system-wide changes at the levels of phenotype, physiology and biochemistry appear to be governed by the family of C-repeat / dehydration-responsive family of transcription factors (CBF/DREB1). We relate this phenomenon to the semi-dwarf, gibberellic acid insensitive, cereal varieties developed during the “green revolution” of the early 1960s and 1970s. We suggest that genetic manipulation of the family of C-repeat / dehydration-responsive element binding transcription factors (CBF/DREB1) may provide a novel approach for the maintenance and perhaps even the enhancement of plant productivity under conditions of sub-optimal growth conditions predicted for our future climate.

  2. Potential for increased photosynthetic performance and crop productivity in response to climate change: role of CBFs and gibberellic acid.

    PubMed

    Hüner, Norman P A; Dahal, Keshav; Kurepin, Leonid V; Savitch, Leonid; Singh, Jas; Ivanov, Alexander G; Kane, Khalil; Sarhan, Fathey

    2014-01-01

    We propose that targeting the enhanced photosynthetic performance associated with the cold acclimation of winter cultivars of rye (Secale cereale L.), wheat (Triticum aestivum L.), and Brassica napus L. may provide a novel approach to improve crop productivity under abiotic as well as biotic stress conditions. In support of this hypothesis, we provide the physiological, biochemical, and molecular evidence that the dwarf phenotype induced by cold acclimation is coupled to significant enhancement in photosynthetic performance, resistance to photoinhibition, and a decreased dependence on photoprotection through non-photochemical quenching which result in enhanced biomass production and ultimately increased seed yield. These system-wide changes at the levels of phenotype, physiology, and biochemistry appear to be governed by the family of C-repeat/dehydration-responsive family of transcription factors (CBF/DREB1). We relate this phenomenon to the semi-dwarf, gibberellic acid insensitive (GAI), cereal varieties developed during the "green revolution" of the early 1960s and 1970s. We suggest that genetic manipulation of the family of C-repeat/dehydration-responsive element binding transcription factors (CBF/DREB1) may provide a novel approach for the maintenance and perhaps even the enhancement of plant productivity under conditions of sub-optimal growth conditions predicted for our future climate. PMID:24860799

  3. Short-term increase of plasma free fatty acids does not interfere with intrinsic mitochondrial function in healthy young men.

    PubMed

    Brands, Myrte; Hoeks, Joris; Sauerwein, Hans P; Ackermans, Mariette T; Ouwens, Margriet; Lammers, Nicolette M; van der Plas, Mart N; Schrauwen, Patrick; Groen, Albert K; Serlie, Mireille J

    2011-10-01

    Free fatty acid (FFA)- and obesity-induced insulin resistance has been associated with disturbed mitochondrial function. Elevated plasma FFA can impair insulin-induced increase of adenosine triphosphate synthesis and downregulate the expression of genes important in the biogenesis of mitochondria in human skeletal muscle. Whether FAs have a direct effect on intrinsic mitochondrial capacity remains to be established. Therefore, we measured ex vivo mitochondrial respiratory capacity in human skeletal muscle after exposure to hyperinsulinemia and high levels of plasma FFA. Nine healthy lean men were studied during a 6-hour hyperinsulinemic (600 pmol/L) euglycemic clamp with concomitant infusion of Intralipid (Fresensius Kabi Nederland, Den Bosch, the Netherlands) (FFA clamped at 0.5 mmol/L) or saline. Mitochondrial respiratory capacity was measured by high-resolution respirometry in permeabilized muscle fibers using an Oxygraph (OROBOROS Instruments, Innsbruck, Austria). Each participant served as his own control. Peripheral glucose uptake (rate of disappearance) was significantly lower during infusion of the lipid emulsion compared with the control saline infusion (68 μmol/kg·min [saline] vs 40 μmol/kg·min [lipid], P = .008). However, adenosine diphosphate-stimulated and maximal carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone-stimulated uncoupled respiration rates were not different in permeabilized skeletal muscle fibers after exposure to high levels of FFA compared with the control condition. We conclude that short-term elevation of FFA within the physiological range induces insulin resistance but does not affect intrinsic mitochondrial capacity in skeletal muscle in humans. PMID:21489571

  4. Hempseed Products Fed to Hens Effectively Increased n-3 Polyunsaturated Fatty Acids in Total Lipids, Triacylglycerol and Phospholipid of Egg Yolk.

    PubMed

    Neijat, M; Suh, M; Neufeld, J; House, J D

    2016-05-01

    Hempseed products represent potential alternative feed ingredients for poultry. However, their usage is not currently approved due to a lack of data to support their safety and efficacy. In this regard, the current study was conducted to assess the impact of dietary concentration of hempseed (HS) products and duration of their feeding to hens on the polyunsaturated fatty acid (PUFA) composition of egg yolk lipids. In the current study, 48 Lohmann LSL-Classic hens were individually housed in metabolism cages, in a completely randomized design, and provided one of six diets (wheat-barley-soybean-based) containing either HS (10, 20 and 30 %), hempseed oil (HO; 4.5 and 9.0 %) or no hempseed product (control) over 12 weeks. Increasing alpha-linolenic acid (ALA) intake via increasing dietary hempseed product inclusion, significantly (p < 0.0001) increased the n-3 PUFA contents of yolk total lipid. The values of ALA increased by 12-fold (152 ± 3.56 and 156 ± 2.42 mg/yolk) and docosahexaenoic acid (DHA) by twofold to threefold (41.3 ±