Yiguanjian cataplasm attenuates opioid dependence in a mouse

Science.gov (United States)

Gao, Shuai; Gao, Hong; Fan, Yuchen; Zhang, Guanghua; Sun, Fengkai; Zhao, Jing; Li, Feng; Yang, Yang; Wang, Kai

2016-08-01

To investigate the effect of Yiguanjian (YGJ) cataplasm on the development of opioid dependence in a mouse model of naloxone-induced opioid withdrawal syndrome. One hundred Swiss albino mice, of equal male to female ratio, were randomly and equally divided into 10 groups. A portion (3 cm2) of the backside hair of the mice was removed 1 day prior to the experiment. Morphine (5 mg/kg) was intraperitoneally administered twice daily for 5 days. YGJ cataplasm was prepared and pasted on the bare region of the mice immediately before morphine administration on day 3 and subsequently removed at the end day 5. On day 6, naloxone (8 mg/kg) was intraperitoneally injected to precipitate opioid withdrawal syndrome. Behavioral observation was performed in two 30-min phases immediately after naloxone injection. The YGJ cataplasm significantly and dose-dependently attenuated morphine-naloxone- induced experimental opioid withdrawal, in terms of withdrawal severity score and the frequencies of jumping, rearing, forepaw licking, and circling behaviors. However, YGJ cataplasm treatment did not alter the acute analgesic effect of morphine. YGJ cataplasm could attenuate opioid dependence and its associated withdrawal symptoms. Therefore, YGJ cataplasm could serve as a potential therapy for opioid addiction in the future.

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

DEFF Research Database (Denmark)

Klausen, Thomas Kjaer; Bergdahl, Andreas; Christophersen, Palle

2007-01-01

Recent evidence implicates the volume-regulated anion current (VRAC) and other anion currents in control or modulation of cell cycle progression; however, the precise involvement of anion channels in this process is unclear. Here, Cl- currents in Ehrlich Lettre Ascites (ELA) cells were monitored...... during cell cycle progression, under three conditions: (i) after osmotic swelling (i.e., VRAC), (ii) after an increase in the free intracellular Ca2+ concentration (i.e., the Ca2+-activated Cl- current, CaCC), and (iii) under steady-state isotonic conditions. The maximal swelling-activated VRAC current......+ in the pipette), was unaltered from G0 to G1, but decreased in early S phase. A novel high-affinity anion channel inhibitor, the acidic di-aryl-urea NS3728, which inhibited both VRAC and CaCC, attenuated ELA cell growth, suggesting a possible mechanistic link between cell cycle progression and cell cycle...

2-Oxoglutarate: linking TCA cycle function with amino acid, glucosinolate, flavonoid, alkaloid, and gibberellin biosynthesis.

Science.gov (United States)

Araújo, Wagner L; Martins, Auxiliadora O; Fernie, Alisdair R; Tohge, Takayuki

2014-01-01

The tricarboxylic acid (TCA) cycle intermediate 2-oxoglutarate (2-OG) is used as an obligatory substrate in a range of oxidative reactions catalyzed by 2-OG-dependent dioxygenases. These enzymes are widespread in nature being involved in several important biochemical processes. We have recently demonstrated that tomato plants in which the TCA cycle enzyme 2-OG dehydrogenase (2-ODD) was antisense inhibited were characterized by early senescence and modified fruit ripening associated with differences in the levels of bioactive gibberellin (GA). Accordingly, there is now compelling evidence that the TCA cycle plays an important role in modulating the rate of flux from 2-OG to amino acid metabolism. Here we discuss recent advances in the biochemistry and molecular biology of 2-OG metabolism occurring in different biological systems indicating the importance of 2-OG and 2-OG dependent dioxygenases not only in glucosinolate, flavonoid and alkaloid metabolism but also in GA and amino acid metabolism. We additionally summarize recent findings regarding the impact of modification of 2-OG metabolism on biosynthetic pathways involving 2-ODDs.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

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Zuo, Li; Diaz, Philip T; Chien, Michael T; Roberts, William J; Kishek, Juliana; Best, Thomas M; Wagner, Peter D

2014-01-01

Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr) followed by a high oxygen level (550 Torr), can reduce intracellular reactive oxygen species (ROS) as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe) was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

PO2 cycling reduces diaphragm fatigue by attenuating ROS formation.

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Li Zuo

Full Text Available Prolonged muscle exposure to low PO2 conditions may cause oxidative stress resulting in severe muscular injuries. We hypothesize that PO2 cycling preconditioning, which involves brief cycles of diaphragmatic muscle exposure to a low oxygen level (40 Torr followed by a high oxygen level (550 Torr, can reduce intracellular reactive oxygen species (ROS as well as attenuate muscle fatigue in mouse diaphragm under low PO2. Accordingly, dihydrofluorescein (a fluorescent probe was used to monitor muscular ROS production in real time with confocal microscopy during a lower PO2 condition. In the control group with no PO2 cycling, intracellular ROS formation did not appear during the first 15 min of the low PO2 period. However, after 20 min of low PO2, ROS levels increased significantly by ∼30% compared to baseline, and this increase continued until the end of the 30 min low PO2 condition. Conversely, muscles treated with PO2 cycling showed a complete absence of enhanced fluorescence emission throughout the entire low PO2 period. Furthermore, PO2 cycling-treated diaphragm exhibited increased fatigue resistance during prolonged low PO2 period compared to control. Thus, our data suggest that PO2 cycling mitigates diaphragm fatigue during prolonged low PO2. Although the exact mechanism for this protection remains to be elucidated, it is likely that through limiting excessive ROS levels, PO2 cycling initiates ROS-related antioxidant defenses.

An iso-α-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice.

Science.gov (United States)

Hege, Marianne; Jung, Finn; Sellmann, Cathrin; Jin, Chengjun; Ziegenhardt, Doreen; Hellerbrand, Claus; Bergheim, Ina

2018-01-01

Results of in vitro and in vivo studies suggest that consumption of beer is less harmful for the liver than consumption of spirits. It also has been suggested that secondary plant compounds derived from hops such as xanthohumol or iso-α-acids may have beneficial effects on the development of liver diseases of various etiologies. The aim of this study was to determine whether iso-α-acids consumed in doses achieved by "normal" beer consumption have beneficial effects on health. Female C57 Bl/6 J mice, pretreated for 4 d with an iso-α-acid-rich extract (∼30% iso-α-acids from hops, 0.75 mg/kg body weight), were fed one bolus of ethanol (6 g/kg body weight intragastric) or an iso-caloric maltodextrin solution. Markers of liver damage, toll-like receptor-4 signaling, and lipid peroxidation were determined. Furthermore, the effect of isohumulone on the lipopolysaccharide-dependent activation of J774 A.1 macrophages, used as a model of Kupffer cells, was determined. In the liver, acute ethanol administration led to a significant accumulation of fat (∼10-fold), which was accompanied by significantly higher inducible nitric oxide synthase protein level, elevated nitric oxide production, and increased plasminogen activator inhibitor 1 protein concentration when compared to controls. In mice pretreated with iso-α-acids, these effects of alcohol were markedly attenuated. Pretreatment of J774 A.1 macrophages with isohumulone significantly attenuated lipopolysaccharide-induced mRNA expression of inducible nitric oxide synthase and interleukin-6 as well as the release of nitric oxide. Taken together, iso-α-acids markedly attenuated the development of acute alcohol-induced damage in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Attenuation of polychlorinated biphenyl sorption to charcoal by humic acids

NARCIS (Netherlands)

Koelmans, A.A.; Meulman, B.; Meijer, T.; Jonker, M.T.O.

2009-01-01

Strong sorption to black carbon may limit the environmental risks of organic pollutants, but interactions with cosorbing humic acid (HA) may interfere. We studied the attenuative effect of HA additions on the sorption of polychlorinated biphenyls (PCBs) to a charcoal. "Intrinsic" sorption to

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

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Chang, Shih-Sheng; Lee, Viola S. Y.; Tseng, Yu-Lun; Chang, Kuan-Cheng; Chen, Kuen-Bao; Chen, Yuh-Lien; Li, Chi-Yuan

2012-01-01

Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid. PMID:22811749

Gallic Acid Attenuates Platelet Activation and Platelet-Leukocyte Aggregation: Involving Pathways of Akt and GSK3β

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Shih-Sheng Chang

2012-01-01

Full Text Available Platelet activation and its interaction with leukocytes play an important role in atherothrombosis. Cardiovascular diseases resulted from atherothrombosis remain the major causes of death worldwide. Gallic acid, a major constituent of red wine and tea, has been believed to have properties of cardiovascular protection, which is likely to be related to its antioxidant effects. Nonetheless, there were few and inconsistent data regarding the effects of gallic acid on platelet function. Therefore, we designed this in vitro study to determine whether gallic acid could inhibit platelet activation and the possible mechanisms. From our results, gallic acid could concentration-dependently inhibit platelet aggregation, P-selectin expression, and platelet-leukocyte aggregation. Gallic acid prevented the elevation of intracellular calcium and attenuated phosphorylation of PKCα/p38 MAPK and Akt/GSK3β on platelets stimulated by the stimulants ADP or U46619. This is the first mechanistic explanation for the inhibitory effects on platelets from gallic acid.

Blockade of acid sensing ion channels attenuates the exercise pressor reflex in cats.

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Hayes, Shawn G; Kindig, Angela E; Kaufman, Marc P

2007-06-15

Although thin fibre muscle afferents possess acid sensing ion channels (ASICs), their contribution to the exercise pressor reflex is not known. This lack of information is partly attributable to the fact that there is no known selective in vivo antagonist for ASICs. Although amiloride has been shown to antagonize ASICs, it also has been shown to antagonize voltage-gated sodium channels, thereby impairing impulse conduction in sensory nerves. Our aim was to test the hypothesis that lactic acid accumulation in exercising muscle acted on ASICs located on thin fibre muscle afferents to evoke the metabolic component of the exercise pressor reflex. To test this hypothesis, we determined in decerebrate cats if amiloride attenuated the pressor and cardioaccelerator responses to static contraction, to tendon stretch and to arterial injections of lactic acid and capsaicin. We found a dose of amiloride (0.5 microg kg(-1); i.a.) that attenuated the pressor and cardioaccelerator responses to both contraction and lactic acid injection, but had no effect on the responses to stretch and capsaicin. A higher dose of amiloride (5 microg kg(-1), i.a.) not only blocked the pressor and cardioaccelerator responses to lactic acid and contraction, but also attenuated the responses to stretch and to capsaicin, manoeuvers in which ASICs probably play no significant role. In addition, we found that the low dose of amiloride (0.5 microg kg(-1)) had no effect on the responses of muscle spindles to tendon stretch and to succinylcholine, whereas the high dose (5 microg kg(-1)) attenuated the responses to both. Our data suggest the low dose of amiloride used in our experiments selectively blocked ASICs, whereas the high dose blocked ASICs and impulse conduction in muscle afferents. We conclude that ASICs play a role in the metabolic component of the exercise pressor reflex.

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

Science.gov (United States)

Bodner, George M.

1986-01-01

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

A comparison study for mass attenuation coefficients of some amino acids using MCNP code

Energy Technology Data Exchange (ETDEWEB)

Vahabi, Seyed Milad; Bahreynipour, Mostean; Shamsaie-Zafarghandi, Mojtaba [Amirkabir Univ. of Technology, Tehran (Iran, Islamic Republic of). Dept. of Energy Engineering and Physics

2017-07-15

In this study, a novel model of MCNP4C code reported recently was used to determine the photon mass attenuation coefficients of some amino acids at energies, 123, 360, 511, 662, 1170, 1280 and 1330 keV. The simulation results were compared with the XCOM data. It was indicated that the results were highly close to the calculated XCOM values. Obtained results were used to calculate the molar extinction coefficient. All the results showed the convenience and usefulness of the model in calculation of mass attenuation coefficients of amino acids.

Redox cycles of vitamin E: Hydrolysis and ascorbic acid dependent reduction of 8a-(alkyldioxy)tocopherones

International Nuclear Information System (INIS)

Liebler, D.C.; Kaysen, K.L.; Kennedy, T.A.

1989-01-01

Oxidation of the biological antioxidant α-tocopherol (vitamin E; TH) by peroxyl radicals yields 8a-(alkyldioxy)tocopherones, which either may hydrolyze to α-tocopheryl quinone (TQ) or may be reduced by ascorbic acid to regenerate TH. To define the chemistry of this putative two-electron TH redox cycle, we studied the hydrolysis and reduction of 8a-[(2,4-dimethyl-1-nitrilopent-2-yl)dioxyl]tocopherone (1) in acetonitrile/buffer mixtures and in phospholipid liposomes. TQ formation in acetonitrile/buffer mixtures, which was monitored spectrophotometrically, declined with increasing pH and could not be detected above pH 4. The rate of TQ formation from 1 first increased with time and then decreased in a first-order terminal phase. Rearrangement of 8a-hydroxy-α-tocopherone (2) to TQ displayed first-order kinetics identical with the terminal phase for TQ formation from 1. Both rate constants increased with decreasing pH. Hydrolysis of 1 in acetonitrile/H 2 18 O yielded [ 18 O]TQ. These observations suggest that 1 loses the 8a-(alkyldioxy) moiety to produce the tocopherone cation (T + ), which hydrolyzes to 2, the TQ-forming intermediate. Incubation of either 1 or 2 with ascorbic acid in acetonitrile/buffer yielded TH. Reduction of both 1 and 2 decreased with increasing pH. In phosphatidylcholine liposomes at pH 7, approximately 10% of the T + generated from 1 was reduced to TH by 5 mM ascorbic acid. The results collectively demonstrate that T + is the ascorbic acid reducible intermediate in a two-electron TH redox cycle, a process that probably would require biocatalysis to proceed in biological membranes

Palmitoleic Acid (N-7 Attenuates the Immunometabolic Disturbances Caused by a High-Fat Diet Independently of PPARα

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Camila O. Souza

2014-01-01

Full Text Available Palmitoleic acid (PMA has anti-inflammatory and antidiabetic activities. Here we tested whether these effects of PMA on glucose homeostasis and liver inflammation, in mice fed with high-fat diet (HFD, are PPAR-α dependent. C57BL6 wild-type (WT and PPAR-α-knockout (KO mice fed with a standard diet (SD or HFD for 12 weeks were treated after the 10th week with oleic acid (OLA, 300 mg/kg of b.w. or PMA 300 mg/kg of b.w. Steatosis induced by HFD was associated with liver inflammation only in the KO mice, as shown by the increased hepatic levels of IL1-beta, IL-12, and TNF-α; however, the HFD increased the expression of TLR4 and decreased the expression of IL1-Ra in both genotypes. Treatment with palmitoleate markedly attenuated the insulin resistance induced by the HFD, increased glucose uptake and incorporation into muscle in vitro, reduced the serum levels of AST in WT mice, decreased the hepatic levels of IL1-beta and IL-12 in KO mice, reduced the expression of TLR-4 and increased the expression of IL-1Ra in WT mice, and reduced the phosphorylation of NF B (p65 in the livers of KO mice. We conclude that palmitoleate attenuates diet-induced insulin resistance, liver inflammation, and damage through mechanisms that do not depend on PPAR-α.

Evaluation of frequency-dependent ultrasound attenuation in transparent medium using focused shadowgraph technique

Science.gov (United States)

Iijima, Yukina; Kudo, Nobuki

2017-07-01

Acoustic fields of a short-pulsed ultrasound propagating through a transparent medium with ultrasound attenuation were visualized by the focused shadowgraph technique. A brightness waveform and its spatial integrations were derived from a visualized field image and compared with a pressure waveform measured by a membrane hydrophone. The experimental results showed that first-order integration of the brightness wave has good agreement with the pressure waveforms. Frequency-dependent attenuation of the pulse propagating through castor oil was derived from brightness and pressure waveforms, and attenuation coefficients determined from focused shadowgraphy and hydrophone techniques showed good agreement. The results suggest the usefulness of the shadowgraph technique not only for the visualization of ultrasound fields but also for noncontact estimation of rough pressure waveforms and correct ultrasound attenuation.

Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ injury in rats.

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Tsong-Long Hwang

Full Text Available Neutrophil activation is associated with the development of organ injury after trauma-hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma-hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma-hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma-hemorrhagic shock-induced organ injury in rats.

Blood metabolomics analysis identifies abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism in bipolar disorder.

Science.gov (United States)

Yoshimi, Noriko; Futamura, Takashi; Kakumoto, Keiji; Salehi, Alireza M; Sellgren, Carl M; Holmén-Larsson, Jessica; Jakobsson, Joel; Pålsson, Erik; Landén, Mikael; Hashimoto, Kenji

2016-06-01

Bipolar disorder (BD) is a severe and debilitating psychiatric disorder. However, the precise biological basis remains unknown, hampering the search for novel biomarkers. We performed a metabolomics analysis to discover novel peripheral biomarkers for BD. We quantified serum levels of 116 metabolites in mood-stabilized male BD patients (n = 54) and age-matched male healthy controls (n = 39). After multivariate logistic regression, serum levels of pyruvate, N-acetylglutamic acid, α-ketoglutarate, and arginine were significantly higher in BD patients than in healthy controls. Conversely, serum levels of β-alanine, and serine were significantly lower in BD patients than in healthy controls. Chronic (4-weeks) administration of lithium or valproic acid to adult male rats did not alter serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, or arginine, but lithium administration significantly increased serum levels of α-ketoglutarate. The metabolomics analysis demonstrated altered serum levels of pyruvate, N-acetylglutamic acid, β-alanine, serine, and arginine in BD patients. The present findings suggest that abnormalities in the citric acid cycle, urea cycle, and amino acid metabolism play a role in the pathogenesis of BD.

Dietary High-Oleic Acid Soybean Oil Dose Dependently Attenuates Egg Yolk Content of n-3 Polyunsaturated Fatty Acids in Laying Hens Fed Supplemental Flaxseed Oil.

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Elkin, Robert G; Kukorowski, Alexandra N; Ying, Yun; Harvatine, Kevin J

2018-02-01

Chickens can hepatically synthesize eicosapentaenoic acid (20:5 n-3) and docosahexaenoic acid (22:6 n-3) from α-linolenic acid (ALA; 18:3 n-3); however, the process is inefficient and competitively inhibited by dietary linoleic acid (LNA; 18:2 n-6). In the present study, the influence of dietary high-oleic acid (OLA; 18:1 n-9) soybean oil (HOSO) on egg and tissue deposition of ALA and n-3 polyunsaturated fatty acids (PUFA) synthesized from dietary ALA was investigated in laying hens fed a reduced-LNA base diet supplemented with high-ALA flaxseed oil (FLAX). We hypothesized that reducing the dietary level of LNA would promote greater hepatic conversion of ALA to very long-chain (VLC; >20C) n-3 PUFA, while supplemental dietary HOSO would simultaneously further enrich eggs with OLA without influencing egg n-3 PUFA contents. Nine 51-week-old hens each were fed 0, 10, 20, or 40 g HOSO/kg diet for 12 weeks. Within each group, supplemental dietary FLAX was increased every 3 weeks from 0 to 10 to 20 to 40 g/kg diet. Compared to controls, dietary FLAX maximally enriched the total n-3 and VLC n-3 PUFA contents in egg yolk by 9.4-fold and 2.2-fold, respectively, while feeding hens 40 g HOSO/kg diet maximally attenuated the yolk deposition of ALA, VLC n-3 PUFA, and total n-3 PUFA by 37, 15, and 32%, respectively. These results suggest that dietary OLA is not neutral with regard to the overall process by which dietary ALA is absorbed, metabolized, and deposited into egg yolk, either intact or in the form of longer-chain/more unsaturated n-3 PUFA derivatives. © 2018 AOCS.

Serum uric acid in relation to endogenous reproductive hormones during the menstrual cycle: findings from the BioCycle study

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Mumford, Sunni L.; Dasharathy, Sonya S.; Pollack, Anna Z.; Perkins, Neil J.; Mattison, Donald R.; Cole, Stephen R.; Wactawski-Wende, Jean; Schisterman, Enrique F.

2013-01-01

STUDY QUESTION Do uric acid levels across the menstrual cycle show associations with endogenous estradiol (E2) and reproductive hormone concentrations in regularly menstruating women? SUMMARY ANSWER Mean uric acid concentrations were highest during the follicular phase, and were inversely associated with E2 and progesterone, and positively associated with FSH. WHAT IS KNOWN ALREADY E2 may decrease serum levels of uric acid in post-menopausal women; however, the interplay between endogenous reproductive hormones and uric acid levels among regularly menstruating women has not been elucidated. STUDY DESIGN, SIZE, DURATION The BioCycle study was a prospective cohort study conducted at the University at Buffalo research centre from 2005 to 2007, which followed healthy women for one (n = 9) or 2 (n = 250) menstrual cycle(s). PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were healthy women aged 18–44 years. Hormones and uric acid were measured in serum eight times each cycle for up to two cycles. Marginal structural models with inverse probability of exposure weights were used to evaluate the associations between endogenous hormones and uric acid concentrations. MAIN RESULTS AND THE ROLE OF CHANCE Uric acid levels were observed to vary across the menstrual cycle, with the lowest levels observed during the luteal phase. Every log-unit increase in E2 was associated with a decrease in uric acid of 1.1% (β = −0.011; 95% confidence interval (CI): −0.019, −0.004; persistent-effects model), and for every log-unit increase in progesterone, uric acid decreased by ∼0.8% (β = −0.008; 95% CI: −0.012, −0.004; persistent-effects model). FSH was positively associated with uric acid concentrations, such that each log-unit increase was associated with a 1.6% increase in uric acid (β = 0.016; 95% CI: 0.005, 0.026; persistent-effects model). Progesterone and FSH were also associated with uric acid levels in acute-effects models. Of 509 cycles, 42 were anovulatory

Metabolic Interaction between Urea Cycle and Citric Acid Cycle Shunt: A Guided Approach

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Pesi, Rossana; Balestri, Francesco; Ipata, Piero L.

2018-01-01

This article is a guided pedagogical approach, devoted to postgraduate students specializing in biochemistry, aimed at presenting all single reactions and overall equations leading to the metabolic interaction between ureagenesis and citric acid cycle to be incorporated into a two-three lecture series about the interaction of urea cycle with other…

Docosahexaenoic acid inhibits monocrotaline-induced pulmonary hypertension via attenuating endoplasmic reticulum stress and inflammation.

Science.gov (United States)

Chen, Rui; Zhong, Wei; Shao, Chen; Liu, Peijing; Wang, Cuiping; Wang, Zhongqun; Jiang, Meiping; Lu, Yi; Yan, Jinchuan

2018-02-01

Endoplasmic reticulum (ER) stress and inflammation contribute to pulmonary hypertension (PH) pathogenesis. Previously, we confirmed that docosahexaenoic acid (DHA) could improve hypoxia-induced PH. However, little is known about the link between DHA and monocrotaline (MCT)-induced PH. Our aims were, therefore, to evaluate the effects and molecular mechanisms of DHA on MCT-induced PH in rats. Rat PH was induced by MCT. Rats were treated with DHA daily in the prevention group (following MCT injection) and the reversal group (after MCT injection for 2 wk) by gavage. After 4 wk, mean pulmonary arterial pressure (mPAP), right ventricular (RV) hypertrophy index, and morphological and immunohistochemical analyses were evaluated. Rat pulmonary artery smooth muscle cells (PASMCs) were used to investigate the effects of DHA on cell proliferation stimulated by platelet-derived growth factor (PDGF)-BB. DHA decreased mPAP and attenuated pulmonary vascular remodeling and RV hypertrophy, which were associated with suppressed ER stress. DHA blocked the mitogenic effect of PDGF-BB on PASMCs and arrested the cell cycle via inhibiting nuclear factor of activated T cells-1 (NFATc1) expression and activation and regulating cell cycle-related proteins. Moreover, DHA ameliorated inflammation in lung and suppressed macrophage and T lymphocyte accumulation in lung and adventitia of resistance pulmonary arteries. These findings suggest that DHA could protect against MCT-induced PH by reducing ER stress, suppressing cell proliferation and inflammation.

Rethinking cell-cycle-dependent gene expression in Schizosaccharomyces pombe.

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Cooper, Stephen

2017-11-01

Three studies of gene expression during the division cycle of Schizosaccharomyces pombe led to the proposal that a large number of genes are expressed at particular times during the S. pombe cell cycle. Yet only a small fraction of genes proposed to be expressed in a cell-cycle-dependent manner are reproducible in all three published studies. In addition to reproducibility problems, questions about expression amplitudes, cell-cycle timing of expression, synchronization artifacts, and the problem with methods for synchronizing cells must be considered. These problems and complications prompt the idea that caution should be used before accepting the conclusion that there are a large number of genes expressed in a cell-cycle-dependent manner in S. pombe.

Amino Acids Attenuate Insulin Action on Gluconeogenesis and Promote Fatty Acid Biosynthesis via mTORC1 Signaling Pathway in trout Hepatocytes

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Weiwei Dai

2015-06-01

Full Text Available Background/Aims: Carnivores exhibit poor utilization of dietary carbohydrates and glucose intolerant phenotypes, yet it remains unclear what are the causal factors and underlying mechanisms. We aimed to evaluate excessive amino acids (AAs-induced effects on insulin signaling, fatty acid biosynthesis and glucose metabolism in rainbow trout and determine the potential involvement of mTORC1 and p38 MAPK pathway. Methods: We stimulated trout primary hepatocytes with different AA levels and employed acute administration of rapamycin to inhibit mTORC1 activation. Results: Increased AA levels enhanced the phosphorylation of ribosomal protein S6 kinase (S6K1, S6, and insulin receptor substrate 1 (IRS-1 on Ser302 but suppressed Akt and p38 phosphorylation; up-regulated the expression of genes related to gluconeogenesis and fatty acid biosynthesis. mTORC1 inhibition not only inhibited the phosphorylation of mTORC1 downstream targets, but also blunted IRS-1 Ser302 phosphorylation and restored excessive AAs-suppressed Akt phosphorylation. Rapamycin also inhibited fatty acid biosynthetic and gluconeogenic gene expression. Conclusion: High levels of AAs up-regulate hepatic fatty acid biosynthetic gene expression through an mTORC1-dependent manner, while attenuate insulin-mediated repression of gluconeogenesis through elevating IRS-1 Ser302 phosphorylation, which in turn impairs Akt activation and thereby weakening insulin action. We propose that p38 MAPK probably also involves in these AAs-induced metabolic changes.

Foot-and-mouth disease virus type O specific mutations determine RNA-dependent RNA polymerase fidelity and virus attenuation.

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Li, Chen; Wang, Haiwei; Yuan, Tiangang; Woodman, Andrew; Yang, Decheng; Zhou, Guohui; Cameron, Craig E; Yu, Li

2018-05-01

Previous studies have shown that the FMDV Asia1/YS/CHA/05 high-fidelity mutagen-resistant variants are attenuated (Zeng et al., 2014). Here, we introduced the same single or multiple-amino-acid substitutions responsible for increased 3D pol fidelity of type Asia1 FMDV into the type O FMDV O/YS/CHA/05 infectious clone. The rescued viruses O-DA and O-DAMM are lower replication fidelity mutants and showed an attenuated phenotype. These results demonstrated that the same amino acid substitution of 3D pol in different serotypes of FMDV strains had different effects on viral fidelity. In addition, nucleoside analogues were used to select high-fidelity mutagen-resistant type O FMDV variants. The rescued mutagen-resistant type O FMDV high-fidelity variants exhibited significantly attenuated fitness and a reduced virulence phenotype. These results have important implications for understanding the molecular mechanism of FMDV evolution and pathogenicity, especially in developing a safer modified live-attenuated vaccine against FMDV. Copyright © 2018 Elsevier Inc. All rights reserved.

Pipecolic Acid Orchestrates Plant Systemic Acquired Resistance and Defense Priming via Salicylic Acid-Dependent and -Independent Pathways.

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Bernsdorff, Friederike; Döring, Anne-Christin; Gruner, Katrin; Schuck, Stefan; Bräutigam, Andrea; Zeier, Jürgen

2016-01-01

We investigated the relationships of the two immune-regulatory plant metabolites, salicylic acid (SA) and pipecolic acid (Pip), in the establishment of plant systemic acquired resistance (SAR), SAR-associated defense priming, and basal immunity. Using SA-deficient sid2, Pip-deficient ald1, and sid2 ald1 plants deficient in both SA and Pip, we show that SA and Pip act both independently from each other and synergistically in Arabidopsis thaliana basal immunity to Pseudomonas syringae. Transcriptome analyses reveal that SAR establishment in Arabidopsis is characterized by a strong transcriptional response systemically induced in the foliage that prepares plants for future pathogen attack by preactivating multiple stages of defense signaling and that SA accumulation upon SAR activation leads to the downregulation of photosynthesis and attenuated jasmonate responses systemically within the plant. Whereas systemic Pip elevations are indispensable for SAR and necessary for virtually the whole transcriptional SAR response, a moderate but significant SA-independent component of SAR activation and SAR gene expression is revealed. During SAR, Pip orchestrates SA-dependent and SA-independent priming of pathogen responses in a FLAVIN-DEPENDENT-MONOOXYGENASE1 (FMO1)-dependent manner. We conclude that a Pip/FMO1 signaling module acts as an indispensable switch for the activation of SAR and associated defense priming events and that SA amplifies Pip-triggered responses to different degrees in the distal tissue of SAR-activated plants. © 2016 American Society of Plant Biologists. All rights reserved.

Blockade of acid sensing ion channels attenuates the augmented exercise pressor reflex in rats with chronic femoral artery occlusion.

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Tsuchimochi, Hirotsugu; Yamauchi, Katsuya; McCord, Jennifer L; Kaufman, Marc P

2011-12-15

We found previously that static contraction of the hindlimb muscles of rats whose femoral artery was ligated evoked a larger reflex pressor response (i.e. exercise pressor reflex) than did static contraction of the contralateral hindlimb muscles which were freely perfused. Ligating a femoral artery in rats results in blood flow patterns to the muscles that are remarkably similar to those displayed by humans with peripheral artery disease. Using decerebrated rats, we tested the hypothesis that the augmented exercise pressor reflex in rats with a ligated femoral artery is attenuated by blockade of the acid sensing ion channel (ASIC) 3. We found that femoral arterial injection of either amiloride (5 and 50 μg kg(-1)) or APETx2 (100 μg kg(-1)) markedly attenuated the reflex in rats with a ligated femoral artery. In contrast, these ASIC antagonists had only modest effects on the reflex in rats with freely perfused hindlimbs. Tests of specificity of the two antagonists revealed that the low dose of amiloride and APETx2 greatly attenuated the pressor response to lactic acid, an ASIC agonist, but did not attenuate the pressor response to capsaicin, a TRPV1 agonist. In contrast, the high dose of amiloride attenuated the pressor responses to lactic acid, but also attenuated the pressor response to capsaicin. We conclude that ASIC3 on thin fibre muscle afferents plays an important role in evoking the exercise pressor reflex in rats with a compromised arterial blood supply to the working muscles.

Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles.

Science.gov (United States)

Pedroso, José Eduardo de Sá; Brasil, Osíris Camponês do; Martins, João Roberto Maciel; Nader, Helena Bociane; Simões, Manuel de Jesus

2009-01-01

Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the estral cycle and in the second group, 20 animals were submitted to the same procedure but during the gravidic-puerperal cycle. Variations in hyaluronic acid concentration was not observed during the estral cycle. In the gravidic puerperal cycle group, an increase in hyaluronic acid concentration was observed in the puerperal subgroup. Comparing the two groups of estral and gravidic-puerperal cycles, no difference was observed. In comparing all subgroups of estral and gravidic-puerperal cycles, an increase in hyaluronic acid concentration was noticed only in the puerperal phase.

Attenuation and diel cycling of coal-mine drainage constituents in a passive treatment wetland: A case study from Lambert Run, West Virginia, USA

International Nuclear Information System (INIS)

Vesper, Dorothy J.; Smilley, Michael J.

2010-01-01

This study reports changes in coal-mine drainage constituent concentrations through a passive treatment wetland and over diel cycles. The purpose of the study was to determine what physiochemical mechanisms control attenuation of metals and if they varied by location and through time. The source water was slightly acidic (average pH 5.43); downstream degassing of CO 2 contributed to an increase in pH prior to discharge from the site (average pH 7.05). Aluminum, Fe, rare earth elements (REE) and Y were removed to a greater extent than were Mn, Co and Ni. At acidic pH, the REE and Y were generally complexed by SO 4 . At higher pH, carbonate complexes became more important. The REE and Y concentrations were normalized to the North American Shale Composite standard; the normalized patterns were coherent near the source but anomalies of Ce and Y were present further downstream indicating oxidation and sorption processes. Four sets of diel-based samples were collected, one from a shallow, surface-flow wetland and three from a deeper, newly constructed wetland. Well-defined diel cycles were observed for concentrations of Si, Mn, Fe, Co, Ni, As, REE and Y in the shallow wetland. In all cases, the concentrations increased (up to 863%) during night and decreased during the day. These cycles had an inverse relationship with the temperature cycle (pH had no discernable cycle). The consistency of concentration cycles suggests a common mechanism, most likely associated with the formation of Fe oxyhydroxides. The increased rate of Fe 2+ oxidation in warm water can account for the cycles in Fe; scavenging of the other elements by the Fe precipitate can account for the consistency of the cycles even though the elements include cations, anions (H 2 AsO 4 - or HAsO 4 -2 ), and neutral species (H 4 SiO 4 0 ). While REE and Y had clear cycles in the constructed wetland, the other elements did not. This is partially due to the lower elemental concentrations (including Fe) but the cycles

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence

Science.gov (United States)

Flynn, Padrig B.; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P.; Elliott, Christopher T.; Laverty, Garry; Gorman, Sean P.; Graham, William G.; Gilmore, Brendan F.

2016-01-01

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa. PMID:27242335

Attenuation measurements of ultrasound in a kaolin-water slurry. A linear dependence upon frequency

International Nuclear Information System (INIS)

Greenwood, M.S.; Mai, J.L.; Good, M.S.

1993-01-01

The attenuation of ultrasound through a kaolin-water slurry was measured for frequencies ranging from 0.5 to 3.0 MHz. The maximum concentration of the slurry was for a weight percentage of 44% (or a volume fraction of 0.24). The goal of these measurements was to assess the feasibility of using ultrasonic attenuation to determine the concentration of a slurry of known composition. The measurements were obtained by consecutively adding kaolin to the slurry and measuring the attenuation at each concentration. After reaching a maximum concentration a dilution technique was used, in which an amount of slurry was removed and water was added, to obtain the attenuation as a function of the concentration. The dilution technique was the more effective method to obtain calibration data. These measurements were carried out using two transducers, having a center frequency of 2.25 MHz, separated by 0.1016m (4.0 in.). The maximum attenuation measured in these experiments was about 100Np/m, but the experimental apparatus has the capability of measuring a larger attenuation if the distance between the two transducers is decreased. For a given frequency, the data show that ln V/V 0 depends linearly upon the volume fraction (V is the received voltage for the slurry and V 0 is that obtained for water). This indicated that each particle acts independently in attenuating ultrasound. 12 refs., 7 figs., 3 tabs

A downy mildew effector attenuates salicylic acid-triggered immunity in Arabidopsis by interacting with the host mediator complex.

Directory of Open Access Journals (Sweden)

Marie-Cécile Caillaud

2013-12-01

Full Text Available Plants are continually exposed to pathogen attack but usually remain healthy because they can activate defences upon perception of microbes. However, pathogens have evolved to overcome plant immunity by delivering effectors into the plant cell to attenuate defence, resulting in disease. Recent studies suggest that some effectors may manipulate host transcription, but the specific mechanisms by which such effectors promote susceptibility remain unclear. We study the oomycete downy mildew pathogen of Arabidopsis, Hyaloperonospora arabidopsidis (Hpa, and show here that the nuclear-localized effector HaRxL44 interacts with Mediator subunit 19a (MED19a, resulting in the degradation of MED19a in a proteasome-dependent manner. The Mediator complex of ∼25 proteins is broadly conserved in eukaryotes and mediates the interaction between transcriptional regulators and RNA polymerase II. We found MED19a to be a positive regulator of immunity against Hpa. Expression profiling experiments reveal transcriptional changes resembling jasmonic acid/ethylene (JA/ET signalling in the presence of HaRxL44, and also 3 d after infection with Hpa. Elevated JA/ET signalling is associated with a decrease in salicylic acid (SA-triggered immunity (SATI in Arabidopsis plants expressing HaRxL44 and in med19a loss-of-function mutants, whereas SATI is elevated in plants overexpressing MED19a. Using a PR1::GUS reporter, we discovered that Hpa suppresses PR1 expression specifically in cells containing haustoria, into which RxLR effectors are delivered, but not in nonhaustoriated adjacent cells, which show high PR1::GUS expression levels. Thus, HaRxL44 interferes with Mediator function by degrading MED19, shifting the balance of defence transcription from SA-responsive defence to JA/ET-signalling, and enhancing susceptibility to biotrophs by attenuating SA-dependent gene expression.

Expression of Genes Encoding Enzymes Involved in the One Carbon Cycle in Rat Placenta is Determined by Maternal Micronutrients (Folic Acid, Vitamin B12 and Omega-3 Fatty Acids

Directory of Open Access Journals (Sweden)

Vinita Khot

2014-01-01

Full Text Available We have reported that folic acid, vitamin B12, and omega-3 fatty acids are interlinked in the one carbon cycle and have implications for fetal programming. Our earlier studies demonstrate that an imbalance in maternal micronutrients influence long chain polyunsaturated fatty acid metabolism and global methylation in rat placenta. We hypothesize that these changes are mediated through micronutrient dependent regulation of enzymes in one carbon cycle. Pregnant dams were assigned to six dietary groups with varying folic acid and vitamin B12 levels. Vitamin B12 deficient groups were supplemented with omega-3 fatty acid. Placental mRNA levels of enzymes, levels of phospholipids, and glutathione were determined. Results suggest that maternal micronutrient imbalance (excess folic acid with vitamin B12 deficiency leads to lower mRNA levels of methylene tetrahydrofolate reductase (MTHFR and methionine synthase , but higher cystathionine b-synthase (CBS and Phosphatidylethanolamine-N-methyltransferase (PEMT as compared to control. Omega-3 supplementation normalized CBS and MTHFR mRNA levels. Increased placental phosphatidylethanolamine (PE, phosphatidylcholine (PC, in the same group was also observed. Our data suggests that adverse effects of a maternal micronutrient imbalanced diet may be due to differential regulation of key genes encoding enzymes in one carbon cycle and omega-3 supplementation may ameliorate most of these changes.

Geochemistry of acid mine drainage from a coal mining area and processes controlling metal attenuation in stream waters, southern Brazil

Directory of Open Access Journals (Sweden)

VERIDIANA P. CAMPANER

2014-06-01

Full Text Available Acid drainage influence on the water and sediment quality was investigated in a coal mining area (southern Brazil. Mine drainage showed pH between 3.2 and 4.6 and elevated concentrations of sulfate, As and metals, of which, Fe, Mn and Zn exceeded the limits for the emission of effluents stated in the Brazilian legislation. Arsenic also exceeded the limit, but only slightly. Groundwater monitoring wells from active mines and tailings piles showed pH interval and chemical concentrations similar to those of mine drainage. However, the river and ground water samples of municipal public water supplies revealed a pH range from 7.2 to 7.5 and low chemical concentrations, although Cd concentration slightly exceeded the limit adopted by Brazilian legislation for groundwater. In general, surface waters showed large pH range (6 to 10.8, and changes caused by acid drainage in the chemical composition of these waters were not very significant. Locally, acid drainage seemed to have dissolved carbonate rocks present in the local stratigraphic sequence, attenuating the dispersion of metals and As. Stream sediments presented anomalies of these elements, which were strongly dependent on the proximity of tailings piles and abandoned mines. We found that precipitation processes in sediments and the dilution of dissolved phases were responsible for the attenuation of the concentrations of the metals and As in the acid drainage and river water mixing zone. In general, a larger influence of mining activities on the chemical composition of the surface waters and sediments was observed when enrichment factors in relation to regional background levels were used.

Geochemistry of acid mine drainage from a coal mining area and processes controlling metal attenuation in stream waters, southern Brazil.

Science.gov (United States)

Campaner, Veridiana P; Luiz-Silva, Wanilson; Machado, Wilson

2014-05-14

Acid drainage influence on the water and sediment quality was investigated in a coal mining area (southern Brazil). Mine drainage showed pH between 3.2 and 4.6 and elevated concentrations of sulfate, As and metals, of which, Fe, Mn and Zn exceeded the limits for the emission of effluents stated in the Brazilian legislation. Arsenic also exceeded the limit, but only slightly. Groundwater monitoring wells from active mines and tailings piles showed pH interval and chemical concentrations similar to those of mine drainage. However, the river and ground water samples of municipal public water supplies revealed a pH range from 7.2 to 7.5 and low chemical concentrations, although Cd concentration slightly exceeded the limit adopted by Brazilian legislation for groundwater. In general, surface waters showed large pH range (6 to 10.8), and changes caused by acid drainage in the chemical composition of these waters were not very significant. Locally, acid drainage seemed to have dissolved carbonate rocks present in the local stratigraphic sequence, attenuating the dispersion of metals and As. Stream sediments presented anomalies of these elements, which were strongly dependent on the proximity of tailings piles and abandoned mines. We found that precipitation processes in sediments and the dilution of dissolved phases were responsible for the attenuation of the concentrations of the metals and As in the acid drainage and river water mixing zone. In general, a larger influence of mining activities on the chemical composition of the surface waters and sediments was observed when enrichment factors in relation to regional background levels were used.

Attenuation of Morphine-Induced Tolerance and Dependence by Pretreatment with Cerebrolysin in Male rats.

Science.gov (United States)

Ghavimi, Hamed; Darvishi, Sara; Ghanbarzadeh, Saeed

2018-01-01

Dependence and tolerance to morphine are major problems which limit its chronic clinical application. This study was aimed to investigate the attenuation effect of Cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,), on the development of Morphine-induced dependence and tolerance. Male Wistar rats were selected randomly and divided into different groups (n=8) including: a control group, groups received additive doses of morphine (5-25 mg/kg, ip, at an interval of 12 h until tolerance completion), and groups pretreated with Cerebrolysin (40, 80 and 160 mg/kg, ip, before morphine administration). Development of tolerance was assessed by tail-flick test and the attenuation effect of Cerebrolysin on morphine-induced dependence was evaluated after injection of naloxone (4 mg/kg, ip, 12 h after the morning dose of morphine). Seven distinct withdrawal signs including: jumping, rearing, genital grooming, abdominal writhing, wet dog shake and teeth grinding were recorded for 45 min and total withdrawal score (TWS) was calculated. Results showed that administration of Cerebrolysin could prolonged development (10 and 14 days in administration of 80 mg/kg and 160 mg/kg Cerebrolysin) and completion (4, 10 and 14 days in administration of 40, 80 and 160 mg/kg Cerebrolysin, respectively) of tolerance. Results also indicated that administration of Cerebrolysin (40, 80 and 160 mg/kg) could significantly decreased the TWS value (62±2, 77±4 and 85±6%, respectively). In conclusion, it was found that pretreatment with Cerebrolysin could attenuated morphine-induced tolerance and dependence. © Georg Thieme Verlag KG Stuttgart · New York.

An artificial TCA cycle selects for efficient α-ketoglutarate dependent hydroxylase catalysis in engineered Escherichia coli.

Science.gov (United States)

Theodosiou, Eleni; Breisch, Marina; Julsing, Mattijs K; Falcioni, Francesco; Bühler, Bruno; Schmid, Andreas

2017-07-01

Amino acid hydroxylases depend directly on the cellular TCA cycle via their cosubstrate α-ketoglutarate (α-KG) and are highly useful for the selective biocatalytic oxyfunctionalization of amino acids. This study evaluates TCA cycle engineering strategies to force and increase α-KG flux through proline-4-hydroxylase (P4H). The genes sucA (α-KG dehydrogenase E1 subunit) and sucC (succinyl-CoA synthetase β subunit) were alternately deleted together with aceA (isocitrate lyase) in proline degradation-deficient Escherichia coli strains (ΔputA) expressing the p4h gene. Whereas, the ΔsucCΔaceAΔputA strain grew in minimal medium in the absence of P4H, relying on the activity of fumarate reductase, growth of the ΔsucAΔaceAΔputA strictly depended on P4H activity, thus coupling growth to proline hydroxylation. P4H restored growth, even when proline was not externally added. However, the reduced succinyl-CoA pool caused a 27% decrease of the average cell size compared to the wildtype strain. Medium supplementation partially restored the morphology and, in some cases, enhanced proline hydroxylation activity. The specific proline hydroxylation rate doubled when putP, encoding the Na + /l-proline transporter, was overexpressed in the ΔsucAΔaceAΔputA strain. This is in contrast to wildtype and ΔputA single-knock out strains, in which α-KG availability obviously limited proline hydroxylation. Such α-KG limitation was relieved in the ΔsucAΔaceAΔputA strain. Furthermore, the ΔsucAΔaceAΔputA strain was used to demonstrate an agar plate-based method for the identification and selection of active α-KG dependent hydroxylases. This together with the possibility to waive selection pressure and overcome α-KG limitation in respective hydroxylation processes based on living cells emphasizes the potential of TCA cycle engineering for the productive application of α-KG dependent hydroxylases. Biotechnol. Bioeng. 2017;114: 1511-1520. © 2017 Wiley Periodicals, Inc. �

A structural basis for the pH-dependent xanthophyll cycle in Arabidopsis thaliana.

Science.gov (United States)

Arnoux, Pascal; Morosinotto, Tomas; Saga, Giorgia; Bassi, Roberto; Pignol, David

2009-07-01

Plants adjust their photosynthetic activity to changing light conditions. A central regulation of photosynthesis depends on the xanthophyll cycle, in which the carotenoid violaxanthin is converted into zeaxanthin in strong light, thus activating the dissipation of the excess absorbed energy as heat and the scavenging of reactive oxygen species. Violaxanthin deepoxidase (VDE), the enzyme responsible for zeaxanthin synthesis, is activated by the acidification of the thylakoid lumen when photosynthetic electron transport exceeds the capacity of assimilatory reactions: at neutral pH, VDE is a soluble and inactive enzyme, whereas at acidic pH, it attaches to the thylakoid membrane where it binds its violaxanthin substrate. VDE also uses ascorbate as a cosubstrate with a pH-dependent Km that may reflect a preference for ascorbic acid. We determined the structures of the central lipocalin domain of VDE (VDEcd) at acidic and neutral pH. At neutral pH, VDEcd is monomeric with its active site occluded within a lipocalin barrel. Upon acidification, the barrel opens up and the enzyme appears as a dimer. A channel linking the two active sites of the dimer can harbor the entire carotenoid substrate and thus may permit the parallel deepoxidation of the two violaxanthin beta-ionone rings, making VDE an elegant example of the adaptation of an asymmetric enzyme to its symmetric substrate.

Omega-3 polyunsaturated fatty acid and ursodeoxycholic acid have an additive effect in attenuating diet-induced nonalcoholic steatohepatitis in mice.

Science.gov (United States)

Kim, Ja Kyung; Lee, Kwan Sik; Lee, Dong Ki; Lee, Su Yeon; Chang, Hye Young; Choi, Junjeong; Lee, Jung Il

2014-12-19

Nonalcoholic steatohepatitis (NASH) can progress into liver cirrhosis; however, no definite treatment is available. Omega-3 polyunsaturated fatty acid (omega-3) has been reported to alleviate experimental NASH, although its beneficial effect was not evident when tested clinically. Thus, this study aimed to investigate the additive effect of omega-3 and ursodeoxycholic acid (UDCA) on diet-induced NASH in mice. C57BL/6 mice were given a high-fat diet (HFD) for 24 weeks, at which point the mice were divided into three groups and fed HFD alone, HFD with omega-3 or HFD with omega-3 in combination with UDCA for another 24 weeks. Feeding mice an HFD and administering omega-3 improved histologically assessed liver fibrosis, and UDCA in combination with omega-3 further attenuated this disease. The assessment of collagen α1(I) expression agreed with the histological evaluation. Omega-3 in combination with UDCA resulted in a significant attenuation of inflammation whereas administering omega-3 alone failed to improve histologically assessed liver inflammation. Quantitative analysis of tumor necrosis factor α showed an additive effect of omega-3 and UDCA on liver inflammation. HFD-induced hepatic triglyceride accumulation was attenuated by omega-3 and adding UDCA accentuated this effect. In accordance with this result, the expression of sterol regulatory binding protein-1c decreased after omega-3 administration and adding UDCA further diminished SREBP-1c expression. The expression of inducible nitric oxide synthase (iNOS), which may reflect oxidative stress-induced tissue damage, was suppressed by omega-3 administration and adding UDCA further attenuated iNOS expression. These results demonstrated an additive effect of omega-3 and UDCA for alleviating fibrosis, inflammation and steatosis in diet-induced NASH.

Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions.

Science.gov (United States)

Liu, Di; Gao, Yuan; Li, Xiao-Xi; Li, Zheng; Pan, Qiu-Hong

2015-09-17

This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv.) under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A) and 99% (film B) invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA) revealed that (E)-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E)-2-heptenal, styrene, α-phenylethanol, and (Z)-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

Attenuated UV Radiation Alters Volatile Profile in Cabernet Sauvignon Grapes under Field Conditions

Directory of Open Access Journals (Sweden)

Di Liu

2015-09-01

Full Text Available This study aimed to explore the effect of attenuated UV radiation around grape clusters on the volatile profile of Cabernet Sauvignon grapes (Vitis vinifera L. cv. under field conditions. Grape bunches were wrapped with two types of polyester films that cut off 89% (film A and 99% (film B invisible sunlight of less than 380 nm wavelength, respectively. Solar UV radiation reaching the grape berry surface was largely attenuated, and an increase in the concentrations of amino acid-derived benzenoid volatiles and fatty acid-derived esters was observed in the ripening grapes. Meanwhile, the attenuated UV radiation significantly reduced the concentrations of fatty acid-derived aldehydes and alcohols and isoprenoid-derived norisoprenoids. No significant impact was observed for terpenes. In most case, these positive or negative effects were stage-dependent. Reducing UV radiation from the onset of veraison to grape harvest, compared to the other stages, caused a larger alteration in the grape volatile profile. Partial Least Square Discriminant Analysis (PLS-DA revealed that (E-2-hexenal, 4-methyl benzaldehyde, 2-butoxyethyl acetate, (E-2-heptenal, styrene, α-phenylethanol, and (Z-3-hexen-1-ol acetate were affected most significantly by the attenuated UV radiation.

Identification of critical amino acids in the proximal C-terminal of TREK-2 K+ channel for activation by acidic pHi and ATP-dependent inhibition.

Science.gov (United States)

Woo, Joohan; Jun, Young Keul; Zhang, Yin-Hua; Nam, Joo Hyun; Shin, Dong Hoon; Kim, Sung Joon

2018-02-01

TWIK-related two-pore domain K + channels (TREKs) are regulated by intracellular pH (pH i ) and Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 ). Previously, Glu 306 in proximal C-terminal (pCt) of mouse TREK-1 was identified as the pH i -sensing residue. The direction of PI(4,5)P 2 sensitivity is controversial, and we have recently shown that TREKs are inhibited by intracellular ATP via endogenous PI(4,5)P 2 formation. Here we investigate the anionic and cationic residues of pCt for the pH i and ATP-sensitivity in human TREK-2 (hTREK-2). In inside-out patch clamp recordings (I TREK-2,i-o ), acidic pH i -induced activation was absent in E332A and was partly attenuated in E335A. Neutralization of cationic Lys (K330A) also eliminated the acidic pH i sensitivity of I TREK-2,i-o . Unlike the inhibition of wild-type (WT) I TREK-2,i-o by intracellular ATP, neither E332A nor K330A was sensitive to ATP. Nevertheless, exogenous PI(4,5)P 2 (10 μM) abolished I TREK-2 i-o in all the above mutants as well as in WT, indicating unspecific inhibition by exogenous PI(4,5)P 2 . In whole-cell recordings of TREK-2 (I TREK-2,w-c ), K330A and E332A showed higher or fully active basal activity, showing attenuated or insignificant activation by 2-APB, arachidonic acid, or acidic pH e 6.9. I TREK-1,w-c of WT is largely suppressed by pH e 6.9, and the inhibition is slightly attenuated in K312A and E315A. The results show concerted roles of the oppositely charged Lys and Glu in pCt for the ATP-dependent low basal activity and pH i sensitivity.

GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis.

Science.gov (United States)

Ooi, Makoto; Nishiumi, Shin; Yoshie, Tomoo; Shiomi, Yuuki; Kohashi, Michitaka; Fukunaga, Ken; Nakamura, Shiro; Matsumoto, Takayuki; Hatano, Naoya; Shinohara, Masakazu; Irino, Yasuhiro; Takenawa, Tadaomi; Azuma, Takeshi; Yoshida, Masaru

2011-09-01

The roles that amino acids play in immunity and inflammation are well defined, and the relationship between inflammatory bowel disease (IBD) and certain amino acids has recently attracted attention. In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile. Colonic biopsy samples from 22 UC patients were used, as well as serum samples from UC patients (n = 13), Crohn's disease (CD) patients (n = 21), and healthy volunteers (n = 17). In the GC/MS-based profiling of amino acids and TCA cycle-related molecules, lower levels of 16 amino acids and 5 TCA cycle-related molecules were observed in the colonic lesion tissues of the UC patients, and the serum profiles of amino acids and TCA cycle-related molecules of the UC patients were different from those of the CD patients and healthy volunteers. Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC.

Application of natural attenuation to ground water contaminated by phenoxy acid herbicides at an old landfill in Sjoelund

DEFF Research Database (Denmark)

Tuxen, Nina; Ejlskov, P.; Albrechtsen, Hans-Jørgen

2003-01-01

Investigations of geology, hydrogeology, and ground water chemistry in the aquifer downgradient from Sjoelund Landfill, Denmark, formed the basis for an evaluation of natural attenuation as a remediation technology for phenoxy acid herbicides at the site. Concentrations of phenoxy acids were up......, such as specific metabolites, changes in enantiomeric fractions, compound-specific stable carbon isotope ratios, or microbial fingerprints....

Solar Cycle Phase Dependence of Supergranular Fractal Dimension

Indian Academy of Sciences (India)

Solar Cycle Phase Dependence of Supergranular Fractal Dimension ... NIE Institute of Technology, Mysore, India. ... This means that each accepted article is being published immediately online with DOI and article citation ID with starting page ...

Theoretical study of temperature dependent acoustic attenuation and non-linearity parameters in alkali metal hydride and deuteride

Energy Technology Data Exchange (ETDEWEB)

Singh, Rishi Pal [Department of Physics, Banaras Hindu University, Varanasi 221005 (India); Singh, Rajendra Kumar, E-mail: rksingh_17@rediffmail.com [Department of Physics, Banaras Hindu University, Varanasi 221005 (India)

2010-11-01

Temperature dependence of acoustic attenuation and non-linearity parameters in lithium hydride and lithium deuteride have been studied for longitudinal and shear modes along various crystallographic directions of propagation in a wide temperature range. Lattice parameter and repulsive parameters have been used as input data and interactions up to next nearest neighbours have been considered to calculate second and third order elastic constants which in turn have been used for evaluating acoustic attenuation and related parameters. The results have been discussed and compared with available data. It is hoped that the present results will serve to stimulate the determination of the acoustic attenuation of these compounds at different temperatures.

Cell cycle dependent RRM2 may serve as proliferation marker and pharmaceutical target in adrenocortical cancer.

Science.gov (United States)

Grolmusz, Vince Kornél; Karászi, Katalin; Micsik, Tamás; Tóth, Eszter Angéla; Mészáros, Katalin; Karvaly, Gellért; Barna, Gábor; Szabó, Péter Márton; Baghy, Kornélia; Matkó, János; Kovalszky, Ilona; Tóth, Miklós; Rácz, Károly; Igaz, Péter; Patócs, Attila

2016-01-01

Adrenocortical cancer (ACC) is a rare, but agressive malignancy with poor prognosis. Histopathological diagnosis is challenging and pharmacological options for treatment are limited. By the comparative reanalysis of the transcriptional malignancy signature with the cell cycle dependent transcriptional program of ACC, we aimed to identify novel biomarkers which may be used in the histopathological diagnosis and for the prediction of therapeutical response of ACC. Comparative reanalysis of publicly available microarray datasets included three earlier studies comparing transcriptional differences between ACC and benign adrenocortical adenoma (ACA) and one study presenting the cell cycle dependent gene expressional program of human ACC cell line NCI-H295R. Immunohistochemical analysis was performed on ACC samples. In vitro effects of antineoplastic drugs including gemcitabine, mitotane and 9-cis-retinoic acid alone and in combination were tested in the NCI-H295R adrenocortical cell line. Upon the comparative reanalysis, ribonucleotide reductase subunit 2 (RRM2), responsible for the ribonucleotide dezoxyribonucleotide conversion during the S phase of the cell cycle has been validated as cell cycle dependently expressed. Moreover, its expression was associated with the malignancy signature, as well. Immunohistochemical analysis of RRM2 revealed a strong correlation with Ki67 index in ACC. Among the antiproliferative effects of the investigated compounds, gemcitabine showed a strong inhibition of proliferation and an increase of apoptotic events. Additionally, RRM2 has been upregulated upon gemcitabine treatment. Upon our results, RRM2 might be used as a proliferation marker in ACC. RRM2 upregulation upon gemcitabine treatment might contribute to an emerging chemoresistance against gemcitabine, which is in line with its limited therapeutical efficacy in ACC, and which should be overcome for successful clinical applications.

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

Science.gov (United States)

Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

1999-01-01

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P BCAA supplementation attenuates the N loss during short-term bed rest.

Analysis of sulfur-iodine thermochemical cycle for solar hydrogen production. Part 1: decomposition of sulfuric acid

Energy Technology Data Exchange (ETDEWEB)

Huang, Cunping; T-Raissi, Ali [Central Florida Univ., Florida Solar Energy Center, Cocoa, FL (United States)

2005-05-01

The sulfur-iodine (S-I) thermochemical water splitting cycle is one of the most studied cycles for hydrogen (H{sub 2}) production. S-I cycle consists of four sections: (I) acid production and separation and oxygen purification, (II) sulfuric acid concentration and decomposition, (III) hydroiodic acid (HI) concentration, and (IV) HI decomposition and H{sub 2} purification. Section II of the cycle is an endothermic reaction driven by the heat input from a high temperature source. Analysis of the S-I cycle in the past thirty years have been focused mostly on the utilization of nuclear power as the high temperature heat source for the sulfuric acid decomposition step. Thermodynamic as well as kinetic considerations indicate that both the extent and rate of sulfuric acid decomposition can be improved at very high temperatures (in excess of 1000 deg C) available only from solar concentrators. The beneficial effect of high temperature solar heat for decomposition of sulfuric acid in the S-I cycle is described in this paper. We used Aspen Technologies' HYSYS chemical process simulator (CPS) to develop flowsheets for sulfuric acid (H{sub 2}SO{sub 4}) decomposition that include all mass and heat balances. Based on the HYSYS analyses, two new process flowsheets were developed. These new sulfuric acid decomposition processes are simpler and more stable than previous processes and yield higher conversion efficiencies for the sulfuric acid decomposition and sulfur dioxide and oxygen formation. (Author)

The response of amino acid cycling to global change across multiple biomes: Feedbacks on soil nitrogen availability

Science.gov (United States)

Brzostek, E. R.; Finzi, A. C.

2010-12-01

The cycling of organic nitrogen (N) in soil links soil organic matter decomposition to ecosystem productivity. Amino acids are a key pool of organic N in the soil, whose cycling is sensitive to alterations in microbial demand for carbon and N. Further, the amino acids released from the breakdown of protein by proteolytic enzymes are an important source of N that supports terrestrial productivity. The objective of this study was to measure changes in amino acid cycling in response to experimental alterations of precipitation and temperature in twelve global change experiments during the 2009 growing season. The study sites ranged from arctic tundra to xeric grasslands. The treatments experimentally increased temperature, increased or decreased precipitation, or some combination of both factors. The response of amino acid cycling to temperature and precipitation manipulations tended to be site specific, but the responses could be placed into a common framework. Changes in soil moisture drove a large response in amino acid cycling. Precipitation augmentation in xeric and mesic sites increased both amino acid pool sizes and production. However, treatments that decreased precipitation drove decreases in amino acid cycling in xeric sites, but led to increases in amino acid cycling in more mesic sites. Across sites, the response to soil warming was horizon specific. Amino acid cycling in organic rich horizons responded positively to warming, while negative responses were exhibited in lower mineral soil horizons. The variable response likely reflects a higher availability of protein substrate to sustain high rates of proteolytic enzyme activity in organic rich horizons. Overall, these results suggest that soil moisture and the availability of protein substrate may be important factors that mediate the response of amino acid cycling to predicted increases in soil temperatures.

Oscillating in synchrony with a metronome: serial dependence, limit cycle dynamics, and modeling.

Science.gov (United States)

Torre, Kjerstin; Balasubramaniam, Ramesh; Delignières, Didier

2010-07-01

We analyzed serial dependencies in periods and asynchronies collected during oscillations performed in synchrony with a metronome. Results showed that asynchronies contain 1/f fluctuations, and the series of periods contain antipersistent dependence. The analysis of the phase portrait revealed a specific asymmetry induced by synchronization. We propose a hybrid limit cycle model including a cycle-dependent stiffness parameter provided with fractal properties, and a parametric driving function based on velocity. This model accounts for most experimentally evidenced statistical features, including serial dependence and limit cycle dynamics. We discuss the results and modeling choices within the framework of event-based and emergent timing.

Fatty acid and amino acid modulation of glucose cycling in isolated rat hepatocytes

NARCIS (Netherlands)

Gustafson, LA; Neeft, M; Reijngoud, DJ; Kuipers, F; Sauerwein, HP; Romijn, JA; Herling, AW; Burger, HJ; Meijer, AJ

2001-01-01

We studied the influence of glucose/glucose 6-phosphate cycling on glycogen deposition from glucose in fasted-rat hepatocytes using S4048 and CP320626, specific inhibitors of glucose-6-phosphate translocase and glycogen phosphorylase respectively. The effect of amino acids and oleate was also

Attenuation of morphine tolerance and dependence by thymoquinone in mice

Directory of Open Access Journals (Sweden)

Hossein Hosseinzadeh

2016-01-01

Full Text Available Objectives: Dependence and tolerance are major restricting factors in the clinical use of opioid analgesics. In the present study, the effects of thymoquinone, the major constituent of Nigella sativa seeds, on morphine dependence and tolerance were investigated in mice. Materials and Methods: Male adult NMRI mice were made tolerant and dependent by repeated injections of morphine (50, 50, and 75 mg/kg, i.p. on 9 a.m., 1 p.m., and 5 p.m., respectively during a 3-day administration schedule. The hot-plate test was used to assess tolerance to the analgesic effects of morphine. Naloxone (2 mg/kg, i.p. was injected to precipitate withdrawal syndrome in order to assess the morphine dependence. To evaluate the effects of thymoquinone on tolerance and dependence to morphine, different single or repeated doses of thymoquinone were administered in mice. Rotarod was used to assess the motor coordination. Results: Administration of single or repeated doses of thymoquinone (20 and 40 mg/kg, i.p. significantly decreased the number of jumps in morphine dependent animals. Repeated administration of thymoquinone (20 and 40 mg/kg, for 3 days and also single injection of thymoquinone (40 mg/kg, on the fourth day attenuated tolerance to the analgesic effect of morphine. None of the thymoquinone doses (10, 20, and 40 mg/kg produced any antinociceptive effects on their own. Motor coordination of animals was impaired by the high dose of thymoquinone (40 mg/kg. Conclusion: Based on these results, it can be concluded that thymoquinone prevents the development of tolerance and dependence to morphine.

Branched-chain amino acid supplementation in treatment of liver cirrhosis: Updated views on how to attenuate their harmful effects on cataplerosis and ammonia formation.

Science.gov (United States)

Holeček, Milan

2017-09-01

Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles. The article also demonstrates that the favorable effects of BCAA supplementation might be associated with three adverse effects: draining of α-KG from tricarboxylic acid cycle (cataplerosis), increased GLN content and altered glutamatergic neurotransmission in the brain, and activated GLN catabolism to ammonia in the gut and kidneys. Cataplerosis of α-KG can be attenuated by dimethyl-α-ketoglutarate, l-ornithine-l-aspartate, and ornithine salt of α-KG. The pros and cons of GLN elimination from the body using phenylbutyrate (phenylacetate), which may impair liver regeneration and decrease BCAA levels, should be examined. The therapeutic potential of BCAA might be enhanced also by optimizing its supplementation protocol. It is concluded that the search for strategies attenuating adverse and increasing positive effects of the BCAA is needed to include the BCAA among standard medications for patients with cirrhosis of the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

α-Terpineol attenuates morphine-induced physical dependence and tolerance in mice: role of nitric oxide.

Science.gov (United States)

Parvardeh, Siavash; Moghimi, Mahsa; Eslami, Pegah; Masoudi, Alireza

2016-02-01

Dependence and tolerance to opioid analgesics are major problems limiting their clinical application. α-Terpineol is a monoterpenoid alcohol with neuroprotective effects which is found in several medicinal plants such as Myrtus communis, Laurus nobilis, and Stachys byzantina. It has been shown that some of these medicinal plants such as S. byzantina attenuate dependence and tolerance to morphine. Since α-terpineol is one of the bioactive phytochemical constituent of these medicinal plants, the present study was conducted to investigate the effects of α-terpineol on morphine-induced dependence and tolerance in mice. The mice were rendered dependent or tolerant to morphine by a 3-day administration schedule. The hot-plate test and naloxone-induced withdrawal syndrome were used to evaluate tolerance and dependence on morphine, respectively. To investigate a possible role for nitric oxide (NO) in the protective effect of α-terpineol, the NO synthase inhibitor, L-N(G)-nitroarginine methyl ester (L-NAME) and NO precursor, L-arginine, were used. Administration of α-terpineol (5, 10, and 20 mg/kg, IP) significantly decreased the number of jumps in morphine dependent animals. Moreover, α-terpineol (20 and 40 mg/kg, IP) attenuated tolerance to the analgesic effect of morphine. The inhibitory effects of α-terpineol on morphine-induced dependence and tolerance were enhanced by pretreatment with L-NAME (10 mg/kg, IP). However, L-arginine (300 mg/kg, IP) antagonized the protective effects of α-terpineol on dependence and tolerance to morphine. These findings indicate that α-terpineol prevents the development of dependence and tolerance to morphine probably through the influence on NO production.

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

Science.gov (United States)

Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

Glutamine Attenuates Acute Lung Injury Caused by Acid Aspiration

Directory of Open Access Journals (Sweden)

Chih-Cheng Lai

2014-08-01

Full Text Available Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI in patients with acute respiratory distress syndrome (ARDS. Here, we examined potential benefits of glutamine (GLN on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer’s solution (vehicle control thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV of 15 mL/kg and zero positive end-expiratory pressure (PEEP or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology, neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.

Quantification of numerical aperture-dependence of the OCT attenuation coefficient (Conference Presentation)

Science.gov (United States)

Peinado, Liliana M.; Bloemen, Paul R.; Almasian, Mitra; van Leeuwen, Ton G.; Faber, Dirk J.

2016-03-01

Despite the improvements in early cancer diagnosis, adequate diagnostic tools for early staging of bladder cancer tumors are lacking [1]. MEMS-probes based on optical coherence tomography (OCT) provide cross-sectional imaging with a high-spatial resolution at a high-imaging speed, improving visualization of cancerous tissue [2-3]. Additionally, studies show that the measurement of localized attenuation coefficient allows discrimination between healthy and cancerous tissue [4]. We have designed a new miniaturized MEMS-probe based on OCT that will optimize early diagnosis by improving functional visualization of suspicious lesions in bladder. During the optical design phase of the probe, we have studied the effect of the numerical aperture (NA) on the OCT signal attenuation. For this study, we have employed an InnerVision Santec OCT system with several numerical apertures (25mm, 40mm, 60mm, 100mm, 150mm and 200mm using achromatic lenses). The change in attenuation coefficient was studied using 15 dilutions of intralipid ranging between 6*10-5 volume% and 20 volume%. We obtained the attenuation coefficient from the OCT images at several fixed positions of the focuses using established OCT models (e.g. single scattering with known confocal point spread function (PSF) [5] and multiple scattering using the Extended Huygens Fresnel model [6]). As a result, a non-linear increase of the scattering coefficient as a function of intralipid concentration (due to dependent scattering) was obtained for all numerical apertures. For all intralipid samples, the measured attenuation coefficient decreased with a decrease in NA. Our results suggest a non-negligible influence of the NA on the measured attenuation coefficient. [1] Khochikar MV. Rationale for an early detection program for bladder cancer. Indian J Urol 2011 Apr-Jun; 27(2): 218-225. [2] Sun J and Xie H. Review Article MEMS-Based Endoscopic Optical Coherence Tomography. IJO 2011, Article ID 825629, 12 pages. doi:10

Cell cycle age dependence for radiation-induced G2 arrest: evidence for time-dependent repair

International Nuclear Information System (INIS)

Rowley, R.

1985-01-01

Exponentially growing eucaryotic cells, irradiated in interphase, are delayed in progression to mitosis chiefly by arrest in G 2 . The sensitivity of Chinese hamster ovary cells to G 2 arrest induction by X rays increases through the cell cycle, up to the X-ray transition point (TP) in G 2 . This age response can be explained by cell cycle age-dependent changes in susceptibility of the target(s) for G 2 arrest and/or by changes in capability for postirradiation recovery from G 2 arrest damage. Discrimination between sensitivity changes and repair phenomena is possible only if the level of G 2 arrest-causing damage sustained by a cell at the time of irradiation and the level ultimately expressed as arrest can be determined. The ability of caffeine to ameliorate radiation-induced G 2 arrest, while inhibiting repair of G 2 arrest-causing damage makes such an analysis possible. In the presence of caffeine, progression of irradiated cells was relatively unperturbed, but on caffeine removal, G 2 arrest was expressed. The duration of G 2 arrest was independent of the length of the prior caffeine exposure. This finding indicates that the target for G 2 arrest induction is present throughout the cell cycle and that the level of G 2 arrest damage incurred is initially constant for all cell cycle phases. The data are consistent with the existence of a time-dependent recovery mechanism to explain the age dependence for radiation induction of G 2 arrest

A Structural Basis for the pH-Dependent Xanthophyll Cycle in Arabidopsis thaliana[C][W

Science.gov (United States)

Arnoux, Pascal; Morosinotto, Tomas; Saga, Giorgia; Bassi, Roberto; Pignol, David

2009-01-01

Plants adjust their photosynthetic activity to changing light conditions. A central regulation of photosynthesis depends on the xanthophyll cycle, in which the carotenoid violaxanthin is converted into zeaxanthin in strong light, thus activating the dissipation of the excess absorbed energy as heat and the scavenging of reactive oxygen species. Violaxanthin deepoxidase (VDE), the enzyme responsible for zeaxanthin synthesis, is activated by the acidification of the thylakoid lumen when photosynthetic electron transport exceeds the capacity of assimilatory reactions: at neutral pH, VDE is a soluble and inactive enzyme, whereas at acidic pH, it attaches to the thylakoid membrane where it binds its violaxanthin substrate. VDE also uses ascorbate as a cosubstrate with a pH-dependent Km that may reflect a preference for ascorbic acid. We determined the structures of the central lipocalin domain of VDE (VDEcd) at acidic and neutral pH. At neutral pH, VDEcd is monomeric with its active site occluded within a lipocalin barrel. Upon acidification, the barrel opens up and the enzyme appears as a dimer. A channel linking the two active sites of the dimer can harbor the entire carotenoid substrate and thus may permit the parallel deepoxidation of the two violaxanthin β-ionone rings, making VDE an elegant example of the adaptation of an asymmetric enzyme to its symmetric substrate. PMID:19638474

JMJD2A attenuation affects cell cycle and tumourigenic inflammatory gene regulation in lipopolysaccharide stimulated neuroectodermal stem cells

Energy Technology Data Exchange (ETDEWEB)

Das, Amitabh, E-mail: amitabhdas.kn@gmail.com [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Chai, Jin Choul, E-mail: jincchai@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Jung, Kyoung Hwa, E-mail: khjung2@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Das, Nando Dulal, E-mail: nando.hu@gmail.com [Clinical Research Centre, Inha University School of Medicine, Incheon 400-711 (Korea, Republic of); Kang, Sung Chul, E-mail: gujiju11@gmail.com [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Lee, Young Seek, E-mail: yslee@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Seo, Hyemyung, E-mail: hseo@hanyang.ac.kr [Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of); Chai, Young Gyu, E-mail: ygchai@hanyang.ac.kr [Department of Bionanotechnology, Hanyang University, Seoul 133-791 (Korea, Republic of); Department of Molecular and Life Science, Hanyang University, 1271 Sa 3-dong, Ansan 426-791, Gyeonggi-do (Korea, Republic of)

2014-11-01

JMJD2A is a lysine trimethyl-specific histone demethylase that is highly expressed in a variety of tumours. The role of JMJD2A in tumour progression remains unclear. The objectives of this study were to identify JMJD2A-regulated genes and understand the function of JMJD2A in p53-null neuroectodermal stem cells (p53{sup −/−} NE-4Cs). We determined the effect of LPS as a model of inflammation in p53{sup −/−} NE-4Cs and investigated whether the epigenetic modifier JMJD2A alter the expression of tumourigenic inflammatory genes. Global gene expression was measured in JMJD2A knockdown (kd) p53{sup −/−} NE-4Cs and in LPS-stimulated JMJD2A-kd p53{sup −/−} NE-4C cells. JMJD2A attenuation significantly down-regulated genes were Cdca2, Ccnd2, Ccnd1, Crebbp, IL6rα, and Stat3 related with cell cycle, proliferation, and inflammatory-disease responses. Importantly, some tumour-suppressor genes including Dapk3, Timp2 and TFPI were significantly up-regulated but were not affected by silencing of the JMJD2B. Furthermore, we confirmed the attenuation of JMJD2A also down-regulated Cdca2, Ccnd2, Crebbp, and Rest in primary NSCs isolated from the forebrains of E15 embryos of C57/BL6J mice with effective p53 inhibitor pifithrin-α (PFT-α). Transcription factor (TF) motif analysis revealed known binding patterns for CDC5, MYC, and CREB, as well as three novel motifs in JMJD2A-regulated genes. IPA established molecular networks. The molecular network signatures and functional gene-expression profiling data from this study warrants further investigation as an effective therapeutic target, and studies to elucidate the molecular mechanism of JMJD2A-kd-dependent effects in neuroectodermal stem cells should be performed. - Highlights: • Significant up-regulation of epigenetic modifier JMJD2A mRNA upon LPS treatment. • Inhibition of JMJD2A attenuated key inflammatory and tumourigenic genes. • Establishing IPA based functional genomics in JMJD2A-attenuated p53{sup �

Mapping of the mutations present in the genome of the Rift Valley fever virus attenuated MP12 strain and their putative role in attenuation.

Science.gov (United States)

Vialat, P; Muller, R; Vu, T H; Prehaud, C; Bouloy, M

1997-11-01

The MP12 attenuated strain of Rift Valley fever virus was obtained by 12 serial passages of a virulent isolate ZH548 in the presence of 5-fluorouracil (Caplen et al., 1985. Mutagen-directed attenuation of Rift Valley fever virus as a method for vaccine development. J. Gen. Virol., 66, 2271-2277). The comparison of the M segment of the two strains has already been reported by Takehara et al. (Takehara et al., 1989. Identification of mutations in the M RNA of a candidate vaccine strain of Rift Valley fever virus. Virology 169, 452-457). We have completed the comparison and found that altogether a total of nine, 12 and four nucleotides were changed in the L, M and S segments of the two strains, respectively. Three mutations induced amino acid changes in the L protein but none of them was located in the recognized motifs conserved among RNA dependent polymerases. In the S segment, a single change modified an amino acid in the NSs protein and in the M segment, seven of the mutations resulted in amino acid changes in each of the four encoded G1, G2, 14 kDa and 78 kDa proteins. Characterization of the MP12 virus indicated that determinants for attenuation were present in each segment and that they were introduced progressively during the 12 passages in the presence of the mutagen (Saluzzo and Smith, 1990. Use of reassortant viruses to map attenuating and temperature-sensitive mutations of the Rift Valley fever virus MP-12 vaccine. Vaccine 8, 369-375). Passages 4 and 7-9 were found to be essential for introduction of temperature-sensitive lesions and attenuation. In an attempt to correlate some of the mutations with the attenuated or temperature-sensitive phenotypes, we determined by sequencing the passage level at which the different mutations appeared. This work should help to address the question of the role of the viral gene products in Rift Valley fever pathogenesis.

Localisation of gluconeogenesis and tricarboxylic acid (TCA)-cycle enzymes and first functional analysis of the TCA cycle in Toxoplasma gondii.

Science.gov (United States)

Fleige, Tobias; Pfaff, Nils; Gross, Uwe; Bohne, Wolfgang

2008-08-01

The apicomplexan parasite Toxoplasma gondii displays some unusual localisations of carbohydrate converting enzymes, which is due to the presence of a vestigial, non-photosynthetic plastid, referred to as the apicoplast. It was recently demonstrated that the single pyruvate dehydrogenase complex (PDH) in T. gondii is exclusively localised inside the apicoplast but absent in the mitochondrion. This raises the question about expression, localisation and function of enzymes for the tricarboxylic acid (TCA)-cycle, which normally depends on PDH generated acetyl-CoA. Based on the expression and localisation of epitope-tagged fusion proteins, we show that all analysed TCA cycle enzymes are localised in the mitochondrion, including both isoforms of malate dehydrogenase. The absence of a cytosolic malate dehydrogenase suggests that a typical malate-aspartate shuttle for transfer of reduction equivalents is missing in T. gondii. We also localised various enzymes which catalyse the irreversible steps in gluconeogenesis to a cellular compartment and examined mRNA expression levels for gluconeogenesis and TCA cycle genes between tachyzoites and in vitro bradyzoites. In order to get functional information on the TCA cycle for the parasite energy metabolism, we created a conditional knock-out mutant for the succinyl-CoA synthetase. Disruption of the sixth step in the TCA cycle should leave the biosynthetic parts of the cycle intact, but prevent FADH2 production. The succinyl-CoA synthetase depletion mutant displayed a 30% reduction in growth rate, which could be restored by supplementation with 2 microM succinate in the tissue culture medium. The mitochondrial membrane potential in these parasites was found to be unaltered. The lack of a more severe phenotype suggests that a functional TCA cycle is not essential for T. gondii replication and for maintenance of the mitochondrial membrane potential.

Integrated gasification combined cycle for acid rain control

Energy Technology Data Exchange (ETDEWEB)

Simbeck, D.R.; Dickenson, R.L.

1986-10-01

The role of integrated coal gasification combined-cycle power plants in the abatement of emission of SO/sub 2/ and NO/sub 2/ which lead to acid rain is discussed. The economics of this IGCC approach are assessed for a nominal 500 MW plant size. Phased construction of IGCC plants is recommended as a means of reducing SO/sub 2/ and NO/sub x/ emissions noting that high-sulfur coals could continue to be used. It is also noted that phased construction IGCC is the only acid rain control technology that greatly reduces NO/sub x/. 17 references.

Attenuation of the protein wasting associated with bed rest by branched-chain amino acids

Science.gov (United States)

Stein, T. P.; Schluter, M. D.; Leskiw, M. J.; Boden, G.

1999-01-01

Bed rest is generally accepted as being an appropriate ground-based model for human spaceflight. The objectives of this study were to test the hypothesis that increasing the amount of branched-chain amino acids (BCAAs) in the diet could attenuate the protein loss associated with bed rest. Nineteen healthy subjects were randomized into two groups according to diet. During the 6 d of bed rest, the diets were supplemented with either 30 mmol/d each of three non-essential amino acids, glycine, serine, and alanine (control group), or with 30 mmol/d each of the BCAAs, leucine, isoleucine, and valine (BCAA group). Nutrition was supplied as a commercially available defined formula diet at a rate of 1.3 x REE. Nitrogen (N) balance and urinary 3-MeH excretion were determined for the 6 d. In our results, the urine-based estimate of N balance was 22.2 +/- 14.4 (n = 9) mg N.kg-1.d-1 and 60.5 +/- 10.1 mg (n = 8) N.kg-1.d-1 for the control and BCAA-supplemented groups, respectively (P < 0.05). Urinary 3-MeH excretion was unchanged in both groups with bed rest. We conclude that BCAA supplementation attenuates the N loss during short-term bed rest.

Foreign Assistance Dependency: Breaking the Cycle Through Advanced Education

Science.gov (United States)

2010-12-01

Devesh, and Megan Crowley. Beyond the ABCs: Higher Education and Developing Countries. Center for Global Development, 2008. Keyes, Charley , Laurie Ure...AND DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE Foreign Assistance Dependency: Breaking the Cycle Through Advanced Education 6. AUTHOR(S...dependency on U.S. appropriations or NGO donations. This thesis evaluates these factors in the context of three higher education foreign assistance programs

Bile acids cycle disruption in patients with nasopharyngeal ...

African Journals Online (AJOL)

2014-12-31

Dec 31, 2014 ... Cite as: Wang C-S, Liu S-H, Peng J, Tang C, Zhu W-G. Bile acids cycle disruption in patients .... stein-Barr virus in the development of nasopharyngeal carcinoma. Chin. J. Cancer 2014; 33(11): 556 PubMed. -568. 2. Mrizak D, Martin N, Barjon C, Jimenez-Pailhes AS,. Mustapha R, Niki T, Guigay J, Pancre V, ...

Ultrasound fields in an attenuating medium

DEFF Research Database (Denmark)

Jensen, Jørgen Arendt; Gandhi,, D; O'Brien,, W.D., Jr.

1993-01-01

of the rectangles and sums all contributions to arrive at the spatial impulse response for the aperture and field point. This approach makes it possible to model all transducer apertures, and the program can readily calculate the emitted, pulse-echo and continuous wave field. Attenuation is included by splitting...... it into a frequency dependent part and frequency independent part. The latter results in an attenuation factor that is multiplied onto the responses from the individual elements, and the frequency dependent part is handled by attenuating the basic one-dimensional pulse. The influence on ultrasound fields from......Ultrasound fields propagating in tissue will undergo changes in shape not only due to diffraction, but also due to the frequency dependent attenuation. Linear fields can be fairly well predicted for a non-attenuating medium like water by using the Tupholme-Stepanishen method for calculating...

Attenuation of Morphine Physical Dependence and Blood Levels of Cortisol by Central and Systemic Administration of Ramelteon in Rat

Directory of Open Access Journals (Sweden)

Majid Motaghinejad

2015-05-01

Full Text Available Background: Chronic administration of morphine cause physical dependence but the exact mechanism of this phenomenon remains unclear. The aim of this study is the assessment of systemic and intracerebroventricular (icv administration of ramelteon (a melatonin receptor agonist on morphine physical dependence. Methods: 88 adult male rats were divided into 2 major groups, namely “systematic” and “central” administration of ramelteon. In the first category, systemic administration of ramelteon at various dosages (10, 20, and 40 mg/kg was assessed on dependent animals and withdrawal signs were compared with positive (received morphine and saline as systemic administration, negative control (saline and group under treatment by ramelteon (40 mg/kg groups. In the second category, central administration of ramelteon at various dosages (25, 50, or 100 μg, was assessed on dependent animals and withdrawal signs were compared with the positive control (received morphine and saline as icv and negative control (saline groups, and the group under treatment by ramelteon (50 μg/5 μl/rat. On the test day, all animals received naloxone (3 mg/kg and were observed for withdrawal signs. Total withdrawal score (TWS was also determined. Finally, to evaluate the stress level of dependent rats, blood cortisols were measured. Results: Central administration of ramelteon in all doses and systemic administration in high doses attenuate withdrawal syndrome in comparison with the dependent positive control group (P<0.05. Both central and systemic administrations of ramelteon can attenuate the blood cortisol level in comparison with the dependent positive control group (P<0.05. Conclusion: In conclusion, we found that central administration of ramelteon attenuated morphine withdrawal symptoms and cortisol level as a stress marker.

Studies on the Growth Effects of the Canaline-Urea Cycle Amino Acids with Lemna minor L. 1

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Rosenthal, Gerald A.; Gulati, Dushyant K.; Sabharwal, P. S.

1975-01-01

The aquatic microphyte, Lemna minor L., was utilized to assess the relative toxicity and general growth effects of canavanine, canaline, ureidohomoserine (UHS), and canavaninosuccinate (CSA). These amino acids are constituents of the canaline-urea cycle and structural analogues of the ornithine-urea cycle amino acids. Comparative growth studies with L. minor revealed that the canaline-urea cycle amino acids are potent antimetabolites. With the exception of CSA, they are extremely toxic at a concentration of 5 μm. Over a concentration range of 1 to 4 μm, canavanine is the most growth-inhibiting of the canaline-urea cycle amino acids. At or above 5 μm, canavanine and canaline possess comparable toxicity. UHS is less growth-inhibiting than canavanine or canaline, and CSA is the least toxic of the canaline-urea cycle intermediates. PMID:16659316

Dependence of ultrasound attenuation in rare earth metals on ratio of grain size and wavelength

International Nuclear Information System (INIS)

Kanevskij, I.N.; Nisnevich, M.M.; Spasskaya, A.A.; Kaz'mina, V.I.

1978-01-01

Results of investigation of dependences of ultrasound attenuation coefficient α on the ratio of grain average size D and wavelength lambda are presented. The investigations were carried out on rare earth metal samples produced by arc remelting in a vacuum furnace. It is shown that the way of α dependence curves of D/lambda for each of the rare earth metal is determined only by the D. This fact permits to use ultrasound measurement for control average diameter of the rare earth metal grain

The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes

DEFF Research Database (Denmark)

Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S

2017-01-01

, and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13 C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA...... tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13 C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U-13 C]glucose. The presence of metformin did not compromise the viability of cultured...

Sun-controlled spatial and time-dependent cycles in the climatic/weather system

International Nuclear Information System (INIS)

Njau, E.C.

1990-11-01

We show, on the basis of meteorological records, that certain spatial and time-dependent cycles exist in the earth-atmosphere system (EAS). These cycles seem to be associated with sunspot cycles and hence have been referred to in the text as ''data-derived solar cycles''. Our analysis establishes three important characteristics of the data-derived solar cycles (DSC's). Firstly the crests and troughs of these data-derived solar cycles are mostly latitudinally aligned and have (zonal) spatial wavelengths greater than about 7 degrees of longitude. Secondly the DSC's have periods mostly lying between 6 years and 12 years. In certain stations, some DSC's coincide quite well with corresponding sunspot cycles. Thirdly the crests and troughs of the DSC's drift eastwards at speeds exceeding about 1.5 longitude degrees per year. Furthermore, these DSC's display peak-to-peak amplitudes of about 2 deg. C along East Africa. On the basis of earlier work and bearing in mind the considerable temperature-dependence of the stratospheric ozone layer, we predict existence of latitudinally aligned enhancement and depletion structures (corresponding to the DSC's) in the stratospheric ozone layer within cloudless midnight-to-predawn sectors. (author). 9 refs, 5 figs

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

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Jin, Li; Piao, Zhe Hao; Sun, Simei; Liu, Bin; Ryu, Yuhee; Choi, Sin Young; Kim, Gwi Ran; Kim, Hyung-Seok; Kee, Hae Jin; Jeong, Myung Ho

2017-12-01

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical Applications of a CT Window Blending Algorithm: RADIO (Relative Attenuation-Dependent Image Overlay).

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Mandell, Jacob C; Khurana, Bharti; Folio, Les R; Hyun, Hyewon; Smith, Stacy E; Dunne, Ruth M; Andriole, Katherine P

2017-06-01

A methodology is described using Adobe Photoshop and Adobe Extendscript to process DICOM images with a Relative Attenuation-Dependent Image Overlay (RADIO) algorithm to visualize the full dynamic range of CT in one view, without requiring a change in window and level settings. The potential clinical uses for such an algorithm are described in a pictorial overview, including applications in emergency radiology, oncologic imaging, and nuclear medicine and molecular imaging.

Modelling the CDK-dependent transcription cycle in fission yeast.

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Sansó, Miriam; Fisher, Robert P

2013-12-01

CDKs (cyclin-dependent kinases) ensure directionality and fidelity of the eukaryotic cell division cycle. In a similar fashion, the transcription cycle is governed by a conserved subfamily of CDKs that phosphorylate Pol II (RNA polymerase II) and other substrates. A genetic model organism, the fission yeast Schizosaccharomyces pombe, has yielded robust models of cell-cycle control, applicable to higher eukaryotes. From a similar approach combining classical and chemical genetics, fundamental principles of transcriptional regulation by CDKs are now emerging. In the present paper, we review the current knowledge of each transcriptional CDK with respect to its substrate specificity, function in transcription and effects on chromatin modifications, highlighting the important roles of CDKs in ensuring quantity and quality control over gene expression in eukaryotes.

Development of an improved two-cycle process for recovering uranium from wet-process phosphoric acid

International Nuclear Information System (INIS)

Chen, H.M.; Chen, H.J.; Tsai, Y.M.; Lee, T.W.; Ting, G.

1987-01-01

An improved two-cycle separation process for the recovery of uranium from wet-process phosphoric acid by extraction with bis(2-ethylhexyl)phosphoric acid (D2EHPA) plus dibutyl butylphosphonate (DBBP) in kerosene has been developed and demonstrated successfully in bench-scale, continuous mixer-settler tests. The sulfuric acid and water scrubbing steps for the recycled extraction in the second cycle solve the problems of the contamination and dilution of the phosphoric acid by the ammonium ion and water and also avoid the formation of undesirable phosphatic precipitates during the subsequent extraction of uranium by recycled organic extractant

Prebiotic Amino Acid Thioester Synthesis: Thiol-Dependent Amino Acid Synthesis from Formose substrates (Formaldehyde and Glycolaldehyde) and Ammonia

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Weber, Arthur L.

1998-01-01

Formaldehyde and glycolaldehyde (substrates of the formose autocatalytic cycle) were shown to react with ammonia yielding alanine and homoserine under mild aqueous conditions in the presence of thiol catalysts. Since similar reactions carried out without ammonia yielded alpha-hydroxy acid thioesters, the thiol-dependent synthesis of alanine and homoserine is presumed to occur via amino acid thioesters-intermediates capable of forming peptides. A pH 5.2 solution of 20 mM formaldehyde, 20 mM glycolaldehyde, 20 mM ammonium chloride, 23 mM 3-mercaptopropionic acid, and 23 mM acetic acid that reacted for 35 days at 40 C yielded (based on initial formaldehyde) 1.8% alanine and 0.08% homoserine. In the absence of thiol catalyst, the synthesis of alanine and homoserine was negligible. Alanine synthesis required both formaldehyde and glycolaldehyde, but homoserine synthesis required only glycolaldehyde. At 25 days the efficiency of alanine synthesis calculated from the ratio of alanine synthesized to formaldehyde reacted was 2.1%, and the yield (based on initial formaldehyde) of triose and tetrose intermediates involved in alanine and homoserine synthesis was 0.3 and 2.1%, respectively. Alanine synthesis was also seen in similar reactions containing only 10 mM each of aldehyde substrates, ammonia, and thiol. The prebiotic significance of these reactions that use the formose reaction to generate sugar intermediates that are converted to reactive amino acid thioesters is discussed.

MK-801, but not drugs acting at strychnine-insensitive glycine receptors, attenuate methamphetamine nigrostriatal toxicity.

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Layer, R T; Bland, L R; Skolnick, P

1993-10-15

Repeated administration of methamphetamine (METH) results in damage to nigrostriatal dopaminergic neurons. Both competitive N-methyl-D-aspartate (NMDA) receptor antagonists and use-dependent cation channel blockers attenuate METH-induced damage. The objectives of the present study were to examine whether comparable reductions in METH-induced damage could be obtained by compounds acting at strychnine-insensitive glycine receptors on the NMDA receptor complex. Four injections of METH (5 mg/kg i.p.) resulted in a approximately 70.9% depletion of striatal dopamine (DA) and approximately 62.7% depletion of dihydroxyphenylacetic acid (DOPAC) content, respectively. A significant protection against METH-induced DA and DOPAC depletion was afforded by the use-dependent channel blocker, MK-801. The competitive glycine antagonist 7-chlorokynurenic acid (7-Cl-KA), the low efficacy glycine partial agonist (+)-3-amino-1-hydroxy-2-pyrrolidone ((+)-HA-966), and the high efficacy partial glycine agonist 1-aminocyclopropane-carboxylic acid (ACPC) were ineffective against METH-induced toxicity despite their abilities to attenuate glutamate-induced neurotoxicity under both in vivo and in vitro conditions. These results indicate that glycinergic ligands do not possess the same broad neuroprotective spectrum as other classes of NMDA antagonists.

Endoplasmic Reticulum Chaperon Tauroursodeoxycholic Acid Attenuates Aldosterone-Infused Renal Injury

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Honglei Guo

2016-01-01

Full Text Available Aldosterone (Aldo is critically involved in the development of renal injury via the production of reactive oxygen species and inflammation. Endoplasmic reticulum (ER stress is also evoked in Aldo-induced renal injury. In the present study, we investigated the role of ER stress in inflammation-mediated renal injury in Aldo-infused mice. C57BL/6J mice were randomized to receive treatment for 4 weeks as follows: vehicle infusion, Aldo infusion, vehicle infusion plus tauroursodeoxycholic acid (TUDCA, and Aldo infusion plus TUDCA. The effect of TUDCA on the Aldo-infused inflammatory response and renal injury was investigated using periodic acid-Schiff staining, real-time PCR, Western blot, and ELISA. We demonstrate that Aldo leads to impaired renal function and inhibition of ER stress via TUDCA attenuates renal fibrosis. This was indicated by decreased collagen I, collagen IV, fibronectin, and TGF-β expression, as well as the downregulation of the expression of Nlrp3 inflammasome markers, Nlrp3, ASC, IL-1β, and IL-18. This paper presents an important role for ER stress on the renal inflammatory response to Aldo. Additionally, the inhibition of ER stress by TUDCA negatively regulates the levels of these inflammatory molecules in the context of Aldo.

Neutralization and attenuation of metal species in acid mine drainage and mine leachates using magnesite: a batch experimental approach

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2014-08-01

Full Text Available International Mine Water Association Conference – An Interdisciplinary Response to Mine Water Challenges, China University of Mining and Technogy, China, China, 18-22 August 2014 Neutralization and Attenuation of Metal Species in Acid Mine Drainage and Mine...

Tracer attenuation in groundwater

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Cvetkovic, Vladimir

2011-12-01

The self-purifying capacity of aquifers strongly depends on the attenuation of waterborne contaminants, i.e., irreversible loss of contaminant mass on a given scale as a result of coupled transport and transformation processes. A general formulation of tracer attenuation in groundwater is presented. Basic sensitivities of attenuation to macrodispersion and retention are illustrated for a few typical retention mechanisms. Tracer recovery is suggested as an experimental proxy for attenuation. Unique experimental data of tracer recovery in crystalline rock compare favorably with the theoretical model that is based on diffusion-controlled retention. Non-Fickian hydrodynamic transport has potentially a large impact on field-scale attenuation of dissolved contaminants.

β2-Adrenergic receptor-dependent attenuation of hypoxic pulmonary vasoconstriction prevents progression of pulmonary arterial hypertension in intermittent hypoxic rats.

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Hisashi Nagai

Full Text Available In sleep apnea syndrome (SAS, intermittent hypoxia (IH induces repeated episodes of hypoxic pulmonary vasoconstriction (HPV during sleep, which presumably contribute to pulmonary arterial hypertension (PAH. However, the prevalence of PAH was low and severity is mostly mild in SAS patients, and mild or no right ventricular hypertrophy (RVH was reported in IH-exposed animals. The question then arises as to why PAH is not a universal finding in SAS if repeated hypoxia of sufficient duration causes cycling HPV. In the present study, rats underwent IH at a rate of 3 min cycles of 4-21% O2 for 8 h/d for 6 w. Assessment of diameter changes in small pulmonary arteries in response to acute hypoxia and drugs were performed using synchrotron radiation microangiography on anesthetized rats. In IH-rats, neither PAH nor RVH was observed and HPV was strongly reversed. Nadolol (a hydrophilic β(1, 2-blocker augmented the attenuated HPV to almost the same level as that in N-rats, but atenolol (a hydrophilic β1-blocker had no effect on the HPV in IH. These β-blockers had almost no effect on the HPV in N-rats. Chronic administration of nadolol during 6 weeks of IH exposure induced PAH and RVH in IH-rats, but did not in N-rats. Meanwhile, atenolol had no effect on morphometric and hemodynamic changes in N and IH-rats. Protein expression of the β1-adrenergic receptor (AR was down-regulated while that of β2AR was preserved in pulmonary arteries of IH-rats. Phosphorylation of p85 (chief component of phosphoinositide 3-kinase (PI3K, protein kinase B (Akt, and endothelial nitric oxide synthase (eNOS were abrogated by chronic administration of nadolol in the lung tissue of IH-rats. We conclude that IH-derived activation of β2AR in the pulmonary arteries attenuates the HPV, thereby preventing progression of IH-induced PAH. This protective effect may depend on the β2AR-Gi mediated PI3K/Akt/eNOS signaling pathway.

Alternative carbohydrate reserves used in the daily cycle of crassulacean acid metabolism

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C.C. Black; J.-Q. Chen; R.L. Doong; M.N. Angelov; Shi-Jean S. Sung

1996-01-01

Each day a massive interlocked biochemical cycle occurs in the green tissues of crassulacean acid metabolism plants.The function of this interlocked cycle, in its simplest context, is to furnish most of the CO2 for CAM plant photosynthesis.In this unified presentation our aims are (1) to divide CAM plants into two metabolic groups, (2) to...

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

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Meguro, Ayano; Sato, Yutaka

2014-04-01

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

Tauroursodeoxycholic acid attenuates gentamicin-induced cochlear hair cell death in vitro.

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Jia, Zhanwei; He, Qiang; Shan, Chunguang; Li, Fengyi

2018-09-15

Gentamycin is one of the most clinically used aminoglycoside antibiotics which induce intrinsic apoptosis of hair cells. Tauroursodeoxycholic acid (TUDCA) is known as safe cell-protective agent in disorders associated with apoptosis. We aimed to investigate the protective effects of TUDCA against gentamicin-induced ototoxicity. House Ear Institute-Organ of Corti 1(HEI-OC1) cells and explanted cochlear tissue were treated with gentamicin and TUDCA, followed by serial analyses including cell viability assay, hair cell staining, qPCR, ELISA and western blotting to determine the cell damage by the parameters relevant to cell apoptosis and endoplasmic reticulum stress. TUDCA significantly attenuated gentamicin-induced cell damage in cultured HEI-OC1 cells and explanted cochlear hair cells. TUDCA alleviated gentamicin-induced cell apoptosis, supported by the decreased Bax/Bcl2 ratio compared with that of gentamicin treated alone. TUDCA decreased gentamicin-induced nitric oxide production and protein nitration in both models. In addition, TUDCA suppressed gentamicin-induced endoplasmic reticulum stress as reflected by inversing the expression levels of Binding immunoglobulin protein (Bip), CCAAT/-enhancer-binding protein homologous protein (CHOP) and Caspase 3. TUDCA attenuated gentamicin-induced hair cell death by inhibiting protein nitration activation and ER stress, providing new insights into the new potential therapies for sensorineural deafness. Copyright © 2018 Elsevier B.V. All rights reserved.

Role of hydrous iron oxide formation in attenuation and diel cycling of dissolved trace metals in a stream affected by acid rock drainage

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Parker, S.R.; Gammons, C.H.; Jones, Clain A.; Nimick, D.A.

2007-01-01

Mining-impacted streams have been shown to undergo diel (24-h) fluctuations in concentrations of major and trace elements. Fisher Creek in south-central Montana, USA receives acid rock drainage (ARD) from natural and mining-related sources. A previous diel field study found substantial changes in dissolved metal concentrations at three sites with differing pH regimes during a 24-h period in August 2002. The current work discusses follow-up field sampling of Fisher Creek as well as field and laboratory experiments that examine in greater detail the underlying processes involved in the observed diel concentration changes. The field experiments employed in-stream chambers that were either transparent or opaque to light, filled with stream water and sediment (cobbles coated with hydrous Fe and Al oxides), and placed in the stream to maintain the same temperature. Three sets of laboratory experiments were performed: (1) equilibration of a Cu(II) and Zn(II) containing solution with Fisher Creek stream sediment at pH 6.9 and different temperatures; (2) titration of Fisher Creek water from pH 3.1 to 7 under four different isothermal conditions; and (3) analysis of the effects of temperature on the interaction of an Fe(II) containing solution with Fisher Creek stream sediment under non-oxidizing conditions. Results of these studies are consistent with a model in which Cu, Fe(II), and to a lesser extent Zn, are adsorbed or co-precipitated with hydrous Fe and Al oxides as the pH of Fisher Creek increases from 5.3 to 7.0. The extent of metal attenuation is strongly temperature-dependent, being more pronounced in warm vs. cold water. Furthermore, the sorption/co-precipitation process is shown to be irreversible; once the Cu, Zn, and Fe(II) are removed from solution in warm water, a decrease in temperature does not release the metals back to the water column. ?? 2006 Springer Science+Business Media B.V.

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

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

2016-09-15

Mobile and persistent organic micropollutants may impact raw and drinking waters and are thus of concern for human health. To identify such possible substances of concern nineteen water samples from five European countries (France, Switzerland, The Netherlands, Spain and Germany) and different compartments of the water cycle (urban effluent, surface water, ground water and drinking water) were enriched with mixed-mode solid phase extraction. Hydrophilic interaction liquid chromatography - high resolution mass spectrometry non-target screening of these samples led to the detection and structural elucidation of seven novel organic micropollutants. One structure could already be confirmed by a reference standard (trifluoromethanesulfonic acid) and six were tentatively identified based on experimental evidence (chloromethanesulfonic acid, dichloromethanesulfonic acid, trichloromethanesulfonic acid, bromomethanesulfonic acid, dibromomethanesulfonic acid and bromochloromethanesulfonic acid). Approximated concentrations for these substances show that trifluoromethanesulfonic acid, a chemical registered under the European Union regulation REACH with a production volume of more than 100 t/a, is able to spread along the water cycle and may be present in concentrations up to the μg/L range. Chlorinated and brominated methanesulfonic acids were predominantly detected together which indicates a common source and first experimental evidence points towards water disinfection as a potential origin. Halogenated methanesulfonic acids were detected in drinking waters and thus may be new substances of concern. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inorganic contaminants attenuation in acid mine drainage by fly ash and fly ash-ordinary Portland cement (OPC) blends : column experiments

International Nuclear Information System (INIS)

Gitari, W.M.; Petrik, L.F.; Etchebers, O.; Key, D.L.; Okujeni, C.

2010-01-01

The infiltration of acid mine drainage (AMD) material into mine voids is one of the environmental impacts of underground coal mining. In this study, the mitigation of AMD in a mine void was simulated in laboratory conditions. Various mixtures of fly ash, solid residues, and Portland cement were added to packed columns over a 6-month period. The fly ash additions generated near-neutral to alkaline pH levels, which in turn induced precipitation, co-precipitation, and adsorption contaminant attenuation mechanisms. A modelling study demonstrated that the precipitation of ferrihydrite, Al-hydroxides, Al-oxyhydroxysulphates, gypsum, ettringite, manganite, and rhodochrosite lowered contaminant levels. Results of the study indicated that the pH regime and acidity level of the AMD strongly influenced both the leaching of the toxic trace elements as well as the attenuation of the AMD. 3 refs., 2 figs.

NAC-NOR mutations in tomato Penjar accessions attenuate multiple metabolic processes and prolong the fruit shelf life.

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Kumar, Rakesh; Tamboli, Vajir; Sharma, Rameshwar; Sreelakshmi, Yellamaraju

2018-09-01

Several Penjar accessions of tomato grown in the Mediterranean exhibit prolonged shelf life and harbor alcobaca mutation. To uncover the metabolic basis underlying shelf life, we compared four Penjar accessions to Ailsa Craig. Three accessions bore alcobaca mutation, whereas the fourth was a novel NAC-NOR allele. Cuticle composition of Penjars varied widely during fruit ripening. All Penjars exhibited delayed ripening, prolonged on-vine and off-vine shelf life, low ethylene emission, and carotenoid levels. Metabolic profiling revealed shifts in Krebs cycle intermediates, amino acids, and γ-aminobutyric acid levels indicating the attenuation of respiration in Penjars during post-harvest storage. Penjar fruits also showed concerted downregulation of several cell-wall modifying genes and related metabolites. The high ABA and sucrose levels at the onset of senescence in Penjar fruits likely contribute to reduced water loss. Our analyses reveal that the attenuation of various metabolic processes by NAC-NOR mutation likely prolongs the shelf life of Penjar fruits. Copyright © 2018 Elsevier Ltd. All rights reserved.

Wild type measles virus attenuation independent of type I IFN

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Horvat Branka

2008-02-01

Full Text Available Abstract Background Measles virus attenuation has been historically performed by adaptation to cell culture. The current dogma is that attenuated virus strains induce more type I IFN and are more resistant to IFN-induced protection than wild type (wt. Results The adaptation of a measles virus isolate (G954-PBL by 13 passages in Vero cells induced a strong attenuation of this strain in vivo. The adapted virus (G954-V13 differs from its parental strain by only 5 amino acids (4 in P/V/C and 1 in the M gene. While a vaccine strain, Edmonston Zagreb, could replicate equally well in various primate cells, both G954 strains exhibited restriction to the specific cell type used initially for their propagation. Surprisingly, we observed that both G954 strains induced type I IFN, the wt strain inducing even more than the attenuated ones, particularly in human plasmacytoid Dendritic Cells. Type I IFN-induced protection from the infection of both G954 strains depended on the cell type analyzed, being less efficient in the cells used to grow the viral strain. Conclusion Thus, mutations in M and P/V/C proteins can critically affect MV pathogenicity, cellular tropism and lead to virus attenuation without interfering with the α/β IFN system.

Changes in sodium and uric acid concentrations in plasma during the menstrual cycle.

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Mira, M; Stewart, P M; Gebski, V; Llewellyn-Jones, D; Abraham, S F

1984-03-01

Hormonal changes during the menstrual cycle are well documented, but many other biochemical variables have not been studied. We find that in the luteal phase of the menstrual cycle the concentrations of sodium and uric acid are significantly lower. The changes may be of significance for the determination of the normal reference interval.

Gallic Acid Protects 6-OHDA Induced Neurotoxicity by Attenuating Oxidative Stress in Human Dopaminergic Cell Line.

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Chandrasekhar, Y; Phani Kumar, G; Ramya, E M; Anilakumar, K R

2018-04-18

Gallic acid is one of the most important polyphenolic compounds, which is considered an excellent free radical scavenger. 6-Hydroxydopamine (6-OHDA) is a neurotoxin, which has been implicated in mainly Parkinson's disease (PD). In this study, we investigated the molecular mechanism of the neuroprotective effects of gallic acid on 6-OHDA induced apoptosis in human dopaminergic cells, SH-SY5Y. Our results showed that 6-OHDA induced cytotoxicity in SH-SY5Y cells was suppressed by pre-treatment with gallic acid. The percentage of live cells (90%) was high in the pre-treatment of gallic acid when compared with 6-OHDA alone treated cell line. Moreover, gallic acid was very effective in attenuating the disruption of mitochondrial membrane potential, elevated levels of intracellular ROS and apoptotic cell death induced by 6-OHDA. Gallic acid also lowered the ratio of the pro-apoptotic Bax protein and the anti-apoptotic Bcl-2 protein in SH-SY5Y cells. 6-OHDA exposure was up-regulated caspase-3 and Keap-1 and, down-regulated Nrf2, BDNF and p-CREB, which were sufficiently reverted by gallic acid pre-treatment. These findings indicate that gallic acid is able to protect the neuronal cells against 6-OHDA induced injury and proved that gallic acid might potentially serve as an agent for prevention of several human neurodegenerative diseases caused by oxidative stress and apoptosis.

Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats.

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Panchal, Sunil K; Ward, Leigh; Brown, Lindsay

2013-03-01

Fruits and nuts may prevent or reverse common human health conditions such as obesity, diabetes and hypertension; together, these conditions are referred to as metabolic syndrome, an increasing problem. This study has investigated the responses to ellagic acid, present in many fruits and nuts, in a diet-induced rat model of metabolic syndrome. Eight- to nine-week-old male Wistar rats were divided into four groups for 16-week feeding with cornstarch diet (C), cornstarch diet supplemented with ellagic acid (CE), high-carbohydrate, high-fat diet (H) and high-carbohydrate, high-fat diet supplemented with ellagic acid (HE). CE and HE rats were given 0.8 g/kg ellagic acid in food from week 8 to 16 only. At the end of 16 weeks, cardiovascular, hepatic and metabolic parameters along with protein levels of Nrf2, NF-κB and CPT1 in the heart and the liver were characterised. High-carbohydrate, high-fat diet-fed rats developed cardiovascular remodelling, impaired ventricular function, impaired glucose tolerance, non-alcoholic fatty liver disease with increased protein levels of NF-κB and decreased protein levels of Nrf2 and CPT1 in the heart and the liver. Ellagic acid attenuated these diet-induced symptoms of metabolic syndrome with normalisation of protein levels of Nrf2, NF-κB and CPT1. Ellagic acid derived from nuts and fruits such as raspberries and pomegranates may provide a useful dietary supplement to decrease the characteristic changes in metabolism and in cardiac and hepatic structure and function induced by a high-carbohydrate, high-fat diet by suppressing oxidative stress and inflammation.

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

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

2004-04-01

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

Spheroid cancer stem cells display reprogrammed metabolism and obtain energy by actively running the tricarboxylic acid (TCA) cycle.

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Sato, Masakazu; Kawana, Kei; Adachi, Katsuyuki; Fujimoto, Asaha; Yoshida, Mitsuyo; Nakamura, Hiroe; Nishida, Haruka; Inoue, Tomoko; Taguchi, Ayumi; Takahashi, Juri; Eguchi, Satoko; Yamashita, Aki; Tomio, Kensuke; Wada-Hiraike, Osamu; Oda, Katsutoshi; Nagamatsu, Takeshi; Osuga, Yutaka; Fujii, Tomoyuki

2016-05-31

The Warburg effect is a metabolic hallmark of cancer cells; cancer cells, unlike normal cells, exclusively activate glycolysis, even in the presence of enough oxygen. On the other hand, intratumoral heterogeneity is currently of interest in cancer research, including that involving cancer stem cells (CSCs). In the present study, we attempted to gain an understanding of metabolism in CSCs that is distinct from that in non-CSCs. After forming spheroids from the OVTOKO (ovarian clear cell adenocarcinoma) and SiHa (cervical squamous cell carcinoma) cell lines, the metabolites of these cells were compared with the metabolites of cancer cells that were cultured in adherent plates. A principle components analysis clearly divided their metabolic features. Amino acids that participate in tricarboxylic acid (TCA) cycle reactions, such as serine and glutamine, were significantly increased in the spheroids. Indeed, spheroids from each cell line contained more total adenylates than did their corresponding cells in adherent cultures. This study demonstrated that cancer metabolism is not limited to aerobic glycolysis (i.e. the Warburg effect), but is flexible and context-dependent. In addition, activation of TCA cycles was suggested to be a metabolic feature of CSCs that was distinct from non-CSCs. The amino acid metabolic pathways discussed here are already considered as targets for cancer therapy, and they are additionally proposed as potential targets for CSC treatment.

PPARα inhibition modulates multiple reprogrammed metabolic pathways in kidney cancer and attenuates tumor growth.

Science.gov (United States)

Abu Aboud, Omran; Donohoe, Dallas; Bultman, Scott; Fitch, Mark; Riiff, Tim; Hellerstein, Marc; Weiss, Robert H

2015-06-01

Kidney cancer [renal cell carcinoma (RCC)] is the sixth-most-common cancer in the United States, and its incidence is increasing. The current progression-free survival for patients with advanced RCC rarely extends beyond 1-2 yr due to the development of therapeutic resistance. We previously identified peroxisome proliferator-activating receptor-α (PPARα) as a potential therapeutic target for this disease and showed that a specific PPARα antagonist, GW6471, induced apoptosis and cell cycle arrest at G0/G1 in RCC cell lines associated with attenuation of cell cycle regulatory proteins. We now extend that work and show that PPARα inhibition attenuates components of RCC metabolic reprogramming, capitalizing on the Warburg effect. The specific PPARα inhibitor GW6471, as well as a siRNA specific to PPARα, attenuates the enhanced fatty acid oxidation and oxidative phosphorylation associated with glycolysis inhibition, and PPARα antagonism also blocks the enhanced glycolysis that has been observed in RCC cells; this effect did not occur in normal human kidney epithelial cells. Such cell type-specific inhibition of glycolysis corresponds with changes in protein levels of the oncogene c-Myc and has promising clinical implications. Furthermore, we show that treatment with GW6471 results in RCC tumor growth attenuation in a xenograft mouse model, with minimal obvious toxicity, a finding associated with the expected on-target effects on c-Myc. These studies demonstrate that several pivotal cancer-relevant metabolic pathways are inhibited by PPARα antagonism. Our data support the concept that targeting PPARα, with or without concurrent inhibition of glycolysis, is a potential novel and effective therapeutic approach for RCC that targets metabolic reprogramming in this tumor.

IDH1 deficiency attenuates gluconeogenesis in mouse liver by impairing amino acid utilization.

Science.gov (United States)

Ye, Jing; Gu, Yu; Zhang, Feng; Zhao, Yuanlin; Yuan, Yuan; Hao, Zhenyue; Sheng, Yi; Li, Wanda Y; Wakeham, Andrew; Cairns, Rob A; Mak, Tak W

2017-01-10

Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or adipose tissue by generating NADPH, but we show here that lipid contents are relatively unchanged in both IDH1-null mouse liver and IDH1-deficient HepG2 cells generated using the CRISPR-Cas9 system. Instead, we found that IDH1 is critical for liver amino acid (AA) utilization. Body weights of IDH1-null mice fed a high-protein diet (HPD) were abnormally low. After prolonged fasting, IDH1-null mice exhibited decreased blood glucose but elevated blood alanine and glycine compared with wild-type (WT) controls. Similarly, in IDH1-deficient HepG2 cells, glucose consumption was increased, but alanine utilization and levels of intracellular α-KG and glutamate were reduced. In IDH1-deficient primary hepatocytes, gluconeogenesis as well as production of ammonia and urea were decreased. In IDH1-deficient whole livers, expression levels of genes involved in AA metabolism were reduced, whereas those involved in gluconeogenesis were up-regulated. Thus, IDH1 is critical for AA utilization in vivo and its deficiency attenuates gluconeogenesis primarily by impairing α-KG-dependent transamination of glucogenic AAs such as alanine.

Comparison of Monte Carlo simulation of gamma ray attenuation coefficients of amino acids with XCOM program and experimental data

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Elbashir, B. O.; Dong, M. G.; Sayyed, M. I.; Issa, Shams A. M.; Matori, K. A.; Zaid, M. H. M.

2018-06-01

The mass attenuation coefficients (μ/ρ), effective atomic numbers (Zeff) and electron densities (Ne) of some amino acids obtained experimentally by the other researchers have been calculated using MCNP5 simulations in the energy range 0.122-1.330 MeV. The simulated values of μ/ρ, Zeff, and Ne were compared with the previous experimental work for the amino acids samples and a good agreement was noticed. Moreover, the values of mean free path (MFP) for the samples were calculated using MCNP5 program and compared with the theoretical results obtained by XCOM. The investigation of μ/ρ, Zeff, Ne and MFP values of amino acids using MCNP5 simulations at various photon energies when compared with the XCOM values and previous experimental data for the amino acids samples revealed that MCNP5 code provides accurate photon interaction parameters for amino acids.

Administration of Tauroursodeoxycholic Acid Attenuates Early Brain Injury via Akt Pathway Activation

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Dongdong Sun

2017-07-01

Full Text Available Traumatic brain injury (TBI is one of the leading causes of trauma-induced mortality and disability, and emerging studies have shown that endoplasmic reticulum (ER stress plays an important role in the pathophysiology of TBI. Tauroursodeoxycholic acid (TUDCA, a hydrophilic bile acid, has been reported to act as an ER stress inhibitor and chemical chaperone and to have the potential to attenuate apoptosis and inflammation. To study the effects of TUDCA on brain injury, we subjected mice to TBI with a controlled cortical impact (CCI device. Using western blotting, we first examined TBI-induced changes in the expression levels of GRP78, an ER stress marker, p-PERK, PERK, p-eIF2a, eIF2a, ATF4, p-Akt, Akt, Pten, Bax, Bcl-2, Caspase-12 and CHOP, as well as changes in the mRNA levels of Akt, GRP78, Caspase-12 and CHOP using RT-PCR. Neuronal cell death was assessed by a terminal deoxynucleotidyl transferase (TdT-mediated dUTP nick end-labeling (TUNEL assay, and CHOP expression in neuronal cells was detected by double-immunofluorescence staining. Neurological and motor deficits were assessed by modified neurological severity scores (mNSS and beam balance and beam walking tests, and brain water content was also assessed. Our results indicated that ER stress peaked at 72 h after TBI and that TUDCA abolished ER stress and inhibited p-PERK, p-eIF2a, ATF4, Pten, Caspase-12 and CHOP expression levels. Moreover, our results show that TUDCA also improved neurological function and alleviated brain oedema. Additionally, TUDCA increased p-Akt expression and the Bcl-2/Bax ratio. However, the administration of the Akt inhibitor MK2206 or siRNA targeting of Akt abolished the beneficial effects of TUDCA. Taken together, our results indicate that TUDCA may attenuate early brain injury via Akt pathway activation.

Frequency-dependent squeeze-amplitude attenuation and squeeze-angle rotation by electromagnetically induced transparency for gravitational-wave interferometers

International Nuclear Information System (INIS)

Mikhailov, Eugeniy E.; Goda, Keisuke; Corbitt, Thomas; Mavalvala, Nergis

2006-01-01

We study the effects of frequency-dependent squeeze-amplitude attenuation and squeeze-angle rotation by electromagnetically induced transparency (EIT) on gravitational-wave (GW) interferometers. We propose the use of low-pass, bandpass, and high-pass EIT filters, an S-shaped EIT filter, and an intracavity EIT filter to generate frequency-dependent squeezing for injection into the antisymmetric port of GW interferometers. We find that the EIT filters have several advantages over the previous filter designs with regard to optical losses, compactness, and the tunability of the filter linewidth

Novel Intriguing Strategies Attenuating to Sarcopenia

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Kunihiro Sakuma

2012-01-01

Full Text Available Sarcopenia, the age-related loss of skeletal muscle mass, is characterized by a deterioration of muscle quantity and quality leading to a gradual slowing of movement, a decline in strength and power, increased risk of fall-related injury, and, often, frailty. Since sarcopenia is largely attributed to various molecular mediators affecting fiber size, mitochondrial homeostasis, and apoptosis, the mechanisms responsible for these deleterious changes present numerous therapeutic targets for drug discovery. Resistance training combined with amino acid-containing supplements is often utilized to prevent age-related muscle wasting and weakness. In this review, we summarize more recent therapeutic strategies (myostatin or proteasome inhibition, supplementation with eicosapentaenoic acid (EPA or ursolic acid, etc. for counteracting sarcopenia. Myostatin inhibitor is the most advanced research with a Phase I/II trial in muscular dystrophy but does not try the possibility for attenuating sarcopenia. EPA and ursolic acid seem to be effective as therapeutic agents, because they attenuate the degenerative symptoms of muscular dystrophy and cachexic muscle. The activation of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α in skeletal muscle by exercise and/or unknown supplementation would be an intriguing approach to attenuating sarcopenia. In contrast, muscle loss with age may not be influenced positively by treatment with a proteasome inhibitor or antioxidant.

Attenuation of Vrancea events revisited

International Nuclear Information System (INIS)

Radulian, M.; Popa, M.; Grecu, B.; Panza, G.F.

2003-11-01

New aspects of the frequency-dependent attenuation of the seismic waves traveling from Vrancea subcrustal sources toward NW (Transylvanian Basin) and SE (Romanian Plain) are evidenced by the recent experimental data made available by the CALIXTO'99 tomography experiment. The observations validate the previous theoretical computations performed for the assessment, by means of a deterministic approach, of the seismic hazard in Romania. They reveal an essential aspect of the seismic ground motion attenuation, that has important implications on the probabilistic assessment of seismic hazard from Vrancea intermediate-depth earthquakes. The attenuation toward NW is shown to be a much stronger frequency-dependent effect than the attenuation toward SE and the seismic hazard computed by the deterministic approach fits satisfactorily well the observed ground motion distribution in the low-frequency band (< 1 Hz). The apparent contradiction with the historically-based intensity maps arises mainly from a systematic difference in the vulnerability (buildings eigenperiod) of the buildings in the intra- and extra-Carpathians regions. (author)

When and Why Mimicry is Facilitated and Attenuated

NARCIS (Netherlands)

Stel, Mariëlle; van Dijk, Eric; van Baaren, Rick B.

2016-01-01

Although people tend to mimic others automatically, mimicry is facilitated or attenuated depending on the specific context. In the current paper, the authors discuss when mimicry is facilitated and attenuated depending on characteristics of situations, targets, and observers. On the basis of the

Isthmus Dependent Atrial Flutter Cycle Length Correlates with Right Atrial Cross-Sectional Area

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Kousik Krishnan

2009-05-01

Full Text Available Background: Right atrial flutter cycle length can prolong in the presence of antiarrhythmic drug therapy. We hypothesized that the cycle length of right atrial isthmus dependent flutter would correlate with right atrial cross-sectional area measurements. Methods: 60 patients who underwent ablation for electrophysiologically proven isthmus dependent right atrial flutter, who were not on Class I or Class III antiarrhythmic drugs and had recent 2-dimensional echocardiographic data comprised the study group. Right atrial length and width were measured in the apical four chamber view. Cross-sectional area was estimated by multiplying the length and width. 35 patients had an atrial flutter rate ≥250 bpm (Normal Flutter Group and 25 patients had an atrial flutter rate < 250 bpm (Slow Flutter Group. Results: Mean atrial flutter rate was 283 bpm in the normal flutter group and 227 bpm in the slow flutter group. Mean atrial flutter cycle length was 213 ms in the Normal Flutter Group and 265 ms in the Slow Flutter Group (p<0.0001. Mean right atrial cross sectional area was 1845 mm2 in the Normal Flutter group and 2378 mm2 in the Slow Flutter Group, (p< 0.0001. Using linear regression, CSA was a significant predictor of cycle length (β =0.014 p = 0.0045. For every 1 mm2 increase in cross-sectional area, cycle length is 0.014 ms longer.Conclusion: In the absence of antiarrhythmic medications, right atrial cross sectional area enlargement correlates with atrial flutter cycle length. These findings provide further evidence that historical rate-related definitions of typical isthmus dependent right atrial are not mechanistically valid.

Alteration of tricarboxylic acid cycle metabolism in rat brain slices by halothane

International Nuclear Information System (INIS)

Cheng, S.C.; Brunner, E.A.

1978-01-01

Metabolism of [2- 14 C] pyruvate, [1- 14 C] acetate and [5- 14 C] citrate in rat cerebral cortex slices was studied in the presence of halothane. Metabolites assayed include acetylcholine (ACh), citrate, glutamate, glutamineγ-aminobutyrate (GABA) and aspartate. The trichloroacetic acid soluble extract, the trichloracetic acid insoluble precipitate and its lipid extract were also studied. In control experiments, pyruvate preferentially labelled ACh, citrate, glutamate, GABA and aspartate. Acetate labelled ACh, but to a lesser extent than pyruvate. Acetate also labelled lipids and glutamine. Citrate labelled lipids but not ACh and served as a preferential precursor for glutamine. These data support a three-compartment model for cerebral tricarboxylic acid cycle metabolism. Halothane caused increases in GABA and aspartate contents and a decrease in ACh content. It has no effect on the contents of citrate, glutamate and glutamine. Halothane preferentially inhibited the metabolic transfer of radioactivity from pyruvate into almost all metabolites, an effect probably not related to pyruvate permeability. This is interpreted as halothane depression of the large metabolic compartment which includes the nerve endings. Halothane increased the metabolic transfer of radioactivity from acetate into lipids but did not alter such a transfer into the trichloroacetic acid extract. Halothane increased the metabolic transfer of radioactivity from citrate into the trichloroacetic acid precipitate, lipids and especially glutamine. Transfer of citrate radioactivity into GABA was somewhat decreased. The differential effects of halothane on acetate and citrate utilization suggest that the small metabolic compartment should be subdivided. Therefore, at least three metabolic compartments are demonstrated. Halothane did not interfere with the dicarboxylic acid portion of the tricarboxylic acid cycle. (author)

Effects of hyaluronic acid- chitosan-gelatin complex on the apoptosis and cell cycle of L929 cells

Institute of Scientific and Technical Information of China (English)

MAO Jinshu; WANG Xianghui; CUI Yuanlu; YAO Kangde

2003-01-01

With the development in the field of tissue engineering, the interaction between biomaterials and cells has been deeply studied. Viewing the cells seeded on the surface of materials as an organic whole, cell cycle and apoptosis are analyzed to deepen the study of cell compatibility on biomaterials, while cellproliferation and differentiation are studied at the same time. In this paper, hyaluronic acid is incorporated into the chitosan-gelatin system. Propidium iodide (PI) was used in cell cycle analysis and the double-staining of cells with annexin-V and PI was applied in cell apoptosis analysis. The results show that incorporated hyaluronic acid shortens the adaptation period of cells on the material surface, and then cells enter the normal cell cycle quickly. In addition, added hyaluronic acid inhibits cell apoptosis triggered by the membranes. Therefore,hyaluronic acid improves the cell compatibility of chitosan-gelatin system and benefits the design of biomimetic materials.

Eutectic mixtures of some fatty acids for latent heat storage: Thermal properties and thermal reliability with respect to thermal cycling

International Nuclear Information System (INIS)

Sari, Ahmet

2006-01-01

Accelerated thermal cycle tests have been conducted to study the change in melting temperatures and latent heats of fusion of the eutectic mixtures of lauric acid (LA)-myristic acid (MA), lauric acid (LA)-palmitic acid (PA) and myristic acid (MA)-stearic acid (SA) as latent heat storage materials. The thermal properties of these materials were determined by the differential scanning calorimetry (DSC) analysis method. The thermal reliability of the eutectic mixtures after melt/freeze cycles of 720, 1080 and 1460 was also evaluated using the DSC curves. The accelerated thermal cycle tests indicate that the melting temperatures usually tend to decrease, and the variations in the latent heats of fusion are irregular with increasing number of thermal cycles. Moreover, the probable reasons for the change in thermal properties of the eutectic mixtures after repeated thermal cycles were investigated. Fourier Transform Infrared (FT-IR) spectroscopic analysis indicates that the accelerated melt/freeze processes do not cause any degradation in the chemical structure of the mixtures. The change in thermal properties of the eutectic mixtures with increasing number of thermal cycles is only because of the presence of certain amounts of impurities in the fatty acids used in their preparation. It is concluded that the tested eutectic mixtures have reasonable thermal properties and thermal reliability as phase change materials (PCMs) for latent heat storage in any solar heating applications that include a four year utilization period

Business Cycle Dependent Unemployment Benefits with Wealth Heterogeneity and Precautionary Savings

DEFF Research Database (Denmark)

Kristoffersen, Mark Strøm

In the wake of the financial and economic crisis the discussion about social insurance and optimal stabilization policies has re-blossomed. This paper adds to the literature by studying the effects of a business cycle dependent level of unemployment benefits in a model with labor market matching......, wealth heterogeneity, precautionary savings, and aggregate fluctuations in productivity. The results are ambiguous: both procyclical and countercyclical unemployment benefits can increase welfare relative to business cycle invariant benefits. Procyclical benefits are beneficial due to countercyclicality...

Withania somnifera attenuates acid production, acid tolerance and extra-cellular polysaccharide formation of Streptococcus mutans biofilms.

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Pandit, Santosh; Song, Kwang-Yeob; Jeon, Jae-Gyu

2014-01-01

Withania somnifera (Ashwagandha) is a plant of the Solanaceae family. It has been widely used as a remedy for a variety of ailments in India and Nepal. The plant has also been used as a controlling agent for dental diseases. The aim of the present study was to evaluate the activity of the methanol extract of W. somnifera against the physiological ability of cariogenic biofilms and to identify the components of the extract. To determine the activity of the extract, assays for sucrose-dependent bacterial adherence, glycolytic acid production, acid tolerance, and extracellular polysaccharide formation were performed using Streptococcus mutans biofilms. The viability change of S. mutans biofilms cells was also determined. A phytochemical analysis of the extract was performed using TLC and LC/MS/MS. The extract showed inhibitory effects on sucrose-dependent bacterial adherence (≥ 100 μg/ml), glycolytic acid production (≥ 300 μg/ml), acid tolerance (≥ 300 μg/ml), and extracellular polysaccharide formation (≥ 300 μg/ml) of S. mutans biofilms. However, the extract did not alter the viability of S. mutans biofilms cells in all concentrations tested. Based on the phytochemical analysis, the activity of the extract may be related to the presence of alkaloids, anthrones, coumarines, anthraquinones, terpenoids, flavonoids, and steroid lactones (withanolide A, withaferin A, withanolide B, withanoside IV, and 12-deoxy withastramonolide). These data indicate that W. somnifera may be a potential agent for restraining the physiological ability of cariogenic biofilms.

Low dose of L-glutamic acid attenuated the neurological dysfunctions and excitotoxicity in bilateral common carotid artery occluded mice.

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Ramanathan, Muthiah; Abdul, Khadar K; Justin, Antony

2016-10-01

Glutamate, an excitatory neurotransmitter in the brain, produces excitotoxicity through its agonistic action on postsynaptic N-methyl-D-aspartate receptor, resulting in neurodegeneration. We hypothesized that the administration of low doses of glutamate in cerebral ischemia could attenuate the excitotoxicity in neurons through its autoreceptor regulatory mechanism, and thereby control neurodegeneration. To test the hypothesis, the effect of L-glutamic acid (L-GA) 400 μmol/l/kg was evaluated in a bilateral common carotid artery occlusion-induced global ischemic mouse model. Memantine was used as a positive control. Global ischemia in mice was induced by occlusion of both the common carotid artery (bilateral common carotid artery occlusion) for 20 min, followed by reperfusion injury. L-GA was infused slowly through the tail vein 30 min before the surgery and every 24 h thereafter until the end of the experiment. The time-dependent change in cerebral blood flow was monitored using a laser Doppler image analyzer. The neurotransmitters glutamate and γ-aminobutyric acid (GABA) and the neurobiochemicals ATP, glutathione, and nitric oxide were measured in the different regions of brain at 0, 24, 48, and 72 h after reperfusion injury. L-GA increased locomotor activity, muscle coordination, and cerebral blood flow in ischemic mice at 72 h after ischemic insult. L-GA reduced glutamate levels in the cortex, striatum, and hippocampus at 72 h, whereas GABA levels were elevated in all three brain regions studied. Further, L-GA elevated glutathione levels and attenuated nitric oxide levels, but failed to restore ATP levels 72 h after ischemia-reperfusion. We conclude that the gradual reduction of glutamate along with elevation of GABA in different brain regions could have contributed toward the neuroprotective effect of L-GA. Hence, a slow infusion of a low dose of L-GA could be beneficial in controlling excitotoxicity-induced neurodegeneration following ischemia.

Attenuation of abnormalities in the lipid metabolism during experimental myocardial infarction induced by isoproterenol in rats: beneficial effect of ferulic acid and ascorbic acid.

Science.gov (United States)

Yogeeta, Surinder Kumar; Hanumantra, Rao Balaji Raghavendran; Gnanapragasam, Arunachalam; Senthilkumar, Subramanian; Subhashini, Rajakannu; Devaki, Thiruvengadam

2006-05-01

The present study aims at evaluating the effect of the combination of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism. The rats were divided into eight groups: Control, isoproterenol, ferulic acid alone, ascorbic acid alone, ferulic acid+ascorbic acid, ferulic acid+isoproterenol, ascorbic acid+isoproterenol and ferulic acid+ascorbic acid+isoproterenol. Ferulic acid (20 mg/kg b.w.t.) and ascorbic acid (80 mg/kg b.w.t.) both alone and in combination was administered orally for 6 days and on the fifth and the sixth day, isoproterenol (150 mg/kg b.w.t.) was injected intraperitoneally to induce myocardial injury to rats. Induction of rats with isoproterenol resulted in a significant increase in the levels of triglycerides, total cholesterol, free fatty acids, free and ester cholesterol in both serum and cardiac tissue. A rise in the levels of phospholipids, lipid peroxides, low density lipoprotein and very low density lipoprotein-cholesterol was also observed in the serum of isoproterenol-intoxicated rats. Further, a decrease in the level of high density lipoprotein in serum and in the phospholipid levels, in the heart of isoproterenol-intoxicated rats was observed, which was paralleled by abnormal activities of lipid metabolizing enzymes: total lipase, cholesterol ester synthase, lipoprotein lipase and lecithin: cholesterol acyl transferase. Pre-cotreatment with the combination of ferulic acid and ascorbic acid significantly attenuated these alterations and restored the levels to near normal when compared to individual treatment groups. Histopathological observations were also in correlation with the biochemical parameters. These findings indicate the synergistic protective effect of ferulic acid and ascorbic acid on isoproterenol-induced abnormalities in lipid metabolism.

Metabolic Effects of Cholecystectomy: Gallbladder Ablation Increases Basal Metabolic Rate through G-Protein Coupled Bile Acid Receptor Gpbar1-Dependent Mechanisms in Mice

Science.gov (United States)

Cortés, Víctor; Amigo, Ludwig; Zanlungo, Silvana; Galgani, José; Robledo, Fermín; Arrese, Marco; Bozinovic, Francisco; Nervi, Flavio

2015-01-01

Background & Aims Bile acids (BAs) regulate energy expenditure by activating G-protein Coupled Bile Acid Receptor Gpbar1/TGR5 by cAMP-dependent mechanisms. Cholecystectomy (XGB) increases BAs recirculation rates resulting in increased tissue exposure to BAs during the light phase of the diurnal cycle in mice. We aimed to determine: 1) the effects of XGB on basal metabolic rate (BMR) and 2) the roles of TGR5 on XGB-dependent changes in BMR. Methods BMR was determined by indirect calorimetry in wild type and Tgr5 deficient (Tgr5-/-) male mice. Bile flow and BAs secretion rates were measured by surgical diversion of biliary duct. Biliary BAs and cholesterol were quantified by enzymatic methods. BAs serum concentration and specific composition was determined by liquid chromatography/tandem mass spectrometry. Gene expression was determined by qPCR analysis. Results XGB increased biliary BAs and cholesterol secretion rates, and elevated serum BAs concentration in wild type and Tgr5-/- mice during the light phase of the diurnal cycle. BMR was ~25% higher in cholecystectomized wild type mice (p <0.02), whereas no changes were detected in cholecystectomized Tgr5-/- mice compared to wild-type animals. Conclusion XGB increases BMR by TGR5-dependent mechanisms in mice. PMID:25738495

Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.

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Martina Reske

Full Text Available Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate, which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.158 occasional stimulants users (OSU and 50 comparison subjects (CS performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions". The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42, or <50 lifetime marijuana uses (n = 32, were compared to CS with <50 lifetime uses (n = 46 to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring

Arginine-dependent acid resistance in Salmonella enterica serovar Typhimurium

NARCIS (Netherlands)

Kieboom, J.; Abee, T.

2006-01-01

Salmonella enterica serovar Typhimurium does not survive a pH 2.5 acid challenge under conditions similar to those used for Escherichia coli (J. W. Foster, Nat. Rev. Microbiol. 2:898-907, 2004). Here, we provide evidence that S. enterica serovar Typhimurium can display arginine-dependent acid

Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice.

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Kia J Jackson

Full Text Available The influx of Ca(2+ through calcium-permeable nicotinic acetylcholine receptors (nAChRs leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB, which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/- mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

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

Science.gov (United States)

Weber, Jean-Michel; Reidy, Shannon P

2012-05-01

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

Proteasome-mediated degradation of cell division cycle 25C and cyclin-dependent kinase 1 in phenethyl isothiocyanate-induced G2-M-phase cell cycle arrest in PC-3 human prostate cancer cells.

Science.gov (United States)

Xiao, Dong; Johnson, Candace S; Trump, Donald L; Singh, Shivendra V

2004-05-01

Phenethyl isothiocyanate (PEITC), a constituent of many cruciferous vegetables, offers significant protection against cancer in animals induced by a variety of carcinogens. The present study demonstrates that PEITC suppresses proliferation of PC-3 cells in a dose-dependent manner by causing G(2)-M-phase cell cycle arrest and apoptosis. Interestingly, phenyl isothiocyanate (PITC), which is a structural analogue of PEITC but lacks the -CH(2) spacers that link the aromatic ring to the -N=C=S group, neither inhibited PC-3 cell viability nor caused cell cycle arrest or apoptosis. These results indicated that even a subtle change in isothiocyanate (ITC) structure could have a significant impact on its biological activity. The PEITC-induced cell cycle arrest was associated with a >80% reduction in the protein levels of cyclin-dependent kinase 1 (Cdk1) and cell division cycle 25C (Cdc25C; 24 h after treatment with 10 micro M PEITC), which led to an accumulation of Tyr(15) phosphorylated (inactive) Cdk1. On the other hand, PITC treatment neither reduced protein levels of Cdk1 or Cdc25C nor affected Cdk1 phosphorylation. The PEITC-induced decline in Cdk1 and Cdc25C protein levels and cell cycle arrest were significantly blocked on pretreatment of PC-3 cells with proteasome inhibitor lactacystin. A 24 h exposure of PC-3 cells to 10 micro M PEITC, but not PITC, resulted in about 56% and 44% decrease in the levels of antiapoptotic proteins Bcl-2 and Bcl-X(L), respectively. However, ectopic expression of Bcl-2 failed to alter sensitivity of PC-3 cells to growth inhibition or apoptosis induction by PEITC. Treatment of cells with PEITC, but not PITC, also resulted in cleavage of procaspase-3, procaspase-9, and procaspase-8. Moreover, the PEITC-induced apoptosis was significantly attenuated in the presence of general caspase inhibitor and specific inhibitors of caspase-8 and caspase-9. In conclusion, our data indicate that PEITC-induced cell cycle arrest in PC-3 cells is likely due

Extracellular matrix-dependent myosin dynamics during G1-S phase cell cycle progression in hepatocytes

International Nuclear Information System (INIS)

Bhadriraju, Kiran; Hansen, Linda K.

2004-01-01

Cell spreading and proliferation are tightly coupled in anchorage-dependent cells. While adhesion-dependent proliferation signals require an intact actin cytoskeleton, and some of these signals such as ERK activation have been characterized, the role of myosin in spreading and cell cycle progression under different extracellular matrix (ECM) conditions is not known. Studies presented here examine changes in myosin activity in freshly isolated hepatocytes under ECM conditions that promote either proliferation (high fibronectin density) or growth arrest (low fibronectin density). Three different measures were obtained and related to both spreading and cell cycle progression: myosin protein levels and association with cytoskeleton, myosin light chain phosphorylation, and its ATPase activity. During the first 48 h in culture, corresponding with transit through G1 phase, there was a six-fold increase in both myosin protein levels and myosin association with actin cytoskeleton. There was also a steady increase in myosin light chain phosphorylation and ATPase activity with spreading, which did not occur in non-spread, growth-arrested cells on low density of fibronectin. Myosin-inhibiting drugs blocked ERK activation, cyclin D1 expression, and S phase entry. Overexpression of the cell cycle protein cyclin D1 overcame both ECM-dependent and actomyosin-dependent inhibition of DNA synthesis, suggesting that cyclin D1 is a key event downstream of myosin-dependent cell cycle regulation

EGFR-dependent signalling reduced and p38 dependent apoptosis required by Gallic acid in Malignant Mesothelioma cells.

Science.gov (United States)

Demiroglu-Zergeroglu, Asuman; Candemir, Gulsife; Turhanlar, Ebru; Sagir, Fatma; Ayvali, Nurettin

2016-12-01

The unrestrained EGFR signalling contributes to malignant phenotype in a number of cancers including Malignant Mesotheliomas. Present study was designed to evaluate EGFR-dependent anti-proliferative and apoptotic effects of Gallic acid in transformed Mesothelial (MeT-5A) and Malignant Mesothelioma (SPC212) cells. Gallic acid reduced the viability of Malignant Mesothelioma cells in a concentration and time-dependent manner. However, viability of mesothelial cells reduced only at high concentration and longer time periods. Gallic acid restrained the activation of EGFR, ERK1/2 and AKT proteins and down regulated expression of Cyclin D and Bcl-2 genes, but upregulated the expression of p21 gene in EGF-induced SPC212 cells. GA-induced transitory G1 arrest and triggered mitochondrial and death receptor mediated apoptosis, which requires p38MAPK activation. The data provided here indicate that GA is able to inhibit EGFR dependent proliferation and survival signals and induces p38 pathway dependent apoptosis in Malignant Mesothelioma cells. On the basis of these experimental findings it is worthwhile to investigate further the biological activity of Gallic acid on other Mesothelioma cell lines harbouring aberrant EGFR signals. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Dependency of climate change and carbon cycle on CO2 emission pathways

International Nuclear Information System (INIS)

Nohara, Daisuke; Yoshida, Yoshikatsu; Misumi, Kazuhiro; Ohba, Masamichi

2013-01-01

Previous research has indicated that the response of globally average temperature is approximately proportional to cumulative CO 2 emissions, yet evidence of the robustness of this relationship over a range of CO 2 emission pathways is lacking. To address this, we evaluate the dependency of climate and carbon cycle change on CO 2 emission pathways using a fully coupled climate–carbon cycle model. We design five idealized pathways (including an overshoot scenario for cumulative emissions), each of which levels off to final cumulative emissions of 2000 GtC. The cumulative emissions of the overshoot scenario reach 4000 GtC temporarily, subsequently reducing to 2000 GtC as a result of continuous negative emissions. Although we find that responses of climatic variables and the carbon cycle are largely independent of emission pathways, a much weakened Atlantic meridional overturning circulation (AMOC) is projected in the overshoot scenario despite cessation of emissions. This weakened AMOC is enhanced by rapid warming in the Arctic region due to considerable temporary elevation of atmospheric CO 2 concentration and induces the decline of surface air temperature and decrease of precipitation over the northern Atlantic and Europe region. Moreover, the weakened AMOC reduces CO 2 uptake by the Atlantic and Arctic oceans. However, the weakened AMOC contributes little to the global carbon cycle. In conclusion, although climate variations have been found to be dependent on emission pathways, the global carbon cycle is relatively independent of these emission pathways, at least superficially. (letter)

Estrogen receptor alpha is cell cycle-regulated and regulates the cell cycle in a ligand-dependent fashion.

Science.gov (United States)

JavanMoghadam, Sonia; Weihua, Zhang; Hunt, Kelly K; Keyomarsi, Khandan

2016-06-17

Estrogen receptor alpha (ERα) has been implicated in several cell cycle regulatory events and is an important predictive marker of disease outcome in breast cancer patients. Here, we aimed to elucidate the mechanism through which ERα influences proliferation in breast cancer cells. Our results show that ERα protein is cell cycle-regulated in human breast cancer cells and that the presence of 17-β-estradiol (E2) in the culture medium shortened the cell cycle significantly (by 4.5 hours, P cycle duration were observed in the S and G2/M phases, whereas the G1 phase was indistinguishable under liganded and unliganded conditions. In addition, ERα knockdown in MCF-7 cells accelerated mitotic exit, whereas transfection of ERα-negative MDA-MB-231 cells with exogenous ERα significantly shortened the S and G2/M phases (by 9.1 hours, P cycle progression through the S and G2/M phases than fulvestrant does, presumably because of the destabilizing effect of fulvestrant on ERα protein. Together, these results show that ERα modulates breast cancer cell proliferation by regulating events during the S and G2/M phases of the cell cycle in a ligand-dependent fashion. These results provide the rationale for an effective treatment strategy that includes a cell cycle inhibitor in combination with a drug that lowers estrogen levels, such as an aromatase inhibitor, and an antiestrogen that does not result in the degradation of ERα, such as tamoxifen.

Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

Science.gov (United States)

Kaiser, Julienne C; King, Alyssa N; Grigg, Jason C; Sheldon, Jessica R; Edgell, David R; Murphy, Michael E P; Brinsmade, Shaun R; Heinrichs, David E

2018-01-01

Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

Repression of branched-chain amino acid synthesis in Staphylococcus aureus is mediated by isoleucine via CodY, and by a leucine-rich attenuator peptide.

Directory of Open Access Journals (Sweden)

Julienne C Kaiser

2018-01-01

Full Text Available Staphylococcus aureus requires branched-chain amino acids (BCAAs; isoleucine, leucine, valine for protein synthesis, branched-chain fatty acid synthesis, and environmental adaptation by responding to their availability via the global transcriptional regulator CodY. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Indeed S. aureus uses specialized transporters to scavenge BCAAs, however, its ability to synthesize them has remained conflicted by reports that it is auxotrophic for leucine and valine despite carrying an intact BCAA biosynthetic operon. In revisiting these findings, we have observed that S. aureus can engage in leucine and valine synthesis, but the level of BCAA synthesis is dependent on the BCAA it is deprived of, leading us to hypothesize that each BCAA differentially regulates the biosynthetic operon. Here we show that two mechanisms of transcriptional repression regulate the level of endogenous BCAA biosynthesis in response to specific BCAA availability. We identify a trans-acting mechanism involving isoleucine-dependent repression by the global transcriptional regulator CodY and a cis-acting leucine-responsive attenuator, uncovering how S. aureus regulates endogenous biosynthesis in response to exogenous BCAA availability. Moreover, given that isoleucine can dominate CodY-dependent regulation of BCAA biosynthesis, and that CodY is a global regulator of metabolism and virulence in S. aureus, we extend the importance of isoleucine availability for CodY-dependent regulation of other metabolic and virulence genes. These data resolve the previous conflicting observations regarding BCAA biosynthesis, and reveal the environmental signals that not only induce BCAA biosynthesis, but that could also have broader consequences on S. aureus environmental adaptation and virulence via CodY.

Down-regulation of tricarboxylic acid (TCA) cycle genes blocks progression through the first mitotic division in Caenorhabditis elegans embryos.

Science.gov (United States)

Rahman, Mohammad M; Rosu, Simona; Joseph-Strauss, Daphna; Cohen-Fix, Orna

2014-02-18

The cell cycle is a highly regulated process that enables the accurate transmission of chromosomes to daughter cells. Here we uncover a previously unknown link between the tricarboxylic acid (TCA) cycle and cell cycle progression in the Caenorhabditis elegans early embryo. We found that down-regulation of TCA cycle components, including citrate synthase, malate dehydrogenase, and aconitase, resulted in a one-cell stage arrest before entry into mitosis: pronuclear meeting occurred normally, but nuclear envelope breakdown, centrosome separation, and chromosome condensation did not take place. Mitotic entry is controlled by the cyclin B-cyclin-dependent kinase 1 (Cdk1) complex, and the inhibitory phosphorylation of Cdk1 must be removed in order for the complex to be active. We found that following down-regulation of the TCA cycle, cyclin B levels were normal but CDK-1 remained inhibitory-phosphorylated in one-cell stage-arrested embryos, indicative of a G2-like arrest. Moreover, this was not due to an indirect effect caused by checkpoint activation by DNA damage or replication defects. These observations suggest that CDK-1 activation in the C. elegans one-cell embryo is sensitive to the metabolic state of the cell, and that down-regulation of the TCA cycle prevents the removal of CDK-1 inhibitory phosphorylation. The TCA cycle was previously shown to be necessary for the development of the early embryo in mammals, but the molecular processes affected were not known. Our study demonstrates a link between the TCA cycle and a specific cell cycle transition in the one-cell stage embryo.

Endogenous n-3 polyunsaturated fatty acids attenuate T cell-mediated hepatitis via autophagy activation

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Yanli Li

2016-09-01

Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A was administered intravenously to wild-type (WT and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase (ALT activity, and inhibited production of pro-inflammatory cytokines (e.g. TNF-α, IL-6, IL-17A and IFN-γ. In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism, and could be exploited as a new therapeutic approach for autoimmune hepatitis.

Ascorbic acid attenuates endothelial permeability triggered by cell-free hemoglobin.

Science.gov (United States)

Kuck, Jamie L; Bastarache, Julie A; Shaver, Ciara M; Fessel, Joshua P; Dikalov, Sergey I; May, James M; Ware, Lorraine B

2018-01-01

Increased endothelial permeability is central to shock and organ dysfunction in sepsis but therapeutics targeted to known mediators of increased endothelial permeability have been unsuccessful in patient studies. We previously reported that cell-free hemoglobin (CFH) is elevated in the majority of patients with sepsis and is associated with organ dysfunction, poor clinical outcomes and elevated markers of oxidant injury. Others have shown that Vitamin C (ascorbate) may have endothelial protective effects in sepsis. In this study, we tested the hypothesis that high levels of CFH, as seen in the circulation of patients with sepsis, disrupt endothelial barrier integrity. Human umbilical vein endothelial cells (HUVEC) were grown to confluence and treated with CFH with or without ascorbate. Monolayer permeability was measured by Electric Cell-substrate Impedance Sensing (ECIS) or transfer of 14 C-inulin. Viability was measured by trypan blue exclusion. Intracellular ascorbate was measured by HPLC. CFH increased permeability in a dose- and time-dependent manner with 1 mg/ml of CFH increasing inulin transfer by 50% without affecting cell viability. CFH (1 mg/ml) also caused a dramatic reduction in intracellular ascorbate in the same time frame (1.4 mM without CFH, 0.23 mM 18 h after 1 mg/ml CFH, p < 0.05). Pre-treatment of HUVECs with ascorbate attenuated CFH induced permeability. CFH increases endothelial permeability in part through depletion of intracellular ascorbate. Supplementation of ascorbate can attenuate increases in permeability mediated by CFH suggesting a possible therapeutic approach in sepsis. Copyright © 2017 Elsevier Inc. All rights reserved.

Ketogenesis in isolated rat liver mitochondria I. Relationships with the citric acid cycle and with the mitochondrial energy state

NARCIS (Netherlands)

Lopes-Cardozo, M.; Bergh, S.G. van den

1972-01-01

1. A method is described to calculate the distribution of acetyl-CoA over the citric acid cycle and ketogenesis during the oxidation of fatty acids in the presence of added malate. 2. Increasing concentrations of added Krebs cycle intermediates lower the rate of ketogenesis both in the low-energy

Oxaloacetate-to-malate conversion by mineral photoelectrochemistry: implications for the viability of the reductive tricarboxylic acid cycle in prebiotic chemistry

Science.gov (United States)

Guzman, Marcelo I.; Martin, Scot T.

2008-10-01

The carboxylic acids produced by the reductive tricarboxylic acid (rTCA) cycle are possibly a biosynthetic core of initial life, although several steps such as the reductive kinetics of oxaloacetate (OAA) to malate (MA) are problematic by conventional chemical routes. In this context, we studied the kinetics of this reaction as promoted by ZnS mineral photoelectrochemistry. The quantum efficiency φMA of MA production from the photoelectrochemical reduction of OAA followed φMA=0.13 [OAA] (2.1×10-3+[OAA])-1 and was independent of temperature (5 to 50°C). To evaluate the importance of this forward rate under a prebiotic scenario, we also studied the temperature-dependent rate of the backward thermal decarboxylation of OAA to pyruvate (PA), which followed an Arrhenius behavior as log (k-2)=11.74 4956/T, where k-2 is in units of s-1. These measured rates were employed in conjunction with the indirectly estimated carboxylation rate of PA to OAA to assess the possible importance of mineral photoelectrochemistry in the conversion of OAA to MA under several scenarios of prebiotic conditions on early Earth. As an example, our analysis shows that there is 90% efficiency with a forward velocity of 3 yr/cycle for the OAA→MA step of the rTCA cycle at 280 K. Efficiency and velocity both decrease for increasing temperature. These results suggest high viability for mineral photoelectrochemistry as an enzyme-free engine to drive the rTCA cycle through the early aeons of early Earth, at least for the investigated OAA→MA step.

Anti-Diabetic Effects of Madecassic Acid and Rotundic Acid

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Yuan-Man Hsu

2015-12-01

Full Text Available Anti-diabetic effects of madecassic acid (MEA and rotundic acid (RA were examined. MEA or RA at 0.05% or 0.1% was supplied to diabetic mice for six weeks. The intake of MEA, not RA, dose-dependently lowered plasma glucose level and increased plasma insulin level. MEA, not RA, intake dose-dependently reduced plasminogen activator inhibitor-1 activity and fibrinogen level; as well as restored antithrombin-III and protein C activities in plasma of diabetic mice. MEA or RA intake decreased triglyceride and cholesterol levels in plasma and liver. Histological data agreed that MEA or RA intake lowered hepatic lipid droplets, determined by ORO stain. MEA intake dose-dependently declined reactive oxygen species (ROS and oxidized glutathione levels, increased glutathione content and maintained the activity of glutathione reductase and catalase in the heart and kidneys of diabetic mice. MEA intake dose-dependently reduced interleukin (IL-1β, IL-6, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels in the heart and kidneys of diabetic mice. RA intake at 0.1% declined cardiac and renal levels of these inflammatory factors. These data indicated that MEA improved glycemic control and hemostatic imbalance, lowered lipid accumulation, and attenuated oxidative and inflammatory stress in diabetic mice. Thus, madecassic acid could be considered as an anti-diabetic agent.

Poly(aspartic acid) with adjustable pH-dependent solubility.

Science.gov (United States)

Németh, Csaba; Gyarmati, Benjámin; Abdullin, Timur; László, Krisztina; Szilágyi, András

2017-02-01

Poly(aspartic acid) (PASP) derivatives with adjustable pH-dependent solubility were synthesized and characterized to establish the relationship between their structure and solubility in order to predict their applicability as a basic material for enteric coatings. Polysuccinimide, the precursor of PASP, was modified with short chain alkylamines, and the residual succinimide rings were subsequently opened to prepare the corresponding PASP derivatives. Study of the effect of the type and concentration of the side groups on the pH-dependent solubility of PASP showed that solubility can be adjusted by proper selection of the chemical structure. The Henderson-Hasselbalch (HH) and the extended HH equations were used to describe the pH-dependent solubility of the polymers quantitatively. The estimate provided by the HH equation is poor, but an accurate description of the pH-dependent solubility can be found with the extended HH equation. The dissolution rate of a polymer film prepared from a selected PASP derivative was determined by fluorescence marking. The film dissolved rapidly when the pH was increased above its pK a . Cellular viability tests show that PASP derivatives are non-toxic to a human cell line. These polymers are thus of great interest as starting materials for enteric coatings. Poly(amino acid) type biocompatible polymers were synthesized for future use as pharmaceutical film coatings. To this end, we tailored the pH-dependent solubility of poly(aspartic acid) (PASP). It was found that both the solubility and the pK a values of the modified PASP depended strongly on composition. Fluorescent marking was used to characterize the dissolution of a chosen PASP derivative. In acidic media only a negligible amount of the polymer dissolved, but dissolution was very fast and complete at the pH values that prevail in the small intestine. As a consequence, enteric coatings based on such PASP derivatives may be used for drug delivery in the gastrointestinal tract

Ursodeoxycholic acid suppresses mitochondria-dependent programmed cell death induced by sodium nitroprusside in SH-SY5Y cells

International Nuclear Information System (INIS)

Chun, Hong Sung; Low, Walter C.

2012-01-01

Although ursodeoxycholic acid (UDCA) and its highly water-soluble formula (Yoo's solution; YS) have been shown to prevent neuronal damage, the effects of UDCA or YS against Parkinson's disease (PD)-related dopaminergic cell death has not been studied. This study investigated the protective effects of UDCA and YS on sodium nitroprusside (SNP)-induced cytotoxicity in human dopaminergic SH-SY5Y cells. Both UDCA (50–200 μM) and YS (100–200 μM) dose-dependently prevented SNP (1 mM)-induced cell death. Results showed that both UDCA and YS effectively attenuated the production of total reactive oxygen species (ROS), peroxynitrite (ONOO − ) and nitric oxide (NO), and markedly inhibited the mitochondrial membrane potential (MMP) loss and intracellular reduced glutathione (GSH) depletion. SNP-induced programmed cell death events, such as nuclear fragmentation, caspase-3/7 and -9 activation, Bcl-2/Bax ratio decrease, and cytochrome c release, were significantly attenuated by both UDCA and YS. Furthermore, selective inhibitor of phosphatidylinositiol-3-kinase (PI3K), LY294002, and Akt/PKB inhibitor, triciribine, reversed the preventive effects of UDCA on the SNP-induced cytotoxicity and Bax translocation. These results suggest that UDCA can protect SH-SY5Y cells under programmed cell death process by regulating PI3K-Akt/PKB pathways.

Photostimulated attenuation of hypersound in superlattice

International Nuclear Information System (INIS)

Mensah, S.Y.; Allotey, F.K.; Adjepong, S.K.

1992-10-01

Photostimulated attenuation of hypersound in semiconductor superlattice has been investigated. It is shown that the attenuation coefficient depends on the phonon wave vector q in an oscillatory manner and that from this oscillation the band width Δ of superlattice can be found. (author). 14 refs, 1 fig

S-52, a novel nootropic compound, protects against β-amyloid induced neuronal injury by attenuating mitochondrial dysfunction.

Science.gov (United States)

Gao, Xin; Zheng, Chun Yan; Qin, Guo Wei; Tang, Xi Can; Zhang, Hai Yan

2012-10-01

Accumulating evidence suggests that β-amyloid (Aβ)-induced oxidative DNA damage and mitochondrial dysfunction may initiate and contribute to the progression of Alzheimer's disease (AD). This study evaluated the neuroprotective effects of S-52, a novel nootropic compound, on Aβ-induced mitochondrial failure. In an established paradigm of moderate cellular injury induced by Aβ, S-52 was observed to attenuate the toxicity of Aβ to energy metabolism, mitochondrial membrane structure, and key enzymes in the electron transport chain and tricarboxylic acid cycle. In addition, S-52 also effectively inhibited reactive oxygen species accumulation dose dependently not only in Aβ-harmed cells but also in unharmed, normal cells. The role of S-52 as a scavenger of free radicals is involved in the antioxidative effect of this compound. The beneficial effects on mitochondria and oxidative stress extend the neuroprotective effects of S-52. The present study provides crucial information for better understanding the beneficial profiles of this compound and discovering novel potential drug candidates for AD therapy. Copyright © 2012 Wiley Periodicals, Inc.

Antioxidant treatment attenuates lactate production in diabetic nephropathy

DEFF Research Database (Denmark)

Laustsen, Christoffer; Nielsen, Per Mose; Stokholm Nørlinger, Thomas

2017-01-01

-IDEAL spiral sequence. Untreated diabetic rats showed increased renal lactate production compared with that shown by the controls. However, chronic TEMPOL treatment significantly attenuated diabetes-induced lactate production. No significant effects of diabetes or TEMPOL were observed on [13C]alanine levels......, indicating an intact glucose-alanine cycle, or [13C]bicarbonate, indicating normal flux through the Krebs cycle. In conclusion, this study demonstrates that diabetes-induced pseudohypoxia, as indicated by an increased lactate-to-pyruvate ratio, is significantly attenuated by antioxidant treatment......The early progression of diabetic nephropathy is notoriously difficult to detect and quantify before the occurrence of substantial histological damage. Recently, hyperpolarized [1-13C]pyruvate has demonstrated increased lactate production in the kidney early after the onset of diabetes, implying...

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

Science.gov (United States)

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

2015-07-02

Succinic acid produced by yeast during bread dough fermentation can significantly affect the rheological properties of the dough. By introducing mutations in the model S288C yeast strain, we show that the oxidative pathway of the TCA cycle and the glyoxylate shunt contribute significantly to succinic acid production during dough fermentation. More specifically, deletion of ACO1 and double deletion of ACO1 and ICL1 resulted in a 36 and 77% decrease in succinic acid levels in fermented dough, respectively. Similarly, double deletion of IDH1 and IDP1 decreased succinic acid production by 85%, while also affecting the fermentation rate. By contrast, double deletion of SDH1 and SDH2 resulted in a two-fold higher succinic acid accumulation compared to the wild-type. Deletion of fumarate reductase activity (FRD1 and OSM1) in the reductive pathway of the TCA cycle did not affect the fermentation rate and succinic acid production. The changes in the levels of succinic acid produced by mutants Δidh1Δidp1 (low level) and Δsdh1Δsdh2 (high level) in fermented dough only resulted in small pH differences, reflecting the buffering capacity of dough at a pH of around 5.1. Moreover, Rheofermentometer analysis using these mutants revealed no difference in maximum dough height and gas retention capacity with the dough prepared with S288C. The impact of the changed succinic acid profile on the organoleptic or antimicrobial properties of bread remains to be demonstrated. Copyright © 2015 Elsevier B.V. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Marie Izac

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

Fatty acid-induced gut-brain signaling attenuates neural and behavioral effects of sad emotion in humans.

Science.gov (United States)

Van Oudenhove, Lukas; McKie, Shane; Lassman, Daniel; Uddin, Bilal; Paine, Peter; Coen, Steven; Gregory, Lloyd; Tack, Jan; Aziz, Qasim

2011-08-01

Although a relationship between emotional state and feeding behavior is known to exist, the interactions between signaling initiated by stimuli in the gut and exteroceptively generated emotions remain incompletely understood. Here, we investigated the interaction between nutrient-induced gut-brain signaling and sad emotion induced by musical and visual cues at the behavioral and neural level in healthy nonobese subjects undergoing functional magnetic resonance imaging. Subjects received an intragastric infusion of fatty acid solution or saline during neutral or sad emotion induction and rated sensations of hunger, fullness, and mood. We found an interaction between fatty acid infusion and emotion induction both in the behavioral readouts (hunger, mood) and at the level of neural activity in multiple pre-hypothesized regions of interest. Specifically, the behavioral and neural responses to sad emotion induction were attenuated by fatty acid infusion. These findings increase our understanding of the interplay among emotions, hunger, food intake, and meal-induced sensations in health, which may have important implications for a wide range of disorders, including obesity, eating disorders, and depression.

Using physical approaches for the attenuation of lactic acid bacteria in an organic rice beverage.

Science.gov (United States)

Bevilacqua, Antonio; Casanova, Francesco Pio; Petruzzi, Leonardo; Sinigaglia, Milena; Corbo, Maria Rosaria

2016-02-01

A wild strain of Lactobacillus plantarum, isolated from an Italian sourdough, was inoculated in an organic rice drink; however, it caused a strong acidification. Thus, it was preliminary processed through homogenization (single or multiple passes) or sonication (US) and then inoculated in the beverage. The samples were stored at 4 °C and analyzed to assess pH, production of lactic acid, viable count and sensory scores. A US-2-step process (power, 80%) could control acidification; viability and sensory traits were never affected by sonication. This result was confirmed on two commercial probiotics (Lactobacillus casei LC01 and Bifidobacterium animalis subsp. lactis Bb12). In the 2nd step samples inoculated with attenuated strains were also stored under thermal abuse conditions (25 or 37 °C for 4 or 24 h, then at 4 °C) and the results showed that US could control acidification for a short thermal abuse. Finally, US-attenuated starter cultures were inoculated in the rice drink containing β-glucans as healthy compounds; the targets did not cause any significant change of prebiotic. Copyright © 2015 Elsevier Ltd. All rights reserved.

Arecoline-induced growth arrest and p21WAF1 expression are dependent on p53 in rat hepatocytes

International Nuclear Information System (INIS)

Chou, W.-W.; Guh, J.-Y.; Tsai, J.-F.; Hwang, C.-C.; Chen, H.-C.; Huang, J.-S.; Yang, Y.-L.; Hung, W.-C.; Chuang, L.-Y.

2008-01-01

Betel-quid use is associated with the risk of liver cirrhosis and hepatocellular carcinoma and arecoline, the major alkaloid of betel-quid, is hepatotoxic in mice. Therefore, we studied the cytotoxic and genotoxic effects of arecoline in normal rat hepatocytes (Clone-9 cells). Arecoline dose-dependently (0.1-1 mM) decreased cell cycle-dependent proliferation while inducing DNA damage at 24 h. Moreover, arecoline (1 mM)-induced apoptosis and necrosis at 24 h. Arecoline dose-dependently (0.1-0.5 mM) increased transforming growth factor-β (TGF-β) mRNA, gene transcription and bioactivity and neutralizing TGF-β antibody attenuated arecoline (0.5 mM)-inhibited cell proliferation at 24 h. Arecoline (0.5 mM) also increased p21 WAF1 protein expression and p21 WAF1 gene transcription. Moreover, arecoline (0.5 mM) time-dependently (8-24 h) increased p53 serine 15 phosphorylation. Pifithrin-α (p53 inhibitor) and the loss of the two p53-binding elements in the p21 WAF1 gene promoter attenuated arecoline-induced p21 WAF1 gene transcription at 24 h. Pifithrin-α also attenuated arecoline (0.5 mM)-inhibited cell proliferation at 24 h. We concluded that arecoline induces cytotoxicity, DNA damage, G 0 /G 1 cell cycle arrest, TGF-β1, p21 WAF1 and activates p53 in Clone-9 cells. Moreover, arecoline-induced p21 WAF1 is dependent on p53 while arecoline-inhibited growth is dependent on both TGF-β and p53

Improvement of quantitation in SPECT: Attenuation and scatter correction using non-uniform attenuation data

International Nuclear Information System (INIS)

Mukai, T.; Torizuka, K.; Douglass, K.H.; Wagner, H.N.

1985-01-01

Quantitative assessment of tracer distribution with single photon emission computed tomography (SPECT) is difficult because of attenuation and scattering of gamma rays within the object. A method considering the source geometry was developed, and effects of attenuation and scatter on SPECT quantitation were studied using phantoms with non-uniform attenuation. The distribution of attenuation coefficients (μ) within the source were obtained by transmission CT. The attenuation correction was performed by an iterative reprojection technique. The scatter correction was done by convolution of the attenuation corrected image and an appropriate filter made by line source studies. The filter characteristics depended on μ and SPEC measurement at each pixel. The SPECT obtained by this method showed the most reasonable results than the images reconstructed by other methods. The scatter correction could compensate completely for a 28% scatter components from a long line source, and a 61% component for thick and extended source. Consideration of source geometries was necessary for effective corrections. The present method is expected to be valuable for the quantitative assessment of regional tracer activity

Perception of low red:far-red ratio comprises both salicylic acid- and jasmonic acid-dependent pathogen defences in Arabidopsis

NARCIS (Netherlands)

De Wit, M. de; Spoel, S.H.; Sanchez-Perez, G.F.; Gommers, C.M.M.; Pieterse, C.M.J.; Voesenek, L.A.C.J.; Pierik, R.

2013-01-01

In dense stands of plants, such as agricultural monocultures, plants are exposed simultaneously to competition for light and other stresses such as pathogen infection. Here, we show that both salicylic acid (SA)-dependent and jasmonic acid (JA)-dependent disease resistance is inhibited by a

Attenuation coefficients of soils

International Nuclear Information System (INIS)

Martini, E.; Naziry, M.J.

1989-01-01

As a prerequisite to the interpretation of gamma-spectrometric in situ measurements of activity concentrations of soil radionuclides the attenuation of 60 to 1332 keV gamma radiation by soil samples varying in water content and density has been investigated. A useful empirical equation could be set up to describe the dependence of the mass attenuation coefficient upon photon energy for soil with a mean water content of 10%, with the results comparing well with data in the literature. The mean density of soil in the GDR was estimated at 1.6 g/cm 3 . This value was used to derive the linear attenuation coefficients, their range of variation being 10%. 7 figs., 5 tabs. (author)

Viscothermal Coupling Effects on Sound Attenuation in Concentrated Colloidal Dispersions.

Science.gov (United States)

Han, Wei

1995-11-01

This thesis describes a Unified Coupled Phase Continuum (UCPC) model to analyze sound propagation through aerosols, emulsions and suspensions in terms of frequency dependent attenuation coefficient and sound speed. Expressions for the viscous and thermal coupling coefficients explicitly account for the effects of particle size, shape factor, orientation as well as concentration and the sound frequency. The UCPC model also takes into account the intrinsic acoustic absorption within the fluid medium due to its viscosity and heat conductivity. The effective complex wave number as a function of frequency is derived. A frequency- and concentration-dependent complex Nusselt number for the interfacial thermal coupling coefficient is derived using an approximate similarity between the 'viscous skin drag' and 'heat conduction flux' associated with the discontinuous suspended phase, on the basis of a cell model. The theoretical predictions of attenuation spectra provide satisfactory agreement with reported experimental data on two concentrated suspensions (polystyrene latex and kaolin pigment), two concentrated emulsions (toluene -in-water, n-hexadecane-in-water), and two aerosols (oleic acid droplets-in-nitrogen, alumina-in-air), covering a wide range of relative magnitudes (from 10^ {-3} to 10^{3}) of thermal versus viscous contributions, for dispersed phase volume fractions as high as 50%. The relative differences between the additive result of separate viscous and thermal loss estimates and combined viscothermal absorption results are also presented. Effects of particle shape on viscous attenuation of sound in concentrated suspensions of non-spherical clay particles are studied. Attenuation spectra for 18 frequencies from 3 to 100 MHz are measured and analyzed for eleven kaolin clay slurries with solid concentrations ranging from 0.6% to 35% (w/w). A modified viscous drag coefficient that considers frequency, concentration, particle size, shape and orientation of

Growth inhibitory effect of 4-phenyl butyric acid on human gastric cancer cells is associated with cell cycle arrest.

Science.gov (United States)

Li, Long-Zhu; Deng, Hong-Xia; Lou, Wen-Zhu; Sun, Xue-Yan; Song, Meng-Wan; Tao, Jing; Xiao, Bing-Xiu; Guo, Jun-Ming

2012-01-07

To investigate the growth effects of 4-phenyl butyric acid (PBA) on human gastric carcinoma cells and their mechanisms. Moderately-differentiated human gastric carcinoma SGC-7901 and lowly-differentiated MGC-803 cells were treated with 5, 10, 20, 40, and 60 μmol/L PBA for 1-4 d. Cell proliferation was detected using the MTT colorimetric assay. Cell cycle distributions were examined using flow cytometry. The proliferation of gastric carcinoma cells was inhibited by PBA in a dose- and time-dependent fashion. Flow cytometry showed that SGC-7901 cells treated with low concentrations of PBA were arrested at the G₀/G₁ phase, whereas cells treated with high concentrations of PBA were arrested at the G₂/M phase. Although MGC-803 cells treated with low concentrations of PBA were also arrested at the G₀/ G₁ phase, cells treated with high concentrations of PBA were arrested at the S phase. The growth inhibitory effect of PBA on gastric cancer cells is associated with alteration of the cell cycle. For moderately-differentiated gastric cancer cells, the cell cycle was arrested at the G₀ /G₁ and G₂/M phases. For lowly-differentiated gastric cancer cells, the cell cycle was arrested at the G₀/G₁ and S phases.

Attenuation in Melting Layer of Precipitation

NARCIS (Netherlands)

Klaassen, W.

1988-01-01

A model of the melting layer is employed on radar measurements to simulate the attenuation of radio waves at 12, 20 and 30GHz. The attenuation in the melting layer is simulated to be slightly larger than that of rain with the same path length and precipitation intensity. The result appears to depend

Effect of the Menstrual Cycle on Maximum Oxygen Consumption and Endothelium-Dependent Vasodilation

National Research Council Canada - National Science Library

Andrews, Thomas

1997-01-01

.... We studied endothelium-dependent vasodilation of the brachial artery during three phases of the menstrual cycle in 20 eumenorrheic subjects to determine the effect of endogenous estradiol and progesterone...

Proper balance of omega-3 and omega-6 fatty acid supplements with topical cyclosporine attenuated contact lens-related dry eye syndrome.

Science.gov (United States)

Wang, Ling; Chen, Xi; Hao, Jingfang; Yang, Lu

2016-12-01

Essential fatty acids had been applied in the treatment of dry eye syndrome (DES), but the effects of different combinations of fatty acids have not been investigated. 360 long-term contact lens wearers were included in this double-blinded study. Omega-3 and omega-6 fatty acids were combined in different ratios and supplied to the participants that were randomly divided into six groups, and the effects of different essential fatty acids mixture on DES with or without topical cyclosporine were investigated. More than half of long-term contact lens wearers suffered from DES, which were found to be attenuated by oral supplement of properly balanced O3FA and O6FA fatty acid. The topical cyclosporine treatment considerably inhibited the production of cytokines compared to the cyclosporine negative groups, which further relieved DES. Proper balance of omega-3 and omega-6 fatty acid combination significantly alleviated contact lens-related DES.

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

Science.gov (United States)

Scott, Durelle T.; Runkel, Robert L.; McKnight, Diane M.; Voelker, Bettina M.; Kimball, Briant A.; Carraway, Elizabeth R.

2003-01-01

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

The antidiabetic drug metformin decreases mitochondrial respiration and tricarboxylic acid cycle activity in cultured primary rat astrocytes.

Science.gov (United States)

Hohnholt, Michaela C; Blumrich, Eva-Maria; Waagepetersen, Helle S; Dringen, Ralf

2017-11-01

Metformin is an antidiabetic drug that is used daily by millions of patients worldwide. Metformin is able to cross the blood-brain barrier and has recently been shown to increase glucose consumption and lactate release in cultured astrocytes. However, potential effects of metformin on mitochondrial tricarboxylic acid (TCA) cycle metabolism in astrocytes are unknown. We investigated this by mapping 13 C labeling in TCA cycle intermediates and corresponding amino acids after incubation of primary rat astrocytes with [U- 13 C]glucose. The presence of metformin did not compromise the viability of cultured astrocytes during 4 hr of incubation, but almost doubled cellular glucose consumption and lactate release. Compared with control cells, the presence of metformin dramatically lowered the molecular 13 C carbon labeling (MCL) of the cellular TCA cycle intermediates citrate, α-ketoglutarate, succinate, fumarate, and malate, as well as the MCL of the TCA cycle intermediate-derived amino acids glutamate, glutamine, and aspartate. In addition to the total molecular 13 C labeling, analysis of the individual isotopomers of TCA cycle intermediates confirmed a severe decline in labeling and a significant lowering in TCA cycling ratio in metformin-treated astrocytes. Finally, the oxygen consumption of mitochondria isolated from metformin-treated astrocytes was drastically reduced in the presence of complex I substrates, but not of complex II substrates. These data demonstrate that exposure to metformin strongly impairs complex I-mediated mitochondrial respiration in astrocytes, which is likely to cause the observed decrease in labeling of mitochondrial TCA cycle intermediates and the stimulation of glycolytic lactate production. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Analysis of hyaluronic acid concentration in rat vocal folds during estral and gravidic puerperal cycles

OpenAIRE

de Sá Pedroso, José Eduardo; Camponês do Brasil, Osíris; Maciel Martins, João Roberto; Nader, Helena Bociane; Simões, Manuel de Jesus

2009-01-01

Hormone plays an important role in the larynx. Among other substances, vocal folds contain hyaluronic acid, which tissue concentration may vary according to hormone action. AIM: the objective of this study is to analyze hyaluronic acid concentration in the vocal folds during estral and gravidic-puerperal cycles. MATERIALS AND METHODS: Experimental study. 40 adult rats were divided into two groups. In the first group we used 20 rats to establish the concentration of hyaluronic acid during the ...

Integration of the tricarboxylic acid (TCA) cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing and hyphal development in Candida albicans.

Science.gov (United States)

Tao, Li; Zhang, Yulong; Fan, Shuru; Nobile, Clarissa J; Guan, Guobo; Huang, Guanghua

2017-08-01

Morphological transitions and metabolic regulation are critical for the human fungal pathogen Candida albicans to adapt to the changing host environment. In this study, we generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA) cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. albicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. By integrating the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and hyphal development. The TCA cycle and cAMP signaling pathways coordinately regulate hyphal growth through the molecular linkers ATP and CO2. Inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA) catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and hypha-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Our study reveals the regulatory role of the TCA cycle in CO2 sensing and hyphal development and establishes a novel link between the TCA cycle and Ras1-cAMP signaling pathways.

Integration of the tricarboxylic acid (TCA cycle with cAMP signaling and Sfl2 pathways in the regulation of CO2 sensing and hyphal development in Candida albicans.

Directory of Open Access Journals (Sweden)

Li Tao

2017-08-01

Full Text Available Morphological transitions and metabolic regulation are critical for the human fungal pathogen Candida albicans to adapt to the changing host environment. In this study, we generated a library of central metabolic pathway mutants in the tricarboxylic acid (TCA cycle, and investigated the functional consequences of these gene deletions on C. albicans biology. Inactivation of the TCA cycle impairs the ability of C. albicans to utilize non-fermentable carbon sources and dramatically attenuates cell growth rates under several culture conditions. By integrating the Ras1-cAMP signaling pathway and the heat shock factor-type transcription regulator Sfl2, we found that the TCA cycle plays fundamental roles in the regulation of CO2 sensing and hyphal development. The TCA cycle and cAMP signaling pathways coordinately regulate hyphal growth through the molecular linkers ATP and CO2. Inactivation of the TCA cycle leads to lowered intracellular ATP and cAMP levels and thus affects the activation of the Ras1-regulated cAMP signaling pathway. In turn, the Ras1-cAMP signaling pathway controls the TCA cycle through both Efg1- and Sfl2-mediated transcriptional regulation in response to elevated CO2 levels. The protein kinase A (PKA catalytic subunit Tpk1, but not Tpk2, may play a major role in this regulation. Sfl2 specifically binds to several TCA cycle and hypha-associated genes under high CO2 conditions. Global transcriptional profiling experiments indicate that Sfl2 is indeed required for the gene expression changes occurring in response to these elevated CO2 levels. Our study reveals the regulatory role of the TCA cycle in CO2 sensing and hyphal development and establishes a novel link between the TCA cycle and Ras1-cAMP signaling pathways.

Influence of safety vlave pressure on gelled electrolyte valve-regulated lead/acid batteries under deep cycling applications

International Nuclear Information System (INIS)

Oh, Sang Hyub; Kim, Myung Soo; Lee, Jin Bok; Lee, Heung Lark

2002-01-01

Cycle life tests have been carried out to evaluate the influence of safety valve pressure on vlave regulated lead/acid batteries under deep cycling applications. Batteries were cycled at 5 hour rates at 100 % DOD, and safety valve pressure was set to 1.08 and 2.00 bar, respectively. The batteries lost 248.3 g of water for each case after about 1,200 cycles, but the cyclic performances of the batteries were comparable. Most of the gas of the battery during discharging was hydrogen, and the oxygen concentration increased to 18 % after 3 hours of charging. The micro structure of the positive active materials was completely changed and the corrosion layer of the positive grid was less than 50 μm, regardless of the pressure of the safety valve after cycle life tests. The cause of discharge capacity decrease was found to water loss and the shedding of the positive active materials. The pressure of safety valve does not give little effect to the cyclic performance and the failure modes of the gelled electrolyte valve-regulated lead acid batteries

Cell cycle-dependent transcription factors control the expression of yeast telomerase RNA.

Science.gov (United States)

Dionne, Isabelle; Larose, Stéphanie; Dandjinou, Alain T; Abou Elela, Sherif; Wellinger, Raymund J

2013-07-01

Telomerase is a specialized ribonucleoprotein that adds repeated DNA sequences to the ends of eukaryotic chromosomes to preserve genome integrity. Some secondary structure features of the telomerase RNA are very well conserved, and it serves as a central scaffold for the binding of associated proteins. The Saccharomyces cerevisiae telomerase RNA, TLC1, is found in very low copy number in the cell and is the limiting component of the known telomerase holoenzyme constituents. The reasons for this low abundance are unclear, but given that the RNA is very stable, transcriptional control mechanisms must be extremely important. Here we define the sequences forming the TLC1 promoter and identify the elements required for its low expression level, including enhancer and repressor elements. Within an enhancer element, we found consensus sites for Mbp1/Swi4 association, and chromatin immunoprecipitation (ChIP) assays confirmed the binding of Mbp1 and Swi4 to these sites of the TLC1 promoter. Furthermore, the enhancer element conferred cell cycle-dependent regulation to a reporter gene, and mutations in the Mbp1/Swi4 binding sites affected the levels of telomerase RNA and telomere length. Finally, ChIP experiments using a TLC1 RNA-binding protein as target showed cell cycle-dependent transcription of the TLC1 gene. These results indicate that the budding yeast TLC1 RNA is transcribed in a cell cycle-dependent fashion late in G1 and may be part of the S phase-regulated group of genes involved in DNA replication.

Does autophagy in the midgut epithelium of centipedes depend on the day/night cycle?

Science.gov (United States)

Rost-Roszkowska, M M; Chajec, Ł; Vilimova, J; Tajovský, K; Kszuk-Jendrysik, M

2015-01-01

The midgut epithelium of two centipedes, Lithobius forficatus and Scolopendra cingulata, is composed of digestive, secretory and regenerative cells. In L. forficatus, the autophagy occurred only in the cytoplasm of the digestive cells as a sporadic process, while in S. cingulata, it occurred intensively in the digestive, secretory and regenerative cells of the midgut epithelium. In both of the species that were analyzed, this process proceeded in a continuous manner and did not depend on the day/night cycle. Ultrastructural analysis showed that the autophagosomes and autolysosomes were located mainly in the apical and perinuclear cytoplasm of the digestive cells in L. forficatus. However, in S. cingulata, the entire cytoplasm was filled with autophagosomes and autolysosomes. Initially the membranes of phagophores surround organelles during autophagosome formation. Autolysosomes result from the fusion of autophagosomes and lysosomes. Residual bodies which are the last stage of autophagy were released into the midgut lumen due to necrosis. Autophagy in the midgut epithelia that were analyzed was confirmed using acid phosphatase and mono-dansyl-cadaverine stainings. Copyright © 2014 Elsevier Ltd. All rights reserved.

Leukocyte Overexpression of Intracellular NAMPT Attenuates Atherosclerosis by Regulating PPARγ-Dependent Monocyte Differentiation and Function.

Science.gov (United States)

Bermudez, Beatriz; Dahl, Tuva Borresdatter; Medina, Indira; Groeneweg, Mathijs; Holm, Sverre; Montserrat-de la Paz, Sergio; Rousch, Mat; Otten, Jeroen; Herias, Veronica; Varela, Lourdes M; Ranheim, Trine; Yndestad, Arne; Ortega-Gomez, Almudena; Abia, Rocio; Nagy, Laszlo; Aukrust, Pal; Muriana, Francisco J G; Halvorsen, Bente; Biessen, Erik Anna Leonardus

2017-06-01

Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) mediates inflammatory and potentially proatherogenic effects, whereas the role of intracellular NAMPT (iNAMPT), the rate limiting enzyme in the salvage pathway of nicotinamide adenine dinucleotide (NAD) + generation, in atherogenesis is largely unknown. Here we investigated the effects of iNAMPT overexpression in leukocytes on inflammation and atherosclerosis. Low-density lipoprotein receptor-deficient mice with hematopoietic overexpression of human iNAMPT (iNAMPT hi ), on a western type diet, showed attenuated plaque burden with features of lesion stabilization. This anti-atherogenic effect was caused by improved resistance of macrophages to apoptosis by attenuated chemokine (C-C motif) receptor 2-dependent monocyte chemotaxis and by skewing macrophage polarization toward an anti-inflammatory M2 phenotype. The iNAMPT hi phenotype was almost fully reversed by treatment with the NAMPT inhibitor FK866, indicating that iNAMPT catalytic activity is instrumental in the atheroprotection. Importantly, iNAMPT overexpression did not induce any increase in eNAMPT, and eNAMPT had no effect on chemokine (C-C motif) receptor 2 expression and promoted an inflammatory M1 phenotype in macrophages. The iNAMPT-mediated effects at least partly involved sirtuin 1-dependent molecular crosstalk of NAMPT and peroxisome proliferator-activated receptor γ. Finally, iNAMPT and peroxisome proliferator-activated receptor γ showed a strong correlation in human atherosclerotic, but not healthy arteries, hinting to a relevance of iNAMPT/peroxisome proliferator-activated receptor γ pathway also in human carotid atherosclerosis. This study highlights the functional dichotomy of intracellular versus extracellular NAMPT, and unveils a critical role for the iNAMPT-peroxisome proliferator-activated receptor γ axis in atherosclerosis. © 2017 American Heart Association, Inc.

A dynamic, dependent type system for nuclear fuel cycle code generation

Energy Technology Data Exchange (ETDEWEB)

Scopatz, A. [The University of Chicago 5754 S. Ellis Ave, Chicago, IL 60637 (United States)

2013-07-01

The nuclear fuel cycle may be interpreted as a network or graph, thus allowing methods from formal graph theory to be used. Nodes are often idealized as nuclear fuel cycle facilities (reactors, enrichment cascades, deep geologic repositories). With the advent of modern object-oriented programming languages - and fuel cycle simulators implemented in these languages - it is natural to define a class hierarchy of facility types. Bright is a quasi-static simulator, meaning that the number of material passes through a facility is tracked rather than natural time. Bright is implemented as a C++ library that models many canonical components such as reactors, storage facilities, and more. Cyclus is a discrete time simulator, meaning that natural time is tracked through out the simulation. Therefore a robust, dependent type system was developed to enable inter-operability between Bright and Cyclus. This system is capable of representing any fuel cycle facility. Types declared in this system can then be used to automatically generate code which binds a facility implementation to a simulator front end. Facility model wrappers may be used either internally to a fuel cycle simulator or as a mechanism for inter-operating multiple simulators. While such a tool has many potential use cases it has two main purposes: enabling easy performance of code-to-code comparisons and the verification and the validation of user input.

Plasma Ascorbic Acid in Insulin and Non-insulin Dependent Diabetes

African Journals Online (AJOL)

Blood glucose, plasma ascorbic acid and haemoglobin levels were estimated in insulin dependent diabetics, non-insulin dependent diabetics and controls matched for number, sex and age. Significantly higher levels of these parameters were found in control group than in the other two groups. Statistically differences were ...

Seasonal and tidal cycles of suspended particulates in the Irish Sea

International Nuclear Information System (INIS)

Weeks, Alison.

1989-07-01

The distribution of suspended particulate material (SPM) in the shelf seas and the processes controlling its variation are little known. This thesis reports an exploratory study of the spatial and time dependent variability of SPM in an area of the northern Irish Sea. SPM was determined both directly by gravimetric methods and via measurements of beam attenuation. Spatial distributions were determined from grid surveys using a profiling transmissometer. In addition a six month record of beam attenuation and current velocity was obtained from a site off the north coast of Anglesey. A strong seasonal cycle of beam attenuation was observed in mixed water, with values decreasing in June, July and August which suggested a reduction in the supply of SPM during summer. In stratified water, high concentrations of SPM remained confined to the dense layer below the thermocline. A regression model was found to explain 35% of the variance in data from a 5 week time series. 70% of the variance was explained for four day time series, near spring tides. The relationship between beam attenuation and tidal flows was more marked at spring tides than at neaps. (author)

Dimethylfumarate attenuates restenosis after acute vascular injury by cell-specific and Nrf2-dependent mechanisms

Directory of Open Access Journals (Sweden)

Chang Joo Oh

2014-01-01

Full Text Available Excessive proliferation of vascular smooth muscle cells (VSMCs and incomplete re-endothelialization is a major clinical problem limiting the long-term efficacy of percutaneous coronary angioplasty. We tested if dimethylfumarate (DMF, an anti-psoriasis drug, could inhibit abnormal vascular remodeling via NF−E2-related factor 2 (Nrf2-NAD(PH quinone oxidoreductase 1 (NQO1 activity. DMF significantly attenuated neointimal hyperplasia induced by balloon injury in rat carotid arteries via suppression of the G1 to S phase transition resulting from induction of p21 protein in VSMCs. Initially, DMF increased p21 protein stability through an enhancement in Nrf2 activity without an increase in p21 mRNA. Later on, DMF stimulated p21 mRNA expression through a process dependent on p53 activity. However, heme oxygenase-1 (HO-1 or NQO1 activity, well-known target genes induced by Nrf2, were dispensable for the DMF induction of p21 protein and the effect on the VSMC proliferation. Likewise, DMF protected endothelial cells from TNF-α-induced apoptosis and the dysfunction characterized by decreased eNOS expression. With knock-down of Nrf2 or NQO1, DMF failed to prevent TNF-α-induced cell apoptosis and decreased eNOS expression. Also, CD31 expression, an endothelial specific marker, was restored in vivo by DMF. In conclusion, DMF prevented abnormal proliferation in VSMCs by G1 cell cycle arrest via p21 upregulation driven by Nrf2 and p53 activity, and had a beneficial effect on TNF-α-induced apoptosis and dysfunction in endothelial cells through Nrf2–NQO1 activity suggesting that DMF might be a therapeutic drug for patients with vascular disease.

Zinc-ion-dependent acid phosphatase exhibits magnesium-ion-dependent myo-inositol-1-phosphatase activity.

Science.gov (United States)

Fujimoto, S; Okano, I; Tanaka, Y; Sumida, Y; Tsuda, J; Kawakami, N; Shimohama, S

1996-06-01

We have purified bovine brain Zn(2+)-dependent acid phosphatase (Zn(2+)-APase), which requires Zn2+ ions to hydrolyze the substrate p-nitrophenyl phosphate (pNPP) in an acidic environment. The substrate specificity and metal requirement of Zn(2+)-APase at a physiological pH was also studied. The enzyme exhibited hydrolytic activity on myo-inositol-1- and -2-monophosphates, 2'-adenosine monophosphate, 2'-guanosine monophosphate, and the alpha- and beta-glycerophosphates, glucose-1-phosphate, and fructose-6-phosphate in 50 mM Tris-HCl buffer (pH 7.4) in the presence of Mg2+ ions, but not on pNPP and phosphotyrosine. Zn2+, Mn2+ and Co2+ ions were less effective for activation. Among the above substrates, myo-inositol-1-phosphate was the most susceptible to hydrolysis by the enzyme in the presence of 3 mM Mg2+ ions. The enzyme exhibited an optimum pH at around 8 for myo-inositol-1-phosphate in the presence of 3 mM Mg2+ ions. The Mg(2+)-dependent myo-inositol-1-phosphatase activity of the enzyme was significantly inhibited by Li+ ions. The Zn(2+)-dependent p-nitrophenyl phosphatase activity and Mg(2+)-dependent myo-inositol-1-phosphatase activity of the purified enzyme fraction exhibited similar behavior on Sephadex G-100 and Mono Q colomns. These findings suggest that Zn(2+)-APase also exhibits Mg(2+)-dependent myo-inositol-1-phosphatase activity under physiological conditions.

Natural attenuation of herbicides

DEFF Research Database (Denmark)

Tuxen, Nina; Højberg, Anker Lajer; Broholm, Mette Martina

2002-01-01

A field injection experiment in a sandy, aerobic aquifer showed that two phenoxy acids MCPP (mecoprop) and dichlorprop were degraded within I in downgradient of the injection wells after an apparent lag period. The plume development and microbial measurements indicated that microbial growth gover....... The observations may be important for application of natural attenuation as a remedy in field scale systems....

Anomalies of ultrasound attenuation in metals under hydrostatic pressure

International Nuclear Information System (INIS)

Galkin, A.A.; Datsko, O.I.; Varyukhin, V.N.; Pilipenko, N.P.

1978-01-01

Ultrasonic attenuation was measured in polycrystal specimens of molybdenum, chromium and zinc under hydrostatic pressure up to 6 kbar. On the plot of ultrasound attenuation dependence on the pressure in molybdenum the maxima are observed under the pressure of 2 kbar. The anomaly of ultrasound attenuation is shown to connect only with brittle-ductile transtion

Vitamin E δ-tocotrienol induces p27(Kip1-dependent cell-cycle arrest in pancreatic cancer cells via an E2F-1-dependent mechanism.

Directory of Open Access Journals (Sweden)

Pamela J Hodul

Full Text Available Vitamin E δ-tocotrienol has been shown to have antitumor activity, but the precise molecular mechanism by which it inhibits the proliferation of cancer cells remains unclear. Here, we demonstrated that δ-tocotrienol exerted significant cell growth inhibition pancreatic ductal cancer (PDCA cells without affecting normal human pancreatic ductal epithelial cell growth. We also showed that δ-tocotrienol-induced growth inhibition occurred concomitantly with G(1 cell-cycle arrest and increased p27(Kip1 nuclear accumulation. This finding is significant considering that loss of nuclear p27(Kip1 expression is a well-established adverse prognostic factor in PDCA. Furthermore, δ-tocotrienol inactivated RAF-MEK-ERK signaling, a pathway known to suppress p27(Kip1 expression. To determine whether p27(Kip1 induction is required for δ-tocotrienol inhibition of PDCA cell proliferation, we stably silenced the CDKN1B gene, encoding p27(Kip1, in MIAPaCa-2 PDCA cells and demonstrated that p27(Kip1 silencing suppressed cell-cycle arrest induced by δ-tocotrienol. Furthermore, δ-tocotrienol induced p27(Kip1 mRNA expression but not its protein degradation. p27(Kip1 gene promoter activity was induced by δ-tocotrienol through the promoter's E2F-1 binding site, and this activity was attenuated by E2F-1 depletion using E2F-1 small interfering RNA. Finally, decreased proliferation, mediated by Ki67 and p27(Kip1 expression by δ-tocotrienol, was confirmed in vivo in a nude mouse xenograft pancreatic cancer model. Our findings reveal a new mechanism, dependent on p27(Kip1 induction, by which δ-tocotrienol can inhibit proliferation in PDCA cells, providing a new rationale for p27(Kip1 as a biomarker for δ-tocotrienol efficacy in pancreatic cancer prevention and therapy.

Variation in incorporation of tritiated amino acids into rhodopsin and opsin during the 12 hour light-dark cycle

International Nuclear Information System (INIS)

Matsumoto, B.

1981-01-01

This is a study of the variation in incorporation of labeled amino acids into opsin and rhodopsin during the 12 hour light-dark cycle. Groups of 12 adult, light-entrained R. pipiens were injected with tritiated amino acids at selected times of the day and night. Twenty four hours later, the frogs were sacrificed and their rhodopsin purified by column chromatography. It was found that the peak incorporation of amino acids into rhodopsin occurred shortly after light onset and declined to lower levels at later hours. Light microscopic autoradiography revealed the presence of radioactive disc membranes in the rod outer segments. However there was no correlation between outer segment grain density and rhodopsin specific activity. Succeeding experiments showed that light onset, rather than the time of day, played an important role in stimulating isotope incorporation. Electro-immunoprecipitation experiments revealed a changing specific activity for inner segment opsin during the light-dark cycle. Peak levels of amino acid incorporation occurred shortly after light onset and then declined to lower levels. For all time points, opsin was found to be radioactive, indicating opsin biosynthesis occurred continually throughout the diurnal cycle

Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

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Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

2013-01-01

The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

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Yoshinori Kagawa

Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

RNASEK is required for internalization of diverse acid-dependent viruses.

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Hackett, Brent A; Yasunaga, Ari; Panda, Debasis; Tartell, Michael A; Hopkins, Kaycie C; Hensley, Scott E; Cherry, Sara

2015-06-23

Viruses must gain entry into cells to establish infection. In general, viruses enter either at the plasma membrane or from intracellular endosomal compartments. Viruses that use endosomal pathways are dependent on the cellular factors that control this process; however, these genes have proven to be essential for endogenous cargo uptake, and thus are of limited value for therapeutic intervention. The identification of genes that are selectively required for viral uptake would make appealing drug targets, as their inhibition would block an early step in the life cycle of diverse viruses. At this time, we lack pan-antiviral therapeutics, in part because of our lack of knowledge of such cellular factors. RNAi screening has begun to reveal previously unknown genes that play roles in viral infection. We identified dRNASEK in two genome-wide RNAi screens performed in Drosophila cells against West Nile and Rift Valley Fever viruses. Here we found that ribonuclease kappa (RNASEK) is essential for the infection of human cells by divergent and unrelated positive- and negative-strand-enveloped viruses from the Flaviviridae, Togaviridae, Bunyaviridae, and Orthomyxoviridae families that all enter cells from endosomal compartments. In contrast, RNASEK was dispensable for viruses, including parainfluenza virus 5 and Coxsackie B virus, that enter at the plasma membrane. RNASEK is dispensable for attachment but is required for uptake of these acid-dependent viruses. Furthermore, this requirement appears specific, as general endocytic uptake of transferrin is unaffected in RNASEK-depleted cells. Therefore, RNASEK is a potential host cell Achilles' heel for viral infection.

Activation and Repression of Epstein-Barr Virus and Kaposi's Sarcoma-Associated Herpesvirus Lytic Cycles by Short- and Medium-Chain Fatty Acids

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Gorres, Kelly L.; Daigle, Derek; Mohanram, Sudharshan

2014-01-01

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

Eight weeks of citicoline treatment does not perturb sleep/wake cycles in cocaine-dependent adults.

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Bracken, Bethany K; Penetar, David M; Rodolico, John; Ryan, Elizabeth T; Lukas, Scott E

2011-06-01

Citicoline (cytidine-5'-diphosphate) is a mononucleotide composed of ribose, cytosine, pyrophosphate, and choline, and is involved in the biosynthesis of the structural phosopholipids of cell membranes. Treatment with citicoline, improves memory in patients with dementia, and reduces damage to the brain after traumatic brain injury or stroke. Recent research has been conducted to assess whether citicoline is an effective treatment for cocaine dependence. In cocaine-dependent individuals, withdrawal from cocaine is associated with disturbed sleep, which may contribute to the high rate of relapse to cocaine use. Therefore, it is important to know the impact of citicoline on the sleep/wake cycle in these individuals in order to rate its overall efficacy. In this double-blind, placebo-controlled trial, the effects of citicoline treatment on the sleep/wake cycles of cocaine dependent participants were assessed. The results of the current study are reported as part of a larger study, consisting of an eight-week treatment period to assess the efficacy of longer-term treatment with citicoline at decreasing cocaine consumption in cocaine-dependent polydrug using participants. In this non-abstinent, cocaine-dependent population, citicoline had no effect on any of the sleep parameters measured including sleep efficiency, sleep latency, total sleep time, number of waking episodes, time awake per episode, amount of time in bed spent moving, number of sleep episodes, time asleep per episode, and amount of time in bed spent immobile. These data suggest that eight weeks of citicoline administration does not disturb sleep/wake cycles of cocaine-dependent individuals. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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

2012-08-01

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

Okadaic Acid, a Bioactive Fatty Acid from Halichondria okadai, Stimulates Lipolysis in Rat Adipocytes: The Pivotal Role of Perilipin Translocation

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Nen-Chung Chang

2013-01-01

Full Text Available Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the black sponge Halichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes. However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin remain unclear. We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release. Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis. Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment. Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor, calphostin C (PKC inhibitor, or KT-5823 (PKG inhibitor did not attenuate okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor blocked okadaic-acid-dependent lipolysis. These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

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Li, Ying [Faculty of Basic Medical Sciences, Chongqing Medical University, Chongqing 400016 (China); Wang, Jianwei, E-mail: wangjianwei1968@gmail.com [Department of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016 (China); Gu, Tieguang [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia); Yamahara, Johji [Pharmafood Institute, Kyoto 602-8136 (Japan); Li, Yuhao, E-mail: yuhao@sitcm.edu.au [Endocrinology and Metabolism Group, Sydney Institute of Health Sciences, Sydney, NSW 2000 Australia (Australia)

2014-06-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Oleanolic acid supplement attenuates liquid fructose-induced adipose tissue insulin resistance through the insulin receptor substrate-1/phosphatidylinositol 3-kinase/Akt signaling pathway in rats

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Li, Ying; Wang, Jianwei; Gu, Tieguang; Yamahara, Johji; Li, Yuhao

2014-01-01

Oleanolic acid, a triterpenoid contained in more than 1620 plants including various fruits and foodstuffs, has numerous metabolic effects, such as hepatoprotection. However, its underlying mechanisms remain poorly understood. Adipose tissue insulin resistance (Adipo-IR) may contribute to the development and progress of metabolic abnormalities through release of excessive free fatty acids from adipose tissue. This study investigated the effect of oleanolic acid on Adipo-IR. The results showed that supplement with oleanolic acid (25 mg/kg, once daily, by oral gavage) over 10 weeks attenuated liquid fructose-induced increase in plasma insulin concentration and the homeostasis model assessment of insulin resistance (HOMA-IR) index in rats. Simultaneously, oleanolic acid reversed the increase in the Adipo-IR index and plasma non-esterified fatty acid concentrations during the oral glucose tolerance test assessment. In white adipose tissue, oleanolic acid enhanced mRNA expression of the genes encoding insulin receptor, insulin receptor substrate (IRS)-1 and phosphatidylinositol 3-kinase. At the protein level, oleanolic acid upregulated total IRS-1 expression, suppressed the increased phosphorylated IRS-1 at serine-307, and restored the increased phosphorylated IRS-1 to total IRS-1 ratio. In contrast, phosphorylated Akt to total Akt ratio was increased. Furthermore, oleanolic acid reversed fructose-induced decrease in phosphorylated-Akt/Akt protein to plasma insulin concentration ratio. However, oleanolic acid did not affect IRS-2 mRNA expression. Therefore, these results suggest that oleanolic acid supplement ameliorates fructose-induced Adipo-IR in rats via the IRS-1/phosphatidylinositol 3-kinase/Akt pathway. Our findings may provide new insights into the mechanisms of metabolic actions of oleanolic acid. - Highlights: • Adipose insulin resistance (Adipo-IR) contributes to metabolic abnormalities. • We investigated the effect of oleanolic acid (OA) on adipo-IR in

Metabolic regulation at the tricarboxylic acid and glyoxylate cycles of the lignin-degrading basidiomycete Phanerochaete chrysosporium against exogenous addition of vanillin.

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Shimizu, Motoyuki; Yuda, Naoki; Nakamura, Tomofumi; Tanaka, Hiroo; Wariishi, Hiroyuki

2005-10-01

A proteomic differential display technique was utilized to study cellular responses of Phanerochaete chrysosporium exposed to vanillin, one of the key intermediates found during lignin biodegradation. Intracellular proteins were resolved by 2-DE and target protein spots were identified using MALDI-MS after in-gel tryptic digestions. Upon addition of vanillin to P. chrysosporium, up-regulation of homogentisate 1,2-dioxygenase, 1,4-benzoquinone reductases, aldehyde dehydrogenase, and aryl-alcohol dehydrogenase, which seem to play roles in vanillin metabolism, was observed. Furthermore, enzymes involved in glycolysis, the tricarboxylic acid cycle, the pentose-phosphate cycle, and heme biosynthesis were also activated. Up-regulation of extracellular peroxidase was also observed. One of the most unique phenomena against exogenous vanillin was a switch from the glyoxylate cycle to the tricarboxylic acid cycle, where a drastic increase in isocitrate dehydrogenase activity was observed. The exogenous addition of other aromatic compounds also caused an increase in its activity, which in turn triggered NAD(P)H production via the action of dehydrogenases in the tricarboxylic acid cycle, heme biosynthesis via the action of aminolevulinic acid synthase on succinyl-CoA, and energy production via activation of the mitochondrial electron transfer system. These metabolic shifts seem to be required for activating a metabolic system for aromatic compounds.

Determination of mass attenuation coefficient in wood and leaves of typical trees by gamma-ray attenuation technique

International Nuclear Information System (INIS)

Miranda, Regina M. de; Pascholati, Elisabete M.

1997-01-01

Using an 241 Am source the mass attenuation coefficient of different woods and leaves of typical species of the Atlantic Forest were measured. The results for natural wood, dry wood and dry leaves indicate that the variation is very small among different species. However, woods present a higher attenuation than leaves, both depending on their water content. (author). 10 refs., 3 figs., 1 tab

Low Protein Diet Inhibits Uric Acid Synthesis and Attenuates Renal Damage in Streptozotocin-Induced Diabetic Rats

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Jianmin Ran

2014-01-01

Full Text Available Aim. Several studies indicated that hyperuricemia may link to the worsening of diabetic nephropathy (DN. Meanwhile, low protein diet (LPD retards exacerbation of renal damage in chronic kidney disease. We then assessed whether LPD influences uric acid metabolism and benefits the progression of DN in streptozotocin- (STZ- induced diabetic rats. Methods. STZ-induced and control rats were both fed with LPD (5% and normal protein diet (18%, respectively, for 12 weeks. Vital signs, blood and urinary samples for UA metabolism were taken and analyzed every 3 weeks. Kidneys were removed at the end of the experiment. Results. Diabetic rats developed into constantly high levels of serum UA (SUA, creatinine (SCr and 24 h amounts of urinary albumin excretion (UAE, creatintine (UCr, urea nitrogen (UUN, and uric acid (UUA. LPD significantly decreased SUA, UAE, and blood glucose, yet left SCr, UCr, and UUN unchanged. A stepwise regression showed that high UUA is an independent risk factor for DN. LPD remarkably ameliorated degrees of enlarged glomeruli, proliferated mesangial cells, and hyaline-degenerated tubular epithelial cells in diabetic rats. Expression of TNF-α in tubulointerstitium significantly decreased in LPD-fed diabetic rats. Conclusion. LPD inhibits endogenous uric acid synthesis and might accordingly attenuate renal damage in STZ-induced diabetic rats.

Modeling Cycle Dependence in Credit Insurance

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Anisa Caja

2014-03-01

Full Text Available Business and credit cycles have an impact on credit insurance, as they do on other businesses. Nevertheless, in credit insurance, the impact of the systemic risk is even more important and can lead to major losses during a crisis. Because of this, the insurer surveils and manages policies almost continuously. The management actions it takes limit the consequences of a downturning cycle. However, the traditional modeling of economic capital does not take into account this important feature of credit insurance. This paper proposes a model aiming to estimate future losses of a credit insurance portfolio, while taking into account the insurer’s management actions. The model considers the capacity of the credit insurer to take on less risk in the case of a cycle downturn, but also the inverse, in the case of a cycle upturn; so, losses are predicted with a more dynamic perspective. According to our results, the economic capital is over-estimated when not considering the management actions of the insurer.

Factors influencing seismic wave attenuation in the lithosphere in continental rift zones

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А. А. Dobrynina

2017-01-01

Full Text Available Attenuation of seismic waves in the crust and the upper mantle has been studied in three global rift systems: the Baikal rift system (Eurasia, the North Tanzanian divergence zone (Africa and the Basin and Range Province (North America. Using the records of direct and coda waves of regional earthquakes, the single scattering theory [Aki, Chouet, 1975], the hybrid model from [Zeng, 1991] and the approach described in [Wennerberg, 1993], we estimated the seismic quality factor (QC, frequency parameter (n, attenuation coefficient (δ, and total attenuation (QT. In addition, we evaluated the contributions of two components into total attenuation: intrinsic attenuation (Qi, and scattering attenuation (Qsc. Values of QC are strongly dependent on the frequency within the range of 0.2–16 Hz, as well as on the length of the coda processing window. The observed increase of QC with larger lengths of the coda processing window can be interpreted as a decrease in attenuation with increasing depth. Having compared the depth variations in the attenuation coefficient (δ and the frequency (n with the velocity structures of the studied regions, we conclude that seismic wave attenuation changes at the velocity boundaries in the medium. Moreover, the comparison results show that the estimated variations in the attenuation parameters with increasing depth are considerably dependent on utilized velocity models of the medium. Lateral variations in attenuation of seismic waves correlate with the geological and geophysical characteristics of the regions, and attenuation is primarily dependent on the regional seismic activity and regional heat flow. The geological inhomogeneities of the medium and the age of crust consolidation are secondary factors. Our estimations of intrinsic attenuation (Qi and scattering attenuation (Qsc show that in all the three studied regions, intrinsic attenuation is the major contributor to total attenuation. Our study shows that the

DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation

International Nuclear Information System (INIS)

Li, C.-C.; Lii, C.-K.; Liu, K.-L.; Yang, J.-J.; Chen, H.-W.

2007-01-01

The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation by n-6 and n-3 PUFAs of PB-induced CYP 2B1 expression in rat primary hepatocytes. We used 100 μM arachidonic acid, linoleic acid, eicosapentaenoic acid, and DHA to test this hypothesis. PB triggered the translocation of CAR from the cytosol into the nucleus in a dose-dependent and time-dependent manner in our hepatocyte system, and the CAR distribution in rat primary hepatocytes was significantly affected by DHA. DHA treatment decreased PB-inducible accumulation of CAR in the nuclear fraction and increased it in the cytosolic fraction in a dose-dependent manner. The down-regulation of CYP 2B1 expression by DHA occurred in a dose-dependent manner, and a similar pattern was found for the nuclear accumulation of CAR. The results of immunoprecipitation showed a CAR/RXR heterodimer bound to nuclear receptor binding site 1 (NR-1) of the PB-responsive enhancer module (PBREM) of the CYP 2B1gene. The EMSA results showed that PB-induced CAR binding to NR-1 was attenuated by DHA. Taken together, these results suggest that attenuation of CAR translocation and decreased subsequent binding to NR-1 are involved in DHA's down-regulation of PB-induced CYP 2B1 expression

Residual Tensile Property of Plain Woven Jute Fiber/Poly(Lactic Acid) Green Composites during Thermal Cycling.

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Katogi, Hideaki; Takemura, Kenichi; Akiyama, Motoki

2016-07-14

This study investigated the residual tensile properties of plain woven jute fiber reinforced poly(lactic acid) (PLA) during thermal cycling. Temperature ranges of thermal cycling tests were 35-45 °C and 35-55 °C. The maximum number of cycles was 10³ cycles. The quasi-static tensile tests of jute fiber, PLA, and composite were conducted after thermal cycling tests. Thermal mechanical analyses of jute fiber and PLA were conducted after thermal cycling tests. Results led to the following conclusions. For temperatures of 35-45 °C, tensile strength of composite at 10³ cycles decreased 10% compared to that of composite at 0 cycles. For temperatures of 35-55 °C, tensile strength and Young's modulus of composite at 10³ cycles decreased 15% and 10%, respectively, compared to that of composite at 0 cycles. Tensile properties and the coefficient of linear expansion of PLA and jute fiber remained almost unchanged after thermal cycling tests. From observation of a fracture surface, the length of fiber pull out in the fracture surface of composite at 10³ cycles was longer than that of composite at 0 cycles. Therefore, tensile properties of the composite during thermal cycling were decreased, probably because of the decrease of interfacial adhesion between the fiber and resin.

Glucagon Couples Hepatic Amino Acid Catabolism to mTOR-Dependent Regulation of α-Cell Mass

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Mark J. Solloway

2015-07-01

Full Text Available Understanding the regulation of islet cell mass has important implications for the discovery of regenerative therapies for diabetes. The liver plays a central role in metabolism and the regulation of endocrine cell number, but liver-derived factors that regulate α-cell and β-cell mass remain unidentified. We propose a nutrient-sensing circuit between liver and pancreas in which glucagon-dependent control of hepatic amino acid metabolism regulates α-cell mass. We found that glucagon receptor inhibition reduced hepatic amino acid catabolism, increased serum amino acids, and induced α-cell proliferation in an mTOR-dependent manner. In addition, mTOR inhibition blocked amino-acid-dependent α-cell replication ex vivo and enabled conversion of α-cells into β-like cells in vivo. Serum amino acids and α-cell proliferation were increased in neonatal mice but fell throughout postnatal development in a glucagon-dependent manner. These data reveal that amino acids act as sensors of glucagon signaling and can function as growth factors that increase α-cell proliferation.

High night temperature strongly impacts TCA cycle, amino acid and polyamine biosynthetic pathways in rice in a sensitivity-dependent manner.

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Glaubitz, Ulrike; Erban, Alexander; Kopka, Joachim; Hincha, Dirk K; Zuther, Ellen

2015-10-01

Global climate change combined with asymmetric warming can have detrimental effects on the yield of crop plants such as rice (Oryza sativa L.). Little is known about metabolic responses of rice to high night temperature (HNT) conditions. Twelve cultivars with different HNT sensitivity were used to investigate metabolic changes in the vegetative stage under HNT compared to control conditions. Central metabolism, especially TCA cycle and amino acid biosynthesis, were strongly affected particularly in sensitive cultivars. Levels of several metabolites were correlated with HNT sensitivity. Furthermore, pool sizes of some metabolites negatively correlated with HNT sensitivity under control conditions, indicating metabolic pre-adaptation in tolerant cultivars. The polyamines putrescine, spermidine and spermine showed increased abundance in sensitive cultivars under HNT conditions. Correlations between the content of polyamines and 75 other metabolites indicated metabolic shifts from correlations with sugar-phosphates and 1-kestose under control to correlations with sugars and amino and organic acids under HNT conditions. Increased expression levels of ADC2 and ODC1, genes encoding enzymes catalysing the first committed steps of putrescine biosynthesis, were restricted to sensitive cultivars under HNT. Additionally, transcript levels of eight polyamine biosynthesis genes were correlated with HNT sensitivity. Responses to HNT in the vegetative stage result in distinct differences between differently responding cultivars with a dysregulation of central metabolism and an increase of polyamine biosynthesis restricted to sensitive cultivars under HNT conditions and a pre-adaptation of tolerant cultivars already under control conditions with higher levels of potentially protective compatible solutes. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Cooperative effect of the attenuation determinants derived from poliovirus sabin 1 strain is essential for attenuation of enterovirus 71 in the NOD/SCID mouse infection model.

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Arita, Minetaro; Ami, Yasushi; Wakita, Takaji; Shimizu, Hiroyuki

2008-02-01

Enterovirus 71 (EV71) is a causative agent of hand, foot, and mouth disease and is also associated with serious neurological disorders. An attenuated EV71 strain [EV71(S1-3')] has been established in the cynomolgus monkey infection model; this strain contains the attenuation determinants derived from the type 1 poliovirus vaccine strain, Sabin 1 [PV1(Sabin)], in the 5' nontranslated region (NTR), 3D polymerase, and 3' NTR. In this study, we analyzed the effect of the attenuation determinants of PV1(Sabin) on EV71 infection in a NOD/SCID mouse infection model. We isolated a mouse-adapted EV71 strain [EV71(NOD/SCID)] that causes paralysis of the hind limbs in 3- to 4-week-old NOD/SCID mice by adaptation of the virulent EV71(Nagoya) strain in the brains of NOD/SCID mice. A single mutation at nucleotide 2876 that caused an amino acid change in capsid protein VP1 (change of the glycine at position 145 to glutamic acid) was essential for the mouse-adapted phenotype in NOD/SCID mice. Next, we introduced attenuation determinants derived from PV1(Sabin) along with the mouse adaptation mutation into the EV71(Nagoya) genome. In 4-week-old mice, the determinants in the 3D polymerase and 3' NTR, which are the major temperature-sensitive determinants, had a strong effect on attenuation. In contrast, the effect of individual determinants was weak in 3-week-old NOD/SCID mice, and all the determinants were required for substantial attenuation. These results suggest that a cooperative effect of the attenuation determinants of PV1(Sabin) is essential for attenuated neurovirulence of EV71.

Dependence of the metabolic fecal amino acids on the amino acid content of the feed. 1

International Nuclear Information System (INIS)

Krawielitzki, K.; Schadereit, R.; Voelker, T.; Reichel, K.

1981-01-01

The amount of metabolic fecal amino acids (MFAA) in dependence on the amino acid intake was determined for graded maize rations in 15 N-labelled rats and the part of labelled endogenous amino acids in feces was calculated by the isotope dilution method. The excretion of amino acids and MFAA in feces are described as functions of the amino acid intake for 17 amino acids and calculated regressively. For all 17 amino acids investigated, there was a more or less steep increase of MFAA according to an increasing amino acid intake. In contrast to N-free feeding, the MFAA increase to the 2- to 4.5-fold value in feeding with pure maize (16.5% crude protein). The thesis of the constancy of the excretion of MFAA can consequently be no longer maintained. The true digestibility according to the conventional method is, on an average of all amino acids, 7.3 units below ascertained according to the 15 N method. The limiting amino acids lysine and threonine revealed the greatest difference. Tryptophane as first limiting amino acid could not be determined. The true digestibility of nearly all amino acids ascertained for maize by the isotope method is above 90%. (author)

Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells

International Nuclear Information System (INIS)

Ryu, Chang Seon; Kwak, Hui Chan; Lee, Kye Sook; Kang, Keon Wook; Oh, Soo Jin; Lee, Ki Ho; Kim, Hwan Mook; Ma, Jin Yeul; Kim, Sang Kyum

2011-01-01

Although methionine dependency is a phenotypic characteristic of tumor cells, it remains to be determined whether changes in sulfur amino acid metabolism occur in cancer cells resistant to chemotherapeutic medications. We compared expression/activity of sulfur amino acid metabolizing enzymes and cellular levels of sulfur amino acids and their metabolites between normal MCF-7 cells and doxorubicin-resistant MCF-7 (MCF-7/Adr) cells. The S-adenosylmethionine/S-adenosylhomocysteine ratio, an index of transmethylation potential, in MCF-7/Adr cells decreased to ∼ 10% relative to that in MCF-7 cells, which may have resulted from down-regulation of S-adenosylhomocysteine hydrolase. Expression of homocysteine-clearing enzymes, such as cystathionine beta-synthase, methionine synthase/methylene tetrahydrofolate reductase, and betaine homocysteine methyltransferase, was up-regulated in MCF-7/Adr cells, suggesting that acquiring doxorubicin resistance attenuated methionine-dependence and activated transsulfuration from methionine to cysteine. Homocysteine was similar, which is associated with a balance between the increased expressions of homocysteine-clearing enzymes and decreased extracellular homocysteine. Despite an elevation in cysteine, cellular GSH decreased in MCF-7/Adr cells, which was attributed to over-efflux of GSH into the medium and down-regulation of the GSH synthesis enzyme. Consequently, MCF-7/Adr cells were more sensitive to the oxidative stress induced by bleomycin and menadione than MCF-7 cells. In conclusion, our results suggest that regulating sulfur amino acid metabolism may be a possible therapeutic target for chemoresistant cancer cells. These results warrant further investigations to determine the role of sulfur amino acid metabolism in acquiring anticancer drug resistance in cancer cells using chemical and biological regulators involved in sulfur amino acid metabolism. - Research highlights: → MCF-7/Adr cells showed decreases in cellular GSH

Measurement of carbon nanotube microstructure relative density by optical attenuation and observation of size-dependent variations.

Science.gov (United States)

Park, Sei Jin; Schmidt, Aaron J; Bedewy, Mostafa; Hart, A John

2013-07-21

Engineering the density of carbon nanotube (CNT) forest microstructures is vital to applications such as electrical interconnects, micro-contact probes, and thermal interface materials. For CNT forests on centimeter-scale substrates, weight and volume can be used to calculate density. However, this is not suitable for smaller samples, including individual microstructures, and moreover does not enable mapping of spatial density variations within the forest. We demonstrate that the relative mass density of individual CNT microstructures can be measured by optical attenuation, with spatial resolution equaling the size of the focused spot. For this, a custom optical setup was built to measure the transmission of a focused laser beam through CNT microstructures. The transmittance was correlated with the thickness of the CNT microstructures by Beer-Lambert-Bouguer law to calculate the attenuation coefficient. We reveal that the density of CNT microstructures grown by CVD can depend on their size, and that the overall density of arrays of microstructures is affected significantly by run-to-run process variations. Further, we use the technique to quantify the change in CNT microstructure density due to capillary densification. This is a useful and accessible metrology technique for CNTs in future microfabrication processes, and will enable direct correlation of density to important properties such as stiffness and electrical conductivity.

Principles for generation of time-dependent collimator settings during the LHC cycle

CERN Document Server

Bruce, R; Redaelli, S

2011-01-01

The settings of the LHC collimators have to be changed during the cycle of injection, ramp and squeeze to account for variations in the orbit, beam size and normalized distance to the beam center. We discuss the principles for how the settings are calculated and show a software tool that computes them as time-dependent functions from beambased data and theoretical optics models.

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

International Nuclear Information System (INIS)

Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

2016-01-01

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

Energy Technology Data Exchange (ETDEWEB)

Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

2016-04-15

In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

Science.gov (United States)

Obanda, Diana N; Zhao, Peng; Richard, Allison J; Ribnicky, David; Cefalu, William T; Stephens, Jacqueline M

2016-01-01

Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

Science.gov (United States)

Takahara, Ikuko; Akazawa, Yuko; Tabuchi, Maiko; Matsuda, Katsuya; Miyaaki, Hisamitsu; Kido, Youko; Kanda, Yasuko; Taura, Naota; Ohnita, Ken; Takeshima, Fuminao; Sakai, Yusuke; Eguchi, Susumu; Nakashima, Masahiro; Nakao, Kazuhiko

2017-01-01

A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.

Residual Tensile Property of Plain Woven Jute Fiber/Poly(Lactic Acid Green Composites during Thermal Cycling

Directory of Open Access Journals (Sweden)

Hideaki Katogi

2016-07-01

Full Text Available This study investigated the residual tensile properties of plain woven jute fiber reinforced poly(lactic acid (PLA during thermal cycling. Temperature ranges of thermal cycling tests were 35–45 °C and 35–55 °C. The maximum number of cycles was 103 cycles. The quasi-static tensile tests of jute fiber, PLA, and composite were conducted after thermal cycling tests. Thermal mechanical analyses of jute fiber and PLA were conducted after thermal cycling tests. Results led to the following conclusions. For temperatures of 35–45 °C, tensile strength of composite at 103 cycles decreased 10% compared to that of composite at 0 cycles. For temperatures of 35–55 °C, tensile strength and Young’s modulus of composite at 103 cycles decreased 15% and 10%, respectively, compared to that of composite at 0 cycles. Tensile properties and the coefficient of linear expansion of PLA and jute fiber remained almost unchanged after thermal cycling tests. From observation of a fracture surface, the length of fiber pull out in the fracture surface of composite at 103 cycles was longer than that of composite at 0 cycles. Therefore, tensile properties of the composite during thermal cycling were decreased, probably because of the decrease of interfacial adhesion between the fiber and resin.

The efficacy of (+)-Naltrexone on alcohol preference and seeking behaviour is dependent on light-cycle.

Science.gov (United States)

Jacobsen, Jonathan Henry W; Buisman-Pijlman, Femke T A; Mustafa, Sanam; Rice, Kenner C; Hutchinson, Mark R

2018-01-01

Circadian rhythm affects drug-induced reward behaviour and the innate immune system. Peaks in reward-associated behaviour and immune responses typically occur during the active (dark) phase of rodents. While the role of the immune system, specifically, Toll-like receptor 4 (TLR4, an innate immune receptor) in drug-induced reward is becoming increasingly appreciated, it is unclear whether its effects vary according to light-cycle. Therefore, the aim of this study was to characterise the effects of the phase of the light-cycle and the state of the innate immune system on alcohol reward behaviour and subsequently determine whether the efficacy of targeting the immune component of drug reward depends upon the light-cycle. This study demonstrates that mice exhibit greater alcohol-induced conditioned place preference and alcohol two-bottle choice preference during the dark cycle. This effect overlapped with elevations in reward-, thirst- and immune-related genes. Administration of (+)-Naltrexone, a TLR4 antagonist, reduced immune-related gene mRNA expression and alcohol preference with its effects most pronounced during the dark cycle. However, (+)-Naltrexone, like other TLR4 antagonists exhibited off-target side effects, with a significant reduction in overall saccharin intake - an effect likely attributable to a reduction in tyrosine hydroxylase (Th) mRNA expression levels. Collectively, the study highlights a link between a time-of-day dependent influence of TLR4 on natural and alcohol reward-like behaviour in mice. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of tricarboxylic acid cycle regulator on carbon retention and organic component transformation during food waste composting.

Science.gov (United States)

Lu, Qian; Zhao, Yue; Gao, Xintong; Wu, Junqiu; Zhou, Haixuan; Tang, Pengfei; Wei, Qingbin; Wei, Zimin

2018-05-01

Composting is an environment friendly method to recycling organic waste. However, with the increasing concern about greenhouse gases generated in global atmosphere, it is significant to reduce the emission of carbon dioxide (CO 2 ). This study analyzes tricarboxylic acid (TCA) cycle regulators on the effect of reducing CO 2 emission, and the relationship among organic component (OC) degradation and transformation and microorganism during composting. The results showed that adding adenosine tri-phosphate (ATP) and nicotinamide adenine dinucleotide (NADH) could enhance the transformation of OC and increase the diversity of microorganism community. Malonic acid (MA) as a competitive inhibitor could decrease the emission of CO 2 by inhibiting the TCA cycle. A structural equation model was established to explore effects of different OC and microorganism on humic acid (HA) concentration during composting. Furthermore, added MA provided an environmental benefit in reducing the greenhouse gas emission for manufacture sustainable products. Copyright © 2018 Elsevier Ltd. All rights reserved.

Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle

DEFF Research Database (Denmark)

Pedersen, Line; Holkmann Olsen, Caroline; Pedersen, Bente Klarlund

2012-01-01

Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expres...... in muscle angiogenesis. In conclusion, our data show that overexpression of CXCL1 within a physiological range attenuates diet-induced obesity, likely mediated through a CXCL1-induced improvement of fatty acid oxidation and oxidative capacity in skeletal muscle tissue....

Systematic engineering of TCA cycle for optimal production of a four-carbon platform chemical 4-hydroxybutyric acid in Escherichia coli.

Science.gov (United States)

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

2016-11-01

To address climate change and environmental problems, it is becoming increasingly important to establish biorefineries for the production of chemicals from renewable non-food biomass. Here we report the development of Escherichia coli strains capable of overproducing a four-carbon platform chemical 4-hybroxybutyric acid (4-HB). Because 4-HB production is significantly affected by aeration level, genome-scale metabolic model-based engineering strategies were designed under aerobic and microaerobic conditions with emphasis on oxidative/reductive TCA branches and glyoxylate shunt. Several different metabolic engineering strategies were employed to develop strains suitable for fermentation both under aerobic and microaerobic conditions. It was found that microaerobic condition was more efficient than aerobic condition in achieving higher titer and productivity of 4-HB. The final engineered strain produced 103.4g/L of 4-HB by microaerobic fed-batch fermentation using glycerol. The aeration-dependent optimization strategy of TCA cycle will be useful for developing microbial strains producing other reduced derivative chemicals of TCA cycle intermediates. Copyright © 2016 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase.

Science.gov (United States)

Liu, Xinran; Musser, Derek M; Lee, Cheri A; Yang, Xiaorong; Arnold, Jamie J; Cameron, Craig E; Boehr, David D

2015-10-26

The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I) in the RNA-dependent RNA polymerase (RdRp). We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E) help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.

Use of Activated Carbon in Packaging to Attenuate Formaldehyde-Induced and Formic Acid-Induced Degradation and Reduce Gelatin Cross-Linking in Solid Dosage Forms.

Science.gov (United States)

Colgan, Stephen T; Zelesky, Todd C; Chen, Raymond; Likar, Michael D; MacDonald, Bruce C; Hawkins, Joel M; Carroll, Sophia C; Johnson, Gail M; Space, J Sean; Jensen, James F; DeMatteo, Vincent A

2016-07-01

Formaldehyde and formic acid are reactive impurities found in commonly used excipients and can be responsible for limiting drug product shelf-life. Described here is the use of activated carbon in drug product packaging to attenuate formaldehyde-induced and formic acid-induced drug degradation in tablets and cross-linking in hard gelatin capsules. Several pharmaceutical products with known or potential vulnerabilities to formaldehyde-induced or formic acid-induced degradation or gelatin cross-linking were subjected to accelerated stability challenges in the presence and absence of activated carbon. The effects of time and storage conditions were determined. For all of the products studied, activated carbon attenuated drug degradation or gelatin cross-linking. This novel use of activated carbon in pharmaceutical packaging may be useful for enhancing the chemical stability of drug products or the dissolution stability of gelatin-containing dosage forms and may allow for the 1) extension of a drug product's shelf-life when the limiting attribute is a degradation product induced by a reactive impurity, 2) marketing of a drug product in hotter and more humid climatic zones than currently supported without the use of activated carbon, and 3) enhanced dissolution stability of products that are vulnerable to gelatin cross-linking. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells

Directory of Open Access Journals (Sweden)

Li HF

2015-06-01

Full Text Available Huai-Feng Li,1–3,* Xu-An Wang,1–3,* Shan-Shan Xiang,1–3,* Yun-Ping Hu,1–3 Lin Jiang,1–3 Yi-Jun Shu,1–3 Mao-Lan Li,1–3 Xiang-Song Wu,1–3 Fei Zhang,1–3 Yuan-Yuan Ye,1–3 Hao Weng,1–3 Run-Fa Bao,1–3 Yang Cao,1–3 Wei Lu,1–3 Qian Dong,1–3 Ying-Bin Liu1–3 1Department of General Surgery, 2Laboratory of General Surgery, 3Institute of Biliary Tract Disease, Xinhua Hospital, Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Oleanolic acid (OA, a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma. Keywords: oleanolic acid, gallbladder carcinoma, apoptosis, cell cycle arrest, mitochondrial pathway

Sulfuric acid nucleation: power dependencies, variation with relative humidity, and effect of bases

Directory of Open Access Journals (Sweden)

J. H. Zollner

2012-05-01

Full Text Available Nucleation of particles composed of sulfuric acid, water, and nitrogen base molecules was studied using a continuous flow reactor. The particles formed from these vapors were detected with an ultrafine condensation particle counter, while vapors of sulfuric acid and nitrogen bases were detected by chemical ionization mass spectrometry. Variation of particle numbers with sulfuric acid concentration yielded a power dependency on sulfuric acid of 5 ± 1 for relative humidities of 14–68% at 296 K; similar experiments with varying water content yielded power dependencies on H₂O of ~7. The critical cluster contains about 5 H₂SO₄ molecules and a new treatment of the power dependency for H₂O suggests about 12 H₂O molecules for these conditions. Addition of 2-to-45 pptv of ammonia or methyl amine resulted in up to millions of times more particles than in the absence of these compounds. Particle detection capabilities, sulfuric acid and nitrogen base detection, wall losses, and the extent of particle growth are discussed. Results are compared to previous laboratory nucleation studies and they are also discussed in terms of atmospheric nucleation scenarios.

Systemic treatment with n-6 polyunsaturated fatty acids attenuates EL4 thymoma growth and metastasis through enhancing specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines.

Science.gov (United States)

Salem, Mohamed Labib

2005-06-01

Recently, there has been a great interest in the effects of different types of n-6 polyunsaturated acids (n-6 PUFAs) upon the immune system and cancer development. However, the effects of n-6 PUFAs are still controversial and as yet undefined. The present study aimed to investigate the anti-tumor effects of n-6 PUFAs against EL4 thymoma and the associated immune mechanisms. To this, sesame oil, a vegetable oil enriched with n-6 PUFAs, or free linoleic acid (LA) were administered intraperitoneally into C57BL/6 mice before and after challenge with EL4 lymphoma cells. Treatment with either sesame oil or LA attenuated the growth and metastasis of EL4 lymphoma. The anti-tumor effect of LA was superior to that of sesame oil, and associated with an increase in the survival rate of the tumor-bearing mice. In addition, both sesame oil and LA showed dose-dependent anti-lymphoma growth in vitro. Treatment with LA generated significant increases in the anti-lymphoma cytolytic and cytostatic activities of T cells and macrophages, respectively, and enhanced production of IL-2 and IFN-gamma while decreased production of IL-4, IL-6 and IL-10. In summation, the results suggest that n-6 PUFAs, represented by LA, can attenuate EL4 lymphoma growth and metastasis through enhancing the specific and non-specific anti-tumor cytolytic activities and production of TH1 cytokines. These findings might be of great importance for a proper design of systemic nourishment with PUFAs emulsions for cancer patients.

Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK.

Science.gov (United States)

Siddesha, Jalahalli M; Valente, Anthony J; Sakamuri, Siva S V P; Gardner, Jason D; Delafontaine, Patrice; Noda, Makoto; Chandrasekar, Bysani

2014-07-01

The pathogenesis of cardiac fibrosis and adverse remodeling is thought to involve the ROS-dependent induction of inflammatory cytokines and matrix metalloproteinases (MMPs), and the activation and migration of cardiac fibroblasts (CF). Here we investigated the role of RECK (reversion-inducing-cysteine-rich protein with Kazal motifs), a unique membrane-anchored MMP regulator, on IL-18-induced CF migration, and the effect of acetylsalicylic acid (ASA) on this response. In a Matrigel invasion assay, IL-18-induced migration of primary mouse CF was dependent on both IKK/NF-κB- and JNK/AP-1-mediated MMP9 induction and Sp1-mediated RECK suppression, mechanisms that required Nox4-dependent H(2)O(2) generation. Notably, forced expression of RECK attenuated IL-18-induced MMP9 activation and CF migration. Further, therapeutic concentrations of ASA inhibited IL-18-induced H(2)O(2) generation, MMP9 activation, RECK suppression, and CF migration. The salicylic acid moiety of ASA similarly attenuated IL-18-induced CF migration. Thus, ASA may exert potential beneficial effect in cardiac fibrosis through multiple protective mechanisms. © 2013 Wiley Periodicals, Inc.

Ketoconazole attenuates radiation-induction of tumor necrosis factor

Energy Technology Data Exchange (ETDEWEB)

Hallahan, D.E.; Virudachalam, S.; Kufe, D.W.; Weichselbaum, R.R. [Dana Farber Cancer Institute, Boston, MA (United States)

1994-07-01

Previous work has demonstrated that inhibitors of phospholipase A2 attenuate ionizing radiation-induced arachidonic acid production, protein kinase C activation, and prevent subsequent induction of the tumor necrosis factor gene. Because arachidonic acid contributes to radiation-induced tumor necrosis factor expression, the authors analyzed the effects of agents which alter arachidonate metabolism on the regulation of this gene. Phospholipase A2 inhibitors quinicrine, bromphenyl bromide, and pentoxyfylline or the inhibitor of lipoxygenase (ketoconazole) or the inhibitor of cycloxygenase (indomethacine) were added to cell culture 1 h prior to irradiation. Radiation-induced tumor necrosis factor gene expression was attenuated by each of the phospholipase A2 inhibitors (quinicrine, bromphenylbromide, and pentoxyfylline). Furthermore, ketoconazole attenuated X ray induced tumor necrosis factor gene expression. Conversely, indomethacin enhanced tumor necrosis factor expression following irradiation. The finding that radiation-induced tumor necrosis factor gene expression was attenuated by ketoconazole suggests that the lipoxygenase pathway participates in signal transduction preceding tumor necrosis factor induction. Enhancement of tumor necrosis factor expression by indomethacin following irradiation suggests that prostaglandins produced by cyclooxygenase act as negative regulators of tumor necrosis factor expression. Inhibitors of tumor necrosis factor induction ameliorate acute and subacute sequelae of radiotherapy. The authors propose therefore, that ketoconazole may reduce acute radiation sequelae such as mucositis and esophagitis through a reduction in tumor necrosis factor induction or inhibition of phospholipase A2 in addition to its antifungal activity. 25 refs., 2 figs.

Attenuation of methamphetamine-induced nigrostriatal dopaminergic neurotoxicity in mice by lipopolysaccharide pretreatment.

Science.gov (United States)

Lin, Yin Chiu; Kuo, Yu-Min; Liao, Pao-Chi; Cherng, Chianfang G; Su, Su-Wen; Yu, Lung

2007-04-30

Immunological activation has been proposed to play a role in methamphetamine-induced dopaminergic terminal damage. In this study, we examined the roles of lipopolysaccharide, a pro-inflammatory and inflammatory factor, treatment in modulating the methamphetamine-induced nigrostriatal dopamine neurotoxicity. Lipopolysaccharide pretreatment did not affect the basal body temperature or methamphetamine-elicited hyperthermia three days later. Such systemic lipopolysaccharide treatment mitigated methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions in a dose-dependent manner. As the most potent dose (1 mg/kg) of lipopolysaccharide was administered two weeks, one day before or after the methamphetamine dosing regimen, methamphetamine-induced striatal dopamine and 3,4-dihydroxyphenylacetic acid depletions remained unaltered. Moreover, systemic lipopolysaccharide pretreatment (1 mg/kg) attenuated local methamphetamine infusion-produced dopamine and 3,4-dihydroxyphenylacetic acid depletions in the striatum, indicating that the protective effect of lipopolysaccharide is less likely due to interrupted peripheral distribution or metabolism of methamphetamine. We concluded a critical time window for systemic lipopolysaccharide pretreatment in exerting effective protection against methamphetamine-induced nigrostriatal dopamine neurotoxicity.

Presence of bile acids in human follicular fluid and their relation with embryo development in modified natural cycle IVF

NARCIS (Netherlands)

Nagy, R. A.; van Montfoort, A. P. A.; Dikkers, A.; van Echten-Arends, J.; Homminga, I.; Land, J. A.; Hoek, A.; Tietge, U. J. F.

STUDY QUESTION: Are bile acids (BA) and their respective subspecies present in human follicular fluid (FF) and do they relate to embryo quality in modified natural cycle IVF (MNC-IVF)? SUMMARY ANSWER: BAconcentrations are 2-fold higher in follicular fluid than in serum and ursodeoxycholic acid

Numerical analysis and field study of time dependent exergy-energy of a gas-steam combined cycle

Directory of Open Access Journals (Sweden)

Barari Bamdad

2012-01-01

Full Text Available In this study, time dependent exergy analysis of the Fars Combined Power Plant Cycle has been investigated. Exergy analysis has been used for investigating each part of actual combined cycle by considering irreversibility from Apr 2006 to Oct 2010. Performance analysis has been done for each part by evaluating exergy destruction in each month. By using of exergy analysis, aging of each part has been evaluated respect to time duration. In addition, the rate of lost work for each month has been calculated and variation of this parameter has been considered as a function of aging rate. Finally, effects of exergy destruction of each part have been investigated on exergy destruction of whole cycle. Entire analysis has been done for Unit 3 and 4 of gas turbine cycle which combined by Unit B of steam cycle in Fars Combined Power Plant Cycle located in Fars province in Iran.

Believing and perceiving: authorship belief modulates sensory attenuation.

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Andrea Desantis

Full Text Available Sensory attenuation refers to the observation that self-generated stimuli are attenuated, both in terms of their phenomenology and their cortical response compared to the same stimuli when generated externally. Accordingly, it has been assumed that sensory attenuation might help individuals to determine whether a sensory event was caused by themselves or not. In the present study, we investigated whether this dependency is reciprocal, namely whether sensory attenuation is modulated by prior beliefs of authorship. Participants had to judge the loudness of auditory effects that they believed were either self-generated or triggered by another person. However, in reality, the sounds were always triggered by the participants' actions. Participants perceived the tones' loudness attenuated when they believed that the sounds were self-generated compared to when they believed that they were generated by another person. Sensory attenuation is considered to contribute to the emergence of people's belief of authorship. Our results suggest that sensory attenuation is also a consequence of prior belief about the causal link between an action and a sensory change in the environment.

Betulinic Acid Inhibits Growth of Cultured Vascular Smooth Muscle Cells In Vitro by Inducing G1 Arrest and Apoptosis

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Raja Kumar Vadivelu

2012-01-01

Full Text Available Betulinic acid is a widely available plant-derived triterpene which is reported to possess selective cytotoxic activity against cancer cells of neuroectodermal origin and leukemia. However, the potential of betulinic acid as an antiproliferative and cytotoxic agent on vascular smooth muscle (VSMC is still unclear. This study was carried out to demonstrate the antiproliferative and cytotoxic effect of betulinic acid on VSMCs using 3-[4,5-dimethylthizol-2-yl]-2,5-diphenyltetrazolium bromide (MTT assay, flow cytometry cell cycle assay, BrdU proliferation assay, acridine orange/propidium iodide staining, and comet assay. Result from MTT and BrdU assays indicated that betulinic acid was able to inhibit the growth and proliferation of VSMCs in a dose-dependent manner with IC50 of 3.8 μg/mL significantly (P<0.05. Nevertheless, betulinic acid exhibited G1 cell cycle arrest in flow cytometry cell cycle profiling and low level of DNA damage against VSMC in acridine orange/propidium iodide and comet assay after 24 h of treatment. In conclusion, betulinic acid induced G1 cell cycle arrest and dose-dependent DNA damage on VSMC.

Stimulation of apical sodium-dependent bile acid transporter expands the bile acid pool and generates bile acids with positive feedback properties.

Science.gov (United States)

Rudling, Mats; Bonde, Ylva

2015-01-01

Bile acid synthesis has been considered a prototype for how a physiological process is controlled by end product feedback inhibition. By this feedback inhibition, bile acid concentrations are kept within safe ranges. However, careful examination of published rodent data strongly suggests that bile acid synthesis is also under potent positive feedback control by hydrophilic bile acids. Current concepts on the regulation of bile acid synthesis are derived from mouse models. Recent data have shown that mice have farnesoid X receptor (FXR) antagonistic bile acids capable of quenching responses elicited by FXR agonistic bile acids. This is important to recognize to understand the regulation of bile acid synthesis in the mouse, and in particular to clarify if mouse model findings are valid also in the human situation. In addition to classic end product feedback inhibition, regulation of bile acid synthesis in the mouse largely appears also to be driven by changes in hepatic levels of murine bile acids such as α- and β-muricholic acids. This has not been previously recognized. Stimulated bile acid synthesis or induction of the apical sodium-dependent bile acid transporter in the intestine, increase the availability of chenodeoxycholic acid in the liver, thereby promoting hepatic conversion of this bile acid into muricholic acids. Recognition of these mechanisms is essential for understanding the regulation of bile acid synthesis in the mouse, and for our awareness of important species differences in the regulation of bile acid synthesis in mice and humans. 2015 S. Karger AG, Basel.

Angular-dependent light scattering from cancer cells in different phases of the cell cycle.

Science.gov (United States)

Lin, Xiaogang; Wan, Nan; Weng, Lingdong; Zhou, Yong

2017-10-10

Cancer cells in different phases of the cell cycle result in significant differences in light scattering properties. In order to harvest cancer cells in particular phases of the cell cycle, we cultured cancer cells through the process of synchronization. Flow cytometric analysis was applied to check the results of cell synchronization and prepare for light scattering measurements. Angular-dependent light scattering measurements of cancer cells arrested in the G1, S, and G2 phases have been performed. Based on integral calculations for scattering intensities from 5° to 10° and from 110° to 150°, conclusions have been reached. Clearly, the sizes of the cancer cells in different phases of the cell cycle dominated the forward scatter. Accompanying the increase of cell size with the progression of the cell cycle, the forward scattering intensity also increased. Meanwhile, the DNA content of cancer cells in every phase of the cell cycle is responsible for light scattering at large scatter angles. The higher the DNA content of cancer cells was, the greater the positive effect on the high-scattering intensity. As expected, understanding the relationships between the light scattering from cancer cells and cell cycles will aid in the development of cancer diagnoses. Also, it may assist in the guidance of antineoplastic drugs clinically.

Arabidopsis MAP kinase 4 regulates salicylic acid- and jasmonic acid/ethylene-dependent responses via EDS1 and PAD4

DEFF Research Database (Denmark)

Brodersen, P; Petersen, M; Nielsen, Henrik Bjørn

2006-01-01

Arabidopsis MPK4 has been implicated in plant defense regulation because mpk4 knockout plants exhibit constitutive activation of salicylic acid (SA)-dependent defenses, but fail to induce jasmonic acid (JA) defense marker genes in response to JA. We show here that mpk4 mutants are also defective...

Photosynthetic efficiency of Chlamydomonas reinhardtii in attenuated, flashing light

NARCIS (Netherlands)

Vejrazka, C.; Janssen, M.G.J.; Streefland, M.; Wijffels, R.H.

2012-01-01

As a result of mixing and light attenuation, algae in a photobioreactor (PBR) alternate between light and dark zones and, therefore, experience variations in photon flux density (PFD). These variations in PFD are called light/dark (L/D) cycles. The objective of this study was to determine how these

Diversion of phagosome trafficking by pathogenic Rhodococcus equi depends on mycolic acid chain length.

Science.gov (United States)

Sydor, Tobias; von Bargen, Kristine; Hsu, Fong-Fu; Huth, Gitta; Holst, Otto; Wohlmann, Jens; Becken, Ulrike; Dykstra, Tobias; Söhl, Kristina; Lindner, Buko; Prescott, John F; Schaible, Ulrich E; Utermöhlen, Olaf; Haas, Albert

2013-03-01

Rhodococcus equi is a close relative of Mycobacterium spp. and a facultative intracellular pathogen which arrests phagosome maturation in macrophages before the late endocytic stage. We have screened a transposon mutant library of R. equi for mutants with decreased capability to prevent phagolysosome formation. This screen yielded a mutant in the gene for β-ketoacyl-(acyl carrier protein)-synthase A (KasA), a key enzyme of the long-chain mycolic acid synthesizing FAS-II system. The longest kasA mutant mycolic acid chains were 10 carbon units shorter than those of wild-type bacteria. Coating of non-pathogenic E. coli with purified wild-type trehalose dimycolate reduced phagolysosome formation substantially which was not the case with shorter kasA mutant-derived trehalose dimycolate. The mutant was moderately attenuated in macrophages and in a mouse infection model, but was fully cytotoxic.Whereas loss of KasA is lethal in mycobacteria, R. equi kasA mutant multiplication in broth was normal proving that long-chain mycolic acid compounds are not necessarily required for cellular integrity and viability of the bacteria that typically produce them. This study demonstrates a central role of mycolic acid chain length in diversion of trafficking by R. equi. © 2012 Blackwell Publishing Ltd.

Effects of valproic acid and pioglitazone on cell cycle progression and proliferation of T-cell acute lymphoblastic leukemia Jurkat cells

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Marie Saghaeian Jazi

2016-07-01

Full Text Available Objective(s: T-cell acute lymphoblastic leukemia (T-ALL is an aggressive hematologic malignant tumor. Administration of chemical compounds influencing apoptosis and T cell development has been discussed as promising novel therapeutic strategies. Valproic acid (VPA as a recently emerged anti-neoplastic histone deacetylase (HDAC inhibitor and pioglitazone (PGZ as a high-affinity peroxisome proliferator-activated receptor-gamma (PPARγ agonist have been shown to induce apoptosis and cell cycle arrest in different studies. Here, we aimed to investigate the underlying molecular mechanisms involved in anti-proliferative effects of these compounds on human Jurkat cells. Materials and Methods: Treated cells were evaluated for cell cycle progression and apoptosis using flowcytometry and MTT viability assay. Real-time RT-PCR was carried out to measure the alterations in key genes associated with cell death and cell cycle arrest. Results: Our findings illustrated that both VPA and PGZ can inhibit Jurkat E6.1 cells in vitro after   24 hr; however, PGZ 400 μM presents the most anti-proliferative effect. Interestingly, treated cells have been arrested in G2/M with deregulated cell division cycle 25A (Cdc25A phosphatase and cyclin-dependent kinase inhibitor 1B (CDKN1B or p27 expression. Expression of cyclin D1 gene was inhibited when DNA synthesis entry was declined. Cell cycle deregulation in PGZ and VPA-exposed cells generated an increase in the proportion of aneuploid cell population, which has not reported before. Conclusion: These findings define that anti-proliferative effects of PGZ and VPA on Jurkat cell line are mediated by cell cycle deregulation. Thus, we suggest PGZ and VPA may relieve potential therapeutic application against apoptosis-resistant malignancies.

Cell cycle dependent changes in the plasma membrane organization of mammalian cells.

Science.gov (United States)

Denz, Manuela; Chiantia, Salvatore; Herrmann, Andreas; Mueller, Peter; Korte, Thomas; Schwarzer, Roland

2017-03-01

Lipid membranes are major structural elements of all eukaryotic and prokaryotic organisms. Although many aspects of their biology have been studied extensively, their dynamics and lateral heterogeneity are still not fully understood. Recently, we observed a cell-to-cell variability in the plasma membrane organization of CHO-K1 cells (Schwarzer et al., 2014). We surmised that cell cycle dependent changes of the individual cells from our unsynchronized cell population account for this phenomenon. In the present study, this hypothesis was tested. To this aim, CHO-K1 cells were arrested in different cell cycle phases by chemical treatments, and the order of their plasma membranes was determined by various fluorescent lipid analogues using fluorescence lifetime imaging microscopy. Our experiments exhibit significant differences in the membrane order of cells arrested in the G2/M or S phase compared to control cells. Our single-cell analysis also enabled the specific selection of mitotic cells, which displayed a significant increase of the membrane order compared to the control. In addition, the lipid raft marker GPImYFP was used to study the lateral organization of cell cycle arrested cells as well as mitotic cells and freely cycling samples. Again, significant differences were found between control and arrested cells and even more pronounced between control and mitotic cells. Our data demonstrate a direct correlation between cell cycle progression and plasma membrane organization, underlining that cell-to-cell heterogeneities of membrane properties have to be taken into account in cellular studies especially at the single-cell level. Copyright © 2016 Elsevier B.V. All rights reserved.

Ammonium generation during SRAT cycle

International Nuclear Information System (INIS)

Hsu, C.W.

1992-01-01

During the IDMS noble-metal demonstration runs ammonium nitrate deposition was found in the vessel vent system of the feed preparation area. In the bench-scale experiments of studying the hydrogen generation during the sludge treatment cycle, ammonium ion production was also monitored. It was found that: During a simulation of the DWPF Cold Chemical Runs SRAT cycle no detectable amount of ammonium ions was generated when treating a non-noble-metal containing sludge simulant according to the nitric acid flowsheet. Ammonium ions were generated during the SRAT-SME cycle when treating the noble-metal containing sludge with either formic acid or nitric acid/late-washing PHA. This is due to the reaction between formic acid and nitrate catalyzed by the noble metals in the sludge simulant. Ammonium ion production closely followed the hydrogen evolution from the catalytic decomposition of formic acid. This report summarizes the results of the production of ammonia during the SRAT cycle

The mitochondrial pyruvate carrier mediates high fat diet-induced increases in hepatic TCA cycle capacity.

Science.gov (United States)

Rauckhorst, Adam J; Gray, Lawrence R; Sheldon, Ryan D; Fu, Xiaorong; Pewa, Alvin D; Feddersen, Charlotte R; Dupuy, Adam J; Gibson-Corley, Katherine N; Cox, James E; Burgess, Shawn C; Taylor, Eric B

2017-11-01

Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions. The goal of this investigation was to test whether hepatocyte MPC disruption provides sustained protection from hyperglycemia during long-term HFD and the differential effects of hepatocyte MPC disruption on TCA cycle metabolism in NCD versus HFD conditions. We utilized long-term high fat feeding, serial measurements of postabsorptive blood glucose and metabolomic profiling and 13 C-lactate/ 13 C-pyruvate tracing to investigate the contribution of the MPC to hyperglycemia and altered hepatic TCA cycle metabolism during HFD-induced obesity. Hepatocyte MPC disruption resulted in long-term attenuation of hyperglycemia induced by HFD. HFD increased hepatic mitochondrial pyruvate utilization and TCA cycle capacity in an MPC-dependent manner. Furthermore, MPC disruption decreased progression of fibrosis and levels of transcript markers of inflammation. By contributing to chronic hyperglycemia, fibrosis, and TCA cycle expansion, the hepatocyte MPC is a key mediator of the pathophysiology induced in the HFD model of T2D. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

TOOLS OF MARKETING COMMUNICATIONS IN POLITICS AND THE ECONOMY, DEPENDING ON THE LIFE CYCLE

Directory of Open Access Journals (Sweden)

Tatyana L. Shklyar

2014-01-01

Full Text Available This article demonstrates how much can be similar absolutely different areas as politics and economy.Analyzing the approaches to marketing in these areas, you can gather a lot of valuable and useful. The authors discuss the tools of marketing communications, depending on the life cycle of goods and drawa parallel between business and politics. Note that thetools of marketing communications are very numerousand diverse but is most effective at a particular time. Provides specific recommendations on the relevance of tools, aimed at promotion of the goods in the certaintime intervals life cycle.

Genetic Investigation of Tricarboxylic Acid Metabolism during the Plasmodium falciparum Life Cycle

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Hangjun Ke

2015-04-01

Full Text Available New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO lines that delete six of the eight mitochondrial tricarboxylic acid (TCA cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of 13C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development.

PET attenuation coefficients from CT images: experimental evaluation of the transformation of CT into PET 511-keV attenuation coefficients.

Science.gov (United States)

Burger, C; Goerres, G; Schoenes, S; Buck, A; Lonn, A H R; Von Schulthess, G K

2002-07-01

The CT data acquired in combined PET/CT studies provide a fast and essentially noiseless source for the correction of photon attenuation in PET emission data. To this end, the CT values relating to attenuation of photons in the range of 40-140 keV must be transformed into linear attenuation coefficients at the PET energy of 511 keV. As attenuation depends on photon energy and the absorbing material, an accurate theoretical relation cannot be devised. The transformation implemented in the Discovery LS PET/CT scanner (GE Medical Systems, Milwaukee, Wis.) uses a bilinear function based on the attenuation of water and cortical bone at the CT and PET energies. The purpose of this study was to compare this transformation with experimental CT values and corresponding PET attenuation coefficients. In 14 patients, quantitative PET attenuation maps were calculated from germanium-68 transmission scans, and resolution-matched CT images were generated. A total of 114 volumes of interest were defined and the average PET attenuation coefficients and CT values measured. From the CT values the predicted PET attenuation coefficients were calculated using the bilinear transformation. When the transformation was based on the narrow-beam attenuation coefficient of water at 511 keV (0.096 cm(-1)), the predicted attenuation coefficients were higher in soft tissue than the measured values. This bias was reduced by replacing 0.096 cm(-1) in the transformation by the linear attenuation coefficient of 0.093 cm(-1) obtained from germanium-68 transmission scans. An analysis of the corrected emission activities shows that the resulting transformation is essentially equivalent to the transmission-based attenuation correction for human tissue. For non-human material, however, it may assign inaccurate attenuation coefficients which will also affect the correction in neighbouring tissue.

Stinging Nettle (Urtica dioica L. Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

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Diana N Obanda

Full Text Available Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle improves insulin action, yet the precise mechanism(s are not known. Hence, we examined the effects of Urtica dioica L. (UT on adipocytes.We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined.As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation.In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

Business Cycle Dependent Unemployment Insurance

DEFF Research Database (Denmark)

Andersen, Torben M.; Svarer, Michael

The consequences of business cycle contingencies in unemployment insurance systems are considered in a search-matching model allowing for shifts between "good" and "bad" states of nature. We show that not only is there an insurance argument for such contingencies, but there may also be an incentive...

An incomplete TCA cycle increases survival of Salmonella Typhimurium during infection of resting and activated murine macrophages.

Science.gov (United States)

Bowden, Steven D; Ramachandran, Vinoy K; Knudsen, Gitte M; Hinton, Jay C D; Thompson, Arthur

2010-11-08

In comparison to the comprehensive analyses performed on virulence gene expression, regulation and action, the intracellular metabolism of Salmonella during infection is a relatively under-studied area. We investigated the role of the tricarboxylic acid (TCA) cycle in the intracellular replication of Salmonella Typhimurium in resting and activated macrophages, epithelial cells, and during infection of mice. We constructed deletion mutations of 5 TCA cycle genes in S. Typhimurium including gltA, mdh, sdhCDAB, sucAB, and sucCD. We found that the mutants exhibited increased net intracellular replication in resting and activated murine macrophages compared to the wild-type. In contrast, an epithelial cell infection model showed that the S. Typhimurium ΔsucCD and ΔgltA strains had reduced net intracellular replication compared to the wild-type. The glyoxylate shunt was not responsible for the net increased replication of the TCA cycle mutants within resting macrophages. We also confirmed that, in a murine infection model, the S. Typhimurium ΔsucAB and ΔsucCD strains are attenuated for virulence. Our results suggest that disruption of the TCA cycle increases the ability of S. Typhimurium to survive within resting and activated murine macrophages. In contrast, epithelial cells are non-phagocytic cells and unlike macrophages cannot mount an oxidative and nitrosative defence response against pathogens; our results show that in HeLa cells the S. Typhimurium TCA cycle mutant strains show reduced or no change in intracellular levels compared to the wild-type. The attenuation of the S. Typhimurium ΔsucAB and ΔsucCD mutants in mice, compared to their increased net intracellular replication in resting and activated macrophages suggest that Salmonella may encounter environments within the host where a complete TCA cycle is advantageous.

Duty cycle dependence of a periodically poled LiNbO3-based electro-optic Solc filter.

Science.gov (United States)

Rabia, Eyal; Arie, Ady

2006-01-20

We demonstrate that the performance of a periodically poled LiNbO3- (PPLN-) based electro-optic Solc filter is dependent on the duty cycle of the crystal. This may limit the performance of the device for applications such as add-drop filtering and switching, owing to the deterioration of the extinction ratio. It is shown that by adding a retarder to the Solc filter it is possible to improve the extinction ratio; thus the dependence of the filter on the duty cycle can be reduced. Using Jones calculus, we analyzed the effect of a variable retarder that can also be rotated on the extinction ratio. We experimentally observed a 6 dB increase in the extinction ratio when we used a half-wavelength retarder.

Omega-3 polyunsaturated fatty acid docosahexaenoic acid and its role in exhaustive-exercise-induced changes in female rat ovulatory cycle.

Science.gov (United States)

Mostafa, Abeer F; Samir, Shereen M; Nagib, R M

2018-04-01

Exhaustive exercises can cause delayed menarche or menstrual cycle irregularities in females. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) are incorporated into a wide range of benefits in many physiological systems. Our work aimed to assess the role of ω-3 PUFA docosahexaenoic acid (DHA) on the deleterious effects of exhaustive exercise on the female reproductive system in rats. Virgin female rats were randomly divided into 4 groups (12 rats in each): control group, omega-3 group treated with DHA, exhaustive exercise group, and exhaustive exercised rats treated with DHA. Omega-3 was given orally to the rats once daily for 4 estrous cycles. Exhaustive exercises revealed lower levels in progesterone and gonadotropins together with histopathological decrease in number of growing follicles and corpora lutea. Moreover, the exercised rats showed low levels of ovarian antioxidants with high level of caspase-3 and plasma cortisol level that lead to disruption of hypothalamic-pituitary-gonadal axis. ω-3 PUFA DHA has beneficial effects on the number of newly growing follicles in both sedentary and exercised rats with decreasing the level of caspase-3 and increasing the antioxidant activity in ovaries. Exhaustive exercises can cause ovulatory problems in female rats that can be improved by ω-3 supplementation.

Determination of intrinsic attenuation in the oceanic lithosphere-asthenosphere system

Science.gov (United States)

Takeuchi, Nozomu; Kawakatsu, Hitoshi; Shiobara, Hajime; Isse, Takehi; Sugioka, Hiroko; Ito, Aki; Utada, Hisashi

2017-12-01

We recorded P and S waves traveling through the oceanic lithosphere-asthenosphere system (LAS) using broadband ocean-bottom seismometers in the northwest Pacific, and we quantitatively separated the intrinsic (anelastic) and extrinsic (scattering) attenuation effects on seismic wave propagation to directly infer the thermomechanical properties of the oceanic LAS. The strong intrinsic attenuation in the asthenosphere obtained at higher frequency (~3 hertz) is comparable to that constrained at lower frequency (~100 seconds) by surface waves and suggests frequency-independent anelasticity, whereas the intrinsic attenuation in the lithosphere is frequency dependent. This difference in frequency dependence indicates that the strong and broad peak dissipation recently observed in the laboratory exists only in the asthenosphere and provides new insight into what distinguishes the asthenosphere from the lithosphere.

Backup pathways of NHEJ in cells of higher eukaryotes: Cell cycle dependence

International Nuclear Information System (INIS)

Iliakis, George

2009-01-01

DNA double-strand breaks (DSBs) induced by ionizing radiation (IR) in cells of higher eukaryotes are predominantly repaired by a pathway of non-homologous end joining (NHEJ) utilizing Ku, DNA-PKcs, DNA ligase IV, XRCC4 and XLF/Cernunnos (D-NHEJ) as central components. Work carried out in our laboratory and elsewhere shows that when this pathway is chemically or genetically compromised, cells do not shunt DSBs to homologous recombination repair (HRR) but instead use another form of NHEJ operating as a backup (B-NHEJ). Here I review our efforts to characterize this repair pathway and discuss its dependence on the cell cycle as well as on the growth conditions. I present evidence that B-NHEJ utilizes ligase III, PARP-1 and histone H1. When B-NHEJ is examined throughout the cell cycle, significantly higher activity is observed in G2 phase that cannot be attributed to HRR. Furthermore, the activity of B-NHEJ is compromised when cells enter the plateau phase of growth. Together, these observations uncover a repair pathway with unexpected biochemical constitution and interesting cell cycle and growth factor regulation. They generate a framework for investigating the mechanistic basis of HRR contribution to DSB repair.

Cycle length dependence of the chronotropic effects of adrenaline, acetylcholine, Ca2+ and Mg2+ in the Guinea-pig sinoatrial node

NARCIS (Netherlands)

Opthof, T.; de Jonge, B.; Schade, B.; Jongsma, H. J.; Bouman, L. N.

1984-01-01

Ca (1.1-5.5 mM) has a positive chronotropic action on isolated right atria of the guinea-pig. The magnitude of the response depends on the cycle length. Magnitude and cycle length dependence of the Ca response are independent of beta-blockade by propranolol. Mg (0.6-6.0 mM) has a negative

Two modes of regulation of the fatty acid elongase ELOVL6 by the 3-ketoacyl-CoA reductase KAR in the fatty acid elongation cycle.

Directory of Open Access Journals (Sweden)

Tatsuro Naganuma

Full Text Available Fatty acids (FAs are diverse molecules, and such diversity is important for lipids to exert their functions under several environmental conditions. FA elongation occurs at the endoplasmic reticulum and produces a variety of FA species; the FA elongation cycle consists of four distinct enzyme reactions. For this cycle to be driven efficiently, there must exist coordinated regulation of protein components of the FA elongation machinery. However, such regulation is poorly understood. In the present study, we performed biochemical analyses using the FA elongase ELOVL6 and the 3-ketoacyl-CoA reductase KAR, which catalyze the first and second steps of the FA elongation cycle, respectively. In vitro FA elongation assays using membrane fractions demonstrated that ELOVL6 activity was enhanced ∼10-fold in the presence of NADPH, although ELOVL6 itself did not require NADPH for its catalysis. On the other hand, KAR does use NADPH as a reductant in its enzyme reaction. Activity of purified ELOVL6 was enhanced by ∼3-fold in the presence of KAR. This effect was KAR enzyme activity-independent, since it was observed in the absence of NADPH and in the KAR mutant. However, ELOVL6 enzyme activity was further enhanced in a KAR enzyme activity-dependent manner. Therefore, KAR regulates ELOVL6 via two modes. In the first mode, KAR may induce conformational changes in ELOVL6 to become structure that can undergo catalysis. In the second mode, conversion of 3-ketoacyl-CoA to 3-hydroxyacyl-CoA by KAR may facilitate release of the product from the presumed ELOVL6-KAR complex.

Omega-3 Polyunsaturated Fatty Acids Attenuate Radiation-induced Oxidative Stress and Organ Dysfunctions in Rats

International Nuclear Information System (INIS)

Abdel Aziz, N.; Yacoub, S.F.

2013-01-01

The Aim of the present study was to determine the possible protective effect of omega-3 polyunsaturated fatty acids (omega-3 PUFA) against radiation-induced oxidative stress associated with organ dysfunctions. Omega-3 PUFA was administered by oral gavages to male albino rats at a dose of 0.4 g/ kg body wt daily for 4 weeks before whole body γ-irradiation with 4Gy. Significant increase of serum lipid peroxidation end product as malondialdehyde (MDA) along with the reduction in blood glutathione (GSH) content, superoxide dismutase (SOD) and glutathione peroxidase (GPX) enzyme activities were recorded on 3rd and 8th days post-irradiation. Oxidative stress was associated with a significant increase in lactate dehydrogenase (LDH) and creatine phosphokinase (CPK) enzyme activities, markers of heart damage, significant increases in uric acid, urea and creatinine levels, markers of kidney damage, significant increases of alkaline phosphatase (ALP) and transaminases (ALT and AST) activities, markers of liver damage. Moreover significant increases in total cholesterol and triglycerides levels were recorded. Omega-3 PUFA administration pre-irradiation significantly attenuated the radiation-induced oxidative stress and organ dysfunctions tested in this study. It could be concluded that oral supplementation of omega-3 PUFA before irradiation may afford protection against radiation-induced oxidative stress and might preserve the integrity of tissue functions of the organs under investigations.

Intensity attenuation relation at Chamba–Garhwal area in north-west ...

Indian Academy of Sciences (India)

Seismic hazard assessment of any region depends on the attenuation relation ... The present study includes 10 moderate and major earthquakes (Ms ≥ 4.9) that had occurred during the ... city and attenuation of strong seismic ground motion. ... Seismologists have benefitted from the development .... In that case, we inferred.

Spatially resolved ultrasonic attenuation in resistance spot welds: implications for nondestructive testing.

Science.gov (United States)

Mozurkewich, George; Ghaffari, Bita; Potter, Timothy J

2008-09-01

Spatial variation of ultrasonic attenuation and velocity has been measured in plane parallel specimens extracted from resistance spot welds. In a strong weld, attenuation is larger in the nugget than in the parent material, and the region of increased attenuation is surrounded by a ring of decreased attenuation. In the center of a stick weld, attenuation is even larger than in a strong weld, and the low-attenuation ring is absent. These spatial variations are interpreted in terms of differences in grain size and martensite formation. Measured frequency dependences indicate the presence of an additional attenuation mechanism besides grain scattering. The observed attenuations do not vary as commonly presumed with weld quality, suggesting that the common practice of using ultrasonic attenuation to indicate weld quality is not a reliable methodology.

Patient position alters attenuation effects in multipinhole cardiac SPECT.

Science.gov (United States)

Timmins, Rachel; Ruddy, Terrence D; Wells, R Glenn

2015-03-01

Dedicated cardiac cameras offer improved sensitivity over conventional SPECT cameras. Sensitivity gains are obtained by large numbers of detectors and novel collimator arrangements such as an array of multiple pinholes that focus on the heart. Pinholes lead to variable amounts of attenuation as a source is moved within the camera field of view. This study evaluated the effects of this variable attenuation on myocardial SPECT images. Computer simulations were performed for a set of nine point sources distributed in the left ventricular wall (LV). Sources were placed at the location of the heart in both an anthropomorphic and a water-cylinder computer phantom. Sources were translated in x, y, and z by up to 5 cm from the center. Projections were simulated with and without attenuation and the changes in attenuation were compared. A LV with an inferior wall defect was also simulated in both phantoms over the same range of positions. Real camera data were acquired on a Discovery NM530c camera (GE Healthcare, Haifa, Israel) for five min in list-mode using an anthropomorphic phantom (DataSpectrum, Durham, NC) with 100 MBq of Tc-99m in the LV. Images were taken over the same range of positions as the simulations and were compared based on the summed perfusion score (SPS), defect width, and apparent defect uptake for each position. Point sources in the water phantom showed absolute changes in attenuation of ≤8% over the range of positions and relative changes of ≤5% compared to the apex. In the anthropomorphic computer simulations, absolute change increased to 20%. The changes in relative attenuation caused a change in SPS of position-dependent changes were removed with attenuation correction. Translation of a source relative to a multipinhole camera caused only small changes in homogeneous phantoms with SPS changing position-dependent changes in attenuation.

DNA methyltransferase mediates dose-dependent stimulation of neural stem cell proliferation by folate.

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Li, Wen; Yu, Min; Luo, Suhui; Liu, Huan; Gao, Yuxia; Wilson, John X; Huang, Guowei

2013-07-01

The proliferative response of neural stem cells (NSCs) to folate may play a critical role in the development, function and repair of the central nervous system. It is important to determine the dose-dependent effects of folate in NSC cultures that are potential sources of transplantable cells for therapies for neurodegenerative diseases. To determine the optimal concentration and mechanism of action of folate for stimulation of NSC proliferation in vitro, NSCs were exposed to folic acid or 5-methyltetrahydrofolate (5-MTHF) (0-200 μmol/L) for 24, 48 or 72 h. Immunocytochemistry and methyl thiazolyl tetrazolium assay showed that the optimal concentration of folic acid for NSC proliferation was 20-40 μmol/L. Stimulation of NSC proliferation by folic acid was associated with DNA methyltransferase (DNMT) activation and was attenuated by the DNMT inhibitor zebularine, which implies that folate dose-dependently stimulates NSC proliferation through a DNMT-dependent mechanism. Based on these new findings and previously published evidence, we have identified a mechanism by which folate stimulates NSC growth. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of a Fatigue Model for Low Alloy Steels Using a Cycle-Dependent Cohesive Zone Law

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Kyungmok Kim

2014-03-01

Full Text Available A fatigue model for SAE 4130 steels is developed using a cycle-dependent cohesive zone law. Reduction of fracture energy and degradation of stiffness are considered to describe failure resistance after certain number of cycles. The reduction rate of fracture energy is determined with experimental stress (S- number of cycles to failure (N scatter found in the literature. Three-dimensional finite element models containing a cohesive zone are generated with commercial software (ABAQUS. Calculated fatigue lives at different stress ratios are in good agreement with experimental ones. In addition, fatigue behavior of hardened SAE 4130 steels is predicted with that of normalized material.

Role of gallic and p-coumaric acids in the AHL-dependent expression of flgA gene and in the process of biofilm formation in food-associated Pseudomonas fluorescens KM120.

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Myszka, Kamila; Schmidt, Marcin T; Białas, Wojciech; Olkowicz, Mariola; Leja, Katarzyna; Czaczyk, Katarzyna

2016-09-01

In the process of Pseudomonas fluorescens biofilm formation, N-acyl-l-homoserine lactone (AHL)-mediated flagella synthesis plays a key role. Inhibition of AHL production may attenuate P. fluorescens biofilm on solid surfaces. This work validated the anti-biofilm properties of p-coumaric and gallic acids via the ability of phenolics to suppress AHL synthesis in P. fluorescens KM120. The dependence between synthesis of AHL molecules, expression of flagella gene (flgA) and the ability of biofilm formation by P. fluorescens KM120 on a stainless steel surface (type 304L) was also investigated. Research was carried out in a purpose-built flow cell device. Limitations on AHL synthesis in P. fluorescens KM120 were observed at concentrations of 120 and 240 µmol L(-1) of phenolic acids in medium. At such levels of gallic and p-coumaric acids the ability of P. fluorescens KM120 to synthesize 3-oxo-C6-homoserine lactone (HSL) was not observed. These concentrations caused decreased expression of flgA gene in P. fluorescens KM120. The changes in expression of AHL-dependent flgA gene significantly decreased the rate of microorganism colonization on the stainless steel surface. Phenolic acids are able to inhibit biofilm formation. The results obtained in the work may help to develop alternative techniques for anti-biofilm treatment in the food industry. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

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Tellier, Stéphanie; Dallocchio, Aymeric; Guigonis, Vincent; Saint-Marcoux, Frank; Llanas, Brigitte; Ichay, Lydia; Bandin, Flavio; Godron, Astrid; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane

2016-01-01

Background and objectives Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid–dependent nephrotic syndrome. Design, setting, participants, & measurements This was a retrospective multicenter study including 95 children with steroid–dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. Results In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30–60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). Conclusions Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid–dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population. PMID:27445161

Cyclin G2 is a centrosome-associated nucleocytoplasmic shuttling protein that influences microtubule stability and induces a p53-dependent cell cycle arrest

International Nuclear Information System (INIS)

Arachchige Don, Aruni S.; Dallapiazza, Robert F.; Bennin, David A.; Brake, Tiffany; Cowan, Colleen E.; Horne, Mary C.

2006-01-01

Cyclin G2 is an atypical cyclin that associates with active protein phosphatase 2A. Cyclin G2 gene expression correlates with cell cycle inhibition; it is significantly upregulated in response to DNA damage and diverse growth inhibitory stimuli, but repressed by mitogenic signals. Ectopic expression of cyclin G2 promotes cell cycle arrest, cyclin dependent kinase 2 inhibition and the formation of aberrant nuclei [Bennin, D. A., Don, A. S., Brake, T., McKenzie, J. L., Rosenbaum, H., Ortiz, L., DePaoli-Roach, A. A., and Horne, M. C. (2002). Cyclin G2 associates with protein phosphatase 2A catalytic and regulatory B' subunits in active complexes and induces nuclear aberrations and a G 1 /S-phase cell cycle arrest. J Biol Chem 277, 27449-67]. Here we report that endogenous cyclin G2 copurifies with centrosomes and microtubules (MT) and that ectopic G2 expression alters microtubule stability. We find exogenous and endogenous cyclin G2 present at microtubule organizing centers (MTOCs) where it colocalizes with centrosomal markers in a variety of cell lines. We previously reported that cyclin G2 forms complexes with active protein phosphatase 2A (PP2A) and colocalizes with PP2A in a detergent-resistant compartment. We now show that cyclin G2 and PP2A colocalize at MTOCs in transfected cells and that the endogenous proteins copurify with isolated centrosomes. Displacement of the endogenous centrosomal scaffolding protein AKAP450 that anchors PP2A at the centrosome resulted in the depletion of centrosomal cyclin G2. We find that ectopic expression of cyclin G2 induces microtubule bundling and resistance to depolymerization, inhibition of polymer regrowth from MTOCs and a p53-dependent cell cycle arrest. Furthermore, we determined that a 100 amino acid carboxy-terminal region of cyclin G2 is sufficient to both direct GFP localization to centrosomes and induce cell cycle inhibition. Colocalization of endogenous cyclin G2 with only one of two GFP-centrin-tagged centrioles, the

Analysis of lead/acid battery life cycle factors: their impact on society and the lead industry

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Robertson, J. G. S.; Wood, J. R.; Ralph, B.; Fenn, R.

The underlying theme of this paper is that society, globally, is undergoing a fundamental conceptual shift in the way it views the environment and the role of industry within it. There are views in certain quarters that this could result in the virtual elimination of the lead industry's entire product range. Despite these threats, it is argued that the prospects for the lead industry appear to be relatively favourable in a number of respects. The industry's future depends to a significant degree, however, upon its ability to argue its case in a number of key areas. It is contended, therefore, that if appropriate strategies and means are promulgated, the prospects of the industry would appear to be relatively healthy. But, for this to happen with optimal effectiveness, a conceptual change will be necessary within the industry. New strategies and tools will have to be developed. These will require a significantly more integrated, holistically based and 'reflexive' approach than previously. The main elements of such an approach are outlined. With reference to the authors' ongoing research into automotive lead/acid starting lighting ignition (SLI) batteries, the paper shows how the technique of in-depth life cycle assessment (LCA), appropriately adapted to the needs of the industry, will provide a crucial role in this new approach. It also shows how it may be used as an internal design and assessment tool to identify those stages in the battery life cycle that give rise to the greatest environmental burdens, and to assess the effects of changes in the cycle to those burdens. It is argued that the development of this approach requires the serious and urgent attention of the whole of the lead industry. Also to make the LCA tool fully effective, it must be based on a 'live' database that is produced, maintained and continually updated by the industry.

Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

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Alpers Charles N

2007-10-01

Full Text Available Abstract Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5. The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1 preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2 stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2–3 ‰ heavier in the mine water, relative to those in surface waters; (3 reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA and denaturing gradient gel electrophoresis (DGGE analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures.

Microbial sulfate reduction and metal attenuation in pH 4 acid mine water

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Church, C.D.; Wilkin, R.T.; Alpers, Charles N.; Rye, R.O.; Blaine, R.B.

2007-01-01

Sediments recovered from the flooded mine workings of the Penn Mine, a Cu-Zn mine abandoned since the early 1960s, were cultured for anaerobic bacteria over a range of pH (4.0 to 7.5). The molecular biology of sediments and cultures was studied to determine whether sulfate-reducing bacteria (SRB) were active in moderately acidic conditions present in the underground mine workings. Here we document multiple, independent analyses and show evidence that sulfate reduction and associated metal attenuation are occurring in the pH-4 mine environment. Water-chemistry analyses of the mine water reveal: (1) preferential complexation and precipitation by H2S of Cu and Cd, relative to Zn; (2) stable isotope ratios of 34S/32S and 18O/16O in dissolved SO4 that are 2-3 ??? heavier in the mine water, relative to those in surface waters; (3) reduction/oxidation conditions and dissolved gas concentrations consistent with conditions to support anaerobic processes such as sulfate reduction. Scanning electron microscope (SEM) analyses of sediment show 1.5-micrometer, spherical ZnS precipitates. Phospholipid fatty acid (PLFA) and denaturing gradient gel electrophoresis (DGGE) analyses of Penn Mine sediment show a high biomass level with a moderately diverse community structure composed primarily of iron- and sulfate-reducing bacteria. Cultures of sediment from the mine produced dissolved sulfide at pH values near 7 and near 4, forming precipitates of either iron sulfide or elemental sulfur. DGGE coupled with sequence and phylogenetic analysis of 16S rDNA gene segments showed populations of Desulfosporosinus and Desulfitobacterium in Penn Mine sediment and laboratory cultures. ?? 2007 Church et al; licensee BioMed Central Ltd.

Organic acid formation in steam–water cycles: Influence of temperature, retention time, heating rate and O2

International Nuclear Information System (INIS)

Moed, D.H.; Verliefde, A.R.D.; Heijman, S.G.J.; Rietveld, L.C.

2014-01-01

Organic carbon breaks down in boilers by hydrothermolysis, leading to the formation of organic acid anions, which are suspected to cause corrosion of steam–water cycle components. Prediction of the identity and quantity of these anions, based on feedwater organic carbon concentrations, has not been attempted, making it hard to establish a well-founded organic carbon guideline. By using a batch-reactor and flow reactor, the influence of temperature (276–352 °C), retention time (1–25 min), concentration (150–2400 ppb) and an oxygen scavenger (carbohydrazide) on organic acid anion formation from organic carbon was investigated. By comparing this to data gathered at a case-study site, the validity of setups was tested as well. The flow reactor provided results more representative for steam–water cycles than the batch reactor. It was found that lower heating rates give more organic acid anions as degradation products of organic carbon, both in quantity and species variety. The thermal stability of the organic acid anions is key. As boiler temperature increases, acetate becomes the dominant degradation product, due to its thermal stability. Shorter retention times lead to more variety and quantity of organic acid anions, due to a lack of time for the thermally less stable ones to degrade. Reducing conditions (or the absence of oxygen) increase the thermal stability of organic acid anions. As the feedwater organic carbon concentration decreases, there are relatively more organic acid anions formed. - Highlights: •Formation of organic acids from hydrothermolysis of organic carbon has been investigated. •The lower the temperature, the higher the variety of organic acid anions. •At the higher tested temperatures (331–352 °C) acetate is the dominant degradation product. •At longer retention times acetate is the dominant degradation product. •There is no linear relation between the organic carbon concentration and formed organic acids

Epigenetic control of viral life-cycle by a DNA-methylation dependent transcription factor.

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Kirsty Flower

Full Text Available Epstein-Barr virus (EBV encoded transcription factor Zta (BZLF1, ZEBRA, EB1 is the prototype of a class of transcription factor (including C/EBPalpha that interact with CpG-containing DNA response elements in a methylation-dependent manner. The EBV genome undergoes a biphasic methylation cycle; it is extensively methylated during viral latency but is reset to an unmethylated state following viral lytic replication. Zta is expressed transiently following infection and again during the switch between latency and lytic replication. The requirement for CpG-methylation at critical Zta response elements (ZREs has been proposed to regulate EBV replication, specifically it could aid the activation of viral lytic gene expression from silenced promoters on the methylated genome during latency in addition to preventing full lytic reactivation from the non-methylated EBV genome immediately following infection. We developed a computational approach to predict the location of ZREs which we experimentally assessed using in vitro and in vivo DNA association assays. A remarkably different binding motif is apparent for the CpG and non-CpG ZREs. Computational prediction of the location of these binding motifs in EBV revealed that the majority of lytic cycle genes have at least one and many have multiple copies of methylation-dependent CpG ZREs within their promoters. This suggests that the abundance of Zta protein coupled with the methylation status of the EBV genome act together to co-ordinate the expression of lytic cycle genes at the majority of EBV promoters.

Genetic investigation of tricarboxylic acid metabolism during the Plasmodium falciparum life cycle.

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Ke, Hangjun; Lewis, Ian A; Morrisey, Joanne M; McLean, Kyle J; Ganesan, Suresh M; Painter, Heather J; Mather, Michael W; Jacobs-Lorena, Marcelo; Llinás, Manuel; Vaidya, Akhil B

2015-04-07

New antimalarial drugs are urgently needed to control drug-resistant forms of the malaria parasite Plasmodium falciparum. Mitochondrial electron transport is the target of both existing and new antimalarials. Herein, we describe 11 genetic knockout (KO) lines that delete six of the eight mitochondrial tricarboxylic acid (TCA) cycle enzymes. Although all TCA KOs grew normally in asexual blood stages, these metabolic deficiencies halted life-cycle progression in later stages. Specifically, aconitase KO parasites arrested as late gametocytes, whereas α-ketoglutarate-dehydrogenase-deficient parasites failed to develop oocysts in the mosquitoes. Mass spectrometry analysis of (13)C-isotope-labeled TCA mutant parasites showed that P. falciparum has significant flexibility in TCA metabolism. This flexibility manifested itself through changes in pathway fluxes and through altered exchange of substrates between cytosolic and mitochondrial pools. Our findings suggest that mitochondrial metabolic plasticity is essential for parasite development. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Persistence of attenuated HIV-1 rev alleles in an epidemiologically linked cohort of long-term survivors infected with nef-deleted virus

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Wesselingh Steven L

2007-07-01

Full Text Available Abstract Background The Sydney blood bank cohort (SBBC of long-term survivors consists of multiple individuals infected with nef-deleted, attenuated strains of human immunodeficiency virus type 1 (HIV-1. Although the cohort members have experienced differing clinical courses and now comprise slow progressors (SP as well as long-term nonprogressors (LTNP, longitudinal analysis of nef/long-terminal repeat (LTR sequences demonstrated convergent nef/LTR sequence evolution in SBBC SP and LTNP. Thus, the in vivo pathogenicity of attenuated HIV-1 strains harboured by SBBC members is dictated by factors other than nef/LTR. Therefore, to determine whether defects in other viral genes contribute to attenuation of these HIV-1 strains, we characterized dominant HIV-1 rev alleles that persisted in 4 SBBC subjects; C18, C64, C98 and D36. Results The ability of Rev derived from D36 and C64 to bind the Rev responsive element (RRE in RNA binding assays was reduced by approximately 90% compared to Rev derived from HIV-1NL4-3, C18 or C98. D36 Rev also had a 50–60% reduction in ability to express Rev-dependent reporter constructs in mammalian cells. In contrast, C64 Rev had only marginally decreased Rev function despite attenuated RRE binding. In D36 and C64, attenuated RRE binding was associated with rare amino acid changes at 3 highly conserved residues; Gln to Pro at position 74 immediately N-terminal to the Rev activation domain, and Val to Leu and Ser to Pro at positions 104 and 106 at the Rev C-terminus, respectively. In D36, reduced Rev function was mapped to an unusual 13 amino acid extension at the Rev C-terminus. Conclusion These findings provide new genetic and mechanistic insights important for Rev function, and suggest that Rev function, not Rev/RRE binding may be rate limiting for HIV-1 replication. In addition, attenuated rev alleles may contribute to viral attenuation and long-term survival of HIV-1 infection in a subset of SBBC members.

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

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

2014-01-01

Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.

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Li, Ge; Park, Hyeon U; Liang, Dong; Zhao, Richard Y

2010-07-07

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R

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Liang Dong

2010-07-01

Full Text Available Abstract Background Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. Results To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU and ultraviolet light (UV also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. Conclusions These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Na--dependent transport of basic, zwitterionic, and bicyclic amino acids by a broad-scope system in mouse blastocysts

International Nuclear Information System (INIS)

Van Winkle, L.J.; Christensen, H.N.; Campione, A.L.

1985-01-01

Mouse blastocysts which had been activated from diapause in utero appeared to take up amino acids via a Na - -dependent transport system with novel characteristics. In contrast to other cell types, uptake of 3-aminoendobicyclo [3,2,1]octane-3-carboxylic acid (BCO) by blastocysts was largely Na - dependent. Moreover, L-alanine and BCO met standard criteria for mutual competitive inhibition of the Na - -dependent transport of each other. The Ki for each of these amino acids as an inhibitor of transport of the other had a value similar to the value of its Km for transport. In addition, both 2-aminoendobicyclo [2,2,1]heptane-2-carboxylic acid and L-valine appeared to inhibit Na - -dependent transport of alanine and BCO competitively. Finally, alanine and L-lysine appeared to compete for the same Na+-dependent transport sites in blastocysts. For these reasons, the authors conclude that lysine, alanine, and BCO are transported by a common Na+-dependent system in blastocysts. In addition, the apparent interaction of the system with other basic amino acids, such as 1-dimethylpiperidine-4-amino-4-carboxylic acid, which has a nondissociable positive charge on its side chain, and L-arginine and L-homoarginine, whose cationic forms are highly predominant at neutral pH, suggests that the cationic forms of basic amino acids are transported by the wide-scope system

Nucleobase but not Sugar Fidelity is Maintained in the Sabin I RNA-Dependent RNA Polymerase

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Xinran Liu

2015-10-01

Full Text Available The Sabin I poliovirus live, attenuated vaccine strain encodes for four amino acid changes (i.e., D53N, Y73H, K250E, and T362I in the RNA-dependent RNA polymerase (RdRp. We have previously shown that the T362I substitution leads to a lower fidelity RdRp, and viruses encoding this variant are attenuated in a mouse model of poliovirus. Given these results, it was surprising that the nucleotide incorporation rate and nucleobase fidelity of the Sabin I RdRp is similar to that of wild-type enzyme, although the Sabin I RdRp is less selective against nucleotides with modified sugar groups. We suggest that the other Sabin amino acid changes (i.e., D53N, Y73H, K250E help to re-establish nucleotide incorporation rates and nucleotide discrimination near wild-type levels, which may be a requirement for the propagation of the virus and its efficacy as a vaccine strain. These results also suggest that the nucleobase fidelity of the Sabin I RdRp likely does not contribute to viral attenuation.

Cell-cycle variation in the induction of lethality and mitotic recombination after treatment with UV and nitrous acid in the yeast, Saccharomyces cerevisiae

International Nuclear Information System (INIS)

Davies, P.J.; Tippins, R.S.; Parry, J.M.

1978-01-01

Exponentially growing yeast cultures separated into discrete periods of the cell cycle by zonal rotor centrifugation show cyclic variation in both UV and nitrous acid induced cell lethality, mitotic gene conversion and mitotic crossing-over. Maximum cell survival after UV treatment was observed in the S and G2 phases of the cell cycle at a time when UV induction of both types of mitotic recombination was at a minumum. In contrast, cell inactivation by the chemical mutagen nitrous acid showed a single discrete period of sensitivity which occurred in S phase cells which are undergoing DNA synthesis. Mitotic gene conversion ahd mitotic crossing-over were induced by nitrous acid in cells at all stages of the cell cycle with a peak of induction of both events occurring at the time of maximum cell lethality. The lack of correlation observed between maximum cell survival and the maximum induction of mitotic intragenic recombination suggest that other DNA-repair mechanisms besides DNA-recombination repair are involved in the recovery of inactivated yeast cells during the cell cycle. (Auth.)

Lipid profiling demonstrates that suppressing Arabidopsis phospholipase Dδ retards ABA-promoted leaf senescence by attenuating lipid degradation.

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Yanxia Jia

Full Text Available Senescence is the last phase of the plant life cycle and has an important role in plant development. Degradation of membrane lipids is an essential process during leaf senescence. Several studies have reported fundamental changes in membrane lipids and phospholipase D (PLD activity as leaves senesce. Suppression of phospholipase Dα1 (PLDα1 retards abscisic acid (ABA-promoted senescence. However, given the absence of studies that have profiled changes in the compositions of membrane lipid molecules during leaf senescence, there is no direct evidence that PLD affects lipid composition during the process. Here, we show that application of n-butanol, an inhibitor of PLD, and N-Acylethanolamine (NAE 12∶0, a specific inhibitor of PLDα1, retarded ABA-promoted senescence to different extents. Furthermore, phospholipase Dδ (PLDδ was induced in leaves treated with ABA, and suppression of PLDδ retarded ABA-promoted senescence in Arabidopsis. Lipid profiling revealed that detachment-induced senescence had different effects on plastidic and extraplastidic lipids. The accelerated degradation of plastidic lipids during ABA-induced senescence in wild-type plants was attenuated in PLDδ-knockout (PLDδ-KO plants. Dramatic increases in phosphatidic acid (PA and decreases in phosphatidylcholine (PC during ABA-induced senescence were also suppressed in PLDδ-KO plants. Our results suggest that PLDδ-mediated hydrolysis of PC to PA plays a positive role in ABA-promoted senescence. The attenuation of PA formation resulting from suppression of PLDδ blocks the degradation of membrane lipids, which retards ABA-promoted senescence.

Electromagnetic Wave Attenuation in Atmospheric Pressure Plasma

International Nuclear Information System (INIS)

Zhang Shu; Hu Xiwei; Liu Minghai; Luo Fang; Feng Zelong

2007-01-01

When an electromagnetic (EM) wave propagates in an atmospheric pressure plasma (APP) layer, its attenuation depends on the APP parameters such as the layer width, the electron density and its profile and collision frequency between electrons and neutrals. This paper proposes that a combined parameter-the product of the line average electron density n-bar and width d of the APP layer (i.e., the total number of electrons in a unit volume along the wave propagation path) can play a more explicit and decisive role in the wave attenuation than any of the above individual parameters does. The attenuation of the EM wave via the product of n-bar and d with various collision frequencies between electrons and neutrals is presented

Mobility and natural attenuation of metals and arsenic in acidic waters of the drainage system of Timok River from Bor copper mines (Serbia) to Danube River.

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Đorđievski, Stefan; Ishiyama, Daizo; Ogawa, Yasumasa; Stevanović, Zoran

2018-06-22

Bor, Krivelj, and Bela Rivers belong to the watershed of Timok River, which is a tributary of transboundary Danube River. These rivers receive metal-rich acidic wastewater from metallurgical facilities and acid mine drainage (AMD) from mine wastes around Bor copper mines. The aim of this study was to determine the mobility and natural attenuation of metals and arsenic in rivers from Bor copper mines to Danube River during the year 2015. The results showed that metallurgical facilities had the largest impact on Bor River by discharging about 400 t of Cu per year through highly acidic wastewater (pH = 2.6). The highest measured concentrations of Cu in river water and sediments were 40 mg L -1 and 1.6%, respectively. Dissolution of calcite from limestone bedrock and a high concentration of bicarbonate ions in natural river water (about 250 mg L -1 ) enhanced the neutralization of acidic river water and subsequent chemical precipitation of metals and arsenic. Decreases in the concentrations of Al, Fe, Cu, As, and Pb in river water were mainly due to precipitation on the river bed. On the other hand, dilution played an important role in the decreases in concentrations of Mn, Ni, Zn, and Cd. Chemically precipitated materials and flotation tailings containing Fe-rich minerals (fayalite, magnetite, and pyrite) were transported toward Danube River during the periods of high discharge. This study showed that processes of natural attenuation in catchments with limestone bedrock play an important role in reducing concentrations of metals and arsenic in AMD-bearing river water.

Dynorphin-dependent reduction of excitability and attenuation of inhibitory afferents of NPS neurons in the pericoerulear region of mice

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Kay eJuengling

2016-03-01

Full Text Available The Neuropeptide S system, consisting of the 20-amino acid peptide neuropeptide S (NPS and its G-protein coupled receptor (NPSR, modulates arousal, wakefulness, anxiety, and fear-extinction in mice. In addition, recent evidence indicates that the NPS system attenuates stress-dependent impairment of fear extinction, and that NPS-expressing neurons in close proximity to the locus coeruleus (pericoerulear, periLC region are activated by stress. Furthermore, periLC NPS neurons receive afferents from neurons of the centrolateral nucleus of the amygdala (CeL, of which a substantial population expresses the kappa opioid receptor (KOR ligand precursor prodynorphin. This study aims to identify the effect of the dynorphinergic system on NPS neurons in the periLC via pre- and postsynaptic mechanisms. Using electrophysiological recordings in mouse brain slices, we provide evidence that NPS neurons in the periLC region are directly inhibited by dynorphin A via activation of κ-opioid receptor 1 (KOR1 and a subsequent increase of potassium conductances. Thus, the dynorphinergic system is suited to inactivate NPS neurons in the periLC. In addition to this direct, somatic effect, dynorphin A reduces the efficacy of GABAergic synapses on NPS neurons via KOR1 and KOR2. In conclusion, the present study provides evidence for the interaction of the NPS and the kappa opioid system in the periLC. Therefore, the endogenous opioid dynorphin is suited to inhibit NPS neurons with a subsequent decrease in NPS release in putative target regions leading to a variety of physiological consequences such as increased anxiety or vulnerability to stress exposure.

Rosmarinic acid potentiates carnosic acid induced apoptosis in lung fibroblasts.

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Sana Bahri

Full Text Available Pulmonary fibrosis is characterized by over-population and excessive activation of fibroblasts and myofibroblasts disrupting normal lung structure and functioning. Rosemary extract rich in carnosic acid (CA and rosmarinic acid (RA was reported to cure bleomycin-(BLM-induced pulmonary fibrosis. We demonstrate that CA decreased human lung fibroblast (HLF viability with IC50 value of 17.13±1.06 μM, while RA had no cytotoxic effect. In the presence of 50 μM of RA, dose-response for CA shifted to IC50 value of 11.70±1.46 μM, indicating synergic action. TGFβ-transformed HLF, rat lung fibroblasts and L929 cells presented similar sensitivity to CA and CA+RA (20μM+100μM, respectively treatment. Rat alveolar epithelial cells died only under CA+RA treatment, while A549 cells were not affected. Annexin V staining and DNA quantification suggested that HLF are arrested in G0/G1 cell cycle phase and undergo apoptosis. CA caused sustained activation of phospho-Akt and phospho-p38 expression and inhibition of p21 protein.Addition of RA potentiated these effects, while RA added alone had no action.Only triple combination of inhibitors (MAPK-p38, pan-caspase, PI3K/Akt/autophagy partially attenuated apoptosis; this suggests that cytotoxicity of CA+RA treatment has a complex mechanism involving several parallel signaling pathways. The in vivo antifibrotic effect of CA and RA was compared with that of Vitamine-E in BLM-induced fibrosis model in rats. We found comparable reduction in fibrosis score by CA, RA and CA+RA, attenuation of collagen deposition and normalization of oxidative stress markers. In conclusion, antifibrotic effect of CA+RA is due to synergistic pro-apoptotic action on lung fibroblasts and myofibroblasts.

Dexmedetomidine in premedication to attenuate the acute ...

African Journals Online (AJOL)

Background: The choice of anaesthetic agent for electroconvulsive therapy (ECT) depends on seizure duration, haemodynamic ... and infarction. To attenuate this acute ... scheduled for ECT, physical status ASA I and II, age between 18 and.

Monitoring Low-Cycle Fatigue Material-Degradation by Ultrasonic Methods

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R. Himawan

2010-08-01

Full Text Available Any system consisting of structural material often undergoes fatigue, which is caused by dynamic load cycle. As a structural system, nuclear power plant is very likely to have low-cycle fatigue at many of its components. Taking into account the importance of monitoring low-cycle fatigue on structural components to prevent them from getting failure, the authors have conducted a work to monitor material degradation caused by low-cycle fatigue by using ultrasonic method. An alloy of Cu-40Zn was used as a test specimen. Ultrasonic water immersion procedure was employed in this ultrasonic test. The probe used is a focusing type and has frequency as high as 15 MHz. The specimen area tested is in the middle part divided into 14 points × 23 points. The results, which were frequency spectrums, were analyzed using two parameters: frequency spectrum peak intensity and attenuation function gradient. The analysis indicates that peak intensity increases at the beginning of load cycle and then decreases. Meanwhile, gradient of attenuation function is lower at the beginning of fatigue process, and then consistently gets higher. It concludes that low-fatigue material degradation can be monitored by using ultrasonic method.

The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane.

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Tanimura, Natsuko; Saitoh, Shin-Ichiroh; Ohto, Umeharu; Akashi-Takamura, Sachiko; Fujimoto, Yukari; Fukase, Koichi; Shimizu, Toshiyuki; Miyake, Kensuke

2014-06-01

TLR4/MD-2 senses lipid A, activating the MyD88-signaling pathway on the plasma membrane and the TRIF-signaling pathway after CD14-mediated TLR4/MD-2 internalization into endosomes. Monophosphoryl lipid A (MPL), a detoxified derivative of lipid A, is weaker than lipid A in activating the MyD88-dependent pathway. Little is known, however, about mechanisms underlying the attenuated activation of MyD88-dependent pathways. We here show that MPL was impaired in induction of CD14-dependent TLR4/MD-2 dimerization compared with lipid A. Impaired TLR4/MD-2 dimerization decreased CD14-mediated TNFα production. In contrast, MPL was comparable to lipid A in CD14-independent MyD88-dependent TNFα production and TRIF-dependent responses including cell surface CD86 up-regulation and IFNβ induction. Although CD86 up-regulation is dependent on TRIF signaling, it was induced by TLR4/MD-2 at the plasma membrane. These results revealed that the attenuated MPL responses were due to CD14-initiated responses at the plasma membrane, but not just to responses initiated by MyD88, that is, MPL was specifically unable to induce CD14-dependent TLR4/MD-2 dimerization that selectively enhances MyD88-mediated responses at the plasma membrane. © The Japanese Society for Immunology. 2013. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Investigation of the Dependences of the Attenuation Properties of Cryogenic Metal-Powder Filters on the Preparation Method

Science.gov (United States)

Lee, Sung Hoon; Lee, Soon-Gul

2018-04-01

We fabricated low-pass metal powder filters for use in low-noise measurements at cryogenic temperatures and investigated their attenuation characteristics for different wire-turn densities, metalpowder shapes, and preparation methods at frequencies up to 20 GHz. We used nominally 30-μmsized stainless-steel 304L powder and mixed it with low-temperature binders. The low-temperature binders used were Stycast 2850FT (Emerson and Cumming) with catalyst 23LV and GE-7031 varnish. A 0.1-mm insulated copper wire was wound on preformed powder-mixture bobbins in the shape of a circular rod and was encapsulated in metal tubes with the powder mixture. All the fabricated powder filters showed a large attenuation at high frequencies with a cut-off frequency near 1 GHz. For filters of the same wire length, a lower wiring density showed a larger attenuation, which implies that the amount of powder in close contact with the wire determines the attenuation. Filters made of a powder/varnish mixture showed significantly larger attenuations than those of a powder/stycast mixture, and the attenuation improved with increasing powder ratio in the mixture. The low-temperature thermal conductivities of a 2 : 1 powder/Stycast mixture and a 5 : 1 powder/varnish mixture showed similar values at temperatures up to 4.2 K.

Bias-dependent amino-acid-induced conductance changes in short semi-metallic carbon nanotubes

International Nuclear Information System (INIS)

Abadir, G B; Walus, K; Pulfrey, D L

2010-01-01

We study the interaction between short semi-metallic carbon nanotubes and different amino acids using molecular dynamics and ab initio (density functional theory/non-equilibrium Green's function) simulations. We identify two different mechanisms of nanotube conductance change upon adsorption of amino acids: one due to the change of the coordinates of the nanotube arising from van der Waals forces of interaction with the adsorbed amino acid; and one due to electrostatic interactions, which appear only in the case of charged amino acids. We also find that the transport mechanism and the changes in the conductance of the tube upon amino acid adsorption are bias dependent.

Time-dependent tritium inventories and flow rates in fuel cycle components of a tokamak fusion reactor

International Nuclear Information System (INIS)

Kuan, W.

1995-01-01

Time-dependent inventories and flow rates for several components of the fuel cycle are modeled and studied through the use of a new modular-type model for the dynamic simulation of the fuel cycle in a fusion reactor. The complex dynamic behavior in the modeled subsystems is analyzed using this new model. Preliminary results using fuel cycle design configurations similar to ITER are presented and analyzed. The inventories and flow rates inside the primary vacuum pumping, fuel cleanup unit and isotope separation system are studied. Ways to minimize the tritium inventory are also assessed. This was performed by looking at various design options that could be used to minimize tritium inventory for specific components. (orig.)

The role of cell cycle in retinal development: cyclin-dependent kinase inhibitors co-ordinate cell-cycle inhibition, cell-fate determination and differentiation in the developing retina.

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Bilitou, Aikaterini; Ohnuma, Shin-ichi

2010-03-01

The mature retina is formed through multi-step developmental processes, including eye field specification, optic vesicle evagination, and cell-fate determination. Co-ordination of these developmental events with cell-proliferative activity is essential to achieve formation of proper retinal structure and function. In particular, the molecular and cellular dynamics of the final cell cycle significantly influence the identity that a cell acquires, since cell fate is largely determined at the final cell cycle for the production of postmitotic cells. This review summarizes our current understanding of the cellular mechanisms that underlie the co-ordination of cell-cycle and cell-fate determination, and also describes a molecular role of cyclin-dependent kinase inhibitors (CDKIs) as co-ordinators of cell-cycle arrest, cell-fate determination and differentiation. Copyright (c) 2010 Wiley-Liss, Inc.

A reverse KREBS cycle in photosynthesis: consensus at last

Science.gov (United States)

Buchanan, B. B.; Arnon, D. I.

1990-01-01

The Krebs cycle (citric acid or tricarboxylic acid cycle), the final common pathway in aerobic metabolism for the oxidation of carbohydrates, fatty acids and amino acids, is known to be irreversible. It liberates CO2 and generates NADH whose aerobic oxidation yields ATP but it does not operate in reverse as a biosynthetic pathway for CO2 assimilation. In 1966, our laboratory described a cyclic pathway for CO2 assimilation (Evans, Buchanan and Arnon 1966) that was unusual in two respects: (i) it provided the first instance of an obligate photoautotroph that assimilated CO2 by a pathway different from Calvin's reductive pentose phosphate cycle (Calvin 1962) and (ii) in its overall effect the new cycle was a reversal of the Krebs cycle. Named the 'reductive carboxylic acid cycle' (sometimes also called the reductive tricarboxylic acid cycle) the new cycle appeared to be the sole CO2 assimilation pathway in Chlorobium thiosulfatophilum (Evans et al. 1966) (now known as Chlorobium limicola forma thiosulfatophilum). Chlorobium is a photosynthetic green sulfur bacterium that grows anaerobically in an inorganic medium with sulfide and thiosulfate as electron donors and CO2 as an obligatory carbon source. In the ensuing years, the new cycle was viewed with skepticism. Not only was it in conflict with the prevailing doctrine that the 'one important property ... shared by all (our emphasis) autotrophic species is the assimilation of CO2 via the Calvin cycle' (McFadden 1973) but also some of its experimental underpinnings were challenged. It is only now that in the words of one of its early skeptics (Tabita 1988) 'a long and tortuous controversy' has ended with general acceptance of the reductive carboxylic acid cycle as a photosynthetic CO2 assimilation pathway distinct from the pentose cycle. (Henceforth, to minimize repetitiveness, the reductive pentose phosphate cycle will often be referred to as the pentose cycle and the reductive carboxylic acid cycle as the carboxylic

Dynamic Contractility and Efficiency Impairments in Stretch-Shortening Cycle Are Stretch-Load-Dependent After Training-Induced Muscle Damage

NARCIS (Netherlands)

Vaczi, Mark; Racz, Levente; Hortobagyi, Tibor; Tihanyi, Jozsef

Vaczi, M, Racz, L, Hortobagyi, T, and Tihanyi, J. Dynamic contractility and efficiency impairments in stretch-shortening cycle are stretch-load-dependent after training-induced muscle damage. J Strength Cond Res 27(8): 2171-2179, 2013To determine the acute task and stretch-load dependency of

Ultrasonic attenuation in niobium II: measurements near Bsub(c2)

International Nuclear Information System (INIS)

Forgan, E.M.; Gough, C.E.

1978-01-01

The attenuation of 10 to 90 MHz longitudinal sound waves has been measured from 1.2 K upwards in the superconducting mixed state of niobium near Bsub(c2). The attenuation was determined as a function of the directly measured average induction, B, within single crystal specimens which had resistance ratios ranging from 83 to 3380. The specimens tended to the 'clean' limit (electron mean free path, 1 much greater than xi 0 , the superconducting coherence length) in which there is a strong purity dependence of the relative attenuation. For the purest crystals close to Bsub(C2), the results are in reasonable agreement with the purity and field dependence predicted by microscopic theories, and agree over a much wider field range with a phenomenological modification of these theories. Measurements of attenuation and other transport properties in clean type II superconductors by other authors are discussed and it is shown that many of the evident discrepancies can be attributed to neglect of the effects of magnetic irreversibility and crystalline anisotropy. (author)

ENERGY EFFICIENCY LIMITS FOR A RECUPERATIVE BAYONET SULFURIC ACID DECOMPOSITION REACTOR FOR SULFUR CYCLE THERMOCHEMICAL HYDROGEN PRODUCTION

Energy Technology Data Exchange (ETDEWEB)

Gorensek, M.; Edwards, T.

2009-06-11

A recuperative bayonet reactor design for the high-temperature sulfuric acid decomposition step in sulfur-based thermochemical hydrogen cycles was evaluated using pinch analysis in conjunction with statistical methods. The objective was to establish the minimum energy requirement. Taking hydrogen production via alkaline electrolysis with nuclear power as the benchmark, the acid decomposition step can consume no more than 450 kJ/mol SO{sub 2} for sulfur cycles to be competitive. The lowest value of the minimum heating target, 320.9 kJ/mol SO{sub 2}, was found at the highest pressure (90 bar) and peak process temperature (900 C) considered, and at a feed concentration of 42.5 mol% H{sub 2}SO{sub 4}. This should be low enough for a practical water-splitting process, even including the additional energy required to concentrate the acid feed. Lower temperatures consistently gave higher minimum heating targets. The lowest peak process temperature that could meet the 450-kJ/mol SO{sub 2} benchmark was 750 C. If the decomposition reactor were to be heated indirectly by an advanced gas-cooled reactor heat source (50 C temperature difference between primary and secondary coolants, 25 C minimum temperature difference between the secondary coolant and the process), then sulfur cycles using this concept could be competitive with alkaline electrolysis provided the primary heat source temperature is at least 825 C. The bayonet design will not be practical if the (primary heat source) reactor outlet temperature is below 825 C.

Lipoteichoic Acid of Probiotic Lactobacillus plantarum Attenuates Poly I:C-Induced IL-8 Production in Porcine Intestinal Epithelial Cells

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Kyoung Whun Kim

2017-09-01

Full Text Available Probiotics in livestock feed supplements are considered a replacement for antibiotics that enhance gastrointestinal immunity. Although bacterial cell wall components have been proposed to be associated with probiotic function, little evidence demonstrates that they are responsible for probiotic functions in livestock. The present study demonstrated that lipoteichoic acid (LTA of Lactobacillus plantarum (Lp.LTA confers anti-inflammatory responses in porcine intestinal epithelial cell line, IPEC-J2. A synthetic analog of viral double-stranded RNA, poly I:C, dose-dependently induced IL-8 production at the mRNA and protein levels in IPEC-J2 cells. Lp.LTA, but not lipoprotein or peptidoglycan from L. plantarum, exclusively suppressed poly I:C-induced IL-8 production. Compared with LTAs from other probiotic Lactobacillus strains including L. delbrueckii, L. sakei, and L. rhamnosus GG, Lp.LTA had higher potential to suppress poly I:C-induced IL-8 production. Dealanylated or deacylated Lp.LTA did not suppress poly I:C-induced IL-8 production, suggesting that D-alanine and lipid moieties in the Lp.LTA structure were responsible for the inhibition. Furthermore, Lp.LTA attenuated the phosphorylation of ERK and p38 kinase as well as the activation of NF-κB, resulting in decreased IL-8 production. Taken together, these results suggest that Lp.LTA acts as an effector molecule to inhibit viral pathogen-induced inflammatory responses in porcine intestinal epithelial cells.

Airborne non-contact and contact broadband ultrasounds for frequency attenuation profile estimation of cementitious materials.

Science.gov (United States)

Gosálbez, J; Wright, W M D; Jiang, W; Carrión, A; Genovés, V; Bosch, I

2018-08-01

In this paper, the study of frequency-dependent ultrasonic attenuation in strongly heterogeneous cementitious materials is addressed. To accurately determine the attenuation over a wide frequency range, it is necessary to have suitable excitation techniques. We have analysed two kinds of ultrasound techniques: contact ultrasound and airborne non-contact ultrasound. The mathematical formulation for frequency-dependent attenuation has been established and it has been revealed that each technique may achieve similar results but requires specific different calibration processes. In particular, the airborne non-contact technique suffers high attenuation due to energy losses at the air-material interfaces. Thus, its bandwidth is limited to low frequencies but it does not require physical contact between transducer and specimen. In contrast, the classical contact technique can manage higher frequencies but the measurement depends on the pressure between the transducer and the specimen. Cement specimens have been tested with both techniques and frequency attenuation dependence has been estimated. Similar results were achieved at overlapping bandwidth and it has been demonstrated that the airborne non-contact ultrasound technique could be a viable alternative to the classical contact technique. Copyright © 2018 Elsevier B.V. All rights reserved.

Economic Value Added as a Dependence on the Corporate- and Market-life Cycle

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Konečný Zdeněk

2011-06-01

Full Text Available Economic value added (EVA is an indicator which is widely used as the main tool for financial analysis. There are two methods of calculating it. The original method which was made by Stern & Stewart is defined as the net operating profit after taxes minus the cost of capital. The second method which was developed and used by the “Czech Ministry of Industry and Trade” indicates that, the economic value added is the difference between return on equity and the alternate cost of equity that is composed of separate risk rewards, and this “spread” is consequently multiplied by the equity. Economic value added depends on many factors. Whereas some of them are controllable by the company, others are not. This article is focused on the relationship between economic value added and the corporate- vs. market life cycle. This is because, there is an assumption that conditions for developing EVA changes depending on the actual phase of corporate- and market life cycle. In this research, the model by Reiners (2004 is used to identify the phases of corporate- and market life cycle and the method provided by the “Czech Ministry of Industry and Trade” is used to calculate EVA. However, there is a consideration of the relativity of EVA in the form of “spread” because of the intercompany comparison. The study found that, the highest spread is achieved by companies that are in the phase of expansion and phase of market expansion. On the contrary, companies in the phase of declension during market declension achieved the lowest and negative spread.

Mycophenolate mofetil attenuates pulmonary arterial hypertension in rats

International Nuclear Information System (INIS)

Suzuki, Chihiro; Takahashi, Masafumi; Morimoto, Hajime; Izawa, Atsushi; Ise, Hirohiko; Hongo, Minoru; Hoshikawa, Yasushi; Ito, Takayuki; Miyashita, Hiroshi; Kobayashi, Eiji; Shimada, Kazuyuki; Ikeda, Uichi

2006-01-01

Pulmonary arterial hypertension (PAH) is characterized by abnormal proliferation of smooth muscle cells (SMCs), leading to occlusion of pulmonary arterioles, right ventricular (RV) hypertrophy, and death. We investigated whether mycophenolate mofetil (MMF), a potent immunosuppresssant, prevents the development of monocrotaline (MCT)-induced PAH in rats. MMF effectively decreased RV systolic pressure and RV hypertrophy, and reduced the medial thickness of pulmonary arteries. MMF significantly inhibited the number of proliferating cell nuclear antigen (PCNA)-positive cells, infiltration of macrophages, and expression of P-selectin and interleukin-6 on the endothelium of pulmonary arteries. The infiltration of T cells and mast cells was not affected by MMF. In vitro experiments revealed that mycophenolic acid (MPA), an active metabolite of MMF, dose-dependently inhibited proliferation of human pulmonary arterial SMCs. MMF attenuated the development of PAH through its anti-inflammatory and anti-proliferative properties. These findings provide new insight into the potential role of immunosuppressants in the treatment of PAH

Concomitant ingestion of lactic acid bacteria and black tea synergistically enhances flavonoid bioavailability and attenuates d-galactose-induced oxidative stress in mice via modulating glutathione antioxidant system.

Science.gov (United States)

Zhao, Danyue; Shah, Nagendra P

2016-12-01

Black tea (BT) has been positively linked to improved redox status, while its efficacy is limited due to the low bioavailability of BT flavonoids. In addition to the direct antioxidant activity, flavonoids regulate redox balance via inducing endogenous antioxidants, particularly glutathione (GSH) and GSH-dependent antioxidant enzymes. This work first examined the effect of lactic acid bacteria (LAB) and BT alone or in combination on flavonoid bioavailability and metabolism; next, the effect of LAB-fermented BT diet in attenuating oxidative stress in mice and the underlying mechanisms were studied. Phenolic profiles of plasma, urine and feces from healthy mice consuming plain yogurt, BT milk (BTM) or BT yogurt (BTY) were acquired using LC-MS/MS. Plasma antioxidant capacity, lipid peroxidation level, content of nonprotein thiols and expression of GSH-related antioxidant enzymes and Nrf2 were examined in d-galactose-treated mice. Total flavonoid content in plasma following a single dose of BTY attained 0.657 μmol/l, increased by 50% compared with the BTM group. Increased excretion of phenolic metabolite and hippuric acid in urine and feces indicated enhanced metabolism of flavonoids in BTY-fed mice. In the second study, 8-week concomitant LAB-BT treatment of oxidatively stressed mice effectively restored plasma antioxidant capacity and GSH levels, and mitigated lipid peroxidation, which were associated with significant induction of GSH-dependent antioxidant enzymes and nuclear accumulation of Nrf2. Our results demonstrated the effect of LAB fermentation in enhancing BT flavonoid bioavailability in vivo. The synergistic antioxidant efficacy of LAB-BT diet implied its therapeutic potential in enhancing antioxidant defenses and protecting organisms from oxidative damage. Copyright © 2016. Published by Elsevier Inc.

The ent-15α-Acetoxykaur-16-en-19-oic Acid Relaxes Rat Artery Mesenteric Superior via Endothelium-Dependent and Endothelium-Independent Mechanisms

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Êurica Adélia Nogueira Ribeiro

2012-01-01

Full Text Available The objective of the study was to investigate the mechanism of the relaxant activity of the ent-15α-acetoxykaur-16-en-19-oic acid (KA-acetoxy. In rat mesenteric artery rings, KA-acetoxy induced a concentration-dependent relaxation in vessels precontracted with phenylephrine. In the absence of endothelium, the vasorelaxation was significantly shifted to the right without reduction of the maximum effect. Endothelium-dependent relaxation was significantly attenuated by pretreatment with L-NAME, an inhibitor of the NO-synthase (NOS, indomethacin, an inhibitor of the cyclooxygenase, L-NAME + indomethacin, atropine, a nonselective antagonist of the muscarinic receptors, ODQ, selective inhibitor of the guanylyl cyclase enzyme, or hydroxocobalamin, a nitric oxide scavenger. The relaxation was completely reversed in the presence of L-NAME + 1 mM L-arginine or L-arginine, an NO precursor. Diterpene-induced relaxation was not affected by TEA, a nonselective inhibitor of K+ channels. The KA-acetoxy antagonized CaCl2-induced contractions in a concentration-dependent manner and also inhibited an 80 mM KCl-induced contraction. The KA-acetoxy did not interfere with Ca2+ release from intracellular stores. The vasorelaxant induced by KA-acetoxy seems to involve the inhibition of the Ca2+ influx and also, at least in part, by endothelial muscarinic receptors activation, NO and PGI2 release.

Effect of sodium hypochlorite and peracetic acid on the surface roughness of acrylic resin polymerized by heated water for short and long cycles.

Science.gov (United States)

Sczepanski, Felipe; Sczepanski, Claudia Roberta Brunnquell; Berger, Sandrine Bittencourt; Consani, Rafael Leonardo Xediek; Gonini-Júnior, Alcides; Guiraldo, Ricardo Danil

2014-10-01

To evaluate the surface roughness of acrylic resin submitted to chemical disinfection via 1% sodium hypochlorite (NaClO) or 1% peracetic acid (C2H4O3). The disc-shaped resin specimens (30 mm diameter ×4 mm height) were polymerized by heated water using two cycles (short cycle: 1 h at 74°C and 30 min at 100°C; conventional long cycle: 9 h at 74°C). The release of substances by these specimens in water solution was also quantified. Specimens were fabricated, divided into four groups (n = 10) depending on the polymerization time and disinfectant. After polishing, the specimens were stored in distilled deionized water. Specimens were immersed in 1% NaClO or 1% C2H4O3 for 30 min, and then were immersed in distilled deionized water for 20 min. The release of C2H4O3 and NaClO was measured via visual colorimetric analysis. Roughness was measured before and after disinfection. Roughness data were subjected to two-way ANOVA and Tukey's test. There was no interaction between polymerization time and disinfectant in influencing the average surface roughness (Ra, P = 0.957). Considering these factors independently, there were significant differences between short and conventional long cycles (P = 0.012), but no significant difference between the disinfectants hypochlorite and C2H4O3 (P = 0.366). Visual colorimetric analysis did not detect release of substances. It was concluded that there was the difference in surface roughness between short and conventional long cycles, and disinfection at acrylic resins polymerized by heated water using a short cycle modified the properties of roughness.

Circadian cycle-dependent MeCP2 and brain chromatin changes.

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Alexia Martínez de Paz

Full Text Available Methyl CpG binding protein 2 (MeCP2 is a chromosomal protein of the brain, very abundant especially in neurons, where it plays an important role in the regulation of gene expression. Hence it has the potential to be affected by the mammalian circadian cycle. We performed expression analyses of mice brain frontal cortices obtained at different time points and we found that the levels of MeCP2 are altered circadianly, affecting overall organization of brain chromatin and resulting in a circadian-dependent regulation of well-stablished MeCP2 target genes. Furthermore, this data suggests that alterations of MeCP2 can be responsible for the sleeping disorders arising from pathological stages, such as in autism and Rett syndrome.

Blocking anaplerotic entry of glutamine into the TCA cycle sensitizes K-Ras mutant cancer cells to cytotoxic drugs.

Science.gov (United States)

Saqcena, M; Mukhopadhyay, S; Hosny, C; Alhamed, A; Chatterjee, A; Foster, D A

2015-05-14

Cancer cells undergo a metabolic transformation that allows for increased anabolic demands, wherein glycolytic and tricarboxylic acid (TCA) cycle intermediates are shunted away for the synthesis of biological molecules required for cell growth and division. One of the key shunts is the exit of citrate from the mitochondria and the TCA cycle for the generation of cytosolic acetyl-coenzyme A that can be used for fatty acid and cholesterol biosynthesis. With the loss of mitochondrial citrate, cancer cells rely on the 'conditionally essential' amino acid glutamine (Q) as an anaplerotic carbon source for TCA cycle intermediates. Although Q deprivation causes G1 cell cycle arrest in non-transformed cells, its impact on the cancer cell cycle is not well characterized. We report here a correlation between bypass of the Q-dependent G1 checkpoint and cancer cells harboring K-Ras mutations. Instead of arresting in G1 in response to Q-deprivation, K-Ras-driven cancer cells arrest in either S- or G2/M-phase. Inhibition of K-Ras effector pathways was able to revert cells to G1 arrest upon Q deprivation. Blocking anaplerotic utilization of Q mimicked Q deprivation--causing S- and G2/M-phase arrest in K-Ras mutant cancer cells. Significantly, Q deprivation or suppression of anaplerotic Q utilization created synthetic lethality to the cell cycle phase-specific cytotoxic drugs, capecitabine and paclitaxel. These data suggest that disabling of the G1 Q checkpoint could represent a novel vulnerability of cancer cells harboring K-Ras and possibly other mutations that disable the Q-dependent checkpoint.

Real-time electrochemical monitoring of isothermal helicase-dependent amplification of nucleic acids.

Science.gov (United States)

Kivlehan, Francine; Mavré, François; Talini, Luc; Limoges, Benoît; Marchal, Damien

2011-09-21

We described an electrochemical method to monitor in real-time the isothermal helicase-dependent amplification of nucleic acids. The principle of detection is simple and well-adapted to the development of portable, easy-to-use and inexpensive nucleic acids detection technologies. It consists of monitoring a decrease in the electrochemical current response of a reporter DNA intercalating redox probe during the isothermal DNA amplification. The method offers the possibility to quantitatively analyze target nucleic acids in less than one hour at a single constant temperature, and to perform at the end of the isothermal amplification a DNA melt curve analysis for differentiating between specific and non-specific amplifications. To illustrate the potentialities of this approach for the development of a simple, robust and low-cost instrument with high throughput capability, the method was validated with an electrochemical system capable of monitoring up to 48 real-time isothermal HDA reactions simultaneously in a disposable microplate consisting of 48-electrochemical microwells. Results obtained with this approach are comparable to that obtained with a well-established but more sophisticated and expensive fluorescence-based method. This makes for a promising alternative detection method not only for real-time isothermal helicase-dependent amplification of nucleic acid, but also for other isothermal DNA amplification strategies.

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

Science.gov (United States)

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

2010-12-15

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

Diel cycling of zinc in a stream impacted by acid rock drainage: Initial results from a new in situ Zn analyzer

Science.gov (United States)

Chapin, T.P.; Nimick, D.A.; Gammons, C.H.; Wanty, R.B.

2007-01-01

Recent work has demonstrated that many trace metals undergo dramatic diel (24-h) cycles in near neutral pH streams with metal concentrations reproducibly changing up to 500% during the diel period (Nimick et al., 2003). To examine diel zinc cycles in streams affected by acid rock drainage, we have developed a novel instrument, the Zn-DigiScan, to continuously monitor in situ zinc concentrations in near real-time. Initial results from a 3-day deployment at Fisher Creek, Montana have demonstrated the ability of the Zn-DigiScan to record diel Zn cycling at levels below 100 ??g/l. Longer deployments of this instrument could be used to examine the effects of episodic events such as rainstorms and snowmelt pulses on zinc loading in streams affected by acid rock drainage. ?? Springer Science+Business Media B.V. 2006.

Haloperidol Disrupts Opioid-Antinociceptive Tolerance and Physical Dependence

Science.gov (United States)

Yang, Cheng; Chen, Yan; Tang, Lei

2011-01-01

Previous studies from our laboratory and others have implicated a critical role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in opioid tolerance and dependence. Translational research targeting the CaMKII pathway is challenging, if not impossible, because of a lack of selective inhibitors. We discovered in a preliminary study that haloperidol, a butyrophenone antipsychotic drug, inhibited CaMKII, which led us to hypothesize that haloperidol can attenuate opioid tolerance and dependence by inhibiting CaMKII. The hypothesis was tested in two rodent models of opioid tolerance and dependence. Pretreatment with haloperidol (0.2–1.0 mg/kg i.p.) prevented the development of morphine tolerance and dependence in a dose-dependent manner. Short-term treatment with haloperidol (0.06–0.60 mg/kg i.p.) dose-dependently reversed the established morphine-antinociceptive tolerance and physical dependence. Correlating with behavioral effects, pretreatment or short-term treatment with haloperidol dose-dependently inhibited morphine-induced up-regulation of supraspinal and spinal CaMKIIα activity. Moreover, haloperidol given orally was also effective in attenuating morphine-induced CaMKIIα activity, antinociceptive tolerance, and physical dependence. Taken together, these data suggest that haloperidol attenuates opioid tolerance and dependence by suppressing CaMKII activity. Because haloperidol is a clinically used drug that can be taken orally, we propose that the drug may be of use in attenuating opioid tolerance and dependence. PMID:21436292

Assessment of a volume-dependent dynamic respiratory system compliance in ALI/ARDS by pooling breathing cycles

International Nuclear Information System (INIS)

Zhao, Zhanqi; Möller, Knut; Guttmann, Josef

2012-01-01

New methods were developed to calculate the volume-dependent dynamic respiratory system compliance (C rs ) in mechanically ventilated patients. Due to noise in respiratory signals and different characteristics of the methods, their results can considerably differ. The aim of the study was to establish a practical procedure to validate the estimation of intratidal dynamic C rs . A total of 28 patients from intensive care units of eight German university hospitals with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) were studied retrospectively. Dynamic volume-dependent C rs was determined during ongoing mechanical ventilation with the SLICE method, dynostatic algorithm and adaptive slice method. Conventional two-point compliance C 2P was calculated for comparison. A number of consecutive breathing cycles were pooled to reduce noise in the respiratory signals. C rs -volume curves produced with different methods converged when the number of pooling cycles increased (n ≥ 7). The mean volume-dependent C rs of 20 breaths was highly correlated with mean C 2P (C 2P,mean = 0.945 × C rs,mean − 0.053, r 2 = 0.968, p < 0.0001). The Bland–Altman analysis indicated that C 2P,mean was lower than C rs,mean (−2.4 ± 6.4 ml cm −1 H 2 O, mean bias ± 2 SD), but not significant according to the paired t-test (p > 0.05). Methods for analyzing dynamic respiratory mechanics are sensitive to noise and will converge to a unique solution when the number of pooled cycles increases. Under steady-state conditions, assessment of the volume-dependent C rs in ALI/ARDS patients can be validated by pooling respiratory data of consecutive breaths regardless of which method is applied. Confidence in dynamic C rs determination may be increased with the proposed pooling. (note)

Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells.

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Mazen Alzaharna

Full Text Available Andrographolide (Andro has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death.

Taxifolin synergizes Andrographolide-induced cell death by attenuation of autophagy and augmentation of caspase dependent and independent cell death in HeLa cells

Science.gov (United States)

Alzaharna, Mazen; Alqouqa, Iyad; Cheung, Hon-Yeung

2017-01-01

Andrographolide (Andro) has emerged recently as a potential and effective anticancer agent with induction of apoptosis in some cancer cell lines while induction of G2/M arrest with weak apoptosis in others. Few studies have proved that Andro is also effective in combination therapy. The flavonoid Taxifolin (Taxi) has showed anti-oxidant and antiproliferative effects against different cancer cells. Therefore, the present study investigated the cytotoxic effects of Andro alone or in combination with Taxi on HeLa cells. The combination of Andro with Taxi was synergistic at all tested concentrations and combination ratios. Andro alone induced caspase-dependent apoptosis which was enhanced by the combination with Taxi and attenuated partly by using Z-Vad-Fmk. Andro induced a protective reactive oxygen species (ROS)-dependent autophagy which was attenuated by Taxi. The activation of p53 was involved in Andro-induced autophagy where the use of Taxi or pifithrin-α (PFT-α) decreased it while the activation of JNK was involved in the cell death of HeLa cells but not in the induction of autophagy. The mitochondrial outer-membrane permeabilization (MOMP) plays an important role in Andro-induced cell death in HeLa cells. Andro alone increased the MOMP which was further increased in the case of combination. This led to the increase in AIF and cytochrome c release from mitochondria which consequently increased caspase-dependent and independent cell death. In conclusion, Andro induced a protective autophagy in HeLa cells which was reduced by Taxi and the cell death was increased by increasing the MOMP and subsequently the caspase-dependent and independent cell death. PMID:28182713

Measurement of attenuation coefficients of the fundamental and second harmonic waves in water

Science.gov (United States)

Zhang, Shuzeng; Jeong, Hyunjo; Cho, Sungjong; Li, Xiongbing

2016-02-01

Attenuation corrections in nonlinear acoustics play an important role in the study of nonlinear fluids, biomedical imaging, or solid material characterization. The measurement of attenuation coefficients in a nonlinear regime is not easy because they depend on the source pressure and requires accurate diffraction corrections. In this work, the attenuation coefficients of the fundamental and second harmonic waves which come from the absorption of water are measured in nonlinear ultrasonic experiments. Based on the quasilinear theory of the KZK equation, the nonlinear sound field equations are derived and the diffraction correction terms are extracted. The measured sound pressure amplitudes are adjusted first for diffraction corrections in order to reduce the impact on the measurement of attenuation coefficients from diffractions. The attenuation coefficients of the fundamental and second harmonics are calculated precisely from a nonlinear least squares curve-fitting process of the experiment data. The results show that attenuation coefficients in a nonlinear condition depend on both frequency and source pressure, which are much different from a linear regime. In a relatively lower drive pressure, the attenuation coefficients increase linearly with frequency. However, they present the characteristic of nonlinear growth in a high drive pressure. As the diffraction corrections are obtained based on the quasilinear theory, it is important to use an appropriate source pressure for accurate attenuation measurements.

Developmentally dependent and different roles of fatty acids OMEGA-6 and OMEGA-3

DEFF Research Database (Denmark)

Mourek, J; Mourek, J

2011-01-01

The developmentally-dependent differences in the biological significances and effects of PUFA-OMEGA-6 (namely of arachidonic acid) and PUFA-OMEGA-3 (namely of docosahexaenoic acid) are discussed. The clinical results as well as developmental experiences are indicating a hypothesis of the evolution...... that created mutual relationship between those two substances (with immunological basis and following recuperation). The anti-inflammatory actions of PUFA-OMEGA-3 are the most visible (and significant) contrasts as compared with the large affects of namely arachidonic acid and its metabolites....

Gallic acid attenuates type I diabetic nephropathy in rats.

Science.gov (United States)

Garud, Mayuresh Sudamrao; Kulkarni, Yogesh Anant

2018-02-25

Literature suggests that TGF-β1 has a central role in the progression of diabetic nephropathy and its down regulation can improve the disease condition. Oxidative stress, generation of advanced glycation end products and activation of renin angiotensin system are the connecting links between hyperglycemia and TGF-β1 over expression. Gallic acid is a phytochemical having wide range of biological activities. Gallic acid is reported to have antioxidant and advanced glycation inhibitory activity. It has also shown inhibitory effects on angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be tested in the diabetic nephropathy, one of the important complication of diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic nephropathy was used as an experimental model. Gallic acid was evaluated for its possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment significantly lowered plasma levels of the creatinine and blood urea nitrogen and elevated the levels of the protein and albumin. Gallic acid also improved creatinine clearance. Determination of oxidative stress parameters showed that the oxidative stress in kidney tissues was reduced significantly in gallic acid treated animals. Results of the plasma, urine and oxidative stress parameters were also reflected in the histopathological evaluation showing improvement in kidney pathophysiology. ELISA assay for circulating TGF-β1 evaluation and immunohistochemical study for determination of kidney expression of TGF-β1 revealed that gallic acid significantly lowered both the circulating and tissue levels of TGF-β1. Results support the hypothesis that gallic acid can be effectively used in the treatment of diabetic nephropathy. Copyright © 2018 Elsevier B.V. All rights reserved.

Degradation and contamination of perfluorinated sulfonic acid membrane due to swelling-dehydration cycles

DEFF Research Database (Denmark)

Andersen, Shuang Ma; Morgen, Per; Skou, Eivind Morten

Formation of sulfonic anhydride S-O-S (from the condensation of sulfonic acids) was known one of the important degradation mechanisms [i] for Nafion membrane under hydrothermal aging condition, which is especially critical for hydrogen fuel cells. Similar mechanism would also have be desirable...... to the membrane degradation in direct methanol fuel cells (DMFCs), where liquid water has direct contact with the electrolyte. An ex-situ experiment was established with swelling-dehydration cycles on the membrane. However, formation of sulfonic anhydride was not detected during the entire treatment; instead...

Applicability test of glass lining material for high-temperature acidic solutions of sulfuric acid in thermochemical water-splitting IS process

International Nuclear Information System (INIS)

Iwatsuki, Jin; Tanaka, Nobuyuki; Terada, Atsuhiko; Onuki, Kaoru; Watanabe, Yutaka

2010-01-01

A key issue for realizing the thermochemical IS process for hydrogen production is the selection of materials for working with high-temperature acidic solutions of sulfuric acid and hydriodic acid. Glass lining material is a promising candidate, which is composed of steel having good strength and glass having good corrosion resistance. Since the applicability of glass lining material depends strongly on the service condition, corrosion tests using glass used in glass lining material and heat cycle tests using glass lining piping were carried out to examine the possibility of using the glass lining material with high-temperature acidic solutions of sulfuric acid. It was confirmed that the glass lining materials exhibited sufficient corrosion resistance and heat resistance in high-temperature sulfuric acid of the IS process. (author)

Poly(3-hydroxybutyrate) fuels the tricarboxylic acid cycle and de novo lipid biosynthesis during Bacillus anthracis sporulation.

Science.gov (United States)

Sadykov, Marat R; Ahn, Jong-Sam; Widhelm, Todd J; Eckrich, Valerie M; Endres, Jennifer L; Driks, Adam; Rutkowski, Gregory E; Wingerd, Kevin L; Bayles, Kenneth W

2017-06-01

Numerous bacteria accumulate poly(3-hydroxybutyrate) (PHB) as an intracellular reservoir of carbon and energy in response to imbalanced nutritional conditions. In Bacillus spp., where PHB biosynthesis precedes the formation of the dormant cell type called the spore (sporulation), the direct link between PHB accumulation and efficiency of sporulation was observed in multiple studies. Although the idea of PHB as an intracellular carbon and energy source fueling sporulation was proposed several decades ago, the mechanisms underlying PHB contribution to sporulation have not been defined. Here, we demonstrate that PHB deficiency impairs Bacillus anthracis sporulation through diminishing the energy status of the cells and by reducing carbon flux into the tricarboxylic acid (TCA) cycle and de novo lipid biosynthesis. Consequently, this metabolic imbalance decreased biosynthesis of the critical components required for spore integrity and resistance, such as dipicolinic acid (DPA) and the spore's inner membrane. Supplementation of the PHB deficient mutant with exogenous fatty acids overcame these sporulation defects, highlighting the importance of the TCA cycle and lipid biosynthesis during sporulation. Combined, the results of this work reveal the molecular mechanisms of PHB contribution to B. anthracis sporulation and provide valuable insight into the metabolic requirements for this developmental process in Bacillus species. © 2017 John Wiley & Sons Ltd.

Pretreatment with oleic acid accelerates the entrance into the mitotic cycle of EGF-stimulated fibroblasts.

Science.gov (United States)

Zugaza, J L; Casabiell, X A; Bokser, L; Eiras, A; Beiras, A; Casanueva, F F

1995-07-01

We have previously demonstrated that pretreatment of several cell lines with cis-unsaturated fatty acids, like oleic acid, blocks epidermal growth factor (EGF)-induced early ionic signals, and in particular the [Ca2+]i rise. In the present work we show that this blockade does not alter EGF-stimulated cellular proliferation evaluated by direct cell counting, but induces a powerful enhancement in the pulsed thymidine incorporation assay. The lack of effect of oleic acid on EGF-stimulated cellular proliferation was confirmed by repeated cell counts, cumulative thymidine incorporation, and protein synthesis, but a clear synergistic effect between oleic acid and EGF was again obtained by means of time course experiments with pulsed thymidine. Combined flow cytometry analysis and cell counts at earlier times in EGF-stimulated cells showed that oleic acids accelerates the entrance of cells into the replicative cycle leading to an earlier cell division. Afterward, these oleic acid-pretreated cells became delayed by an unknown compensatory mechanism in such a way that at 48 h post-EGF, the cell count in control and oleic acid-pretreated cells was equal. In conclusion (a) oleic acid accelerates or enhances the EGF mitogenic action and (b) in the long term cells compensate the initial perturbation with respect to untreated cells. As a side observation, the widely employed pulsed thymidine incorporation method as a measure of cell division could be extremely misleading unless experimental conditions are well controlled.

Toxoplasma gondii influences aversive behaviors of female rats in an estrus cycle dependent manner.

Science.gov (United States)

Golcu, Doruk; Gebre, Rahiwa Z; Sapolsky, Robert M

2014-08-01

The protozoan Toxoplasma gondii (T. gondii) manipulates the behavior of its rodent intermediate host to facilitate its passage to its feline definitive host. This is accomplished by a reduction of the aversive response that rodents show towards cat odors, which likely increases the predation risk. Females on average show similar changes as males. However, behaviors that relate to aversion and attraction are usually strongly influenced by the estrus cycle. In this study, we replicated behavioral effects of T. gondii in female rats, as well as expanded it to two novel behavioral paradigms. We also characterized the role of the estrus cycle in the behavioral effects of T. gondii on female rats. Uninfected females preferred to spend more time in proximity to rabbit rather than bobcat urine, and in a dark chamber rather than a lit chamber. Infected females lost both of these preferences, and also spent more time investigating social novelty (foreign bedding in their environment). Taken together, these data suggest that infection makes females less risk averse and more exploratory. Furthermore, this effect was influenced by the estrus cycle. Uninfected rats preferred rabbit urine to bobcat urine throughout the cycle except at estrus and metestrus. In contrast, infected rats lost this preference at every stage of the cycle except estrus. Commensurate with the possibility that this was a hormone-dependent effect, infected rats had elevated levels of circulating progesterone, a known anxiolytic. Copyright © 2014 Elsevier Inc. All rights reserved.

Metabonomics Indicates Inhibition of Fatty Acid Synthesis, β-Oxidation, and Tricarboxylic Acid Cycle in Triclocarban-Induced Cardiac Metabolic Alterations in Male Mice.

Science.gov (United States)

Xie, Wenping; Zhang, Wenpeng; Ren, Juan; Li, Wentao; Zhou, Lili; Cui, Yuan; Chen, Huiming; Yu, Wenlian; Zhuang, Xiaomei; Zhang, Zhenqing; Shen, Guolin; Li, Haishan

2018-02-14

Triclocarban (TCC) has been identified as a new environmental pollutant that is potentially hazardous to human health; however, the effects of short-term TCC exposure on cardiac function are not known. The aim of this study was to use metabonomics and molecular biology techniques to systematically elucidate the molecular mechanisms of TCC-induced effects on cardiac function in mice. Our results show that TCC inhibited the uptake, synthesis, and oxidation of fatty acids, suppressed the tricarboxylic acid (TCA) cycle, and increased aerobic glycolysis levels in heart tissue after short-term TCC exposure. TCC also inhibited the nuclear peroxisome proliferator-activated receptor α (PPARα), confirming its inhibitory effects on fatty acid uptake and oxidation. Histopathology and other analyses further confirm that TCC altered mouse cardiac physiology and pathology, ultimately affecting normal cardiac metabolic function. We elucidate the molecular mechanisms of TCC-induced harmful effects on mouse cardiac metabolism and function from a new perspective, using metabonomics and bioinformatics analysis data.

Dietary Deficiency of Essential Amino Acids Rapidly Induces Cessation of the Rat Estrous Cycle

Science.gov (United States)

Bannai, Makoto; Ichimaru, Toru; Nakano, Sayako; Murata, Takuya; Higuchi, Takashi; Takahashi, Michio

2011-01-01

Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to

Ursolic acid mediates photosensitization by initiating mitochondrial-dependent apoptosis

Science.gov (United States)

Lee, Yuan-Hao; Wang, Exing; Kumar, Neeru; Glickman, Randolph D.

2013-02-01

The signaling pathways PI3K/Akt and MAPK play key roles in transcription, translation and carcinogenesis, and may be activated by light exposure. These pathways may be modulated or inhibited by naturally-occurring compounds, such as the triterpenoid, ursolic acid (UA). Previously, the transcription factors p53 and NF-kB, which transactivate mitochondrial apoptosis-related genes, were shown to be differentially modulated by UA. Our current work indicates that UA causes these effects via the mTOR and insulin-mediated pathways. UA-modulated apoptosis, following exposure to UV radiation, is observed to correspond to differential levels of oxidative stress in retinal pigment epithelial (RPE) and skin melanoma (SM) cells. Flow cytometry analysis, DHE (dihydroethidium) staining and membrane permeability assay showed that UA pretreatment potentiated cell cycle arrest and radiation-induced apoptosis selectively on SM cells while DNA photo-oxidative damage (i.e. strand breakage) was reduced, presumably by some antioxidant activity of UA in RPE cells. The UA-mediated NF-κB activation in SM cells was reduced by rapamycin pretreatment, which indicates that these agents exert inter-antagonistic effects in the PI3K/Akt/mTOR pathway. In contrast, the antagonistic effect of UA on the PI3K/Akt pathway was reversed by insulin leading to greater NF-κB and p53 activation in RPE cells. MitoTracker, a mitochondrial functional assay, indicated that mitochondria in RPE cells experienced reduced oxidative stress while those in SM cells exhibited increased oxidative stress upon UA pretreatment. When rapamycin administration was followed by UA, mitochondrial oxidative stress was increased in RPE cells but decreased in SM cells. These results indicate that UA modulates p53 and NF-κB, initiating a mitogenic response to radiation that triggers mitochondria-dependent apoptosis.

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

International Nuclear Information System (INIS)

Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung; Chang, Ki Churl; Park, Sang Won

2015-01-01

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated protein kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty

Honokiol activates the LKB1–AMPK signaling pathway and attenuates the lipid accumulation in hepatocytes

Energy Technology Data Exchange (ETDEWEB)

Seo, Min Suk; Kim, Jung Hwan; Kim, Hye Jung; Chang, Ki Churl; Park, Sang Won, E-mail: parksw@gnu.ac.kr

2015-04-15

Honokiol is a bioactive neolignan compound isolated from the species of Magnolia. This study was designed to elucidate the cellular mechanism by which honokiol alleviates the development of non-alcoholic steatosis. HepG2 cells were treated with honokiol for 1 h, and then exposed to 1 mM free fatty acid (FFA) for 24 h to simulate non-alcoholic steatosis in vitro. C57BL/6 mice were fed with a high-fat diet for 28 days, and honokiol (10 mg/kg/day) was daily treated. Honokiol concentration-dependently attenuated intracellular fat overloading and triglyceride (TG) accumulation in FFA-exposed HepG2 cells. These effects were blocked by pretreatment with an AMP-activated protein kinase (AMPK) inhibitor. Honokiol significantly inhibited sterol regulatory element-binding protein-1c (SREBP-1c) maturation and the induction of lipogenic proteins, stearoyl-CoA desaturase-1 (SCD-1) and fatty acid synthase (FAS) in FFA-exposed HepG2 cells, but these effects were blocked by pretreatment of an AMPK inhibitor. Honokiol induced AMPK phosphorylation and subsequent acetyl-CoA carboxylase (ACC) phosphorylation, which were inhibited by genetic deletion of liver kinase B1 (LKB1). Honokiol stimulated LKB1 phosphorylation, and genetic deletion of LKB1 blocked the effect of honokiol on SREBP-1c maturation and the induction of SCD-1 and FAS proteins in FFA-exposed HepG2 cells. Honokiol attenuated the increases in hepatic TG and lipogenic protein levels and fat accumulation in the mice fed with high-fat diet, while significantly induced LKB1 and AMPK phosphorylation. Taken together, our findings suggest that honokiol has an anti-lipogenic effect in hepatocytes, and this effect may be mediated by the LKB1–AMPK signaling pathway, which induces ACC phosphorylation and inhibits SREBP-1c maturation in hepatocytes. - Highlights: • Honokiol attenuates lipid accumulation induced by free fatty acid in hepatocyte. • Honokiol inhibits the increase in lipogenic enzyme levels induced by free fatty

Transient attenuation in optical fibers

International Nuclear Information System (INIS)

Hopkins, A.A.; Kelly, R.E.; Looney, L.D.; Lyons, P.B.

1984-01-01

Low and high energy pulsed electron beams were used to generate radiation-induced transient attenuation in high-OH, Suprasil core, PCS fibers, demonstrating the energy dependence of the radiation damage and recovery mechanisms. A radiation resistant low-OH fiber was studied and its performance contrasted to that of high-OH materials. Several fibers with differing core compositions were also studied

Patient position alters attenuation effects in multipinhole cardiac SPECT

International Nuclear Information System (INIS)

Timmins, Rachel; Ruddy, Terrence D.; Wells, R. Glenn

2015-01-01

position-dependent changes were removed with attenuation correction. Conclusions: Translation of a source relative to a multipinhole camera caused only small changes in homogeneous phantoms with SPS changing <1.5. Inhomogeneous attenuating media cause much larger changes to occur when the source is translated. Changes in SPS of up to six were seen in an anthropomorphic phantom for axial translations. Attenuation correction removes the position-dependent changes in attenuation

Simulation of Cycle-to-Cycle Variation in Dual-Fuel Engines

KAUST Repository

Jaasim, Mohammed; Pasunurthi, Shyamsundar; Jupudi, Ravichandra S.; Gubba, Sreenivasa Rao; Primus, Roy; Klingbeil, Adam; Wijeyakulasuriya, Sameera; Im, Hong G.

2017-01-01

Standard practices of internal combustion (IC) engine experiments are to conduct the measurements of quantities averaged over a large number of cycles. Depending on the operating conditions, the cycle-to-cycle variation (CCV) of quantities

A primordial and reversible TCA cycle in a facultatively chemolithoautotrophic thermophile.

Science.gov (United States)

Nunoura, Takuro; Chikaraishi, Yoshito; Izaki, Rikihisa; Suwa, Takashi; Sato, Takaaki; Harada, Takeshi; Mori, Koji; Kato, Yumiko; Miyazaki, Masayuki; Shimamura, Shigeru; Yanagawa, Katsunori; Shuto, Aya; Ohkouchi, Naohiko; Fujita, Nobuyuki; Takaki, Yoshihiro; Atomi, Haruyuki; Takai, Ken

2018-02-02

Inorganic carbon fixation is essential to sustain life on Earth, and the reductive tricarboxylic acid (rTCA) cycle is one of the most ancient carbon fixation metabolisms. A combination of genomic, enzymatic, and metabolomic analyses of a deeply branching chemolithotrophic Thermosulfidibacter takaii ABI70S6 T revealed a previously unknown reversible TCA cycle whose direction was controlled by the available carbon source(s). Under a chemolithoautotrophic condition, a rTCA cycle occurred with the reverse reaction of citrate synthase (CS) and not with the adenosine 5'-triphosphate-dependent citrate cleavage reactions that had been regarded as essential for the conventional rTCA cycle. Phylometabolic evaluation suggests that the TCA cycle with reversible CS may represent an ancestral mode of the rTCA cycle and raises the possibility of a facultatively chemolithomixotrophic origin of life. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Cell cycle-dependent SUMO-1 conjugation to nuclear mitotic apparatus protein (NuMA)

Energy Technology Data Exchange (ETDEWEB)

Seo, Jae Sung; Kim, Ha Na; Kim, Sun-Jick; Bang, Jiyoung; Kim, Eun-A; Sung, Ki Sa [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Yoon, Hyun-Joo [TissueGene Inc. 9605 Medical Center Dr., Rockville, MD 20850 (United States); Yoo, Hae Yong [Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Samsung Medical Center, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of); Choi, Cheol Yong, E-mail: choicy@skku.ac.kr [Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of)

2014-01-03

Highlights: •NuMA is modified by SUMO-1 in a cell cycle-dependent manner. •NuMA lysine 1766 is the primary target site for SUMOylation. •SUMOylation-deficient NuMA induces multiple spindle poles during mitosis. •SUMOylated NuMA induces microtubule bundling. -- Abstract: Covalent conjugation of proteins with small ubiquitin-like modifier 1 (SUMO-1) plays a critical role in a variety of cellular functions including cell cycle control, replication, and transcriptional regulation. Nuclear mitotic apparatus protein (NuMA) localizes to spindle poles during mitosis, and is an essential component in the formation and maintenance of mitotic spindle poles. Here we show that NuMA is a target for covalent conjugation to SUMO-1. We find that the lysine 1766 residue is the primary NuMA acceptor site for SUMO-1 conjugation. Interestingly, SUMO modification of endogenous NuMA occurs at the entry into mitosis and this modification is reversed after exiting from mitosis. Knockdown of Ubc9 or forced expression of SENP1 results in impairment of the localization of NuMA to mitotic spindle poles during mitosis. The SUMOylation-deficient NuMA mutant is defective in microtubule bundling, and multiple spindles are induced during mitosis. The mitosis-dependent dynamic SUMO-1 modification of NuMA might contribute to NuMA-mediated formation and maintenance of mitotic spindle poles during mitosis.

Abnormal mitosis triggers p53-dependent cell cycle arrest in human tetraploid cells.

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Kuffer, Christian; Kuznetsova, Anastasia Yurievna; Storchová, Zuzana

2013-08-01

Erroneously arising tetraploid mammalian cells are chromosomally instable and may facilitate cell transformation. An increasing body of evidence shows that the propagation of mammalian tetraploid cells is limited by a p53-dependent arrest. The trigger of this arrest has not been identified so far. Here we show by live cell imaging of tetraploid cells generated by an induced cytokinesis failure that most tetraploids arrest and die in a p53-dependent manner after the first tetraploid mitosis. Furthermore, we found that the main trigger is a mitotic defect, in particular, chromosome missegregation during bipolar mitosis or spindle multipolarity. Both a transient multipolar spindle followed by efficient clustering in anaphase as well as a multipolar spindle followed by multipolar mitosis inhibited subsequent proliferation to a similar degree. We found that the tetraploid cells did not accumulate double-strand breaks that could cause the cell cycle arrest after tetraploid mitosis. In contrast, tetraploid cells showed increased levels of oxidative DNA damage coinciding with the p53 activation. To further elucidate the pathways involved in the proliferation control of tetraploid cells, we knocked down specific kinases that had been previously linked to the cell cycle arrest and p53 phosphorylation. Our results suggest that the checkpoint kinase ATM phosphorylates p53 in tetraploid cells after abnormal mitosis and thus contributes to proliferation control of human aberrantly arising tetraploids.

Carnosic Acid, a Natural Diterpene, Attenuates Arsenic-Induced Hepatotoxicity via Reducing Oxidative Stress, MAPK Activation, and Apoptotic Cell Death Pathway

Directory of Open Access Journals (Sweden)

Sonjit Das

2018-01-01

Full Text Available The present studies have been executed to explore the protective mechanism of carnosic acid (CA against NaAsO2-induced hepatic injury. CA exhibited a concentration dependent (1–4 μM increase in cell viability against NaAsO2 (12 μM in murine hepatocytes. NaAsO2 treatment significantly enhanced the ROS-mediated oxidative stress in the hepatic cells both in in vitro and in vivo systems. Significant activation of MAPK, NF-κB, p53, and intrinsic and extrinsic apoptotic signaling was observed in NaAsO2-exposed hepatic cells. CA could significantly counteract with redox stress and ROS-mediated signaling and thereby attenuated NaAsO2-mediated hepatotoxicity. NaAsO2 (10 mg/kg treatment caused significant increment in the As bioaccumulation, cytosolic ATP level, DNA fragmentation, and oxidation in the liver of experimental mice (n=6. The serum biochemical and haematological parameters were significantly altered in the NaAsO2-exposed mice (n=6. Simultaneous treatment with CA (10 and 20 mg/kg could significantly reinstate the NaAsO2-mediated toxicological effects in the liver. Molecular docking and dynamics predicted the possible interaction patterns and the stability of interactions between CA and signal proteins. ADME prediction anticipated the drug-likeness characteristics of CA. Hence, there would be an option to employ CA as a new therapeutic agent against As-mediated toxic manifestations in future.

Inflammation and ER Stress Regulate Branched-Chain Amino Acid Uptake and Metabolism in Adipocytes

Science.gov (United States)

Burrill, Joel S.; Long, Eric K.; Reilly, Brian; Deng, Yingfeng; Armitage, Ian M.; Scherer, Philipp E.

2015-01-01

Inflammation plays a critical role in the pathology of obesity-linked insulin resistance and is mechanistically linked to the effects of macrophage-derived cytokines on adipocyte energy metabolism, particularly that of the mitochondrial branched-chain amino acid (BCAA) and tricarboxylic acid (TCA) pathways. To address the role of inflammation on energy metabolism in adipocytes, we used high fat-fed C57BL/6J mice and lean controls and measured the down-regulation of genes linked to BCAA and TCA cycle metabolism selectively in visceral but not in subcutaneous adipose tissue, brown fat, liver, or muscle. Using 3T3-L1 cells, TNFα, and other proinflammatory cytokine treatments reduced the expression of the genes linked to BCAA transport and oxidation. Consistent with this, [14C]-leucine uptake and conversion to triglycerides was markedly attenuated in TNFα-treated adipocytes, whereas the conversion to protein was relatively unaffected. Because inflammatory cytokines lead to the induction of endoplasmic reticulum stress, we evaluated the effects of tunicamycin or thapsigargin treatment of 3T3-L1 cells and measured a similar down-regulation in the BCAA/TCA cycle pathway. Moreover, transgenic mice overexpressing X-box binding protein 1 in adipocytes similarly down-regulated genes of BCAA and TCA metabolism in vivo. These results indicate that inflammation and endoplasmic reticulum stress attenuate lipogenesis in visceral adipose depots by down-regulating the BCAA/TCA metabolism pathway and are consistent with a model whereby the accumulation of serum BCAA in the obese insulin-resistant state is linked to adipose inflammation. PMID:25635940

Effect of sodium hypochlorite and peracetic acid on the surface roughness of acrylic resin polymerized by heated water for short and long cycles

Science.gov (United States)

Sczepanski, Felipe; Sczepanski, Claudia Roberta Brunnquell; Berger, Sandrine Bittencourt; Consani, Rafael Leonardo Xediek; Gonini-Júnior, Alcides; Guiraldo, Ricardo Danil

2014-01-01

Objective: To evaluate the surface roughness of acrylic resin submitted to chemical disinfection via 1% sodium hypochlorite (NaClO) or 1% peracetic acid (C2H4O3). Materials and Methods: The disc-shaped resin specimens (30 mm diameter ×4 mm height) were polymerized by heated water using two cycles (short cycle: 1 h at 74°C and 30 min at 100°C; conventional long cycle: 9 h at 74°C). The release of substances by these specimens in water solution was also quantified. Specimens were fabricated, divided into four groups (n = 10) depending on the polymerization time and disinfectant. After polishing, the specimens were stored in distilled deionized water. Specimens were immersed in 1% NaClO or 1% C2H4O3 for 30 min, and then were immersed in distilled deionized water for 20 min. The release of C2H4O3 and NaClO was measured via visual colorimetric analysis. Roughness was measured before and after disinfection. Roughness data were subjected to two-way ANOVA and Tukey's test. Results: There was no interaction between polymerization time and disinfectant in influencing the average surface roughness (Ra, P = 0.957). Considering these factors independently, there were significant differences between short and conventional long cycles (P = 0.012), but no significant difference between the disinfectants hypochlorite and C2H4O3 (P = 0.366). Visual colorimetric analysis did not detect release of substances. Conclusion: It was concluded that there was the difference in surface roughness between short and conventional long cycles, and disinfection at acrylic resins polymerized by heated water using a short cycle modified the properties of roughness. PMID:25512737

A method to attenuate U(VI) mobility in acidic waste plumes using humic acids

Energy Technology Data Exchange (ETDEWEB)

Wan, J.; Dong, W.; Tokunaga, T.K.

2011-02-01

Acidic uranium (U) contaminated plumes have resulted from acid-extraction of plutonium during the Cold War and from U mining and milling operations. A sustainable method for in-situ immobilization of U under acidic conditions is not yet available. Here, we propose to use humic acids (HAs) for in-situ U immobilization in acidic waste plumes. Our laboratory batch experiments show that HA can adsorb onto aquifer sediments rapidly, strongly and practically irreversibly. Adding HA greatly enhanced U adsorption capacity to sediments at pH below 5.0. Our column experiments using historically contaminated sediments from the Savannah River Site under slow flow rates (120 and 12 m/y) show that desorption of U and HA were non-detectable over 100 pore-volumes of leaching with simulated acidic groundwaters. Upon HA-treatment, 99% of the contaminant [U] was immobilized at pH < 4.5, compared to 5% and 58% immobilized in the control columns at pH 3.5 and 4.5, respectively. These results demonstrated that HA-treatment is a promising in-situ remediation method for acidic U waste plumes. As a remediation reagent, HAs are resistant to biodegradation, cost effective, nontoxic, and easily introducible to the subsurface.

Time-dependent inhibition of CYP3A4 by gallic acid in human liver microsomes and recombinant systems.

Science.gov (United States)

Pu, Qiang-Hong; Shi, Liang; Yu, Chao

2015-03-01

1.Gallic acid is a main polyphenol in various fruits and plants. Inhibitory characteristics of gallic acid on CYP3A4 were still unclear. The objective of this work is hence to investigate inhibitory characteristics of gallic acid on CYP3A4 using testosterone as the probe substrate in human liver microsomes (HLMs) and recombinant CYP3A4 (rCYP3A4) systems. 2.Gallic acid caused concentration-dependent loss of CYP3A4 activity with IC50 values of 615.2 μM and 669.5 μM in HLM and rCYP3A4 systems, respectively. IC50-shift experiments showed that pre-incubation with gallic acid in the absence of NADPH contributed to 12- or 14-fold reduction of IC50 in HLM and rCYP3A4 systems, respectively, supporting a time-dependent inhibition. In HLM, time-dependent inactivation variables KI and Kinact were 485.8 μM and 0.05 min(-1), respectively. 3.Compared with the presence of NADPH, pre-incubation of gallic acid in the absence of NADPH markedly increased its inhibitory effects in HLM and rCYP3A4 systems. Those results indicate that CYP3A4 inactivation by gallic acid was independent on NADPH and was mainly mediated its oxidative products. 4.In conclusion, we showed that gallic acid weakly and time-dependently inactivated CYP3A4 via its oxidative products.

A Critical Review on the Effect of Docosahexaenoic Acid (DHA) on Cancer Cell Cycle Progression.

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Newell, Marnie; Baker, Kristi; Postovit, Lynne M; Field, Catherine J

2017-08-17

Globally, there were 14.1 million new cancer diagnoses and 8.2 million cancer deaths in 2012. For many cancers, conventional therapies are limited in their successes and an improved understanding of disease progression is needed in conjunction with exploration of alternative therapies. The long chain polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to enhance many cellular responses that reduce cancer cell viability and decrease proliferation both in vitro and in vivo. A small number of studies suggest that DHA improves chemotherapy outcomes in cancer patients. It is readily incorporated into cancer cell membranes and, as a result there has been considerable research regarding cell membrane initiated events. For example, DHA has been shown to mediate the induction of apoptosis/reduction of proliferation in vitro and in vivo. However, there is limited research into the effect of DHA on cell cycle regulation in cancer cells and the mechanism(s) by which DHA acts are not fully understood. The purpose of the current review is to provide a critical examination of the literature investigating the ability of DHA to stall progression during different cell cycle phases in cancer cells, as well as the consequences that these changes may have on tumour growth, independently and in conjunction with chemotherapy.

Mammary inflammation around parturition appeared to be attenuated by consumption of fish oil rich in n-3 polyunsaturated fatty acids.

Science.gov (United States)

Lin, Sen; Hou, Jia; Xiang, Fang; Zhang, Xiaoling; Che, Lianqiang; Lin, Yan; Xu, Shengyu; Tian, Gang; Zeng, Qiufeng; Yu, Bing; Zhang, Keying; Chen, Daiwen; Wu, De; Fang, Zhengfeng

2013-12-31

Mastitis endangers the health of domestic animals and humans, and may cause problems concerning food safety. It is documented that n-3 polyunsaturated fatty acids (PUFA) play significant roles in attenuating saturated fatty acids (SFA)-induced inflammation. This study was therefore conducted to determine whether mammary inflammation could be affected by consumption of diets rich in n-3 PUFA. Forty-eight rats after mating began to receive diets supplemented with 5% fish oil (FO) or 7% soybean oil (SO). Blood and mammary tissue samples (n = 6) at day 0 and 14 of gestation and day 3 postpartum were collected 9 hours after intramammary infusion of saline or lipopolysaccharide (LPS) to determine free fatty acids (FFA) concentration and FA composition in plasma and inflammation mediators in mammary tissues. At day 14 of gestation and day 3 postpartum, the FO-fed rats had lower plasma concentrations of C18:2n6, C20:4n6, total n-6 PUFA and SFA, and higher plasma concentrations of C20:5n3 and total n-3 PUFA than the SO-fed rats. Plasma C22:6n3 concentration was also higher in the FO-fed than in the SO-fed rats at day 3 postpartum. Compared with the SO-fed rats, the FO-fed rats had lower mammary mRNA abundance of xanthine oxidoreductase (XOR) and protein level of tumor necrosis factor (TNF)-α, but had higher mammary mRNA abundances of interleukin (IL)-10 and peroxisome proliferator-activated receptor (PPAR)-γ at day 14 of gestation. Following LPS infusion at day 3 postpartum, the SO-fed rats had increased plasma concentrations of FFA, C18:1n9, C18:3n3, C18:2n6 and total n-6 PUFA, higher mammary mRNA abundances of IL-1β, TNF-α and XOR but lower mammary mRNA abundance of IL-10 than the FO-fed rats. Mammary inflammation around parturition appeared to be attenuated by consumption of a diet rich in n-3 PUFA, which was associated with up-regulated expression of IL-10 and PPAR-γ.

Mathematical modeling of (13)C label incorporation of the TCA cycle: the concept of composite precursor function.

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Uffmann, Kai; Gruetter, Rolf

2007-11-15

A novel approach for the mathematical modeling of (13)C label incorporation into amino acids via the TCA cycle that eliminates the explicit calculation of the labeling of the TCA cycle intermediates is described, resulting in one differential equation per measurable time course of labeled amino acid. The equations demonstrate that both glutamate C4 and C3 labeling depend in a predictable manner on both transmitochondrial exchange rate, V(X), and TCA cycle rate, V(TCA). For example, glutamate C4 labeling alone does not provide any information on either V(X) or V(TCA) but rather a composite "flux". Interestingly, glutamate C3 simultaneously receives label not only from pyruvate C3 but also from glutamate C4, described by composite precursor functions that depend in a probabilistic way on the ratio of V(X) to V(TCA): An initial rate of labeling of glutamate C3 (or C2) being close to zero is indicative of a high V(X)/V(TCA). The derived analytical solution of these equations shows that, when the labeling of the precursor pool pyruvate reaches steady state quickly compared with the turnover rate of the measured amino acids, instantaneous labeling can be assumed for pyruvate. The derived analytical solution has acceptable errors compared with experimental uncertainty, thus obviating precise knowledge on the labeling kinetics of the precursor. In conclusion, a substantial reformulation of the modeling of label flow via the TCA cycle turnover into the amino acids is presented in the current study. This approach allows one to determine metabolic rates by fitting explicit mathematical functions to measured time courses.

Selective Cyclin-Dependent Kinase Inhibitors Discriminating between Cell Cycle and Transcriptional Kinases Future Reality or Utopia?

Czech Academy of Sciences Publication Activity Database

Wesierska-Gadek, J.; Kryštof, Vladimír

2009-01-01

Roč. 1171, - (2009), s. 228-241 ISSN 0077-8923 R&D Projects: GA ČR GA204/08/0511 Institutional research plan: CEZ:AV0Z50380511 Keywords : cell cycle * CYC202 * cyclin-dependent kinase Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.670, year: 2009

Light Signaling-Dependent Regulation of Photoinhibition and Photoprotection in Tomato.

Science.gov (United States)

Wang, Feng; Wu, Nan; Zhang, Luyue; Ahammed, Golam Jalal; Chen, Xiaoxiao; Xiang, Xun; Zhou, Jie; Xia, Xiaojian; Shi, Kai; Yu, Jingquan; Foyer, Christine H; Zhou, Yanhong

2018-02-01

Photoreceptor-mediated light signaling plays a critical role in plant growth, development, and stress responses but its contribution to the spatial regulation of photoinhibition and photoprotection within the canopy remains unclear. Here, we show that low-red/far-red ( L - R / FR ) ratio light conditions significantly alleviate PSII and PSI photoinhibition in the shade leaves of tomato ( Solanum lycopersicum ) plants. This protection is accompanied by a phytochrome A-dependent induction of LONG HYPOCOTYL5 (HY5). HY5 binds to the promoter of ABA INSENSITIVE 5 ( ABI5 ), triggering RESPIRATORY BURST OXIDASE HOMOLOG1 ( RBOH1 )-dependent H 2 O 2 production in the apoplast. Decreased levels of HY5 , ABI5 , and RBOH1 transcripts increased cold-induced photoinhibition and abolished L - R / FR -induced alleviation of photoinhibition. L - R / FR illumination induced nonphotochemical quenching (NPQ) of chlorophyll a fluorescence and increased the activities of Foyer-Halliwell-Asada cycle enzymes and cyclic electron flux (CEF) around PSI. In contrast, decreased HY5 , ABI5 , and RBOH1 transcript levels abolished the positive effect of L - R / FR on photoprotection. Loss of PROTON GRADIENT REGULATION5 -dependent CEF led to increased photoinhibition and attenuated L - R / FR -dependent NPQ. These data demonstrate that HY5 is an important hub in the cross talk between light and cold response pathways, integrating ABA and reactive oxygen species signaling, leading to the attenuation of photoinhibition by enhanced induction of photoprotection in shade leaves. © 2018 American Society of Plant Biologists. All Rights Reserved.

Sleep deprivation impairs memory by attenuating mTORC1-dependent protein synthesis.

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Tudor, Jennifer C; Davis, Emily J; Peixoto, Lucia; Wimmer, Mathieu E; van Tilborg, Erik; Park, Alan J; Poplawski, Shane G; Chung, Caroline W; Havekes, Robbert; Huang, Jiayan; Gatti, Evelina; Pierre, Philippe; Abel, Ted

2016-04-26

Sleep deprivation is a public health epidemic that causes wide-ranging deleterious consequences, including impaired memory and cognition. Protein synthesis in hippocampal neurons promotes memory and cognition. The kinase complex mammalian target of rapamycin complex 1 (mTORC1) stimulates protein synthesis by phosphorylating and inhibiting the eukaryotic translation initiation factor 4E-binding protein 2 (4EBP2). We investigated the involvement of the mTORC1-4EBP2 axis in the molecular mechanisms mediating the cognitive deficits caused by sleep deprivation in mice. Using an in vivo protein translation assay, we found that loss of sleep impaired protein synthesis in the hippocampus. Five hours of sleep loss attenuated both mTORC1-mediated phosphorylation of 4EBP2 and the interaction between eukaryotic initiation factor 4E (eIF4E) and eIF4G in the hippocampi of sleep-deprived mice. Increasing the abundance of 4EBP2 in hippocampal excitatory neurons before sleep deprivation increased the abundance of phosphorylated 4EBP2, restored the amount of eIF4E-eIF4G interaction and hippocampal protein synthesis to that seen in mice that were not sleep-deprived, and prevented the hippocampus-dependent memory deficits associated with sleep loss. These findings collectively demonstrate that 4EBP2-regulated protein synthesis is a critical mediator of the memory deficits caused by sleep deprivation. Copyright © 2016, American Association for the Advancement of Science.

Gallic acid and p-coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats.

Science.gov (United States)

Abdel-Moneim, Adel; Yousef, Ahmed I; Abd El-Twab, Sanaa M; Abdel Reheim, Eman S; Ashour, Mohamed B

2017-08-01

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

Kinetic characterization for hemicellulose hydrolysis of corn stover in a dilute acid cycle spray flow-through reactor at moderate conditions

International Nuclear Information System (INIS)

Jin, Qiang; Zhang, Hongman; Yan, Lishi; Qu, Liang; Huang, He

2011-01-01

The kinetic characterization of hemicellulose hydrolysis of corn stover was investigated using a new reactor of dilute acid cycle spray flow-through (DCF) pretreatment. The primary purpose was to obtain kinetic data for hemicellulose hydrolysis with sulfuric acid concentrations (10-30 kg m -3 ) at relatively low temperatures (90-100 o C). A simplified kinetic model was used to describe its performance at moderate conditions. The results indicate that the rates of xylose formation and degradation are sensitive to flow rate, temperature and acid concentration. Moreover, the kinetic data of hemicellulose hydrolysis fit a first-order reaction model and the experimental data with actual acid concentration after accounting for the neutralization effect of the substrates at different temperatures. Over 90% of the xylose monomer yield and below 5.5% of degradation product (furfural) yield were observed in this reactor. Kinetic constants for hemicellulose hydrolysis models were analyzed by an Arrhenius-type equation, and the activation energy of xylose formation were 111.6 kJ mol -1 , and 95.7 kJ mol -1 for xylose degradation, respectively. -- Highlights: → Investigating a novel pretreatment reactor of dilute acid cycle spray flow-through. → Xylose yield is sensitive to flow rate, temperature and acid concentration. → Obtaining relatively higher xylose monomer yield and lower fermentation inhibitor. → Lumping hemicellulose and xylan oligmers together in the model is a valid way. → The kinetic model as a guide for reactor design, and operation strategy optimization.

FabQ, a Dual-Function Dehydratase/Isomerase, Circumvents the Last Step of the Classical Fatty Acid Synthesis Cycle

OpenAIRE

Bi, Hongkai; Wang, Haihong; Cronan, John E.

2013-01-01

In the classical anaerobic pathway of unsaturated fatty acid biosynthesis, that of Escherichia coli, the double bond is introduced into the growing acyl chain by the FabA dehydratase/isomerase. Another dehydratase, FabZ, functions in the chain elongation cycle. In contrast, Aerococcus viridans has only a single FabA/FabZ homolog we designate FabQ. FabQ can not only replace the function of E. coli FabZ in vivo, but it also catalyzes the isomerization required for unsaturated fatty acid biosynt...

Cell cycle-dependent induction of autophagy, mitophagy and reticulophagy.

Science.gov (United States)

Tasdemir, Ezgi; Maiuri, M Chiara; Tajeddine, Nicolas; Vitale, Ilio; Criollo, Alfredo; Vicencio, José Miguel; Hickman, John A; Geneste, Olivier; Kroemer, Guido

2007-09-15

When added to cells, a variety of autophagy inducers that operate through distinct mechanisms and target different organelles for autophagic destruction (mitochondria in mitophagy, endoplasmic reticulum in reticulophagy) rarely induce autophagic vacuolization in more than 50% or the cells. Here we show that this heterogeneity may be explained by cell cycle-specific effects. The BH3 mimetic ABT737, lithium, rapamycin, tunicamycin or nutrient depletion stereotypically induce autophagy preferentially in the G(1) and S phases of the cell cycle, as determined by simultaneous monitoring of cell cycle markers and the cytoplasmic aggregation of GFP-LC3 in autophagic vacuoles. These results point to a hitherto neglected crosstalk between autophagic vacuolization and cell cycle regulation.

Life cycle, techno-economic and dynamic simulation assessment of bioelectrochemical systems: A case of formic acid synthesis.

Science.gov (United States)

Shemfe, Mobolaji; Gadkari, Siddharth; Yu, Eileen; Rasul, Shahid; Scott, Keith; Head, Ian M; Gu, Sai; Sadhukhan, Jhuma

2018-05-01

A novel framework, integrating dynamic simulation (DS), life cycle assessment (LCA) and techno-economic assessment (TEA) of a bioelectrochemical system (BES), has been developed to study for the first time wastewater treatment by removal of chemical oxygen demand (COD) by oxidation in anode and thereby harvesting electron and proton for carbon dioxide reduction reaction or reuse to produce products in cathode. Increases in initial COD and applied potential increase COD removal and production (in this case formic acid) rates. DS correlations are used in LCA and TEA for holistic performance analyses. The cost of production of HCOOH is €0.015-0.005 g -1 for its production rate of 0.094-0.26 kg yr -1 and a COD removal rate of 0.038-0.106 kg yr -1 . The life cycle (LC) benefits by avoiding fossil-based formic acid production (93%) and electricity for wastewater treatment (12%) outweigh LC costs of operation and assemblage of BES (-5%), giving a net 61MJkg -1 HCOOH saving. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Microbial contributions to coupled arsenic and sulfur cycling in the acid-sulfide hot spring Champagne Pool, New Zealand.

Science.gov (United States)

Hug, Katrin; Maher, William A; Stott, Matthew B; Krikowa, Frank; Foster, Simon; Moreau, John W

2014-01-01

Acid-sulfide hot springs are analogs of early Earth geothermal systems where microbial metal(loid) resistance likely first evolved. Arsenic is a metalloid enriched in the acid-sulfide hot spring Champagne Pool (Waiotapu, New Zealand). Arsenic speciation in Champagne Pool follows reaction paths not yet fully understood with respect to biotic contributions and coupling to biogeochemical sulfur cycling. Here we present quantitative arsenic speciation from Champagne Pool, finding arsenite dominant in the pool, rim and outflow channel (55-75% total arsenic), and dithio- and trithioarsenates ubiquitously present as 18-25% total arsenic. In the outflow channel, dimethylmonothioarsenate comprised ≤9% total arsenic, while on the outflow terrace thioarsenates were present at 55% total arsenic. We also quantified sulfide, thiosulfate, sulfate and elemental sulfur, finding sulfide and sulfate as major species in the pool and outflow terrace, respectively. Elemental sulfur concentration reached a maximum at the terrace. Phylogenetic analysis of 16S rRNA genes from metagenomic sequencing revealed the dominance of Sulfurihydrogenibium at all sites and an increased archaeal population at the rim and outflow channel. Several phylotypes were found closely related to known sulfur- and sulfide-oxidizers, as well as sulfur- and sulfate-reducers. Bioinformatic analysis revealed genes underpinning sulfur redox transformations, consistent with sulfur speciation data, and illustrating a microbial role in sulfur-dependent transformation of arsenite to thioarsenate. Metagenomic analysis also revealed genes encoding for arsenate reductase at all sites, reflecting the ubiquity of thioarsenate and a need for microbial arsenate resistance despite anoxic conditions. Absence of the arsenite oxidase gene, aio, at all sites suggests prioritization of arsenite detoxification over coupling to energy conservation. Finally, detection of methyl arsenic in the outflow channel, in conjunction with

Amino acid infusion during anesthesia attenuates the surgery induced decline in IGF-1 and diminishes the "diabetes of injury"

Directory of Open Access Journals (Sweden)

Eksborg Staffan

2007-01-01

infusion to the volunteers did not affect any of the variables studied. Conclusion Amino acid infusion during surgery attenuates the decrease in IGF-1 and diminishes the "diabetes of injury".

Mapping Pn amplitude spreading and attenuation in Asia

Energy Technology Data Exchange (ETDEWEB)

Yang, Xiaoning [Los Alamos National Laboratory; Phillips, William S [Los Alamos National Laboratory; Stead, Richard J [Los Alamos National Laboratory

2010-12-06

Pn travels most of its path in the mantle lid. Mapping the lateral variation of Pn amplitude attenuation sheds light on material properties and dynamics of the uppermost region of the mantle. Pn amplitude variation depends on the wavefront geometric spreading as well as material attenuation. We investigated Pn geometric spreading, which is much more complex than a traditionally assumed power-law spreading model, using both synthetic and observed amplitude data collected in Asia. We derived a new Pn spreading model based on the formulation that was proposed previously to account for the spherical shape of the Earth (Yang et. al., BSSA, 2007). New parameters derived for the spreading model provide much better correction for Pn amplitudes in terms of residual behavior. Because we used observed Pn amplitudes to construct the model, the model incorporates not only the effect of the Earth's spherical shape, but also the effect of potential upper-mantle velocity gradients in the region. Using the new spreading model, we corrected Pn amplitudes measured at 1, 2, 4 and 6 Hz and conducted attenuation tomography. The resulting Pn attenuation model correlates well with the regional geology. We see high attenuation in regions such as northern Tibetan Plateau and the western Pacific subduction zone, and low attenuation for stable blocks such as Sichuan and Tarim basins.

Effects of attenuation map accuracy on attenuation-corrected micro-SPECT images

NARCIS (Netherlands)

Wu, C.; Gratama van Andel, H.A.; Laverman, P.; Boerman, O.C.; Beekman, F.J.

2013-01-01

Background In single-photon emission computed tomography (SPECT), attenuation of photon flux in tissue affects quantitative accuracy of reconstructed images. Attenuation maps derived from X-ray computed tomography (CT) can be employed for attenuation correction. The attenuation coefficients as well

Low-ω3 Fatty Acid and Soy Protein Attenuate Alcohol-Induced Fatty Liver and Injury by Regulating the Opposing Lipid Oxidation and Lipogenic Signaling Pathways

Directory of Open Access Journals (Sweden)

Karina Reyes-Gordillo

2016-01-01

Full Text Available Chronic ethanol-induced downregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-beta (PGC1β affect hepatic lipid oxidation and lipogenesis, respectively, leading to fatty liver injury. Low-ω3 fatty acid (Low-ω3FA that primarily regulates PGC1α and soy protein (SP that seems to have its major regulatory effect on PGC1β were evaluated for their protective effects against ethanol-induced hepatosteatosis in rats fed with Lieber-deCarli control or ethanol liquid diets with high or low ω3FA fish oil and soy protein. Low-ω3FA and SP opposed the actions of chronic ethanol by reducing serum and liver lipids with concomitant decreased fatty liver. They also prevented the downregulation of hepatic Sirtuin 1 (SIRT1 and PGC1α and their target fatty acid oxidation pathway genes and attenuated the upregulation of hepatic PGC1β and sterol regulatory element-binding protein 1c (SREBP1c and their target lipogenic pathway genes via the phosphorylation of 5′ adenosine monophosphate-activated protein kinase (AMPK. Thus, these two novel modulators attenuate ethanol-induced hepatosteatosis and consequent liver injury potentially by regulating the two opposing lipid oxidation and lipogenic pathways.

Role of NPR1 dependent and NPR1 independent genes in response to Salicylic acid

Directory of Open Access Journals (Sweden)

Neha Agarwal

2017-10-01

Full Text Available NPR1 (Nonexpressor of pathogenesis-related gene is a transcription coactivator and central regulator of systemic acquired resistance (SAR pathway. It controls wide range of pathogenesis related genes involved in various defense responses, acts by sensing SAR signal molecule, Salicylic acid (SA. Mutation in NPR1 results in increased susceptibility to pathogen infection and less expression of pathogenesis related genes. The present study aimed to identify the role of NPR1 in gene expression after the Salicylic acid induction. For this RNA-seq was performed in Arabidopsis thaliana Col-0 and npr1-1 in response to Salicylic acid. RNA-seq analysis revealed a total of 3811 differentially expressed gene in which 2109 genes are up-regulated and 1702 genes are down-regulated. We have divided these genes in 6 categories SA induced (SI, SA repressed (SR, NPR1 dependent SI (ND-SI, NPR1 dependent SR (ND-SR, NPR1 independent SI (NI-SI, NPR1 independent SR (NI-SR. Further, Gene ontology and MapMan pathway analysis of differentially expressed genes suggested variety of biological processes and metabolic pathways that are enriched during SAR defense pathway. These results contribute to shed light on importance of both NPR1-dependent (ND and NPR1-independent (NI gene acting downstream to Salicylic acid induction in SAR pathway. The present study aimed to identify the role of NPR1 in gene expression after the Salicylic acid induction.

Cell cycle-dependent regulation of kainate-induced inward currents in microglia

International Nuclear Information System (INIS)

Yamada, Jun; Sawada, Makoto; Nakanishi, Hiroshi

2006-01-01

Microglia are reported to have α-amino-hydroxy-5-methyl-isoxazole-4-propionate/kainate (KA) types. However, only small population of primary cultured rat microglia (approximately 20%) responded to KA. In the present study, we have attempted to elucidate the regulatory mechanism of responsiveness to KA in GMIR1 rat microglial cell line. When the GMIR1 cells were plated at a low density in the presence of granulocyte macrophage colony-stimulating factor, the proliferation rate increased and reached the peak after 2 days in culture and then gradually decreased because of density-dependent inhibition. At cell proliferation stage, approximately 80% of the GMIR1 cells exhibited glutamate (Glu)- and KA-induced inward currents at cell proliferation stage, whereas only 22.5% of the cells showed responsiveness to Glu and KA at cell quiescent stage. Furthermore, the mean amplitudes of inward currents induced by Glu and KA at cell proliferation stage (13.8 ± 3.0 and 8.4 ± 0.6 pA) were significantly larger than those obtained at cell quiescent stage (4.7 ± 0.8 and 6.2 ± 1.2 pA). In the GMIR1 cells, KA-induced inward currents were markedly inhibited by (RS)-3-(2-carboxybenzyl) willardiine (UBP296), a selective antagonist for KA receptors. The KA-responsive cells also responded to (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl) propanoic acid (ATPA), a selective agonist for GluR5, in both GMIR1 cells and primary cultured rat microglia. Furthermore, mRNA levels of the KA receptor subunits, GluR5 and GluR6, at the cell proliferation stage were significantly higher than those at the cell quiescent stage. Furthermore, the immunoreactivity for GluR6/7 was found to increase in activated microglia in the post-ischemic hippocampus. These results strongly suggest that microglia have functional KA receptors mainly consisting of GluR5 and GluR6, and the expression levels of these subunits are closely regulated by the cell cycle mechanism

Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats.

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Felix Ulbrich

Full Text Available Retinal ischemia and reperfusion injuries (IRI permanently affect neuronal tissue and function by apoptosis and inflammation due to the limited regenerative potential of neurons. Recently, evidence emerged that the noble gas Argon exerts protective properties, while lacking any detrimental or adverse effects. We hypothesized that Argon inhalation after IRI would exert antiapoptotic effects in the retina, thereby protecting retinal ganglion cells (RGC of the rat's eye.IRI was performed on the left eyes of rats (n = 8 with or without inhaled Argon postconditioning (25, 50 and 75 Vol% for 1 hour immediately or delayed after ischemia (i.e. 1.5 and 3 hours. Retinal tissue was harvested after 24 hours to analyze mRNA and protein expression of Bcl-2, Bax and Caspase-3, NF-κB. Densities of fluorogold-prelabeled RGCs were analyzed 7 days after injury in whole-mounts. Histological tissue samples were prepared for immunohistochemistry and blood was analyzed regarding systemic effects of Argon or IRI. Statistics were performed using One-Way ANOVA.IRI induced RGC loss was reduced by Argon 75 Vol% inhalation and was dose-dependently attenuated by lower concentrations, or by delayed Argon inhalation (1504±300 vs. 2761±257; p<0.001. Moreover, Argon inhibited Bax and Bcl-2 mRNA expression significantly (Bax: 1.64±0.30 vs. 0.78±0.29 and Bcl-2: 2.07±0.29 vs. 0.99±0.22; both p<0.01, as well as caspase-3 cleavage (1.91±0.46 vs. 1.05±0.36; p<0.001. Expression of NF-κB was attenuated significantly. Immunohistochemistry revealed an affection of Müller cells and astrocytes. In addition, IRI induced leukocytosis was reduced significantly after Argon inhalation at 75 Vol%.Immediate and delayed Argon postconditioning protects IRI induced apoptotic loss of RGC in a time- and dose-dependent manner, possibly mediated by the inhibition of NF-κB. Further studies need to evaluate Argon's possible role as a therapeutic option.

Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

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2015-01-01

Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by 1H NMR and LC–MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC–MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC–MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice. PMID:24702026

A review of acidity generation and consumption in acidic coal mine lakes and their watersheds.

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Blodau, Christian

2006-10-01

Lakes developing in former coal mine pits are often characterized by high concentrations of sulfate and iron and low pH. The review focuses on the causes for and fate of acidity in these lakes and their watersheds. Acidification is primarily caused by the generation of ferrous iron bearing and mineralized groundwater, transport through the groundwater-surface water interface, and subsequent iron oxidation and precipitation. Rates of acidity generation in mine tailings and dumps, and surface water are often similar (1 to >10 mol m(-2) yr(-1)). Weathering processes, however, often suffice to buffer groundwaters to only moderately acidic or neutral pH, depending on the suite of minerals present. In mine lakes, the acidity balance is further influenced by proton release from transformation of metastable iron hydroxysulfate minerals to goethite, and proton and ferrous iron sequestration by burial of iron sulfides and carbonates in sediments. These processes mostly cannot compensate acidity loading from the watershed, though. A master variable for almost all processes is the pH: rates of pyrite oxidation, ferrous iron oxidation, mineral dissolution, iron precipitation, iron hydroxide transformation, and iron and sulfate reduction are strongly pH dependent. While the principle mechanism of acidity generation and consumption and several controls are mostly understood, this cannot be said about the fate of acidity on larger spatial and temporal scales. Little is also known about critical loads and the internal regulation of biogeochemical iron, sulfur, and carbon cycling in acidic mine lakes.

A review of acidity generation and consumption in acidic coal mine lakes and their watersheds

International Nuclear Information System (INIS)

Blodau, Christian

2006-01-01

Lakes developing in former coal mine pits are often characterized by high concentrations of sulfate and iron and low pH. The review focuses on the causes for and fate of acidity in these lakes and their watersheds. Acidification is primarily caused by the generation of ferrous iron bearing and mineralized groundwater, transport through the groundwater-surface water interface, and subsequent iron oxidation and precipitation. Rates of acidity generation in mine tailings and dumps, and surface water are often similar (1 to >10 mol m -2 yr -1 ). Weathering processes, however, often suffice to buffer groundwaters to only moderately acidic or neutral pH, depending on the suite of minerals present. In mine lakes, the acidity balance is further influenced by proton release from transformation of metastable iron hydroxysulfate minerals to goethite, and proton and ferrous iron sequestration by burial of iron sulfides and carbonates in sediments. These processes mostly cannot compensate acidity loading from the watershed, though. A master variable for almost all processes is the pH: rates of pyrite oxidation, ferrous iron oxidation, mineral dissolution, iron precipitation, iron hydroxide transformation, and iron and sulfate reduction are strongly pH dependent. While the principle mechanism of acidity generation and consumption and several controls are mostly understood, this cannot be said about the fate of acidity on larger spatial and temporal scales. Little is also known about critical loads and the internal regulation of biogeochemical iron, sulfur, and carbon cycling in acidic mine lakes. (author)

2D Coda Attenuation Analysis of Active Sources: The Rockall Basin

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Sketsiou, P.; De Siena, L.; Asena, K.

2017-12-01

Passive seismic surveys are used for the evaluation of seismic attenuation parameters to characterise the Earth's lithosphere. Attenuation imaging is rarely applied to active datasets, attenuation being considered a hindrance than an efficient parameter when imaging reservoirs. In this study, we use one-component active source signals to study coda attenuation in the sub-basaltic North-Eastern Atlantic Margin, the Rockall Basin. Although this technique has been primarily used in volcanic and lithospheric environments, we apply it here to the oil and gas industrial setting. The Rockall Basin data consist of publicly available waveforms from the Oil and Gas Authority of the UK. The selected signals were band-passed filtered. A multiple scattering model was adopted, assuming dominant contributions from intrinsic absorption over scattering at large lapse times. The residual dependency of Q_c on the geometrical spreading factor was additionally investigated. The distribution of Q_c over a seismic line and its dependence on frequency were plotted, revealing high Q_c near a well in Rockall. The power law Q_c=Q_0(f/f_0)^\\gamma was used to express Q_c as a function of frequency.

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3) Leads to Increase of the Fatty Acid Biotransformation Activity.

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Woo, Ji-Min; Kim, Ji-Won; Song, Ji-Won; Blank, Lars M; Park, Jin-Byung

The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid)-induced stress. The metabolic and genomic responses of E. coli BL21(DE3) and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR) system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3). Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3) expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1)) into n-heptanoic acid (5) and 11-hydroxyundec-9-enoic acid (4). This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

Activation of the Glutamic Acid-Dependent Acid Resistance System in Escherichia coli BL21(DE3 Leads to Increase of the Fatty Acid Biotransformation Activity.

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Ji-Min Woo

Full Text Available The biosynthesis of carboxylic acids including fatty acids from biomass is central in envisaged biorefinery concepts. The productivities are often, however, low due to product toxicity that hamper whole-cell biocatalyst performance. Here, we have investigated factors that influence the tolerance of Escherichia coli to medium chain carboxylic acid (i.e., n-heptanoic acid-induced stress. The metabolic and genomic responses of E. coli BL21(DE3 and MG1655 grown in the presence of n-heptanoic acid indicated that the GadA/B-based glutamic acid-dependent acid resistance (GDAR system might be critical for cellular tolerance. The GDAR system, which is responsible for scavenging intracellular protons by catalyzing decarboxylation of glutamic acid, was inactive in E. coli BL21(DE3. Activation of the GDAR system in this strain by overexpressing the rcsB and dsrA genes, of which the gene products are involved in the activation of GadE and RpoS, respectively, resulted in acid tolerance not only to HCl but also to n-heptanoic acid. Furthermore, activation of the GDAR system allowed the recombinant E. coli BL21(DE3 expressing the alcohol dehydrogenase of Micrococcus luteus and the Baeyer-Villiger monooxygenase of Pseudomonas putida to reach 60% greater product concentration in the biotransformation of ricinoleic acid (i.e., 12-hydroxyoctadec-9-enoic acid (1 into n-heptanoic acid (5 and 11-hydroxyundec-9-enoic acid (4. This study may contribute to engineering E. coli-based biocatalysts for the production of carboxylic acids from renewable biomass.

Importance of glutamine metabolism in leukemia cells by energy production through TCA cycle and by redox homeostasis.

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Goto, Mineaki; Miwa, Hiroshi; Shikami, Masato; Tsunekawa-Imai, Norikazu; Suganuma, Kazuto; Mizuno, Shohei; Takahashi, Miyuki; Mizutani, Motonori; Hanamura, Ichiro; Nitta, Masakazu

2014-07-01

Some cancer cells depend on glutamine despite of pronounced glycolysis. We examined the glutamine metabolism in leukemia cells, and found that HL-60 cells most depended on glutamine in the 4 acute myelogenous leukemia (AML) cell lines examined: growth of HL-60 cells was most suppressed by glutamine deprivation and by inhibition of glutaminolysis, which was rescued by tricarboxylic acid (TCA) cycle intermediate, oxaloacetic acid. Glutamine is also involved in antioxidant defense function by increasing glutathione. Glutamine deprivation suppressed the glutathione content and elevated reactive oxygen species most evidently in HL-60 cells. Glutamine metabolism might be a therapeutic target in some leukemia.

A novel technology for neutralizing acidity and attenuating toxic chemical species from acid mine drainage using cryptocrystalline magnesite tailings

CSIR Research Space (South Africa)

Masindi, Vhahangwele

2016-04-01

Full Text Available neutralize and attenuate elevated concentrations of chemical species in AMD to within prescribed legal frameworks for water use in agricultural and industrial sectors in South Africa....

Lg Attenuation Modeling in the Middle East

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Pasyanos, M. E.; Matzel, E. M.; Walter, W. R.; Rodgers, A. J.

2008-12-01

We present a broadband tomographic model of Lg attenuation in the Middle East derived from source- and site-corrected amplitudes. The study region spans from Turkey through the Arabian Peninsula and Iran to Pakistan, Afghanistan, and northwest India. Absolute amplitude measurements are made on hand-selected and carefully windowed seismograms for tens of stations and thousands of crustal earthquakes resulting in excellent coverage of the region. We have modified the standard attenuation tomography technique to more explicitly define the earthquake source expression in terms of the seismic moment. This facilitates the use of the model to predict the expected amplitudes of new events, an important consideration for earthquake hazard or explosion monitoring applications. We will discuss the updated method and implications of this parameterization. A conjugate gradient method is used to tomographically invert the amplitude dataset of over 8000 paths. We solve for Q variation, as well as site and source terms, for a wide range of frequencies ranging from 0.5 -- 10 Hz. The attenuation results have a strong correlation to tectonics. Shields have low attenuation, while tectonic regions have high attenuation, with the highest attenuation at 1 Hz found in eastern Turkey. The results also compare favorably to other studies in the region made using Lg propagation efficiency, Lg/Pg amplitude ratios and two-station methods. We tomographically invert the amplitude measurements for each frequency independently. In doing so, it appears the frequency-dependence of attenuation is not compatible with the power law representation of Q(f). This research was performed under the auspices of the U.S. Department of Energy by the Lawrence Livermore National Laboratory under contract number DE-AC52-07NA27344. This is LLNL contribution LLNL-ABS-406761.

Effect of inhibitors on acid production by baker's yeast.

Science.gov (United States)

Sigler, K; Knotková, A; Kotyk, A

1978-01-01

Glucose-induced acid extrusion, respiration and anaerobic fermentation in baker's yeast was studied with the aid of sixteen inhibitors. Uranyl(2+) nitrate affected the acid extrusion more anaerobically than aerobically; the complexing of Mg2+ and Ca2+ by EDTA at the membrane had no effect. Inhibitors of glycolysis (iodoacetamide, N-ethylmaleimide, fluoride) suppressed acid production markedly, and so did the phosphorylation-blocking arsenate. Fluoroacetate, inhibiting the citric-acid cycle, had no effect. Inhibition by uncouplers depended on their pKa values: 2,4,6-trinitrophenol (pKa 0.4) less than 2,4-dinitrophenol (4.1) less than azide (4.7) less than 3-chlorophenylhydrazonomalononitrile (6.0). Inhibition by trinitrophenol was only slightly increased by its acetylation. Cyanide and nonpermeant oligomycin showed practically no effect; inhibition by dicyclohexylcarbodiimide was delayed but potent. The concentration profiles of inhibition of acid production differed from those of respiration and fermentation. Thus, though the acid production is a metabolically dependent process, it does not reflect the intensity of metabolism, except partly in the first half of glycolysis.

The bile acids, deoxycholic acid and ursodeoxycholic acid, regulate colonic epithelial wound healing.

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Mroz, Magdalena S; Lajczak, Natalia K; Goggins, Bridie J; Keely, Simon; Keely, Stephen J

2018-03-01

The intestinal epithelium constitutes an innate barrier which, upon injury, undergoes self-repair processes known as restitution. Although bile acids are known as important regulators of epithelial function in health and disease, their effects on wound healing processes are not yet clear. Here we set out to investigate the effects of the colonic bile acids, deoxycholic acid (DCA) and ursodeoxycholic acid (UDCA), on epithelial restitution. Wound healing in T 84 cell monolayers grown on transparent, permeable supports was assessed over 48 h with or without bile acids. Cell migration was measured in Boyden chambers. mRNA and protein expression were measured by RT-PCR and Western blotting. DCA (50-150 µM) significantly inhibited wound closure in cultured epithelial monolayers and attenuated cell migration in Boyden chamber assays. DCA also induced nuclear accumulation of the farnesoid X receptor (FXR), whereas an FXR agonist, GW4064 (10 µM), inhibited wound closure. Both DCA and GW4064 attenuated the expression of CFTR Cl - channels, whereas inhibition of CFTR activity with either CFTR- inh -172 (10 µM) or GlyH-101 (25 µM) also prevented wound healing. Promoter/reporter assays revealed that FXR-induced downregulation of CFTR is mediated at the transcriptional level. In contrast, UDCA (50-150 µM) enhanced wound healing in vitro and prevented the effects of DCA. Finally, DCA inhibited and UDCA promoted mucosal healing in an in vivo mouse model. In conclusion, these studies suggest bile acids are important regulators of epithelial wound healing and are therefore good targets for development of new drugs to modulate intestinal barrier function in disease treatment. NEW & NOTEWORTHY The secondary bile acid, deoxycholic acid, inhibits colonic epithelial wound healing, an effect which appears to be mediated by activation of the nuclear bile acid receptor, FXR, with subsequent downregulation of CFTR expression and activity. In contrast, ursodeoxycholic acid promotes

Combined effects of spatially variable flow and mineralogy on the attenuation of acid mine drainage in groundwater

International Nuclear Information System (INIS)

Malmstroem, Maria E.; Berglund, Sten; Jarsjoe, Jerker

2008-01-01

Quantifications of the spreading of acid mine drainage (AMD) in groundwater are needed for risk assessments of mining sites. However, due to subsurface heterogeneity, available field data may prove insufficient for deterministic process descriptions, even at well-characterized sites. Here, the probabilistic LaSAR-PHREEQC model is used to consider multicomponent reactions and transport in heterogeneous (flow and geochemistry) groundwater surrounding a mine waste site, with specific focus on the spreading of Zn. Model results, using field data from a mill tailings impoundment in northern Sweden (including major component geochemistry), indicate that precipitation of smithsonite (ZnCO 3 ) may drastically delay the downstream arrival of Zn, but may also cause a peak concentration once the retained Zn is released. The amount of smithsonite formed is, however, minute and its spatial variation large, such that detection of smithsonite in soil samples may be difficult. Results further show that even a low degree of flow heterogeneity can effectively smooth otherwise distinctive temporal concentration changes attributed to the considered chemical reactions, and thereby mask the attenuation processes. By contrast, the existence of preferential flow paths can cause temporally separated concentration peaks in response to a single chemical reaction chain, even in a geochemically homogeneous domain, making the interpretation of the concentration curves non-trivial. The stochastic modelling results for Zn considering flow and/or mineralogical heterogeneity indicate a less efficient Zn attenuation than predicted by standard, deterministic reactive-transport models. In addition, in all considered probabilistic Zn and SO 4 2- scenarios, the spatial variability in downstream pollutant concentration was high, implying that a relatively large number of point samples are needed to determine field-scale mean concentrations

pH-, Lactic acid-, and non-lactic acid-dependent activities of probiotic Lactobacilli against Salmonella enterica Serovar Typhimurium.

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Fayol-Messaoudi, Domitille; Berger, Cédric N; Coconnier-Polter, Marie-Hélène; Liévin-Le Moal, Vanessa; Servin, Alain L

2005-10-01

The mechanism(s) underlying the antibacterial activity of probiotic Lactobacillus strains appears to be multifactorial and includes lowering of the pH and the production of lactic acid and of antibacterial compounds, including bacteriocins and nonbacteriocin, non-lactic acid molecules. Addition of Dulbecco's modified Eagle's minimum essential medium to the incubating medium delays the killing activity of lactic acid. We found that the probiotic strains Lactobacillus johnsonii La1, Lactobacillus rhamnosus GG, Lactobacillus casei Shirota YIT9029, L. casei DN-114 001, and L. rhamnosus GR1 induced a dramatic decrease in the viability of Salmonella enterica serovar Typhimurium SL1344 mainly attributable to non-lactic acid molecule(s) present in the cell-free culture supernatant (CFCS). These molecules were more active against serovar Typhimurium SL1344 in the exponential growth phase than in the stationary growth phase. We also showed that the production of the non-lactic acid substance(s) responsible for the killing activity was dependent on growth temperature and that both unstable and stable substances with killing activity were present in the CFCSs. We found that the complete inhibition of serovar Typhimurium SL1344 growth results from a pH-lowering effect.

Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

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Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

2015-09-01

Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

HIV-1 and its gp120 inhibits the influenza A(H1N1)pdm09 life cycle in an IFITM3-dependent fashion.

Science.gov (United States)

Mesquita, Milene; Fintelman-Rodrigues, Natalia; Sacramento, Carolina Q; Abrantes, Juliana L; Costa, Eduardo; Temerozo, Jairo R; Siqueira, Marilda M; Bou-Habib, Dumith Chequer; Souza, Thiago Moreno L

2014-01-01

HIV-1-infected patients co-infected with A(H1N1)pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1)pdm09 life cycle in vitro. We show here that exposure of A(H1N1)pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1)pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs) to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1)pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA) gene from in vitro experiments and from samples of HIV-1/A(H1N1)pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1)pdm09 co-infected patients during the recent influenza form 2009/2010.

HIV-1 and its gp120 inhibits the influenza A(H1N1pdm09 life cycle in an IFITM3-dependent fashion.

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Milene Mesquita

Full Text Available HIV-1-infected patients co-infected with A(H1N1pdm09 surprisingly presented benign clinical outcome. The knowledge that HIV-1 changes the host homeostatic equilibrium, which may favor the patient resistance to some co-pathogens, prompted us to investigate whether HIV-1 infection could influence A(H1N1pdm09 life cycle in vitro. We show here that exposure of A(H1N1pdm09-infected epithelial cells to HIV-1 viral particles or its gp120 enhanced by 25% the IFITM3 content, resulting in a decrease in influenza replication. This event was dependent on toll-like receptor 2 and 4. Moreover, knockdown of IFITM3 prevented HIV-1 ability to inhibit A(H1N1pdm09 replication. HIV-1 infection also increased IFITM3 levels in human primary macrophages by almost 100%. Consequently, the arrival of influenza ribonucleoproteins (RNPs to nucleus of macrophages was inhibited, as evaluated by different approaches. Reduction of influenza RNPs entry into the nucleus tolled A(H1N1pdm09 life cycle in macrophages earlier than usual, limiting influenza's ability to induce TNF-α. As judged by analysis of the influenza hemagglutin (HA gene from in vitro experiments and from samples of HIV-1/A(H1N1pdm09 co-infected individuals, the HIV-1-induced reduction of influenza replication resulted in delayed viral evolution. Our results may provide insights on the mechanisms that may have attenuated the clinical course of Influenza in HIV-1/A(H1N1pdm09 co-infected patients during the recent influenza form 2009/2010.

Research on strength attenuation law of concrete in freezing - thawing environment

Science.gov (United States)

Xiao, qianhui; Cao, zhiyuan; Li, qiang

2018-03-01

By rapid freezing and thawing method, the experiments of concrete have been 300 freeze-thaw cycles specimens in the water. The cubic compression strength value under different freeze-thaw cycles was measured. By analyzing the test results, the water-binder ratio of the concrete under freeze-thaw environments, fly ash and air entraining agent is selected dosage recommendations. The exponential attenuation prediction model and life prediction model of compression strength of concrete under freezing-thawing cycles considering the factors of water-binder ratio, fly ash content and air-entraining agent dosage were established. The model provides the basis for predicting the durability life of concrete under freezing-thawing environment. It also provides experimental basis and references for further research on concrete structures with antifreeze requirements.

Ellagic acid derivatives from Terminalia chebula Retz. downregulate the expression of quorum sensing genes to attenuate Pseudomonas aeruginosa PAO1 virulence.

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Sajal Sarabhai

Full Text Available BACKGROUND: Burgeoning antibiotic resistance in Pseudomonas aeruginosa has necessitated the development of anti pathogenic agents that can quench acylhomoserine lactone (AHL mediated QS with least risk of resistance. This study explores the anti quorum sensing potential of T. chebula Retz. and identification of probable compounds(s showing anti QS activity and the mechanism of attenuation of P. aeruginosa PAO1 virulence factors. METHODS AND RESULTS: Methanol extract of T. chebula Retz. fruit showed anti QS activity using Agrobacterium tumefaciens A136. Bioactive fraction (F7, obtained by fractionation of methanol extract using Sephadex LH20, showed significant reduction (p<0.001 in QS regulated production of extracellular virulence factors in P. aeruginosa PAO1. Biofilm formation and alginate were significantly (p<0.05 reduced with enhanced (20% susceptibility to tobramycin. Real Time PCR of F7 treated P. aeruginosa showed down regulation of autoinducer synthase (lasI and rhlI and their cognate receptor (lasR and rhlR genes by 89, 90, 90 and 93%, respectively. Electrospray Ionization Mass Spectrometry also showed 90 and 64% reduction in the production of 3-oxo-C(12HSL and C(4HSL after treatment. Decrease in AHLs as one of the mechanisms of quorum quenching by F7 was supported by the reversal of inhibited swarming motility in F7-treated P. aeruginosa PAO1 on addition of C(4HSL. F7 also showed antagonistic activity against 3-oxo-C(12HSL-dependent QS in E. coli bioreporter. C. elegans fed on F7-treated P. aeruginosa showed enhanced survival with LT50 increasing from 24 to 72 h. LC-ESI-MS of F7 revealed the presence of ellagic acid derivatives responsible for anti QS activity in T. chebula extract. CONCLUSIONS: This is the first report on anti QS activity of T. chebula fruit linked to EADs which down regulate the expression of lasIR and rhlIR genes with concomitant decrease in AHLs in P. aeruginosa PAO1 causing attenuation of its virulence factors

Bile acids induce necrosis in pancreatic stellate cells dependent on calcium entry and sodium‐driven bile uptake

Science.gov (United States)

Jakubowska, Monika A.; Gerasimenko, Julia V.; Gerasimenko, Oleg V.; Petersen, Ole H.

2016-01-01

Key points Acute biliary pancreatitis is a sudden and severe condition initiated by bile reflux into the pancreas.Bile acids are known to induce Ca2+ signals and necrosis in isolated pancreatic acinar cells but the effects of bile acids on stellate cells are unexplored.Here we show that cholate and taurocholate elicit more dramatic Ca2+ signals and necrosis in stellate cells compared to the adjacent acinar cells in pancreatic lobules; whereas taurolithocholic acid 3‐sulfate primarily affects acinar cells.Ca2+ signals and necrosis are strongly dependent on extracellular Ca2+ as well as Na+; and Na+‐dependent transport plays an important role in the overall bile acid uptake in pancreatic stellate cells.Bile acid‐mediated pancreatic damage can be further escalated by bradykinin‐induced signals in stellate cells and thus killing of stellate cells by bile acids might have important implications in acute biliary pancreatitis. Abstract Acute biliary pancreatitis, caused by bile reflux into the pancreas, is a serious condition characterised by premature activation of digestive enzymes within acinar cells, followed by necrosis and inflammation. Bile acids are known to induce pathological Ca2+ signals and necrosis in acinar cells. However, bile acid‐elicited signalling events in stellate cells remain unexplored. This is the first study to demonstrate the pathophysiological effects of bile acids on stellate cells in two experimental models: ex vivo (mouse pancreatic lobules) and in vitro (human cells). Sodium cholate and taurocholate induced cytosolic Ca2+ elevations in stellate cells, larger than those elicited simultaneously in the neighbouring acinar cells. In contrast, taurolithocholic acid 3‐sulfate (TLC‐S), known to induce Ca2+ oscillations in acinar cells, had only minor effects on stellate cells in lobules. The dependence of the Ca2+ signals on extracellular Na+ and the presence of sodium–taurocholate cotransporting polypeptide (NTCP) indicate a Na+‐dependent

Molecular cloning and expression analysis of jasmonic acid dependent but salicylic acid independent LeWRKY1.

Science.gov (United States)

Lu, M; Wang, L F; Du, X H; Yu, Y K; Pan, J B; Nan, Z J; Han, J; Wang, W X; Zhang, Q Z; Sun, Q P

2015-11-30

Various plant genes can be activated or inhibited by phytohormones under conditions of biotic and abiotic stress, especially in response to jasmonic acid (JA) and salicylic acid (SA). Interactions between JA and SA may be synergistic or antagonistic, depending on the stress condition. In this study, we cloned a full-length cDNA (LeWRKY1, GenBank accession No. FJ654265) from Lycopersicon esculentum by rapid amplification of cDNA ends. Sequence analysis showed that this gene is a group II WRKY transcription factor. Analysis of LeWRKY1 mRNA expression in various tissues by qRT-PCR showed that the highest and lowest expression occurred in the leaves and stems, respectively. In addition, LeWRKY1 expression was induced by JA and Botrytis cinerea Pers., but not by SA.

Levels of Arabidopsis thaliana leaf phosphatidic acids, phosphatidylserines, and most trienoate-containing polar lipid molecular species increase during the dark period of the diurnal cycle

Directory of Open Access Journals (Sweden)

Sara eMaatta

2012-03-01

Full Text Available Previous work has demonstrated that plant leaf polar lipid fatty acid composition varies during the diurnal (dark-light cycle. Fatty acid synthesis occurs primarily during the light, but fatty acid desaturation continues in the absence of light, resulting in polyunsaturated fatty acids reaching their highest levels toward the end of the dark period. In this work, Arabidopsis thaliana were grown at constant (21°C temperature with 12-h light and 12-h dark periods. Collision induced dissociation time-of-flight mass spectrometry demonstrated that 16:3 and 18:3 fatty acid content in membrane lipids of leaves are higher at the end of the dark than at the end of the light period, while 16:1, 16:2, 18:0, and 18:1 content are higher at the end of the light period. Lipid profiling of membrane galactolipids, phospholipids, and lysophospholipids by electrospray ionization triple quadrupole mass spectrometry indicated that the monogalactosyldiacylglycerol, phosphatidylglycerol, and phosphatidylcholine classes include molecular species whose levels are highest at end of the light period and others that are highest at the end of the dark period. The levels of phosphatidic acid and phosphatidylserine classes were higher at the end of the dark period, and molecular species within these classes either followed the class pattern or were not significantly changed in the diurnal cycle. Phospholipase D (PLD is a family of enzymes that hydrolyzes phospholipids to produce phosphatidic acid. Analysis of several PLD mutant lines suggests that PLDζ2 and possibly PLDα1 may contribute to diurnal cycling of phosphatidic acid. The polar lipid compositional changes are considered in relation to recent data that demonstrate phosphatidylcholine acyl editing.

Note: Attenuation motion of acoustically levitated spherical rotor

Science.gov (United States)

Lü, P.; Hong, Z. Y.; Yin, J. F.; Yan, N.; Zhai, W.; Wang, H. P.

2016-11-01

Here we observe the attenuation motion of spherical rotors levitated by near-field acoustic radiation force and analyze the factors that affect the duration time of free rotation. It is found that the rotating speed of freely rotating rotor decreases exponentially with respect to time. The time constant of exponential attenuation motion depends mainly on the levitation height, the mass of rotor, and the depth of concave ultrasound emitter. Large levitation height, large mass of rotor, and small depth of concave emitter are beneficial to increase the time constant and hence extend the duration time of free rotation.

Nucleolar TRF2 attenuated nucleolus stress-induced HCC cell-cycle arrest by altering rRNA synthesis.

Science.gov (United States)

Yuan, Fuwen; Xu, Chenzhong; Li, Guodong; Tong, Tanjun

2018-05-03

The nucleolus is an important organelle that is responsible for the biogenesis of ribosome RNA (rRNA) and ribosomal subunits assembly. It is also deemed to be the center of metabolic control, considering the critical role of ribosomes in protein translation. Perturbations of rRNA synthesis are closely related to cell proliferation and tumor progression. Telomeric repeat-binding factor 2 (TRF2) is a member of shelterin complex that is responsible for telomere DNA protection. Interestingly, it was recently reported to localize in the nucleolus of human cells in a cell-cycle-dependent manner, while the underlying mechanism and its role on the nucleolus remained unclear. In this study, we found that nucleolar and coiled-body phosphoprotein 1 (NOLC1), a nucleolar protein that is responsible for the nucleolus construction and rRNA synthesis, interacted with TRF2 and mediated the shuttle of TRF2 between the nucleolus and nucleus. Abating the expression of NOLC1 decreased the nucleolar-resident TRF2. Besides, the nucleolar TRF2 could bind rDNA and promoted rRNA transcription. Furthermore, in hepatocellular carcinoma (HCC) cell lines HepG2 and SMMC7721, TRF2 overexpression participated in the nucleolus stress-induced rRNA inhibition and cell-cycle arrest.

Temperature dependence of relaxation times in proton components of fatty acids

International Nuclear Information System (INIS)

Kuroda, Kagayaki; Iwabuchi, Taku; Saito, Kensuke; Obara, Makoto; Honda, Masatoshi; Imai, Yutaka

2011-01-01

We examined the temperature dependence of relaxation times in proton components of fatty acids in various samples in vitro at 11 tesla as a standard calibration data for quantitative temperature imaging of fat. The spin-lattice relaxation time, T 1 , of both the methylene (CH 2 ) chain and terminal methyl (CH 3 ) was linearly related to temperature (r>0.98, P 2 signal for calibration and observed the signal with 18% of CH 3 to estimate temperature. These findings suggested that separating the fatty acid components would significantly improve accuracy in quantitative thermometry for fat. Use of the T 1 of CH 2 seems promising in terms of reliability and reproducibility in measuring temperature of fat. (author)

Carotid baroreflex function at the onset of cycling in men

DEFF Research Database (Denmark)

Barbosa, Thales C; Vianna, Lauro C; Hashimoto, Takeshi

2016-01-01

moderate-intensity exercise (P mediated by an increase in the total vascular conductance. These findings evidence altered carotid baroreflex function during the first 35 s of cycling compared with rest, with attenuated bradycardic......Arterial baroreflex function is important for blood pressure control during exercise, but its contribution to cardiovascular adjustments at the onset of cycling exercise remains unclear. Fifteen healthy male subjects (24 ± 1 yr) performed 45-s trials of low- and moderate-intensity cycling...... during moderate-intensity exercise, compared with the response at rest (P

Postprandial triglyceride-rich lipoproteins promote lipid accumulation and apolipoprotein B-48 receptor transcriptional activity in human circulating and murine bone marrow neutrophils in a fatty acid-dependent manner.

Science.gov (United States)

Ortega-Gómez, Almudena; Varela, Lourdes M; López, Sergio; Montserrat de la Paz, Sergio; Sánchez, Rosario; Muriana, Francisco J G; Bermúdez, Beatriz; Abia, Rocío

2017-09-01

Postprandial triglyceride-rich lipoproteins (TRLs) promote atherosclerosis. Recent research points the bone marrow (BM) as a primary site in atherosclerosis. We elucidated how the acute administration of monounsaturated fatty acids (MUFAs) MUFAs, omega-3 polyunsaturated fatty acids (PUFAs) PUFAs and saturated fatty acids (SFAs) affects human circulating and murine BM neutrophil lipid accumulation and functionality. Postprandial hypertriglyceridemia was induced in healthy subjects and Apoe -/- mice by the acute administration of dietary fats enriched in MUFAs, PUFAs, or SFAs. Postprandial hypertriglyceridemia increased apolipoprotein-B48 receptor (ApoB48R) transcriptional activity that was linearly correlated with intracellular triglycerides (TGs) TGs accumulation in human circulating and murine BM neutrophils. MUFA and omega-3 PUFAs attenuated ApoB48R gene expression and intracellular TG accumulation compared to SFAs. TRLs induced apoB48R-dependent TG accumulation in human neutrophils ex vivo. Murine BM neutrophils showed a decrease in surface L-selectin and an increase in TNF-α and IL-1β mRNA expressions only after SFAs administration. TRLs enriched in SFAs induced BM neutrophil degranulation ex vivo suggesting cell priming/activation. Postprandial TRLs disrupts the normal biology and function of circulating and BM neutrophils. MUFA- and omega-3 PUFA-rich dietary fats such as virgin olive oil or fish oil has the potential to prevent excessive neutrophil lipid accumulation and activation by targeting the fatty acid composition of TRLs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

ADVANCING THE SCIENCE OF NATURAL AND ENHANCED ATTENUATION FOR CHLORINATED SOLVENTS

Energy Technology Data Exchange (ETDEWEB)

Looney, B; TOM O. EARLY, T; TYLER GILMORE, T; FRANCIS H. CHAPELLE, F; NORMAN H. CUTSHALL, N; JEFF ROSS, J; MARK ANKENY, M; Michael Heitkamp, M; DAVID MAJOR, D; CHARLES J. NEWELL, C; W. JODY WAUGH, W; GARY WEIN, G; Karen Vangelas, K; Karen-M Adams, K; CLAIRE H. SINK, C

2006-12-27

This report summarizes the results of a three-year program that addressed key scientific and technical aspects related to natural and enhanced attenuation of chlorinated organics. The results from this coordinated three-year program support a variety of technical and regulatory advancements. Scientists, regulators, engineers, end-users and stakeholders participated in the program, which was supported by the U.S. Department of Energy (DOE) and the Interstate Technology and Regulatory Council (ITRC). The overarching objective of the effort was to examine environmental remedies that are based on natural processes--remedies such as Monitored Natural Attenuation (MNA) or Enhanced Attenuation (EA). A key result of the recent effort was the general affirmation of the approaches and guidance in the original U.S. Environmental Protection Agency (EPA) chlorinated solvent MNA protocols and directives from 1998 and 1999, respectively. The research program did identify several specific opportunities for advances based on: (1) mass balance as the central framework for attenuation based remedies, (2) scientific advancements and achievements during the past ten years, (3) regulatory and policy development and real-world experience using MNA, and (4) exploration of various ideas for integrating attenuation remedies into a systematic set of ''combined remedies'' for contaminated sites. These opportunities are summarized herein and are addressed in more detail in referenced project documents and journal articles, as well as in the technical and regulatory documents being developed within the ITRC. Natural attenuation processes occur in all soil and groundwater systems and act, to varying degrees, on all contaminants. Thus, a decision to rely on natural attenuation processes as part of a site-remediation strategy does not depend on the occurrence of natural attenuation, but on its effectiveness in meeting site-specific remediation goals. Meeting these goals

Tricarboxylic acid cycle activity measured by 13C magnetic resonance spectroscopy in rats subjected to the kaolin model of obstructed hydrocephalus

DEFF Research Database (Denmark)

Melø, Torun M; Håberg, Asta K; Risa, Øystein

2011-01-01

in the amounts of glutamate, alanine and taurine. In addition, the concentration of the neuronal marker N-acetyl aspartate was decreased. (13)C Labelling of most amino acids derived from [1,6-(13)C]glucose was unchanged 2 weeks after hydrocephalus induction. The only indication of astrocyte impairment......Evaluating early changes in cerebral metabolism in hydrocephalus can help in the decision making and the timing of surgical intervention. This study was aimed at examining the tricarboxylic acid (TCA) cycle rate and (13)C label incorporation into neurotransmitter amino acids and other compounds 2...

E1A FUNCTIONS AS A COACTIVATOR OF RETINOIC ACID-DEPENDENT RETINOIC ACID RECEPTOR-BETA-2 PROMOTER ACTIVATION

NARCIS (Netherlands)

KRUYT, FAE; FOLKERS, GE; WALHOUT, AJM; VANDERLEEDE, BM; VANDERSAAG, PT; Kruyt, Frank

The retinoic acid (RA) receptor (RAR) beta2 promoter is strongly activated by RA in embryonal carcinoma (EC) cells. We examined this activation in the P19 EC-derived END-2 cell line and in E1A-expressing counterparts and found strong RA-dependent RARbeta2 promoter activation in the E1A-expressing

Palmitoleic Acid Improves Metabolic Functions in Fatty Liver by PPARα-Dependent AMPK Activation.

Science.gov (United States)

de Souza, Camila O; Teixeira, Alexandre A S; Biondo, Luana A; Lima Junior, Edson A; Batatinha, Helena A P; Rosa Neto, Jose C

2017-08-01

Palmitoleic acid, since described as lipokine, increases glucose uptake by modulation of 5'AMP-activated protein kinase (AMPK), as well as increasing lipolysis by activation of peroxisome proliferator-activated receptor-α (PPARα), in adipose tissue. However, in liver, the effects of palmitoleic acid on glucose metabolism and the role of PPARα remain unknown. To investigate whether palmitoleic acid improved the hepatic insulin sensitivity of obese mice. C57BL6 and PPARα knockout (KO) mice were fed for 12 weeks with a standard diet (SD) or high-fat diet (HF), and in the last 2 weeks were treated with oleic or palmitoleic acid. Palmitoleic acid promoted a faster uptake of glucose in the body, associated with higher insulin concentration; however, even when stimulated with insulin, palmitoleic acid did not modulate the insulin pathway (AKT, IRS). Palmitoleic acid increased the phosphorylation of AMPK, upregulated glucokinase and downregulated SREBP-1. Regarding AMPK downstream, palmitoleic acid increased the production of FGF-21 and stimulated the expression of PPARα. Palmitoleic acid treatment did not increase AMPK phosphorylation, modulate glucokinase or increase FGF-21 in liver of PPARα KO mice. In mice fed with a high-fat diet, palmitoleic acid supplementation stimulated the uptake of glucose in liver through activation of AMPK and FGF-21, dependent on PPARα. J. Cell. Physiol. 232: 2168-2177, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

International Nuclear Information System (INIS)

Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing; Guo Chun; Zhu Faliang; Yang Qiaozi; Gao Guimin; Gong Yaoqin; Shao Changshun

2009-01-01

Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis

Berberine induces p53-dependent cell cycle arrest and apoptosis of human osteosarcoma cells by inflicting DNA damage

Energy Technology Data Exchange (ETDEWEB)

Liu Zhaojian; Liu Qiao; Xu Bing; Wu Jingjing [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Guo Chun; Zhu Faliang [Institute of Immunology, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Yang Qiaozi [Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States); Gao Guimin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Gong Yaoqin [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China)], E-mail: yxg8@sdu.edu.cn; Shao Changshun [Key Laboratory of Experimental Teratology of Ministry of Education and Institute of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)], E-mail: shao@biology.rutgers.edu

2009-03-09

Alkaloid berberine is widely used for the treatment of diarrhea and other diseases. Many laboratory studies showed that it exhibits anti-proliferative activity against a wide spectrum of cancer cells in culture. In this report we studied the mechanisms underlying the inhibitory effects of berberine on human osteosarcoma cells and on normal osteoblasts. The inhibition was largely attributed to cell cycle arrest at G1 and G2/M, and to a less extent, to apoptosis. The G1 arrest was dependent on p53, as G1 arrest was abolished in p53-deficient osteosarcoma cells. The induction of G1 arrest and apoptosis was accompanied by a p53-dependent up-regulation of p21 and pro-apoptotic genes. However, the G2/M arrest could be induced by berberine regardless of the status of p53. Interestingly, DNA double-strand breaks, as measured by the phosphorylation of H2AX, were remarkably accumulated in berberine-treated cells in a dose-dependent manner. Thus, one major mechanism by which berberine exerts its growth-inhibitory effect is to inflict genomic lesions on cells, which in turn trigger the activation of p53 and the p53-dependent cellular responses including cell cycle arrest and apoptosis.

Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

Science.gov (United States)

Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

2007-10-01

Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

Interconnection between tricarboxylic acid cycle and energy generation in microbial fuel cell performed by desulfuromonas acetoxidans IMV B-7384

Science.gov (United States)

Vasyliv, Oresta M.; Maslovska, Olga D.; Ferensovych, Yaroslav P.; Bilyy, Oleksandr I.; Hnatush, Svitlana O.

2015-05-01

Desulfuromonas acetoxidans IMV B-7384 is exoelectrogenic obligate anaerobic sulfur-reducing bacterium. Its one of the first described electrogenic bacterium that performs complete oxidation of an organic substrate with electron transfer directly to the electrode in microbial fuel cell (MFC). This bacterium is very promising for MFC development because of inexpensive cultivation medium, high survival rate and selective resistance to various heavy metal ions. The size of D. acetoxidans IMV B-7384 cells is comparatively small (0.4-0.8×1-2 μm) that is highly beneficial while application of porous anode material because of complete bacterial cover of an electrode area with further significant improvement of the effectiveness of its usage. The interconnection between functioning of reductive stage of tricarboxylic acid (TCA) cycle under anaerobic conditions, and MFC performance was established. Malic, pyruvic, fumaric and succinic acids in concentration 42 mM were separately added into the anode chamber of MFC as the redox agents. Application of malic acid caused the most stabile and the highest power generation in comparison with other investigated organic acids. Its maximum equaled 10.07±0.17mW/m2 on 136 hour of bacterial cultivation. Under addition of pyruvic, succinic and fumaric acids into the anode chamber of MFC the maximal power values equaled 5.80±0.25 mW/m2; 3.2±0.11 mW/m2, and 2.14±0.19 mW/m2 respectively on 40, 56 and 32 hour of bacterial cultivation. Hence the malic acid conversion via reductive stage of TCA cycle is shown to be the most efficient process in terms of electricity generation by D. acetoxidans IMV B-7384 in MFC under anaerobic conditions.

Prompt payment depends on revenue-cycle diligence.

Science.gov (United States)

Barber, Robert L

2002-12-01

How effectively you manage the revenue cycle is reflected in the cycle's outcome-whether you receive full and timely payment for all services billed to payers. To ensure prompt and full payment, you should: Educate your patient financial services (PFS) staff on all relevant laws and regulations regarding payment for healthcare services. Make sure your staff is well versed in all of the provisions of your payer contracts. Implement a state-of-the-art patient accounting system that is capable of producing drill-down reports of all aspects of contract performance by payer. Enforce payer compliance by maintaining complete records of dates of service, final billing dates, dates claims were mailed or electronically submitted to the payer, all actions performed by your staff regarding claims, and all communications with the payer.

Performance Evaluation of the Spectral Centroid Downshift Method for Attenuation Estimation

OpenAIRE

Samimi, Kayvan; Varghese, Tomy

2015-01-01

Estimation of frequency-dependent ultrasonic attenuation is an important aspect of tissue characterization. Along with other acoustic parameters studied in quantitative ultrasound, the attenuation coefficient can be used to differentiate normal and pathological tissue. The spectral centroid downshift (CDS) method is one the most common frequency-domain approaches applied to this problem. In this study, a statistical analysis of this method’s performance was carried out based on a parametric m...

Variable optical attenuator fabricated by direct UV writing

DEFF Research Database (Denmark)

Svalgaard, Mikael; Færch, Kjartan Ullitz; Andersen, L.U.

2003-01-01

It is demonstrated that direct ultraviolet writing of waveguides is a method suitable for mass production of compact variable optical attenuators with low insertion loss, low polarization-dependent loss, and high dynamic range. The fabrication setup is shown to be robust, providing good device...

Single-cycle immunodeficiency viruses provide strategies for uncoupling in vivo expression levels from viral replicative capacity and for mimicking live-attenuated SIV vaccines

International Nuclear Information System (INIS)

Kuate, Seraphin; Stahl-Hennig, Christiane; Haaft, Peter ten; Heeney, Jonathan; Ueberla, Klaus

2003-01-01

To reduce the risks associated with live-attenuated immunodeficiency virus vaccines, single-cycle immunodeficiency viruses (SCIVs) were developed by primer complementation and production of the vaccine in the absence of vif in a vif-independent cell line. After a single intravenous injection of SCIVs into rhesus monkeys, peak viral RNA levels of 10 3 to 10 4 copies/ml plasma were observed, indicating efficient expression of SCIV in the vaccinee. After booster immunizations with SCIVs, SIV-specific humoral and cellular immune responses were observed. Although the vaccine doses used in this pilot study could not protect vaccinees from subsequent intravenous challenge with pathogenic SIVmac239, our results demonstrate that the novel SCIV approach allows us to uncouple in vivo expression levels from the viral replicative capacity facilitating the analysis of the relationship between viral expression levels or viral genes and immune responses induced by SIV

Effect of ellagic acid on proliferation, cell adhesion and apoptosis in SH-SY5Y human neuroblastoma cells.

Science.gov (United States)

Fjaeraa, Christina; Nånberg, Eewa

2009-05-01

Ellagic acid, a polyphenolic compound found in berries, fruits and nuts, has been shown to possess growth-inhibiting and apoptosis promoting activities in cancer cell lines in vitro. The objective of this study was to investigate the effect of ellagic acid in human neuroblastoma SH-SY5Y cells. In cultures of SH-SY5Y cells incubated with ellagic acid, time- and concentration-dependent inhibitory effects on cell number were demonstrated. Ellagic acid induced cell detachment, decreased cell viability and induced apoptosis as measured by DNA strand breaks. Ellagic acid-induced alterations in cell cycle were also observed. Simultaneous treatment with all-trans retinoic acid did not rescue the cells from ellagic acid effects. Furthermore, the results suggested that pre-treatment with all-trans retinoic acid to induce differentiation and cell cycle arrest did not rescue the cells from ellagic acid-induced cell death.

Korean Red Ginseng Extract Attenuates 3-Nitropropionic Acid-Induced Huntington’s-Like Symptoms

Directory of Open Access Journals (Sweden)

Minhee Jang

2013-01-01

Full Text Available Korean red ginseng (KRG possesses neuroprotective activity. However, the potential neuroprotective value of KRG for the striatal toxicity is largely unknown. We investigated whether KRG extract (KRGE could have a neuroprotective effect in a 3-nitropropionic acid- (3-NP induced (i.p. Huntington’s disease (HD model. KRGE (50, 100, and 250 mg/kg/day, p.o. was administrated 10 days before 3-NP injection (pre-administration, from the same time with 3-NP injection (co-administration, or from the peak point of neurological impairment by 3-NP injection (post-administration. Pre-administration of KRGE produced the greatest neuroprotective effect in this model. Pre-administration of KRGE significantly decreased 3-NP-induced neurological impairment, lethality, lesion area, and neuronal loss in the 3-NP-injected striatum. KRGE attenuated microglial activation and phosphorylation of mitogen-activated protein kinases (MAPKs and nuclear factor-kappa B (NF-κB signal pathway. KRGE also reduced the level of mRNA expression of tumor necrosis factor-alpha, interleukin- (IL- 1β, IL-6, inducible nitric oxide synthase, and OX-42. Interestingly, the intrathecal administration of SB203580 (a p38 inhibitor or PD98059 (an inhibitor of MAPK Kinase, MEK increased the survival rate in the 3-NP-induced HD model. Pre-administration of KRGE may effectively inhibit 3-NP-induced striatal toxicity via the inhibition of the phosphorylation of MAPKs and NF-κB pathways, indicating its therapeutic potential for suppressing Huntington’s-like symptoms.

A plant pathogenic bacterium exploits the tricarboxylic acid cycle metabolic pathway of its insect vector

Science.gov (United States)

Nehela, Yasser; Hijaz, Faraj; Vincent, Christopher I.

2018-01-01

ABSTRACT Huanglongbing in citrus is caused by a phloem-limited, uncultivable, gram-negative α-proteobacterium, Candidatus Liberibacter asiaticus (CLas). CLas is transmitted by the phloem-sucking insect, Diaphorina citri (Hemiptera: Liviidae), in a persistent, circulative, and propagative manner. In this study, we investigated the metabolomic and respiration rates changes in D. citri upon infection with CLas using gas chromatography-mass spectrometry (GC-MS) and gas exchange analysis. The level of glycine, L-serine, L-threonine, and gamma-amino butyric acid were higher in CLas-infected D. citri, while L-proline, L-aspartic acid, and L-pyroglutamic acid were lower in CLas-infected D. citri compared with the control. Citric acid was increased in CLas-infected D. citri, whereas malic and succinic acids were reduced. Interestingly, most of the reduced metabolites such as malate, succinate, aspartate, and L-proline are required for the growth of CLas. The increase in citric acid, serine, and glycine indicated that CLas induced glycolysis and the tricarboxylic acid cycle (TCA) in its vector. In agreement with the GC-MS results, the gene expression results also indicated that glycolysis and TCA were induced in CLas-infected D. citri and this was accompanied with an increases in respiration rate. Phosphoric acid and most of the sugar alcohols were higher in CLas-infected D. citri, indicating a response to the biotic stress or cell damage. Only slight increases in the levels of few sugars were observed in CLas-infected D. citri, which indicated that sugars are tightly regulated by D. citri. Our results indicated that CLas induces nutrient and energetic stress in its host insect. This study may provide some insights into the mechanism of colonization of CLas in its vector. PMID:28594267

Phenazine-1-carboxylic acid influences biofilm development and turnover of rhizobacterial biomass in a soil moisture-dependent manner

Science.gov (United States)

Rhizobacterial biofilm development influences terrestrial carbon and nitrogen cycles with ramifications for crop and soil health. Phenazine-1-carboxylic acid (PCA) is a redox-active metabolite produced by rhizobacteria in dryland wheat fields of Washington and Oregon, USA. PCA promotes biofilm dev...

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

Science.gov (United States)

Santa Ana, Elizabeth J; Prisciandaro, James J; Saladin, Michael E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Nietert, Paul J; Brady, Kathleen T

2015-04-01

Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity. © American Academy of Addiction Psychiatry.

Hyperoside attenuates hydrogen peroxide-induced L02 cell damage via MAPK-dependent Keap{sub 1}-Nrf{sub 2}-ARE signaling pathway

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Xing, Hai-Yan; Liu, Yao; Chen, Jian-Hong; Sun, Feng-Jun; Shi, Hui-Qing [Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China); Xia, Pei-Yuan, E-mail: py_xia@yahoo.com.cn [Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038 (China)

2011-07-15

Highlights: {yields} Hyperoside attenuated H{sub 2}O{sub 2}-induced L02 cell damage. {yields} Hyperoside up-regulated HO-1 expression at both mRNA and protein levels. {yields} Hyperoside activated both Nrf{sub 2} nuclear translocation and gene expression. {yields} Hyperoside may inhibit Keap{sub 1} mRNA translation or protein degradation. {yields} Phosphorylation of ERK and p38 is involved in hyperoside-mediated Nrf{sub 2} activation. -- Abstract: The flavonoid hyperoside has been reported to elicit cytoprotection against oxidative stress partly by increasing the activity of antioxidant enzymes, such as glutathione peroxidase, superoxide dismutase and catalase. However, the cellular and molecular mechanisms underlying this effect remain unclear. Here, hepatic L02 cells exposed to H{sub 2}O{sub 2} (100 {mu}M) were used to demonstrate that hyperoside protected cells by significantly inhibiting overproduction of intracellular ROS, depletion of the mitochondrial membrane potential and leakage of lactate dehydrogenase. Hyperoside further enhanced the cellular antioxidant defense system through increasing the activity of heme oxygenase-1 (HO-1), and by up-regulating HO-1 expression. Meanwhile, real time PCR, western blot and immunofluorescence studies revealed that hyperoside stimulated nuclear translocation of the Nrf{sub 2} transcription factor in a dose-dependent manner, and this effect was significantly suppressed by pharmacological inhibition of the mitogen-activated protein kinases (MAPK) p38 and ERK. Collectively, our data provide the first description of the mechanism underlying hyperoside's ability to attenuate H{sub 2}O{sub 2}-induced cell damage, namely this compound interacts with the MAPK-dependent Keap{sub 1}-Nrf{sub 2}-ARE signaling pathway to up-regulate HO-1 expression and enhance intracellular antioxidant activity.

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

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Carla R V Coelho

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

Impairment of exercise performance following cold water immersion is not attenuated after 7 days of cold acclimation.

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Jones, Douglas M; Roelands, Bart; Bailey, Stephen P; Buono, Michael J; Meeusen, Romain

2018-03-19

It is well-documented that severe cold stress impairs exercise performance. Repeated immersion in cold water induces an insulative type of cold acclimation, wherein enhanced vasoconstriction leads to greater body heat retention, which may attenuate cold-induced exercise impairments. The purpose of this study, therefore, was to investigate changes in exercise performance during a 7-day insulative type of cold acclimation. Twelve healthy participants consisting of eight males and four females (mean ± SD age: 25.6 ± 5.2 years, height: 174.0 ± 8.9 cm, weight: 75.6 ± 13.1 kg) performed a 20 min self-paced cycling test in 23 °C, 40% humidity without prior cold exposure. Twenty-four hours later they began a 7-day cold acclimation protocol (daily 90 min immersion in 10 °C water). On days one, four, and seven of cold acclimation, participants completed the same cycling test. Measurements of work completed, core and skin temperatures, heart rate, skin blood flow, perceived exertion, and thermal sensation were measured during each cycling test. Successful insulative cold acclimation was observed. Work produced during the baseline cycling test (220 ± 70 kJ) was greater (p immersions (195 ± 58, 197 ± 60, and 194 ± 62 kJ) despite similar ratings of perceived exertion during each test, suggesting that cold exposure impaired cycling performance. This impairment, however, was not attenuated over the cold acclimation period. Results suggest that insulative cold acclimation does not attenuate impairments in exercise performance that were observed following acute cold water immersion.

Fast neutron attenuation measurements for detection of illicit materials

International Nuclear Information System (INIS)

Lee, Hee Seock; Chung, Chin Wha; Guon, Ki Il; Lee, Bo Young; Ko, Seung Kook; Shin, Yong Mu

2002-01-01

Experiments were carried out to develop a novel method using neutron attenuation for the detection of illicit materials. By using pulsed fast neutrons generated from a Bi target bombarded with a 2 GeV electron beam, attenuation spectra of C, N, and O have been measured to study the feasibility of a practical application. The spectral dependence on the material thickness and the geometrical distribution as well as the ability to identify different elements in a layered environment have been studied. For the elements mentioned here, the total cross sections have been obtained from the measured attenuation spectra and compared with ENDF-VI, which showed good agreement. The study confirms that a conventional low energy electron linac can be put into a practical use, and some practical idea is presented

Novel Mechanism of Fatty Acid Sensing in Enteroendocrine Cells: Specific Structures in Oxo-Fatty Acids Produced by Gut Bacteria are Responsible for CCK Secretion in STC-1 Cells via GPR40.

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Hira, Tohru; Ogasawara, Shono; Yahagi, Asuka; Kamachi, Minami; Li, Jiaxin; Nishimura, Saki; Sakaino, Masayoshi; Yamashita, Takatoshi; Kishino, Shigenobu; Ogawa, Jun; Hara, Hiroshi

2018-06-25

The secretion of gut hormones, such as cholecystokinin (CCK) is stimulated by fatty acids. Although a chain length-dependent mechanism has been proposed, other structural relationships to releasing activity remain unclear. We aimed to elucidate specific structures in fatty acids that are responsible for their CCK-releasing activity, and related sensing mechanisms in enteroendocrine cells. We examined CCK secretory activities in a murine CCK-producing cell line STC-1 by exposing the cells to various modified fatty acids produced by gut lactic acid bacteria. The effects of fatty acids on gastric emptying rate as a CCK-mediated function were examined using acetaminophen- and phenol red-methods in rats. Out of more than thirty octadecanoic (C18)-derived fatty acids tested, five oxo-fatty acids potently stimulated CCK secretion without cytotoxic effects in STC-1 cells. Three fatty acids had a distinct specific structure containing one double-bond, whereas the other two had two double-bonds, nearby an oxo residue. CCK secretion induced by representative fatty acids (10-oxo-trans-11-18:1 and 13-oxo-cis-9,cis-15-18:2) was attenuated by a fatty acid-receptor GPR40 antagonist. Oral administration of 13-oxo-cis-9,cis-15-18:2 lowered the gastric emptying rate in rats in a dose- and structure-dependent manner. These results revealed a novel fatty acid-sensing mechanism in enteroendocrine cells. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism.

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Mourtzakis, M; Graham, T E; González-Alonso, J; Saltin, B

2008-08-01

Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops approximately 40-80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (VO2peak) in the T thigh was greater than that in the UT thigh (PTCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33+/-0.07 vs. 0.02+/-0.01 mmol/kg dry wt (dw), PTCA cycle, glutamate and TCA cycle intermediates do not directly affect VO2peak in either trained or untrained muscle.

Origin of the Reductive Tricarboxylic Acid (rTCA Cycle-Type CO2 Fixation: A Perspective

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Norio Kitadai

2017-10-01

Full Text Available The reductive tricarboxylic acid (rTCA cycle is among the most plausible candidates for the first autotrophic metabolism in the earliest life. Extant enzymes fixing CO2 in this cycle contain cofactors at the catalytic centers, but it is unlikely that the protein/cofactor system emerged at once in a prebiotic process. Here, we discuss the feasibility of non-enzymatic cofactor-assisted drive of the rTCA reactions in the primitive Earth environments, particularly focusing on the acetyl-CoA conversion to pyruvate. Based on the energetic and mechanistic aspects of this reaction, we propose that the deep-sea hydrothermal vent environments with active electricity generation in the presence of various sulfide catalysts are a promising setting for it to progress. Our view supports the theory of an autotrophic origin of life from primordial carbon assimilation within a sulfide-rich hydrothermal vent.

Excretion and intestinal absorption of tritiated glutamic acid by carp, Cyprinus Carpio

International Nuclear Information System (INIS)

Watabe, Terushia; Kistner, G.

1986-01-01

Excretion and intestinal absorption of tritiated glutamic acid by carp was investigated. Approximately 80% of orally administered tritium was excreted at a half life value of 1.4 h and an observed slower excretion of 7 days for the remainder. Tritium incorporated in glutamic acid was efficiently retained at the site of absorption, i.e. intestine, liver, gill, kidney, blood and muscle. A dual marking experiment using tritiated glutamic acid and 14 C-market glutamic acid showed higher excretion of tritium by factors 2.0 to 4.9 than that of 14 C. Tritiated glutamic acid is considered to be mainly incorporated in the citric acid cycle soon after administration and the release of tritium in tritiated water through the cycle is assumed as causing the initial rapid excretion of tritium in carp. The intestinal absorption of glutamic acid was likely to depend on its concentration in the administered solution. The maximum level of absorption is estimated to be 0.1 m mol/0.5 h for one year old carp. The results obtained here would make it possible to estimate the tritium contamination of fish due to tritiated glutamic acid entering the food chain. (orig.)

Estimation of Coda Wave Attenuation in Northern Morocco

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Boulanouar, Abderrahim; Moudnib, Lahcen El; Padhy, Simanchal; Harnafi, Mimoun; Villaseñor, Antonio; Gallart, Josep; Pazos, Antonio; Rahmouni, Abdelaali; Boukalouch, Mohamed; Sebbani, Jamal

2018-03-01

We studied the attenuation of coda waves and its frequency and lapse-time dependence in northern Morocco. We analysed coda waves of 66 earthquakes recorded in this region during 2008 for four lapse time windows of length 30, 40, 50, and 60 s, and at five frequency bands with central frequency in the range of 0.75-12 Hz. We determined the frequency dependent Q c relation for the horizontal (NS and EW) and vertical (Z) component seismograms. We analyzed three-component broadband seismograms of 66 local earthquakes for determining coda-Q based on the single back-scattering model. The Q c values show strong frequency dependence in 1.5-12 Hz that is related to high degree of heterogeneity of the medium. The lapse time dependence of Q c shows that Q 0 ( Q c at 1 Hz) significantly increases with lapse time that is related to the depth dependence of attenuation and hence of the level of heterogeneity of the medium. The average frequency-dependent Q c( f) values are Qc = (143.75 ± 1.09)f^{(0.864 ± 0.006)}, Qc = (149.12 ± 1.08)f^{(0.85 ± 0.005)} and Qc = (140.42 ± 1.81)f^{(0.902 ± 0.004)} for the vertical, north-south and east-west components of motion, respectively. The frequency-dependent Q c(f) relations are useful for evaluating source parameters (Singh et al. 2001), which are the key inputs for seismic hazard assessment of the region.

Natural Docosahexaenoic Acid in the Triglyceride Form Attenuates In Vitro Microglial Activation and Ameliorates Autoimmune Encephalomyelitis in Mice

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Pilar Mancera

2017-06-01

Full Text Available Many neurodegenerative diseases are associated, at least in part, to an inflammatory process in which microglia plays a major role. The effect of the triglyceride form of the omega-3 polyunsaturated fatty acid docosahexaenoic acid (TG-DHA was assayed in vitro and in vivo to assess the protective and anti-inflammatory activity of this compound. In the in vitro study, BV-2 microglia cells were previously treated with TG-DHA and then activated with Lipopolysaccharide (LPS and Interferon-gamma (IFN-γ. TG-DHA treatment protected BV-2 microglia cells from oxidative stress toxicity attenuating NO production and suppressing the induction of inflammatory cytokines. When compared with DHA in the ethyl-ester form, a significant difference in the ability to inhibit NO production in favor of TG-DHA was observed. TG-DHA inhibited significantly splenocyte proliferation but isolated CD4+ lymphocyte proliferation was unaffected. In a mice model of autoimmune encephalomyelitis (EAE, 250 mg/kg/day oral TG-DHA treatment was associated with a significant amelioration of the course and severity of the disease as compared to untreated animals. TG-DHA-treated EAE mice showed a better weight profile, which is a symptom related to a better course of encephalomyelitis. TG-DHA may be a promising therapeutic agent in neuroinflammatory processes and merit to be more extensively studied in human neurodegenerative disorders.

The Gcn2 Regulator Yih1 Interacts with the Cyclin Dependent Kinase Cdc28 and Promotes Cell Cycle Progression through G2/M in Budding Yeast.

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Richard C Silva

Full Text Available The Saccharomyces cerevisiae protein Yih1, when overexpressed, inhibits the eIF2 alpha kinase Gcn2 by competing for Gcn1 binding. However, deletion of YIH1 has no detectable effect on Gcn2 activity, suggesting that Yih1 is not a general inhibitor of Gcn2, and has no phenotypic defect identified so far. Thus, its physiological role is largely unknown. Here, we show that Yih1 is involved in the cell cycle. Yeast lacking Yih1 displays morphological patterns and DNA content indicative of a delay in the G2/M phases of the cell cycle, and this phenotype is independent of Gcn1 and Gcn2. Accordingly, the levels of phosphorylated eIF2α, which show a cell cycle-dependent fluctuation, are not altered in cells devoid of Yih1. We present several lines of evidence indicating that Yih1 is in a complex with Cdc28. Yih1 pulls down endogenous Cdc28 in vivo and this interaction is enhanced when Cdc28 is active, suggesting that Yih1 modulates the function of Cdc28 in specific stages of the cell cycle. We also demonstrate, by Bimolecular Fluorescence Complementation, that endogenous Yih1 and Cdc28 interact with each other, confirming Yih1 as a bona fide Cdc28 binding partner. Amino acid substitutions within helix H2 of the RWD domain of Yih1 enhance Yih1-Cdc28 association. Overexpression of this mutant, but not of wild type Yih1, leads to a phenotype similar to that of YIH1 deletion, supporting the view that Yih1 is involved through Cdc28 in the regulation of the cell cycle. We further show that IMPACT, the mammalian homologue of Yih1, interacts with CDK1, the mammalian counterpart of Cdc28, indicating that the involvement with the cell cycle is conserved. Together, these data provide insights into the cellular function of Yih1/IMPACT, and provide the basis for future studies on the role of this protein in the cell cycle.

Perception of low red:far-red ratio compromises both salicylic acid- and jasmonic acid-dependent pathogen defences in Arabidopsis.

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de Wit, Mieke; Spoel, Steven H; Sanchez-Perez, Gabino F; Gommers, Charlotte M M; Pieterse, Corné M J; Voesenek, Laurentius A C J; Pierik, Ronald

2013-07-01

In dense stands of plants, such as agricultural monocultures, plants are exposed simultaneously to competition for light and other stresses such as pathogen infection. Here, we show that both salicylic acid (SA)-dependent and jasmonic acid (JA)-dependent disease resistance is inhibited by a simultaneously reduced red:far-red light ratio (R:FR), the early warning signal for plant competition. Conversely, SA- and JA-dependent induced defences did not affect shade-avoidance responses to low R:FR. Reduced pathogen resistance by low R:FR was accompanied by a strong reduction in the regulation of JA- and SA-responsive genes. The severe inhibition of SA-responsive transcription in low R:FR appeared to be brought about by the repression of SA-inducible kinases. Phosphorylation of the SA-responsive transcription co-activator NPR1, which is required for full induction of SA-responsive transcription, was indeed reduced and may thus play a role in the suppression of SA-mediated defences by low R:FR-mediated phytochrome inactivation. Our results indicate that foraging for light through the shade-avoidance response is prioritised over plant immune responses when plants are simultaneously challenged with competition and pathogen attack. © 2013 The Authors The Plant Journal © 2013 John Wiley & Sons Ltd.

Cross-talk between abscisic acid-dependent and abscisic acid-independent pathways during abiotic stress.

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Roychoudhury, Aryadeep; Paul, Saikat; Basu, Supratim

2013-07-01

Salinity, drought and low temperature are the common forms of abiotic stress encountered by land plants. To cope with these adverse environmental factors, plants execute several physiological and metabolic responses. Both osmotic stress (elicited by water deficit or high salt) and cold stress increase the endogenous level of the phytohormone abscisic acid (ABA). ABA-dependent stomatal closure to reduce water loss is associated with small signaling molecules like nitric oxide, reactive oxygen species and cytosolic free calcium, and mediated by rapidly altering ion fluxes in guard cells. ABA also triggers the expression of osmotic stress-responsive (OR) genes, which usually contain single/multiple copies of cis-acting sequence called abscisic acid-responsive element (ABRE) in their upstream regions, mostly recognized by the basic leucine zipper-transcription factors (TFs), namely, ABA-responsive element-binding protein/ABA-binding factor. Another conserved sequence called the dehydration-responsive element (DRE)/C-repeat, responding to cold or osmotic stress, but not to ABA, occurs in some OR promoters, to which the DRE-binding protein/C-repeat-binding factor binds. In contrast, there are genes or TFs containing both DRE/CRT and ABRE, which can integrate input stimuli from salinity, drought, cold and ABA signaling pathways, thereby enabling cross-tolerance to multiple stresses. A strong candidate that mediates such cross-talk is calcium, which serves as a common second messenger for abiotic stress conditions and ABA. The present review highlights the involvement of both ABA-dependent and ABA-independent signaling components and their interaction or convergence in activating the stress genes. We restrict our discussion to salinity, drought and cold stress.

The mAb against adipocyte fatty acid-binding protein 2E4 attenuates the inflammation in the mouse model of high-fat diet-induced obesity via toll-like receptor 4 pathway.

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Miao, Xiaoliang; Wang, Ying; Wang, Wang; Lv, Xiaobo; Wang, Min; Yin, Hongping

2015-03-05

Adipocyte fatty acid-binding protein (A-FABP) plays an important role in fatty acid-mediated processes and related metabolic and inflammatory responses. In this study, we prepared a novel monoclonal antibody against A-FABP, designated 2E4. Our data showed that 2E4 specifically binded to the recombinant A-FABP and native A-FABP of mice adipose tissue. Furthermore, we investigated the effect of 2E4 on metabolic and inflammatory responses in C57BL/6J obese mice fed on a high fat diet. 2E4 administration improved glucose response in high-fat-diet induced obese mice. The 2E4 treated groups exhibited lower free fatty acids, cholesterol, and triglycerides in a concentration-dependent manner. These changes were accompanied by down-regulated expression of pro-inflammatory cytokines in adipose tissue, including tumor necrosis factor α, monocyte chemotactic protein-1, and interleukin-6. Meanwhile, our data demonstrated that 2E4 significantly decreased the mRNA and protein levels of A-FABP in adipose tissue of mice. Further experiments showed that 2E4 notably suppressed the phosphorylation of IκBα and jun-N-terminal kinase through toll-like receptor 4 signaling pathway. Taken together, 2E4 is an effective monoclonal antibody against A-FABP, which attenuated the inflammatory responses induced in the high-fat-diet mice. These findings may provide scientific insight into the treatment of chronic low-grade inflammation in obesity. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

β-Hydroxy-β-methylbutyrate (HMB)-free acid attenuates circulating TNF-α and TNFR1 expression postresistance exercise.

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Townsend, Jeremy R; Fragala, Maren S; Jajtner, Adam R; Gonzalez, Adam M; Wells, Adam J; Mangine, Gerald T; Robinson, Edward H; McCormack, William P; Beyer, Kyle S; Pruna, Gabriel J; Boone, Carleigh H; Scanlon, Tyler M; Bohner, Jonathan D; Stout, Jeffrey R; Hoffman, Jay R

2013-10-15

The purpose of this study was to examine the effect of β-hydroxy-β-methylbutyrate-free acid (HMB-FA) and cold-water immersion (CWI) on circulating concentrations of TNF-α and monocyte TNF-α receptor 1 (TNFR1) expression. Forty resistance-trained men (22.3 ± 2.4 yr) were randomized into four groups [placebo (PL), HMB-FA, CWI, and HMB-FA-CWI] and performed an acute, intense exercise protocol (four sets of up to 10 repetitions of the squat, dead lift, and split squat). Participants also performed four sets of up to 10 repetitions of the squat at 24 and 48 h following the initial exercise bout. Blood was sampled before exercise (PRE), immediately postexercise (IP), and 30 min, 24 h, and 48 h postexercise (30P, 24P, and 48P, respectively). Circulating TNF-α was assayed, and TNFR1 expression on CD14+ monocytes was measured by flow cytometry. The exercise protocol significantly elevated TNF-α in only PL (P = 0.006) and CWI (P = 0.045) IP. Mean percent changes show that TNF-α significantly increased from PRE to IP for only PL and CWI groups (P < 0.05), whereas the percent change of TNF-α for HMB-FA and HMB-FA-CWI was not significant. TNFR1 expression was elevated in PL (P = 0.023) and CWI (P = 0.02) at 30P compared with PRE, whereas both HMB-FA-treated groups did not increase significantly. In conclusion, HMB-FA attenuated circulating TNF-α IP and TNFR1 expression during recovery compared with PL and CWI. HMB-FA supplementation may attenuate the initial immune response to intense exercise, which may reduce recovery time following intense exercise.

Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity*

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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

2013-01-01

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

Viscoacoustic wave-equation traveltime inversion with correct and incorrect attenuation profiles

KAUST Repository

Yu, Han

2017-08-17

A visco-acoustic wave-equation traveltime inversion method is presented that inverts for a shallow subsurface velocity distribution with correct and incorrect attenuation profiles. Similar to the classical wave equation traveltime inversion, this method applies the misfit functional that minimizes the first break differences between the observed and predicted data. Although, WT can partly avoid the cycle skipping problem, an initial velocity model approaches to the right or wrong velocity models under different setups of the attenuation profiles. However, with a Q model far away from the real model, the inverted tomogram is obviously different from the true velocity model while a small change of the Q model does not improve the inversion quality in a strong manner if low frequency information is not lost.

Herpes simplex virus 1 regulatory protein ICP22 interacts with a new cell cycle-regulated factor and accumulates in a cell cycle-dependent fashion in infected cells.

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Bruni, R; Roizman, B

1998-11-01

The herpes simplex virus 1 infected cell protein 22 (ICP22), the product of the alpha22 gene, is a nucleotidylylated and phosphorylated nuclear protein with properties of a transcriptional factor required for the expression of a subset of viral genes. Here, we report the following. (i) ICP22 interacts with a previously unknown cellular factor designated p78 in the yeast two-hybrid system. The p78 cDNA encodes a polypeptide with a distribution of leucines reminiscent of a leucine zipper. (ii) In uninfected and infected cells, antibody to p78 reacts with two major bands with an apparent Mr of 78,000 and two minor bands with apparent Mrs of 62, 000 and 55,000. (ii) p78 also interacts with ICP22 in vitro. (iii) In uninfected cells, p78 was dispersed largely in the nucleoplasm in HeLa cells and in the nucleoplasm and cytoplasm in HEp-2 cells. After infection, p78 formed large dense bodies which did not colocalize with the viral regulatory protein ICP0. (iv) Accumulation of p78 was cell cycle dependent, being highest very early in S phase. (v) The accumulation of ICP22 in synchronized cells was highest in early S phase, in contrast to the accumulation of another protein, ICP27, which was relatively independent of the cell cycle. (vi) In the course of the cell cycle, ICP22 was transiently modified in an aberrant fashion, and this modification coincided with expression of p78. The results suggest that ICP22 interacts with and may be stabilized by cell cycle-dependent proteins.

Attenuated hypocholesterolemia following severe trauma signals risk for late ventilator-associated pneumonia, ventilator dependency, and death: a retrospective study of consecutive patients

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Chirichella Thomas J

2011-03-01

Full Text Available Abstract Background Post-traumatic ventilator-associated pneumonia (VAP is a substantial clinical problem that increases hospital costs and typically adds to the duration of mechanical ventilation. We evaluated the impact of VAP on ventilator days. We also assessed 48-hour total blood cholesterol (TC and other potential risk factors for the development of VAP. Methods We performed a retrospective study of consecutive trauma patients requiring emergency tracheal intubation and evaluated TC, age, gender, ethanol status, smoker status, injury mechanism, chest injury, brain injury, Injury Severity Score (ISS, shock, day-one hypoxemia, and RBC transfusion as potential risks for VAP. Results The 152 patients had ISS 28.1, brain injury 68.4%, VAP 50.0%, ventilator days 14.3, and death 9.9%. Ventilator days were increased with late VAP (p Conclusions Severe traumatic injury produced substantial hypocholesterolemia that is greater with chest injury, shock, and RBC transfusion, but less with brain injury. Total blood cholesterol tended to decrease with increasing injury severity. However, attenuated hypocholesterolemia (ISS ≥ 20-&-TC ≥ 90 mg/dL represents a unique response that can occur with critical injury. Attenuated hypocholesterolemia signals early risk for late VAP, ventilator dependency, and death.

Is there in vivo evidence for amino acid shuttles carrying ammonia from neurons to astrocytes?

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Rothman, Douglas L; De Feyter, Henk M; Maciejewski, Paul K; Behar, Kevin L

2012-11-01

The high in vivo flux of the glutamate/glutamine cycle puts a strong demand on the return of ammonia released by phosphate activated glutaminase from the neurons to the astrocytes in order to maintain nitrogen balance. In this paper we review several amino acid shuttles that have been proposed for balancing the nitrogen flows between neurons and astrocytes in the glutamate/glutamine cycle. All of these cycles depend on the directionality of glutamate dehydrogenase, catalyzing reductive glutamate synthesis (forward reaction) in the neuron in order to capture the ammonia released by phosphate activated glutaminase, while catalyzing oxidative deamination of glutamate (reverse reaction) in the astrocytes to release ammonia for glutamine synthesis. Reanalysis of results from in vivo experiments using (13)N and (15)N labeled ammonia and (15)N leucine in rats suggests that the maximum flux of the alanine/lactate or branched chain amino acid/branched chain amino acid transaminase shuttles between neurons and astrocytes are approximately 3-5 times lower than would be required to account for the ammonia transfer from neurons to astrocytes needed for glutamine synthesis (amide nitrogen) to sustain the glutamate/glutamine cycle. However, in the rat brain both the total ammonia fixation rate by glutamate dehydrogenase and the total branched chain amino acid transaminase activity are sufficient to support a branched chain amino acid/branched chain keto acid shuttle, as proposed by Hutson and coworkers, which would support the de novo synthesis of glutamine in the astrocyte to replace the ~20 % of neurotransmitter glutamate that is oxidized. A higher fraction of the nitrogen needs of total glutamate neurotransmitter cycling could be supported by hybrid cycles in which glutamate and tricarboxylic acid cycle intermediates act as a nitrogen shuttle. A limitation of all in vivo studies in animals conducted to date is that none have shown transfer of nitrogen for glutamine amide

Dextromethorphan attenuated inflammation and combined opioid use in humans undergoing methadone maintenance treatment.

Science.gov (United States)

Chen, Shiou-Lan; Lee, Sheng-Yu; Tao, Pao-Luh; Chang, Yun-Hsuan; Chen, Shih-Heng; Chu, Chun-Hsien; Chen, Po See; Lee, I Hui; Yeh, Tzung Lieh; Yang, Yen Kuang; Hong, Jau-Shyong; Lu, Ru-Band

2012-12-01

Recent studies show that proinflammatory cytokines might be related to the development of opioid dependence (physiological, psychological, or both). In a double-blind, randomly stratified clinical trial investigating whether add-on dextromethorphan (60-120 mg/day) attenuated inflammation and the combined use of opioids in heroin-dependent patients undergoing methadone maintenance treatment, we evaluated whether inflammation is related to the progression of opioid dependence. All participants (107 heroin-dependent patients and 84 nondependent healthy controls) were recruited from National Cheng Kung University Hospital. Their plasma cytokine levels were measured to evaluate the effect of add-on dextromethorphan. Plasma TNF-α and IL-8 levels were significantly higher in long-term heroin-dependent patients than in healthy controls (p dextromethorphan. Moreover, both tolerance to methadone and the combined use of opioids were significantly (p dextromethorphan. We conclude that dextromethorphan might be a feasible adjuvant therapeutic for attenuating inflammation and inhibiting methadone tolerance and combined opioid use in heroin-dependent patients.

The acid and alkalinity budgets of weathering in the Andes-Amazon system: Insights into the erosional control of global biogeochemical cycles

Science.gov (United States)

Torres, Mark A.; West, A. Joshua; Clark, Kathryn E.; Paris, Guillaume; Bouchez, Julien; Ponton, Camilo; Feakins, Sarah J.; Galy, Valier; Adkins, Jess F.

2016-09-01

The correlation between chemical weathering fluxes and denudation rates suggests that tectonic activity can force variations in atmospheric pCO2 by modulating weathering fluxes. However, the effect of weathering on pCO2 is not solely determined by the total mass flux. Instead, the effect of weathering on pCO2 also depends upon the balance between 1) alkalinity generation by carbonate and silicate mineral dissolution and 2) sulfuric acid generation by the oxidation of sulfide minerals. In this study, we explore how the balance between acid and alkalinity generation varies with tectonic uplift to better understand the links between tectonics and the long-term carbon cycle. To trace weathering reactions across the transition from the Peruvian Andes to the Amazonian foreland basin, we measured a suite of elemental concentrations (Na, K, Ca, Mg, Sr, Si, Li, SO4, and Cl) and isotopic ratios (87Sr/86Sr and δ34S) on both dissolved and solid phase samples. Using an inverse model, we quantitatively link systematic changes in solute geochemistry with elevation to downstream declines in sulfuric acid weathering as well as the proportion of cations sourced from silicates. With a new carbonate-system framework, we show that weathering in the Andes Mountains is a CO2 source whereas foreland weathering is a CO2 sink. These results are consistent with the theoretical expectation that the ratio of sulfide oxidation to silicate weathering increases with increasing erosion. Altogether, our results suggest that the effect of tectonically-enhanced weathering on atmospheric pCO2 is strongly modulated by sulfide mineral oxidation.