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Sample records for cd36 activity reduces

  1. The Natural Compound Dansameum Reduces foam Cell Formation by Downregulating CD36 and Peroxisome Proliferator-activated Receptor-gamma; Expression.

    Science.gov (United States)

    Park, Kang-Seo; Ahn, Sang Hyun; Lee, Kang Pa; Park, Sun-Young; Cheon, Jin Hong; Choi, Jun-Yong; Kim, Kibong

    2018-01-01

    Atherosclerosis-induced vascular disorders are major causes of death in most western countries. During the development of atherosclerotic lesions, foam cell formation is essential and formed through the expression of CD36 and the peroxisome proliferator-activated receptor gamma (PPAR-γ). To investigate whether dansameum extract (DSE) could show anti-atherosclerotic effect through down-regulating cellular redox state including CD36 and PARP-γ expression in oxidative low-density lipoprotein (oxLDL)-treated RAW264.7 cells and on differentiated foam cells in ApoE Knockout (ApoE-/-) mice. The Korean polyherbal medicine DSE was prepared from three plants in the following proportions: 40 g of Salvia miltiorrhiza root, 4 g of Amomumxanthioides fruit, and 4 g of Santalum album lignum. The immunohistochemistry and reverse transcription-polymerase chain reaction was used for analysis of protein and mRNA involved in foam cell formation. We first showed that effects of DSE on foam cell formation in both oxLDL-induced RAW264.7 cells and in blood vessels from apolipoprotein E deficientApoE-/- mice with high fat diet-fed. DSE treatment significantly reduced the expression of CD36 and PPAR-γ in oxLDL-stimulated RAW264.7 cells and ApoE-/-mice, in the latter case by regulating heme oxygenase-1. Furthermore, DSE treatment also reduced cellular lipid content in vitro and in vivo experiments. Our data suggest that DSE may have anti-atherosclerotic properties through regulating foam cell formation. Dansameum extract (DSE) Regulates the expression of CD36 and peroxisome proliferator-activated receptor gamma in oxidative low-density lipoprotein-stimulated RAW264.7 Cells and ApoE Knockout (ApoE Knockout [ApoE-/-]) miceDSE Regulates Cholesterol Levels in the Serum of ApoE-deficient (ApoE-/-) miceDSE Reduced the Formation of Foam Cells by Regulating heme oxygenase-1 in ApoE-/- mice with high fat diet-fed. Abbreviations used: DSE: Dansameum extract, PPAR-γ: Peroxisome proliferator-activated

  2. CD36 participates in PrP(106-126-induced activation of microglia.

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    Mohammed Kouadir

    Full Text Available Microglial activation is a characteristic feature of the pathogenesis of prion diseases. The molecular mechanisms that underlie prion-induced microglial activation are not very well understood. In the present study, we investigated the role of the class B scavenger receptor CD36 in microglial activation induced by neurotoxic prion protein (PrP fragment 106-126 (PrP(106-126. We first examined the time course of CD36 mRNA expression upon exposure to PrP(106-126 in BV2 microglia. We then analyzed different parameters of microglial activation in PrP(106-126-treated cells in the presence or not of anti-CD36 monoclonal antibody (mAb. The cells were first incubated for 1 h with CD36 monoclonal antibody to block the CD36 receptor, and were then treated with neurotoxic prion peptides PrP(106-126. The results showed that PrP(106-126 treatment led to a rapid yet transitory increase in the mRNA expression of CD36, upregulated mRNA and protein levels of proinflammatory cytokines (IL-1β, IL-6 and TNF-α, increased iNOS expression and nitric oxide (NO production, stimulated the activation of NF-κB and caspase-1, and elevated Fyn activity. The blockade of CD36 had no effect on PrP(106-126-stimulated NF-κB activation and TNF-α protein release, abrogated the PrP(106-126-induced iNOS stimulation, downregulated IL-1β and IL-6 expression at both mRNA and protein levels as well as TNF-α mRNA expression, decreased NO production and Fyn phosphorylation, reduced caspase-1 cleavage induced by moderate PrP(106-126-treatment, but had no effect on caspase-1 activation after treatment with a high concentration of PrP(106-126. Together, these results suggest that CD36 is involved in PrP(106-126-induced microglial activation and that the participation of CD36 in the interaction between PrP(106-126 and microglia may be mediated by Src tyrosine kinases. Our findings provide new insights into the mechanisms underlying the activation of microglia by neurotoxic prion peptides

  3. Oxidized LDL Induces Alternative Macrophage Phenotype through Activation of CD36 and PAFR

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    Francisco J. Rios

    2013-01-01

    Full Text Available OxLDL is recognized by macrophage scavenger receptors, including CD36; we have recently found that Platelet-Activating Factor Receptor (PAFR is also involved. Since PAFR in macrophages is associated with suppressor function, we examined the effect of oxLDL on macrophage phenotype. It was found that the presence of oxLDL during macrophage differentiation induced high mRNA levels to IL-10, mannose receptor, PPARγ and arginase-1 and low levels of IL-12 and iNOS. When human THP-1 macrophages were pre-treated with oxLDL then stimulated with LPS, the production of IL-10 and TGF-β significantly increased, whereas that of IL-6 and IL-8 decreased. In murine TG-elicited macrophages, this protocol significantly reduced NO, iNOS and COX2 expression. Thus, oxLDL induced macrophage differentiation and activation towards the alternatively activated M2-phenotype. In murine macrophages, oxLDL induced TGF-β, arginase-1 and IL-10 mRNA expression, which were significantly reduced by pre-treatment with PAFR antagonists (WEB and CV or with antibodies to CD36. The mRNA expression of IL-12, RANTES and CXCL2 were not affected. We showed that this profile of macrophage activation is dependent on the engagement of both CD36 and PAFR. We conclude that oxLDL induces alternative macrophage activation by mechanisms involving CD36 and PAFR.

  4. Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

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    Chuan Wang

    Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

  5. Rac1-NADPH oxidase signaling promotes CD36 activation under glucotoxic conditions in pancreatic beta cells.

    Science.gov (United States)

    Elumalai, Suma; Karunakaran, Udayakumar; Lee, In Kyu; Moon, Jun Sung; Won, Kyu Chang

    2017-04-01

    We recently reported that cluster determinant 36 (CD36), a fatty acid transporter, plays a pivotal role in glucotoxicity-induced β-cell dysfunction. However, little is known about how glucotoxicity influences CD36 expression. Emerging evidence suggests that the small GTPase Rac1 is involved in the pathogenesis of beta cell dysfunction in type 2 diabetes (T2D). The primary objective of the current study was to determine the role of Rac1 in CD36 activation and its impact on β-cell dysfunction in diabetes mellitus. To address this question, we subjected INS-1 cells and human beta cells (1.1B4) to high glucose conditions (30mM) in the presence or absence of Rac1 inhibition either by NSC23766 (Rac1 GTPase inhibitor) or small interfering RNA. High glucose exposure in INS-1 and human beta cells (1.1b4) resulted in the activation of Rac1 and induced cell apoptosis. Rac1 activation mediates NADPH oxidase (NOX) activation leading to elevated ROS production in both cells. Activation of the Rac1-NOX complex by high glucose levels enhanced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. The inhibition of Rac1 by NSC23766 inhibited NADPH oxidase activity and ROS generation induced by high glucose concentrations in INS-1 & human 1.1b4 beta cells. Inhibition of Rac1-NOX complex activation by NSC23766 significantly reduced CD36 expression in INS-1 and human 1.1b4 beta cell membrane fractions. In addition, Rac1 inhibition by NSC23766 significantly reduced high glucose-induced mitochondrial dysfunction. Furthermore, NADPH oxidase inhibition by VAS2870 also attenuated high glucose-induced ROS generation and cell apoptosis. These results suggest that Rac1-NADPH oxidase dependent CD36 expression contributes to high glucose-induced beta cell dysfunction and cell death. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

    International Nuclear Information System (INIS)

    Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan; Kim, Hyung Sik; Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung; Oh, Seon-Hee; Jun, Dae Won; Lee, Byung-Hoon

    2017-01-01

    Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

  7. Activation of AMPK by berberine induces hepatic lipid accumulation by upregulation of fatty acid translocase CD36 in mice

    Energy Technology Data Exchange (ETDEWEB)

    Choi, You-Jin; Lee, Kang-Yo; Jung, Seung-Hwan [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kim, Hyung Sik [School of Pharmacy, Sungkyunkwan University, Suwon 440-746 (Korea, Republic of); Shim, Gayong; Kim, Mi-Gyeong; Oh, Yu-Kyoung [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Oh, Seon-Hee [The Division of Natural Medical Sciences, College of Health Science, Chosun University, Gwangju 501-759 (Korea, Republic of); Jun, Dae Won [Internal Medicine, Hanyang University School of Medicine, Seoul 133-791 (Korea, Republic of); Lee, Byung-Hoon, E-mail: lee@snu.ac.kr [College of Pharmacy, Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of)

    2017-02-01

    Emerging evidence has shown that berberine has a protective effect against metabolic syndrome such as obesity and type II diabetes mellitus by activating AMP-activated protein kinase (AMPK). AMPK induces CD36 trafficking to the sarcolemma for fatty acid uptake and oxidation in contracting muscle. However, little is known about the effects of AMPK on CD36 regulation in the liver. We investigated whether AMPK activation by berberine affects CD36 expression and fatty acid uptake in hepatocytes and whether it is linked to hepatic lipid accumulation. Activation of AMPK by berberine or transduction with adenoviral vectors encoding constitutively active AMPK in HepG2 and mouse primary hepatocytes increased the expression and membrane translocation of CD36, resulting in enhanced fatty acid uptake and lipid accumulation as determined by BODIPY-C16 and Nile red fluorescence, respectively. Activation of AMPK by berberine induced the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) and subsequently induced CCAAT/enhancer-binding protein β (C/EBPβ) binding to the C/EBP-response element in the CD36 promoter in hepatocytes. In addition, hepatic CD36 expression and triglyceride levels were increased in normal diet-fed mice treated with berberine, but completely prevented when hepatic CD36 was silenced with adenovirus containing CD36-specific shRNA. Taken together, prolonged activation of AMPK by berberine increased CD36 expression in hepatocytes, resulting in fatty acid uptake via processes linked to hepatocellular lipid accumulation and fatty liver. - Highlights: • Berberine increases the expression and membrane translocation of CD36 in hepatocytes. • The increase of CD36 results in enhanced fatty acid uptake and lipid accumulation. • Berberine-induced fatty liver is mediated by AMPK-ERK-C/EBPβ pathway. • CD36-specific shRNA inhibited berberine-induced lipid accumulation in liver.

  8. Ubiquitinated CD36 sustains insulin-stimulated Akt activation by stabilizing insulin receptor substrate 1 in myotubes.

    Science.gov (United States)

    Sun, Shishuo; Tan, Pengcheng; Huang, Xiaoheng; Zhang, Wei; Kong, Chen; Ren, Fangfang; Su, Xiong

    2018-02-16

    Both the magnitude and duration of insulin signaling are important in executing its cellular functions. Insulin-induced degradation of insulin receptor substrate 1 (IRS1) represents a key negative feedback loop that restricts insulin signaling. Moreover, high concentrations of fatty acids (FAs) and glucose involved in the etiology of obesity-associated insulin resistance also contribute to the regulation of IRS1 degradation. The scavenger receptor CD36 binds many lipid ligands, and its contribution to insulin resistance has been extensively studied, but the exact regulation of insulin sensitivity by CD36 is highly controversial. Herein, we found that CD36 knockdown in C2C12 myotubes accelerated insulin-stimulated Akt activation, but the activated signaling was sustained for a much shorter period of time as compared with WT cells, leading to exacerbated insulin-induced insulin resistance. This was likely due to enhanced insulin-induced IRS1 degradation after CD36 knockdown. Overexpression of WT CD36, but not a ubiquitination-defective CD36 mutant, delayed IRS1 degradation. We also found that CD36 functioned through ubiquitination-dependent binding to IRS1 and inhibiting its interaction with cullin 7, a key component of the multisubunit cullin-RING E3 ubiquitin ligase complex. Moreover, dissociation of the Src family kinase Fyn from CD36 by free FAs or Fyn knockdown/inhibition accelerated insulin-induced IRS1 degradation, likely due to disrupted IRS1 interaction with CD36 and thus enhanced binding to cullin 7. In summary, we identified a CD36-dependent FA-sensing pathway that plays an important role in negative feedback regulation of insulin activation and may open up strategies for preventing or managing type 2 diabetes mellitus. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Circulating CD36 is reduced in HNF1A-MODY carriers.

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    Bacon, Siobhan; Kyithar, Ma P; Schmid, Jasmin; Costa Pozza, Andre; Handberg, Aase; Byrne, Maria M

    2013-01-01

    Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY) accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A) accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36) are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus. We recruited 37 participants with HNF1A-MODY diabetes and compared levels of sCD36 with BMI-matched participants with type 2 diabetes mellitus and normoglycaemic HNF1A-MODY negative family controls. Levels of sCD36 were correlated with phenotypic and biochemical parameters. HNF1A-MODY participants were lean, normotensive, with higher HDL and lower triglyceride levels when compared to controls and participants with type 2 diabetes mellitus. sCD36 was also significantly lower in HNF1A-MODY participants when compared to both the normoglycaemic family controls and to lean participants with type 2 diabetes mellitus. In conclusion, sCD36 is significantly lower in lean participants with HNF1A-MODY diabetes when compared to weight-matched normoglycaemic familial HNF1A-MODY negative controls and to lean participants with type 2 diabetes mellitus. Lower levels of this pro-atherogenic marker may result from the higher HDL component in the lipid profile of

  10. Circulating CD36 is reduced in HNF1A-MODY carriers.

    Directory of Open Access Journals (Sweden)

    Siobhan Bacon

    Full Text Available INTRODUCTION: Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36 are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus. METHODS: We recruited 37 participants with HNF1A-MODY diabetes and compared levels of sCD36 with BMI-matched participants with type 2 diabetes mellitus and normoglycaemic HNF1A-MODY negative family controls. Levels of sCD36 were correlated with phenotypic and biochemical parameters. RESULTS: HNF1A-MODY participants were lean, normotensive, with higher HDL and lower triglyceride levels when compared to controls and participants with type 2 diabetes mellitus. sCD36 was also significantly lower in HNF1A-MODY participants when compared to both the normoglycaemic family controls and to lean participants with type 2 diabetes mellitus. CONCLUSION: In conclusion, sCD36 is significantly lower in lean participants with HNF1A-MODY diabetes when compared to weight-matched normoglycaemic familial HNF1A-MODY negative controls and to lean participants with type 2 diabetes mellitus. Lower levels of this pro-atherogenic marker may

  11. Circulating CD36 Is Reduced in HNF1A-MODY Carriers.

    LENUS (Irish Health Repository)

    Bacon, Siobhan

    2013-01-01

    Premature atherosclerosis is a significant cause of morbidity and mortality in type 2 diabetes mellitus. Maturity onset diabetes of the young (MODY) accounts for approximately 2% of all diabetes, with mutations in the transcription factor; hepatocyte nuclear factor 1 alpha (HNF1A) accounting for the majority of MODY cases. There is somewhat limited data available on the prevalence of macrovascular disease in HNF1A-MODY carriers with diabetes. Marked insulin resistance and the associated dyslipidaemia are not clinical features of HNF1A-MODY carriers. The scavenger protein CD36 has been shown to play a substantial role in the pathogenesis of atherosclerosis, largely through its interaction with oxidised LDL. Higher levels of monocyte CD36 and plasma CD36(sCD36) are seen to cluster with insulin resistance and diabetes. The aim of this study was to determine levels of sCD36 in participants with HNF1A-MODY diabetes and to compare them with unaffected normoglycaemic family members and participants with type 2 diabetes mellitus.

  12. CD36 overexpression predisposes to arrhythmias but reduces infarct size in spontaneously hypertensive rats: gene expression profile analysis

    Czech Academy of Sciences Publication Activity Database

    Neckář, Jan; Šilhavý, Jan; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Šimáková, Miroslava; Seidman, J. G.; Seidman, Ch.; Kazdová, L.; Klevstig, M.; Novák, F.; Vecka, M.; Papoušek, František; Houštěk, Josef; Drahota, Zdeněk; Kurtz, T. W.; Kolář, František; Pravenec, Michal

    2012-01-01

    Roč. 44, č. 2 (2012), s. 173-182 ISSN 1094-8341 R&D Projects: GA MŠk(CZ) ME08006; GA MŠk(CZ) 1M0520; GA MŠk(CZ) OC08017; GA MŠk(CZ) 1M0510; GA MZd(CZ) NR9359; GA MZd(CZ) NR9387; GA MZd(CZ) NS9757; GA MZd(CZ) NS10504; GA AV ČR(CZ) IAA500110805; GA AV ČR(CZ) IAAX01110901; GA AV ČR(CZ) KAN200520703; GA ČR(CZ) GD305/08/H037; GA ČR GAP301/10/0756; GA MŠk 7E10067 Institutional research plan: CEZ:AV0Z50110509 Keywords : Cd36 * spontaneously hypertensive rat * arrhythmias * infarct size * gene expression profiles Subject RIV: FA - Cardiovascular Diseases incl. Cardiotharic Surgery Impact factor: 2.806, year: 2012

  13. Role of FAT/CD36 in novel PKC isoform activation in heart of spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Klevstig, M. J.; Marková, I.; Burianová, J.; Kazdová, L.; Pravenec, Michal; Nováková, O.; Novák, F.

    2011-01-01

    Roč. 357, 1-2 (2011), s. 163-169 ISSN 0300-8177 R&D Projects: GA ČR(CZ) GD305/08/H037; GA MŠk(CZ) ME08006 Grant - others:Univerzita Karlova(CZ) SVV33779266 Institutional research plan: CEZ:AV0Z50110509 Keywords : CD36 * novel PKC * spontaneously hypertensive rat * insulin resistance Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 2.057, year: 2011

  14. Cluster Differentiating 36 (CD36) Deficiency Attenuates Obesity-Associated Oxidative Stress in the Heart.

    Science.gov (United States)

    Gharib, Mohamed; Tao, Huan; Fungwe, Thomas V; Hajri, Tahar

    2016-01-01

    Obesity is often associated with a state of oxidative stress and increased lipid deposition in the heart. More importantly, obesity increases lipid influx into the heart and induces excessive production of reactive oxygen species (ROS) leading to cell toxicity and metabolic dysfunction. Cluster differentiating 36 (CD36) protein is highly expressed in the heart and regulates lipid utilization but its role in obesity-associated oxidative stress is still not clear. The aim of this study was to determine the impact of CD36 deficiency on cardiac steatosis, oxidative stress and lipotoxicity associated with obesity. Studies were conducted in control (Lean), obese leptin-deficient (Lepob/ob) and leptin-CD36 double null (Lepob/obCD36-/-) mice. Compared to lean mice, cardiac steatosis, and fatty acid (FA) uptake and oxidation were increased in Lepob/ob mice, while glucose uptake and oxidation was reduced. Moreover, insulin resistance, oxidative stress markers and NADPH oxidase-dependent ROS production were markedly enhanced. This was associated with the induction of NADPH oxidase expression, and increased membrane-associated p47phox, p67phox and protein kinase C. Silencing CD36 in Lepob/ob mice prevented cardiac steatosis, increased insulin sensitivity and glucose utilization, but reduced FA uptake and oxidation. Moreover, CD36 deficiency reduced NADPH oxidase activity and decreased NADPH oxidase-dependent ROS production. In isolated cardiomyocytes, CD36 deficiency reduced palmitate-induced ROS production and normalized NADPH oxidase activity. CD36 deficiency prevented obesity-associated cardiac steatosis and insulin resistance, and reduced NADPH oxidase-dependent ROS production. The study demonstrates that CD36 regulates NADPH oxidase activity and mediates FA-induced oxidative stress.

  15. Soluble CD36 and risk markers of insulin resistance and atherosclerosis are elevated in polycystic ovary syndrome and significantly reduced during pioglitazone treatment

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Højlund, Kurt; Andersen, Marianne

    2007-01-01

    Objective: We investigated the relation between soluble CD36 (sCD36), risk markers of atherosclerosis and body composition, and glucose and lipid metabolism in polycystic ovary syndrome (PCOS) Research Design and Methods: Thirty PCOS patients were randomized to pioglitazone, 30 mg/day or placebo...... units), oxLDL (44.9 (26.9 - 75.1) vs. 36.1 (23.4 - 55.5) U/l), and hsCRP (0.26 (0.03 - 2.41) vs. 0.12 (0.02 - 0.81) mg/dl) were significantly increased in PCOS patients vs. controls (geometric mean (+/- 2SD)). In PCOS, positive correlations were found between central fat mass and sCD36 (r=0.43), hs......CRP (r=0.43), and IL-6 (r=0.42), all pPCOS patients and controls (n=44). sCD36 and oxLDL were significant...

  16. CD36 is indispensable for thermogenesis under conditions of fasting and cold stress

    Energy Technology Data Exchange (ETDEWEB)

    Putri, Mirasari [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Syamsunarno, Mas Rizky A.A. [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Department of Biochemistry, Universitas Padjadjaran, Jl. Raya Bandung Sumedang KM 21, Jatinangor, West Java 45363 (Indonesia); Iso, Tatsuya, E-mail: isot@gunma-u.ac.jp [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Education and Research Support Center, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamaguchi, Aiko; Hanaoka, Hirofumi [Department of Bioimaging Information Analysis, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Sunaga, Hiroaki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Koitabashi, Norimichi [Department of Medicine and Biological Science, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Matsui, Hiroki [Department of Laboratory Sciences, Gunma University Graduate School of Health Sciences, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Yamazaki, Chiho; Kameo, Satomi [Department of Public Health, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); Tsushima, Yoshito [Department of Diagnostic Radiology and Nuclear Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511 (Japan); and others

    2015-02-20

    Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36{sup −/−} mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36{sup −/−} mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue {sup 125}I-BMIPP and the glucose analogue {sup 18}F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36{sup −/−} mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36{sup −/−} mice after cold exposure. These findings strongly suggest that CD36{sup −/−} mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation. - Highlights: • We examined the role of CD36 in thermogenesis during cold exposure. • CD36{sup −/−} mice exhibit rapid hypothermia after cold exposure during fasting. • Uptake of fatty acid and glucose is impaired in thermogenic tissues during fasting. • Storage of energy substrates is

  17. CD36 is indispensable for thermogenesis under conditions of fasting and cold stress

    International Nuclear Information System (INIS)

    Putri, Mirasari; Syamsunarno, Mas Rizky A.A.; Iso, Tatsuya; Yamaguchi, Aiko; Hanaoka, Hirofumi; Sunaga, Hiroaki; Koitabashi, Norimichi; Matsui, Hiroki; Yamazaki, Chiho; Kameo, Satomi; Tsushima, Yoshito

    2015-01-01

    Hypothermia can occur during fasting when thermoregulatory mechanisms, involving fatty acid (FA) utilization, are disturbed. CD36/FA translocase is a membrane protein which facilitates membrane transport of long-chain FA in the FA consuming heart, skeletal muscle (SkM) and adipose tissues. It also accelerates uptake of triglyceride-rich lipoprotein by brown adipose tissue (BAT) in a cold environment. In mice deficient for CD36 (CD36 −/− mice), FA uptake is markedly reduced with a compensatory increase in glucose uptake in the heart and SkM, resulting in lower levels of blood glucose especially during fasting. However, the role of CD36 in thermogenic activity during fasting remains to be determined. In fasted CD36 −/− mice, body temperature drastically decreased shortly after cold exposure. The hypothermia was accompanied by a marked reduction in blood glucose and in stores of triacylglycerols in BAT and of glycogen in glycolytic SkM. Biodistribution analysis using the FA analogue 125 I-BMIPP and the glucose analogue 18 F-FDG revealed that uptake of FA and glucose was severely impaired in BAT and glycolytic SkM in cold-exposed CD36 −/− mice. Further, induction of the genes of thermogenesis in BAT was blunted in fasted CD36 −/− mice after cold exposure. These findings strongly suggest that CD36 −/− mice exhibit pronounced hypothermia after fasting due to depletion of energy storage in BAT and glycolytic SkM and to reduced supply of energy substrates to these tissues. Our study underscores the importance of CD36 for nutrient homeostasis to survive potentially life-threatening challenges, such as cold and starvation. - Highlights: • We examined the role of CD36 in thermogenesis during cold exposure. • CD36 −/− mice exhibit rapid hypothermia after cold exposure during fasting. • Uptake of fatty acid and glucose is impaired in thermogenic tissues during fasting. • Storage of energy substrates is reduced in thermogenic tissues during

  18. CD36 deficiency leads to choroidal involution via COX2 down-regulation in rodents.

    Directory of Open Access Journals (Sweden)

    Marianne Houssier

    2008-02-01

    Full Text Available BACKGROUND: In the Western world, a major cause of blindness is age-related macular degeneration (AMD. Recent research in angiogenesis has furthered the understanding of choroidal neovascularization, which occurs in the "wet" form of AMD. In contrast, very little is known about the mechanisms of the predominant, "dry" form of AMD, which is characterized by retinal atrophy and choroidal involution. The aim of this study is to elucidate the possible implication of the scavenger receptor CD36 in retinal degeneration and choroidal involution, the cardinal features of the dry form of AMD. METHODS AND FINDINGS: We here show that deficiency of CD36, which participates in outer segment (OS phagocytosis by the retinal pigment epithelium (RPE in vitro, leads to significant progressive age-related photoreceptor degeneration evaluated histologically at different ages in two rodent models of CD36 invalidation in vivo (Spontaneous hypertensive rats (SHR and CD36-/- mice. Furthermore, these animals developed significant age related choroidal involution reflected in a 100%-300% increase in the avascular area of the choriocapillaries measured on vascular corrosion casts of aged animals. We also show that proangiogenic COX2 expression in RPE is stimulated by CD36 activating antibody and that CD36-deficient RPE cells from SHR rats fail to induce COX2 and subsequent vascular endothelial growth factor (VEGF expression upon OS or antibody stimulation in vitro. CD36-/- mice express reduced levels of COX2 and VEGF in vivo, and COX2-/- mice develop progressive choroidal degeneration similar to what is seen in CD36 deficiency. CONCLUSIONS: CD36 deficiency leads to choroidal involution via COX2 down-regulation in the RPE. These results show a novel molecular mechanism of choroidal degeneration, a key feature of dry AMD. These findings unveil a pathogenic process, to our knowledge previously undescribed, with important implications for the development of new therapies.

  19. β-Amyloid promotes accumulation of lipid peroxides by inhibiting CD36-mediated clearance of oxidized lipoproteins

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    Khan Tayeba

    2004-11-01

    Full Text Available Abstract Background Recent studies suggest that hypercholesterolemia, an established risk factor for atherosclerosis, is also a risk factor for Alzheimer's disease. The myeloid scavenger receptor CD36 binds oxidized lipoproteins that accumulate with hypercholesterolemia and mediates their clearance from the circulation and peripheral tissues. Recently, we demonstrated that CD36 also binds fibrillar β-amyloid and initiates a signaling cascade that regulates microglial recruitment and activation. As increased lipoprotein oxidation and accumulation of lipid peroxidation products have been reported in Alzheimer's disease, we investigated whether β-amyloid altered oxidized lipoprotein clearance via CD36. Methods The availability of mice genetically deficient in class A (SRAI & II and class B (CD36 scavenger receptors has facilitated studies to discriminate their individual actions. Using primary microglia and macrophages, we assessed the impact of Aβ on: (a cholesterol ester accumulation by GC-MS and neutral lipid staining, (b binding, uptake and degradation of 125I-labeled oxidized lipoproteins via CD36, SR-A and CD36/SR-A-independent pathways, (c expression of SR-A and CD36. In addition, using mice with targeted deletions in essential kinases in the CD36-signaling cascade, we investigated whether Aβ-CD36 signaling altered metabolism of oxidized lipoproteins. Results In primary microglia and macrophages, Aβ inhibited binding, uptake and degradation of oxidized low density lipoprotein (oxLDL in a dose-dependent manner. While untreated cells accumulated abundant cholesterol ester in the presence of oxLDL, cells treated with Aβ were devoid of cholesterol ester. Pretreatment of cells with Aβ did not affect subsequent degradation of oxidized lipoproteins, indicating that lysosomal accumulation of Aβ did not disrupt this degradation pathway. Using mice with targeted deletions of the scavenger receptors, we demonstrated that Aβ inhibited oxidized

  20. CD36 Differently Regulates Macrophage Responses to Smooth and Rough Lipopolysaccharide.

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    Rafał Biedroń

    Full Text Available Lipopolysaccharide (LPS is the major pathogen-associated molecular pattern of Gram-negative bacterial infections, and includes smooth (S-LPS and rough (R-LPS chemotypes. Upon activation by LPS through CD14, TLR4/MD-2 heterodimers sequentially induce two waves of intracellular signaling for macrophage activation: the MyD88-dependent pathway from the plasma membrane and, following internalization, the TRIF-dependent pathway from endosomes. We sought to better define the role of scavenger receptors CD36 and CD204/SR-A as accessory LPS receptors that can contribute to pro-inflammatory and microbicidal activation of macrophages. We have found that CD36 differently regulates activation of mouse macrophages by S-LPS versus R-LPS. The ability of CD36 to substitute for CD14 in loading R-LPS, but not S-LPS onto TLR4/MD-2 allows CD14-independent macrophage responses to R-LPS. Conversely, S-LPS, but not R-LPS effectively stimulates CD14 binding to CD36, which favors S-LPS transfer from CD14 onto TLR4/MD-2 under conditions of low CD14 occupancy with S-LPS in serum-free medium. In contrast, in the presence of serum, CD36 reduces S-LPS binding to TLR4/MD-2 and the subsequent MyD88-dependent signaling, by mediating internalization of S-LPS/CD14 complexes. Additionally, CD36 positively regulates activation of TRIF-dependent signaling by both S-LPS and R-LPS, by promoting TLR4/MD-2 endocytosis. In contrast, we have found that SR-A does not function as a S-LPS receptor. Thus, by co-operating with CD14 in both R- and S-LPS loading onto TLR4/MD-2, CD36 can enhance the sensitivity of tissue-resident macrophages in detecting infections by Gram-negative bacteria. However, in later phases, following influx of serum to the infection site, the CD36-mediated negative regulation of MyD88-dependent branch of S-LPS-induced TLR4 signaling might constitute a mechanism to prevent an excessive inflammatory response, while preserving the adjuvant effect of S-LPS for adaptive

  1. Nobiletin Inhibits CD36-Dependent Tumor Angiogenesis, Migration, Invasion, and Sphere Formation Through the Cd36/Stat3/Nf-Κb Signaling Axis

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    Nipin Sp

    2018-06-01

    Full Text Available Targeted cancer therapy with natural compounds is more effective than nontargeted therapy. Nobiletin is a flavonoid derived from citrus peel that has anticancer activity. Cluster of differentiation 36 (CD36 is a member of the class B scavenger receptor family that is involved in importing fatty acids into cells. CD36 plays a role in tumor angiogenesis by binding to its ligand, thrombospondin-1 (TSP-1, and then interacting with transforming growth factor beta 1 (TGFβ1. CD36 is implicated in tumor metastasis through its roles in fatty acid metabolism. This study investigated the molecular mechanisms underlying nobiletin’s anticancer activity by characterizing its interactions with CD36 as the target molecule. We hypothesize that the anti-angiogenic activity of nobiletin involving its regulation of CD36 via signal transducer and activator of transcription 3 (STAT3 rather than through TSP-1. Gene analysis identified a Gamma interferon activation site (GAS element in the CD36 gene promoter that acts as a STAT3 binding site, an interaction that was confirmed by ChIP assay. STAT3 interacts with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB, suggesting that nobiletin also acts through the CD36/ (STAT3/NF-κB signaling axis. Nobiletin inhibited CD36-dependent breast cancer cell migration and invasion as well as CD36-mediated tumor sphere formation. Taken together, these results suggest that nobiletin inhibits cancer stem cells in multiple ways.

  2. Soluble CD36- a marker of the (pathophysiological) role of CD36 in the metabolic syndrome?

    DEFF Research Database (Denmark)

    Koonen, Debby P Y; Jensen, Majken K; Handberg, Aase

    2011-01-01

    associated with obesity and lipid components of the metabolic syndrome, with risk of heart disease and type 2 diabetes. Recently, non-cell bound CD36 was identified in human plasma and was termed soluble CD36 (sCD36). In this review we will describe the functions of CD36 in tissues and address the role of s......CD36 in the context of the metabolic syndrome. We will also highlight recent findings from human genetic studies looking at the CD36 locus in relation to metabolic profile in the general population. Finally, we present a model in which insulin resistance, oxLDL, low-grade inflammation and liver...

  3. The CD36-PPARγ Pathway in Metabolic Disorders

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    Loïze Maréchal

    2018-05-01

    Full Text Available Uncovering the biological role of nuclear receptor peroxisome proliferator-activated receptors (PPARs has greatly advanced our knowledge of the transcriptional control of glucose and energy metabolism. As such, pharmacological activation of PPARγ has emerged as an efficient approach for treating metabolic disorders with the current use of thiazolidinediones to improve insulin resistance in diabetic patients. The recent identification of growth hormone releasing peptides (GHRP as potent inducers of PPARγ through activation of the scavenger receptor CD36 has defined a novel alternative to regulate essential aspects of lipid and energy metabolism. Recent advances on the emerging role of CD36 and GHRP hexarelin in regulating PPARγ downstream actions with benefits on atherosclerosis, hepatic cholesterol biosynthesis and fat mitochondrial biogenesis are summarized here. The response of PPARγ coactivator PGC-1 is also discussed in these effects. The identification of the GHRP-CD36-PPARγ pathway in controlling various tissue metabolic functions provides an interesting option for metabolic disorders.

  4. CML/CD36 accelerates atherosclerotic progression via inhibiting foam cell migration.

    Science.gov (United States)

    Xu, Suining; Li, Lihua; Yan, Jinchuan; Ye, Fei; Shao, Chen; Sun, Zhen; Bao, Zhengyang; Dai, Zhiyin; Zhu, Jie; Jing, Lele; Wang, Zhongqun

    2018-01-01

    Among the various complications of type 2 diabetes mellitus, atherosclerosis causes the highest disability and morbidity. A multitude of macrophage-derived foam cells are retained in atherosclerotic plaques resulting not only from recruitment of monocytes into lesions but also from a reduced rate of macrophage migration from lesions. Nε-carboxymethyl-Lysine (CML), an advanced glycation end product, is responsible for most complications of diabetes. This study was designed to investigate the mechanism of CML/CD36 accelerating atherosclerotic progression via inhibiting foam cell migration. In vivo study and in vitro study were performed. For the in vivo investigation, CML/CD36 accelerated atherosclerotic progression via promoting the accumulation of macrophage-derived foam cells in aorta and inhibited macrophage-derived foam cells in aorta migrating to the para-aorta lymph node of diabetic apoE -/- mice. For the in vitro investigation, CML/CD36 inhibited RAW264.7-derived foam cell migration through NOX-derived ROS, FAK phosphorylation, Arp2/3 complex activation and F-actin polymerization. Thus, we concluded that CML/CD36 inhibited foam cells of plaque migrating to para-aorta lymph nodes, accelerating atherosclerotic progression. The corresponding mechanism may be via free cholesterol, ROS generation, p-FAK, Arp2/3, F-actin polymerization. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Behavioral characterization of CD36 knockout mice with SHIRPA primary screen.

    Science.gov (United States)

    Zhang, Shuxiao; Wang, Wei; Li, Juan; Cheng, Ke; Zhou, Jingjing; Zhu, Dan; Yang, Deyu; Liang, Zihong; Fang, Liang; Liao, Li; Xie, Peng

    2016-02-15

    CD36 is a member of the class B scavenger receptor family of cell surface proteins, which plays a major role in fatty acid, glucose and lipid metabolism. Besides, CD36 functions as a microglial surface receptor for amyloid beta peptide. Regarding this, we suggest CD36 might also contribute to neuropsychiatric disease. The aim of this study was to achieve a behavioral phenotype of CD36 knockout (CD36(-/-)) mice. We characterized the behavior of CD36(-/-) mice and C57BL/6J mice by subjecting them to a series of tests, which include SHIRPA primary behavioral screen test, 1% sucrose preference test, elevated plus-maze test, open-field test and forced swimming test. The results showed that CD36(-/-) mice traversed more squares, emitted more defecation, exhibited higher tail elevation and had more aggressive behaviors than C57BL/6J mice. The CD36(-/-) mice spent more time and traveled longer distance in periphery zone in the open-field test. Meanwhile, the numbers that CD36(-/-) mice entered in the open arms of elevated plus-maze were reduced. These findings suggest that CD36(-/-) mice present an anxious phenotype and might be involved in neuropsychiatric disorders. Copyright © 2015. Published by Elsevier B.V.

  6. CD36- and GPR120-mediated Ca²⁺ signaling in human taste bud cells mediates differential responses to fatty acids and is altered in obese mice.

    Science.gov (United States)

    Ozdener, Mehmet Hakan; Subramaniam, Selvakumar; Sundaresan, Sinju; Sery, Omar; Hashimoto, Toshihiro; Asakawa, Yoshinori; Besnard, Philippe; Abumrad, Nada A; Khan, Naim Akhtar

    2014-04-01

    It is important to increase our understanding of gustatory detection of dietary fat and its contribution to fat preference. We studied the roles of the fat taste receptors CD36 and GPR120 and their interactions via Ca(2+) signaling in fungiform taste bud cells (TBC). We measured Ca(2+) signaling in human TBC, transfected with small interfering RNAs against messenger RNAs encoding CD36 and GPR120 (or control small interfering RNAs). We also studied Ca(2+) signaling in TBC from CD36(-/-) mice and from wild-type lean and obese mice. Additional studies were conducted with mouse enteroendocrine cell line STC-1 that express GPR120 and stably transfected with human CD36. We measured release of serotonin and glucagon-like peptide-1 from human and mice TBC in response to CD36 and GPR120 activation. High concentrations of linoleic acid induced Ca(2+) signaling via CD36 and GPR120 in human and mice TBC, as well as in STC-1 cells, and low concentrations induced Ca(2+) signaling via only CD36. Incubation of human and mice fungiform TBC with lineoleic acid down-regulated CD36 and up-regulated GPR120 in membrane lipid rafts. Obese mice had decreased spontaneous preference for fat. Fungiform TBC from obese mice had reduced Ca(2+) and serotonin responses, but increased release of glucagon-like peptide-1, along with reduced levels of CD36 and increased levels of GPR120 in lipid rafts. CD36 and GPR120 have nonoverlapping roles in TBC signaling during orogustatory perception of dietary lipids; these are differentially regulated by obesity. Copyright © 2014 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Role of FAT/CD36 in fatty acid sensing, energy, and glucose homeostasis regulation in DIO and DR rats.

    Science.gov (United States)

    Le Foll, Christelle; Dunn-Meynell, Ambrose A; Levin, Barry E

    2015-02-01

    Hypothalamic fatty acid (FA) sensing neurons alter their activity utilizing the FA translocator/receptor, FAT/CD36. Depletion of ventromedial hypothalamus (VMH) CD36 with adeno-associated viral vector expressing CD36 shRNA (AAV CD36 shRNA) leads to redistribution of adipose stores and insulin resistance in outbred rats. This study assessed the requirement of VMH CD36-mediated FA sensing for the regulation of energy and glucose homeostasis in postnatal day 5 (P5) and P21 selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats using VMH AAV CD36 shRNA injections. P5 CD36 depletion altered VMH neuronal FA sensing predominantly in DIO rats. After 10 wk on a 45% fat diet, DIO rats injected with VMH AAV CD36 shRNA at P21 ate more and gained more weight than DIO AAV controls, while DR AAV CD36 shRNA-injected rats gained less weight than DR AAV controls. VMH CD36 depletion increased inguinal fat pad weights and leptin levels in DIO and DR rats. Although DR AAV CD36 shRNA-injected rats became as obese as DIO AAV controls, only DIO control and CD36 depleted rats became insulin-resistant on a 45% fat diet. VMH CD36 depletion stunted linear growth in DIO and DR rats. DIO rats injected with AAV CD36 shRNA at P5 had increased fat mass, mostly due to a 45% increase in subcutaneous fat. They were also insulin-resistant with an associated 71% increase of liver triglycerides. These results demonstrate that VMH CD36-mediated FA sensing is a critical factor in the regulation of energy and glucose homeostasis and fat deposition in DIO and DR rats.

  8. Cholesteryl ester hydroperoxides increase macrophage CD36 gene expression via PPARα

    International Nuclear Information System (INIS)

    Jedidi, Iness; Couturier, Martine; Therond, Patrice; Gardes-Albert, Monique; Legrand, Alain; Barouki, Robert; Bonnefont-Rousselot, Dominique; Aggerbeck, Martine

    2006-01-01

    The uptake of oxidized LDL by macrophages is a key event in the development of atherosclerosis. The scavenger receptor CD36 is one major receptor that internalizes oxidized LDL. In differentiated human macrophages, we compared the regulation of CD36 expression by copper-oxidized LDL or their products. Only oxidized derivatives of cholesteryl ester (CEOOH) increased the amount of CD36 mRNA (2.5-fold). Both oxidized LDL and CEOOH treatment increased two to fourfold the transcription of promoters containing peroxisome-proliferator-activated-receptor responsive elements (PPRE) in the presence of PPARα or γ. Electrophoretic-mobility-shift-assays with nuclear extracts prepared from macrophages treated by either oxidized LDL or CEOOH showed increased binding of PPARα to the CD36 gene promoter PPRE. In conclusion, CEOOH present in oxidized LDL increase CD36 gene expression in a pathway involving PPARα

  9. CD36 is involved in oleic acid detection by the murine olfactory system.

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    Sonja eOberland

    2015-09-01

    Full Text Available Olfactory signals influence food intake in a variety of species. To maximize the chances of finding a source of calories, an animal’s preference for fatty foods and triglycerides already becomes apparent during olfactory food search behavior. However, the molecular identity of both receptors and ligands mediating olfactory-dependent fatty acid recognition are, so far, undescribed. We here describe that a subset of olfactory sensory neurons expresses the fatty acid receptor CD36 and demonstrate a receptor-like localization of CD36 in olfactory cilia by STED microscopy. CD36-positive olfactory neurons share olfaction-specific transduction elements and project to numerous glomeruli in the ventral olfactory bulb. In accordance with the described roles of CD36 as fatty acid receptor or co-receptor in other sensory systems, the number of olfactory neurons responding to oleic acid, a major milk component, in Ca2+ imaging experiments is drastically reduced in young CD36 knock-out mice. Strikingly, we also observe marked age-dependent changes in CD36 localization, which is prominently present in the ciliary compartment only during the suckling period. Our results support the involvement of CD36 in fatty acid detection by the mammalian olfactory system.

  10. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

    Science.gov (United States)

    Huynh, David N; Bessi, Valérie L; Ménard, Liliane; Piquereau, Jérôme; Proulx, Caroline; Febbraio, Maria; Lubell, William D; Carpentier, André C; Burelle, Yan; Ong, Huy; Marleau, Sylvie

    2018-02-01

    CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv) were associated with an increase in circulating adiponectin levels, epididymal fat adiponectin gene expression, and adiponectin transcriptional regulators ( Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative stress and apoptosis were observed along with an increase in expression of myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK, and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated hearts, whereas blockade of adiponectin with an anti-adiponectin antibody abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and reperfusion (MI/R) injury and dysfunction, at least in part, by increasing circulating and myocardial adiponectin levels. Hence, both paracrine and endocrine effects of adiponectin may contribute to reduced reactive oxygen species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh, D. N., Bessi, V. L., Ménard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell, W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

  11. Multiple metabolic hits converge on CD36 as novel mediator of tubular epithelial apoptosis in diabetic nephropathy.

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    Katalin Susztak

    2005-02-01

    Full Text Available Diabetic nephropathy (DNP is a common complication of type 1 and type 2 diabetes mellitus and the most common cause of kidney failure. While DNP manifests with albuminuria and diabetic glomerulopathy, its progression correlates best with tubular epithelial degeneration (TED and interstitial fibrosis. However, mechanisms leading to TED in DNP remain poorly understood.We found that expression of scavenger receptor CD36 coincided with proximal tubular epithelial cell (PTEC apoptosis and TED specifically in human DNP. High glucose stimulated cell surface expression of CD36 in PTECs. CD36 expression was necessary and sufficient to mediate PTEC apoptosis induced by glycated albumins (AGE-BSA and CML-BSA and free fatty acid palmitate through sequential activation of src kinase, and proapoptotic p38 MAPK and caspase 3. In contrast, paucity of expression of CD36 in PTECs in diabetic mice with diabetic glomerulopathy was associated with normal tubular epithelium and the absence of tubular apoptosis. Mouse PTECs lacked CD36 and were resistant to AGE-BSA-induced apoptosis. Recombinant expression of CD36 in mouse PTECs conferred susceptibility to AGE-BSA-induced apoptosis.Our findings suggest a novel role for CD36 as an essential mediator of proximal tubular apoptosis in human DNP. Because CD36 expression was induced by glucose in PTECs, and because increased CD36 mediated AGE-BSA-, CML-BSA-, and palmitate-induced PTEC apoptosis, we propose a two-step metabolic hit model for TED, a hallmark of progression in DNP.

  12. CD36 is required for myoblast fusion during myogenic differentiation

    International Nuclear Information System (INIS)

    Park, Seung-Yoon; Yun, Youngeun; Kim, In-San

    2012-01-01

    Highlights: ► CD36 expression was induced during myogenic differentiation. ► CD36 expression was localized in multinucleated myotubes. ► The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. ► Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

  13. CD36 is required for myoblast fusion during myogenic differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Park, Seung-Yoon [Department of Biochemistry, College of Medicine, Dongguk University and Medical Institute of Dongguk University, Gyeongju 780-714 (Korea, Republic of); Yun, Youngeun [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, In-San, E-mail: iskim@knu.ac.kr [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Biomedical Research Institute, Korea Institute Science and Technology, Seoul (Korea, Republic of)

    2012-11-02

    Highlights: Black-Right-Pointing-Pointer CD36 expression was induced during myogenic differentiation. Black-Right-Pointing-Pointer CD36 expression was localized in multinucleated myotubes. Black-Right-Pointing-Pointer The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. Black-Right-Pointing-Pointer Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

  14. The effect of albumin on podocytes: The role of the fatty acid moiety and the potential role of CD36 scavenger receptor

    International Nuclear Information System (INIS)

    Pawluczyk, I.Z.A.; Pervez, A.; Ghaderi Najafabadi, M.; Saleem, M.A.; Topham, P.S.

    2014-01-01

    Evidence is emerging that podocytes are able to endocytose proteins such as albumin using kinetics consistent with a receptor-mediated process. To date the role of the fatty acid moiety on albumin uptake kinetics has not been delineated and the receptor responsible for uptake is yet to be identified. Albumin uptake studies were carried out on cultured human podocytes exposed to FITC-labelled human serum albumin either carrying fatty acids (HSA +FA ) or depleted of them (HSA −FA ). Receptor-mediated endocytosis of FITC-HSA +FA over 60 min was 5 times greater than that of FITC-HSA −FA . 24 h exposure of podocytes to albumin up-regulated nephrin expression and induced the activation of caspase-3. These effects were more pronounced in response to HSA −FA. Individually, anti-CD36 antibodies had no effect upon endocytosis of FITC-HSA. However, a cocktail of 2 antibodies reduced uptake by nearly 50%. Albumin endocytosis was enhanced in the presence of the CD36 specific inhibitor sulfo-N-succinimidyl oleate (SSO) while knock-down of CD36 using CD36siRNA had no effect on uptake. These data suggest that receptor-mediated endocytosis of albumin by podocytes is regulated by the fatty acid moiety, although, some of the detrimental effects are induced independently of it. CD36 does not play a direct role in the uptake of albumin. - Highlights: • The fatty acid moiety is essential for receptor mediated endocytosis of albumin. • Fatty acid depleted albumin is more pathogenic to podocytes. • CD36 is not directly involved in albumin uptake by podocytes

  15. Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36

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    Roger S. Holmes

    2012-09-01

    Full Text Available Platelet glycoprotein 4 (CD36 (or fatty acyl translocase [FAT], or scavenger receptor class B, member 3 [SCARB3] is an essential cell surface and skeletal muscle outer mitochondrial membrane glycoprotein involved in multiple functions in the body. CD36 serves as a ligand receptor of thrombospondin, long chain fatty acids, oxidized low density lipoproteins (LDLs and malaria-infected erythrocytes. CD36 also influences various diseases, including angiogenesis, thrombosis, atherosclerosis, malaria, diabetes, steatosis, dementia and obesity. Genetic deficiency of this protein results in significant changes in fatty acid and oxidized lipid uptake. Comparative CD36 amino acid sequences and structures and CD36 gene locations were examined using data from several vertebrate genome projects. Vertebrate CD36 sequences shared 53–100% identity as compared with 29–32% sequence identities with other CD36-like superfamily members, SCARB1 and SCARB2. At least eight vertebrate CD36 N-glycosylation sites were conserved which are required for membrane integration. Sequence alignments, key amino acid residues and predicted secondary structures were also studied. Three CD36 domains were identified including cytoplasmic, transmembrane and exoplasmic sequences. Conserved sequences included N- and C-terminal transmembrane glycines; and exoplasmic cysteine disulphide residues; TSP-1 and PE binding sites, Thr92 and His242, respectively; 17 conserved proline and 14 glycine residues, which may participate in forming CD36 ‘short loops’; and basic amino acid residues, and may contribute to fatty acid and thrombospondin binding. Vertebrate CD36 genes usually contained 12 coding exons. The human CD36 gene contained transcription factor binding sites (including PPARG and PPARA contributing to a high gene expression level (6.6 times average. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate CD36 gene with vertebrate

  16. [Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency].

    Science.gov (United States)

    Watanabe, K; Toba, K; Ogawa, Y; Aizawa, Y; Tanabe, N; Miyajima, S; Kusano, Y; Nagatomo, T; Hirokawa, Y

    1997-12-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases [44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases] using a flow cytometer. 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases.

  17. Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency

    International Nuclear Information System (INIS)

    Watanabe, Kenichi; Nagatomo, Takafumi; Toba, Ken; Ogawa, Yusuke; Aizawa, Yoshifusa; Tanabe, Naohito; Miyajima, Seiichi; Kusano, Yoriko; Hirokawa, Yoichi.

    1997-01-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases (44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases) using a flow cytometer. 123 I-β-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases. (author)

  18. Different patterns of {sup 123}I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Kenichi; Nagatomo, Takafumi [Niigata Coll. of Pharmacy (Japan); Toba, Ken; Ogawa, Yusuke; Aizawa, Yoshifusa; Tanabe, Naohito; Miyajima, Seiichi; Kusano, Yoriko; Hirokawa, Yoichi

    1997-12-01

    The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases (44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases) using a flow cytometer. {sup 123}I-{beta}-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases. (author)

  19. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

    Directory of Open Access Journals (Sweden)

    Marjorie Buttet

    Full Text Available The metabolic syndrome (MetS greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD. By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP and blood clearance (ApoC2. These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG, while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the

  20. CD36 Modulates Fasting and Preabsorptive Hormone and Bile Acid Levels.

    Science.gov (United States)

    Shibao, Cyndya A; Celedonio, Jorge E; Tamboli, Robyn; Sidani, Reem; Love-Gregory, Latisha; Pietka, Terri; Xiong, Yanhua; Wei, Yan; Abumrad, Naji N; Abumrad, Nada A; Flynn, Charles Robb

    2018-05-01

    Abnormal fatty acid (FA) metabolism contributes to diabetes and cardiovascular disease. The FA receptor CD36 has been linked to risk of metabolic syndrome. In rodents CD36 regulates various aspects of fat metabolism, but whether it has similar actions in humans is unknown. We examined the impact of a coding single-nucleotide polymorphism in CD36 on postprandial hormone and bile acid (BA) responses. To examine whether the minor allele (G) of coding CD36 variant rs3211938 (G/T), which reduces CD36 level by ∼50%, influences hormonal responses to a high-fat meal (HFM). Obese African American (AA) women carriers of the G allele of rs3211938 (G/T) and weight-matched noncarriers (T/T) were studied before and after a HFM. Two-center study. Obese AA women. HFM. Early preabsorptive responses (10 minutes) and extended excursions in plasma hormones [C-peptide, insulin, incretins, ghrelin fibroblast growth factor (FGF)19, FGF21], BAs, and serum lipoproteins (chylomicrons, very-low-density lipoprotein) were determined. At fasting, G-allele carriers had significantly reduced cholesterol and glycodeoxycholic acid and consistent but nonsignificant reductions of serum lipoproteins. Levels of GLP-1 and pancreatic polypeptide (PP) were reduced 60% to 70% and those of total BAs were 1.8-fold higher. After the meal, G-allele carriers displayed attenuated early (-10 to 10 minute) responses in insulin, C-peptide, GLP-1, gastric inhibitory peptide, and PP. BAs exhibited divergent trends in G allele carriers vs noncarriers concomitant with differential FGF19 responses. CD36 plays an important role in the preabsorptive hormone and BA responses that coordinate brain and gut regulation of energy metabolism.

  1. CD36 gene polymorphism is associated with Alzheimer's disease

    Czech Academy of Sciences Publication Activity Database

    Šerý, Omar; Janoutová, J.; Ewerlingová, Laura; Hálová, Alice; Lochman, J.; Janout, V.; Khan, N. A.; Balcar, Vladimír Josef

    2017-01-01

    Roč. 135, č. 1 (2017), s. 46-53 ISSN 0300-9084 Institutional support: RVO:67985904 Keywords : polymorphism * association * CD36 Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 3.112, year: 2016

  2. Molecular cloning, characterization, and expression analysis of fatty acid translocase (FAT/CD36) in the pigeon (Columba livia domestica).

    Science.gov (United States)

    Xie, P; Zhang, A T; Wang, C; Azzam, M M M; Zou, X T

    2012-07-01

    Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein that plays an important role in transporting long-chain fatty acids. In the current study, a full-length cDNA of FAT/CD36 was first cloned from the intestine of White King pigeon by rapid amplification of cDNA ends (RACE) method. The full-length cDNA of pigeon FAT/CD36 was 2,282 bp, including a 5'-untranslated region of 224 bp, a 3'-untranslated region of 642 bp, and an open reading frame of 1,416 bp encoding a protein of 471 amino acids with the predicted molecular weight of 52.7 kDa. Sequence comparison indicated that FAT/CD36 of pigeon had high identity with other avian FAT/CD36. Using quantitative real-time PCR, expression of FAT/CD36 was the greatest in the duodenum at 28 d posthatch, and in the jejunum, the expression of FAT/CD36 at 14 d posthatch was greater than at 8 d but the same as 28 d posthatch. However, in the ileum, expression of FAT/CD36 peaked at embryonic d 15 and 8 d posthatch. The effects of long-chain fatty acids on pigeon FAT/CD36 and peroxisome proliferator activated receptor γ (PPARγ) mRNA expression were also investigated in vitro. It showed that a low concentration (5 μM) of oleic acid, palmitic acid, and linoleic acid can significantly increase FAT/CD36 and PPARγ mRNA level in pigeon jejunum. However, for linolenic acid or arachidonic acid, the induction of both gene expressions needed a higher concentration (50 μM or 250 μM). Two hundred and 50 μM palmitic acid was shown to suppress FAT/CD36 gene expression. The results suggest that FAT/CD36 may be a representative of intestine development in pigeon, and it could be regulated by long-chain fatty acids via PPARγ pathway.

  3. Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

    Science.gov (United States)

    Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

    2017-07-01

    Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Alternative promoter usage of the membrane glycoprotein CD36

    Directory of Open Access Journals (Sweden)

    Whatling Carl

    2006-03-01

    Full Text Available Abstract Background CD36 is a membrane glycoprotein involved in a variety of cellular processes such as lipid transport, immune regulation, hemostasis, adhesion, angiogenesis and atherosclerosis. It is expressed in many tissues and cell types, with a tissue specific expression pattern that is a result of a complex regulation for which the molecular mechanisms are not yet fully understood. There are several alternative mRNA isoforms described for the gene. We have investigated the expression patterns of five alternative first exons of the CD36 gene in several human tissues and cell types, to better understand the molecular details behind its regulation. Results We have identified one novel alternative first exon of the CD36 gene, and confirmed the expression of four previously known alternative first exons of the gene. The alternative transcripts are all expressed in more than one human tissue and their expression patterns vary highly in skeletal muscle, heart, liver, adipose tissue, placenta, spinal cord, cerebrum and monocytes. All alternative first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins. The alternative promoters lack TATA-boxes and CpG islands. The upstream region of exon 1b contains several features common for house keeping gene and monocyte specific gene promoters. Conclusion Tissue-specific expression patterns of the alternative first exons of CD36 suggest that the alternative first exons of the gene are regulated individually and tissue specifically. At the same time, the fact that all first exons are upregulated in THP-1 macrophages in response to oxidized low density lipoproteins may suggest that the alternative first exons are coregulated in this cell type and environmental condition. The molecular mechanisms regulating CD36 thus appear to be unusually complex, which might reflect the multifunctional role of the gene in different tissues and cellular conditions.

  5. CD36 Protein Influences Myocardial Ca2+ Homeostasis and Phospholipid Metabolism CONDUCTION ANOMALIES IN CD36-DEFICIENT MICE DURING FASTING

    Czech Academy of Sciences Publication Activity Database

    Pietka, T. A.; Sulkin, M.S.; Kuda, Ondřej; Wang, W.; Zhou, D.; Yamada, K. A.; Yang, K.; Su, X.; Gross, R. W.; Nerbonne, J. M.; Efimov, I. R.; Abumrad, N. A.

    2012-01-01

    Roč. 287, č. 46 (2012), s. 38901-38912 ISSN 0021-9258 Institutional support: RVO:67985823 Keywords : calcium * cyclic AMP (cAMP) * heart * phospholipid * phospholipid metabolism * polyunsaturated fatty acids * CD36 deficiency * SERCA2a * sudden death Subject RIV: ED - Physiology Impact factor: 4.651, year: 2012

  6. Macrophage heterogeneity and cholesterol homeostasis: classically-activated macrophages are associated with reduced cholesterol accumulation following treatment with oxidized LDL.

    Science.gov (United States)

    Chu, Eugene M; Tai, Daven C; Beer, Jennifer L; Hill, John S

    2013-02-01

    Macrophages are centrally involved during atherosclerosis development and are the predominant cell type that accumulates cholesterol in the plaque. Macrophages however, are heterogeneous in nature reflecting a variety of microenvironments and different phenotypes may be more prone to contribute towards atherosclerosis progression. Using primary human monocyte-derived macrophages, we sought to evaluate one aspect of atherogenic potential of different macrophage phenotypes by determining their propensity to associate with and accumulate oxidized low density lipoprotein (oxLDL). Classically-activated macrophages treated simultaneously with interferon γ (IFNγ) and tumor necrosis factor α (TNFα) associated with less oxLDL and accumulated less cholesterol compared to untreated controls. The combined treatment of IFNγ and TNFα reduced the mRNA expression of CD36 and the expression of both cell surface CD36 and macrophage scavenger receptor 1 (MSR1) protein. Under oxLDL loaded conditions, IFNγ and TNFα did not reduce macrophage protein expression of the transcription factor peroxisome proliferator-actived receptor γ (PPARγ) which is known to positively regulate CD36 expression. However, macrophages treated with IFNγ attenuated the ability of the PPARγ-specific agonist rosiglitazone from upregulating cell surface CD36 protein expression. Our results demonstrate that the observed reduction of cholesterol accumulation in macrophages treated with IFNγ and TNFα following oxLDL treatment was due at least in part to reduced cell surface CD36 and MSR1 protein expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. CD36 and malaria: friends or foes? A decade of data provides some answers.

    Science.gov (United States)

    Cabrera, Ana; Neculai, Dante; Kain, Kevin C

    2014-09-01

    The past 10 years have generated new insights into the complex interaction between CD36 (cluster of differentiation 36) and malaria. These range from the crystallization of the CD36 homolog, LIMPII (lysosomal integral membrane protein II), permitting modeling of CD36 and its binding to diverse ligands, to cell biology-based studies of CD36 and large population genetic studies assessing the association of CD36 polymorphisms and malarial disease severity. Collectively these lines of evidence indicate that a receptor other than CD36 is associated with severity. CD36 plays an important role in innate immunity and in the phagocytic uptake of multiple pathogens including malaria. CD36 polymorphisms lack association with severity, and isolates that cause severe disease primarily bind to endothelial protein C receptor (EPCR) rather than to CD36. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  8. Genetics of Cd36 and the hypertension metabolic syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, T. W.

    2002-01-01

    Roč. 22, č. 2 (2002), s. 148-153 ISSN 0270-9295 R&D Projects: GA ČR(CZ) GA301/00/1636; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015 Grant - others:NIHFogarty(US) RO3TW001236 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.176, year: 2002

  9. Genetics of Cd36 and the hypertension metabolic syndrome

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Kurtz, W. T.

    2002-01-01

    Roč. 22, č. 2 (2002), s. 148-153 ISSN 0270-9295 R&D Projects: GA ČR GV204/98/K015; GA ČR GA301/00/1636; GA MŠk LN00A079 Grant - others:NIHFogarty(US) RO3TW001236 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.176, year: 2002

  10. CD36-Mediated Hematoma Absorption following Intracerebral Hemorrhage: Negative Regulation by TLR4 Signaling

    OpenAIRE

    Fang, Huang; Chen, Jing; Lin, Sen; Wang, PengFei; Wang, YanChun; Xiong, XiaoYi; Yang, QingWu

    2014-01-01

    Promoting hematoma absorption is a novel therapeutic strategy for intracerebral hemorrhage (ICH); however, the mechanism of hematoma absorption is unclear. The present study explored the function and potential mechanism of CD36 in hematoma absorption using in vitro and in vivo ICH models. Hematoma absorption in CD36-deficient ICH patients was examined. Compared with patients with normal CD36 expression, CD36-deficient ICH patients had slower hematoma adsorption and aggravated neurologic defic...

  11. Responses of skeletal muscle lipid metabolism in rat gastrocnemius to hypothyroidism and iodothyronine administration: a putative role for FAT/CD36.

    Science.gov (United States)

    Lombardi, Assunta; De Matteis, Rita; Moreno, Maria; Napolitano, Laura; Busiello, Rosa Anna; Senese, Rosalba; de Lange, Pieter; Lanni, Antonia; Goglia, Fernando

    2012-11-15

    Iodothyronines such as triiodothyronine (T(3)) and 3,5-diiodothyronine (T(2)) influence energy expenditure and lipid metabolism. Skeletal muscle contributes significantly to energy homeostasis, and the above iodothyronines are known to act on this tissue. However, little is known about the cellular/molecular events underlying the effects of T(3) and T(2) on skeletal muscle lipid handling. Since FAT/CD36 is involved in the utilization of free fatty acids by skeletal muscle, specifically in their import into that tissue and presumably their oxidation at the mitochondrial level, we hypothesized that related changes in lipid handling and in FAT/CD36 expression and subcellular redistribution would occur due to hypothyroidism and to T(3) or T(2) administration to hypothyroid rats. In gastrocnemius muscles isolated from hypothyroid rats, FAT/CD36 was upregulated (mRNA levels and total tissue, sarcolemmal, and mitochondrial protein levels). Administration of either T(3) or T(2) to hypothyroid rats resulted in 1) little or no change in FAT/CD36 mRNA level, 2) a decreased total FAT/CD36 protein level, and 3) further increases in FAT/CD36 protein level in sarcolemma and mitochondria. Thus, the main effect of each iodothyronine seemed to be exerted at the level of FAT/CD36 cellular distribution. The effect of further increases in FAT/CD36 protein level in sarcolemma and mitochondria was already evident at 1 h after iodothyronine administration. Each iodothyronine increased the mitochondrial fatty acid oxidation rate. However, the mechanisms underlying their rapid effects seem to differ; T(2) and T(3) each induce FAT/CD36 translocation to mitochondria, but only T(2) induces increases in carnitine palmitoyl transferase system activity and in the mitochondrial substrate oxidation rate.

  12. Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

    DEFF Research Database (Denmark)

    Hempel, Casper; Wang, Christian William; Kurtzhals, Jorgen Anders Lindholm

    2017-01-01

    FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1-4 days after seeding was quantified by using a static binding assay. Results: The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic...... labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody......-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2-4 days. Conclusion: The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has...

  13. miR-758-5p regulates cholesterol uptake via targeting the CD36 3'UTR.

    Science.gov (United States)

    Li, Bi-Rong; Xia, Lin-Qin; Liu, Jing; Liao, Lin-Ling; Zhang, Yang; Deng, Min; Zhong, Hui-Juan; Feng, Ting-Ting; He, Ping-Ping; Ouyang, Xin-Ping

    2017-12-09

    miR-758-3p plays an important role via regulting ABCA1-mediated cholesterol efflux in atherosclerosis. However, the mechanism of miR-758-5p in cholesterol metabolism is still unclear. Here, we revealed that miR-758-5p decreased total cholesterol accumulation in THP-1 macrophage derived foam cells through markedly reducing cholesterol uptake, and no effect on the cholesterol efflux. Interestingly, computational analysis suggests that CD36 may be a target gene of miR-758-5p. Our study further demonstrated that miR-758-5p decreased CD36 expression at both protein and mRNA levels via targeting the CD36 3'UTR in THP-1 macrophage derived foam cells. The present present study concluded that miR-758-5p decreases lipid accumulation of foam cell via regulating CD36-mediated the cholesterol uptake. Therefore, targeting miR-758-5p may offer a promising strategy to treat atherosclerotic vascular disease. Copyright © 2017. Published by Elsevier Inc.

  14. Hepatic fat accumulation and regulation of FAT/CD36: an effect of hepatic irradiation

    Science.gov (United States)

    Martius, Gesa; Alwahsh, Salamah Mohammad; Rave-Fränk, Margret; Hess, Clemens Friedrich; Christiansen, Hans; Ramadori, Giuliano; Malik, Ihtzaz Ahmed

    2014-01-01

    Irradiation is known to induce inflammation and affect fat metabolic pathways. The current study investigates hepatic fat accumulation and fatty acid transportation in a rat model of single dose liver irradiation (25-Gy). Rat livers were selectively irradiated in-vivo (25-Gy), sham-irradiated rats served as controls. Hepatic lipids were studied by colorimetric assays in liver and serum. Intracellular lipids, protein and mRNA were studied by Nile red staining, immunohistology, Western Blot analysis and RT-PCR in liver, respectively. Changes in FAT/CD36 expression were studied in-vitro in a human monocyte cell line U937 after irradiation in presence or absence of infliximab (IFX). Nile Red staining of liver cryosections showed a quick (12-48 h) increase in fat droplets. Accordingly, hepatic triglycerides (TG) and free fatty acids (FFA) were elevated. An early increase (3-6 h) in the serum level of HDL-C, TG and cholesterol was measured after single dose irradiation followed by a decrease thereafter. Furthermore, expression of the fat transporter protein FAT/CD36 was increased, immunohistochemistry revealed basolateral and cytoplasmic expression in hepatocytes. Moreover, apolipoprotein-B100, -C3 and enzymes (acetyl-CoA carboxylase, lipoprotein-lipase, carnitine-palmitoyltransferase, malonyl-CoA-decarboxylase) involved in fat metabolism were induced at 12-24 h. Early activation of the NFkβ pathway (IκBα) by TNF-α was seen, followed by a significant elevation of serum markers for liver damage (AST and GLDH). TNF-α blockage by anti-TNF-α in cell culture (U937) prevented the increase of FAT/CD36 caused by irradiation. Selective liver irradiation is a model for rapid induction of steatosis hepatis and fat accumulation could be triggered by irradiation-induced inflammatory mediators (e.g. TNF-α). PMID:25197426

  15. CD36 deficiency increases insulin sensitivity in muscle, but induces insulin resistance in the liver in mice

    NARCIS (Netherlands)

    Goudriaan, J.R.; Dahlmans, V.E.H.; Teusink, B.; Ouwens, D.M.; Febbraio, M.; Maassen, J.A.; Romijn, J.A.; Havekes, L.M.; Voshol, P.J.

    2003-01-01

    CD36 (fatty acid translocase) is involved in high-affinity peripheral fatty acid uptake. Mice lacking CD36 exhibit increased plasma free fatty acid and triglyceride (TG) levels and decreased glucose levels. Studies in spontaneous hypertensive rats lacking functional CD36 link CD36 to the

  16. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    Science.gov (United States)

    Jeppesen, J.; Albers, P. H.; Rose, A. J.; Birk, J. B.; Schjerling, P.; Dzamko, N.; Steinberg, G. R.; Kiens, B.

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FA translocase CD36 (FAT/CD36) translocation and FA uptake in skeletal muscle during contractions. In one model, wild-type (WT) and AMP-dependent protein kinase kinase dead (AMPK KD) mice were exercised or extensor digitorum longus (EDL) and soleus (SOL) muscles were contracted, ex vivo. In separate studies, FAT/CD36 translocation and FA uptake in response to muscle contractions were investigated in the perfused rat hindlimb. Exercise induced a similar increase in skeletal muscle cell surface membrane FAT/CD36 content in WT (+34%) and AMPK KD (+37%) mice. In contrast, 5-aminoimidazole-4-carboxamide ribonucleoside only induced an increase in cell surface FAT/CD36 content in WT (+29%) mice. Furthermore, in the perfused rat hindlimb, muscle contraction induced a rapid (1 min, +15%) and sustained (10 min, +24%) FAT/CD36 relocation to cell surface membranes. The increase in cell surface FAT/CD36 protein content with muscle contractions was associated with increased FA uptake, both in EDL and SOL muscle from WT and AMPK KD mice and in the perfused rat hindlimb. This suggests that AMPK is not essential in regulation of FAT/CD36 translocation and FA uptake in skeletal muscle during contractions. However, AMPK could be important in regulation of FAT/CD36 distribution in other physiological situations. PMID:21297178

  17. PCSK9 Induces CD36 Degradation and Affects Long-Chain Fatty Acid Uptake and Triglyceride Metabolism in Adipocytes and in Mouse Liver.

    Science.gov (United States)

    Demers, Annie; Samami, Samaneh; Lauzier, Benjamin; Des Rosiers, Christine; Ngo Sock, Emilienne Tudor; Ong, Huy; Mayer, Gaetan

    2015-12-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of the low-density lipoprotein receptor thereby elevating plasma low-density lipoprotein cholesterol levels and the risk of coronary heart disease. Thus, the use of PCSK9 inhibitors holds great promise to prevent heart disease. Previous work found that PCSK9 is involved in triglyceride metabolism, independently of its action on low-density lipoprotein receptor, and that other yet unidentified receptors could mediate this effect. Therefore, we assessed whether PCSK9 enhances the degradation of CD36, a major receptor involved in transport of long-chain fatty acids and triglyceride storage. Overexpressed or recombinant PCSK9 induced CD36 degradation in cell lines and primary adipocytes and reduced the uptake of the palmitate analog Bodipy FL C16 and oxidized low-density lipoprotein in 3T3-L1 adipocytes and hepatic HepG2 cells, respectively. Surface plasmon resonance, coimmunoprecipitation, confocal immunofluorescence microscopy, and protein degradation pathway inhibitors revealed that PCSK9 directly interacts with CD36 and targets the receptor to lysosomes through a mechanism involving the proteasome. Importantly, the level of CD36 protein was increased by >3-fold upon small interfering RNA knockdown of endogenous PCSK9 in hepatic cells and similarly increased in the liver and visceral adipose tissue of Pcsk9(-/-) mice. In Pcsk9(-/-) mice, increased hepatic CD36 was correlated with an amplified uptake of fatty acid and accumulation of triglycerides and lipid droplets. Our results demonstrate an important role of PCSK9 in modulating the function of CD36 and triglyceride metabolism. PCSK9-mediated CD36 degradation may serve to limit fatty acid uptake and triglyceride accumulation in tissues, such as the liver. © 2015 American Heart Association, Inc.

  18. Identification of the Oxidized Low-Density Lipoprotein Scavenger Receptor CD36 in Plasma

    DEFF Research Database (Denmark)

    Handberg, Aase; Levin, Klaus; Højlund, Kurt

    2006-01-01

    BACKGROUND: Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears to be a key proatherogenic molecule. Increased expression of CD36 has been attributed to hyperglycemia and to defective macrophage insulin signaling in insulin resistance. Premature...

  19. Contraction-induced skeletal muscle FAT/CD36 trafficking and FA uptake is AMPK independent

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Albers, Peter Hjorth; Rose, Adam John

    2011-01-01

    The aim of this study was to investigate the molecular mechanisms regulating FAT/CD36 translocation and fatty acid uptake in skeletal muscle during contractions. In one model, WT and AMPK KD mice were exercised or EDL and SOL muscles were contracted, ex vivo. In separate studies, FAT/CD36 translo...

  20. [Hypertrophic cardiomyopathy showing no 123I-BMIPP myocardial accumulation with type I CD36 deficiency].

    Science.gov (United States)

    Watanabe, K; Miyajima, S; Kusano, Y; Tanabe, N; Hirokawa, Y

    1997-07-01

    A 57 years old male consulted our hospital in complaining chest oppression and short of breath. Familial and dilated phase hypertrophic cardiomyopathy (HCM) was detected by ECG, echocardiography, left ventriculography and left ventricular endomyocardial biopsy. 201T1 SPECT showed regional increased accumulation in the ventricular septum, however, no myocardial accumulation of 123I-beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) was observed. We analyzed CD36 in this patient, and found he had type 1 CD36 deficiency. Myocardial uptake of long-chain fatty acids occurs via a specific transporter, which is homologous with human CD36. We hypothesize that CD36 deficiency, especially type 1 CD36 deficiency, might be one factor of no myocardial 123I-BMIPP uptake.

  1. Involvement of CD36 in Modulating the Decrease of NPY and AgRP Induced by Acute Palmitic Acid Stimulation in N1E-115 Cells

    Directory of Open Access Journals (Sweden)

    Yan Ma

    2017-06-01

    Full Text Available Central nervous system (CNS fatty acid sensing plays an important role in the regulation of food intake, and palmitic acid (PA is the most important long chain fatty acid (LCFA in the mammalian diet. To explore the effect of PA on central neuropeptide expression and the role of the cluster of the differentiation of 36 (CD36 in the process, N1E-115 cells were cultured with PA in the presence or absence of sulfosuccinimidyl-oleate (SSO, a CD36 inhibitor. Results showed that 10 μmol/L PA significantly reduced NPY and AgRP mRNA expression after 20 min of exposure, while the expression of CD36 was upregulated. The presence of SSO significantly attenuated the decrease of NPY and AgRP expression that was induced by PA alone, although no notable effect on PA- induced CD36 gene expression was observed. In conclusion, our study suggests the involvement of CD36 in the PA-induced decrease of NPY and AgRP in N1E-115 cells.

  2. Increased soluble CD36 is linked to advanced steatosis in nonalcoholic fatty liver disease.

    Science.gov (United States)

    García-Monzón, Carmelo; Lo Iacono, Oreste; Crespo, Javier; Romero-Gómez, Manuel; García-Samaniego, Javier; Fernández-Bermejo, Miguel; Domínguez-Díez, Agustín; Rodríguez de Cía, Javier; Sáez, Alicia; Porrero, José Luís; Vargas-Castrillón, Javier; Chávez-Jiménez, Enrique; Soto-Fernández, Susana; Díaz, Ainhoa; Gallego-Durán, Rocío; Madejón, Antonio; Miquilena-Colina, María Eugenia

    2014-01-01

    Soluble CD36 (sCD36) clusters with insulin resistance, but no evidence exists on its relationship with hepatic fat content. We determined sCD36 to assess its link to steatosis in nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C (CHC) patients. Two hundred and twenty-seven NAFLD, eighty-seven CHC, and eighty-five patients with histologically normal liver (NL) were studied. Steatosis was graded by Kleiner's histological scoring system. Serum sCD36 and hepatic CD36 expression was assessed by immunoassay and immunohistochemistry, respectively. In NAFLD, serum sCD36 levels were significantly higher in simple steatosis than in NL (361.4 ± 286.4 vs. 173.9 ± 137.4 pg/mL, respectively; P steatosis (387.2 ± 283.6 pg/mL; P = 0.173). A progressive increase in serum sCD36 values was found in NAFLD depending on the histological grade of steatosis (P steatosis in NAFLD when adjusted by demographic and anthropometric features [odds ratio (OR), 1.001; 95% confidence interval (CI), 1.000 to 1.002; P = 0.021] and by metabolic variables (OR, 1.002; 95% CI, 1.000 to 1.003; P = 0.001). Interestingly, a significant correlation was observed between hepatic CD36 and serum sCD36 (ρ = 0.499, P steatosis in NAFLD. © 2013 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

  3. Modulation of cAMP levels by high-fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression.

    Science.gov (United States)

    Zingg, Jean-Marc; Hasan, Syeda T; Nakagawa, Kiyotaka; Canepa, Elisa; Ricciarelli, Roberta; Villacorta, Luis; Azzi, Angelo; Meydani, Mohsen

    2017-01-02

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr -/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of fatty acid transport proteins (CD36/FAT, FABP4/aP2) in peritoneal macrophages. In this study, we analyzed the molecular mechanisms by which curcumin (500, 1000, 1500 mg/kg diet, for 4 months) may influence plasma and tissue lipid levels in Ldlr -/- mice fed an HFD. In liver, HFD significantly suppressed cAMP levels, and curcumin restored almost normal levels. Similar trends were observed in adipose tissues, but not in brain, skeletal muscle, spleen, and kidney. Treatment with curcumin increased phosphorylation of CREB in liver, what may play a role in regulatory effects of curcumin in lipid homeostasis. In cell lines, curcumin increased the level of cAMP, activated the transcription factor CREB and the human CD36 promoter via a sequence containing a consensus CREB response element. Regulatory effects of HFD and Cur on gene expression were observed in liver, less in skeletal muscle and not in brain. Since the cAMP/protein kinase A (PKA)/CREB pathway plays an important role in lipid homeostasis, energy expenditure, and thermogenesis by increasing lipolysis and fatty acid β-oxidation, an increase in cAMP levels induced by curcumin may contribute to its hypolipidemic and anti-atherosclerotic effects. © 2016 BioFactors, 43(1):42-53, 2017. © 2016 International Union of Biochemistry and Molecular Biology.

  4. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue

    2015-01-01

    PURPOSE: We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. METHODS: Double-blinded, placebo-controlled study in 54 men aged 60-78 years...... with bioavailable testosterone 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. OUTCOMES: sCD36, total and regional fat mass were....... units] vs. TT and vs. placebo (p testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta...

  5. Oral Fat Sensing and CD36 Gene Polymorphism in Algerian Lean and Obese Teenagers

    Czech Academy of Sciences Publication Activity Database

    Daoudi, A.; Plesník, J.; Sayed, A.; Šerý, Omar; Rouabah, A.; Rouabah, L.; Khan, N. A.

    2015-01-01

    Roč. 7, č. 11 (2015), s. 9096-9104 ISSN 2072-6643 Institutional support: RVO:67985904 Keywords : CD36 * taste * obesity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.759, year: 2015

  6. CD36 Mediated Fatty Acid-Induced Podocyte Apoptosis via Oxidative Stress.

    Directory of Open Access Journals (Sweden)

    Wei Hua

    Full Text Available Hyperlipidemia-induced apoptosis mediated by fatty acid translocase CD36 is associated with increased uptake of ox-LDL or fatty acid in macrophages, hepatocytes and proximal tubular epithelial cells, leading to atherosclerosis, liver damage and fibrosis in obese patients, and diabetic nephropathy (DN, respectively. However, the specific role of CD36 in podocyte apoptosis in DN with hyperlipidemia remains poorly investigated.The expression of CD36 was measured in paraffin-embedded kidney tissue samples (Ctr = 18, DN = 20 by immunohistochemistry and immunofluorescence staining. We cultured conditionally immortalized mouse podocytes (MPC5 and treated cells with palmitic acid, and measured CD36 expression by real-time PCR, Western blot analysis and immunofluorescence; lipid uptake by Oil red O staining and BODIPY staining; apoptosis by flow cytometry assay, TUNEL assay and Western blot analysis; and ROS production by DCFH-DA fluorescence staining. All statistical analyses were performed using SPSS 21.0 statistical software.CD36 expression was increased in kidney tissue from DN patients with hyperlipidemia. Palmitic acid upregulated CD36 expression and promoted its translocation from cytoplasm to plasma membrane in podocytes. Furthermore, palmitic acid increased lipid uptake, ROS production and apoptosis in podocytes, Sulfo-N-succinimidyloleate (SSO, the specific inhibitor of the fatty acid binding site on CD36, decreased palmitic acid-induced fatty acid accumulation, ROS production, and apoptosis in podocytes. Antioxidant 4-hydroxy-2,2,6,6- tetramethylpiperidine -1-oxyl (tempol inhibited the overproduction of ROS and apoptosis in podocytes induced by palmitic acid.CD36 mediated fatty acid-induced podocyte apoptosis via oxidative stress might participate in the process of DN.

  7. Tet38 Efflux Pump Affects Staphylococcus aureus Internalization by Epithelial Cells through Interaction with CD36 and Contributes to Bacterial Escape from Acidic and Nonacidic Phagolysosomes.

    Science.gov (United States)

    Truong-Bolduc, Q C; Khan, N S; Vyas, J M; Hooper, D C

    2017-02-01

    We previously reported that the Tet38 efflux pump is involved in internalization of Staphylococcus aureus by A549 lung epithelial cells. A lack of tet38 reduced bacterial uptake by A549 cells to 36% of that of the parental strain RN6390. Using invasion assays coupled with confocal microscopy imaging, we studied the host cell receptor(s) responsible for bacterial uptake via interaction with Tet38. We also assessed the ability of S. aureus to survive following alkalinization of the phagolysosomes by chloroquine. Antibody to the scavenger receptor CD36 reduced the internalization of S. aureus RN6390 by A549 cells, but the dependence on CD36 was reduced in QT7 tet38, suggesting that an interaction between Tet38 and CD36 contributed to S. aureus internalization. Following fusion of the S. aureus-associated endosomes with lysosomes, alkalinization of the acidic environment with chloroquine led to a rapid increase in the number of S. aureus RN6390 bacteria in the cytosol, followed by a decrease shortly thereafter. This effect of chloroquine was not seen in the absence of intact Tet38 in mutant QT7. These data taken together suggest that Tet38 plays a role both in bacterial internalization via interaction with CD36 and in bacterial escape from the phagolysosomes. Copyright © 2017 American Society for Microbiology.

  8. FAT/CD36 expression alone is insufficient to enhance cellular uptake of oleate

    International Nuclear Information System (INIS)

    Eyre, Nicholas S.; Cleland, Leslie G.; Mayrhofer, Graham

    2008-01-01

    Fatty acid translocase (FAT/CD36) is one of several proteins implicated in receptor-mediated uptake of long-chain fatty acids (LCFAs). We have tested whether levels of FAT/CD36 correlate with cellular oleic acid import, using a Tet-Off inducible transfected CHO cell line. Consistent with our previous findings, FAT/CD36 was enriched in lipid raft-derived detergent-resistant membranes (DRMs) that also contained caveolin-1, the marker protein of caveolae. Furthermore in transfected cells, plasma membrane FAT/CD36 co-localized extensively with the lipid raft-enriched ganglioside GM1, and partially with a caveolin-1-EGFP fusion protein. Nevertheless, even at high levels of expression, FAT/CD36 did not affect uptake of oleic acid. We propose that the ability of FAT/CD36 to mediate enhanced uptake of LCFAs is dependent on co-expression of other proteins or factors that are lacking in CHO cells

  9. FAT/CD36: a major regulator of neuronal fatty acid sensing and energy homeostasis in rats and mice.

    Science.gov (United States)

    Le Foll, Christelle; Dunn-Meynell, Ambrose; Musatov, Serguei; Magnan, Christophe; Levin, Barry E

    2013-08-01

    Hypothalamic "metabolic-sensing" neurons sense glucose and fatty acids (FAs) and play an integral role in the regulation of glucose, energy homeostasis, and the development of obesity and diabetes. Using pharmacologic agents, we previously found that ~50% of these neurons responded to oleic acid (OA) by using the FA translocator/receptor FAT/CD36 (CD36). For further elucidation of the role of CD36 in neuronal FA sensing, ventromedial hypothalamus (VMH) CD36 was depleted using adeno-associated viral (AAV) vector expressing CD36 short hairpin RNA (shRNA) in rats. Whereas their neuronal glucosensing was unaffected by CD36 depletion, the percent of neurons that responded to OA was decreased specifically in glucosensing neurons. A similar effect was seen in total-body CD36-knockout mice. Next, weanling rats were injected in the VMH with CD36 AAV shRNA. Despite significant VMH CD36 depletion, there was no effect on food intake, body weight gain, or total carcass adiposity on chow or 45% fat diets. However, VMH CD36-depleted rats did have increased plasma leptin and subcutaneous fat deposition and markedly abnormal glucose tolerance. These results demonstrate that CD36 is a critical factor in both VMH neuronal FA sensing and the regulation of energy and glucose homeostasis.

  10. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, Sara; Poulsen, Marianne Kjær; Ørnstrup, Marie Juul

    2017-01-01

    BACKGROUND AND OBJECTIVE: CD36 is implicated in fatty acid uptake in multiple tissues, including hepatocytes and adipocytes. Circulating CD36 (sCD36) is increased in non-alcoholic fatty liver disease (NAFLD).We explored this association further by investigating correlations between sCD36 levels...... resonance imaging (n=94, subcutaneous and visceral adipose tissue) and liver biopsy (n=28 NAFLD patients) performed. Plasma sCD36 was assessed by ELISA. RESULTS: NAFLD patients had elevated sCD36 levels compared to controls (0.68 (0.12-2.27) versus 0.43 (0.10-1.18), P.... An unhealthy and unbalanced CD36 expression in adipose and hepatic tissue may shift the fatty acid load to the liver.Clinical Trials.gov (NCT01464801, NCT01412645, NCT01446276).International Journal of Obesity accepted article preview online, 05 December 2016. doi:10.1038/ijo.2016.223....

  11. [Plasma scavenger receptor BI and CD36 expression change and susceptibility of atherosclerosis in patients post liver transplantation].

    Science.gov (United States)

    Chen, Xin; Xue, Jinhong; Zhang, Shuyi; Sun, Liying; Lu, Chengzhi

    2014-02-01

    To explore the association between expression changes of plasma macrophages scavenger receptor (SR)-BI and CD36 and risk of arteriosclerosis in end-stage liver disease (ESLD) patients post liver transplantation. A total of 20 liver transplantation patients were included. Clinical data including blood pressure, blood lipid, blood glucose, incidence of new-onset cardiovascular events were obtained. Plasma macrophages scavenger receptor SR-BIand CD36 expressions were detected by polymerase chain reaction (RT-PCR) and Western-blot before and at 1 year after liver transplantation. The serum levels of TC [(5.34 ± 0.87) mmol/L vs. (4.27 ± 0.91) mmol/L], TG [(2.47 ± 0.81) mmol/L vs. (1.02 ± 0.49) mmol/L] and LDL-C [(3.36 ± 0.67) mmol/L vs. (2.14 ± 0.74) mmol/L] were significantly increased (P compared to before-transplantation levels. One patient developed non-ST segment elevation myocardial infarction and treated with percutaneous coronary intervention, another patient developed atrial fibrillation at one year after transplantation. The plasma mRNA expression of SR-BI was reduced (20.44 ± 0.60 vs. 23.12 ± 0.69, P compare with that of before the transplantation. Similarly, the plasma protein expression of SR-BIwas reduced (0.21 ± 0.13 vs. 0.64 ± 0.28, P compare with that of before the transplantation. Plasma expression changes of SR-BI and CD36 might contribute to the dyslipidemia and contribute to the atherosclerosis susceptibility after liver transplantation.

  12. Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

    Directory of Open Access Journals (Sweden)

    Grace E Cooper

    Full Text Available Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031 and CD36 gene expression (p = 0.031 by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.

  13. Enhanced hepatic apoA-I secretion and peripheral efflux of cholesterol and phospholipid in CD36 null mice.

    Directory of Open Access Journals (Sweden)

    Pin Yue

    2010-03-01

    Full Text Available CD36 facilitates oxidized low density lipoprotein uptake and is implicated in development of atherosclerotic lesions. CD36 also binds unmodified high and very low density lipoproteins (HDL, VLDL but its role in the metabolism of these particles is unclear. Several polymorphisms in the CD36 gene were recently shown to associate with serum HDL cholesterol. To gain insight into potential mechanisms for these associations we examined HDL metabolism in CD36 null (CD36(-/- mice. Feeding CD36(-/- mice a high cholesterol diet significantly increased serum HDL, cholesterol and phospholipids, as compared to wild type mice. HDL apolipoproteins apoA-I and apoA-IV were increased and shifted to higher density HDL fractions suggesting altered particle maturation. Clearance of dual-labeled HDL was unchanged in CD36(-/- mice and cholesterol uptake from HDL or LDL by isolated CD36(-/- hepatocytes was unaltered. However, CD36(-/- hepatocytes had higher cholesterol and phospholipid efflux rates. In addition, expression and secretion of apoA-I and apoA-IV were increased reflecting enhanced PXR. Similar to hepatocytes, cholesterol and phospholipid efflux were enhanced in CD36(-/- macrophages without changes in protein levels of ABCA1, ABCG1 or SR-B1. However, biotinylation assays showed increased surface ABCA1 localization in CD36(-/- cells. In conclusion, CD36 influences reverse cholesterol transport and hepatic ApoA-I production. Both pathways are enhanced in CD36 deficiency, increasing HDL concentrations, which suggests the potential benefit of CD36 inhibition.

  14. Detection of atherosclerotic lesions and intimal macrophages using CD36-targeted nanovesicles.

    Science.gov (United States)

    Nie, Shufang; Zhang, Jia; Martinez-Zaguilan, Raul; Sennoune, Souad; Hossen, Md Nazir; Lichtenstein, Alice H; Cao, Jun; Meyerrose, Gary E; Paone, Ralph; Soontrapa, Suthipong; Fan, Zhaoyang; Wang, Shu

    2015-12-28

    Current approaches to the diagnosis and therapy of atherosclerosis cannot target lesion-determinant cells in the artery wall. Intimal macrophage infiltration promotes atherosclerotic lesion development by facilitating the accumulation of oxidized low-density lipoproteins (oxLDL) and increasing inflammatory responses. The presence of these cells is positively associated with lesion progression, severity and destabilization. Hence, they are an important diagnostic and therapeutic target. The objective of this study was to noninvasively assess the distribution and accumulation of intimal macrophages using CD36-targeted nanovesicles. Soy phosphatidylcholine was used to synthesize liposome-like nanovesicles. 1-(Palmitoyl)-2-(5-keto-6-octene-dioyl) phosphatidylcholine was incorporated on their surface to target the CD36 receptor. All in vitro data demonstrate that these targeted nanovesicles had a high binding affinity for the oxLDL binding site of the CD36 receptor and participated in CD36-mediated recognition and uptake of nanovesicles by macrophages. Intravenous administration into LDL receptor null mice of targeted compared to non-targeted nanovesicles resulted in higher uptake in aortic lesions. The nanovesicles co-localized with macrophages and their CD36 receptors in aortic lesions. This molecular target approach may facilitate the in vivo noninvasive imaging of atherosclerotic lesions in terms of intimal macrophage accumulation and distribution and disclose lesion features related to inflammation and possibly vulnerability thereby facilitate early lesion detection and targeted delivery of therapeutic compounds to intimal macrophages. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. CD36 expression and lipid metabolism following an oral glucose challenge in South Asians.

    Science.gov (United States)

    Patel, Jeetesh V; Banerjee, Amitava; Montoro-Garcia, Silvia; Shantsila, Eduard; Alam, Mushfique; Flinders, Paul; Houlton, Kathleen Al; Hughes, Elizabeth A; Lip, Gregory Yh; Gill, Paramjit S

    2015-07-10

    To investigate lipid metabolism and the relationship with monocyte expression of the fatty acid translocase CD36 in South Asians. An observational study of South Asians whom as an ethnic group have - a higher risk of developing diabetes. The susceptibility to diabetes is coupled with an earlier and more rapid progression of micro-, and macro-vascular complications. Twenty-nine healthy South Asian participants [mean age 34.6 (8.9) years, 76.2% male, mean body-mass index 25.0 (5.2) kg/m(2)] were recruited from an urban residential area of central Birmingham (United Kingdom). The main outcomes measured were post prandial (30 min) and post absorptive (120 min) changes from fasting (0 min) in circulating lipoproteins, lipds and hormones, and monocyte expression of CD36 post injection of a 75 g oral glucose challenge. The inducements of variations of monocyte CD36 expression were analysed. Our results showed evident changes in monocyte CD36 expression following the glucose challenge (P challenge (P lifestyle exposures have a role in moderating the expression of CD36.

  16. Circulating sCD36 levels in patients with non-alcoholic fatty liver disease and controls

    DEFF Research Database (Denmark)

    Heebøll, Sara; Poulsen, Marianne Kjær; Ørnstrup, Marie Juul

    2017-01-01

    with the level of intrahepatic lipid, insulin resistance and dyslipidemia. The weak association with markers of obesity and the association with hepatic CD36 mRNA expression suggest that excess sCD36 in NAFLD patients is derived from the hepatocytes, which may support that CD36 is involved in NAFLD development...... with intrahepatic lipid (rs=0.30), ALT (r=0.31), HOMA-insulin resistance (r=0.24), HDL (r=-0.32) and triglyceride (r=0.44, all P....04); yet, we found no correlations between sCD36 and other measures of fat distribution except an inverse relation to visceral adipose tissue (rs=-0.21, Phepatic CD36 mRNA expression (r=0.37, P=0.07). CONCLUSIONS: sCD36 levels increased...

  17. Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population

    DEFF Research Database (Denmark)

    Handberg, A; Højlund, K; Gastaldelli, A

    2012-01-01

    Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid...

  18. Study of biochemical parameters of CD36 protein and effect of RNA interference on its function

    Czech Academy of Sciences Publication Activity Database

    Zídková, J.; Kontrová, K.; Sajdok, J.; Káš, J.; Mikulík, Karel; Pěknicová, Jana; Zídek, Václav

    2006-01-01

    Roč. 7, č. 3 (2006), s. 203-203 ISSN 1567-5688 Institutional research plan: CEZ:AV0Z50200510; CEZ:AV0Z50110509; CEZ:AV0Z50520514 Keywords : cd36 protein * spontaneously hypertensive rat * metabolic disorders Subject RIV: EE - Microbiology, Virology Impact factor: 5.875, year: 2006

  19. The structural basis for CD36 binding by the malaria parasite

    DEFF Research Database (Denmark)

    Hsieh, Fu-Lien; Turner, Louise; Bolla, Jani Reddy

    2016-01-01

    CD36 is a scavenger receptor involved in fatty acid metabolism, innate immunity and angiogenesis. It interacts with lipoprotein particles and facilitates uptake of long chain fatty acids. It is also the most common target of the PfEMP1 proteins of the malaria parasite, Plasmodium falciparum...

  20. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    International Nuclear Information System (INIS)

    Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q.

    2014-01-01

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD

  1. Associations between CD36 gene polymorphisms and susceptibility to coronary artery heart disease

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Y.; Ling, Z.Y.; Deng, S.B.; Du, H.A.; Yin, Y.H.; Yuan, J.; She, Q.; Chen, Y.Q. [Department of Cardiology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing (China)

    2014-08-08

    Associations between polymorphisms of the CD36 gene and susceptibility to coronary artery heart disease (CHD) are not clear. We assessed allele frequencies and genotype distributions of CD36 gene polymorphisms in 112 CHD patients and 129 control patients using semi-quantitative polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Additionally, we detected CD36 mRNA expression by real-time quantitative PCR, and we quantified plasma levels of oxidized low-density lipoprotein (ox-LDL) using an enzyme-linked immunosorbent assay (ELISA). There were no significant differences between the two groups (P>0.05) in allele frequencies of rs1761667 or in genotype distribution and allele frequencies of rs3173798. The genotype distribution of rs1761667 significantly differed between CHD patients and controls (P=0.034), with a significantly higher frequency of the AG genotype in the CHD group compared to the control group (P=0.011). The plasma levels of ox-LDL in patients with the AG genotype were remarkably higher than those with the GG and AA genotypes (P=0.010). In a randomized sample taken from patients in the two groups, the CD36 mRNA expression of the CHD patients was higher than that of the controls. In CHD patients, the CD36 mRNA expression in AG genotype patients was remarkably higher than in those with an AA genotype (P=0.005). After adjusted logistic regression analysis, the AG genotype of rs1761667 was associated with an increased risk of CHD (OR=2.337, 95% CI=1.336-4.087, P=0.003). In conclusion, the rs1761667 polymorphism may be closely associated with developing CHD in the Chongqing Han population of China, and an AG genotype may be a genetic susceptibility factor for CHD.

  2. Skeletal Muscle and Liver Lipidomics and the Regulation of FAT/CD36

    DEFF Research Database (Denmark)

    Jordy, Andreas Børsting

    induced obesity in mice, we observed an increased muscle and liver lipid content, analyzed by mass spectrometry, concomitant with decreased glucose tolerance. We observed that treadmill exercise-training in high-fat fed mice resulted in a reduction in the lipid content in the liver, but not in muscle...... that the current worldwide obesity epidemic has resulted in the increased prevalence of “metabolic disease clusters”, including type 2 diabetes, fatty liver disease and dyslipidemia. Excessive plasma lipids can result in the accumulation of lipid metabolites at ectopic sites including skeletal muscle and liver...... during isolated muscle contractions. On the contrary, previous observations suggest that a permanent relocation of FAT/CD36 protein to the sarcolemma induces intracellular lipid accumulation, resulting in insulin resistance. Therefore, FAT/CD36 has been linked to insulin resistance. Whether increased FAT...

  3. Transgenic rescue of defective Cd36 ameliorates insulin resistance in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Landa, Vladimír; Zídek, Václav; Musilová, Alena; Křen, Vladimír; Kazdová, L.; Aitman, T. J.; Glazier, A. M.; Ibrahimi, A.; Abumrad, N. A.; Qi, N.; Wang, J. M.; St.Lezin, E. M.; Kurtz, W. T.

    2001-01-01

    Roč. 27, č. 2 (2001), s. 156-158 ISSN 1061-4036 R&D Projects: GA ČR GA301/00/1636; GA ČR GV204/98/K015; GA MŠk LN00A079 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 (fatty acid transporter) Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 29.600, year: 2001

  4. Transgenic rescue of defective Cd36 enhances myocardial adenylyl cyclase signaling in spontaneously hypertensive rats

    Czech Academy of Sciences Publication Activity Database

    Klevstig, M.; Manakov, D.; Kašparová, D.; Brabcová, I.; Papoušek, František; Žurmanová, J.; Zídek, Václav; Šilhavý, Jan; Neckář, Jan; Pravenec, Michal; Kolář, František; Nováková, O.; Novotný, J.

    2013-01-01

    Roč. 465, č. 10 (2013), s. 1477-1486 ISSN 0031-6768 R&D Projects: GA MŠk(CZ) LL1204; GA AV ČR(CZ) IAAX01110901; GA ČR(CZ) GAP303/10/0505 Institutional support: RVO:67985823 Keywords : SHR rats * Cd36 * heart * beta-Adrenergic receptors * Adenylyl cyclase * Protein kinase A Subject RIV: ED - Physiology Impact factor: 3.073, year: 2013

  5. Treatment with medium chain fatty acids milk of CD36-deficient preschool children.

    Science.gov (United States)

    Nagasaka, Hironori; Hirano, Ken-Ichi; Yorifuji, Tohru; Komatsu, Haruki; Takatani, Tomonozumi; Morioka, Ichiro; Hirayama, Satoshi; Miida, Takashi

    2018-06-01

    CD36 deficiency is characterized by limited cellular long chain fatty acid uptake in the skeletal and cardiac muscles and often causes energy crisis in these muscles. However, suitable treatment for CD36 deficiency remains to be established. The aim of this study was to evaluate the clinical and metabolic effects of medium chain triacylglycerols (MCTs) in two CD36-deficient preschool children who often developed fasting hypoglycemia and exercise-induced myalgia. Fasting blood glucose, total ketone bodies, and free fatty acids were examined and compared for usual supper diets and for diets with replacement of one component with 2 g/kg of 9% MCT-containing milk (MCT milk). Changes in serum creatine kinase and alanine aminotransferase levels, resulting from replacement of glucose water intake with 1 g/kg of MCT milk and determined by using bicycle pedaling tasks, were examined and compared. Hypoglycemic and/or myalgia episodes in daily life were also investigated. Biochemically, participants' blood glucose and total ketone bodies levels after overnight fasting substantially increased after dietary suppers containing MCT milk. Increases in serum creatine kinase and alanine aminotransferase levels resulting from the bicycle pedaling task were suppressed by MCT milk. Hypoglycemia leading to unconsciousness and tachycardia before breakfast decreased after introduction of dietary suppers containing MCT milk. Occurrence of myalgia in the lower limbs also decreased after intakes of MCT milk before long and/or strenuous exercising. Our results suggest that MCTs can prevent fasting hypoglycemia and exercise-induced myalgia in CD36-deficient young children. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Circulating sCD36 is associated with unhealthy fat distribution and elevated circulating triglycerides in morbidly obese individuals

    DEFF Research Database (Denmark)

    Knøsgaard, L; Thomsen, S B; Støckel, M

    2014-01-01

    BACKGROUND: The recently identified circulating sCD36 has been proposed to reflect tissue CD36 expression, and is upregulated in case of obesity, insulin resistance and hepatic steatosis. The aim of this study was to explore the effect of weight loss secondary to bariatric surgery in relation to s......-en-Y gastric bypass were included. Anthropometric measurements and fasting blood samples were collected at a preoperative baseline visit and 3 months after surgery. sCD36 was measured by an in-house assay, whereas insulin sensitivity and the hepatic fat accumulation were estimated by the homeostasis model...

  7. CD36 and Fyn kinase mediate malaria-induced lung endothelial barrier dysfunction in mice infected with Plasmodium berghei.

    Directory of Open Access Journals (Sweden)

    Ifeanyi U Anidi

    Full Text Available Severe malaria can trigger acute lung injury characterized by pulmonary edema resulting from increased endothelial permeability. However, the mechanism through which lung fluid conductance is altered during malaria remains unclear. To define the role that the scavenger receptor CD36 may play in mediating this response, C57BL/6J (WT and CD36-/- mice were infected with P. berghei ANKA and monitored for changes in pulmonary endothelial barrier function employing an isolated perfused lung system. WT lungs demonstrated a >10-fold increase in two measures of paracellular fluid conductance and a decrease in the albumin reflection coefficient (σalb compared to control lungs indicating a loss of barrier function. In contrast, malaria-infected CD36-/- mice had near normal fluid conductance but a similar reduction in σalb. In WT mice, lung sequestered iRBCs demonstrated production of reactive oxygen species (ROS. To determine whether knockout of CD36 could protect against ROS-induced endothelial barrier dysfunction, mouse lung microvascular endothelial monolayers (MLMVEC from WT and CD36-/- mice were exposed to H2O2. Unlike WT monolayers, which showed dose-dependent decreases in transendothelial electrical resistance (TER from H2O2 indicating loss of barrier function, CD36-/- MLMVEC demonstrated dose-dependent increases in TER. The differences between responses in WT and CD36-/- endothelial cells correlated with important differences in the intracellular compartmentalization of the CD36-associated Fyn kinase. Malaria infection increased total lung Fyn levels in CD36-/- lungs compared to WT, but this increase was due to elevated production of the inactive form of Fyn further suggesting a dysregulation of Fyn-mediated signaling. The importance of Fyn in CD36-dependent endothelial signaling was confirmed using in vitro Fyn knockdown as well as Fyn-/- mice, which were also protected from H2O2- and malaria-induced lung endothelial leak, respectively. Our

  8. CD36 mediates the phagocytosis of Plasmodium falciparuminfected erythrocytes by rodent macrophages

    Czech Academy of Sciences Publication Activity Database

    Patel, S. N.; Serghides, L.; Smith, T. G.; Febbraio, M.; Silverstein, R. L.; Kurtz, T. W.; Pravenec, Michal; Kain, K. C.

    2004-01-01

    Roč. 189, č. 2 (2004), s. 204-213 ISSN 0022-1899 R&D Projects: GA MŠk LN00A079 Grant - others:CIHR(CA) MT-13721; Ontario Ministry of Health(CA) Career Scientist award; CIHR(CA) Canada Research Chair; Department of Medicine(CA) Studentship; Canadian Blood Services(CA) Fellowship Institutional research plan: CEZ:AV0Z5011922 Keywords : CD36 * plasmodium falciparum * SHR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.943, year: 2004

  9. Genetics of Cd36 and the clustering of multiple cardiovascular risk factors in spontaneous hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Zídek, Václav; Šimáková, Miroslava; Křen, Vladimír; Křenová, D.; Horký, K.; Jáchymová, M.; Míková, B.; Kazdová, L.; Aitman, T. J.; Churchill, P. C.; Webb, R. C.; Hingarh, N. H.; Yang, Y.; Wang, J. M.; St.Lezin, E. M.; Kurtz, W. T.

    1999-01-01

    Roč. 103, č. 12 (1999), s. 1651-1657 ISSN 0021-9738 R&D Projects: GA ČR GA306/97/0521; GA ČR GV204/98/K015 Grant - others:NIH(US) ROI HL-56028; NIH(US) PO1 HL-35018; NIH(US) HL-18575 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 * cardiovascular risk factors * spontaneous hypertension Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.921, year: 1999

  10. Dependence of Brown Adipose Tissue Function on CD36-Mediated Coenzyme Q Uptake

    Directory of Open Access Journals (Sweden)

    Courtney M. Anderson

    2015-02-01

    Full Text Available Brown adipose tissue (BAT possesses the inherent ability to dissipate metabolic energy as heat through uncoupled mitochondrial respiration. An essential component of the mitochondrial electron transport chain is coenzyme Q (CoQ. While cells synthesize CoQ mostly endogenously, exogenous supplementation with CoQ has been successful as a therapy for patients with CoQ deficiency. However, which tissues depend on exogenous CoQ uptake as well as the mechanism by which CoQ is taken up by cells and the role of this process in BAT function are not well understood. Here, we report that the scavenger receptor CD36 drives the uptake of CoQ by BAT and is required for normal BAT function. BAT from mice lacking CD36 displays CoQ deficiency, impaired CoQ uptake, hypertrophy, altered lipid metabolism, mitochondrial dysfunction, and defective nonshivering thermogenesis. Together, these data reveal an important new role for the systemic transport of CoQ to BAT and its function in thermogenesis.

  11. CD36-dependent Regulation of Muscle FoxO1 and PDK4 in the PPARδ/β-mediated Adaptation to Metabolic Stress*

    OpenAIRE

    Nahlé, Zaher; Hsieh, Michael; Pietka, Terri; Coburn, Chris T.; Grimaldi, Paul A.; Zhang, Michael Q.; Das, Debopriya; Abumrad, Nada A.

    2008-01-01

    The transcription factor FoxO1 contributes to the metabolic adaptation to fasting by suppressing muscle oxidation of glucose, sparing it for glucose-dependent tissues. Previously, we reported that FoxO1 activation in C2C12 muscle cells recruits the fatty acid translocase CD36 to the plasma membrane and increases fatty acid uptake and oxidation. This, together with FoxO1 induction of lipoprotein lipase, would promote the reliance on fatty acid utilization characteristic of the fasted muscle. H...

  12. Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Churchill, P. C.; Churchill, M. C.; Vyklický, O.; Kazdová, L.; Aitman, T. J.; Petretto, E.; Hubner, N.; Wallace, C. A.; Zimdahl, H.; Zídek, Václav; Landa, Vladimír; Dunbar, J.; Bidani, A.; Griffin, K.; Qi, N.; Maxová, M.; Křen, Vladimír; Mlejnek, Petr; Wang, J.; Kurtz, T. W.

    2008-01-01

    Roč. 40, č. 8 (2008), s. 952-954 ISSN 1061-4036 R&D Projects: GA MZd(CZ) NR8545; GA MZd(CZ) NR8495; GA MŠk(CZ) 1M0520; GA MŠk(CZ) ME08006; GA MŠk(CZ) 1P05ME791; GA MZd(CZ) NR9359; GA AV ČR(CZ) IAA500110604; GA AV ČR(CZ) IAA500110805 Grant - others:HHMI(US) 55005624; EC(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Keywords : spontaneously hypertensive rat * Cd36 * hypertension Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 30.259, year: 2008

  13. Fatty acid translocase gene CD36 rs1527483 variant influences oral fat perception in Malaysian subjects.

    Science.gov (United States)

    Ong, Hing-Huat; Tan, Yen-Nee; Say, Yee-How

    2017-01-01

    We determined whether single nucleotide polymorphisms (SNPs; rs1761667 and rs1527483) in the fatty acid translocase CD36 gene - a receptor for fatty acids - is associated with oral fat perception (OFP) of different fat contents in custards and commercially-available foods, and obesity measures in Malaysian subjects (n=313; 118 males, 293 ethnic Chinese; 20 ethnic Indians). A 170-mm visual analogue scale was used to assess the ratings of perceived fat content, oiliness and creaminess of 0%, 2%, 6% and 10% fat content-by-weight custards and low-fat/regular versions of commercially-available milk, mayonnaise and cream crackers. Overall, the subjects managed to significantly discriminate the fat content, oiliness and creaminess between low-fat/regular versions of milk and mayonnaise. Females rated the perception of fat content and oiliness of both milks higher, but ethnicity, obesity and adiposity status did not seem to play a role in influencing most of OFP. The overall minor allele frequencies for rs1761667 and rs1527483 were 0.30 and 0.26, respectively. Females and individuals with rs1527483 TT genotype significantly perceived greater creaminess of 10% fat-by-weight custard. Also, individuals with rs1527483 TT genotype and T allele significantly perceived greater fat content of cream crackers, independent of fat concentration. rs1761667 SNP did not significantly affect OFP, except for cream crackers. Both gene variants were also not associated with obesity measures. Taken together, this study supports the notion that CD36 - specifically rs1527483, plays a role in OFP, but not in influencing obesity in Malaysian subjects. Besides, gender is an important factor for OFP, where females had higher sensitivity. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

    Science.gov (United States)

    Hirooka, K; Yasumura, Y; Ishida, Y; Komamura, K; Hanatani, A; Nakatani, S; Yamagishi, M; Miyatake, K

    2000-09-01

    A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

  15. A patient with type I CD36 deficiency whose myocardium accumulated 123I-BMIPP after 4 years.

    Science.gov (United States)

    Ito, K; Sugihara, H; Tanabe, T; Zen, K; Hikosaka, T; Adachi, Y; Katoh, S; Azuma, A; Nakagawa, M

    2001-06-01

    A 73-year-old man with aortic regurgitation was examined by 123I-alpha-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial single photon emission computed tomography (SPECT) in 1995. Myocardial accumulation was not evident on either the early or the delayed image obtained 15 minutes and 3 hours, respectively, after injecting 123I-BMIPP. Flow cytometric analysis of CD36 expression in monocytes and platelets identified a type I CD36 deficiency. The patient was hospitalized for severe heart failure in 1999. Upon admission, the cardiothoracic ratio on chest X-rays was 73%, and the left ventricular end-diastolic diameter on echocardiograms was enlarged to 77 mm. On the second day, we performed 123I-BMIPP myocardial SPECT. Myocardial accumulation was evident in the delayed, but not in the early image. We repeated 123I-BMIPP myocardial SPECT on the 10th day after admission. Myocardial accumulation was evident on both early and delayed images. 99mTc-tetrofosmin myocardial SPECT was immediately performed after 123I-BMIPP myocardial SPECT to distinguish myocardial from pooling images in the left ventricle, but, because the images from both 99Tc-tetrofosmin and 123I-BMIPP myocardial SPECT were idential, we considered that the 123I-BMIPP myocardial SPECT images reflected the actual myocardial condition. The CD36 molecule transports long-chain fatty acid (LCFA) on the myocardial membrane, but 123I-BMIPP scintigraphy does not show any myocardial accumulation in patients with type I CD36 deficiency, indicating that myocardial LCFA uptake occurs through CD36 on the human myocardial membrane. Even though our patient had type I CD36 deficiency, BMIPP was uptaken by the myocardium during heart failure, suggesting a variant pathway on the human myocardial membrane for LCFA uptake.

  16. Air pollution is associated with the development of atherosclerosis via the cooperation of CD36 and NLRP3 inflammasome in ApoE-/- mice.

    Science.gov (United States)

    Du, Xihao; Jiang, Shuo; Zeng, Xuejiao; Zhang, Jia; Pan, Kun; Zhou, Ji; Xie, Yuquan; Kan, Haidong; Song, Weimin; Sun, Qinghua; Zhao, Jinzhuo

    2018-06-15

    Previous studies have indicated that the main air pollutant fine particulate matter (≤2.5 μm; PM 2.5 ) exposure is associated with the development of atherosclerosis. Although the mechanism is not fully illustrated, the inflammatory responses play an important role. The present study aimed to explore whether PM 2.5 -exacerbated atherosclerosis was mediated by the cooperation of cluster of differentiation 36 (CD36) and nucleotide-binding oligomerization domain-like receptor protein (NLRP3) inflammasome in apolipoprotein E -/- (ApoE -/- ) mice. Thirty-two ApoE -/- mice were randomly divided into two groups. One group was fed with high fat chow (HFC) for 10 weeks to establish atherosclerotic model, and the other was fed with normal chow (NC). From week 11, the mice were exposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic root than that in the FA mice. Compared with the FA mice, PM mice appeared a decrease in high density lipoprotein-cholesterol (HDL-C) and apolipoprotein A1 along with an increase in apolipoprotein B, low density lipoprotein-cholesterol (LDL-C) and oxidized low-density lipoprotein (ox-LDL). Moreover, PM 2.5 exposure induced increase of CD36 in serum and aorta. In both NC and HFC groups, NLRP3 inflammasome activation-related indicators were activated or increased in the aorta of the PM mice when compared with the FA mice. The cooperation of CD36 and NLRP3 inflammasome activation may be the potential mechanisms linkixposed to concentrated PM 2.5 (PM) or filtered air (FA) using Shanghai Meteorological and Environmental Animal Exposure System for 16 weeks. In both NC and HFC groups, PM 2.5 exposure induced the formation of atherosclerosis plaque. Similarly, PM mice appeared higher lipid content in the aortic

  17. CD36 mediates both cellular uptake of very long chain fatty acids and their intestinal absorption in mice.

    Science.gov (United States)

    Drover, Victor A; Nguyen, David V; Bastie, Claire C; Darlington, Yolanda F; Abumrad, Nada A; Pessin, Jeffrey E; London, Erwin; Sahoo, Daisy; Phillips, Michael C

    2008-05-09

    The intestine has an extraordinary capacity for fatty acid (FA) absorption. Numerous candidates for a protein-mediated mechanism of dietary FA absorption have been proposed, but firm evidence for this process has remained elusive. Here we show that the scavenger receptor CD36 is required both for the uptake of very long chain FAs (VLCFAs) in cultured cells and the absorption of dietary VLCFAs in mice. We found that the fraction of CD36-dependent saturated fatty acid association/absorption in these model systems is proportional to the FA chain length and specific for fatty acids and fatty alcohols containing very long saturated acyl chains. Moreover, intestinal VLCFA absorption is completely abolished in CD36-null mice fed a high fat diet, illustrating that the predominant mechanism for VLCFA absorption is CD36-dependent. Together, these findings represent the first direct evidence for protein-facilitated FA absorption in the intestine and identify a novel therapeutic target for the treatment of diseases characterized by elevated VLCFA levels.

  18. Decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats.

    Science.gov (United States)

    Zhang, Xiao-Juan; Zhou, Li-Hong; Ban, Xiang; Liu, Dian-Xin; Jiang, Wei; Liu, Xiao-Min

    2011-10-01

    Mammals spontaneously prefer lipid rich foods. Overconsumption of high-fat diet leads to obesity and related diseases. Recent findings indicate that taste may participate in the orosensory perception of dietary lipids and the fatty taste may contribute to a preference for and excessive consumption of dietary fat. CD36, a trans-membrane glycoprotein, which is located in the taste buds of circumvallate papillae of rodents, appears to be a plausible receptor for this fatty taste. Obese subjects present a stronger preference for fatty foods, though the mechanisms involved are complex and are not fully investigated. Our data from immunofluorescence and real-time RT-PCR showed that the expression levels of CD36 in circumvallate taste buds were significantly lower in high-fat diet induced obese rats as compared with that of control rats fed a normal diet. These results suggest that decreased expression of CD36 in circumvallate taste buds of high-fat diet induced obese rats may be associated with diminished fatty taste sensitivity and in order to compensate the preference for dietary fat, rats consume more fatty foods. Therapeutic strategies designed to alter or manipulate CD36 expression or function in taste buds may have important implications in treating obesity and related diseases. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. Parvovirus B19 integration into human CD36+ erythroid progenitor cells.

    Science.gov (United States)

    Janovitz, Tyler; Wong, Susan; Young, Neal S; Oliveira, Thiago; Falck-Pedersen, Erik

    2017-11-01

    The pathogenic autonomous human parvovirus B19 (B19V) productively infects erythroid progenitor cells (EPCs). Functional similarities between B19V nonstructural protein (NS1), a DNA binding endonuclease, and the Rep proteins of Adeno-Associated Virus (AAV) led us to hypothesize that NS1 may facilitate targeted nicking of the human genome and B19 vDNA integration. We adapted an integration capture sequencing protocol (IC-Seq) to screen B19V infected human CD36+ EPCs for viral integrants, and discovered 40,000 unique B19V integration events distributed throughout the human genome. Computational analysis of integration patterns revealed strong correlations with gene intronic regions, H3K9me3 sites, and the identification of 41 base pair consensus sequence with an octanucleotide core motif. The octanucleotide core has homology to a single region of B19V, adjacent to the P6 promoter TATA box. We present the first direct evidence that B19V infection of erythroid progenitor cells disrupts the human genome and facilitates viral DNA integration. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. System for actively reducing sound

    NARCIS (Netherlands)

    Berkhoff, Arthur P.

    2005-01-01

    A system for actively reducing sound from a primary noise source, such as traffic noise, comprising: a loudspeaker connector for connecting to at least one loudspeaker for generating anti-sound for reducing said noisy sound; a microphone connector for connecting to at least a first microphone placed

  1. FAT/CD36 is localized in sarcolemma and in vesicle-like structures in subsarcolemma regions but not in mitochondria

    DEFF Research Database (Denmark)

    Jeppesen, Jacob; Mogensen, Martin; Prats, Clara

    2010-01-01

    was performed on single muscle fibers dissected from soleus muscle of lean and obese Zucker rats and from the vastus lateralis muscle from humans. Co-staining against FAT/CD36 and MitoNEET clearly show that FAT/CD36 is highly present in sarcolemma and it also associates with some vesicle-like intracellular...

  2. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic β-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic β-cells, and to examine this in relation to β-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  3. Suppression of FAT/CD36 mRNA by human growth hormone in pancreatic ß-cells

    DEFF Research Database (Denmark)

    Dalgaard, Louise Torp; Thams, Peter Grevsen; Gaarn, Louise Winkel

    2011-01-01

    of this study was to examine the effect of human growth hormone (hGH) on mRNAs of fatty acid transport and binding proteins expressed in pancreatic ß-cells, and to examine this in relation to ß-cell survival after exposure to fatty acids. hGH decreased mRNA levels of FAT/CD36, whereas mRNAs of GPR40, FASN, FABP...

  4. Alterations in the cardiac proteome of the spontaneously hypertensive rat induced by transgenic expression of CD36

    Czech Academy of Sciences Publication Activity Database

    Manakov, D.; Ujčíková, Hana; Pravenec, Michal; Novotný, J.

    2016-01-01

    Roč. 145, Aug 11 (2016), s. 177-186 ISSN 1874-3919 R&D Projects: GA MŠk(CZ) ED1.1.00/02.0109; GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LL1204 Institutional support: RVO:67985823 Keywords : SHR * CD36 * heart * left and right ventricles * proteomics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.914, year: 2016

  5. Obesity-driven prepartal hepatic lipid accumulation in dairy cows is associated with increased CD36 and SREBP-1 expression.

    Science.gov (United States)

    Prodanović, Radiša; Korićanac, Goran; Vujanac, Ivan; Djordjević, Ana; Pantelić, Marija; Romić, Snježana; Stanimirović, Zoran; Kirovski, Danijela

    2016-08-01

    We investigated the hypothesis that obesity in dairy cows enhanced expression of proteins involved in hepatic fatty acid uptake and metabolism. Sixteen Holstein-Friesian close-up cows were divided into 2 equal groups based on their body condition score (BCS) as optimal (3.25≤BCS≤3.5) and high (4.0≤BCS≤4.25). Intravenous glucose tolerance test (GTT) and liver biopsies were carried out at day 10 before calving. Blood samples were collected before (basal) and after glucose infusion, and glucose, insulin and non-esterified fatty acid (NEFA) levels were determined at each sample point. In addition, β-hydroxybutyrate and triglycerides levels were measured in the basal samples. The liver biopsies were analyzed for total lipid content and protein expression of insulin receptor beta (IRβ), fatty acid translocase (FAT/CD36) and sterol regulatory element-binding protein-1 (SREBP-1). Basal glucose and insulin were higher in high-BCS cows, which coincided with higher circulating triglycerides and hepatic lipid content. Clearance rate and AUC for NEFA during GTT were higher in optimal-BCS cows. The development of insulin resistance and fatty liver in obese cows was paralleled by increased hepatic expression of the IRβ, CD36 and SREBP-1. These results suggest that increased expression of hepatic CD36 and SREBP-1 is relevant in the obesity-driven lipid accumulation in the liver of dairy cows during late gestation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Ca2+ signaling in taste bud cells and spontaneous preference for fat: unresolved roles of CD36 and GPR120.

    Science.gov (United States)

    Abdoul-Azize, Souleymane; Selvakumar, Subramaniam; Sadou, Hassimi; Besnard, Philippe; Khan, Naim Akhtar

    2014-01-01

    Recent compelling evidences from rodent and human studies raise the possibility for an additional sixth taste modality devoted to oro-gustatory perception of dietary lipids. Understanding the mechanisms underlying oro-gustatory detection of dietary fat is critical for the prevention and treatment of obesity. A number of studies have suggested that lingual CD36, a glycoprotein, highly expressed by circumvallate papillae of the tongue, is implicated in the perception of dietary fat taste. G protein-coupled receptors (GPCRs) are important signaling molecules for many aspects of cellular functions. It has been shown that these receptors, particularly GPR120, are also involved in lipid taste perception. We have shown that dietary long-chain fatty acids (LCFAs), in CD36-positive taste bud cells (TBC), induce increases in free intracellular Ca(2+) concentrations, [Ca(2+)]i, by recruiting Ca(2+) from endoplasmic reticulum (ER) pool via inositol 1,4,5-triphosphate production, followed by Ca(2+) influx via opening of store-operated Ca(2+) (SOC) channels. GPR120 is also coupled to increases in [Ca(2+)]i by dietary fatty acids. We observed that stromal interaction molecule 1 (STIM1), a sensor of Ca(2+) depletion in the ER, mediated fatty acid-induced Ca(2+) signaling and spontaneous preference for fat in the mouse. In this review article, we discuss the recent advances and unresolved roles of CD36 and GPR120 in lipid taste signaling in taste bud cells. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Low Levels of CD36 in Peripheral Blood Monocytes in Subclinical Atherosclerosis in Rheumatoid Arthritis: A Cross-Sectional Study in a Mexican Population

    Directory of Open Access Journals (Sweden)

    Eduardo Gómez-Bañuelos

    2014-01-01

    Full Text Available Patients with rheumatoid arthritis (RA have a higher risk for atherosclerosis. There is no clinical information about scavenger receptor CD36 and the development of subclinical atherosclerosis in patients with RA. The aim of this study was to evaluate the association between membrane expression of CD36 in peripheral blood mononuclear cells (PBMC and carotid intima-media thickness (cIMT in patients with RA. Methods. We included 67 patients with RA from the Rheumatology Department of Hospital Civil “Dr. Juan I. Menchaca,” Guadalajara, Jalisco, Mexico. We evaluated the cIMT, considering subclinical atherosclerosis when >0.6 mm. Since our main objective was to associate the membrane expression of CD36 with subclinical atherosclerosis, other molecules related with cardiovascular risk such as ox-LDL, IL-6, and TNFα were tested. Results. We found low CD36 membrane expression in PBMC from RA patients with subclinical atherosclerosis (P<0.001. CD36 mean fluorescence intensity had negative correlations with cIMT (r = −0.578, P<0.001, ox-LDL (r = −0.427, P = 0.05, TNFα (r = −0.729, P<0.001, and IL-6 (r = −0.822, P<0.001. Conclusion. RA patients with subclinical atherosclerosis showed low membrane expression of CD36 in PBMC and increased serum proinflammatory cytokines. Further studies are needed to clarify the regulation of CD36 in RA.

  8. A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index

    OpenAIRE

    Kim, Ho Jin; Moon, Jun Sung; Park, Il Rae; Kim, Joong Hee; Yoon, Ji Sung; Won, Kyu Chang; Lee, Hyoung Woo

    2017-01-01

    Background Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index ...

  9. Differential effects of strength training and testosterone treatment on soluble CD36 in aging men: Possible relation to changes in body composition

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Christensen, Louise L; Kvorning, Thue

    2015-01-01

    Purpose. We measured soluble CD36 (sCD36) and body composition to determine the effects of testosterone treatment (TT) and/or strength training (ST) on cardiovascular risk in men with low normal testosterone levels. Methods. Double-blinded, placebo-controlled study in 54 men aged 60-78 years...... with bioavailable testosterone 94 cm randomized to TT (gel, 50-100 mg/day, n = 20), placebo (n = 18) or ST (n = 16) for 6 months. Moreover, the ST group was randomized to TT (ST + TT, n = 7) or placebo (ST + placebo, n = 9) after 3 months. Outcomes. sCD36, total and regional fat mass were....... units] vs. TT and vs. placebo (p testosterone and lean body mass. Fat mass measures significantly improved during ST + placebo, ST + TT, and TT vs. placebo. During ST + placebo, delta sCD36 was associated with delta total fat mass (r = 0.81) and delta...

  10. The lipid-sensor candidates CD36 and GPR120 are differentially regulated by dietary lipids in mouse taste buds: impact on spontaneous fat preference.

    Directory of Open Access Journals (Sweden)

    Céline Martin

    Full Text Available BACKGROUND: Recent studies in rodents and humans suggest that the chemoreception of long-chain fatty acids (LCFA in oral cavity is involved in the spontaneous preference for fatty foods and might contribute to the obesity risk. CD36 and GPR120 are LCFA receptors identified in rodent taste bud cells. The fact that CD36 or GPR120 gene inactivation leads to a decrease in the preference for lipids raises the question of the respective role(s played by these gustatory lipid-sensor candidates. METHODOLOGY/PRINCIPAL FINDINGS: Using a combination of biochemical, nutritional and behavioural studies in wild-type, CD36(+/-and CD36(-/- mice, it was found that: 1° CD36 and GPR120 display different diurnal rhythms in the gustatory circumvallate papillae, CD36 mRNA levels being down-regulated during the dark period in contrast to GPR120, 2° this change is due to food intake and strictly dependent of the presence of lipids in the diet, 3° CD36 protein levels are also rapidly but transiently decreased by the food intake, a two-fold drop in CD36 protein levels being found 1 h after refeeding, followed by a progressive return to the pre-prandial values, 4° this down-regulation, which has a post-transcriptional origin, seems sufficient to alter the spontaneous fat preference, independently to change in the GPR120 gene expression. CONCLUSIONS/SIGNIFICANCE: In contrast to GPR120, CD36 appears to be a food-sensitive lipid sensor in the gustatory circumvallate papillae. Lipid-mediated change in lingual CD36 expression might modulate the motivation for fat during a meal, initially high and then gradually decreasing secondary to the food intake. This short-term lipid-mediated effect is reminiscent of sensory-specific satiety. These findings, which highlight the role played by CD36 in the oro-sensory perception of dietary lipids, raise the possibility of novel pharmacological strategies to modify attraction for fatty foods and decrease obesity risks.

  11. A Novel Index Using Soluble CD36 Is Associated with the Prevalence of Type 2 Diabetes Mellitus: Comparison Study with Triglyceride-Glucose Index.

    Science.gov (United States)

    Kim, Ho Jin; Moon, Jun Sung; Park, Il Rae; Kim, Joong Hee; Yoon, Ji Sung; Won, Kyu Chang; Lee, Hyoung Woo

    2017-09-01

    Plasma soluble cluster determinant 36 (sCD36) level is closely related with insulin resistance and atherosclerosis, but little is known whether it could be a surrogate for estimating risk of developing diabetes or not. To address this, we evaluated association between sCD36 index, the product of sCD36 and fasting plasma glucose (FPG), and the prevalence of type 2 diabetes mellitus (T2DM), and then compared with triglyceride-glucose (TyG) index which has been suggested simple index for insulin resistance. This was cross-sectional study, and participants were classified as normal glucose tolerance (NGT), prediabetes, and T2DM according to glucose tolerance. The formula of TyG index was 'ln [FPG (mg/dL)×triglyceride (mg/dL)/2],' and the sCD36 index was 'ln [sCD36 (pg/mL)×FPG (mg/dL)/2].' One hundred and fifty-five subjects (mean age, 55.2 years) were enrolled, and patients with T2DM were 75. Both indexes were significantly increased in prediabetes and T2DM rather than NGT, and sCD36 index was positively correlated with both glycosylated hemoglobin and homeostasis model assessment of insulin resistance (r=0.767 and r=0.453, respectively; Pindex for T2DM was 4.39 (95% confidential interval, 1.51 to 12.77) after adjusting age, gender, blood pressure, smoking, alcohol, non-high density lipoprotein cholesterol and high-sensitivity C-reactive protein. However, OR of TyG index did not remained significance after adjustment. sCD36 index has an independent association with the risk of T2DM, and showed better correlation than TyG index. These results suggest sCD36 index might be useful surrogate marker for the risk of diabetes. Copyright © 2017 Korean Endocrine Society

  12. Identification of defective CD36 as a quantitative trait locus for cardiovascular risk factor clustering in the spontaneously hypertensive rat

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Landa, Vladimír; Zídek, Václav; Křen, Vladimír

    2001-01-01

    Roč. 2, č. 2 (2001), s. 161-169 ISSN 1389-2029 R&D Projects: GA ČR(CZ) GA301/00/1636; GA MŠk(CZ) LN00A079; GA ČR(CZ) GV204/98/K015; GA ČR(CZ) GA305/00/1646 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 (fatty acid transporter) * spontaneously hypertensive rat Subject RIV: EB - Genetics ; Molecular Biology

  13. Oily Fish Consumption Modifies the Association between CD36 rs6969989 Polymorphism and Lipid Profiles in Korean Women.

    Science.gov (United States)

    Shin, Yoonjin; Kim, Yangha

    2016-09-01

    The aim of this study was to investigate the association of CD36, a class B scavenger receptor, rs6969989 polymorphism with the serum lipid profiles in Korean women, together with their modulation by oily fish consumption. Subjects were participants from the Korean Genome Epidemiology Study (KoGES), which was initiated in 2001 as a large-scale. A total of 4,210 women aged 39 to 70 were included in this study. Data were collected using self-administered questionnaires, anthropometric measurements, and blood chemical analysis. Dietary intake was analyzed using a semi-quantitative food frequency questionnaire. The minor allele frequency for rs6969989 was found in 12% of this population. Homozygotes minor G allele at the rs6868989 exhibited significantly higher high density lipoprotein cholesterol (HDL-C) concentrations ( P -trend=0.043) and lower fasting glucose ( P -trend=0.013) than major allele A carriers. The risk of low HDL-C was significantly lower in homozygotes for the G allele than the A allele carriers ( P -trend=0.032). Gene-diet interaction effects between rs6969989 and oily fish intake were significantly associated with the risk of dyslipidemia ( P -interaction= 0.004). Subjects with homozygotes minor G allele and high oily fish intake generally had a lower risk of dyslipidemia than did those with major allele homozygotes and low oily fish intake. These findings supported that oily fish consumption may modulate the contributions of CD36 rs6969989 on genetic predisposition to the risk of dyslipidemia.

  14. The rs1527483, but not rs3212018, CD36 polymorphism associates with linoleic acid detection and obesity in Czech young adults

    Czech Academy of Sciences Publication Activity Database

    Plesník, J.; Šerý, Omar; Khan, A. S.; Bielik, P.; Khan, N. A.

    2018-01-01

    Roč. 119, č. 4 (2018), s. 472-478 ISSN 0007-1145 R&D Projects: GA MZd(CZ) NV16-29900A Institutional support: RVO:67985904 Keywords : CD36 * fat taste * genetic polymorphism * rs1527483 Subject RIV: ED - Physiology OBOR OECD: Physiology (including cytology) Impact factor: 3.706, year: 2016

  15. Effekte des oxidativen Stresses auf die Expression der Scavenger-Rezeptoren CD36 und SR-BI und des Transkriptionsfaktors PPARγ in Makrophagen

    OpenAIRE

    Westendorf, Thomas

    2006-01-01

    Ziel dieser Dissertationsschrift war es, die Effekte des oxidativen Stresses in Form von oxLDL auf die Expression der atherogenen Scavenger-Rezeptoren CD36, SR-BI, des Transkriptionsfaktors PPARγ und pro-inflammatorischer Zytokine zu untersuchen. Die durchgeführten Untersuchungen beruhen auf der Annahme, dass modifizierte LDL durch Induktion der genannten Scavenger-Rezeptoren und nachfolgende unregulierte Aufnahme in Makrophagen mit Bildung von Schaumzellen entscheidend zur Entwicklung einer ...

  16. Transgenic expression of CD36 in the spontaneously hypertensive rat is associated with amelioration of metabolic disturbances but has no effect on hypertension

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Landa, Vladimír; Zídek, Václav; Musilová, Alena; Kazdová, L.; Qi, N.; Wang, J.; St. Lezin, E. S.; Kurtz, T. W.

    2003-01-01

    Roč. 52, č. 6 (2003), s. 681-688 ISSN 0862-8408 R&D Projects: GA ČR GA305/00/1646; GA ČR GA301/00/1636; GA MZd NB4904 Grant - others:HHMI(US) 55000331 Institutional research plan: CEZ:AV0Z5011922 Keywords : Cd36 * dyslipidemia * transgenic SHR Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.939, year: 2003

  17. Advanced glycation end products-modified proteins and oxidized LDL mediate down-regulation of leptin in mouse adipocytes via CD36

    International Nuclear Information System (INIS)

    Unno, Yuka; Sakai, Masakazu; Sakamoto, Yu-ichiro; Kuniyasu, Akihiko; Nakayama, Hitoshi; Nagai, Ryoji; Horiuchi, Seikoh

    2004-01-01

    Advanced glycation end products (AGE)-modified proteins as well as oxidized-LDL (Ox-LDL) undergo receptor-mediated endocytosis by CHO cells overexpressing CD36, a member of class B scavenger receptor family. The purpose of the present study was to examine the effects of glycolaldehyde-modified BSA (GA-BSA) as an AGE-ligand and Ox-LDL on leptin expression in adipocytes. GA-BSA decreased leptin expression at both protein and mRNA levels in 3T3-L1 adipocytes and mouse epididymal adipocytes. Ox-LDL showed a similar inhibitory effect on leptin expression in 3T3-L1 adipocytes, which effect was protected by N-acetylcysteine, a reactive oxygen species (ROS) inhibitor. Binding of 125 I-GA-BSA or 125 I-Ox-LDL to 3T3-L1 adipocytes and subsequent endocytic degradation were inhibited by a neutralizing anti-CD36 antibody. Furthermore, this antibody also suppressed Ox-LDL-induced leptin down-regulation. These results clarify that the interaction of GA-BSA and Ox-LDL with CD36 leads to down-regulation of leptin expression via ROS system(s) in 3T3-L1 adipocytes, suggesting that a potential link of AGE- and/or Ox-LDL-induced leptin down-regulation might be linked to insulin-sensitivity in metabolic syndrome

  18. Phagocytosis of cholesteryl ester is amplified in diabetic mouse macrophages and is largely mediated by CD36 and SR-A.

    Directory of Open Access Journals (Sweden)

    Christopher B Guest

    Full Text Available Type 2 diabetes (T2D is associated with accelerated atherosclerosis, which accounts for approximately 75% of all diabetes-related deaths. Here we investigate the link between diabetes and macrophage cholesteryl ester accumulation. When diabetic (db/db mice are given cholesteryl ester intraperitoneally (IP, peritoneal macrophages (PerMPhis recovered from these animals showed a 58% increase in intracellular cholesteryl ester accumulation over PerMPhis from heterozygote control (db/+ mice. Notably, PerMPhi fluid-phase endocytosis and large particle phagocytosis was equivalent in db/+and db/db mice. However, IP administration of CD36 and SR-A blocking antibodies led to 37% and 25% reductions in cholesteryl ester accumulation in PerMPhi. Finally, in order to determine if these scavenger receptors (SRs were part of the mechanism responsible for the increased accumulation of cholesteryl esters observed in the diabetic mouse macrophages, receptor expression was quantified by flow cytometry. Importantly, db/db PerMPhis showed a 43% increase in CD36 expression and an 80% increase in SR-A expression. Taken together, these data indicate that direct cholesteryl ester accumulation in mouse macrophages is mediated by CD36 and SR-A, and the magnitude of accumulation is increased in db/db macrophages due to increased scavenger receptor expression.

  19. Increased hepatic FAT/CD36, PTP1B and decreased HNF4A expression contributes to dyslipidemia associated with ethanol-induced liver dysfunction: Rescue effect of ginger extract.

    Science.gov (United States)

    Shirpoor, Alireza; Heshmati, Elaheh; Kheradmand, Fatemeh; Gharalari, Farzaneh Hosseini; Chodari, Leila; Naderi, Roya; Majd, Farideh Nezami; Samadi, Mahrokh

    2018-05-28

    The association between chronic alcohol consumption and the development of alcpholic liver disease is a very well known phenomenon, but the precise underlying molecular mediators involved in ethanol-induced liver disease remain elusive. This study aimed to characterize the lipid metabolism alterations and the molecular mediators which are related to lipid metabolism in liver under the heavy ethanol exposure alone or combined with ginger extract. Twenty-four male wistar rats were assigned into three groups, namely control, ethanol, and ginger extract treated ethanol (GETE) groups. Six weeks after the treatment, the ethanol group showed a significant increase in fatty acid translocase (FAT)/CD36, protein tyrosine phosphatase 1B (PTP1B) and decrease hepatocyte nuclear factor 4 Alpha (HNF4A) genes expressions compared to the control group. The ethanol administration also significantly increased plasma LDL, cholesterol, triglyceride, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) compared to the control group. Moreover, compared to the control group, the ethanol group showed liver histhological changes, such as fibrosis, focal microvesicular steatosis, some apoptotic hepatocytes, spotty necrosis, portal lymphocytic inflammation, mallory-denk bodies, giant mitochondria, piecemeal necrosis. Consumption of ginger extract along with ethanol, partially ameliorated gene expression alteration and histological changes, improved undesirable lipid profile and liver enzymes changes compare to those in the ethanol group. These findings indicate that ethanol-induced liver abnormalities may in part be associated with lipid homeostasis changes mediated by overexpression of FAT/CD36, PTP1B and downexpressionof HNF4A genes. It also show that these effects can be reduced by using ginger extract as an antioxidant and anti-inflammatory agent. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  20. Activating Attachments Reduces Memories of Traumatic Images.

    Directory of Open Access Journals (Sweden)

    Richard A Bryant

    Full Text Available Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations.

  1. Protective or deleterious role of scavenger receptors SR-A and CD36 on host resistance to Staphylococcus aureus depends on the site of infection.

    Directory of Open Access Journals (Sweden)

    Charlène Blanchet

    Full Text Available Staphylococcus aureus is a major human opportunistic pathogen responsible for a broad spectrum of infections ranging from benign skin infection to more severe life threatening disorders (e.g. pneumonia, sepsis, particularly in intensive care patients. Scavenger receptors (SR-A and CD36 are known to be involved in S. aureus recognition by immune cells in addition to MARCO, TLR2, NOD2 and α5β1 integrin. In the present study, we further deciphered the contribution of SR-A and CD36 scavenger receptors in the control of infection of mice by S. aureus. Using double SR-A/CD36 knockout mice (S/C-KO and S. aureus strain HG001, a clinically relevant non-mutagenized strain, we showed that the absence of these two scavenger receptors was protective in peritoneal infection. In contrast, the deletion of these two receptors was detrimental in pulmonary infection following intranasal instillation. For pulmonary infection, susceptible mice (S/C-KO had more colony-forming units (CFU in their broncho-alveolar lavages fluids, associated with increased recruitment of macrophages and neutrophils. For peritoneal infection, susceptible mice (wild-type had more CFU in their blood, but recruited less macrophages and neutrophils in the peritoneal cavity than resistant mice. Exacerbated cytokine levels were often observed in the susceptible mice in the infected compartment as well as in the plasma. The exception was the enhanced compartmentalized expression of IL-1β for the resistant mice (S/C-KO after peritoneal infection. A similar mirrored susceptibility to S. aureus infection was also observed for MARCO and TLR2. Marco and tlr2 -/- mice were more resistant to peritoneal infection but more susceptible to pulmonary infection than wild type mice. In conclusion, our results show that innate immune receptors can play distinct and opposite roles depending on the site of infection. Their presence is protective for local pulmonary infection, whereas it becomes detrimental

  2. Active compressor engine silencer reduces exhaust noise

    International Nuclear Information System (INIS)

    Denenberg, J.N.; Miller, S.K.; Jay, M.A.

    1994-01-01

    An active industrial silencer on a compressor engine at a Tenneco Gas station has reduced low-frequency 'rumbling' noise by 8 dB during trials while lowering backpressure about 90$. This 8 dB reduction of the piston firing frequency corresponds to a more than 80% decrease in emitted acoustic power. The silencing unit, installed on one of six engines at the station near Eden, N.Y., continues in operation. Based on the results, the manufacturer is identifying additional compressor sites for further tests. This paper reviews this project

  3. Diabetes mellitus tipo 2: qual o papel da insulina na expressão de NF-kappaB, PPARγ e CD36?

    Directory of Open Access Journals (Sweden)

    Cristina de Oliveira SILVA

    2014-12-01

    Full Text Available No diabetes mellitus tipo 2 (DM2 e na síndrome de resistência à insulina, as complicações cardiovasculares resultam de um conjunto de processos aterogênicos envolvendo hiperglicemia crônica, excessiva glicação de proteínas (AGEs, ativação do fator nuclear kappa B (NKκB associada com o aumento da expressão de citocinas inflamatórias e estresse oxidativo, observando-se ainda alteração de LDL e expressão do receptor de scavenger CD36. A contribuição da hiperinsulinemia nesta sequência não é completamente elucidada. Nesta revisão, relata-se como a insulina pode modular a expressão proteica de NFκB, PPAR gama (PPARγ e CD36 em células da musculatura lisa vascular (CMLV da aorta de ratos estimuladas pelos AGE.

  4. Scavenger Receptor Class B, Type I, a CD36 Related Protein in Macrobrachium nipponense: Characterization, RNA Interference, and Expression Analysis with Different Dietary Lipid Sources

    Directory of Open Access Journals (Sweden)

    Zhili Ding

    2016-01-01

    Full Text Available The scavenger receptor class B, type I (SR-BI, is a member of the CD36 superfamily comprising transmembrane proteins involved in mammalian and fish lipid homeostasis regulation. We hypothesize that this receptor plays an important role in Macrobrachium nipponense lipid metabolism. However, little attention has been paid to SR-BI in commercial crustaceans. In the present study, we report a cDNA encoding M. nipponense scavenger receptor class B, type I (designated as MnSR-BI, obtained from a hepatopancreas cDNA library. The complete MnSR-BI coding sequence was 1545 bp, encoding 514 amino acid peptides. The MnSR-BI primary structure consisted of a CD36 domain that contained two transmembrane regions at the N- and C-terminals of the protein. SR-BI mRNA expression was specifically detected in muscle, gill, ovum, intestine, hepatopancreas, stomach, and ovary tissues. Furthermore, its expression in the hepatopancreas was regulated by dietary lipid sources, with prawns fed soybean and linseed oils exhibiting higher expression levels. RNAi-based SR-BI silencing resulted in the suppression of its expression in the hepatopancreas and variation in the expression of lipid metabolism-related genes. This is the first report of SR-BI in freshwater prawns and provides the basis for further studies on SR-BI in crustaceans.

  5. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...... on transcription requires promoter proximity, as demonstrated using artificial constructs and supported by a genome-wide data set. Importantly, transcription down-regulation can be recapitulated in a gene context devoid of splice sites by placing a functional bona fide pA site/transcription terminator within ∼500...

  6. Effects of CD36 Genotype on Oral Perception of Oleic Acid Supplemented Safflower Oil Emulsions in Two Ethnic Groups: A Preliminary Study.

    Science.gov (United States)

    Burgess, Brenda; Melis, Melania; Scoular, Katelyn; Driver, Michael; Schaich, Karen M; Keller, Kathleen L; Tomassini Barbarossa, Iole; Tepper, Beverly J

    2018-05-01

    Previous studies demonstrate humans can detect fatty acids via specialized sensors on the tongue, such as the CD36 receptor. Genetic variation at the common single nucleotide polymorphism rs1761667 of CD36 has been shown to differentially impact the perception of fatty acids, but comparative data among different ethnic groups are lacking. In a small cohort of Caucasian and East Asian young adults, we investigated if: (1) participants could detect oleic acid (C18:1) added to safflower oil emulsions at a constant ratio of 3% (w/v); (2) supplementation of oleic acid to safflower oil emulsions enhanced perception of fattiness and creaminess; and (3) variation at rs1761667 influenced oleic acid detection and fat taste perception. In a 3-alternate forced choice test, 62% of participants detected 2.9 ± 0.7 mM oleic acid (or 0.08% w/v) in a 2.8% safflower oil emulsion. Supplementation of oleic acid did not enhance fattiness and creaminess perception for the cohort as a whole, though East Asians carrying the GG genotype perceived more overall fattiness and creaminess than their AA genotype counterparts (P < 0.001). No differences were observed for the Caucasians. These preliminary findings indicate that free oleic acid can be detected in an oil-in-water emulsion at concentrations found in commercial oils, but it does not increase fattiness or creaminess perception. Additionally, variation at rs1761667 may have ethnic-specific effects on fat taste perception. © 2018 The Authors Journal of Food Science published by Wiley Periodicals, Inc. on behalf of Institute of Food Technologists.

  7. Filter apparatus for actively reducing noise

    NARCIS (Netherlands)

    Berkhoff, Arthur P.; Nijsse, G.

    2010-01-01

    A filter apparatus for reducing noise from a primary noise source, comprising a secondary source signal connector for generating secondary noise to reduce said primary noise and a sensor connector for connecting to a sensor for measuring said primary and secondary noise as an error signal. A first

  8. A filter apparatus for actively reducing noise

    NARCIS (Netherlands)

    Berkhoff, Arthur P.; Nijsse, G.

    2006-01-01

    A filter apparatus for reducing noise from a primary noise source, comprising a secondary source signal connector for generating secondary noise to reduce said primary noise and a sensor connector for connecting to a sensor for measuring said primary and secondary noise as an error signal. A first

  9. Evaluating Active Interventions to Reduce Student Procrastination

    OpenAIRE

    Martin, Joshua Deckert

    2015-01-01

    Procrastination is a pervasive problem in education. In computer science, procrastination and lack of necessary time management skills to complete programming projects are viewed as primary causes of student attrition. The most effective techniques known to reduce procrastination are resource-intensive and do not scale well to large classrooms. In this thesis, we examine three course interventions designed to both reduce procrastination and be scalable for large classrooms. Reflective writ...

  10. Stimuli reduce the dimensionality of cortical activity

    Directory of Open Access Journals (Sweden)

    Luca eMazzucato

    2016-02-01

    Full Text Available The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models.

  11. Stimuli Reduce the Dimensionality of Cortical Activity.

    Science.gov (United States)

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    2016-01-01

    The activity of ensembles of simultaneously recorded neurons can be represented as a set of points in the space of firing rates. Even though the dimension of this space is equal to the ensemble size, neural activity can be effectively localized on smaller subspaces. The dimensionality of the neural space is an important determinant of the computational tasks supported by the neural activity. Here, we investigate the dimensionality of neural ensembles from the sensory cortex of alert rats during periods of ongoing (inter-trial) and stimulus-evoked activity. We find that dimensionality grows linearly with ensemble size, and grows significantly faster during ongoing activity compared to evoked activity. We explain these results using a spiking network model based on a clustered architecture. The model captures the difference in growth rate between ongoing and evoked activity and predicts a characteristic scaling with ensemble size that could be tested in high-density multi-electrode recordings. Moreover, we present a simple theory that predicts the existence of an upper bound on dimensionality. This upper bound is inversely proportional to the amount of pair-wise correlations and, compared to a homogeneous network without clusters, it is larger by a factor equal to the number of clusters. The empirical estimation of such bounds depends on the number and duration of trials and is well predicted by the theory. Together, these results provide a framework to analyze neural dimensionality in alert animals, its behavior under stimulus presentation, and its theoretical dependence on ensemble size, number of clusters, and correlations in spiking network models.

  12. CD36 AA single nucleotide polymorphism (SNP) is associated with decreased lipid taste perception in Tunisian obese woman: association with pro-inflammatory TNF-a GA and IL-6 GC genotypes

    Czech Academy of Sciences Publication Activity Database

    Plesník, J.; Mřížák, I.; Šerý, Omar; Arfa, A.; Fekih, M.; Bouslema, A.; Zaouali, M.; Tabka, Z.; Khan, N. A.

    2014-01-01

    Roč. 28, Supplement 1 (2014), s. 7-7 ISSN 0767-3981. [Annual Meeting of French Society of Pharmacology and Therapeutics /18./. 22.04.2014-24.04.2014, Poitiers] Institutional support: RVO:67985904 Keywords : CD36 Subject RIV: FH - Neurology

  13. Garcinia kola extract reduced lipopolysaccharide activation of ...

    African Journals Online (AJOL)

    The effect of Garcinia kola heckel seed extract on the promonocytic cell line U937 activated by lipopolysaccharide (LPS) was investigated. 200 l of U937 cells maintained in culture at 5 x 105 cells per ml was delivered into wells of a culture plate according to groups. Cells were pre-treated with 20 l of 100 ng/ml phorbol ...

  14. The development of EUROFER reduced activation steel

    Energy Technology Data Exchange (ETDEWEB)

    Schaaf, B. van der E-mail: vanderschaaf@nrg-nl.com; Tavassoli, F.; Fazio, C.; Rigal, E.; Diegele, E.; Lindau, R.; LeMarois, G

    2003-09-01

    Ferritic martensitic steels show limited swelling and susceptibility to helium effects and can be made with low activation chemical compositions. These properties make them the reference steel for the development of breeding blankets in fusion power plants. EUROFER97 is the European implementation of such a steel, where experience gained from an IEA co-operation with Japan and the US is also implemented. Results obtained so far show that EUROFER steel has attractive mechanical properties even after long ageing times. Compatibility tests in water and PbLi17 are in progress. Oxidised aluminium is the most effective protective layer in PbLi17. The displacement damage and helium formation strongly influence the hydrogen transport in the steel. Present experiments should be backed by tests in a more fusion relevant environment, e.g. IFMIF. The 2.5 dpa neutron irradiations at low temperatures result in a higher DBTT. High dose irradiations, up to 80 dpa, are underway. The early results of ODS grades with EUROFER steel composition show potential of these grades for increasing the operating temperature with 100-150 K.

  15. INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS

    NARCIS (Netherlands)

    Bartoloni, Fernando Heering; Monteiro Leite Ciscato, Luiz Francisco; Augusto, Felipe Alberto; Baader, Wilhelm Josef

    2010-01-01

    INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS. Chemiluminescence properties of the peroxyoxalate reaction in the presence of activators bearing electron withdrawing substituents were studied, to evaluate the possible occurrence of an inverse electron

  16. Effect of polymorphisms in the CD36 and STAT3 genes on different dietary interventions among patients with coronary artery disease: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Portal, Vera Lucia; Markoski, Melissa Medeiros; Quadros, Alexandre Schaan de; Garofallo, Sílvia; Santos, Julia Lorenzon Dos; Oliveira, Aline; Wechenfelder, Camila; Campos, Viviane Paiva de; Souza, Priscilla Azambuja Lopes de; Machado, Luana; Marcadenti, Aline

    2016-09-05

    Cardiovascular disease has become a major health problem, and it has been associated with both environmental and genetic factors. Studies have shown that the Mediterranean Diet (MeDiet), or its components such as nuts and olive oil, may be strongly associated with the improvement of cardiovascular risk factors in specific populations. The purpose of the GENUTRI study is to investigate the interaction of genetics with cardiovascular risk factors in a non-Mediterranean population with coronary artery disease (CAD) according to three different diets: rich in pecan nuts, in extra-virgin olive oil or a control diet. The GENUTRI study is a single-center, randomized, open-label, parallel-group, 12-week pragmatic clinical trial conducted in patients aged 40 to 80 years and diagnosed with CAD. A standardized questionnaire will be applied to data collection and a blood sample will be obtained for lipid, glycemic and inflammatory profile evaluation. Polymorphisms in the CD36 and STAT3 genes will be detected using the TaqMan® SNP Genotyping Assay. Patients will be allocated in three groups: group 1: 30 g/day of pecan nuts; group 2: 30 ml/day of olive oil; and group 3: control diet. The primary outcome will consist of changes in LDL-cholesterol (in mg/dl) after 12 weeks of intervention. Studies have shown the beneficial effects of diets rich in nuts and olive oil mainly in the Mediterranean population. GENUTRI is a clinical trial focusing on the effects of nuts or olive oil supplementation in Brazilian individuals. Additionally, we will try to demonstrate that genetic polymorphisms linked to cardiovascular disease may modulate the effects of different diets on biochemical and inflammatory markers among these subjects. ClinicalTrials.gov Identifier: NCT02202265 (registered on 18 July 2014: first version).

  17. Effect of radiation on activity of sulphate reducing bacteria

    International Nuclear Information System (INIS)

    Agaev, N.M.; Smorodin, A.E.; Gusejnov, M.M.

    1985-01-01

    The effect of γ-radiation on activity of sulphate reducing bacteria has been studied. Concentration of biogenic hydrogen, generated in the medium, is the main criterion, characterizing corrosion activity of the bacteria studied. The developed method of suppression of active development of sulfate reducing bacteria considerably reduces, and at lethal doses of γ-radiation eliminates altogether the bacteria activity and formation of the main corrosion agent-hydrogen sulphide-in the medium and that, in its turn, liquidates hydrogen sulphide corrosion

  18. Recreational Activities to Reduce Behavioural Symptoms in Dementia

    Science.gov (United States)

    Kolanowski, Ann; Fick, Donna M.; Buettner, Linda

    2009-01-01

    Few clinicians have an educational grounding in the use of nonpharmacological therapies for people with dementia. In this article, we explore the utility of recreational activities as one nonpharmacological intervention that has demonstrated effectiveness for reducing the behavioural symptoms of dementia. The implementation of effective recreational activities involves three components: understanding the evidence for this approach; acknowledging the need to reduce medications that have the potential to interfere with activity effectiveness; and individualizing activities so that the maximum benefit from the intervention is obtained. PMID:20046903

  19. Reduced-activation steels: present status and future development

    International Nuclear Information System (INIS)

    Klueh, R.L.

    2007-01-01

    Full text of publication follows: Reduced-activation steels for fusion reactor applications were developed in the 1980's to replace the commercial elevated- temperature steels first considered. In the United States, this involved replacing Sandvik HT9 and modified 9Cr-1Mo steels. Reduced-activation steels, which were developed for more rapid radioactivity decay following exposure in a fusion neutron environment, were patterned after the commercial steels they were to replace. The objective for the reduced-activation steels was that they have strengths (yield stress and ultimate tensile strength from room temperature to 600 deg. C) and impact toughness (measured in a Charpy test) comparable to or better than the steels they were replacing. That objective was achieved in reduced-activation steels developed in Japan, Europe, and the United States. Since the reduced-activation steels were developed in the 1980's, reactor designers have been interested designs for increased efficiency of future fusion plants. This means reactors will need to operate at higher temperatures-above 550 deg. C, which is the upper-temperature limit for the reduced-activation steels. Although the tensile and impact toughness of the reduced-activation steels exceed those of the commercial steels they were patterned after, their creep-rupture properties are inferior to some of the commercial steels they replaced. furthermore, they are much inferior to commercial steels that have been developed since the 1980's. Reasons for why the creep-rupture properties for the new commercial ferritic/martensitic steels are superior to the earlier commercial steels and the reduced-activation steels were examined. The reasons involve compositional changes that were made in the earlier commercial steels to give the new commercial steels their superior properties. Computational thermodynamics calculations were carried out to compare the expected equilibrium phases. It appears that similar changes in composition

  20. Sensitivity study of reduced models of the activated sludge process ...

    African Journals Online (AJOL)

    2009-08-07

    Aug 7, 2009 ... Sensitivity study of reduced models of the activated sludge process, for the purposes of parameter estimation and process optimisation: Benchmark process with ASM1 and UCT reduced biological models. S du Plessis and R Tzoneva*. Department of Electrical Engineering, Cape Peninsula University of ...

  1. Active power decoupling with reduced converter stress for single ...

    Indian Academy of Sciences (India)

    SUJATA BHOWMICK

    Department of Electronic Systems Engineering, Indian Institute of Science, ... Single phase; double-frequency ripple; active power decoupling; reduced stress; ... sation of renewable energy sources (e.g., PV), potential ... In standard grid connected DC/AC H-bridge configuration, ..... solar inverter with reduced-size dc link.

  2. Systematic review of active workplace interventions to reduce sickness absence.

    Science.gov (United States)

    Odeen, M; Magnussen, L H; Maeland, S; Larun, L; Eriksen, H R; Tveito, T H

    2013-01-01

    The workplace is used as a setting for interventions to prevent and reduce sickness absence, regardless of the specific medical conditions and diagnoses. To give an overview of the general effectiveness of active workplace interventions aimed at preventing and reducing sickness absence. We systematically searched PubMed, Embase, Psych-info, and ISI web of knowledge on 27 December 2011. Inclusion criteria were (i) participants over 18 years old with an active role in the intervention, (ii) intervention done partly or fully at the workplace or at the initiative of the workplace and (iii) sickness absence reported. Two reviewers independently screened articles, extracted data and assessed risk of bias. A narrative synthesis was used. We identified 2036 articles of which, 93 were assessed in full text. Seventeen articles were included (2 with low and 15 with medium risk of bias), with a total of 24 comparisons. Five interventions from four articles significantly reduced sickness absence. We found moderate evidence that graded activity reduced sickness absence and limited evidence that the Sheerbrooke model (a comprehensive multidisciplinary intervention) and cognitive behavioural therapy (CBT) reduced sickness absence. There was moderate evidence that workplace education and physical exercise did not reduce sickness absence. For other interventions, the evidence was insufficient to draw conclusions. The review found limited evidence that active workplace interventions were not generally effective in reducing sickness absence, but there was moderate evidence of effect for graded activity and limited evidence for the effectiveness of the Sheerbrooke model and CBT.

  3. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  4. Bringing MapReduce Closer To Data With Active Drives

    Science.gov (United States)

    Golpayegani, N.; Prathapan, S.; Warmka, R.; Wyatt, B.; Halem, M.; Trantham, J. D.; Markey, C. A.

    2017-12-01

    Moving computation closer to the data location has been a much theorized improvement to computation for decades. The increase in processor performance, the decrease in processor size and power requirement combined with the increase in data intensive computing has created a push to move computation as close to data as possible. We will show the next logical step in this evolution in computing: moving computation directly to storage. Hypothetical systems, known as Active Drives, have been proposed as early as 1998. These Active Drives would have a general-purpose CPU on each disk allowing for computations to be performed on them without the need to transfer the data to the computer over the system bus or via a network. We will utilize Seagate's Active Drives to perform general purpose parallel computing using the MapReduce programming model directly on each drive. We will detail how the MapReduce programming model can be adapted to the Active Drive compute model to perform general purpose computing with comparable results to traditional MapReduce computations performed via Hadoop. We will show how an Active Drive based approach significantly reduces the amount of data leaving the drive when performing several common algorithms: subsetting and gridding. We will show that an Active Drive based design significantly improves data transfer speeds into and out of drives compared to Hadoop's HDFS while at the same time keeping comparable compute speeds as Hadoop.

  5. Reduced ceramide synthase 2 activity causes progressive myoclonic epilepsy

    DEFF Research Database (Denmark)

    Mosbech, Mai-Britt; Olsen, Anne S B; Neess, Ditte

    2014-01-01

    between genes involved in SL metabolism and epilepsy. METHODS: We used quantitative real-time PCR, Western blotting, and enzymatic assays to determine the mRNA, protein, and activity levels of ceramide synthase 2 (CERS2) in fiibroblasts isolated from parental control subjects and from a patient diagnosed...... with progressive myoclonic epilepsy (PME). Mass spectrometry and fluorescence microscopy were used to examine the effects of reduced CERS2 activity on cellular lipid composition and plasma membrane functions. RESULTS: We identify a novel 27 kb heterozygous deletion including the CERS2 gene in a proband diagnosed...... with PME. Compared to parental controls, levels of CERS2 mRNA, protein, and activity were reduced by ˜50% in fibroblasts isolated from this proband, resulting in significantly reduced levels of ceramides and sphingomyelins containing the very long-chain fatty acids C24:0 and C26:0. The change in SL...

  6. Systematic review of active workplace interventions to reduce sickness absence

    OpenAIRE

    Odeen, Magnus; Magnussen, Liv Heide; Mæland, Silje; Larun, Lillebeth; Eriksen, Hege Randi; Tveito, Torill Helene

    2013-01-01

    Background: The workplace is used as a setting for interventions to prevent and reduce sickness absence, regardless of the specific medical conditions and diagnoses. Aims: To give an overview of the general effectiveness of active workplace interventions aimed at preventing and reducing sickness absence. Methods: We systematically searched PubMed, Embase, Psych-info, and ISI web of knowledge on 27 December 2011. Inclusion criteria were (i) participants over 18 years old with ...

  7. Hydroxychloroquine reduces microglial activity and attenuates experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Koch, Marcus W; Zabad, Rana; Giuliani, Fabrizio; Hader, Walter; Lewkonia, Ray; Metz, Luanne; Wee Yong, V

    2015-11-15

    Microglial activation is thought to be a key pathophysiological mechanism underlying disease activity in all forms of MS. Hydroxychloroquine (HCQ) is an antimalarial drug with immunomodulatory properties that is widely used in the treatment of rheumatological diseases. In this series of experiments, we explore the effect of HCQ on human microglial activation in vitro and on the development of experimental autoimmune encephalitis (EAE) in vivo. We activated human microglia with lipopolysaccharide (LPS), and measured concentrations of several pro- and anti-inflammatory cytokines in untreated and HCQ pretreated cultures. We investigated the effect of HCQ pretreatment at two doses on the development of EAE and spinal cord histology. HCQ pretreatment reduced the production of pro-inflammatory (TNF-alpha, IL-6, and IL-12) and anti-inflammatory (IL-10 and IL-1 receptor antagonist) cytokines in LPS-stimulated human microglia. HCQ pretreatment delayed the onset of EAE, and reduced the number of Iba-1 positive microglia/macrophages and signs of demyelination in the spinal cords of HCQ treated animals. HCQ treatment reduces the activation of human microglia in vitro, delays the onset of EAE, and decreases the representation of activated macrophages/microglia and demyelination in the spinal cord of treated mice. HCQ is a plausible candidate for further clinical studies in MS. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Arrhythmia causes lipid accumulation and reduced glucose uptake.

    Science.gov (United States)

    Lenski, Matthias; Schleider, Gregor; Kohlhaas, Michael; Adrian, Lucas; Adam, Oliver; Tian, Qinghai; Kaestner, Lars; Lipp, Peter; Lehrke, Michael; Maack, Christoph; Böhm, Michael; Laufs, Ulrich

    2015-01-01

    Atrial fibrillation (AF) is characterized by irregular contractions of atrial cardiomyocytes and increased energy demand. The aim of this study was to characterize the influence of arrhythmia on glucose and fatty acid (FA) metabolism in cardiomyocytes, mice and human left atrial myocardium. Compared to regular pacing, irregular (pseudo-random variation at the same number of contractions/min) pacing of neonatal rat cardiomyocytes induced shorter action potential durations and effective refractory periods and increased diastolic [Ca(2+)]c. This was associated with the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and AMP-activated protein kinase (AMPK). Membrane expression of fatty acid translocase (FAT/CD36) and (14)C-palmitic acid uptake were augmented while membrane expression of glucose transporter subtype 4 (GLUT-4) as well as (3)H-glucose uptake were reduced. Inhibition of AMPK and CaMKII prevented these arrhythmia-induced metabolic changes. Similar alterations of FA metabolism were observed in a transgenic mouse model (RacET) for spontaneous AF. Consistent with these findings samples of left atrial myocardium of patients with AF compared to matched samples of patients with sinus rhythm showed up-regulation of CaMKII and AMPK and increased membrane expression of FAT/CD36, resulting in lipid accumulation. These changes of FA metabolism were accompanied by decreased membrane expression of GLUT-4, increased glycogen content and increased expression of the pro-apoptotic protein bax. Irregular pacing of cardiomyocytes increases diastolic [Ca(2+)]c and activation of CaMKII and AMPK resulting in lipid accumulation, reduced glucose uptake and increased glycogen synthesis. These metabolic changes are accompanied by an activation of pro-apoptotic signalling pathways.

  9. Sensitivity study of reduced models of the activated sludge process ...

    African Journals Online (AJOL)

    The problem of derivation and calculation of sensitivity functions for all parameters of the mass balance reduced model of the COST benchmark activated sludge plant is formulated and solved. The sensitivity functions, equations and augmented sensitivity state space models are derived for the cases of ASM1 and UCT ...

  10. A reduced energy supply strategy in active vibration control

    Science.gov (United States)

    Ichchou, M. N.; Loukil, T.; Bareille, O.; Chamberland, G.; Qiu, J.

    2011-12-01

    In this paper, a control strategy is presented and numerically tested. This strategy aims to achieve the potential performance of fully active systems with a reduced energy supply. These energy needs are expected to be comparable to the power demands of semi-active systems, while system performance is intended to be comparable to that of a fully active configuration. The underlying strategy is called 'global semi-active control'. This control approach results from an energy investigation based on management of the optimal control process. Energy management encompasses storage and convenient restitution. The proposed strategy monitors a given active law without any external energy supply by considering purely dissipative and energy-demanding phases. Such a control law is offered here along with an analysis of its properties. A suboptimal form, well adapted for practical implementation steps, is also given. Moreover, a number of numerical experiments are proposed in order to validate test findings.

  11. A reduced energy supply strategy in active vibration control

    International Nuclear Information System (INIS)

    Ichchou, M N; Loukil, T; Bareille, O; Chamberland, G; Qiu, J

    2011-01-01

    In this paper, a control strategy is presented and numerically tested. This strategy aims to achieve the potential performance of fully active systems with a reduced energy supply. These energy needs are expected to be comparable to the power demands of semi-active systems, while system performance is intended to be comparable to that of a fully active configuration. The underlying strategy is called 'global semi-active control'. This control approach results from an energy investigation based on management of the optimal control process. Energy management encompasses storage and convenient restitution. The proposed strategy monitors a given active law without any external energy supply by considering purely dissipative and energy-demanding phases. Such a control law is offered here along with an analysis of its properties. A suboptimal form, well adapted for practical implementation steps, is also given. Moreover, a number of numerical experiments are proposed in order to validate test findings

  12. Active learning reduces annotation time for clinical concept extraction.

    Science.gov (United States)

    Kholghi, Mahnoosh; Sitbon, Laurianne; Zuccon, Guido; Nguyen, Anthony

    2017-10-01

    To investigate: (1) the annotation time savings by various active learning query strategies compared to supervised learning and a random sampling baseline, and (2) the benefits of active learning-assisted pre-annotations in accelerating the manual annotation process compared to de novo annotation. There are 73 and 120 discharge summary reports provided by Beth Israel institute in the train and test sets of the concept extraction task in the i2b2/VA 2010 challenge, respectively. The 73 reports were used in user study experiments for manual annotation. First, all sequences within the 73 reports were manually annotated from scratch. Next, active learning models were built to generate pre-annotations for the sequences selected by a query strategy. The annotation/reviewing time per sequence was recorded. The 120 test reports were used to measure the effectiveness of the active learning models. When annotating from scratch, active learning reduced the annotation time up to 35% and 28% compared to a fully supervised approach and a random sampling baseline, respectively. Reviewing active learning-assisted pre-annotations resulted in 20% further reduction of the annotation time when compared to de novo annotation. The number of concepts that require manual annotation is a good indicator of the annotation time for various active learning approaches as demonstrated by high correlation between time rate and concept annotation rate. Active learning has a key role in reducing the time required to manually annotate domain concepts from clinical free text, either when annotating from scratch or reviewing active learning-assisted pre-annotations. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Research for Actively Reducing Infrared Radiation by Thermoelectric Refrigerator

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hoon; Kim, Kyomin; Kim, Woochul [Yonsei Univ., Seoul (Korea, Republic of)

    2017-03-15

    We introduced a technology for reducing infrared radiation through the active cooling of hot surfaces by using a thermoelectric refrigerator. Certain surfaces were heated by aerodynamic heating, and the heat generation processes are proposed here. We calculated the temperatures and radiations from surfaces, while using thermoelectric refrigerators to cool the surfaces. The results showed that the contrast between the radiations of certain surfaces and the ambient environments can be removed using thermoelectric refrigerators.

  14. Implementation Intentions Reduce Implicit Stereotype Activation and Application.

    Science.gov (United States)

    Rees, Heather Rose; Rivers, Andrew Michael; Sherman, Jeffrey W

    2018-05-01

    Research has found that implementation intentions, if-then action plans (e.g., "if I see a Black face, I will think safe"), reduce stereotyping on implicit measures. However, it is unknown by what process(es) implementation intentions reduce implicit stereotyping. The present research examines the effects of implementation intentions on stereotype activation (e.g., extent to which stereotypic information is accessible) and stereotype application (e.g., extent to which accessible stereotypes are applied in judgment). In addition, we assessed the efficiency of implementation intentions by manipulating cognitive resources (e.g., digit-span, restricted response window) while participants made judgments on an implicit stereotyping measure. Across four studies, implementation intentions reduced implicit stereotyping. This decrease in stereotyping was associated with reductions in both stereotype activation and application. In addition, these effects of implementation intentions were highly efficient and associated with reduced stereotyping even for groups for which people may have little practice inhibiting stereotypes (e.g., gender).

  15. Reduced auditory efferent activity in childhood selective mutism.

    Science.gov (United States)

    Bar-Haim, Yair; Henkin, Yael; Ari-Even-Roth, Daphne; Tetin-Schneider, Simona; Hildesheimer, Minka; Muchnik, Chava

    2004-06-01

    Selective mutism is a psychiatric disorder of childhood characterized by consistent inability to speak in specific situations despite the ability to speak normally in others. The objective of this study was to test whether reduced auditory efferent activity, which may have direct bearings on speaking behavior, is compromised in selectively mute children. Participants were 16 children with selective mutism and 16 normally developing control children matched for age and gender. All children were tested for pure-tone audiometry, speech reception thresholds, speech discrimination, middle-ear acoustic reflex thresholds and decay function, transient evoked otoacoustic emission, suppression of transient evoked otoacoustic emission, and auditory brainstem response. Compared with control children, selectively mute children displayed specific deficiencies in auditory efferent activity. These aberrations in efferent activity appear along with normal pure-tone and speech audiometry and normal brainstem transmission as indicated by auditory brainstem response latencies. The diminished auditory efferent activity detected in some children with SM may result in desensitization of their auditory pathways by self-vocalization and in reduced control of masking and distortion of incoming speech sounds. These children may gradually learn to restrict vocalization to the minimal amount possible in contexts that require complex auditory processing.

  16. Blockade of mast cell activation reduces cutaneous scar formation.

    Directory of Open Access Journals (Sweden)

    Lin Chen

    Full Text Available Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG, on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound.

  17. Large roads reduce bat activity across multiple species.

    Science.gov (United States)

    Kitzes, Justin; Merenlender, Adina

    2014-01-01

    Although the negative impacts of roads on many terrestrial vertebrate and bird populations are well documented, there have been few studies of the road ecology of bats. To examine the effects of large roads on bat populations, we used acoustic recorders to survey bat activity along ten 300 m transects bordering three large highways in northern California, applying a newly developed statistical classifier to identify recorded calls to the species level. Nightly counts of bat passes were analyzed with generalized linear mixed models to determine the relationship between bat activity and distance from a road. Total bat activity recorded at points adjacent to roads was found to be approximately one-half the level observed at 300 m. Statistically significant road effects were also found for the Brazilian free-tailed bat (Tadarida brasiliensis), big brown bat (Eptesicus fuscus), hoary bat (Lasiurus cinereus), and silver-haired bat (Lasionycteris noctivagans). The road effect was found to be temperature dependent, with hot days both increasing total activity at night and reducing the difference between activity levels near and far from roads. These results suggest that the environmental impacts of road construction may include degradation of bat habitat and that mitigation activities for this habitat loss may be necessary to protect bat populations.

  18. Modulation of cAMP levels by high fat diet and curcumin and regulatory effects on CD36/FAT scavenger receptor/fatty acids transporter gene expression

    Science.gov (United States)

    Curcumin, a polyphenol from turmeric (Curcuma longa), reduces inflammation, atherosclerosis, and obesity in several animal studies. In Ldlr-/- mice fed a high-fat diet (HFD), curcumin reduces plasma lipid levels, therefore contributing to a lower accumulation of lipids and to reduced expression of f...

  19. Development for low-activation concrete design reducing radioactive waste

    International Nuclear Information System (INIS)

    Kimura, Ken-ichi; Kinno, Masaharu; Hasegawa, Akira

    2008-01-01

    Full text: Concrete is very valuable and inexpensive material, however it can be changed to be expensive and hard to deal with in use of a nuclear plant after long operation. One of the counter plans for the above is to use low-activation concrete instead of the ordinary concrete, that will reduce radioactive waste and could be even below clearance level in decommissioning and that is very useful in term of life cycle cost. Radioactive analysis showed that Co and Eu were the major target elements which decide the radioactivity level of reinforced concrete in decommissioning stage, and a several material were selected as a low-activation raw material from wide survey of raw materials for concrete (typically aggregates and cements). With the canditate of raw materials, several low-activation concrete were proposed for various portion of light water reactor plant, which reduction ratio were 1/10 to 1/30 which were mainly consist of limestone and low heat cement or white cement, and 1/100 to 1/300 which were mainly consist of alumina aggregate or quartz and high almina cement, comparing to the ordinary concrete in ΣDi/Ci unit, where 'Di' indicates concentration of each residual radioisotope, Ci defined by IAEA as a clearance level, and suffition of 'i' indicates each radioisotope. National funded project for development of low-activation design method for reduction of radioactive waste below clearance level were started from 2005 with aiming (1) development of a database on the content of target elements, which transform radioactive nuclides, in raw materials of reinforced concrete, (2) development of calculation tools for estimation of residual radioactivity of plant components, and (3) development of low-activation materials for concrete such as cements and reinforcing steel bars for structural components. For the optimized design for applying low-activation concrete to the reactor portion, effective evaluation of neutron spectrum in the certain portion including

  20. Reduced superoxide dismutase activity in xeroderma pigmentosum fibroblasts

    International Nuclear Information System (INIS)

    Nishigori, C.; Miyachi, Y.; Imamura, S.; Takebe, H.

    1989-01-01

    This study was performed in order to assess the possible protective effect of superoxide dismutase (SOD) on ultraviolet (UV) damage in xeroderma pigmentosum (XP) fibroblasts. SOD activity in fibroblasts originating from seven xeroderma pigmentosum (XP) patients was significantly lower than that in normal cells (p less than 0.005). Average SOD activity in XP cells belonging to complementation group A was 3.68 +/- 0.54 (n = 7) and that in normal human cells was 5.79 +/- 1.59 (n = 6). Addition of SOD before and during UV irradiation (UVB and UVC) to the cells caused no change in the amount of unscheduled DNA synthesis and UV survival. A possible involvement of reduced SOD in XP and a possible protective effect by SOD on UV damage is discussed

  1. Meditation leads to reduced default mode network activity beyond an active task.

    Science.gov (United States)

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

  2. Reducing braking distance by control of semi-active suspension

    Energy Technology Data Exchange (ETDEWEB)

    Niemz, T.

    2007-07-01

    This thesis presents a control algorithm for semi-active suspensions to reduce the braking distance of passenger cars. Active shock absorbers are controlled and used to influence the vertical dynamics during ABS-controlled full braking. The core of the approach presented in this paper is based on a switching control logic. The control algorithm is implemented in a compact class passenger car. Test drives on a real road, using a braking machine for reproducibility reasons, have been executed. It could be shown that it is possible to reduce the braking distance by affecting on the vertical dynamics of a passenger car in general. This is the first experimental result of this kind published ever. The amount of reduction depends on the height profile of the testing track chosen and on the initial velocity. On a road with an unevenness comparable to the one on a typical German Autobahn an average reduction of 1-2%, compared to the best passive damping, was achieved. (orig.)

  3. Active fans and grizzly bears: Reducing risks for wilderness campers

    Science.gov (United States)

    Sakals, M. E.; Wilford, D. J.; Wellwood, D. W.; MacDougall, S. A.

    2010-03-01

    Active geomorphic fans experience debris flows, debris floods and/or floods (hydrogeomorphic processes) that can be hazards to humans. Grizzly bears ( Ursus arctos) can also be a hazard to humans. This paper presents the results of a cross-disciplinary study that analyzed both hydrogeomorphic and grizzly bear hazards to wilderness campers on geomorphic fans along a popular hiking trail in Kluane National Park and Reserve in southwestern Yukon Territory, Canada. Based on the results, a method is proposed to reduce the risks to campers associated with camping on fans. The method includes both landscape and site scales and is based on easily understood and readily available information regarding weather, vegetation, stream bank conditions, and bear ecology and behaviour. Educating wilderness campers and providing a method of decision-making to reduce risk supports Parks Canada's public safety program; a program based on the principle of user self-sufficiency. Reducing grizzly bear-human conflicts complements the efforts of Parks Canada to ensure a healthy grizzly bear population.

  4. Reducing vibration transfer from power plants by active methods

    Science.gov (United States)

    Kiryukhin, A. V.; Milman, O. O.; Ptakhin, A. V.

    2017-12-01

    The possibility of applying the methods of active damping of vibration and pressure pulsations for reducing their transfer from power plants into the environment, the seating, and the industrial premises are considered. The results of experimental works implemented by the authors on the active broadband damping of vibration and dynamic forces after shock-absorption up to 15 dB in the frequency band up to 150 Hz, of water pressure pulsations in the pipeline up to 20 dB in the frequency band up to 600 Hz, and of spatial low-frequency air noise indoors of a diesel generator at discrete frequency up to 20 dB are presented. It is shown that a reduction of vibration transfer through a vibration-isolating junction (expansion joints) of pipelines with liquid is the most complicated and has hardly been developed so far. This problem is essential for vibration isolation of power equipment from the seating and the environment through pipelines with water and steam in the power and transport engineering, shipbuilding, and in oil and gas pipelines in pumping stations. For improving efficiency, reducing the energy consumption, and decreasing the overall dimensions of equipment, it is advisable to combine the work of an active system with passive damping means, the use of which is not always sufficient. The executive component of the systems of active damping should be placed behind the vibration isolators (expansion joints). It is shown that the existence of working medium and connection of vibration with pressure pulsations in existing designs of pipeline expansion joints lead to growth of vibration stiffness of the expansion joint with the environment by two and more orders as compared with the static stiffness and makes difficulties for using the active methods. For active damping of vibration transfer through expansion joints of pipelines with a liquid, it is necessary to develop expansion joint structures with minimal connection of vibrations and pulsations and minimal

  5. PARP1 Val762Ala polymorphism reduces enzymatic activity

    International Nuclear Information System (INIS)

    Wang Xiaogan; Wang Zhaoqi; Tong Weimin; Shen Yan

    2007-01-01

    Poly(ADP-ribose) polymerase 1 (PARP1) modifies a variety of nuclear proteins by poly(ADP-ribosyl)ation, and plays diverse roles in molecular and cellular processes. A common PARP1 single nucleotide polymorphism (SNP) at codon 762, resulting in the substitution of alanine (Ala) for valine (Val) in the catalytic domain has been implicated in susceptibility to cancer. To characterize the functional effect of this polymorphism on PARP1, we performed in vitro enzymatic analysis on PARP1-Ala762 and PARP1-Val762. We found that PARP1-Ala762 displayed 57.2% of the activity of PARP1-Val762 for auto-poly(ADP-ribosyl)ation and 61.9% of the activity of PARP1-Val762 for trans-poly(ADP-ribosyl)ation of histone H1. The kinetic characterization revealed that the K m of PARP1-Ala762 was increased to a 1.2-fold of the K m of PARP1-Val762 for trans-poly(ADP-ribosyl)ation. Thus, the PARP1 Val762Ala polymorphism reduces the enzymatic activity of PARP1 by increasing K m . This finding suggests that different levels of poly(ADP-ribosyl)ation by PARP1 might aid in understanding Cancer risk of carriers of the PARP1 Val762Ala polymorphism

  6. Activation of pregnane X receptor by pregnenolone 16 α-carbonitrile prevents high-fat diet-induced obesity in AKR/J mice.

    Directory of Open Access Journals (Sweden)

    Yongjie Ma

    Full Text Available Pregnane X receptor (PXR is known to function as a xenobiotic sensor to regulate xenobiotic metabolism through selective transcription of genes responsible for maintaining physiological homeostasis. Here we report that the activation of PXR by pregnenolone 16α-carbonitrile (PCN in AKR/J mice can prevent the development of high-fat diet-induced obesity and insulin resistance. The beneficial effects of PCN treatment are seen with reduced lipogenesis and gluconeogenesis in the liver, and lack of hepatic accumulation of lipid and lipid storage in the adipose tissues. RT-PCR analysis of genes involved in gluconeogenesis, lipid metabolism and energy homeostasis reveal that PCN treatment on high-fat diet-fed mice reduces expression in the liver of G6Pase, Pepck, Cyp7a1, Cd36, L-Fabp, Srebp, and Fas genes and slightly enhances expression of Cyp27a1 and Abca1 genes. RT-PCR analysis of genes involved in adipocyte differentiation and lipid metabolism in white adipose tissue show that PCN treatment reduces expression of Pparγ2, Acc1, Cd36, but increases expression of Cpt1b and Pparα genes in mice fed with high-fat diet. Similarly, PCN treatment of animals on high-fat diet increases expression in brown adipose tissue of Pparα, Hsl, Cpt1b, and Cd36 genes, but reduces expression of Acc1 and Scd-1 genes. PXR activation by PCN in high-fat diet fed mice also increases expression of genes involved in thermogenesis in brown adipose tissue including Dio2, Pgc-1α, Pgc-1β, Cidea, and Ucp-3. These results verify the important function of PXR in lipid and energy metabolism and suggest that PXR represents a novel therapeutic target for prevention and treatment of obesity and insulin resistance.

  7. High-frequency TRNS reduces BOLD activity during visuomotor learning.

    Directory of Open Access Journals (Sweden)

    Catarina Saiote

    Full Text Available Transcranial direct current stimulation (tDCS and transcranial random noise stimulation (tRNS consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI. We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively and sham stimulation over the primary motor cortex (M1 during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods.

  8. Dynamic mechanical properties of reduced activation ferritic steels

    International Nuclear Information System (INIS)

    Hirose, T.; Kohyama, A.; Tanigawa, H.; Ando, M.; Jitsukawa, S.

    2003-01-01

    A fatigue test method by a miniaturized hourglass-shaped fatigue specimen has been developed for International Fusion Materials Irradiation Facility (IFMIF) and sufficient potential as the alternative to a conventional large specimen was presented. Furthermore, focused ion beam micro- sampling method was successfully applied to microstructural analysis on fracture process. Where, the effects of displacement damage and transmutation helium on the fatigue properties of Reduced Activation Ferritic/Martensitic Steels, RAFs, were investigated. Neutron irradiation and helium-ion-implantation at ambient temperature caused radiation hardening to degrade fatigue lifetime of F82H steel. Microstructural analysis revealed that local brittle fractures occurred at early stage of fatigue tests was the origin of the degradation.. No significant difference in fatigue life degradation was detected with and without implanted helium. This result suggests that 100 appm helium implanted has no impact on fracture life time under neutron irradiation. (author)

  9. Nitrate and sulfate reducers-retrievable number of bacteria and their activities in Indian waters

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.; Nair, S.; Chandramohan, D.

    Culturable heterotrophic, nitrate reducing and sulfate reducing bacteria (HB, NRB and SRB) were enumerated from 25, 50, 100 and 200 m depths at 15 stations and their potential activities viz. Nitrate reducing (NRA) and Sulfate reducing (SRA) were...

  10. A computer language for reducing activation analysis data

    International Nuclear Information System (INIS)

    Friedman, M.H.; Tanner, J.T.

    1978-01-01

    A program, written in FORTRAN, which defines a language for reducing activation analysis data is described. An attempt was made to optimize the choice of commands and their definitions so as to concisely express what should be done, make the language natural to use and easy to learn, arranqe a system of checks to guard against communication errors and have the language be inclusive. Communications are effected through commands, and these can be given in almost any order. Consistency checks are done and diagnostic messages are printed automatically to guard against the incorrect use of commands. Default options on the commands allow instructions to be expressed concisely while providing a capability to specify details for the data reduction process. The program has been implemented on a UNIVAC 1108 computer. A complete description of the commands, the algorithms used, and the internal consistency checks used are given elsewhere. The applications of the program and the methods for obtaining data automatically have already been described. (T.G.)

  11. Materials design data for reduced activation martensitic steel type EUROFER

    Energy Technology Data Exchange (ETDEWEB)

    Tavassoli, A.-A.F. E-mail: tavassoli@cea.fr; Alamo, A.; Bedel, L.; Forest, L.; Gentzbittel, J.-M.; Rensman, J.-W.; Diegele, E.; Lindau, R.; Schirra, M.; Schmitt, R.; Schneider, H.C.; Petersen, C.; Lancha, A.-M.; Fernandez, P.; Filacchioni, G.; Maday, M.F.; Mergia, K.; Boukos, N.; Baluc,; Spaetig, P.; Alves, E.; Lucon, E

    2004-08-01

    Materials design limits derived so far from the data generated in Europe for the reduced activation ferritic/martensitic (RAFM) steel type Eurofer are presented. These data address the short-term needs of the ITER Test Blanket Modules and a DEMOnstration fusion reactor. Products tested include plates, bars, tubes, TIG and EB welds, as well as powder consolidated blocks and solid-solid HIP joints. Effects of thermal ageing and low dose neutron irradiation are also included. Results are sorted and screened according to design code requirements before being introduced in reference databases. From the physical properties databases, variations of magnetic properties, modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. From the tensile and creep properties databases design allowable stresses are derived. From the instrumented Charpy impact and fracture toughness databases, ductile to brittle transition temperature, toughness and behavior of materials in different fracture modes are evaluated. From the fatigue database, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves. Cyclic curves are also derived and compared with monotonic hardening curves. Finally, irradiated and aged materials data are compared to ensure that the safety margins incorporated in unirradiated design limits are not exceeded.

  12. Method of solution mining subsurface orebodies to reduce restoration activities

    Energy Technology Data Exchange (ETDEWEB)

    Hartman, G.J.

    1984-01-24

    A method of solution mining is claimed wherein a lixiviant containing both leaching and oxidizing agents is injected into the subsurface orebody. The composition of the lixiviant is changed by reducing the level of oxidizing agent to zero so that soluble species continue to be removed from the subsurface environment. This reduces the uranium level of the ground water aquifer after termination of the lixiviant injection.

  13. Carbon fiber/SiC composite for reduced activation

    International Nuclear Information System (INIS)

    Noda, T.; Araki, H.; Abe, F.; Okada, M.

    1991-01-01

    A carbon fiber/SiC composite fabricated by a chemical vapor infiltration process at 1173-1623 K was studied to develop a low-activation material. A high-purity composite was obtained with the total amount of impurities less than 0.02 wt%. The microstructure and the mechanical properties using a bend test were examined. A composite with woven carbon yarn showed both high strength and toughness. Further, the induced activity of the material was evaluated by calculations simulating fusion neutron irradiation. The carbon fiber/SiC composite shows an excellent low-activation behavior. (orig.)

  14. On the electrocatalytic activity of nitrogen-doped reduced graphene ...

    Indian Academy of Sciences (India)

    ... battery applications. The heteroatom-doped graphene/reduced graphene oxide (rGO) ... over, in the membrane electrode assembly of fuel cell, the carbon supported ..... Wang Y, Shao Y, Matson D W, Li J and Lin Y 2010. ACS Nano 4 1790.

  15. On the electrocatalytic activity of nitrogen-doped reduced graphene ...

    Indian Academy of Sciences (India)

    The heteroatom-doped graphene/reduced graphene oxide (rGO)is very promising and the nitrogen-doped rGO (N-rGO) is emerging as a new inexpensive electrocatalyst foroxygen reduction reaction (ORR). Herein, we describe the effect of the chemical nature and amount of nitrogenin N-rGO towards ORR in acidic solution ...

  16. Impaired cognitive control and reduced cingulate activity during mental fatigue

    NARCIS (Netherlands)

    Lorist, M.M.; Boksem, M.A.S.; Ridderinkhof, K.R.

    2005-01-01

    Neurocognitive mechanisms underlying the effects of mental fatigue are poorly understood. Here, we examined whether error-related brain activity, indexing performance monitoring by the anterior cingulate cortex (ACC), and strategic behavioural adjustments were modulated by mental fatigue, as induced

  17. Impaired cognitive control and reduced cingulate activity during mental fatigue

    NARCIS (Netherlands)

    Lorist, MM; Boksem, MAS; Ridderinkhof, KR

    Neurocognitive mechanisms underlying the effects of mental fatigue are poorly understood. Here, we examined whether error-related brain activity, indexing performance monitoring by the anterior cingulate cortex (ACC), and strategic behavioural adjustments were modulated by mental fatigue, as induced

  18. Carvacrol, (-)-borneol and citral reduce convulsant activity in rodents ...

    African Journals Online (AJOL)

    ... compounds were efficient in preventing the tonic convulsions (p < 0.05) induced by MES. However, the GABAergic neurotransmitter system might be involved, at least in BOR effects. Henceforth, our results suggest that CARV, BOR and CIT possess anticonvulsant activity effect against PTZ-induced convulsions and MES.

  19. Reduced graphene oxide wrapped Ag nanostructures for enhanced SERS activity

    Science.gov (United States)

    Nair, Anju K.; Kala, M. S.; Thomas, Sabu; Kalarikkal, Nandakumar

    2018-04-01

    Graphene - metal nanoparticle hybrids have received great attention due to their unique electronic properties, large specific surface area, very high conductivity and more charge transfer. Thus, it is extremely advantages to develop a simple and efficient process to disperse metal nanostructures over the surface of graphene sheets. Herein, we report a hydrothermal assisted strategy for developing reduced graphene oxide /Ag nanomorphotypes (cube, wire) for surface enhanced Raman scattering (SERS) applications, considering the advantages of synergistic effect of graphene and plasmonic properties of Ag nanomorphotypes.

  20. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    Directory of Open Access Journals (Sweden)

    Wieke de Vente

    2015-01-01

    Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

  1. Reduced activation calculations for the STARFIRE first wall

    International Nuclear Information System (INIS)

    Mann, F.M.

    1983-10-01

    The activation of 27 elements (Li, Be, B, C, N, O, Mg, Al, Si, P, S, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zr, Nb, Mo, Sn, Hf, Ta, W, and Pb) was calculated for a two-year exposure at the STARFIRE first-wall position. Based on a reasonable extension of current NRC regulations for near-surface land disposal, restrictions on N, Al, Ni, Cu, Nb, Mo, and Pb concentrations in first-wall materials may be required

  2. Recent progress of R and D activities on reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Q., E-mail: qunying.huang@fds.org.cn [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, P.O. Box 1135, Hefei, Anhui 230031 (China); Baluc, N. [CRPP-EPFL, ODGA C110 5232 Villigen PSI (Switzerland); Dai, Y. [LNM, PSI, 5232 Villigen PSI (Switzerland); Jitsukawa, S. [JAEA, 2-4 Shirakata, Tokai-Mura, Ibaraki-Ken 319-1195 (Japan); Kimura, A. [IAE, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Konys, J. [KIT, P.O. Box 3640, 76021 Karlsruhe (Germany); Kurtz, R.J. [PNNL, Richland, WA 99352 (United States); Lindau, R. [KIT, P.O. Box 3640, 76021 Karlsruhe (Germany); Muroga, T. [NIFS, Oroshi, Toki, Gifu 509-5292 (Japan); Odette, G.R. [UCSB, Santa Barbara, CA (United States); Raj, B. [IGCAR, Kalpakkam 603 102 (India); Stoller, R.E.; Tan, L. [ORNL, P.O. Box 2008, Oak Ridge, TN 37831 (United States); Tanigawa, H. [JAEA, Naka, Ibaraki 311-0193 (Japan); Tavassoli, A.-A.F. [DMN/Dir, DEN, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Yamamoto, T. [UCSB, Santa Barbara, CA (United States); Wan, F. [DMPC, USTB, Beijing 100083 (China); Wu, Y. [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, P.O. Box 1135, Hefei, Anhui 230031 (China)

    2013-11-15

    Several types of reduced activation ferritic/martensitic (RAFM) steel have been developed over the past 30 years in China, Europe, India, Japan, Russia and the USA for application in ITER test blanket modules (TBMs) and future fusion DEMO and power reactors. The progress has been particularly important during the past few years with evaluation of mechanical properties of these steels before and after irradiation and in contact with different cooling media. This paper presents recent RAFM steel results obtained in ITER partner countries in relation to different TBM and DEMO options.

  3. Barriers associated with reduced physical activity in COPD patients.

    Science.gov (United States)

    Amorim, Priscila Batista; Stelmach, Rafael; Carvalho, Celso Ricardo Fernandes; Fernandes, Frederico Leon Arrabal; Carvalho-Pinto, Regina Maria; Cukier, Alberto

    2014-10-01

    To evaluate the ability of COPD patients to perform activities of daily living (ADL); to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT), and an ADL limitation score. In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL) scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.

  4. Evaluation of multistage filtration to reduce sand filter exhaust activity

    International Nuclear Information System (INIS)

    Zippler, D.B.

    1975-01-01

    Air from the Savannah River Plant Fuel Reprocessing facilities is filtered through deep bed sand filters consisting of 8 1 / 2 feet of gravel and sand. These filters have performed satisfactorily for the past 18 years in maintaining radioactive release levels to a minimum. The apparent filter efficiency has been determined for many years by measurements of the quantity of radioactivity in the air stream before and after the filter. Such tests have indicated efficiencies of 99.9 percent or better. Even with sand filter efficiency approaching a single stage HEPA filter, new emphasis on further reduction in release of plutonium activity to the environment prompted a study to determine what value backup HEPA filtration could provide. To evaluate the specific effect additional HEPA filtration would have on the removal of Pu from the existing sand filter exhaust stream, a test was conducted by passing a sidestream of sand-filtered air through a standard 24 x 24 x 11 1 / 2 in. HEPA filter. Isokinetic air samples were withdrawn upstream and downstream of the HEPA filter and counted for alpha activity. Efficiency calculations indicated that backup HEPA filtration could be expected to provide an additional 99 percent removal of the Pu activity from the present sand-filter exhaust. (U.S.)

  5. Development of ferritic steels for reduced activation: the US program

    International Nuclear Information System (INIS)

    Klueh, R.L.; Gelles, D.S.; Lechtenberg, T.A.

    1986-01-01

    The Cr-Mo ferritic (martensitic) steels are candidates for the structural components of fusion reactors. Irradiation of such steels in a fusion environment produces long-lived radioactive isotopes, which lead to difficult radioactive waste disposal problems once the structure is removed from service. Such problems could be reduced by using steels that contain only elements that produce radioactive isotopes that decay to low levels in a reasonable time (tens of years instead of hundreds or thousands of years). The US Department of Energy has a program to develop steels to meet the criteria for shallow land burial as opposed to deep geologic storage. A review of the alloy development programs indicates that ferritic steels that meet these criteria can be developed

  6. Myostatin Attenuation In Vivo Reduces Adiposity, but Activates Adipogenesis.

    Science.gov (United States)

    Li, Naisi; Yang, Qiyuan; Walker, Ryan G; Thompson, Thomas B; Du, Min; Rodgers, Buel D

    2016-01-01

    A potentially novel approach for treating obesity includes attenuating myostatin as this increases muscle mass and decreases fat mass. Notwithstanding, conflicting studies report that myostatin stimulates or inhibits adipogenesis and it is unknown whether reduced adiposity with myostatin attenuation results from changes in fat deposition or adipogenesis. We therefore quantified changes in the stem, transit amplifying and progenitor cell pool in white adipose tissue (WAT) and brown adipose tissue (BAT) using label-retaining wild-type and mstn(-/-) (Jekyll) mice. Muscle mass was larger in Jekyll mice, WAT and BAT mass was smaller and label induction was equal in all tissues from both wild-type and Jekyll mice. The number of label-retaining cells, however, dissipated quicker in WAT and BAT of Jekyll mice and was only 25% and 17%, respectively, of wild-type cell counts 1 month after induction. Adipose cell density was significantly higher in Jekyll mice and increased over time concomitant with label-retaining cell disappearance, which is consistent with enhanced expansion and differentiation of the stem, transit amplifying and progenitor pool. Stromal vascular cells from Jekyll WAT and BAT differentiated into mature adipocytes at a faster rate than wild-type cells and although Jekyll WAT cells also proliferated quicker in vitro, those from BAT did not. Differentiation marker expression in vitro, however, suggests that mstn(-/-) BAT preadipocytes are far more sensitive to the suppressive effects of myostatin. These results suggest that myostatin attenuation stimulates adipogenesis in vivo and that the reduced adiposity in mstn(-/-) animals results from nutrient partitioning away from fat and in support of muscle.

  7. Barriers associated with reduced physical activity in COPD patients

    Directory of Open Access Journals (Sweden)

    Priscila Batista Amorim

    2014-10-01

    Full Text Available OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL; to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT, and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001, as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001. The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.

  8. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......]AngII had a protective effect. Together these results demonstrate a cardioprotective effect of simultaneous blockade of G protein signaling and activation of G protein independent signaling through AT(1 )receptors....

  9. PPARγ agonist pioglitazone reduces matrix metalloproteinase-9 activity and neuronal damage after focal cerebral ischemia

    International Nuclear Information System (INIS)

    Lee, Seong-Ryong; Kim, Hahn-Young; Hong, Jung-Suk; Baek, Won-Ki; Park, Jong-Wook

    2009-01-01

    Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, has shown protective effects against ischemic insult in various tissues. Pioglitazone is also reported to reduce matrix metalloproteinase (MMP) activity. MMPs can remodel extracellular matrix components in many pathological conditions. The current study was designed to investigate whether the neuroprotection of pioglitazone is related to its MMP inhibition in focal cerebral ischemia. Mice were subjected to 90 min focal ischemia and reperfusion. In gel zymography, pioglitazone reduced the upregulation of active form of MMP-9 after ischemia. In in situ zymograms, pioglitazone also reduced the gelatinase activity induced by ischemia. After co-incubation with pioglitazone, in situ gelatinase activity was directly reduced. Pioglitazone reduced the infarct volume significantly compared with controls. These results demonstrate that pioglitazone may reduce MMP-9 activity and neuronal damage following focal ischemia. The reduction of MMP-9 activity may have a possible therapeutic effect for the management of brain injury after focal ischemia.

  10. Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

    Science.gov (United States)

    Day, Danielle S; Gozansky, Wendolyn S; Bell, Christopher; Kohrt, Wendy M

    2011-10-01

    Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA. MSNA was measured in 9 women (30±2 years; mean±SE) on three separate occasions: during the mid-luteal menstrual cycle phase, on the fifth day of gonadotropin-releasing hormone antagonist (GnRHant) administration, and after 5 days add-back of either estradiol (n=4) or progesterone (n=3) during continued GnRHant administration. In response to GnRHant, there were significant reductions in serum estradiol and progesterone (both psuppression attenuates MSNA and that this may be related to the suppression of progesterone rather than estradiol.

  11. Aerobic Exercise Training Selectively Changes Oxysterol Levels and Metabolism Reducing Cholesterol Accumulation in the Aorta of Dyslipidemic Mice

    Directory of Open Access Journals (Sweden)

    Guilherme Silva Ferreira

    2017-09-01

    Full Text Available Background: Oxysterols are bioactive lipids that control cellular cholesterol synthesis, uptake, and exportation besides mediating inflammation and cytotoxicity that modulate the development of atherosclerosis. Aerobic exercise training (AET prevents and regresses atherosclerosis by the improvement of lipid metabolism, reverse cholesterol transport (RCT and antioxidant defenses in the arterial wall. We investigated in dyslipidemic mice the role of a 6-week AET program in the content of plasma and aortic arch cholesterol and oxysterols, the expression of genes related to cholesterol flux and the effect of the exercise-mimetic AICAR, an AMPK activator, in macrophage oxysterols concentration.Methods: Sixteen-week old male apo E KO mice fed a chow diet were included in the protocol. Animals were trained in a treadmill running, 15 m/min, 5 days/week, for 60 min (T; n = 29. A control group was kept sedentary (S; n = 32. Plasma lipids and glucose were determined by enzymatic techniques and glucometer, respectively. Cholesterol and oxysterols in aortic arch and macrophages were measured by gas chromatography/mass spectrometry. The expression of genes involved in lipid metabolism was determined by RT-qPCR. The effect of AMPK in oxysterols metabolism was determined in J774 macrophages treated with 0.25 mM AICAR.Results: Body weight and plasma TC, TG, HDL-c, glucose, and oxysterols were similar between groups. As compared to S group, AET enhanced 7β-hydroxycholesterol (70% and reduced cholesterol (32% in aorta. In addition, exercise increased Cyp27a1 (54%, Cd36 (75%, Cat (70%, Prkaa1 (40%, and Prkaa2 (51% mRNA. In macrophages, the activation of AMPK followed by incubation with HDL2 increased Abca1 (52% and Cd36 (220% and decrease Prkaa1 (19%, Cyp27a1 (47% and 7α-hydroxycholesterol level.Conclusion: AET increases 7β-hydroxycholesterol in the aortic arch of dyslipidemic mice, which is related to the enhanced expression of Cd36. In addition, the increase

  12. Oxytocin reduces amygdala activity, increases social interactions, and reduces anxiety-like behavior irrespective of NMDAR antagonism.

    Science.gov (United States)

    Sobota, Rosanna; Mihara, Takuma; Forrest, Alexandra; Featherstone, Robert E; Siegel, Steven J

    2015-08-01

    Standard dopamine therapies for schizophrenia are not efficacious for negative symptoms of the disease, including asociality. This reduced social behavior may be due to glutamatergic dysfunction within the amygdala, leading to increased fear and social anxiety. Several studies have demonstrated the prosocial effects of oxytocin in schizophrenia patients. Therefore, this study evaluates the effect of subchronic oxytocin on EEG activity in amygdala of mice during performance of the three-chamber social choice and open field tests following acute ketamine as a model of glutamatergic dysfunction. Oxytocin did not restore social deficits introduced by ketamine but did significantly increase sociality in comparison to the control group. Ketamine had no effect on time spent in the center during the open field trials, whereas oxytocin increased overall center time across all groups, suggesting a reduction in anxiety. Amygdala activity was consistent across all drug groups during social and nonsocial behavioral trials. However, oxytocin reduced overall amygdala EEG power during the two behavioral tasks. Alternatively, ketamine did not significantly affect EEG power throughout the tasks. Decreased EEG power in the amygdala, as caused by oxytocin, may be related to both reduced anxiety and increased social behaviors. Data suggest that separate prosocial and social anxiety pathways may mediate social preference. (c) 2015 APA, all rights reserved).

  13. Regular physical activity has differential association with reduced obesity among diverse youth in the United States.

    Science.gov (United States)

    Fradkin, Chris; Wallander, Jan L; Elliott, Marc N; Cuccaro, Paula; Schuster, Mark A

    2016-08-01

    This study examined whether daily or almost daily lower-intensity physical activity was associated with reduced obesity, among 4824 African American, Hispanic, and White youth assessed in fifth and seventh grades. Regular lower-intensity physical activity was associated with reduced obesity only among Hispanic and White males and only in seventh grade, and not among youth in fifth grade, females, or African American males or females. Findings from this study suggest that the reduced obesity risk generally attributed to physical activity may not be consistent across racial/ethnic and gender groups of early adolescents. © The Author(s) 2014.

  14. Impurity content of reduced-activation ferritic steels and a vanadium alloy

    International Nuclear Information System (INIS)

    Klueh, R.L.; Grossbeck, M.L.; Bloom, E.E.

    1997-01-01

    Inductively coupled plasma mass spectrometry was used to analyze a reduced-activation ferritic/martensitic steel and a vanadium alloy for low-level impurities that would compromise the reduced-activation characteristics of these materials. The ferritic steel was from the 5-ton IEA heat of modified F82H, and the vanadium alloy was from a 500-kg heat of V-4Cr-4Ti. To compare techniques for analysis of low concentrations of impurities, the vanadium alloy was also examined by glow discharge mass spectrometry. Two other reduced-activation steels and two commercial ferritic steels were also analyzed to determine the difference in the level of the detrimental impurities in the IEA heat and steels for which no extra effort was made to restrict some of the tramp impurities. Silver, cobalt, molybdenum, and niobium proved to be the tramp impurities of most importance. The levels observed in these two materials produced with present technology exceeded the limits for low activation for either shallow land burial or recycling. The chemical analyses provide a benchmark for the improvement in production technology required to achieve reduced activation; they also provide a set of concentrations for calculating decay characteristics for reduced-activation materials. The results indicate the progress that has been made and give an indication of what must still be done before the reduced-activation criteria can be achieved

  15. Trying To Reduce Your Technostress?: Helpful Activities for Teachers and Library Media Specialists.

    Science.gov (United States)

    McKenzie, Barbara K.; And Others

    1997-01-01

    As pressure increases to integrate technology into instruction, many teachers and library media specialists are having difficulty coping with "technostress." Presents suggestions and activities for teachers and library media specialists designed to reduce "technostress." (PEN)

  16. Fetoscopic laser coagulation of intertwin anastomoses reduces discordant placental autophagic activities in discordant twin growth

    Directory of Open Access Journals (Sweden)

    Yao-Lung Chang

    2015-10-01

    Conclusion: The discordance of placenta autophagic activity in the monochorionic twin with sIUGR was reduced after laser coagulation of the intertwin anastomoses, which may result from the effect of correction of the discordant intertwin placenta perfusion.

  17. Recycle Alaska: Reduce, Reuse, Recycle. Activities Handbook, Teacher's Guide, and Student Worksheets.

    Science.gov (United States)

    Alaska State Dept. of Education, Juneau.

    Recycling is a very important aspect of conserving the environment for future generations. This guide addresses the topic of litter prevention for the Alaskan environment and contains 42 activities. Activity topics covered include Natural Cycles, Human Interruption of Natural Cycles, Reduce, Reuse, Recycle and Recycled Classroom. Grade level,…

  18. Solid Waste Educational Resources and Activities: Let's Reduce, Reuse, and Recycle. [CD-ROM].

    Science.gov (United States)

    Environmental Protection Agency, Washington, DC. Solid Waste and Emergency Response.

    This contains games, activities, publications, and resources for students and teachers on how to reduce, reuse, recycle, and properly manage waste. It also contains a screen saver featuring runners-up from the Earth Day 2000 art contest. Activities and games include titles such as "Planet Protectors,""Recycle City,""Trash…

  19. Exceptionally strong sorption of infochemicals to activated carbon reduces their bioavailability to fish

    NARCIS (Netherlands)

    Jonker, Michiel T O; van Mourik, Louise

    2014-01-01

    The addition of activated carbon (AC) to sediments is a relatively new approach to remediate contaminated sites. Activated carbon strongly sorbs hydrophobic organic contaminants, thereby reducing their bioavailability and uptake in organisms. Because of its high sorption capacity, AC might, however,

  20. Promoting physical activity and reducing climate change : Opportunities to replace short car trips with active transportation

    NARCIS (Netherlands)

    Maibach, E.; Steg, L.; Anable, J.

    2009-01-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options - walking or

  1. Activated charcoal and baking soda to reduce odor associated with extensive blistering disorders.

    Science.gov (United States)

    Chakravarthi, Arun; Srinivas, C R; Mathew, Anil C

    2008-01-01

    Skin disease leading to extensive blistering and loss of skin is associated with a characteristic smell. Odor can cause physiologic disturbances such as increase in heart rate and respiratory rate. It can also cause nausea and vomiting and is disturbing to bystanders. To test odor reducing capability of activated charcoal. In this blinded experimental study we used putrefied amniotic membrane to produce odor and studied the effectiveness of activated charcoal and soda-bi-carbonate to reduce odor. Statistical analysis with Kruskal Wall's Chi Square Test and Man Whitney U test showed significant reduction of odor using activated charcoal by itself or along with soda-bi-carbonate. We recommend the usage of activated charcoal with/without soda bicarbonate as an inexpensive practical measure to reduce foul odor associated with extensive skin loss.

  2. Activated charcoal and baking soda to reduce odor associated with extensive blistering disorders

    Directory of Open Access Journals (Sweden)

    Chakravarthi Arun

    2008-01-01

    Full Text Available Background: Skin disease leading to extensive blistering and loss of skin is associated with a characteristic smell. Odor can cause physiologic disturbances such as increase in heart rate and respiratory rate. It can also cause nausea and vomiting and is disturbing to bystanders. Aims: To test odor reducing capability of activated charcoal. Methods: In this blinded experimental study we used putrefied amniotic membrane to produce odor and studied the effectiveness of activated charcoal and soda-bi-carbonate to reduce odor. Results: Statistical analysis with Kruskal Wall′s Chi Square Test and Man Whitney U test showed significant reduction of odor using activated charcoal by itself or along with soda-bi-carbonate. Conclusion: We recommend the usage of activated charcoal with/without soda bicarbonate as an inexpensive practical measure to reduce foul odor associated with extensive skin loss.

  3. Pituitary adenylate cyclase activating polypeptide reduces A-type K+ currents and caspase activity in cultured adult mouse olfactory neurons.

    Science.gov (United States)

    Han, P; Lucero, M T

    2005-01-01

    Pituitary adenylate cyclase activating polypeptide has been shown to reduce apoptosis in neonatal cerebellar and olfactory receptor neurons, however the underlying mechanisms have not been elucidated. In addition, the neuroprotective effects of pituitary adenylate cyclase activating polypeptide have not been examined in adult tissues. To study the effects of pituitary adenylate cyclase activating polypeptide on neurons in apoptosis, we measured caspase activation in adult olfactory receptor neurons in vitro. Interestingly, we found that the protective effects of pituitary adenylate cyclase activating polypeptide were related to the absence of a 4-aminopyridine (IC50=144 microM) sensitive rapidly inactivating potassium current often referred to as A-type current. In the presence of 40 nM pituitary adenylate cyclase activating polypeptide 38, both A-type current and activated caspases were significantly reduced. A-type current reduction by pituitary adenylate cyclase activating polypeptide was blocked by inhibiting the phospholipase C pathway, but not the adenylyl cyclase pathway. Our observation that 5 mM 4-aminopyridine mimicked the caspase inhibiting effects of pituitary adenylate cyclase activating polypeptide indicates that A-type current is involved in apoptosis. This work contributes to our growing understanding that potassium currents are involved with the activation of caspases to affect the balance between cell life and death.

  4. Energy activity guide : simple steps to reduce your household energy use

    Energy Technology Data Exchange (ETDEWEB)

    Byckalo-Khan, F.; Wallace, C.L. (ed.)

    2003-07-01

    This guide presents 13 practical activities that can help households reduce energy consumption in order to create a more sustainable lifestyle and to help meet Canada's Kyoto commitment to reduce greenhouse gas emissions. Most energy sources create pollution that harms both human health and the Earth. The burning of fossil fuels creates greenhouse gas emissions that contribute to climate change, smog, pollution and adverse health effects. This guide offers suggestions on how households can reduce the impact on the environment while saving money. Some of the initiatives include lowering the thermostat, replacing incandescent light bulbs with compact fluorescent light bulbs, turning off appliances when not in use, weatherising building envelopes, using a clothes line to dry clothes instead of a dryer, laundering clothes with cold water, and proper maintenance of heating equipment. An energy use chart is included with this guide to help track activities and to estimate how much time and money is required by each activity. refs., figs.

  5. Energy activity guide : simple steps to reduce your household energy use

    Energy Technology Data Exchange (ETDEWEB)

    Byckalo-Khan, F; Wallace, C L [ed.

    2003-07-01

    This guide presents 13 practical activities that can help households reduce energy consumption in order to create a more sustainable lifestyle and to help meet Canada's Kyoto commitment to reduce greenhouse gas emissions. Most energy sources create pollution that harms both human health and the Earth. The burning of fossil fuels creates greenhouse gas emissions that contribute to climate change, smog, pollution and adverse health effects. This guide offers suggestions on how households can reduce the impact on the environment while saving money. Some of the initiatives include lowering the thermostat, replacing incandescent light bulbs with compact fluorescent light bulbs, turning off appliances when not in use, weatherising building envelopes, using a clothes line to dry clothes instead of a dryer, laundering clothes with cold water, and proper maintenance of heating equipment. An energy use chart is included with this guide to help track activities and to estimate how much time and money is required by each activity. refs., figs.

  6. Experimental investigation of activities and tolerance of denitrifying bacteria under alkaline and reducing condition

    International Nuclear Information System (INIS)

    Mine, Tatsuya; Mihara, Morihiro; Ooi, Takao

    2000-07-01

    In the geological disposal system of TRU wastes, nitrogen generation by denitrifying bacteria could provide significant impact on the assessment of this system, because nitrate contained in process concentrated liquid waste might be electron acceptor for denitrifying bacteria. In this study, the activities and tolerance of denitrifying under disposal condition were investigated. Pseudomonas denitrificans as denitrifying bacteria was used. The results showed that Pseudomonas denitrificans had activity under reducing condition, but under high pH condition (pH>9.5), the activity of Pseudomonas denitrificans was not detected. It is possible that the activity of Pseudomonas denitrificans would be low under disposal condition. (author)

  7. The significance of reduced respiratory chain enzyme activities: clinical, biochemical and radiological associations.

    Science.gov (United States)

    Mordekar, S R; Guthrie, P; Bonham, J R; Olpin, S E; Hargreaves, I; Baxter, P S

    2006-03-01

    Mitochondrial diseases are an important group of neurometabolic disorders in children with varied clinical presentations and diagnosis that can be difficult to confirm. To report the significance of reduced respiratory chain enzyme (RCE) activity in muscle biopsy samples from children. Retrospective odds ratio was used to compare clinical and biochemical features, DNA studies, neuroimaging, and muscle biopsies in 18 children with and 48 without reduced RCE activity. Children with reduced RCE activity were significantly more likely to have consanguineous parents, to present with acute encephalopathy and lactic acidaemia and/or within the first year of life; to have an axonal neuropathy, CSF lactate >4 mmol/l; and/or to have signal change in the basal ganglia. There were positive associations with a maternal family history of possible mitochondrial cytopathy; a presentation with failure to thrive and lactic acidaemia, ragged red fibres, reduced fibroblast fatty acid oxidation and with an abnormal allopurinol loading test. There was no association with ophthalmic abnormalities, deafness, epilepsy or myopathy. The association of these clinical, biochemical and radiological features with reduced RCE activity suggests a possible causative link.

  8. Differential responses of nitrate reducer community size, structure, and activity to tillage systems.

    Science.gov (United States)

    Chèneby, D; Brauman, A; Rabary, B; Philippot, L

    2009-05-01

    The main objective of this study was to determine how the size, structure, and activity of the nitrate reducer community were affected by adoption of a conservative tillage system as an alternative to conventional tillage. The experimental field, established in Madagascar in 1991, consists of plots subjected to conventional tillage or direct-seeding mulch-based cropping systems (DM), both amended with three different fertilization regimes. Comparisons of size, structure, and activity of the nitrate reducer community in samples collected from the top layer in 2005 and 2006 revealed that all characteristics of this functional community were affected by the tillage system, with increased nitrate reduction activity and numbers of nitrate reducers under DM. Nitrate reduction activity was also stimulated by combined organic and mineral fertilization but not by organic fertilization alone. In contrast, both negative and positive effects of combined organic and mineral fertilization on the size of the nitrate reducer community were observed. The size of the nitrate reducer community was a significant predictor of the nitrate reduction rates except in one treatment, which highlighted the inherent complexities in understanding the relationships the between size, diversity, and structure of functional microbial communities along environmental gradients.

  9. Lipid reducing activity and toxicity profiles of a library of polyphenol derivatives.

    Science.gov (United States)

    Urbatzka, Ralph; Freitas, Sara; Palmeira, Andreia; Almeida, Tiago; Moreira, João; Azevedo, Carlos; Afonso, Carlos; Correia-da-Silva, Marta; Sousa, Emilia; Pinto, Madalena; Vasconcelos, Vitor

    2018-05-10

    Obesity is an increasing epidemic worldwide and novel treatments are urgently needed. Polyphenols are natural compounds derived from plants, which are known in particular for their antioxidant properties. However, some polyphenols were described to possess anti-obesity activities in vitro and in vivo. In this study, we aimed to screen a library of 85 polyphenol derivatives for their lipid reducing activity and toxicity. Compounds were analyzed at 5 μM with the zebrafish Nile red fluorescence fat metabolism assay and for general toxicity in vivo. To improve the safety profile, compounds were screened at 50 μM in murine preadipocytes in vitro for cytotoxicity. Obtained activity data were used to create a 2D-QSAR (quantitative structure activity relationship) model. 38 polyphenols showed strong lipid reducing activity. Toxicity analysis revealed that 18 of them did not show any toxicity in vitro or in vivo. QSAR analysis revealed the importance of the number of rings, fractional partial positively charged surface area, relative positive charge, relative number of oxygen atoms, and partial negative surface area for lipid-reducing activity. The five most potent compounds with EC 50 values in the nanomolar range for lipid reducing activity and without any toxic effects are strong candidates for future research and development into anti-obesity drugs. Molecular profiling for fasn, sirt1, mtp and ppary revealed one compound that reduced significantly fasn mRNA expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  10. Stop and revive? The effectiveness of nap and active rest breaks for reducing driver sleepiness.

    Science.gov (United States)

    Watling, Christopher N; Smith, Simon S; Horswill, Mark S

    2014-11-01

    The purpose of this study was to compare the effects of two commonly utilized sleepiness countermeasures: a nap break and an active rest break. The effects of the countermeasures were evaluated by physiological (EEG), subjective, and driving performance measures. Participants completed 2 h of simulated driving, followed by a 15-min nap break or a 15-min active rest break, then completed the final hour of simulated driving. The nap break reduced EEG and subjective sleepiness. The active rest break did not reduce EEG sleepiness, with sleepiness levels eventually increasing, and resulted in an immediate reduction of subjective sleepiness. No difference was found between the two breaks for the driving performance measure. The immediate reduction of subjective sleepiness after the active rest break could leave drivers with erroneous perceptions of their sleepiness, particularly with increases of physiological sleepiness after the break. Copyright © 2014 Society for Psychophysiological Research.

  11. AMP-activated protein kinase reduces inflammatory responses and cellular senescence in pulmonary emphysema.

    Science.gov (United States)

    Cheng, Xiao-Yu; Li, Yang-Yang; Huang, Cheng; Li, Jun; Yao, Hong-Wei

    2017-04-04

    Current drug therapy fails to reduce lung destruction of chronic obstructive pulmonary disease (COPD). AMP-activated protein kinase (AMPK) has emerged as an important integrator of signals that control energy balance and lipid metabolism. However, there are no studies regarding the role of AMPK in reducing inflammatory responses and cellular senescence during the development of emphysema. Therefore, we hypothesize that AMPK reduces inflammatroy responses, senescence, and lung injury. To test this hypothesis, human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (SAECs) were treated with cigarette smoke extract (CSE) in the presence of a specific AMPK activator (AICAR, 1 mM) and inhibitor (Compound C, 5 μM). Elastase injection was performed to induce mouse emphysema, and these mice were treated with a specific AMPK activator metformin as well as Compound C. AICAR reduced, whereas Compound C increased CSE-induced increase in IL-8 and IL-6 release and expression of genes involved in cellular senescence. Knockdown of AMPKα1/α2 increased expression of pro-senescent genes (e.g., p16, p21, and p66shc) in BEAS-2B cells. Prophylactic administration of an AMPK activator metformin (50 and 250 mg/kg) reduced while Compound C (4 and 20 mg/kg) aggravated elastase-induced airspace enlargement, inflammatory responses and cellular senescence in mice. This is in agreement with therapeutic effect of metformin (50 mg/kg) on airspace enlargement. Furthermore, metformin prophylactically protected against but Compound C further reduced mitochondrial proteins SOD2 and SIRT3 in emphysematous lungs. In conclusion, AMPK reduces abnormal inflammatory responses and cellular senescence, which implicates as a potential therapeutic target for COPD/emphysema.

  12. Efficacy of reduced dose of intravitreal triamcinolone acetonide in a case of active serpiginous choroiditis

    Directory of Open Access Journals (Sweden)

    Avirupa Ghose

    2016-01-01

    Full Text Available Active serpiginous choroiditis (SC is a vision-threatening condition which requires intensive treatment using corticosteroids and/or immunosuppressives, especially if the lesions are involving or encroaching on the macula. Use of oral and intravenous high-dose steroids are contraindicated in uncontrolled diabetics. Intravitreal steroid delivers a localized dose in such situations. This case report highlights the efficacy of reduced dose of intravitreal triamcinolone acetonide (2 mg in the treatment of active SC.

  13. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

    Directory of Open Access Journals (Sweden)

    D.V. Vassallo

    2008-09-01

    Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

  14. Altered biomarkers of mucosal immunity and reduced vaginal Lactobacillus concentrations in sexually active female adolescents.

    Directory of Open Access Journals (Sweden)

    Rebecca Pellett Madan

    Full Text Available Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV and Escherichia coli (E. coli, but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females.Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL specimens collected from 20 sexually active adolescent females (15-18 years. Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs.Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females.

  15. Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

    Science.gov (United States)

    Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

    2017-08-01

    Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N   G -nitro-l-arginine methyl ester (eNOS inhibitor; P preeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; P preeclampsia women had lower STBEV-eNOS expression compared with that from NP women ( P preeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

  16. Reduced In-Plane, Low Frequency Helicopter Noise of an Active Flap Rotor

    Science.gov (United States)

    Sim, Ben W.; Janakiram, Ram D.; Barbely, Natasha L.; Solis, Eduardo

    2009-01-01

    Results from a recent joint DARPA/Boeing/NASA/Army wind tunnel test demonstrated the ability to reduce in-plane, low frequency noise of the full-scale Boeing-SMART rotor using active flaps. Test data reported in this paper illustrated that acoustic energy in the first six blade-passing harmonics could be reduced by up to 6 decibels at a moderate airspeed, level flight condition corresponding to advance ratio of 0.30. Reduced noise levels were attributed to selective active flap schedules that modified in-plane blade airloads on the advancing side of the rotor, in a manner, which generated counteracting acoustic pulses that partially offset the negative pressure peaks associated with in-plane, steady thickness noise. These favorable reduced-noise operating states are a strong function of the active flap actuation amplitude, frequency and phase. The associated noise reductions resulted in reduced aural detection distance by up to 18%, but incurred significant vibratory load penalties due to increased hub shear forces. Small reductions in rotor lift-to-drag ratios, of no more than 3%, were also measured

  17. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    Science.gov (United States)

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  18. Tensile and impact behaviour of BATMAN II steels, Ti-bearing reduced activation martensitic alloys

    Science.gov (United States)

    Filacchioni, G.; Casagrande, E.; De Angelis, U.; De Santis, G.; Ferrara, D.; Pilloni, L.

    Two series of Reduced Activation Ferrous alloys (RAF) have been produced and studied by Casaccia's Laboratories. These martensitic alloys are named BATMAN steels. They are among the few presently developed RAF materials to exploit Ti as a carbide forming and grain size stabilizing element instead of Ta. In this work their mechanical properties are illustrated.

  19. High Resolution Ultrasound Imaging Using Adaptive Beamforming with Reduced Number of Active Elements

    DEFF Research Database (Denmark)

    Holfort, Iben Kraglund; Gran, Fredrik; Jensen, Jørgen Arendt

    2009-01-01

    is proposed. By reducing the number of active sensor elements, an increased resolution can be obtained with the MV beamformer. This observation is directly opposite the well-known relation between the spatial extent of the aperture and the achievable resolution. The investigations are based on Field II...

  20. Physiological response of Pseudomonas putida S12 subjected to reduced water activity.

    NARCIS (Netherlands)

    Kets, E.P.W.; Bont, de J.A.M.; Heipieper, H.J.

    1996-01-01

    The effect of osmotic stress, given as decreased water activity (aw), on growth and the accumulation of potassium and the compatible solute betaine by Pseudomonas putida S12 was investigated. Reduced aw was imposed by addition of sodium chloride, sucrose, glycerol or polyethylene glycol to the

  1. A multi coding technique to reduce transition activity in VLSI circuits

    International Nuclear Information System (INIS)

    Vithyalakshmi, N.; Rajaram, M.

    2014-01-01

    Advances in VLSI technology have enabled the implementation of complex digital circuits in a single chip, reducing system size and power consumption. In deep submicron low power CMOS VLSI design, the main cause of energy dissipation is charging and discharging of internal node capacitances due to transition activity. Transition activity is one of the major factors that also affect the dynamic power dissipation. This paper proposes power reduction analyzed through algorithm and logic circuit levels. In algorithm level the key aspect of reducing power dissipation is by minimizing transition activity and is achieved by introducing a data coding technique. So a novel multi coding technique is introduced to improve the efficiency of transition activity up to 52.3% on the bus lines, which will automatically reduce the dynamic power dissipation. In addition, 1 bit full adders are introduced in the Hamming distance estimator block, which reduces the device count. This coding method is implemented using Verilog HDL. The overall performance is analyzed by using Modelsim and Xilinx Tools. In total 38.2% power saving capability is achieved compared to other existing methods. (semiconductor technology)

  2. Initial Evaluation of Active Minds: A Student Organization Dedicated to Reducing the Stigma of Mental Illness

    Science.gov (United States)

    McKinney, Kathleen G.

    2009-01-01

    This study examined whether a new student organization, Active Minds, aimed at increasing awareness of "mental illness" and reducing stigma had an impact on students' stigma and willingness to seek psychological help. Three classes were recruited to become involved in the organization. In a pretest/posttest design, stigma and willingness to seek…

  3. The use of Powdered Activated Carbon in reducing the Doc in water treatment plants

    International Nuclear Information System (INIS)

    Nikravesh, S. H.; Etemad-Shahidi, A.; Razeghi, N.

    2003-01-01

    Today as the technology improves and the application of energy and chemicals enhances, the organic pollutants increases in surface waters in which waste waters are discharged into. In order to reduce water-born diseases, necessary actions should be taken to decrease the pollutants. Common methods of surface water treatment are not sufficient anymore. Therefore complementary methods like using activated carbon, aeration, oxidation and reverse osmosis should be used. In this paper the use of powdered activated carbon, Total organic carbon test and jar test in reducing the concentration of organic carbons in water treatment is investigated. Initial experimental results showed large errors in total organic carbon evaluation so dissolved organic carbon was measured instead. The results showed that using the powdered activated carbon in addition to conventional treatment method using ferric chloride, greatly reduces organic pollutants. Adding about 60 mg/lit of powdered activated carbon may reduce dissolved organic carbon up to 90% in optimum conditions. However, different factors like the quality of surface water, experimental errors, instrumental errors and tool errors can influence the experimental results

  4. Preparation of activated carbon from banana peel waste for reducing air pollutant from motorcycle muffler

    Directory of Open Access Journals (Sweden)

    Chafidz Achmad

    2018-01-01

    Full Text Available The exhaust gas or emission from motor vehicle contains various pollutants and some of them are toxic and very harmful for human health. In the present work, we prepared an activated carbon to reduce the toxic pollutants (via adsorption process from the exhaust gas of the motor vehicle (particularly motorcycle in this work. The activated carbon was prepared from local banana peel which considered as an agricultural waste without economic value. To prepare the activated carbon, banana peel was carbonized using furnace at 500°C. Then the resulted carbon was activated using chemical activation with ZnCl2 and physical activation with either microwave (300 W or furnace (700°C. The prepared activated carbon was then characterized using Scanning Electron Microscope (SEM and Fourier Transform Infrared (FT-IR analysis. The SEM result showed that the pore of microwave induced ZnCl2 activated carbon (ACM was larger than the pore of virgin char/carbon and furnace induced ZnCl2 activataed carbon (ACF. The FT-IR spectrum of ACM showed some peaks at 3408.59 cm-1, 1589.25 cm-1, and 1093.63 cm-1. They are assigned to O-H stretching, C=O stretching, and C-OH stretching. Additionally, the adsorption performance of the prepared activation carbon to reduce the pollutants concentration (i.e. CO and CH from the exhaust gas of motor vehicle was investigated. The results showed that the activated carbon induced by microwave and ZnCl2 activation (ACM gave the best result. The adsorption or removal efficiency of gas CO reached approximately 97.64 %vol.

  5. Troxerutin Reduces Kidney Damage against BDE-47-Induced Apoptosis via Inhibiting NOX2 Activity and Increasing Nrf2 Activity

    Directory of Open Access Journals (Sweden)

    Qun Shan

    2017-01-01

    Full Text Available 2,2,4,4-Tetrabromodiphenyl ether (BDE-47, one of the persistent organic pollutants, seriously influences the quality of life; however, its pathological mechanism remains unclear. Troxerutin is a flavonoid with pharmacological activity of antioxidation and anti-inflammation. In the present study, we investigated troxerutin against BDE-47-induced kidney cell apoptosis and explored the underlying mechanism. The results show that troxerutin reduced renal cell apoptosis and urinary protein secretion in BDE-47-treated mice. Western blot analysis shows that troxerutin supplement enhanced the ratio of Bcl-2/Bax; inhibited the release of cytochrome c from mitochondria, the activation of procaspase-9 and procaspase-3, and the cleavage of PARP; and reduced FAS, FASL, and caspase-8 levels induced by BDE-47. In addition, troxerutin decreased the production of reactive oxygen species (ROS and increased the activities of antioxidative enzymes. Furthermore, troxerutin blunted Nrf2 ubiquitylation, enhanced the activity of Nrf2, decreased the activity of NOX2, and ameliorated kidney oxidant status of BDE-47-treated mice. Together, these results confirm that troxerutin could alleviate the cytotoxicity of BDE-47 through antioxidation and antiapoptosis, which suggests that its protective mechanism is involved in the inhibition of apoptosis via suppressing NOX2 activity and increasing Nrf2 signaling pathway.

  6. Activation of aluminum as an effective reducing agent by pitting corrosion for wet-chemical synthesis.

    Science.gov (United States)

    Li, Wei; Cochell, Thomas; Manthiram, Arumugam

    2013-01-01

    Metallic aluminum (Al) is of interest as a reducing agent because of its low standard reduction potential. However, its surface is invariably covered with a dense aluminum oxide film, which prevents its effective use as a reducing agent in wet-chemical synthesis. Pitting corrosion, known as an undesired reaction destroying Al and is enhanced by anions such as F⁻, Cl⁻, and Br⁻ in aqueous solutions, is applied here for the first time to activate Al as a reducing agent for wet-chemical synthesis of a diverse array of metals and alloys. Specifically, we demonstrate the synthesis of highly dispersed palladium nanoparticles on carbon black with stabilizers and the intermetallic Cu₂Sb/C, which are promising candidates, respectively, for fuel cell catalysts and lithium-ion battery anodes. Atomic hydrogen, an intermediate during the pitting corrosion of Al in protonic solvents (e.g., water and ethylene glycol), is validated as the actual reducing agent.

  7. Experimental investigation on the active range of sulfate-reducing bacteria for geological disposal

    International Nuclear Information System (INIS)

    Fukunaga, S.; Fujiki, K.; Asano, H.; Yoshikawa, H.

    1995-01-01

    The active range of Desulfovibrio desulfuricans, a species of sulfate-reducing bacteria, was examined in terms of pH and Eh using a fermenter at controlled pH and Eh. Such research is important because sulfate-reducing bacteria (SRB) are thought to exist underground at depths equal to those of supposed repositories for high-level radioactive wastes and to be capable of inducing corrosion of the metals used in containment vessels. SRB activity was estimated at 35 C, with lactate as an electron donor, at a pH range from 7 to 11 and Eh range from 0 to -380 mV. Activity increased as pH approached neutral and Eh declined. The upper pH limit for activity was between 9.9 and 10.3, at Eh of -360 to -384 mV. The upper Eh limit for activity was between -68 and -3 mV, at pH 7.1. These results show that SRB can be made active at higher pH by decreasing Eh, and that the higher pH levels of 8 to 10 produced by use of the buffer material bentonite does not suppress SRB completely. A chart was obtained showing the active range of Desulfovibrio desulfuricans in terms of pH and Eh. Such charts can be used to estimate the viability of SRB and other microorganisms when the environmental conditions of a repository are specified

  8. Cognitive emotion regulation enhances aversive prediction error activity while reducing emotional responses.

    Science.gov (United States)

    Mulej Bratec, Satja; Xie, Xiyao; Schmid, Gabriele; Doll, Anselm; Schilbach, Leonhard; Zimmer, Claus; Wohlschläger, Afra; Riedl, Valentin; Sorg, Christian

    2015-12-01

    Cognitive emotion regulation is a powerful way of modulating emotional responses. However, despite the vital role of emotions in learning, it is unknown whether the effect of cognitive emotion regulation also extends to the modulation of learning. Computational models indicate prediction error activity, typically observed in the striatum and ventral tegmental area, as a critical neural mechanism involved in associative learning. We used model-based fMRI during aversive conditioning with and without cognitive emotion regulation to test the hypothesis that emotion regulation would affect prediction error-related neural activity in the striatum and ventral tegmental area, reflecting an emotion regulation-related modulation of learning. Our results show that cognitive emotion regulation reduced emotion-related brain activity, but increased prediction error-related activity in a network involving ventral tegmental area, hippocampus, insula and ventral striatum. While the reduction of response activity was related to behavioral measures of emotion regulation success, the enhancement of prediction error-related neural activity was related to learning performance. Furthermore, functional connectivity between the ventral tegmental area and ventrolateral prefrontal cortex, an area involved in regulation, was specifically increased during emotion regulation and likewise related to learning performance. Our data, therefore, provide first-time evidence that beyond reducing emotional responses, cognitive emotion regulation affects learning by enhancing prediction error-related activity, potentially via tegmental dopaminergic pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost

    Directory of Open Access Journals (Sweden)

    Yinan Zhang

    2016-01-01

    Full Text Available Diabetic retinopathy (DR screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%–35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost.

  10. Reducing prefrontal gamma-aminobutyric acid activity induces cognitive, behavioral, and dopaminergic abnormalities that resemble schizophrenia.

    Science.gov (United States)

    Enomoto, Takeshi; Tse, Maric T; Floresco, Stan B

    2011-03-01

    Perturbations in gamma-aminobutyric acid (GABA)-related markers have been reported in the prefrontal cortex of schizophrenic patients. However, a preclinical assessment of how suppression of prefrontal cortex GABA activity may reflect behavioral and cognitive pathologies observed in schizophrenia is forthcoming. We assessed the effects of pharmacologic blockade of prefrontal cortex GABA(A) receptors in rats on executive functions and other behaviors related to schizophrenia, as well as neural activity of midbrain dopamine neurons. Blockade of prefrontal cortex GABA(A) receptors with bicuculline (12.5-50 ng) did not affect working memory accuracy but did increase response latencies, resembling speed of processing deficits observed in schizophrenia. Prefrontal cortex GABA(A) blockade did not impede simple discrimination or reversal learning but did impair set-shifting in a manner dependent on when these treatments were given. Reducing GABA activity before the set-shift impaired the ability to acquire a novel strategy, whereas treatment before the initial discrimination increased perseveration during the shift. Latent inhibition was unaffected by bicuculline infusions before the preexposure/conditioning phases, suggesting that reduced prefrontal cortex GABA activity does not impair "learned irrelevance." GABA(A) blockade increased locomotor activity and showed synergic effects with a subthreshold dose of amphetamine. Furthermore, reducing medial prefrontal cortex GABA activity selectively increased phasic burst firing of ventral tegmental area dopamine neurons, without altering the their overall population activity. These results suggest that prefrontal cortex GABA hypofunction may be a key contributing factor to deficits in speed of processing, cognitive flexibility, and enhanced phasic dopamine activity observed in schizophrenia. Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  11. Thermally Reduced Graphene Oxide Electrochemically Activated by Bis-Spiro Quaternary Alkyl Ammonium for Capacitors.

    Science.gov (United States)

    He, Tieshi; Meng, Xiangling; Nie, Junping; Tong, Yujin; Cai, Kedi

    2016-06-08

    Thermally reduced graphene oxide (RGO) electrochemically activated by a quaternary alkyl ammonium-based organic electrolytes/activated carbon (AC) electrode asymmetric capacitor is proposed. The electrochemical activation process includes adsorption of anions into the pores of AC in the positive electrode and the interlayer intercalation of cations into RGO in the negative electrode under high potential (4.0 V). The EA process of RGO by quaternary alkyl ammonium was investigated by X-ray diffraction and electrochemical measurements, and the effects of cation size and structure were extensively evaluated. Intercalation by quaternary alkyl ammonium demonstrates a small degree of expansion of the whole crystal lattice (d002) and a large degree of expansion of the partial crystal lattice (d002) of RGO. RGO electrochemically activated by bis-spiro quaternary alkyl ammonium in propylene carbonate/AC asymmetric capacitor exhibits good activated efficiency, high specific capacity, and stable cyclability.

  12. Reduced pyrazinamidase activity and the natural resistance of Mycobacterium kansasii to the antituberculosis drug pyrazinamide.

    Science.gov (United States)

    Sun, Z; Zhang, Y

    1999-03-01

    Pyrazinamide (PZA), an analog of nicotinamide, is a prodrug that requires conversion to the bactericidal compound pyrazinoic acid (POA) by the bacterial pyrazinamidase (PZase) activity of nicotinamidase to show activity against Mycobacterium tuberculosis. Mutations leading to a loss of PZase activity cause PZA resistance in M. tuberculosis. M. kansasii is naturally resistant to PZA and has reduced PZase activity along with an apparently detectable nicotinamidase activity. The role of the reduction in PZase activity in the natural PZA resistance of M. kansasii is unknown. The MICs of PZA and POA for M. kansasii were determined to be 500 and 125 micrograms/ml, respectively. Using [14C]PZA and [14C]nicotinamide, we found that M. kansasii had about 5-fold-less PZase activity and about 25-fold-less nicotinamidase activity than M. tuberculosis. The M. kansasii pncA gene was cloned on a 1.8-kb BamHI DNA fragment, using M. avium pncA probe. Sequence analysis showed that the M. kansasii pncA gene encoded a protein with homology to its counterparts from M. tuberculosis (69.9%), M. avium (65.6%), and Escherichia coli (28.5%). Transformation of naturally PZA-resistant M. bovis BCG with M. kansasii pncA conferred partial PZA susceptibility. Transformation of M. kansasii with M. avium pncA caused functional expression of PZase and high-level susceptibility to PZA, indicating that the natural PZA resistance in M. kansasii results from a reduced PZase activity. Like M. tuberculosis, M. kansasii accumulated POA in the cells at an acidic pH; however, due to its highly active POA efflux pump, the naturally PZA-resistant species M. smegmatis did not. These findings suggest the existence of a weak POA efflux mechanism in M. kansasii.

  13. Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice.

    Science.gov (United States)

    Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; Abbring, Suzanne; van der Horst, Hilma; Broersen, Laus M; Willemsen, Linette; Kas, Martien; Garssen, Johan; Kraneveld, Aletta D

    2017-01-01

    Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs. Based on these results, we designed an mTOR-targeting amino acid diet (Active 1 diet) and assessed the effects of dietary interventions with the amino acid diet or a multi-nutrient supplementation diet (Active 2 diet) on autistic-like behavior and mTOR signaling in food allergic mice and in inbred BTBR T+Itpr3tf/J mice. Cow's milk allergic (CMA) or BTBR male mice were fed a Control, Active 1, or Active 2 diet for 7 consecutive weeks. CMA mice showed reduced social interaction and increased self-grooming behavior. Both diets reversed behavioral impairments and inhibited the mTOR activity in the prefrontal cortex and amygdala of CMA mice. In BTBR mice, only Active 1 diet reduced repetitive self-grooming behavior and attenuated the mTOR activity in the prefrontal and somatosensory cortices. The current results suggest that activated mTOR signaling pathway in the brain may be a convergent pathway in the pathogenesis of ASD bridging genetic background and environmental triggers (food allergy) and that mTOR over-activation could serve as a potential therapeutic target for the treatment of ASD. Copyright © 2016. Published by Elsevier Inc.

  14. Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels

    Directory of Open Access Journals (Sweden)

    Sungpil Yoon

    2013-08-01

    Full Text Available The present study identified a novel salinomycin (Sal-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules PI3K, PDK1, GSK3β, p70S6K, mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal sensitization positively correlates with large reductions in p70S6K activation. Interestingly, Akt was the only signal protein to be significantly activated by Sal treatment. The Akt activation appeared to require the PI3K pathway as its activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt activation by Sal was conserved in the other cell lines analyzed, which originated from other organs. Both Akt activation and C-PARP production were proportionally increased with increased doses of Sal. In addition, the increased levels of pAkt were not reduced over the time course of the experiment. Co-treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The results thereby suggest that Akt activation is increased in cells that survive Sal treatment and resist the cytotoxic effect of Sal. Taken together; these results indicate that Akt activation may promote the resistance of cancer cells to Sal.

  15. Downregulation of cathepsin G reduces the activation of CD4+ T cells in murine autoimmune diabetes.

    Science.gov (United States)

    Zou, Fang; Lai, Xiaoyang; Li, Jing; Lei, Shuihong; Hu, Lei

    2017-01-01

    Type 1 diabetes mellitus (T1DM) is an autoimmune disease due to progressive injury of islet cells mediated by T lymphocytes (T cells). Our previous studies have shown that only cathepsin G (CatG), not other proteases, is involved in the antigen presentation of proinsulin, and if the presentation is inhibited, the activation of CD4+ T cells induced by proinsulin is alleviated in T1DM patients, and CatG-specific inhibitor reduces the activation of CD4+ cells induced by proinsulin in T1DM patients. Therefore, we hypothesize that CatG may play an important role in the activation of CD4+ T cells in T1DM. To this end, mouse studies were conducted to demonstrate that CatG impacts the activation of CD4+ T cells in non-obese diabetic (NOD) mice. CatG gene expression and the activation of CD4+ T cells were examined in NOD mice. The effect of CatG inhibitor was investigated in NOD mice on the activation of CD4+ T cells, islet β cell function, islet inflammation and β-cell apoptosis. Furthermore, NOD mice were injected with CatG siRNA in early stage to observe the effect of CatG knockdown on the activation status of CD4+ T cells and the progression of diabetes. During the pathogenesis of diabetes, the expression level of CatG in NOD mice gradually increased and the CD4+ T cells were gradually activated, resulting in more TH1 cells and less TH2 and Treg cells. Treatment with CatG-specific inhibitor reduced the blood glucose level, improved the function of islet β cells and reduced the activation of CD4+ T cells. Early application of CatG siRNA improved the function of islet β cells, reduced islet inflammation and β cell apoptosis, and lowered the activation level of CD4+ T cells, thus slowing down the progression of diabetes.

  16. Effects of reduced glutathione on acrosin activity in frozen-thawed boar spermatozoa.

    Science.gov (United States)

    Estrada, Efrén; Rodríguez-Gil, Joan E; Rivera Del Álamo, Maria M; Peña, Alejandro; Yeste, Marc

    2017-02-01

    In pigs, acrosin activity in extended semen is correlated with reproductive performance and has recently been identified as a freezability marker. Reduced glutathione (GSH) is known to decrease sperm cryodamage and increase the reproductive performance of frozen-thawed boar spermatozoa. However, the effects of GSH on the acrosin activity of good and poor freezability ejaculates (GFE and PFE, respectively) is yet to be examined. The present study investigated how supplementing cryopreservation media with GSH affected acrosin activity in GFE and PFE, as well as the relationship between acrosin activity and reproductive performance in frozen-thawed boar spermatozoa. In addition, we examined whether the increase in fertility rates and litter sizes observed after the addition of 2mM GSH to cryopreservation extenders was related to acrosin activity. Supplementing freezing media with 2mM GSH partially counteracted the cryopreservation-related decrease in acrosin activity in GFE but not PFE. Acrosin activity was found to be significantly correlated with in vivo reproductive performance of frozen-thawed boar semen. In conclusion, the effects of adding GSH to freezing extenders on the acrosin activity of frozen-thawed boar spermatozoa rely on the intrinsic freezability of the ejaculate. Furthermore, the maintenance of proper acrosin activity could contribute to the increase in reproductive performance mediated by GSH.

  17. Altered fatty acid metabolism and reduced stearoyl-coenzyme a desaturase activity in asthma.

    Science.gov (United States)

    Rodriguez-Perez, N; Schiavi, E; Frei, R; Ferstl, R; Wawrzyniak, P; Smolinska, S; Sokolowska, M; Sievi, N A; Kohler, M; Schmid-Grendelmeier, P; Michalovich, D; Simpson, K D; Hessel, E M; Jutel, M; Martin-Fontecha, M; Palomares, O; Akdis, C A; O'Mahony, L

    2017-11-01

    Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS. Changes in stearoyl-coenzyme A desaturase (SCD) expression and activity were evaluated in the ovalbumin (OVA) and house dust mite (HDM) murine models. Primary human bronchial epithelial cells from asthma patients and controls were evaluated for SCD expression and activity. The serum desaturation index (an indirect measure of SCD) was significantly reduced in nonobese asthma patients and in the OVA murine model. SCD1 gene expression was significantly reduced within the lungs following OVA or HDM challenge. Inhibition of SCD in mice promoted airway hyper-responsiveness. SCD1 expression was suppressed in bronchial epithelial cells from asthma patients. IL-4 and IL-13 reduced epithelial cell SCD1 expression. Inhibition of SCD reduced surfactant protein C expression and suppressed rhinovirus-induced IP-10 secretion, which was associated with increased viral titers. This is the first study to demonstrate decreased fatty acid desaturase activity in humans with asthma. Experimental models in mice and human epithelial cells suggest that inhibition of desaturase activity leads to airway hyper-responsiveness and reduced antiviral defense. SCD may represent a new target for therapeutic intervention in asthma patients. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  18. Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep

    Directory of Open Access Journals (Sweden)

    Shoulong Deng

    2016-01-01

    Full Text Available Toll-like receptor 4 (TLR4 is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4-overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS. Consequently, production of malondialdehyde (MDA was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH-Px, was increased. Real-time PCR showed that expression of activating protein-1 (AP-1 and the antioxidative-related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1 and catalase (CAT were reduced. In transgenic sheep, glutathione (GSH levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ-glutamylcysteine synthetase (γ-GCS was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ-GCS translation through the AP-1 pathway, which was essential for GSH synthesis.

  19. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

  20. Active Lubrication for Reducing Wear and Vibration: A combination of Fluid Power Control and Tribology

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2002-01-01

    The use of fluid power to reduce and control rotor vibration in rotating machines is investigated. An active hybrid bearing is studied, whose main objective is to reduce wear and vibration between rotating and stationary machinery parts. By injecting pressurised oil into the oil film, through...... orifices machined in the bearing pads, one can alter the machine dynamic characteristics, thus enhancing its operational range. A mathematical model of the rotor-bearing system, as well as of the hydraulic system, is presented. Numerical results of the system frequency response show good agreement...

  1. Active commuting reduces sociodemographic differences in adherence to recommendations derived from leisure-time physical activity among Brazilian adults.

    Science.gov (United States)

    Del Duca, G F; Nahas, M V; Garcia, L M T; Silva, S G; Hallal, P C; Peres, M A

    2016-05-01

    To investigate the consequences of including active commuting, compared with the leisure domain only, in the prevalence and sociodemographic factors associated with attending the physical activity recommendations, in Brazilian adults. Population-based cross-sectional study. Adults between 20 and 59 years of age (n = 1720) were face-to-face interviewed from September 2009 to January 2010. Sociodemographic indicators and leisure-time and commuting physical activity were assessed by a validated questionnaire. Poisson regression was used to estimate crude and adjusted prevalence ratio (PR) and 95% confidence interval (95% CI). The prevalence of adherence to recommendations when only leisure-time physical activity was considered was 15.5% (95% CI: 13.6; 17.4) and was associated with men (PR: 1.57, 95% CI: 1.25; 1.96), adults without a partner (PR: 1.38 95% CI: 1.05; 1.81) and higher educational level and income. The prevalence of adherence to physical activity recommendations after the combination of leisure-time and commuting was 29.1% (95% CI: 26.5; 31.6). Percentages differences in favor of men, white adults and those with higher educational level and income were no longer significant after the inclusion of active commuting. The inclusion of active commuting expands the percentage of adults who achieved the health-related physical activity recommendations and reduced important sociodemographic differences derived from the analysis of leisure-time physical activity alone. Public health strategies should consider the different domains of physical activity in the monitoring and promotion of a more active lifestyle. Copyright © 2016. Published by Elsevier Ltd.

  2. [Physical activity programmes to reduce overweight and obesity in children and adolescents; a systematic review].

    Science.gov (United States)

    Aguilar Cordero, M J; Ortegón Piñero, A; Mur Vilar, N; Sánchez García, J C; García Verazaluce, J J; García García, I; Sánchez López, A M

    2014-10-01

    Obesity treatment has been the subject of much controversy; various authors have recommended the application of a comprehensive treatment programme, and in the light of this previous research, we consider the question of what is the most effective programme of physical activity to reduce overweight and obesity in children and adolescents. To analyse major studies on the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. Systematic review of the results of physical activity programmes, published in scientific articles, to reduce overweight and obesity. Using an automated database search in PubMed and Google Scholar, conducted from October 2013 to March 2014, we identified 85 valid items. In selecting the items, the criteria applied included the usefulness and relevance of the subject matter and the credibility or experience of the research study authors. The internal and external validity of each of the articles reviewed was taken into account. This review confirmed the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. The most effective programmes were those combining aerobic and anaerobic exercises. It is generally accepted that at least 180 minutes per week should be dedicated to exercise, in the form of three 60-minute sessions of moderate intensity. Such programmes could be sufficient for persons with overweight or obesity. Researchers in this field agree that when a diet based on an appropriate distribution of meals is combined with regular physical activity, they reinforce each other, and thus optimum results are obtained. Weight reduction programmes that take account of family involvement are more effective than nutrition education itself or other routine interventions that fail to consider family involvement. The role of pa rents and of the persons around the child or adolescent is essential to reinforce positive behaviour toward lifestyle change. Copyright AULA

  3. Reduced salience and default mode network activity in women with anorexia nervosa

    Science.gov (United States)

    McFadden, Kristina L.; Tregellas, Jason R.; Shott, Megan E.; Frank, Guido K.W.

    2014-01-01

    Background The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated. Methods Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis. Results We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate–corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN. Limitations Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates. Conclusion Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach

  4. The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

    Science.gov (United States)

    Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

    2016-04-01

    Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. A review of activated carbon technologies for reducing MSW incinerator emissions

    International Nuclear Information System (INIS)

    Clarke, M.J.

    1991-01-01

    Though activated carbon is, by no means, a newcomer to the pollution control field, having been used as a water purifier and more recently demonstrated as a flue gas cleaner on power plants, it is now attracting considerable attention in Europe as a means to reduce further the quantity of toxic organic and metal emissions from new and existing municipal waste combustors. Since activated carbon is a potentially important future emissions control technology for MWCs in the US, particularly for removal of mercury and dioxin, this paper discusses the impetus which has motivated the experimentation with various activated carbon technologies which is now taking place, will describe how some of the activated carbon systems (e.g., post-emissions control fixed carbon bed and injection of carbon with scrubber reagent) being tested now function and where they fit in existing pollution control trains, and will present available performance data and emissions reductions actually achieved for each system

  6. Aryl Hydrocarbon Receptor Activation Reduces Dendritic Cell Function during Influenza Virus Infection

    Science.gov (United States)

    Jin, Guang-Bi; Moore, Amanda J.; Head, Jennifer L.; Neumiller, Joshua J.; Lawrence, B. Paige

    2010-01-01

    It has long been known that activation of the aryl hydrocarbon receptor (AhR) by ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppresses T cell–dependent immune responses; however, the underlying cellular targets and mechanism remain unclear. We have previously shown that AhR activation by TCDD reduces the proliferation and differentiation of influenza virus–specific CD8+ T cells through an indirect mechanism; suggesting that accessory cells are critical AhR targets during infection. Respiratory dendritic cells (DCs) capture antigen, migrate to lymph nodes, and play a key role in activating naive CD8+ T cells during respiratory virus infection. Herein, we report an examination of how AhR activation alters DCs in the lung and affects their trafficking to and function in the mediastinal lymph nodes (MLN) during infection with influenza virus. We show that AhR activation impairs lung DC migration and reduces the ability of DCs isolated from the MLN to activate naive CD8+ T cells. Using novel AhR mutant mice, in which the AhR protein lacks its DNA-binding domain, we show that the suppressive effects of TCDD require that the activated AhR complex binds to DNA. These new findings suggest that AhR activation by chemicals from our environment impacts DC function to stimulate naive CD8+ T cells and that immunoregulatory genes within DCs are critical targets of AhR. Moreover, our results reinforce the idea that environmental signals and AhR ligands may contribute to differential susceptibilities and responses to respiratory infection. PMID:20498003

  7. Enrichment: CRISLA [chemical reaction by isotope selective activation] aims to reduce costs

    International Nuclear Information System (INIS)

    Eerkens, J.W.

    1989-01-01

    Every year, more than $3 billion is spent on enriching uranium. CRISLA (Chemical Reaction by Isotope Selective Activation) uses a laser-catalyzed chemical reaction which, its proponents claim, could substantially reduce these costs. In CRISLA, an infrared CO laser illuminates the intracavity reaction cell (IC) at a frequency tuned to excite primarily UF 6 . When UF 6 and co-reactant RX are passed through the IC, the tuned laser photons preferentially enhance the reaction of UF 6 with RX ten-thousand-fold over the thermal reaction rate. Thus the laser serves as an activator and the chemical energy for separation is largely chemical. (author)

  8. Structural and mechanical properties of welded joints of reduced activation martensitic steels

    International Nuclear Information System (INIS)

    Filacchioni, G.; Montanari, R.; Tata, M.E.; Pilloni, L.

    2002-01-01

    Gas tungsten arc welding and electron beam welding methods were used to realise welding pools on plates of reduced activation martensitic steels. Structural and mechanical features of these simulated joints have been investigated in as-welded and post-welding heat-treated conditions. The research allowed to assess how each welding technique affects the original mechanical properties of materials and to find suitable post-welding heat treatments. This paper reports results from experimental activities on BATMAN II and F82H mod. steels carried out in the frame of the European Blanket Project - Structural Materials Program

  9. Silver nanoparticles anchored reduced graphene oxide for enhanced electrocatalytic activity towards methanol oxidation

    Science.gov (United States)

    Kumar, Sanjeev; Mahajan, Mani; Singh, Rajinder; Mahajan, Aman

    2018-02-01

    In this report, silver nanoparticles (Ag NPs) anchored reduced graphene oxide (rGO) sheets (rGO/Ag) nanohybrid has been explored as anode material in direct methanol fuel cells (DMFCs). The synthesized rGO/Ag nanohybrid is characterized by XRD, XPS, FTIR spectroscopy and HRTEM techniques. Cyclic voltammograms demonstrate that the rGO/Ag nanohybrid exhibits higher electrocatalytic activity in comparison to rGO sheets for methanol oxidation reaction (MOR). This enhancement is attributed to the synergetic effect produced by the presence of more active sites provided by Ag NPs anchored on a conducting network of large surface area rGO sheets.

  10. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural...... indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP...

  11. Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases

    Directory of Open Access Journals (Sweden)

    Chen Rachman-Tzemah

    2017-04-01

    Full Text Available Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

  12. Enhanced antimicrobial activities of silver-nanoparticle-decorated reduced graphene nanocomposites against oral pathogens.

    Science.gov (United States)

    Peng, Jian-Min; Lin, Jia-Cheng; Chen, Zhuo-Yu; Wei, Meng-Chao; Fu, Yuan-Xiang; Lu, Shu-Shen; Yu, Dong-Sheng; Zhao, Wei

    2017-02-01

    As a means of capitalizing on the synergistic properties between reduced graphene nanosheets (R-GNs) and silver nanoparticles (AgNPs), an efficient and convenient chemical reduction method was used to prepare silver-nanoparticle-decorated reduced graphene nanocomposites (R-GNs/Ag). The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy, which confirmed the loading of well-dispersed silver nanoparticles on reduced graphene sheets. Their antimicrobial activities against oral pathogens such as Candida albicans, Lactobacillus acidophilus, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were investigated by MIC determination, the counting of colony-forming units (CFU), agar diffusion tests, and growth curve observation. Compared with pure R-GNs and AgNPs, R-GNs/Ag composites exhibited enhanced antimicrobial properties owing to highly dispersed AgNPs on R-GNs. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Calcaneal Quantitative Ultrasound Indicates Reduced Bone Status Among Physically Active Adult Forager-Horticulturalists.

    Science.gov (United States)

    Stieglitz, Jonathan; Madimenos, Felicia; Kaplan, Hillard; Gurven, Michael

    2016-03-01

    Sedentary lifestyle contributes to osteoporosis and fragility fracture risks among modern humans, but whether such risks are prevalent in physically active preindustrial societies with lower life expectancies is unclear. Osteoporosis should be readily observable in preindustrial societies if it was regularly experienced over human history. In this study of 142 older adult Tsimane forager-horticulturalists (mean age ± SD, 62.1 ± 8.6 years; range, 50 to 85 years; 51% female) we used calcaneal quantitative ultrasonography (qUS) to assess bone status, document prevalence of adults with reduced bone status, and identify factors (demographic, anthropometric, immunological, kinesthetic) associated with reduced bone status. Men (23%) are as likely as women (25%) to have reduced bone status, although age-related decline in qUS parameters is attenuated for men. Adiposity and fat-free mass positively co-vary with qUS parameters for women but not men. Leukocyte count is inversely associated with qUS parameters controlling for potential confounders; leukocyte count is positively correlated within adults over time, and adults with persistently low counts have higher adjusted qUS parameters (6% to 8%) than adults with a high count. Reduced bone status characteristic of osteoporosis is common among active Tsimane with minimal exposure to osteoporosis risk factors found in industrialized societies, but with energetic constraints and high pathogen burden. © 2015 American Society for Bone and Mineral Research.

  14. Enhanced antimicrobial activities of silver-nanoparticle-decorated reduced graphene nanocomposites against oral pathogens

    Energy Technology Data Exchange (ETDEWEB)

    Peng, Jian-min; Lin, Jia-cheng; Chen, Zhuo-yu; Wei, Meng-chao [Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Fu, Yuan-xiang; Lu, Shu-shen [School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275 (China); Yu, Dong-sheng, E-mail: yudsh@mail.sysu.edu.cn [Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China); Zhao, Wei, E-mail: zhaowei3@mail.sysu.edu.cn [Guanghua School of Stomatology, Hospital of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou 510055 (China)

    2017-02-01

    As a means of capitalizing on the synergistic properties between reduced graphene nanosheets (R-GNs) and silver nanoparticles (AgNPs), an efficient and convenient chemical reduction method was used to prepare silver-nanoparticle-decorated reduced graphene nanocomposites (R-GNs/Ag). The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy, which confirmed the loading of well-dispersed silver nanoparticles on reduced graphene sheets. Their antimicrobial activities against oral pathogens such as Candida albicans, Lactobacillus acidophilus, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were investigated by MIC determination, the counting of colony-forming units (CFU), agar diffusion tests, and growth curve observation. Compared with pure R-GNs and AgNPs, R-GNs/Ag composites exhibited enhanced antimicrobial properties owing to highly dispersed AgNPs on R-GNs. - Highlights: • This study synthesized R-GNs/Ag composites by a chemical reduction method. • AgNPs were successfully dispersed on reduced graphene nanosheets. • R-GNs/Ag composites showed enhanced antimicrobial activities against oral pathogens compared with plain AgNPs or R-GNs.

  15. Enhanced antimicrobial activities of silver-nanoparticle-decorated reduced graphene nanocomposites against oral pathogens

    International Nuclear Information System (INIS)

    Peng, Jian-min; Lin, Jia-cheng; Chen, Zhuo-yu; Wei, Meng-chao; Fu, Yuan-xiang; Lu, Shu-shen; Yu, Dong-sheng; Zhao, Wei

    2017-01-01

    As a means of capitalizing on the synergistic properties between reduced graphene nanosheets (R-GNs) and silver nanoparticles (AgNPs), an efficient and convenient chemical reduction method was used to prepare silver-nanoparticle-decorated reduced graphene nanocomposites (R-GNs/Ag). The products were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and Raman spectroscopy, which confirmed the loading of well-dispersed silver nanoparticles on reduced graphene sheets. Their antimicrobial activities against oral pathogens such as Candida albicans, Lactobacillus acidophilus, Streptococcus mutans, and Aggregatibacter actinomycetemcomitans were investigated by MIC determination, the counting of colony-forming units (CFU), agar diffusion tests, and growth curve observation. Compared with pure R-GNs and AgNPs, R-GNs/Ag composites exhibited enhanced antimicrobial properties owing to highly dispersed AgNPs on R-GNs. - Highlights: • This study synthesized R-GNs/Ag composites by a chemical reduction method. • AgNPs were successfully dispersed on reduced graphene nanosheets. • R-GNs/Ag composites showed enhanced antimicrobial activities against oral pathogens compared with plain AgNPs or R-GNs.

  16. Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

    Directory of Open Access Journals (Sweden)

    Rolf Diezko

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

  17. Peptidase inhibitors reduce opiate narcotic withdrawal signs, including seizure activity, in the rat.

    Science.gov (United States)

    Pinsky, C; Dua, A K; LaBella, F S

    1982-07-15

    Narcotic withdrawal was precipitated by administration of naloxone in a low dose at 2 h after the final dose of morphine in a 9-day dependency-inducing schedule. Withdrawal was characterized by leaps, increased nocifensor activity and by cerebral cortical epileptiform activity, the latter not generally reported to be prominent in narcotic withdrawal. Single large doses of morphine did not provoke epileptiform activity at 2 h postinjection but did induce an acute opioid dependency wherein a moderately high dose of naloxone, ineffective in non-dependent rats, provoked upward leaping and electrocortical epileptiform activity. Pretreatment of the 9-day dependent rats with peptidase inhibitors, administered intracerebroventricularly, significantly reduced withdrawal severity including the epileptiform activity. We propose that peptidase inhibitors protect certain species of endogenous opioids and/or other neuropeptides that tend to suppress expression of the narcotic withdrawal syndrome. Furthermore, our findings suggest that epileptiform activity is a nascent form of cerebral activity hitherto largely unnoticed in narcotic withdrawal and that neuropeptides may be involved in certain epileptic states.

  18. Fatty acid translocase promoted hepatitis B virus replication by upregulating the levels of hepatic cytosolic calcium.

    Science.gov (United States)

    Huang, Jian; Zhao, Lei; Yang, Ping; Chen, Zhen; Ruan, Xiong Z; Huang, Ailong; Tang, Ni; Chen, Yaxi

    2017-09-15

    Hepatitis B virus (HBV) is designated a "metabolovirus" due to the intimate connection between the virus and host metabolism. The nutrition state of the host plays a relevant role in the severity of HBV infection. Metabolic syndrome (MS) is prone to increasing HBV DNA loads and accelerating the progression of liver disease in patients with chronic hepatitis B (CHB). Cluster of differentiation 36 (CD36), also named fatty acid translocase, is known to facilitate long-chain fatty acid uptake and contribute to the development of MS. We recently found that CD36 overexpression enhanced HBV replication. In this study, we further explored the mechanism by which CD36 overexpression promotes HBV replication. Our data showed that CD36 overexpression increased HBV replication, and CD36 knockdown inhibited HBV replication. RNA sequencing found some of the differentially expressed genes were involved in calcium ion homeostasis. CD36 overexpression elevated the cytosolic calcium level, and CD36 knockdown decreased the cytosolic calcium level. Calcium chelator BAPTA-AM could override the HBV replication increased by CD36 overexpression, and the calcium activator thapsigargin could improve the HBV replication reduced by CD36 knockdown. We further found that CD36 overexpression activated Src kinase, which plays an important role in the regulation of the store-operated Ca 2+ channel. An inhibitor of Src kinase (SU6656) significantly reduced the CD36-induced HBV replication. We identified a novel link between CD36 and HBV replication, which is associated with cytosolic calcium and the Src kinase pathway. CD36 may represent a potential therapeutic target for the treatment of CHB patients with MS. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Chromate-reducing activity of Hansenula polymorpha recombinant cells over-producing flavocytochrome b₂.

    Science.gov (United States)

    Smutok, Oleh; Broda, Daniel; Smutok, Halyna; Dmytruk, Kostyantyn; Gonchar, Mykhailo

    2011-04-01

    In spite of the great interest to studies of the biological roles of chromium, as well as the toxic influence of Cr(VI)-species on living organisms, the molecular mechanisms of chromate bioremediation remain vague. A reductive pathway resulting in formation of less toxic Cr(III)-species is suggested to be the most important among possible mechanisms for chromate biodetoxification. The yeast l-lactate:cytochrome c-oxidoreductase (flavocytochrome b(2), FC b(2)) has absolute specificity for l-lactate, yet is non-selective with respect to its electron acceptor. These properties allow us to consider the enzyme as a potential candidate for chromate reduction by living cells in the presence of l-lactate. A recombinant strain of thermotolerant, methylotrophic yeast Hansenula polymorpha with sixfold increased FC b(2) enzyme activity (up to 3μmolmin(-1)mg(-1) protein in cell-free extract) compared to the parental strain was used for approval our suggestion. The recombinant cells, stored in dried state, as well as living yeast cells were tested for chromate-reducing activity in vitro in the presence of l-lactate (as an electron donor for chromate reduction) and different low molecular weight, redox-active mediators facilitating electron transfer from the reduced form of the enzyme to chromate (as a final electron acceptor): dichlorophenolindophenol (DCPIP), Methylene blue, Meldola blue, and Nile blue. It was shown that the highest chromate-reducing activity of the cells was achieved in the presence of DCPIP. The ability of chromate to catch electrons from the reduced flavocytochrome b(2) was confirmed using purified enzyme immobilized on the surface of a platinum electrode. The increasing concentration of Cr(VI) resulted in a decrease of enzyme-mediated current generated on the electrode during l-lactate oxidation. The shift and drop in amplitude of the peak in the cyclic voltammogram are indicative of Cr(VI)-dependent competition between reaction of chromate with reduced FC

  20. Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

    Directory of Open Access Journals (Sweden)

    Shepherd Trevor G

    2010-02-01

    Full Text Available Abstract Background Activation of bone morphogenetic protein (BMP4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, ALK3QD, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT and cell adhesion. Results Unexpectedly, doxycycline-induced ALK3QD expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced ALK3QD expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that ALK3QD-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of ALK3QD-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, ALK3QD signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and

  1. S-phenylpiracetam, a selective DAT inhibitor, reduces body weight gain without influencing locomotor activity.

    Science.gov (United States)

    Zvejniece, Liga; Svalbe, Baiba; Vavers, Edijs; Makrecka-Kuka, Marina; Makarova, Elina; Liepins, Vilnis; Kalvinsh, Ivars; Liepinsh, Edgars; Dambrova, Maija

    2017-09-01

    S-phenylpiracetam is an optical isomer of phenotropil, which is a clinically used nootropic drug that improves physical condition and cognition. Recently, it was shown that S-phenylpiracetam is a selective dopamine transporter (DAT) inhibitor that does not influence norepinephrine (NE) or serotonin (5-HT) receptors. The aim of the present study was to study the effects of S-phenylpiracetam treatment on body weight gain, blood glucose and leptin levels, and locomotor activity. Western diet (WD)-fed mice and obese Zucker rats were treated daily with peroral administration of S-phenylpiracetam for 8 and 12weeks, respectively. Weight gain and plasma metabolites reflecting glucose metabolism were measured. Locomotor activity was detected in an open-field test. S-phenylpiracetam treatment significantly decreased body weight gain and fat mass increase in the obese Zucker rats and in the WD-fed mice. In addition, S-phenylpiracetam reduced the plasma glucose and leptin concentration and lowered hyperglycemia in a glucose tolerance test in both the mice and the rats. S-phenylpiracetam did not influence locomotor activity in the obese Zucker rats or in the WD-fed mice. The results demonstrate that S-phenylpiracetam reduces body weight gain and improves adaptation to hyperglycemia without stimulating locomotor activity. Our findings suggest that selective DAT inhibitors, such as S-phenylpiracetam, could be potentially useful for treating obesity in patients with metabolic syndrome with fewer adverse health consequences compared to other anorectic agents. Copyright © 2017. Published by Elsevier Inc.

  2. Development of Reduced Activation Ferritic-Martensitic Steels in South Korea

    International Nuclear Information System (INIS)

    Chun, Y. B.; Choi, B. K.; Han, C. H.; Lee, D. W.; Cho, S.; Kim, T. K.; Jeong, Y. H.

    2012-01-01

    In the mid-1980s research programs for development of low activation materials began. This is based on the US Nuclear Regulatory Commission Guidelines (10CFR part 61) that were developed to reduce longlived radioactive isotopes, which allows nuclear reactor waste to be disposed of by shallow land burial when removed from service. Development of low activation materials is also key issue in nuclear fusion systems, as the structural components can became radioactive due to nuclear transmutation caused by exposure to high dose neutron irradiation. Reduced-activation ferritic martensitic (RAFM) steels have been developed in the leading countries in nuclear fusion technology, and are now being considered as candidate structural material for the test blanket module (TBM) in the international thermonuclear experiment reactor (ITER). South Korea joined the ITER program in 2003 and since then extensive effort has been made for developing the helium-cooled solid-breeder (HCSB) TBM which is scheduled to be tested in the ITER program. However, there has been no research activity to develop RAFM steels in South Korea, while all the participants in the ITER program have developed their own RAFM steels. It is recently that the Korea Atomic Energy Research Institute (KAERI) started the Korean RAFM steel research program, aiming at an application for the HCSB-type TBM structure in ITER. In what follows, the current status of RAFM steels and the R and D program led by KAERI to develop Korean RAFM steels are summarized

  3. Fraction From Lycium barbarum Polysaccharides Reduces Immunotoxicity and Enhances Antitumor Activity of Doxorubicin in Mice.

    Science.gov (United States)

    Deng, Xiangliang; Luo, Shuang; Luo, Xia; Hu, Minghua; Ma, Fangli; Wang, Yuanyuan; Zhou, Lian; Huang, Rongrong

    2018-01-01

    The aim of the present study was to investigate whether fraction from Lycium barbarum polysaccharide (LBP) could reduce immunotoxicity and enhance antitumor activity of doxorubicin (Dox) in mice. A water-soluble LBP fraction, designated LBP3, was isolated from edible Chinese herbal Lycium barbarum and used in this study. To investigate the effect of LBP3 on Dox-induced immunotoxicity, tumor-free mice were used and treated with either normal saline, Dox, or Dox plus LBP3. To investigate the effect of LBP3 on antitumor activity of Dox, H22 tumor-bearing mice were used and treated with either normal saline, Dox, LBP3, or Dox plus LBP3. The results showed that LBP3 did not protect against the body weight loss caused by Dox, but it promoted the recovery of body weight starting at day 5 after Dox treatment in tumor-free mice. LBP3 also improved peripheral blood lymphocyte counts, promoted cell cycle recovery in bone marrow cells, and restored the cytotoxicity of natural killer cells. Furthermore, in H22 tumor-bearing mice, LBP3 enhanced antitumor activity of Dox and improved peripheral blood lymphocyte counts and the cytotoxicity of splenocytes. In brief, our results demonstrated that LBP3 could reduce the immunotoxicity and enhance antitumor activity of Dox.

  4. Ebselen reduces autophagic activation and cell death in the ipsilateral thalamus following focal cerebral infarction.

    Science.gov (United States)

    Li, Yiliang; Zhang, Jian; Chen, Li; Xing, Shihui; Li, Jingjing; Zhang, Yusheng; Li, Chuo; Pei, Zhong; Zeng, Jinsheng

    2015-07-23

    Previous studies have demonstrated that both oxidative stress and autophagy play important roles in secondary neuronal degeneration in the ipsilateral thalamus after distal middle cerebral artery occlusion (MCAO). This study aimed to investigate whether oxidative stress is associated with autophagy activation within the ipsilateral thalamus after distal MCAO. Sixty stroke-prone renovascular hypertensive rats were subjected to distal MCAO or sham operation, and were killed at 14 days after MCAO. Mn-SOD, LC3-II, Beclin-1 and p62 expression were evaluated by immunostaining and immunoblotting. Secondary damage in the thalamus was assessed with Nissl staining and immunostaining. The association of oxidative stress with autophagy activation was investigated by the antioxidant, ebselen. We found that treatment with ebselen at 24h after MCAO significantly reduced the expression of Mn-SOD in the ipsilateral thalamus at 14 days following focal cerebral infarction. In parallel, it prevented the elevation of LC3-II and Beclin-1, and the reduction of p62. Furthermore, ebselen attenuated the neuronal loss and gliosis in the ipsilateral thalamus. These results suggested that ebselen reduced oxidative stress, autophagy activation and secondary damage in the ipsilateral thalamus following MCAO. There are associations between oxidative stress, autophagy activation and secondary damage in the thalamus after MCAO. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

    Science.gov (United States)

    Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

    2007-09-15

    Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

  6. Reduced graphene oxide is not a universal promoter for photocatalytic activities of TiO2

    Directory of Open Access Journals (Sweden)

    Hui Ling Tan

    2017-03-01

    Full Text Available Addition of reduced graphene oxide (RGO to P25 TiO2 was made and its impacts on photocatalytic oxidation of various organic substances were studied. Although the presence of RGO in TiO2 can enhance certain TiO2-based photocatalytic reactions, it is not a universal observation that can be expected in all types of organic substances. The factor of photocatalytic activity enhancement is strongly affected by the various functional groups appeared in the organic substances. In this work, it is realised that the length of alkyl chain in alcohols and carboxylic acids have the minimum influence on the overall activity while the number of hydroxyl groups can promote the further activity enhancement in the presence of RGO.

  7. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

    Science.gov (United States)

    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions. © 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  8. Amylin receptor activation in the ventral tegmental area reduces motivated ingestive behavior.

    Science.gov (United States)

    Mietlicki-Baase, Elizabeth G; McGrath, Lauren E; Koch-Laskowski, Kieran; Krawczyk, Joanna; Reiner, David J; Pham, Tram; Nguyen, Chan Tran N; Turner, Christopher A; Olivos, Diana R; Wimmer, Mathieu E; Schmidt, Heath D; Hayes, Matthew R

    2017-09-01

    Amylin is produced in the pancreas and the brain, and acts centrally to reduce feeding and body weight. Recent data show that amylin can act in the ventral tegmental area (VTA) to reduce palatable food intake and promote negative energy balance, but the behavioral mechanisms by which these effects occur are not fully understood. The ability of VTA amylin signaling to reduce intake of specific palatable macronutrients (fat or carbohydrate) was tested in rats in several paradigms, including one-bottle acceptance tests, two-bottle choice tests, and a free-choice diet. Data show that VTA amylin receptor activation with the amylin receptor agonist salmon calcitonin (sCT) preferentially and potently reduces intake of fat, with more variable suppression of sucrose intake. Intake of a non-nutritive sweetener is also decreased by intra-VTA administration of sCT. As several feeding-related signals that act in the mesolimbic system also impact motivated behaviors besides feeding, we tested the hypothesis that the suppressive effects of amylin signaling in the VTA extend to other motivationally relevant stimuli. Results show that intra-VTA sCT reduces water intake in response to central administration of the dipsogenic peptide angiotensin II, but has no effect on ad libitum water intake in the absence of food. Importantly, open field and social interaction studies show that VTA amylin signaling does not produce anxiety-like behaviors. Collectively, these findings reveal a novel ability of VTA amylin receptor activation to alter palatable macronutrient intake, and also demonstrate a broader role of VTA amylin signaling for the control of motivated ingestive behaviors beyond feeding. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Subjective Word-Finding Difficulty Reduces Engagement in Social Leisure Activities in Alzheimer’s Disease

    Science.gov (United States)

    Farrell, Meagan T.; Zahodne, Laura B.; Stern, Yaakov; Dorrejo, Jhedy; Yeung, Philip; Cosentino, Stephanie

    2014-01-01

    Objectives To assess the influence of subjective word-finding difficulty on Alzheimer’s disease (AD) patients’ likelihood of engaging in social leisure activities. Design Analysis of data collected from the second cohort of the Multicenter Study of Predictors of Disease Course in Alzheimer’s disease. Setting Four study sites in the U.S. and France. Participants Individuals diagnosed with mild to moderate AD (N = 236) Measurements On separate questionnaires, patients were asked to 1) report whether had trouble finding the right word when speaking (subjective word-finding difficulty), and 2) rate their frequency and enjoyment of both social and nonsocial leisure activities. Objective language measures included object naming and verbal fluency. Measures of dependence, depression, cognitive status, age, sex, and education were also included as covariates in regression analyses. Results Over half (52%) of the sample reported word-finding difficulty, and subjective complaints were correlated with poorer verbal fluency scores. Subjective word-finding difficulty was uniquely related to social activity measures. Endorsers of word-finding difficulty reported reduced frequency and enjoyment of social leisure activities, controlling for covariates. In contrast, engagement in nonsocial activities was associated with higher age and depression scores, but was not related to word-finding complaints. These results were corroborated by the caregivers’ reports, and occurred above and beyond the effect of objective word-finding ability. Conclusion AD patients who are aware of increasing word-finding failures are less likely to participate in and enjoy socially-oriented leisure activities. This finding may have significant implications for clinical and health outcomes in AD. A failure to evaluate subjective language complaints could result in social withdrawal symptoms, thereby threatening the patient’s quality of life as well as increasing caregiver burden. Importantly

  10. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb

    Directory of Open Access Journals (Sweden)

    Jeffrey E Dahlen

    2011-05-01

    Full Text Available Adult born neurons are added to the olfactory bulb (OB throughout life in rodents. While many factors have been identified as regulating the survival and integration of adult-born neurons (ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic (siRNA knock down of voltage gated sodium channels NaV1.1-1.3 and circuit level (naris occlusion reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock down or naris occlusion. In siRNA knock down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  11. Entecavir Exhibits Inhibitory Activity against Human Immunodeficiency Virus under Conditions of Reduced Viral Challenge▿

    Science.gov (United States)

    Lin, Pin-Fang; Nowicka-Sans, Beata; Terry, Brian; Zhang, Sharon; Wang, Chunfu; Fan, Li; Dicker, Ira; Gali, Volodymyr; Higley, Helen; Parkin, Neil; Tenney, Daniel; Krystal, Mark; Colonno, Richard

    2008-01-01

    Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients. PMID:18316521

  12. Intranasal oxytocin reduces social perception in women: Neural activation and individual variation.

    Science.gov (United States)

    Hecht, Erin E; Robins, Diana L; Gautam, Pritam; King, Tricia Z

    2017-02-15

    Most intranasal oxytocin research to date has been carried out in men, but recent studies indicate that females' responses can differ substantially from males'. This randomized, double-blind, placebo-controlled study involved an all-female sample of 28 women not using hormonal contraception. Participants viewed animations of geometric shapes depicting either random movement or social interactions such as playing, chasing, or fighting. Probe questions asked whether any shapes were "friends" or "not friends." Social videos were preceded by cues to attend to either social relationships or physical size changes. All subjects received intranasal placebo spray at scan 1. While the experimenter was not blinded to nasal spray contents at Scan 1, the participants were. Scan 2 followed a randomized, double-blind design. At scan 2, half received a second placebo dose while the other half received 24 IU of intranasal oxytocin. We measured neural responses to these animations at baseline, as well as the change in neural activity induced by oxytocin. Oxytocin reduced activation in early visual cortex and dorsal-stream motion processing regions for the social > size contrast, indicating reduced activity related to social attention. Oxytocin also reduced endorsements that shapes were "friends" or "not friends," and this significantly correlated with reduction in neural activation. Furthermore, participants who perceived fewer social relationships at baseline were more likely to show oxytocin-induced increases in a broad network of regions involved in social perception and social cognition, suggesting that lower social processing at baseline may predict more positive neural responses to oxytocin. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Inactivation of adipose angiotensinogen reduces adipose tissue macrophages and increases metabolic activity.

    Science.gov (United States)

    LeMieux, Monique J; Ramalingam, Latha; Mynatt, Randall L; Kalupahana, Nishan S; Kim, Jung Han; Moustaïd-Moussa, Naïma

    2016-02-01

    The adipose renin-angiotensin system (RAS) has been linked to obesity-induced inflammation, though mechanisms are not completely understood. In this study, adipose-specific angiotensinogen knockout mice (Agt-KO) were generated to determine whether Agt inactivation reduces inflammation and alters the metabolic profile of the Agt-KO mice compared to wild-type (WT) littermates. Adipose tissue-specific Agt-KO mice were created using the Cre-LoxP system with both Agt-KO and WT littermates fed either a low-fat or high-fat diet to assess metabolic changes. White adipose tissue was used for gene/protein expression analyses and WAT stromal vascular cells for metabolic extracellular flux assays. No significant differences were observed in body weight or fat mass between both genotypes on either diet. However, improved glucose clearance was observed in Agt-KO compared to WT littermates, consistent with higher expression of genes involved in insulin signaling, glucose transport, and fatty acid metabolism. Furthermore, Agt inactivation reduced total macrophage infiltration in Agt-KO mice fed both diets. Lastly, stroma vascular cells from Agt-KO mice revealed higher metabolic activity compared to WT mice. These findings indicate that adipose-specific Agt inactivation leads to reduced adipose inflammation and increased glucose tolerance mediated in part via increased metabolic activity of adipose cells. © 2015 The Obesity Society.

  14. Effect of Powdered Activated Carbon to Reduce Fouling in Membrane Bioreactors: A Sustainable Solution. Case Study

    Directory of Open Access Journals (Sweden)

    Giuseppe Mancini

    2013-04-01

    Full Text Available Membrane Bio Reactors (MBRs are mainly used for industrial wastewaters applications where their costs can be more easily afforded. High costs are basically due to energy consumption and membrane cleaning or replacement. Membrane fouling is responsible for reducing treated water production and increasing maintenance as well as operation costs. According to previous researches, the addition of Powdered Activated Carbon (PAC in high dosages could reduce membrane fouling; but such concentrations are economically unsustainable for operative conditions. A MBR pilot plant, fed by mixed liquor of a full-scale activated sludge process from a municipal wastewater treatment plant, was operated dosing low PAC concentrations (0, 2, 5, 10 and 20 mg·L−1, respectively. Experiments were also carried out at two different temperatures corresponding to summer and winter conditions. Results indicated that PAC addition was effective at the low dosages (2 and 5 mg·L−1 by reducing the permeate flux loss (from 16 up to 27%, respectively while higher PAC concentrations turns out in a useless cost increase.

  15. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    Science.gov (United States)

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events. © 2016 John Wiley & Sons Ltd.

  16. Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status

    International Nuclear Information System (INIS)

    Ma, Huiyan; Xu, Xinxin; Ursin, Giske; Simon, Michael S; Marchbanks, Polly A; Malone, Kathleen E; Lu, Yani; McDonald, Jill A; Folger, Suzanne G; Weiss, Linda K; Sullivan-Halley, Jane; Deapen, Dennis M; Press, Michael F; Bernstein, Leslie

    2015-01-01

    Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women’s Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2−) subtypes (both P trend ≤ 0.04), but not with other subtypes (all P trend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2–breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all P trend ≤ 0.06). The test for homogeneity of trends (HER2– vs. HER2+) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (P homogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts

  17. Activation of CO2-reducing methanogens in oil reservoir after addition of nutrient.

    Science.gov (United States)

    Yang, Guang-Chao; Zhou, Lei; Mbadinga, Serge Maurice; You, Jing; Yang, Hua-Zhen; Liu, Jin-Feng; Yang, Shi-Zhong; Gu, Ji-Dong; Mu, Bo-Zhong

    2016-12-01

    Nutrient addition as part of microbial enhanced oil recovery (MEOR) operations have important implications for more energy recovery from oil reservoirs, but very little is known about the in situ response of microorganisms after intervention. An analysis of two genes as biomarkers, mcrA encoding the key enzyme in methanogenesis and fthfs encoding the key enzyme in acetogenesis, was conducted during nutrient addition in oil reservoir. Clone library data showed that dominant mcrA sequences changed from acetoclastic (Methanosaetaceae) to CO 2 -reducing methanogens (Methanomicrobiales and Methanobacteriales), and the authentic acetogens affiliated to Firmicutes decreased after the intervention. Principal coordinates analysis (PCoA) and Jackknife environment clusters revealed evidence on the shift of the microbial community structure among the samples. Quantitative analysis of methanogens via qPCR showed that Methanobacteriales and Methanomicrobiales increased after nutrient addition, while acetoclastic methanogens (Methanosaetaceae) changed slightly. Nutrient treatment activated native CO 2 -reducing methanogens in oil reservoir. The high frequency of Methanobacteriales and Methanomicrobiales (CO 2 -reducers) after nutrient addition in this petroleum system suggested that CO 2 -reducing methanogenesis was involved in methane production. The nutrient addition could promote the methane production. The results will likely improve strategies of utilizing microorganisms in subsurface environments. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  18. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

    Directory of Open Access Journals (Sweden)

    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  19. A practical cooling strategy for reducing the physiological strain associated with firefighting activity in the heat.

    Science.gov (United States)

    Barr, D; Gregson, W; Sutton, L; Reilly, T

    2009-04-01

    The aim of this study was to establish whether a practical cooling strategy reduces the physiological strain during simulated firefighting activity in the heat. On two separate occasions under high ambient temperatures (49.6 +/- 1.8 degrees C, relative humidity (RH) 13 +/- 2%), nine male firefighters wearing protective clothing completed two 20-min bouts of treadmill walking (5 km/h, 7.5% gradient) separated by a 15-min recovery period, during which firefighters were either cooled (cool) via application of an ice vest and hand and forearm water immersion ( approximately 19 degrees C) or remained seated without cooling (control). There was no significant difference between trials in any of the dependent variables during the first bout of exercise. Core body temperature (37.72 +/- 0.34 vs. 38.21 +/- 0.17 degrees C), heart rate (HR) (81 +/- 9 vs. 96 +/- 17 beats/min) and mean skin temperature (31.22 +/- 1.04 degrees C vs. 33.31 +/- 1 degrees C) were significantly lower following the recovery period in cool compared with control (p second bout of activity in cool compared to control. Mean skin temperature, HR and thermal sensation were significantly lower during bout 2 in cool compared with control (p < 0.05). It is concluded that this practical cooling strategy is effective at reducing the physiological strain associated with demanding firefighting activity under high ambient temperatures.

  20. Butyrate reduces appetite and activates brown adipose tissue via the gut-brain neural circuit.

    Science.gov (United States)

    Li, Zhuang; Yi, Chun-Xia; Katiraei, Saeed; Kooijman, Sander; Zhou, Enchen; Chung, Chih Kit; Gao, Yuanqing; van den Heuvel, José K; Meijer, Onno C; Berbée, Jimmy F P; Heijink, Marieke; Giera, Martin; Willems van Dijk, Ko; Groen, Albert K; Rensen, Patrick C N; Wang, Yanan

    2017-11-03

    Butyrate exerts metabolic benefits in mice and humans, the underlying mechanisms being still unclear. We aimed to investigate the effect of butyrate on appetite and energy expenditure, and to what extent these two components contribute to the beneficial metabolic effects of butyrate. Acute effects of butyrate on appetite and its method of action were investigated in mice following an intragastric gavage or intravenous injection of butyrate. To study the contribution of satiety to the metabolic benefits of butyrate, mice were fed a high-fat diet with butyrate, and an additional pair-fed group was included. Mechanistic involvement of the gut-brain neural circuit was investigated in vagotomised mice. Acute oral, but not intravenous, butyrate administration decreased food intake, suppressed the activity of orexigenic neurons that express neuropeptide Y in the hypothalamus, and decreased neuronal activity within the nucleus tractus solitarius and dorsal vagal complex in the brainstem. Chronic butyrate supplementation prevented diet-induced obesity, hyperinsulinaemia, hypertriglyceridaemia and hepatic steatosis, largely attributed to a reduction in food intake. Butyrate also modestly promoted fat oxidation and activated brown adipose tissue (BAT), evident from increased utilisation of plasma triglyceride-derived fatty acids. This effect was not due to the reduced food intake, but explained by an increased sympathetic outflow to BAT. Subdiaphragmatic vagotomy abolished the effects of butyrate on food intake as well as the stimulation of metabolic activity in BAT. Butyrate acts on the gut-brain neural circuit to improve energy metabolism via reducing energy intake and enhancing fat oxidation by activating BAT. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

    Directory of Open Access Journals (Sweden)

    Igor O. Shmarakov

    2014-10-01

    Full Text Available Aiming to reduce the potential in vivo hepato-and nephrotoxicity of Ag/Au bimetallic nanoparticles (NPs stabilized by sodium dodecyl sulphate (SDS, an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp as a reducing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5–15 nm sized were able to form stable aggregates with an average size of 370–450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical parameters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

  2. Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans

    DEFF Research Database (Denmark)

    Rasmussen, Peter; Nielsen, Jannie; Overgaard, M

    2010-01-01

    Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate to th...... indicating that reduced cerebral oxygenation may play a role in the development of central fatigue and may be an exercise capacity limiting factor.......Maximal exercise may be limited by central fatigue defined as an inability of the central nervous system to fully recruit the involved muscles. This study evaluated whether a reduction in the cerebral oxygen-to-carbohydrate index (OCI) and in the cerebral mitochondrial oxygen tension relate...... of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia (0.10) reduced...

  3. Recent results of the reduced activation ferritic/martensitic steel development

    Energy Technology Data Exchange (ETDEWEB)

    Jitsukawa, S. E-mail: jitsukawa@ifmif.tokai.jaeri.go.jp; Kimura, A.; Kohyama, A.; Klueh, R.L.; Tavassoli, A.A.; Schaaf, B. van der; Odette, G.R.; Rensman, J.W.; Victoria, M.; Petersen, C

    2004-08-01

    Significant progress has been achieved in the international research effort on reduced-activation steels. Extensive tensile, fracture toughness, fatigue, and creep properties in unirradiated and irradiated conditions have been performed and evaluated. Since it is not possible to include all work in this limited review, selected areas will be presented to indicate the scope and progress of recent international efforts. These include (1) results from mechanical properties studies that have been combined in databases to determine materials design limits for the preliminary design of an ITER blanket module. (2) Results indicate that the effect of transmutation-produced helium on fracture toughness is smaller than indicated previously. (3) Further efforts to reduce irradiation-induced degradation of fracture toughness. (4) The introduction of a post-irradiation constitutive equation for plastic deformation. (5) The production of ODS steels that have been used to improve high-temperature strength. (6) The method developed to improve fracture toughness of ODS steels.

  4. Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients

    International Nuclear Information System (INIS)

    Takahashi-Niki, Kazuko; Niki, Takeshi; Taira, Takahiro; Iguchi-Ariga, Sanae M.M.; Ariga, Hiroyoshi

    2004-01-01

    DJ-1 is a multi-functional protein that plays roles in transcriptional regulation and anti-oxidative stress, and loss of its function is thought to result in onset of Parkinson's disease. We have previously reported that L166P, a mutant DJ-1 found in Parkinson's disease patients, had no activity to prevent hydrogen peroxide (H 2 O 2 )-induced cell death. In this study, we analyzed other mutants of DJ-1 found in Parkinson's disease patients, including M26I, R98Q, and D149A, as well as L166P. We first found that all of the mutants made heterodimers with wild-type DJ-1, while all of the mutants except for L166P made homodimers. We then found that M26I and L166P, both of which are derived from homozygous mutations of the DJ-1 gene, were unstable and that their stabilities were recovered, in part, in the presence of proteasome inhibitor, MG132. NIH3T3 cell lines stably expressing these mutants of DJ-1 showed that cell lines of L166P and C106S, a mutant for protease activity (-) of DJ-1, had no activity to scavenge even endogenously producing reactive oxygen species. These cell lines also showed that all of the mutants had reduced activities to eliminate exogenously added H 2 O 2 and that these activities, except for that of D149A, were parallel to those preventing H 2 O 2 -induced cell death

  5. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    International Nuclear Information System (INIS)

    Liu, Xin-Hua; Yao, Shen; Qiao, Rui-Fang; Levine, Alice C.; Kirschenbaum, Alexander; Pan, Jiangping; Wu, Yong; Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.

    2011-01-01

    Highlights: → Nerve transection increased Notch signaling in paralyzed muscle. → Nandrolone prevented denervation-induced Notch signaling. → Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. → Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  6. Reduced activation in ventral striatum and ventral tegmental area during probabilistic decision-making in schizophrenia.

    Science.gov (United States)

    Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Esslinger, Christine; Schilling, Claudia; Schirmbeck, Frederike; Englisch, Susanne; Meyer-Lindenberg, Andreas; Kirsch, Peter; Zink, Mathias

    2014-07-01

    Patients with schizophrenia suffer from deficits in monitoring and controlling their own thoughts. Within these so-called metacognitive impairments, alterations in probabilistic reasoning might be one cognitive phenomenon disposing to delusions. However, so far little is known about alterations in associated brain functionality. A previously established task for functional magnetic resonance imaging (fMRI), which requires a probabilistic decision after a variable amount of stimuli, was applied to 23 schizophrenia patients and 28 healthy controls matched for age, gender and educational levels. We compared activation patterns during decision-making under conditions of certainty versus uncertainty and evaluated the process of final decision-making in ventral striatum (VS) and ventral tegmental area (VTA). We replicated a pre-described extended cortical activation pattern during probabilistic reasoning. During final decision-making, activations in several fronto- and parietocortical areas, as well as in VS and VTA became apparent. In both of these regions schizophrenia patients showed a significantly reduced activation. These results further define the network underlying probabilistic decision-making. The observed hypo-activation in regions commonly associated with dopaminergic neurotransmission fits into current concepts of disrupted prediction error signaling in schizophrenia and suggests functional links to reward anticipation. Forthcoming studies with patients at risk for psychosis and drug-naive first episode patients are necessary to elucidate the development of these findings over time and the interplay with associated clinical symptoms. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  8. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  9. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  10. Cocoa consumption reduces NF-κB activation in peripheral blood mononuclear cells in humans.

    Science.gov (United States)

    Vázquez-Agell, M; Urpi-Sarda, M; Sacanella, E; Camino-López, S; Chiva-Blanch, G; Llorente-Cortés, V; Tobias, E; Roura, E; Andres-Lacueva, C; Lamuela-Raventós, R M; Badimon, L; Estruch, R

    2013-03-01

    Epidemiological studies have demonstrated an association between high-polyphenol intake and reduced incidence of atherosclerosis. The healthy effects of cocoa-polyphenols may be due to their antioxidant and anti-inflammatory actions, although the exact mechanisms are unknown and depend on the matrix in which cocoa-polyphenols are delivered. Nuclear factor κB (NF-κB) is a key molecule in the pathophysiology of atherosclerosis involved in the regulation of adhesion molecules(AM) and cytokine expression and its activation is the first step in triggering the inflammatory process. The aim of this study was to evaluate the effect of acute cocoa consumption in different matrices related to the bioavailability of cocoa-polyphenols in NF-κB activation and the expression of AM. Eighteen healthy volunteers randomly received 3 interventions: 40g of cocoa powder with milk (CM), with water (CW), and only milk (M). NF-κB activation in leukocytes and AM (sICAM, sVCAM, E-selectin) were measured before and 6h after each intervention. Consumption of CW significantly decreased NF-κB activation compared to baseline and to CM (P cocoa intake may depend on the bioavailability of bioactive compounds and may be mediated at least in part by the modulation of NF-κB activation and downstream molecules reinforcing the link between cocoa intake and health. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Light pollution reduces activity, food consumption and growth rates in a sandy beach invertebrate.

    Science.gov (United States)

    Luarte, T; Bonta, C C; Silva-Rodriguez, E A; Quijón, P A; Miranda, C; Farias, A A; Duarte, C

    2016-11-01

    The continued growth of human activity and infrastructure has translated into a widespread increase in light pollution. Natural daylight and moonlight cycles play a fundamental role for many organisms and ecological processes, so an increase in light pollution may have profound effects on communities and ecosystem services. Studies assessing ecological light pollution (ELP) effects on sandy beach organisms have lagged behind the study of other sources of disturbance. Hence, we assessed the influence of this stressor on locomotor activity, foraging behavior, absorption efficiency and growth rate of adults of the talitrid amphipod Orchestoidea tuberculata. In the field, an artificial light system was assembled to assess the local influence of artificial light conditions on the amphipod's locomotor activity and use of food patches in comparison to natural (ambient) conditions. Meanwhile in the laboratory, two experimental chambers were set to assess amphipod locomotor activity, consumption rates, absorption efficiency and growth under artificial light in comparison to natural light-dark cycles. Our results indicate that artificial light have significantly adverse effects on the activity patterns and foraging behavior of the amphipods, resulting on reduced consumption and growth rates. Given the steady increase in artificial light pollution here and elsewhere, sandy beach communities could be negatively affected, with unexpected consequences for the whole ecosystem. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Intracellular zinc activates KCNQ channels by reducing their dependence on phosphatidylinositol 4,5-bisphosphate.

    Science.gov (United States)

    Gao, Haixia; Boillat, Aurélien; Huang, Dongyang; Liang, Ce; Peers, Chris; Gamper, Nikita

    2017-08-01

    M-type (Kv7, KCNQ) potassium channels are proteins that control the excitability of neurons and muscle cells. Many physiological and pathological mechanisms of excitation operate via the suppression of M channel activity or expression. Conversely, pharmacological augmentation of M channel activity is a recognized strategy for the treatment of hyperexcitability disorders such as pain and epilepsy. However, physiological mechanisms resulting in M channel potentiation are rare. Here we report that intracellular free zinc directly and reversibly augments the activity of recombinant and native M channels. This effect is mechanistically distinct from the known redox-dependent KCNQ channel potentiation. Interestingly, the effect of zinc cannot be attributed to a single histidine- or cysteine-containing zinc-binding site within KCNQ channels. Instead, zinc dramatically reduces KCNQ channel dependence on its obligatory physiological activator, phosphatidylinositol 4,5-bisphosphate (PIP 2 ). We hypothesize that zinc facilitates interactions of the lipid-facing interface of a KCNQ protein with the inner leaflet of the plasma membrane in a way similar to that promoted by PIP 2 Because zinc is increasingly recognized as a ubiquitous intracellular second messenger, this discovery might represent a hitherto unknown native pathway of M channel modulation and provide a fresh strategy for the design of M channel activators for therapeutic purposes.

  13. Technical issues of fabrication technologies of reduced activation ferritic/martensitic steels

    International Nuclear Information System (INIS)

    Tanigawa, Hiroyasu; Sakasegawa, Hideo; Hirose, Takanori

    2013-01-01

    Highlights: • The key technical issues of RAFM steel fabrication are the control of Ta, and deoxidation of the steel with a limited amount of Al addition. • Addition of Ta with poor deoxidation might results in the agglomeration of inclusions at 1/2t position. • ESR was proved to be effective removing Ta oxide inclusions and avoiding agglomeration of inclusions at 1/2t position, and achieving low oxygen concentration. -- Abstract: The key issue for DEMO application is that Reduced activation ferritic/martensitic (RAFM) steels fabrication technologies has to be highly assured, especially with respect to high availability, reliability and reduced activation capability on the DEMO level fabrication, which requires not a few tons but thousand tons RAFM fabrication. One of the key technical issues of RAFM fabrication is the control of Ta, and deoxidation of the steel with a limited amount of Al addition. The series of F82H (Fe–8Cr–2W–V, Ta) melting revealed that Ta have tendency to form oxide on melting process, and this will have large impact on reliability of the steels. Al is also the key elements, as it is commonly used for deoxidation of steels, and achieving lower oxygen level is essential to obtain good mechanical properties, but the maximum concentration of Al is limited in view of reduced activation capability. These tendency and limitation resulted in the Ta oxide agglomeration in the middle of plate, but the remelting process, ESR (electro slag remelting), was found to be successful on removing those Ta oxides

  14. Reducing the decline in physical activity during pregnancy: a systematic review of behaviour change interventions.

    Directory of Open Access Journals (Sweden)

    Sinead Currie

    Full Text Available PURPOSE: Physical activity (PA typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. SEARCH AND REVIEW METHODOLOGY: Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. FINDINGS: A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n = 6, structured exercise (n = 6 and education (n = 2. Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. CONCLUSIONS AND IMPLICATIONS: Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy

  15. Anethole potentiates dodecanol's fungicidal activity by reducing PDR5 expression in budding yeast.

    Science.gov (United States)

    Fujita, Ken-Ichi; Ishikura, Takayuki; Jono, Yui; Yamaguchi, Yoshihiro; Ogita, Akira; Kubo, Isao; Tanaka, Toshio

    2017-02-01

    trans-Anethole (anethole), a major component of anise oil, has a broad antimicrobial spectrum and a weaker antimicrobial potency than other available antibiotics. When combined with polygodial, nagilactone E, and n-dodecanol, anethole has been shown to exhibit synergistic antifungal activity against a budding yeast, Saccharomyces cerevisiae, and a human opportunistic pathogenic yeast, Candida albicans. However, the mechanism underlying this synergistic effect of anethole has not been characterized. We studied this mechanism using dodecanol-treated S. cerevisiae cells and focusing on genes related to multidrug efflux. Although dodecanol transiently reduced the number of colony forming units, this recovered to levels similar to those of untreated cells with continued incubation beyond 24h. Reverse transcription polymerase chain reaction analysis revealed overexpression of an ATP-binding cassette (ABC) transporter gene, PDR5, in addition to a slight increase in PDR11, PDR12, and PDR15 transcriptions in dodecanol-treated cells. In the presence of anethole, these effects were attenuated and the fungicidal activity of dodecanol was extended. Dodecanol showed longer lasting fungicidal activity against a Δpdr5. In addition, Δpdr3 and Δlge1, lack transcription factors of PDR5 and PDR3, were partly and completely susceptible to dodecanol, respectively. Furthermore, combination of anethole with fluconazole was also found to exhibit synergy on C. albicans. These results indicated that although anethole reduced the transcription of several transporters, PDR5 expression was particularly relevant to dodecanol efflux. Anethole is expected to be a promising candidate drug for the inhibition of efflux by reducing the transcription of several ABC transporters. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    Science.gov (United States)

    DeSmet, Marsha L; Fleet, James C

    2017-10-01

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH) 2 D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH) 2 D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH) 2 D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH) 2 D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Addition of selenium nanoparticles to electrospun silk scaffolds improves mammalian cell activity while reducing bacterial growth

    Directory of Open Access Journals (Sweden)

    Stanley Chung

    2016-07-01

    Full Text Available Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas compared to non-electrospun equivalents. However, purified silk promotes microbial growth. In contrast, selenium nanoparticles have excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics.

  18. Report of IEA workshop on reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    IEA Workshop on Reduced Activation Ferritic/Martensitic Steels under implementing agreement for program of research and development on fusion materials was held at Tokyo Yayoi Kaikan and JAERI headquarter on November 2-3, 2000. The objective of this workshop was a review of the fusion material development programs, the progress of the collaboration and the irradiation effects studies on RAF/M steels in the collaborating parties (Europe, Russia the United States, and Japan). Moreover, the development of plans for future collaboration was discussed. The present report contains viewgraphs presented at the workshop. (author)

  19. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

    Science.gov (United States)

    Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

    2016-10-15

    A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16 + monocytes with a poor activation profile. In survivors, CD16 + monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  20. Mechanical characterization of a reduced activation 9 Cr ferritic/martensitic steel of spanish production

    International Nuclear Information System (INIS)

    Rodriguez, D.; Serrano, M.

    2012-01-01

    This paper shows the first results concerning the characterization of two heats of a reduced activation 9 Cr ferritic/martensitic steel (RAFM) made in Spain, called AF1B and AF2A. The results of this characterization are compared with their European counterparts, EUROFER97-2, which was chosen as reference material. All activities described were performed in the Structural Materials Unit of CIEMAT, within the national project TECNO-FUS CONSOLIDER INGENIO.The two Spanish heats have the same production process and heat treatment. Both heats have a similar tensile behaviour similar to EUROFER97-2, but on the other hand impact properties are lower. The microstructure of AF1B reveals large biphasic inclusions that affecting its mechanical properties, especially the impact properties. AF2A casting was free of these inclusions. (Author) 24 refs.

  1. Gardening as a potential activity to reduce falls in older adults.

    Science.gov (United States)

    Chen, Tuo-Yu; Janke, Megan C

    2012-01-01

    This study examines whether participation in gardening predicts reduced fall risk and performance on balance and gait-speed measures in older adults. Data on adults age 65 and older (N = 3,237) from the Health and Retirement Study and Consumption and Activities Mail Survey were analyzed. Participants who spent 1 hr or more gardening in the past week were defined as gardeners, resulting in a total of 1,585 gardeners and 1,652 nongardeners. Independent t tests, chi square, and regression analyses were conducted to examine the relationship between gardening and health outcomes. Findings indicate that gardeners reported significantly better balance and gait speed and had fewer chronic conditions and functional limitations than nongardeners. Significantly fewer gardeners than nongardeners reported a fall in the past 2 yr. The findings suggest that gardening may be a potential activity to incorporate into future fall-prevention programs.

  2. Reduced-activation materials for fusion reactors: An overview of the proceedings

    International Nuclear Information System (INIS)

    Klueh, R.L.; Packan, N.H.; Gelles, D.S.; Okada, M.

    1988-01-01

    Some of the most serious safety and environmental concerns for future fusion reactors involve induced radioactivity in the first wall and blanket structures. One problem caused by the induced radioactivity in a reactor constructed from the conventional austenitic and ferritic steels presently being considered as structural materials would be the disposal of the highly radioactive structures after their service lifetimes. To simplify the waste-disposal process, ''low-activation'' or ''reduced-activation'' alloys are being developed. The objective for such materials is that they qualify for shallow land burial, as opposed to the much more expensive deep geologic disposal. This paper reviews these classes of materials for this purpose: austenitic stainless steels, ferritic steels, and vanadium alloys

  3. Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa.

    Science.gov (United States)

    Gurunathan, Sangiliyandi; Han, Jae Woong; Dayem, Ahmed Abdal; Eppakayala, Vasuki; Kim, Jin-Hoi

    2012-01-01

    Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO) and reduced graphene oxide (rGO) in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME), for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared. The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation. Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of cell viability, induced oxidative stress, and DNA fragmentation. The antibacterial activities of GO and rGO against P. aeruginosa were compared. The loss of P. aeruginosa viability increased in a dose- and

  4. Industry consequences of reduced petroleum activity; Naeringsmessige konsekvenser av redusert petroleumsaktivitet

    Energy Technology Data Exchange (ETDEWEB)

    2010-10-22

    Norwegian oil production is falling. Top of the petroleum production was reached in 2004, and in line with forecasts from the Norwegian Petroleum Directorate and Econ Poeyry (2009), we anticipate a continued decline in production towards an end around 2080. Petroleum industries accounted for about a quarter of Norwegian value creation in 2008. The industries provide strong growth impetus to the Norwegian economy through investments in new fields and operation of existing ones. The petroleum activity on the Norwegian shelf add to our estimates, the basis for about 90 000 jobs in the petroleum industry and the supplier industry. The prescribed reduction in Norwegian petroleum activities will naturally reduce petroleum-related employment. We calculate in this report the effect of a reduction in the petroleum activity with regard to employment. The calculations show a strong decline in employment in the period 2025-2080. In order to reduce the effects of the fall, the Norwegian authorities can open more areas for petroleum production. We show in this report the employment consequences of an opening of the areas off Lofoten, Vesteraalen and Senja may have for employment. To calculate the employment effects are based on an estimate of 2 billion barrels of oil equivalent (boe), and assuming that it made more commercial discoveries. This estimate lies between the updated estimate of Petroleum Directorate announced 16 April 2010 and the projection industry refers to. Our estimate of 2 billion barrels is based on continued technological advances that increase the recovery rate. Based on an estimate of 2 billion barrels, our calculations show that this can lay the basis for between 3000 and 8000 permanent jobs in the petroleum industry and supplier industry. We do not know today whether it is or how much petroleum resources in the areas concerned. If there is no commercial discoveries, employment effect will only be related to exploration activity. If however, there are more

  5. Spaced sessions of avoidance extinction reduce spontaneous recovery and promote infralimbic cortex activation.

    Science.gov (United States)

    Tapias-Espinosa, Carles; Kádár, Elisabet; Segura-Torres, Pilar

    2018-01-15

    Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA). We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex. The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. An isozyme of acid alpha-glucosidase with reduced catalytic activity for glycogen.

    Science.gov (United States)

    Beratis, N G; LaBadie, G U; Hirschhorn, K

    1980-03-01

    Both the common and a variant isozyme of acid alpha-glucosidase have been purified from a heterozygous placenta with CM-Sephadex, ammonium sulfate precipitation, dialysis, Amicon filtration, affinity chromatography by Sephadex G-100, and DEAE-cellulose chromatography. Three and two activity peaks, from the common and variant isozymes, respectively, were obtained by DEAE-cellulose chromatography using a linear NaCl gradient. The three peaks of activity of the common isozyme were eluted with 0.08, 0.12, and 0.17 M NaCl, whereas the two peaks of the variant, with 0.01 and 0.06 M NaCl. The pH optimum and thermal denaturation at 57 degrees C were the same in all enzyme peaks of both isozymes. Rabbit antiacid alpha-glucosidase antibodies produced against the common isozyme were found to cross-react with both peaks of the variant isozyme. The two isozymes shared antigenic identity and had similar Km's with maltose as substrate. Normal substrate saturation kinetics were observed with the common isozyme when glycogen was the substrate, but the variant produced an S-shaped saturation curve indicating a phase of negative and positive cooperativity at low and high glycogen concentrations, respectively. The activity of the variant was only 8.6% and 19.2% of the common isozyme when assayed with nonsaturating and saturating concentrations of glycogen, respectively. A similar rate of hydrolysis of isomaltose by both isozymes was found indicating that the reduced catalytic activity of the variant isozyme toward glycogen is not the result of a reduced ability of this enzyme to cleave the alpha-1,6 linkages of glycogen.

  7. Anomalous electrical signals associated with microbial activity: Results from Iron and Nitrate-Reducing Columns

    Science.gov (United States)

    Aaron, R. B.; Zheng, Q.; Flynn, P.; Singha, K.; Brantley, S.

    2008-12-01

    Three flow-through columns outfitted with Ag/AgCl electrodes were constructed to test the effects of different microbial processes on the geophysical measurements of self potential (SP), bulk electrical conductivity (σ b), and induced polarization (IP). The columns were filled with sieved, Fe-bearing subsurface sediment from the Delmarva Peninsula near Oyster, VA, inoculated (9:1 ratio) with a freshly-collected, shallow subsurface sediment from a wetland floodplain (Dorn Creek) near Madison, WI. Each of the columns was fed anoxic and sterile PIPES buffered artificial groundwater (PBAGW) containing different concentrations of acetate and nitrate. The medium fed to Column 1 (nitrate-reducing) was amended with 100 μM acetate and 2 mM nitrate. Column 2 (iron-reducing) was run with PBAGW containing 1.0 mM acetate and 0 mM nitrate. Column 3 (alternating redox state) was operated under conditions designed to alternately stimulate nitrate-reducing and iron-reducing populations to provide conditions, i.e., the presence of both nitrate and microbially-produced Fe(II), that would allow growth of nitrate-dependent Fe(II)-oxidizing populations. We operated Column 3 with a cycling strategy of 14-18 days of high C medium (1 mM acetate and 100 μ M nitrate) followed by 14-18 days of low C medium (100 μ M acetate and 2 mM nitrate). Effluent chemistry (NO3-, NO2-, NH4+, acetate, and Fe2+) was sampled daily for four months so as to be concurrent with the electrical measurements. We observed chemical evidence of iron reduction (dissolved [Fe(II)] = 0.2mM) in the effluent from the iron reduction and alternating redox columns. Chemical depletion of NO3- ([NO3-] ranged from 1 to 0.02mM), the production of NO2-, and possible production of NH4+ (0.2 mM) was observed in the nitrate reducing column as well as the alternating redox column. All three columns displayed loss of acetate as microbial activity progressed. σ b remained constant in the alternating redox column (~0.15 S

  8. Activation of KCNQ Channels Suppresses Spontaneous Activity in Dorsal Root Ganglion Neurons and Reduces Chronic Pain after Spinal Cord Injury.

    Science.gov (United States)

    Wu, Zizhen; Li, Lin; Xie, Fuhua; Du, Junhui; Zuo, Yan; Frost, Jeffrey A; Carlton, Susan M; Walters, Edgar T; Yang, Qing

    2017-03-15

    A majority of people who have sustained spinal cord injury (SCI) experience chronic pain after injury, and this pain is highly resistant to available treatments. Contusive SCI in rats at T10 results in hyperexcitability of primary sensory neurons, which contributes to chronic pain. KCNQ channels are widely expressed in nociceptive dorsal root ganglion (DRG) neurons, are important for controlling their excitability, and their activation has proven effective in reducing pain in peripheral nerve injury and inflammation models. The possibility that activators of KCNQ channels could be useful for treating SCI-induced chronic pain is strongly supported by the following findings. First, SCI, unlike peripheral nerve injury, failed to decrease the functional or biochemical expression of KCNQ channels in DRG as revealed by electrophysiology, real-time quantitative polymerase chain reaction, and Western blot; therefore, these channels remain available for pharmacological targeting of SCI pain. Second, treatment with retigabine, a specific KCNQ channel opener, profoundly decreased spontaneous activity in primary sensory neurons of SCI animals both in vitro and in vivo without changing the peripheral mechanical threshold. Third, retigabine reversed SCI-induced reflex hypersensitivity, adding to our previous demonstration that retigabine supports the conditioning of place preference after SCI (an operant measure of spontaneous pain). In contrast to SCI animals, naïve animals showed no effects of retigabine on reflex sensitivity or conditioned place preference by pairing with retigabine, indicating that a dose that blocks chronic pain-related behavior has no effect on normal pain sensitivity or motivational state. These results encourage the further exploration of U.S. Food and Drug Administration-approved KCNQ activators for treating SCI pain, as well as efforts to develop a new generation of KCNQ activators that lack central side effects.

  9. Reduced Frontal Activations at High Working Memory Load in Mild Cognitive Impairment: Near-Infrared Spectroscopy.

    Science.gov (United States)

    Yeung, Michael K; Sze, Sophia L; Woo, Jean; Kwok, Timothy; Shum, David H K; Yu, Ruby; Chan, Agnes S

    2016-01-01

    Some functional magnetic resonance imaging studies have reported altered activations in the frontal cortex during working memory (WM) performance in individuals with mild cognitive impairment (MCI), but the findings have been mixed. The objective of the present study was to utilize near-infrared spectroscopy (NIRS), an alternative imaging technique, to examine neural processing during WM performance in individuals with MCI. Twenty-six older adults with MCI (7 males; mean age 69.15 years) were compared with 26 age-, gender-, handedness-, and education-matched older adults with normal cognition (NC; 7 males; mean age 68.87 years). All of the participants undertook an n-back task with a low (i.e., 0-back) and a high (i.e., 2-back) WM load condition while their prefrontal dynamics were recorded by a 16-channel NIRS system. Although behavioral results showed that the two groups had comparable task performance, neuroimaging results showed that the MCI group, unlike the NC group, did not exhibit significantly increased frontal activations bilaterally when WM load increased. Compared to the NC group, the MCI group had similar frontal activations at low load (p > 0.05 on all channels) but reduced activations at high load (p load in individuals with MCI. © 2016 S. Karger AG, Basel.

  10. Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice.

    Directory of Open Access Journals (Sweden)

    André R A Marques

    Full Text Available The enzyme glucocerebrosidase (GBA hydrolyses glucosylceramide (GlcCer in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2. Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/- mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs, one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.

  11. Performance of an Active Micro Direct Methanol Fuel Cell Using Reduced Catalyst Loading MEAs

    Directory of Open Access Journals (Sweden)

    D.S. Falcão

    2017-10-01

    Full Text Available The micro direct methanol fuel cell (MicroDMFC is an emergent technology due to its special interest for portable applications. This work presents the results of a set of experiments conducted at room temperature using an active metallic MicroDMFC with an active area of 2.25 cm2. The MicroDMFC uses available commercial materials with low platinum content in order to reduce the overall fuel cell cost. The main goal of this work is to provide useful information to easily design an active MicroDMFC with a good performance recurring to cheaper commercial Membrane Electrode Assemblies MEAs. A performance/cost analysis for each MEA tested is provided. The maximum power output obtained was 18.1 mW/cm2 for a hot-pressed MEA with materials purchased from Quintech with very low catalyst loading (3 mg/cm2 Pt–Ru at anode side and 0.5 mg/cm2 PtB at the cathode side costing around 15 euros. Similar power values are reported in literature for the same type of micro fuel cells working at higher operating temperatures and substantially higher cathode catalyst loadings. Experimental studies using metallic active micro direct methanol fuel cells operating at room temperature are very scarce. The results presented in this work are, therefore, very useful for the scientific community.

  12. Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.

    Science.gov (United States)

    Delvendahl, Igor; Jablonski, Lukasz; Baade, Carolin; Matveev, Victor; Neher, Erwin; Hallermann, Stefan

    2015-06-09

    Fast synchronous neurotransmitter release at the presynaptic active zone is triggered by local Ca(2+) signals, which are confined in their spatiotemporal extent by endogenous Ca(2+) buffers. However, it remains elusive how rapid and reliable Ca(2+) signaling can be sustained during repetitive release. Here, we established quantitative two-photon Ca(2+) imaging in cerebellar mossy fiber boutons, which fire at exceptionally high rates. We show that endogenous fixed buffers have a surprisingly low Ca(2+)-binding ratio (∼ 15) and low affinity, whereas mobile buffers have high affinity. Experimentally constrained modeling revealed that the low endogenous buffering promotes fast clearance of Ca(2+) from the active zone during repetitive firing. Measuring Ca(2+) signals at different distances from active zones with ultra-high-resolution confirmed our model predictions. Our results lead to the concept that reduced Ca(2+) buffering enables fast active zone Ca(2+) signaling, suggesting that the strength of endogenous Ca(2+) buffering limits the rate of synchronous synaptic transmission.

  13. The Soul, as an Uninhibited Mental Activity, is Reduced into Consciousness by Rules of Quantum Physics.

    Science.gov (United States)

    Ceylan, Mehmet Emin; Dönmez, Aslıhan; Ünsalver, Barış Önen; Evrensel, Alper; Kaya Yertutanol, Fatma Duygu

    2017-12-01

    This paper is an effort to describe, in neuroscientific terms, one of the most ambiguous concepts of the universe-the soul. Previous efforts to understand what the soul is and where it may exist have accepted the soul as a subjective and individual entity. We will make two additions to this view: (1) The soul is a result of uninhibited mental activity and lacks spatial and temporal information; (2) The soul is an undivided whole and, to become divided, the soul has to be reduced into unconscious and conscious mental events. This reduction process parallels the maturation of the frontal cortex and GABA becoming the main inhibitory neurotransmitter. As examples of uninhibited mental activity, we will discuss the perceptual differences of a newborn, individuals undergoing dissociation, and individuals induced by psychedelic drugs. Then, we will explain the similarities between the structure of the universe and the structure of the brain, and we propose that consideration of the rules of quantum physics is necessary to understand how the soul is reduced into consciousness.

  14. Reduced activation structural materials for fusion power plants - The European Union program

    International Nuclear Information System (INIS)

    Schaaf, B. van der; Le Marois, G.; Moeslang, A.; Victoria, M.

    2003-01-01

    The competition of fusion power plants with the renewable energy sources in the second half of the 21st century requires structural materials operating at high temperatures, and sufficient radiation resistance to ensure high plant efficiency and availability. The reduced activation materials development in the EU counts several steps regarding the radiation damage resistance: 75 dpa for DEMO and 150 dpa and beyond for power plants. The maximum operating temperature development line ranges from the present day from the present day feasible 600 K up to 1300- K in advanced power plants. The reduced activation steel, RAS, forms the reference for the development efforts. EUROFER has been manufactured in the EU on industrial scale with specified purity and mechanical properties up to 825 K. The oxide dispersion strengthened , ODS, variety of RAS should reach the 925 K operation limit. The EU has selected silicon carbide ceramic composite as the primary high temperature, 1300 K, goal. On a small scale the potential of tungsten alloys for higher temperatures is investigated. The present test environments for radiation resistance are insufficient to provide data for DEMO. Hence the support of the EU for the International Fusion Materials Irradiation facility. The computational modelling is expected to guide the materials development and the design of near plasma components. The EU co-operates closely with Japan, the RF and US in IEA and IAEA co-ordinated agreements, which are highly beneficial for the fusion structural materials development. (author)

  15. Epithermal neutron activation analysis of CR(VI)-reducer basalt-inhabiting bacteria

    International Nuclear Information System (INIS)

    Tsibakhashvili, N.Ya.; Kalabegishvili, T.L.; Murusidze, I.G.; Mosulishvili, L.M.; Frontas'eva, M.V.; Kirkesali, E.I.; Aksenova, N.G.; Holman, H.Y.

    2005-01-01

    Epithermal neutron activation analysis (ENAA) has been applied to studying elemental composition of Cr(VI)-reducer bacteria isolated from polluted basalts from the Republic of Georgia. Cr(VI)-reducing ability of the bacteria was examined by electron spin resonance (ESR) demonstrating that the bacteria differ in the rates of Cr(VI) reduction. A well-pronounced correlation between the ability of the bacteria to accumulate Cr(VI) and their ability to reduce Cr(V) to Cr(III) observed in our experiments is discussed. Elemental analysis of these bacteria also revealed that basalt-inhabiting bacteria are distinguished by relative contents of essential elements such as K, Na, Mg, Fe, Mn, Zn, and Co. A high rate of Cr(III) formation correlates with a high concentration of Co in the bacterium. ENAA detected some similarity in the elemental composition of the bacteria. The relatively high contents of Fe detected in the bacteria (140-340 μg/g of dry weight) indicate bacterial adaptation to the environmental conditions typical of the basalts. The concentrations of at least 12-19 different elements ranging from major- to ultratrace ones were determined in each type of bacteria simultaneously. The range of concentrations spans over 8 orders of magnitude

  16. Compatibility of reduced activation ferritic/martensitic steels with liquid breeders

    International Nuclear Information System (INIS)

    Muroga, T.; Nagasaka, T.; Kondo, M.; Sagara, A.; Noda, N.; Suzuki, A.; Terai, T.

    2008-10-01

    The compatibility of Reduced Activation Ferritic/Martensitic Steel (RAFM) with liquid Li and molten-salt Flibe have been characterized and accessed. Static compatibility tests were carried out in which the specimens were immersed into liquid Li or Flibe in isothermal autoclaves. Also carried out were compatibility tests in flowing liquid Li by thermal convection loops. In the case of liquid Li, the corrosion rate increased with temperature significantly. The corrosion was almost one order larger for the loop tests than for the static tests. Chemical analysis showed that the corrosion was enhanced when the level of N in Li is increased. Transformation from martensitic to ferritic phase and the resulting softening were observed in near-surface area of Li-exposed specimens, which were shown to be induced by decarburization. In the case of Flibe, the corrosion loss was much larger in a Ni crucible than in a RAFM crucible. Both fluorides and oxides were observed on the surfaces. Thus, the key corrosion process of Flibe is the competing process of fluoridation and oxidation. Possible mechanism of the enhanced corrosion in Ni crucible is electrochemical circuit effect. It was suggested that the corrosion loss rate of RAFM by liquid Li and Flibe can be reduced by reducing the level of impurity N in Li and avoiding the use of dissimilar materials in Flibe, respectively. (author)

  17. Reduced astrocyte density underlying brain volume reduction in activity-based anorexia rats

    Science.gov (United States)

    Frintrop, Linda; Liesbrock, Johanna; Paulukat, Lisa; Johann, Sonja; Kas, Martien J; Tolba, Rene; Heussen, Nicole; Neulen, Joseph; Konrad, Kerstin; Herpertz-Dahlmann, Beate; Beyer, Cordian; Seitz, Jochen

    2018-04-01

    Severe grey and white matter volume reductions were found in patients with anorexia nervosa (AN) that were linked to neuropsychological deficits while their underlying pathophysiology remains unclear. For the first time, we analysed the cellular basis of brain volume changes in an animal model (activity-based anorexia, ABA). Female rats had 24 h/day running wheel access and received reduced food intake until a 25% weight reduction was reached and maintained for 2 weeks. In ABA rats, the volumes of the cerebral cortex and corpus callosum were significantly reduced compared to controls by 6% and 9%, respectively. The number of GFAP-positive astrocytes in these regions decreased by 39% and 23%, total astrocyte-covered area by 83% and 63%. In neurons no changes were observed. The findings were complemented by a 60% and 49% reduction in astrocyte (GFAP) mRNA expression. Volumetric brain changes in ABA animals mirror those in human AN patients. These alterations are associated with a reduction of GFAP-positive astrocytes as well as GFAP expression. Reduced astrocyte functioning could help explain neuronal dysfunctions leading to symptoms of rigidity and impaired learning. Astrocyte loss could constitute a new research target for understanding and treating semi-starvation and AN.

  18. Epithermal Neutron Activation Analysis (ENAA) of Cr(VI)-reducer Basalt-inhabiting Bacteria

    CERN Document Server

    Tsibakhashvili, N Ya; Kirkesali, E I; Aksenova, N G; Kalabegishvili, T L; Murusidze, I G; Mosulishvili, L M; Holman, H Y N

    2005-01-01

    Epithermal neutron activation analysis (ENAA) has been applied to studying elemental composition of Cr(VI)-reducer bacteria isolated from polluted basalts from the Republic of Georgia. Cr(VI)-reducing ability of the bacteria was examined by electron spin resonance (ESR) demonstrating that the bacteria differ in the rates of Cr(VI) reduction. A well-pronounced correlation between the ability of the bacteria to accumulate Cr(V) and their ability to reduce Cr(V) to Cr(III) observed in our experiments is discussed. Elemental analysis of these bacteria also revealed that basalt-inhabiting bacteria are distinguished by relative contents of essential elements such as K, Na, Mg, Fe, Mn, Zn, and Co. A high rate of Cr(III) formation correlates with a high concentration of Co in the bacterium. ENAA detected some similarity in the elemental composition of the bacteria. The relatively high contents of Fe detected in the bacteria (140-340 $\\mu $g/g of dry weight) indicate bacterial adaptation to the environmental condition...

  19. Parasympathetic activation is involved in reducing epileptiform discharges when listening to Mozart music.

    Science.gov (United States)

    Lin, Lung-Chang; Chiang, Ching-Tai; Lee, Mei-Wen; Mok, Hin-Kiu; Yang, Yi-Hsin; Wu, Hui-Chuan; Tsai, Chin-Lin; Yang, Rei-Cheng

    2013-08-01

    Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect. Our previous work revealed the positive effects of Mozart K.448 in reducing epileptiform discharges in children with epilepsy. However, the mechanism remains unclear. parasympathetic activation has been shown to help seizure control in many studies. In this study, we investigated the effect of Mozart music on epileptiform discharges and autonomic activity. Sixty-four epileptic children with epileptiform discharges were included. They all received electroencephalogram and electrocardiogram examinations simultaneously before, during, and after listening to Mozart K.448 or K.545. The total number of epileptiform discharges during each session (before, during, and after music) were divided by the duration (in minutes) of the session and then compared. Heart rate variability including time and frequency domain analysis was used to represent the autonomic function. The results showed that epileptiform discharges were significantly reduced during and right after listening to Mozart music (33.3 ± 31.1% reduction, pMozart K.448 and 38.6 ± 43.3% reduction, pMozart K.545) (28.1 ± 43.2% reduction, pMozart K.448 and 46.0 ± 40.5% reduction, pMozart K.545). No significant difference was noticed between the two pieces of music. The reduction was greatest in patients with generalized seizures and discharges. Significant increases in high-frequency (HF), the square root of the mean squared differences of successive RR intervals (RMSSD), the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute (bpm) were found during listening to Mozart music. Most of the patients with reduced epileptiform discharges also showed a decreased LF/HF ratio, low-frequency normalized units (LF nu), mean bpm, and an increased high-frequency normalized units (HF nu). Listening to Mozart music decreased epileptiform

  20. Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

    Science.gov (United States)

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

  1. Chronic renin inhibition lowers blood pressure and reduces upright muscle sympathetic nerve activity in hypertensive seniors

    Science.gov (United States)

    Okada, Yoshiyuki; Jarvis, Sara S; Best, Stuart A; Bivens, Tiffany B; Adams-Huet, Beverley; Levine, Benjamin D; Fu, Qi

    2013-01-01

    Cardiovascular risk remains high in patients with hypertension even with adequate blood pressure (BP) control. One possible mechanism may be sympathetic activation via the baroreflex. We tested the hypothesis that chronic inhibition of renin reduces BP without sympathetic activation, but diuresis augments sympathetic activity in elderly hypertensives. Fourteen patients with stage-I hypertension (66 ± 5 (SD) years) were treated with a direct renin inhibitor, aliskiren (n= 7), or a diuretic, hydrochlorothiazide (n= 7), for 6 months. Muscle sympathetic nerve activity (MSNA), BP, direct renin and aldosterone were measured during supine and a graded head-up tilt (HUT; 5 min 30° and 20 min 60°), before and after treatment. Sympathetic baroreflex sensitivity (BRS) was assessed. Both groups had similar BP reductions after treatment (all P < 0.01), while MSNA responses were different between hydrochlorothiazide and aliskiren (P= 0.006 pre/post × drug). Both supine and upright MSNA became greater after hydrochlorothiazide treatment (supine, 72 ± 18 post vs. 64 ± 15 bursts (100 beats)−1 pre; 60° HUT, 83 ± 10 vs. 78 ± 13 bursts (100 beats)−1; P= 0.002). After aliskiren treatment, supine MSNA remained unchanged (69 ± 13 vs. 64 ± 8 bursts (100 beats)−1), but upright MSNA was lower (74 ± 15 vs. 85 ± 10 bursts (100 beats)−1; P= 0.012 for pre/post × posture). Direct renin was greater after both treatments (both P < 0.05), while upright aldosterone was greater after hydrochlorothiazide only (P= 0.002). The change in upright MSNA by the treatment was correlated with the change of aldosterone (r= 0.74, P= 0.002). Upright sympathetic BRS remained unchanged after either treatment. Thus, chronic renin inhibition may reduce upright MSNA through suppressed renin activity, while diuresis may evoke sympathetic activation via the upregulated renin–angiotensin–aldosterone system, without changing intrinsic sympathetic baroreflex function in elderly hypertensive

  2. Reducing conditions are the key for efficient production of active ribonuclease inhibitor in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Neubauer Peter

    2011-05-01

    Full Text Available Abstract Background The eukaryotic RNase ribonuclease/angiogenin inhibitors (RI are a protein group distinguished by a unique structure - they are composed of hydrophobic leucine-rich repeat motifs (LRR and contain a high amount of reduced cysteine residues. The members of this group are difficult to produce in E. coli and other recombinant hosts due to their high aggregation tendency. Results In this work dithiothreitol (DTT was successfully applied for improving the yield of correctly folded ribonuclease/angiogenin inhibitor in E. coli K12 periplasmic and cytoplasmic compartments. The feasibility of the in vivo folding concepts for cytoplasmic and periplasmic production were demonstrated at batch and fed-batch cultivation modes in shake flasks and at the bioreactor scale. Firstly, the best secretion conditions of RI in the periplasmic space were evaluated by using a high throughput multifactorial screening approach of a vector library, directly with the Enbase fed-batch production mode in 96-well plates. Secondly, the effect of the redox environment was evaluated in isogenic dsbA+ and dsbA- strains at the various cultivation conditions with reducing agents in the cultivation medium. Despite the fusion to the signal peptide, highest activities were found in the cytoplasmic fraction. Thus by removing the signal peptide the positive effect of the reducing agent DTT was clearly proven also for the cytoplasmic compartment. Finally, optimal periplasmic and cytoplasmic RI fed-batch production processes involving externally added DTT were developed in shake flasks and scaled up to the bioreactor scale. Conclusions DTT highly improved both, periplasmic and cytoplasmic accumulation and activity of RI at low synthesis rate, i.e. in constructs harbouring weak recombinant synthesis rate stipulating genetic elements together with cultivation at low temperature. In a stirred bioreactor environment RI folding was strongly improved by repeated pulse addition

  3. B cell depletion reduces T cell activation in pancreatic islets in a murine autoimmune diabetes model.

    Science.gov (United States)

    Da Rosa, Larissa C; Boldison, Joanne; De Leenheer, Evy; Davies, Joanne; Wen, Li; Wong, F Susan

    2018-06-01

    Type 1 diabetes is a T cell-mediated autoimmune disease characterised by the destruction of beta cells in the islets of Langerhans, resulting in deficient insulin production. B cell depletion therapy has proved successful in preventing diabetes and restoring euglycaemia in animal models of diabetes, as well as in preserving beta cell function in clinical trials in the short term. We aimed to report a full characterisation of B cell kinetics post B cell depletion, with a focus on pancreatic islets. Transgenic NOD mice with a human CD20 transgene expressed on B cells were injected with an anti-CD20 depleting antibody. B cells were analysed using multivariable flow cytometry. There was a 10 week delay in the onset of diabetes when comparing control and experimental groups, although the final difference in the diabetes incidence, following prolonged observation, was not statistically significant (p = 0.07). The co-stimulatory molecules CD80 and CD86 were reduced on stimulation of B cells during B cell depletion and repopulation. IL-10-producing regulatory B cells were not induced in repopulated B cells in the periphery, post anti-CD20 depletion. However, the early depletion of B cells had a marked effect on T cells in the local islet infiltrate. We demonstrated a lack of T cell activation, specifically with reduced CD44 expression and effector function, including IFN-γ production from both CD4 + and CD8 + T cells. These CD8 + T cells remained altered in the pancreatic islets long after B cell depletion and repopulation. Our findings suggest that B cell depletion can have an impact on T cell regulation, inducing a durable effect that is present long after repopulation. We suggest that this local effect of reducing autoimmune T cell activity contributes to delay in the onset of autoimmune diabetes.

  4. Antimicrobial activity of essential oils and fruits supplement in reduced nitrite salts condition

    Directory of Open Access Journals (Sweden)

    Vujadinović Dragan P.

    2017-01-01

    Full Text Available Because of the growing negative perception of consumers related to the use of meat products produced by conventional curing methods, organic and natural products are increasingly accepted by consumers. Such products contain a large number of natural products derived from plants, spices, as well as their derivatives in form of essential oils, extracts, concentrates, and so on. These derivatives contain large number of active substances which are known to inhibit the metabolic processes of bacteria, yeasts and molds. Therefore, the goal of this paper was to investigate the synergistic antimicrobial activity of the models with a reduced presence of nitrite salt in aqueous solution, emulsions of essential oils in varying concentrations in vivo via antibiogram tests on pathogenic microorganisms. The effect of the six model groups was analyzed. Two groups were fruit powder solutions in concentrations of 0.2% to 1.2% (Acerola powder and fruit powder mix, while the other four groups were models of aqueous emulsion of essential oil in concentrations ranging from 0.05% to 1.2% (tea tree, clove, oregano, and cinnamon essential oils. In all models reduced amount of the sodium salt of 1.80%, 0.0075% nitrite salt and the liquid derivative as a natural source of the nitrate salt of 3% were used. Antibiogram tests were performed on five pathogenic bacteria (C. perfringens, E. coli, S. enterica, L. monocytogenes, and S. aureus. All antibiogram tests were performed according to Kirby-Bauer disk diffusion protocol. Results of antibiograms showed that without the presence of additional antimicrobial agents, in model systems with reduced content of salts, inhibition zones were not detected. Additionally, models with essential oils of tea tree oil and oregano had the widest inhibition zone diameters, ranging from 17.76±0.48mm for E. coli up to 42.50±0.13mm for S. aureus.

  5. Impaired hippocampal glucose metabolism during and after flurothyl-induced seizures in mice: Reduced phosphorylation coincides with reduced activity of pyruvate dehydrogenase.

    Science.gov (United States)

    McDonald, Tanya S; Borges, Karin

    2017-07-01

    To determine changes in glucose metabolism and the enzymes involved in the hippocampus ictally and postictally in the acute mouse flurothyl seizure model. [U- 13 C]-Glucose was injected (i.p.) prior to, or following a 5 min flurothyl-induced seizure. Fifteen minutes later, mice were killed and the total metabolite levels and % 13 C enrichment were analyzed in the hippocampal formation using gas chromatography-mass spectrometry. Activities of key metabolic and antioxidant enzymes and the phosphorylation status of pyruvate dehydrogenase were measured, along with lipid peroxidation. During seizures, total lactate levels increased 1.7-fold; however, [M + 3] enrichment of both lactate and alanine were reduced by 30% and 43%, respectively, along with a 28% decrease in phosphofructokinase activity. Postictally the % 13 C enrichments of all measured tricarboxylic acid (TCA) cycle intermediates and the amino acids were reduced by 46-93%. At this time, pyruvate dehydrogenase (PDH) activity was 56% of that measured in controls, and there was a 1.9-fold increase in the phosphorylation of PDH at ser232. Phosphorylation of PDH is known to decrease its activity. Here, we show that the increase of lactate levels during flurothyl seizures is from a source other than [U- 13 C]-glucose, such as glycogen. Surprisingly, although we saw a reduction in phosphofructokinase activity during the seizure, metabolism of [U- 13 C]-glucose into the TCA cycle seemed unaffected. Similar to our recent findings in the chronic phase of the pilocarpine model, postictally the metabolism of glucose by glycolysis and the TCA cycle was impaired along with reduced PDH activity. Although this decrease in activity may be a protective mechanism to reduce oxidative stress, which is observed in the flurothyl model, ATP is critical to the recovery of ion and neurotransmitter balance and return to normal brain function. Thus we identified promising novel strategies to enhance energy metabolism and recovery from

  6. Interrupted reperfusion reduces the activation of NADPH oxidase after cerebral I/R injury.

    Science.gov (United States)

    Shen, Jia; Bai, Xiao-Yin; Qin, Yuan; Jin, Wei-Wei; Zhou, Jing-Yin; Zhou, Ji-Ping; Yan, Ying-Gang; Wang, Qiong; Bruce, Iain C; Chen, Jiang-Hua; Xia, Qiang

    2011-06-15

    Interrupted reperfusion reduces ischemia/reperfusion (I/R) injury. This study was designed to determine whether NADPH oxidase participates in the neural protection against global I/R injury after interrupted reperfusion. Mice were randomly divided into five groups: sham (sham-operated), I/R (20-min global I/R), RR (I/R+interrupted reperfusion), Apo (I/R+apocynin administration), and RR+Apo. Behavioral tests (pole test, beam walking, and Morris water maze) and Nissl staining were undertaken in all five groups; superoxide levels, expression of gp91(phox) and p47(phox), p47(phox) translocation, and Rac1 activation were measured in the sham, I/R, and RR groups. The motor coordination, bradykinesia, and spatial learning and memory, as well as the neuron survival rates, were better in the RR, Apo, and RR+Apo groups than in the I/R group. The NADPH oxidase-dependent superoxide levels, p47(phox) and gp91(phox) expression, p47(phox) translocation, and Rac1 activation were lower in the RR group than in the I/R group. In conclusion, the neural protective effect of interrupted reperfusion is at least partly mediated by decreasing the expression and assembly of NADPH oxidase and the levels of NADPH oxidase-derived superoxide. The most striking reduction Rac1-GTP in the RR group suggests that interrupted reperfusion also acts on the activation of assembled NADPH oxidase by reducing the availability of Rac1-GTP. Copyright © 2011 Elsevier Inc. All rights reserved.

  7. Efficient degradation of trichloroethylene in water using persulfate activated by reduced graphene oxide-iron nanocomposite.

    Science.gov (United States)

    Ahmad, Ayyaz; Gu, Xiaogang; Li, Li; Lv, Shuguang; Xu, Yisheng; Guo, Xuhong

    2015-11-01

    Graphene oxide (GO) and nano-sized zero-valent iron-reduced graphene oxide (nZVI-rGO) composite were prepared. The GO and nZVI-rGO composite were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), energy-dispersive spectroscopy (EDS), and Raman spectroscopy. The size of nZVI was about 6 nm as observed by TEM. The system of nZVI-rGO and persulfate (PS) was used for the degradation of trichloroethylene (TCE) in water, and showed 26.5% more efficiency as compared to nZVI/PS system. The different parameters were studied to determine the efficiency of nZVI-rGO to activate the PS system for the TCE degradation. By increasing the PS amount, TCE removal was also improved while no obvious effect was observed by varying the catalyst loading. Degradation was decreased as the TCE initial concentration was increased from 20 to 100 mg/L. Moreover, when initial solution pH was increased, efficiency deteriorated to 80%. Bicarbonate showed more negative effect on TCE removal among the solution matrix. To better understand the effects of radical species in the system, the scavenger tests were performed. The •SO4(-) and •O2(-) were predominant species responsible for TCE removal. The nZVI-rGO-activated PS process shows potential applications in remediation of highly toxic organic contaminants such as TCE present in the groundwater. Graphical abstract Persulfate activated by reduced graphene oxide and nano-sized zero-valent iron composite can be used for efficient degradation of trichloroethylene (TCE) in water.

  8. Biotransformation of Bisphenol AF to Its Major Glucuronide Metabolite Reduces Estrogenic Activity

    Science.gov (United States)

    Yin, Jie; Zhang, Jing; Feng, Yixing; Shao, Bing

    2013-01-01

    Bisphenol AF (BPAF), an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER). However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G), BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD) rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR). After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM), and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs) including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings. PMID:24349450

  9. Enhanced butanol production and reduced autolysin activity after chloramphenicol treatment of Clostridium acetobutylicum ATCC 824

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Xiangdong; Traxler, R.W. (Rhode Island Univ., Kingston, RI (United States). Dept. of Food Science and Nutrition)

    1992-06-01

    Release of autolysin during the late exponential growth phase of Clostridium acetobutylicum resulted in early lysis of the culture and reduction of solvent formation. A simple and effective way of reducing autolysin activity and increasing solvent production is partial inhibition of protein synthesis with chloramphenicol (CAP). The extracellular autolytic activity in the culture, determined by following loss of turbidity of washed clostridial cells in 0.04 M sodium phosphate buffer at 37deg C, was decreased by 40% after CAP treatment. This caused an extension of cell viability by 12 h and an increase in butanol production by 30%. The optimal time of CAP addition was 12 h of incubation, and the optimal antibiotic concentration was 120 {mu}g/ml. The effects of CAP on the fermentation are due to the inhibition of protein synthesis leading to a decrease in autolysin level in the culture. The results obtained provide economic advantages for industrial production of solvents by minimizing autolysin activity and maximizing solvent yield during the critical solvent-producing phase. (orig.).

  10. Progress of reduced activation ferritic/martensitic steel development in Japan

    International Nuclear Information System (INIS)

    Jitsukawa, S.; Kimura, A.; Kohyama, A.; Ukai, S.; Sawai, T.; Wakai, E.; Shiba, K.; Miwa, Y.; Furuya, K.; Tanigawa, H.; Ando, M.

    2005-01-01

    Recent accomplishment by the Japanese activity for the reduced activation ferritic/martensitic steel (RAF/M) development has been reviewed. Some of the results obtained in EU and US by international collaborative activities are also introduced. Effect of irradiation on the shift of ductile-to-brittle transition temperature (DBTT) has been evaluated to a dose of 20dpa. Results suggest that RAF/M appears to satisfy the requirement on DBTT-shift for the blanket application in the dose range up to several tens of dpa. Also, enhancement effect of DBTT-shift by transmutation produced helium (He) atoms was revealed to be smaller than has been suggested previously. Preliminary studies about the effect of irradiation on fatigue mechanism, the susceptibility to environmentally assisted cracking in water and flow stress-strain relation have been conducted for the specimens irradiated to several dpa, including the post irradiation tensile property examination of the joints by Hot-isostatic press (HIP) bonding method. The results also indicate that RAF/Ms exhibit suitable properties for ITER test blanket module. (author)

  11. Video-Quality Estimation Based on Reduced-Reference Model Employing Activity-Difference

    Science.gov (United States)

    Yamada, Toru; Miyamoto, Yoshihiro; Senda, Yuzo; Serizawa, Masahiro

    This paper presents a Reduced-reference based video-quality estimation method suitable for individual end-user quality monitoring of IPTV services. With the proposed method, the activity values for individual given-size pixel blocks of an original video are transmitted to end-user terminals. At the end-user terminals, the video quality of a received video is estimated on the basis of the activity-difference between the original video and the received video. Psychovisual weightings and video-quality score adjustments for fatal degradations are applied to improve estimation accuracy. In addition, low-bit-rate transmission is achieved by using temporal sub-sampling and by transmitting only the lower six bits of each activity value. The proposed method achieves accurate video quality estimation using only low-bit-rate original video information (15kbps for SDTV). The correlation coefficient between actual subjective video quality and estimated quality is 0.901 with 15kbps side information. The proposed method does not need computationally demanding spatial and gain-and-offset registrations. Therefore, it is suitable for real-time video-quality monitoring in IPTV services.

  12. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

  13. Human Bile Reduces Antimicrobial Activity of Selected Antibiotics against Enterococcus faecalis and Escherichia coli In Vitro.

    Science.gov (United States)

    Wulkersdorfer, Beatrix; Jaros, David; Eberl, Sabine; Poschner, Stefan; Jäger, Walter; Cosentini, Enrico; Zeitlinger, Markus; Schwameis, Richard

    2017-08-01

    It has been known from previous studies that body fluids, such as cerebrospinal fluid, lung surfactant, and urine, have a strong impact on the bacterial killing of many anti-infective agents. However, the influence of human bile on the antimicrobial activity of antibiotics is widely unknown. Human bile was obtained and pooled from 11 patients undergoing cholecystectomy. After sterilization of the bile fluid by gamma irradiation, its effect on bacterial killing was investigated for linezolid (LZD) and tigecycline (TGC) against Enterococcus faecalis ATCC 29212. Further, ciprofloxacin (CIP), meropenem (MEM), and TGC were tested against Escherichia coli ATCC 25922. Time-kill curves were performed in pooled human bile and Mueller-Hinton broth (MHB) over 24 h. Bacterial counts (in CFU per milliliter after 24 h) of bile growth controls were approximately equal to MHB growth controls for E. coli and approximately 2-fold greater for E. faecalis , indicating a promotion of bacterial growth by bile for the latter strain. Bile reduced the antimicrobial activity of CIP, MEM, and TGC against E. coli as well as the activity of LZD and TGC against E. faecalis This effect was strongest for TGC against the two strains. Degradation of TGC in bile was identified as the most likely explanation. These findings may have important implications for the treatment of bacterial infections of the gallbladder and biliary tract and should be explored in more detail. Copyright © 2017 American Society for Microbiology.

  14. Impact of Educational Activities in Reducing Pre-Analytical Laboratory Errors: A quality initiative.

    Science.gov (United States)

    Al-Ghaithi, Hamed; Pathare, Anil; Al-Mamari, Sahimah; Villacrucis, Rodrigo; Fawaz, Naglaa; Alkindi, Salam

    2017-08-01

    Pre-analytic errors during diagnostic laboratory investigations can lead to increased patient morbidity and mortality. This study aimed to ascertain the effect of educational nursing activities on the incidence of pre-analytical errors resulting in non-conforming blood samples. This study was conducted between January 2008 and December 2015. All specimens received at the Haematology Laboratory of the Sultan Qaboos University Hospital, Muscat, Oman, during this period were prospectively collected and analysed. Similar data from 2007 were collected retrospectively and used as a baseline for comparison. Non-conforming samples were defined as either clotted samples, haemolysed samples, use of the wrong anticoagulant, insufficient quantities of blood collected, incorrect/lack of labelling on a sample or lack of delivery of a sample in spite of a sample request. From 2008 onwards, multiple educational training activities directed at the hospital nursing staff and nursing students primarily responsible for blood collection were implemented on a regular basis. After initiating corrective measures in 2008, a progressive reduction in the percentage of non-conforming samples was observed from 2009 onwards. Despite a 127.84% increase in the total number of specimens received, there was a significant reduction in non-conforming samples from 0.29% in 2007 to 0.07% in 2015, resulting in an improvement of 75.86% ( P educational activities directed primarily towards hospital nursing staff had a positive impact on the quality of laboratory specimens by significantly reducing pre-analytical errors.

  15. Salinity Inhibits Rice Seed Germination by Reducing α-Amylase Activity via Decreased Bioactive Gibberellin Content

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available Seed germination plays important roles in the establishment of seedlings and their subsequent growth; however, seed germination is inhibited by salinity, and the inhibitory mechanism remains elusive. Our results indicate that NaCl treatment inhibits rice seed germination by decreasing the contents of bioactive gibberellins (GAs, such as GA1 and GA4, and that this inhibition can be rescued by exogenous bioactive GA application. To explore the mechanism of bioactive GA deficiency, the effect of NaCl on GA metabolic gene expression was investigated, revealing that expression of both GA biosynthetic genes and GA-inactivated genes was up-regulated by NaCl treatment. These results suggest that NaCl-induced bioactive GA deficiency is caused by up-regulated expression of GA-inactivated genes, and the up-regulated expression of GA biosynthetic genes might be a consequence of negative feedback regulation of the bioactive GA deficiency. Moreover, we provide evidence that NaCl-induced bioactive GA deficiency inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression. Additionally, exogenous bioactive GA rescues NaCl-inhibited seed germination by enhancing α-amylase activity. Thus, NaCl treatment reduces bioactive GA content through promotion of bioactive GA inactivation, which in turn inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression.

  16. Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles

    International Nuclear Information System (INIS)

    Im, A-Rang; Kim, Jee Young; Kim, Yeong Shik; Kim, Hyun-Seok; Cho, Seonho; Park, Youmie

    2013-01-01

    For topical applications in wound healing, silver nanoparticles (AgNPs) have attracted much attention as antibacterial agents. Herein, we describe a green-synthetic route for the production of biocompatible and crystalline AgNPs using two glycosaminoglycans, chondroitin sulfate (CS) and acharan sulfate (AS), as reducing agents. The synthetic approach avoids the use of toxic chemicals, and the yield of AgNPs formation is found to be 98.1% and 91.1% for the chondroitin sulfate-reduced silver nanoparticles (CS-AgNPs) and the acharan sulfate-reduced silver nanoparticles (AS-AgNPs), respectively. Nanoparticles with mostly spherical and amorphous shapes were observed, with an average diameter of 6.16 ± 2.26 nm for CS-AgNPs and 5.79 ± 3.10 nm for AS-AgNPs. Images of the CS-AgNPs obtained from atomic force microscopy revealed the self-assembled structure of CS was similar to a densely packed woven mat with AgNPs sprinkled on the CS. These nanoparticles were stable under cell culture conditions without any noticeable aggregation. An approximately 128-fold enhancement of the antibacterial activities of the AgNPs was observed against Enterobacter cloacae and Escherichia coli when compared to CS and AS alone. In addition, an in vivo animal model of wound healing activity was tested using mice that were subjected to deep incision wounds. In comparison to the controls, the ointments containing CS-AgNPs and AS-AgNPs stimulated wound closure under histological examination and accelerated the deposition of granulation tissue and collagen in the wound area. The wound healing activity of the ointments containing CS-AgNPs and AS-AgNPs are comparable to that of a commercial formulation of silver sulfadiazine even though the newly prepared ointments contain a lower silver concentration. Therefore, the newly prepared AgNPs demonstrate potential for use as an attractive biocompatible nanocomposite for topical applications in the treatment of wounds. (paper)

  17. Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles

    Science.gov (United States)

    Im, A.-Rang; Kim, Jee Young; Kim, Hyun-Seok; Cho, Seonho; Park, Youmie; Kim, Yeong Shik

    2013-10-01

    For topical applications in wound healing, silver nanoparticles (AgNPs) have attracted much attention as antibacterial agents. Herein, we describe a green-synthetic route for the production of biocompatible and crystalline AgNPs using two glycosaminoglycans, chondroitin sulfate (CS) and acharan sulfate (AS), as reducing agents. The synthetic approach avoids the use of toxic chemicals, and the yield of AgNPs formation is found to be 98.1% and 91.1% for the chondroitin sulfate-reduced silver nanoparticles (CS-AgNPs) and the acharan sulfate-reduced silver nanoparticles (AS-AgNPs), respectively. Nanoparticles with mostly spherical and amorphous shapes were observed, with an average diameter of 6.16 ± 2.26 nm for CS-AgNPs and 5.79 ± 3.10 nm for AS-AgNPs. Images of the CS-AgNPs obtained from atomic force microscopy revealed the self-assembled structure of CS was similar to a densely packed woven mat with AgNPs sprinkled on the CS. These nanoparticles were stable under cell culture conditions without any noticeable aggregation. An approximately 128-fold enhancement of the antibacterial activities of the AgNPs was observed against Enterobacter cloacae and Escherichia coli when compared to CS and AS alone. In addition, an in vivo animal model of wound healing activity was tested using mice that were subjected to deep incision wounds. In comparison to the controls, the ointments containing CS-AgNPs and AS-AgNPs stimulated wound closure under histological examination and accelerated the deposition of granulation tissue and collagen in the wound area. The wound healing activity of the ointments containing CS-AgNPs and AS-AgNPs are comparable to that of a commercial formulation of silver sulfadiazine even though the newly prepared ointments contain a lower silver concentration. Therefore, the newly prepared AgNPs demonstrate potential for use as an attractive biocompatible nanocomposite for topical applications in the treatment of wounds.

  18. Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

    Science.gov (United States)

    Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

    2012-09-01

    In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

  19. Denervation-Induced Activation of the Ubiquitin-Proteasome System Reduces Skeletal Muscle Quantity Not Quality.

    Science.gov (United States)

    Baumann, Cory W; Liu, Haiming M; Thompson, LaDora V

    2016-01-01

    It is well known that the ubiquitin-proteasome system is activated in response to skeletal muscle wasting and functions to degrade contractile proteins. The loss of these proteins inevitably reduces skeletal muscle size (i.e., quantity). However, it is currently unknown whether activation of this pathway also affects function by impairing the muscle's intrinsic ability to produce force (i.e., quality). Therefore, the purpose of this study was twofold, (1) document how the ubiquitin-proteasome system responds to denervation and (2) identify the physiological consequences of these changes. To induce soleus muscle atrophy, C57BL6 mice underwent tibial nerve transection of the left hindlimb for 7 or 14 days (n = 6-8 per group). At these time points, content of several proteins within the ubiquitin-proteasome system were determined via Western blot, while ex vivo whole muscle contractility was specifically analyzed at day 14. Denervation temporarily increased several key proteins within the ubiquitin-proteasome system, including the E3 ligase MuRF1 and the proteasome subunits 19S, α7 and β5. These changes were accompanied by reductions in absolute peak force and power, which were offset when expressed relative to physiological cross-sectional area. Contrary to peak force, absolute and relative forces at submaximal stimulation frequencies were significantly greater following 14 days of denervation. Taken together, these data represent two keys findings. First, activation of the ubiquitin-proteasome system is associated with reductions in skeletal muscle quantity rather than quality. Second, shortly after denervation, it appears the muscle remodels to compensate for the loss of neural activity via changes in Ca2+ handling.

  20. Deletion of G-protein-coupled receptor 55 promotes obesity by reducing physical activity.

    Science.gov (United States)

    Meadows, A; Lee, J H; Wu, C-S; Wei, Q; Pradhan, G; Yafi, M; Lu, H-C; Sun, Y

    2016-03-01

    Cannabinoid receptor 1 (CB1) is the best-characterized cannabinoid receptor, and CB1 antagonists are used in clinical trials to treat obesity. Because of the wide range of CB1 functions, the side effects of CB1 antagonists pose serious concerns. G-protein-coupled receptor 55 (GPR55) is an atypical cannabinoid receptor, and its pharmacology and functions are distinct from CB1. GPR55 regulates neuropathic pain, gut, bone, immune functions and motor coordination. GPR55 is expressed in various brain regions and peripheral tissues. However, the roles of GPR55 in energy and glucose homeostasis are unknown. Here we have investigated the roles of GPR55 in energy balance and insulin sensitivity using GPR55-null mice (GPR55(-/-)). Body composition of the mice was measured by EchoMRI. Food intake, feeding behavior, energy expenditure and physical activity of GPR55(-/-) mice were determined by indirect calorimetry. Muscle function was assessed by forced treadmill running test. Insulin sensitivity was evaluated by glucose and insulin tolerance tests. Adipose inflammation was assessed by flow cytometry analysis of adipose tissue macrophages. The expression of inflammatory markers in adipose tissues and orexigenic/anorexigenic peptides in the hypothalamus was also analyzed by real-time PCR. GPR55(-/-) mice had normal total energy intake and feeding pattern (i.e., no changes in meal size, meal number or feeding frequency). Intriguingly, whereas adult GPR55(-/-) mice only showed a modest increase in overall body weight, they exhibited significantly increased fat mass and insulin resistance. The spontaneous locomotor activity of GPR55(-/-) mice was dramatically decreased, whereas resting metabolic rate and non-shivering thermogenesis were unchanged. Moreover, GPR55(-/-) mice exhibited significantly decreased voluntary physical activity, showing reduced running distance on the running wheels, whereas muscle function appeared to be normal. GPR55 has an important role in energy

  1. Oxytocin Reduces Cocaine Cued Fos Activation in a Regionally Specific Manner

    Science.gov (United States)

    Leong, Kah-Chung; Freeman, Linnea R; Berini, Carole R; Ghee, Shannon M; See, Ronald E

    2017-01-01

    Abstract Background Oxytocin may be a possible treatment for multiple neuropsychiatric disorders, including cocaine addiction. Little is known about the site-specific effects of oxytocin on various drug addiction-related brain regions. Furthermore, sexually dimorphic effects of oxytocin on neural function in the addiction circuit have not been established. Here, we studied Fos expression following cocaine-cued reinstatement in both male and female rats. Methods Male and female rats underwent self-administration, extinction, and reinstatement tests. On test days, rats were given oxytocin or vehicle, and lever pressing was measured in response to conditioned cocaine cues. Rats were perfused and Fos staining measured in the central amygdala, medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Fos/oxytocin double labeling occurred in the paraventricular nucleus of the hypothalamus. Results Rats reinstated to cocaine cues relative to extinction responding and oxytocin reduced cocaine seeking. Oxytocin combined with contingent cue presentations increased Fos+ oxytocin cell bodies within the paraventricular nucleus of the hypothalamus relative to vehicle. Fos expression robustly increased in the central amygdala following oxytocin administration. Oxytocin reversed cue-induced Fos expression in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus. Central oxytocin infusion also attenuated reinstated cocaine seeking. Conclusions Oxytocin decreased reinstated cocaine seeking, increased Fos activation in the paraventricular nucleus of the hypothalamus and central amygdala, but normalized cue-induced Fos activation in the medial prefrontal cortex, nucleus accumbens core, and subthalamic nucleus, thereby demonstrating regionally specific activation patterns. No sex differences were seen for the effects of oxytocin on cocaine seeking and Fos activation, indicating that oxytocin acts on similar central neural circuits critical to

  2. Strain-rate behavior in tension of the tempered martensitic reduced activation steel Eurofer97

    Energy Technology Data Exchange (ETDEWEB)

    Cadoni, Ezio; Dotta, Matteo; Forni, Daniele [University of Applied Sciences of Southern Switzerland, P.O. Box 105, CH-6952 Canobbio (Switzerland); Spaetig, Philippe, E-mail: philippe.spatig@psi.ch [Ecole Polytechnique Federale de Lausanne (EPFL), Centre de Recherches en Physique des Plasmas, Association Euratom-Confederation Suisse, CH-5232 Villigen PSI (Switzerland)

    2011-07-31

    The tensile properties of the high-chromium tempered martensitic reduced activation steel Eurofer97 were determined from tests carried out over a wide range of strain-rates on cylindrical specimens. The quasi-static tests were performed with a universal electro-mechanical machine, whereas a hydro-pneumatic machine and a JRC-split Hopkinson tensile bar apparatus were used for medium and high strain-rates respectively. This tempered martensitic stainless steel showed significant strain-rate sensitivity. The constitutive behavior was investigated within a framework of dislocations dynamics model using Kock's approach. The parameters of the model were determined and then used to predict the deformation range of the tensile deformation stability. A very good agreement between the experimental results and predictions of the model was found.

  3. Damage behavior in helium-irradiated reduced-activation martensitic steels at elevated temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Fengfeng [Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Guo, Liping, E-mail: guolp@whu.edu.cn [Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Chen, Jihong; Li, Tiecheng; Zheng, Zhongcheng [Key Laboratory of Artificial Micro- and Nano-Structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Yao, Z. [Department of Mechanical and Materials Engineering, Queen’s University, Kingston K7L 3N6, ON (Canada); Suo, Jinping [State Key Laboratory of Mould Technology, Institute of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2014-12-15

    Dislocation loops induced by helium irradiation at elevated temperatures in reduced-activation martensitic steels were investigated using transmission electron microscopy. Steels were irradiated with 100 keV helium ions to 0.8 dpa between 300 K and 723 K. At irradiation temperatures T{sub irr} ⩽ 573 K, small defects with both Burger vectors b = 1/2〈1 1 1〉 and b = 〈1 0 0〉 were observed, while at T{sub irr} ⩾ 623 K, the microstructure was dominated by large convoluted interstitial dislocation loops with b = 〈1 0 0〉. Only small cavities were found in the steels irradiated at 723 K.

  4. Microstructural evolution of reduced-activation martensitic steel under single and sequential ion irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Fengfeng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Guo, Liping, E-mail: guolp@whu.edu.cn [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Jin, Shuoxue; Li, Tiecheng; Zheng, Zhongcheng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Yang, Feng; Xiong, Xuesong; Suo, Jinping [State Key Laboratory of Mould Technology, Institute of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2013-07-15

    Microstructural evolution of super-clean reduced-activation martensitic steels irradiated with single-beam (Fe{sup +}) and sequential-beam (Fe{sup +} plus He{sup +}) at 350 °C and 550 °C was studied. Sequential-beam irradiation induced smaller size and larger number density of precipitates compared to single-beam irradiation at 350 °C. The largest size of cavities was observed after sequential-beam irradiation at 550 °C. The segregation of Cr and W and depletion of Fe in carbides were observed, and the maximum depletion of Fe and enrichment of Cr occurred under irradiation at 350 °C.

  5. Development of Reduced Activation Ferritic-Martensitic Steels and fabrication technologies for Indian test blanket module

    Energy Technology Data Exchange (ETDEWEB)

    Raj, Baldev [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Jayakumar, T., E-mail: tjk@igcar.gov.in [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India)

    2011-10-01

    For the development of Reduced Activation Ferritic-Martensitic Steel (RAFMS), for the Indian Test Blanket Module for ITER, a 3-phase programme has been adopted. The first phase consists of melting and detailed characterization of a laboratory scale heat conforming to Eurofer 97 composition, to demonstrate the capability of the Indian industry for producing fusion grade steel. In the second phase which is currently in progress, the chemical composition will be optimized with respect to tungsten and tantalum for better combination of mechanical properties. Characterization of the optimized commercial scale India-specific RAFM steel will be carried out in the third phase. The first phase of the programme has been successfully completed and the tensile, impact and creep properties are comparable with Eurofer 97. Laser and electron beam welding parameters have been optimized and welding consumables were developed for Narrow Gap - Gas Tungsten Arc welding and for laser-hybrid welding.

  6. Strain-rate behavior in tension of the tempered martensitic reduced activation steel Eurofer97

    International Nuclear Information System (INIS)

    Cadoni, Ezio; Dotta, Matteo; Forni, Daniele; Spaetig, Philippe

    2011-01-01

    The tensile properties of the high-chromium tempered martensitic reduced activation steel Eurofer97 were determined from tests carried out over a wide range of strain-rates on cylindrical specimens. The quasi-static tests were performed with a universal electro-mechanical machine, whereas a hydro-pneumatic machine and a JRC-split Hopkinson tensile bar apparatus were used for medium and high strain-rates respectively. This tempered martensitic stainless steel showed significant strain-rate sensitivity. The constitutive behavior was investigated within a framework of dislocations dynamics model using Kock's approach. The parameters of the model were determined and then used to predict the deformation range of the tensile deformation stability. A very good agreement between the experimental results and predictions of the model was found.

  7. Solar Light Responsive Photocatalytic Activity of Reduced Graphene Oxide-Zinc Selenide Nanocomposite

    Science.gov (United States)

    Chakraborty, Koushik; Ibrahim, Sk; Das, Poulomi; Ghosh, Surajit; Pal, Tanusri

    2017-10-01

    Solution processable reduced graphene oxide-zinc selenide (RGO-ZnSe) nanocomposite has been successfully synthesized by an easy one-pot single-step solvothermal reaction. The RGO-ZnSe composite was characterized structurally and morphologically by the study of XRD analysis, SEM and TEM imaging. Reduction in graphene oxide was confirmed by FTIR spectroscopy analysis. Photocatalytic efficiency of RGO-ZnSe composite was investigated toward the degradation of Rhodamine B under solar light irradiation. Our study indicates that the RGO-ZnSe composite is catalytically more active compared to the controlled-ZnSe under the solar light illumination. Here, RGO plays an important role for photoinduced charge separation and subsequently hinders the electron-hole recombination probability that consequently enhances photocatalytic degradation efficiency. We expect that this type of RGO-based optoelectronics materials opens up a new avenue in the field of photocatalytic degradation of different organic water pollutants.

  8. TIG of Reduced Activation Ferrite/Martensitic Steel for the Korean ITER-TBM

    International Nuclear Information System (INIS)

    Ku, Duck Young; Ahn, Mu Young; Yu, In Keun; Cho, Seun Gyon; Oh, Seung Jin

    2010-01-01

    Test Blanket Modules (TBM) will be tested in ITER to verify the capability of tritium breeding and recovery and the extraction of thermal energy suitable for the production of electricity. A Helium Cooled Solid Breeder (HCSB) TBM has been developed in Korea to accomplish these goals. Reduced Activation Ferritic/Martensitic (RAFM) steel has been chosen as the primary candidate structural material for Korean TBM. Due to the complexity of the First wall (FW) and Side wall (SW), it is necessary to develop various joining technologies, such as Hot Isostatic Pressing (HIP), Electron Beam Welding (EBW) and Tungsten Inert Gas (TIG) welding, for the successful fabrication of TBM. In this study, the mechanical properties of TIG welded RAFM steel were investigated. Various mechanical tests of TIG-welded RAFM steel were performed to obtain the optimized TIG welding process for RAFM steel

  9. TIG of Reduced Activation Ferrite/Martensitic Steel for the Korean ITER-TBM

    Energy Technology Data Exchange (ETDEWEB)

    Ku, Duck Young; Ahn, Mu Young; Yu, In Keun; Cho, Seun Gyon [ITER Korea, National Fusion Research Institute, Daejeon (Korea, Republic of); Oh, Seung Jin [KHNP, Daejeon (Korea, Republic of)

    2010-10-15

    Test Blanket Modules (TBM) will be tested in ITER to verify the capability of tritium breeding and recovery and the extraction of thermal energy suitable for the production of electricity. A Helium Cooled Solid Breeder (HCSB) TBM has been developed in Korea to accomplish these goals. Reduced Activation Ferritic/Martensitic (RAFM) steel has been chosen as the primary candidate structural material for Korean TBM. Due to the complexity of the First wall (FW) and Side wall (SW), it is necessary to develop various joining technologies, such as Hot Isostatic Pressing (HIP), Electron Beam Welding (EBW) and Tungsten Inert Gas (TIG) welding, for the successful fabrication of TBM. In this study, the mechanical properties of TIG welded RAFM steel were investigated. Various mechanical tests of TIG-welded RAFM steel were performed to obtain the optimized TIG welding process for RAFM steel

  10. Technical issues of reduced activation ferritic/martensitic steels for fabrication of ITER test blanket modules

    International Nuclear Information System (INIS)

    Tanigawa, H.; Hirose, T.; Shiba, K.; Kasada, R.; Wakai, E.; Serizawa, H.; Kawahito, Y.; Jitsukawa, S.; Kimura, A.; Kohno, Y.; Kohyama, A.; Katayama, S.; Mori, H.; Nishimoto, K.; Klueh, R.L.; Sokolov, M.A.; Stoller, R.E.; Zinkle, S.J.

    2008-01-01

    Reduced activation ferritic/martensitic steels (RAFMs) are recognized as the primary candidate structural materials for fusion blanket systems. The RAFM F82H was developed in Japan with emphasis on high-temperature properties and weldability. Extensive irradiation studies have conducted on F82H, and it has the most extensive available database of irradiated and unirradiated properties of all RAFMs. The objective of this paper is to review the R and D status of F82H and to identify the key technical issues for the fabrication of an ITER test blanket module (TBM) suggested from the recent research achievements in Japan. This work clarified that the primary issues with F82H involve welding techniques and the mechanical properties of weld joints. This is the result of the distinctive nature of the joint caused by the phase transformation that occurs in the weld joint during cooling, and its impact on the design of a TBM will be discussed

  11. Thermo-mechanical fatigue behavior of reduced activation ferrite/martensite stainless steels

    International Nuclear Information System (INIS)

    Petersen, C.; Rodrian, D.

    2002-01-01

    The thermo-mechanical cycling fatigue (TMCF) behavior of reduced activation ferrite/martensite stainless steels is examined. The test rig consists of a stiff load frame, which is directly heated by the digitally controlled ohmic heating device. Cylindrical specimens are used with a wall thickness of 0.4 mm. Variable strain rates are applied at TMCF test mode, due to the constant heating rate of 5.8 K/s and variable temperature changes. TMCF results of as received EUROFER 97 in the temperature range between 100 and 500-600 deg. C show a reduction in life time (a factor of 2) compared to F82H mod. and OPTIFER IV. TMCF-experiments with hold times of 100 and 1000 s show dramatic reduction in life time for all three materials

  12. Radiation effects on low cycle fatigue properties of reduced activation ferritic/martensitic steels

    International Nuclear Information System (INIS)

    Hirose, T.; Tanigawa, H.; Ando, M.; Kohyama, A.; Katoh, Y.; Narui, M.

    2002-01-01

    The reduced activation ferritic/martensitic steel, RAFs F82H IEA heat has been fatigue-tested at ambient temperature under diametral strain controlled conditions. In order to evaluate the effects of radiation damage and transmutation damage on fatigue characteristics, post-neutron irradiation and post-helium ion implantation fatigue tests were carried out. Fracture surfaces and fatigue crack initiation on the specimen surface were observed by SEM. Low-temperature irradiation caused an increase in stress amplitude and a reduction in fatigue lifetime corresponding to radiation hardening and loss of ductility. Neutron irradiated samples showed brittle fracture surface, and it was significant for large strain tests. On the other hand, helium implantation caused delay of cyclic softening. However, brittle crack initiation and propagation did not depend on the helium concentration profiles

  13. Diffusion bonding of reduced activation ferritic steel F82H for demo blanket application

    International Nuclear Information System (INIS)

    Kurasawa, T.; Tamura, M.

    1996-01-01

    A reduced activation ferritic steel, a grade F82H developed by JAERI, is a promising candidate structural material for the blanket and the first wall of DEMO reactors. In the present study, diffusion bonding of F82H has been investigated to develop the fabrication procedures of the blanket box and the first wall panel with cooling channels embedded by F82H. The parameters examined are the bonding temperature (810-1050 C), bonding pressure (2-10 MPa) and roughness of the bonding surface (0.5-12.8 μR max ), and metallurgical examination and mechanical tests of the diffusion bonded joints have been conducted. From the tests, sufficient bonding was obtained under the temperatures of 840-1 050 C (compressive stress of 3-12 MPa), and it was found that heat treatment following diffusion bonding is essential to obtain the mechanical properties similar to that of the base metal. (orig.)

  14. Advanced Chemical Reduction of Reduced Graphene Oxide and Its Photocatalytic Activity in Degrading Reactive Black 5

    Directory of Open Access Journals (Sweden)

    Christelle Pau Ping Wong

    2015-10-01

    Full Text Available Textile industries consume large volumes of water for dye processing, leading to undesirable toxic dyes in water bodies. Dyestuffs are harmful to human health and aquatic life, and such illnesses as cholera, dysentery, hepatitis A, and hinder the photosynthetic activity of aquatic plants. To overcome this environmental problem, the advanced oxidation process is a promising technique to mineralize a wide range of dyes in water systems. In this work, reduced graphene oxide (rGO was prepared via an advanced chemical reduction route, and its photocatalytic activity was tested by photodegrading Reactive Black 5 (RB5 dye in aqueous solution. rGO was synthesized by dispersing the graphite oxide into the water to form a graphene oxide (GO solution followed by the addition of hydrazine. Graphite oxide was prepared using a modified Hummers’ method by using potassium permanganate and concentrated sulphuric acid. The resulted rGO nanoparticles were characterized using ultraviolet-visible spectrophotometry (UV-Vis, X-ray powder diffraction (XRD, Raman, and Scanning Electron Microscopy (SEM to further investigate their chemical properties. A characteristic peak of rGO-48 h (275 cm−1 was observed in the UV spectrum. Further, the appearance of a broad peak (002, centred at 2θ = 24.1°, in XRD showing that graphene oxide was reduced to rGO. Based on our results, it was found that the resulted rGO-48 h nanoparticles achieved 49% photodecolorization of RB5 under UV irradiation at pH 3 in 60 min. This was attributed to the high and efficient electron transport behaviors of rGO between aromatic regions of rGO and RB5 molecules.

  15. Interfacial properties of HIP joint between beryllium and reduced activation ferritic/martensitic steel

    International Nuclear Information System (INIS)

    Hirose, T.; Ogiwara, H.; Enoeda, M.; Akiba, M.

    2007-01-01

    Full text of publication follows: ITER test blanket module is the most important components to validate energy production and fuel breeding process for future demonstration reactor. Reduced activation ferritic / martensitic steel is recognized as a promising structural material for breeding blanket systems. And Beryllium must be used as plasma facing materials for ITER in vessel components. In this work, interfacial properties of beryllium/reduced activation ferritic/martensitic steel (RAF/Ms) joint were investigated for a first wall of ITER test blanket module (TBM). The starting materials were ITER grade Beryllium, S65C and a Japanese RAF/M, F82H. The joint was produced by solid state hot isostatic pressing (HIP) method. Chromium layer with the thickness of 1 μm and 10 μm were formed by plasma vapor deposition on the beryllium surface as a diffusion barrier. The HIP was carried out at 1023 K and 1233 K which are determined by standard normalizing and tempering temperature of F82H. The joint made at 1233 K was followed by tempering at 1033 K. The bonding interface was characterized by electron probe microanalysis (EPMA). The bonding strength was also investigated by isometric four point bending tests at ambient temperature. EPMA showed chromium layer effectively worked as a diffusion barrier at 1023 K. However, the beryllium rich layer was formed in F82H after HIP at 1233 K followed by tempering. Bending tests revealed that thin chromium layer and low temperature HIP is preferable. The high temperature HIP introduce brittle BeFe inter metallic compounds along bonding interface. On the other hand, joint with thick chromium layer suffer from brittleness of chromium itself. (authors)

  16. Platinum-doped titanate nanotubes/reduced graphene oxide: photocatalytic activity and flame retardancy

    Science.gov (United States)

    Liu, Guangya; Sang, Bin; Zhou, Zhiqi; Li, Zhiwei

    2018-01-01

    The ‘white pollution’ produced by wasted flexible polyvinyl chloride (PVC) with poor degradation ability and the potential fire hazard of PVC with high flammability not only restrict their application but also cause serious environmental problem. Thus platinum-doped titanate nanotubes/reduced graphene oxide (denoted as Pt-TNTs/rGO) nanocomposites were prepared by a facile method in order to improve the visible photodegradation and get rid of the ‘white pollution’ as well as flame retardancy of PVC. The photodegradation activity and flame retardancy effect of the as-prepared Pt-TNTs/rGO nanocomposites were investigated by ultraviolet and visible light irradiation as well as cone calorimetry. Results show that the Pt-TNTs/rGO-PVC nanocomposites exhibit enhanced visible light photodegradation performance (with mass loss being 6.5%) during 15 day exposure to solar irradiation, and good flame retardancy (providing a 44% reduction of total smoke release as compared with that of PVC matrix). Besides, Pt-TNTs/rGO-PVC nanocomposites show suppressed smoke and reduced CO production as compared with the PVC matrix. These results demonstrate that Pt-TNTs/rGO not only get rid of the ‘white pollution’ as the photocatalyst but also improve the fire safety of PVC as the flame retardant. This could be ascribed to the combination effect between Pt-TNTs and rGO. The present research, hopefully, is to pave a potential pathway to constructing polymer-matrix composites with desired photodegradation activity and flame retardancy, thereby shedding light on simultaneously dealing with the ‘white pollution’ and high flammability of polymer matrix like PVC.

  17. Interfacial properties of HIP joint between beryllium and reduced activation ferritic/martensitic steel

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Ogiwara, H. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Enoeda, M. [Naka Fusion Research Establishment, J.A.E.R.I., Japan Atomic Energy Research Institute, Naka-gun, Ibaraki-ken (Japan); Akiba, M. [Naka Fusion Institute, Japan Atomic Energy Agency, Naka, Ibaraki (Japan)

    2007-07-01

    Full text of publication follows: ITER test blanket module is the most important components to validate energy production and fuel breeding process for future demonstration reactor. Reduced activation ferritic / martensitic steel is recognized as a promising structural material for breeding blanket systems. And Beryllium must be used as plasma facing materials for ITER in vessel components. In this work, interfacial properties of beryllium/reduced activation ferritic/martensitic steel (RAF/Ms) joint were investigated for a first wall of ITER test blanket module (TBM). The starting materials were ITER grade Beryllium, S65C and a Japanese RAF/M, F82H. The joint was produced by solid state hot isostatic pressing (HIP) method. Chromium layer with the thickness of 1 {mu}m and 10 {mu}m were formed by plasma vapor deposition on the beryllium surface as a diffusion barrier. The HIP was carried out at 1023 K and 1233 K which are determined by standard normalizing and tempering temperature of F82H. The joint made at 1233 K was followed by tempering at 1033 K. The bonding interface was characterized by electron probe microanalysis (EPMA). The bonding strength was also investigated by isometric four point bending tests at ambient temperature. EPMA showed chromium layer effectively worked as a diffusion barrier at 1023 K. However, the beryllium rich layer was formed in F82H after HIP at 1233 K followed by tempering. Bending tests revealed that thin chromium layer and low temperature HIP is preferable. The high temperature HIP introduce brittle BeFe inter metallic compounds along bonding interface. On the other hand, joint with thick chromium layer suffer from brittleness of chromium itself. (authors)

  18. Influence of Prior Fatigue Cycling on Creep Behavior of Reduced Activation Ferritic-Martensitic Steel

    Science.gov (United States)

    Sarkar, Aritra; Vijayanand, V. D.; Parameswaran, P.; Shankar, Vani; Sandhya, R.; Laha, K.; Mathew, M. D.; Jayakumar, T.; Rajendra Kumar, E.

    2014-06-01

    Creep tests were carried out at 823 K (550 °C) and 210 MPa on Reduced Activation Ferritic-Martensitic (RAFM) steel which was subjected to different extents of prior fatigue exposure at 823 K at a strain amplitude of ±0.6 pct to assess the effect of prior fatigue exposure on creep behavior. Extensive cyclic softening that characterized the fatigue damage was found to be immensely deleterious for creep strength of the tempered martensitic steel. Creep rupture life was reduced to 60 pct of that of the virgin steel when the steel was exposed to as low as 1 pct of fatigue life. However, creep life saturated after fatigue exposure of 40 pct. Increase in minimum creep rate and decrease in creep rupture ductility with a saturating trend were observed with prior fatigue exposures. To substantiate these findings, detailed transmission electron microscopy studies were carried out on the steel. With fatigue exposures, extensive recovery of martensitic-lath structure was distinctly observed which supported the cyclic softening behavior that was introduced due to prior fatigue. Consequently, prior fatigue exposures were considered responsible for decrease in creep ductility and associated reduction in the creep rupture strength.

  19. The Influence of Robotic Assistance on Reducing Neuromuscular Effort and Fatigue during Extravehicular Activity Glove Use

    Science.gov (United States)

    Madden, Kaci E.; Deshpande, Ashish D.; Peters, Benjamin J.; Rogers, Jonathan M.; Laske, Evan A.; McBryan, Emily R.

    2017-01-01

    The three-layered, pressurized space suit glove worn by Extravehicular Activity (EVA) crew members during missions commonly causes hand and forearm fatigue. The Spacesuit RoboGlove (SSRG), a Phase VI EVA space suit glove modified with robotic grasp-assist capabilities, has been developed to augment grip strength in order to improve endurance and reduce the risk of injury in astronauts. The overall goals of this study were to i) quantify the neuromuscular modulations that occur in response to wearing a conventional Phase VI space suit glove (SSG) during a fatiguing task, and ii) determine the efficacy of Spacesuit RoboGlove (SSRG) in reversing the adverse neuromuscular modulations and restoring altered muscular activity to barehanded levels. Six subjects performed a fatigue sequence consisting of repetitive dynamic-gripping interspersed with isometric grip-holds under three conditions: barehanded, wearing pressurized SSG, and wearing pressurized SSRG. Surface electromyography (sEMG) from six forearm muscles (flexor digitorum superficialis (FDS), flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), extensor digitorum (ED), extensor carpi radialis longus (ECRL), and extensor carpi ulnaris (ECU)) and subjective fatigue ratings were collected during each condition. Trends in amplitude and spectral distributions of the sEMG signals were used to derive metrics quantifying neuromuscular effort and fatigue that were compared across the glove conditions. Results showed that by augmenting finger flexion, the SSRG successfully reduced the neuromuscular effort needed to close the fingers of the space suit glove in more than half of subjects during two types of tasks. However, the SSRG required more neuromuscular effort to extend the fingers compared to a conventional SSG in many subjects. Psychologically, the SSRG aided subjects in feeling less fatigued during short periods of intense work compared to the SSG. The results of this study reveal the promise of the SSRG as a

  20. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    International Nuclear Information System (INIS)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan; Zheng Lan; Zhao Xia

    2011-01-01

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  1. Lifestyle and reduced mortality among active California Mormons, 1980-2004.

    Science.gov (United States)

    Enstrom, James E; Breslow, Lester

    2008-02-01

    The objective is to measure the relationship of several healthy characteristics of the Mormon lifestyle to mortality. We examined 9815 religiously active California Mormon adults followed for mortality during 1980-2004 and 15,832 representative U.S. white adults enrolled in the 1987 National Health Interview Survey (NHIS) and followed for mortality during 1988-1997. The standardized mortality ratio (SMR) and 95% confidence interval (CI) was calculated relative to U.S. whites defined to have a SMR of 1.00. Active California Mormons practice a healthy lifestyle advocated by their religion, which emphasizes a strong family life, education and abstention from tobacco and alcohol. Unusually low SMRs occurred among married never smokers who attended church weekly and had at least 12 years of education. For those aged 25-99 years at entry, the SMR for all causes of death was 0.45 (0.42-0.48) for males and 0.55 (0.51-0.59) for females. For those aged 25-64 years at entry, the SMR for all causes of death was 0.36 (0.32-0.41) for males and 0.46 (0.40-0.53) for females. Life expectancy from age 25 was 84 years for males and 86 years for females. These SMRs were largely replicated among similarly defined persons of all religions within the NHIS cohort. Several healthy characteristics of the Mormon lifestyle are associated with substantially reduced death rates and increased life expectancy.

  2. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles

    Energy Technology Data Exchange (ETDEWEB)

    Gou Maling; Shi Huashan; Guo Gang; Men Ke; Zhang Juan; Li Zhiyong; Luo Feng; Qian Zhiyong; Wei Yuquan [State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041 (China); Zheng Lan; Zhao Xia, E-mail: anderson-qian@163.com [West China Second University Hospital, West China Women' s and Children' s Hospital, Sichuan University, Chengdu 610041 (China)

    2011-03-04

    In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly({epsilon}-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and {approx} 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.

  3. Reduced graphene oxide supported platinum nanocubes composites: one-pot hydrothermal synthesis and enhanced catalytic activity

    International Nuclear Information System (INIS)

    Li, Fumin; Gao, Xueqing; Xue, Qi; Li, Shuni; Chen, Yu; Lee, Jong-Min

    2015-01-01

    Reduced graphene oxide (rGO) supported platinum nanocubes (Pt-NCs) composites (Pt-NCs/rGO) were synthesized successfully by a water-based co-chemical reduction method, in which polyallylamine hydrochloride acted as a multi-functional molecule for the functionalization of graphene oxide, anchorage of Pt II precursor, and control of Pt crystal facets. The morphology, structure, composition, and catalytic property of Pt-NCs/rGO composites were characterized in detail by various spectroscopic techniques. Transmission electron microscopy images showed well-defined Pt-NCs with an average size of 9 nm uniformly distributed on the rGO surface. The as-prepared Pt-NCs/rGO composites had excellent colloidal stability in the aqueous solution, and exhibited superior catalytic activity towards the hydrogenation reduction of nitro groups compared to commercial Pt black. The improved catalytic activity originated from the abundant exposed Pt{100} facets of Pt-NCs, excellent dispersion of Pt-NCs on the rGO surface, and synergistic effect between Pt-NCs and rGO. (paper)

  4. Curcumin reduces Streptococcus mutans biofilm formation by inhibiting sortase A activity.

    Science.gov (United States)

    Hu, Ping; Huang, Ping; Chen, Min Wei

    2013-10-01

    Sortase A is an enzyme responsible for the covalent attachment of Pac proteins to the cell wall in Streptococcus mutans. It has been shown to play a role in modulating the surface properties and the biofilm formation and influence the cariogenicity of S. mutans. Curcumin, an active ingredient of turmeric, was reported to be an inhibitor for Staphylococcus aureus sortase A. The aim of this study was to investigate the inhibitory ability of curcumin against S. mutans sortase A and the effect of curcumin for biofilm formation. The antimicrobial activity of the curcumin to the S. mutans and inhibitory ability of the curcumin against the purified sortase A in vitro were detected. Western-blot and real-time PCR were used to analysis the sortase A mediated Pac protein changes when the S. mutans was cultured with curcumin. The curcumin on the S. mutans biofilm formation was determined by biofilm formation analysis. Curcumin can inhibit purified S. mutans sortase A with a half-maximal inhibitory concentration (IC50) of (10.2±0.7)μmol/l, which is lower than minimum inhibitory concentration (MIC) of 175μmol/l. Curcumin (15μmol/l) was found to release the Pac protein to the supernatant and reduce S. mutans biofilm formation. These results indicated that curcumin is an S. mutans sortase A inhibitor and has promising anti-caries characteristics through an anti-adhesion-mediated mechanism. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  5. Alloying Au surface with Pd reduces the intrinsic activity in catalyzing CO oxidation

    KAUST Repository

    Qian, Kun

    2016-03-30

    © 2016. Various Au-Pd/SiO2 catalysts with a fixed Au loading but different Au:Pd molar ratios were prepared via deposition-precipitation method followed by H2 reduction. The structures were characterized and the catalytic activities in CO oxidation were evaluated. The formation of Au-Pd alloy particles was identified. The Au-Pd alloy particles exhibit enhanced dispersions on SiO2 than Au particles. Charge transfer from Pd to Au within Au-Pd alloy particles. Isolated Pd atoms dominate the surface of Au-Pd alloy particles with large Au:Pd molar ratios while contiguous Pd atoms dominate the surface of Au-Pd alloy particles with small Au:Pd molar ratios. Few synergetic effect of Au-Pd alloy occurs on catalyzing CO oxidation under employed reaction conditions. Alloying Au with Pd reduces the intrinsic activity in catalyzing CO oxidation, and contiguous Pd atoms on the Au-Pd alloy particles are capable of catalyzing CO oxidation while isolated Pd atoms are not. These results advance the fundamental understandings of Au-Pd alloy surfaces in catalyzing CO oxidation.

  6. Allopurinol reduces antigen-specific and polyclonal activation of human T cells

    Directory of Open Access Journals (Sweden)

    Damián ePérez-Mazliah

    2012-09-01

    Full Text Available Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

  7. Reduced Transforming Growth Factor-β Activity in the Endometrium of Women With Heavy Menstrual Bleeding.

    Science.gov (United States)

    Maybin, Jacqueline A; Boswell, Lyndsey; Young, Vicky J; Duncan, William C; Critchley, Hilary O D

    2017-04-01

    Heavy menstrual bleeding (HMB) is common and incapacitating. Aberrant menstrual endometrial repair may result in HMB. The transforming growth factor (TGF)-β superfamily contributes to tissue repair, but its role in HMB is unknown. We hypothesized that TGF-β1 is important for endometrial repair, and women with HMB have aberrant TGF-β1 activity at menses. Endometrial biopsies were collected from women, and menstrual blood loss objectively measured [HMB >80 mL/cycle; normal menstrual bleeding (NMB) endometrial TGF-β1 ligand, receptors, and downstream SMADs in women with NMB and HMB. The function and regulation of TGF-β1 were examined using cell culture. TGFB1 mRNA was maximal immediately prior to menses, but no differences detected between women with NMB and HMB at any cycle stage. Histoscoring of TGFB1 revealed reduced staining in the stroma during menses in women with HMB (P endometrial stromal cells (HES; P Endometrial SMAD2 and SMAD3 were lower in women with HMB during menstruation (P scratch assays revealed increased repair in HES cells treated with TGF-β1 versus control (P endometrial stromal cell repair. Decreased TGF-β1 activity may hinder repair of the denuded menstrual endometrium, resulting in HMB. Copyright © 2017 by the Endocrine Society

  8. Transfection of mouse cytotoxic T lymphocyte with an antisense granzyme A vector reduces lytic activity.

    Science.gov (United States)

    Talento, A; Nguyen, M; Law, S; Wu, J K; Poe, M; Blake, J T; Patel, M; Wu, T J; Manyak, C L; Silberklang, M

    1992-12-15

    Murine CTL have seven serine proteases, known as granzymes, in their lytic granules. Despite considerable effort, convincing evidence that these enzymes play an obligatory role in the lytic process has not been presented. To investigate the function of one of these proteases, granzyme A (GA), we utilized an antisense expression vector to lower the level of the enzyme in the cells. An expression vector containing antisense cDNA for GA and the gene for hygromycin B resistance was constructed and electroporated into the murine CTL line, AR1. Transfectants were selected based on resistance to hygromycin B, and a number of stable lines were developed. One of the antisense lines had greatly reduced levels of GA mRNA, when compared to the parental cells or to control lines transfected with the vector lacking the antisense DNA. The message levels for two other CTL granule proteins, granzyme B and perforin, were unaffected by the antisense vector. The amount of GA, as measured by enzymatic activity, was 3- to 10-fold lower in the transfectant. Most significantly, this line also consistently showed 50 to 70% lower ability to lyse nucleated target cells and to degrade their DNA. Furthermore, it exhibited 90 to 95% lower lytic activity to anti-CD3-coated SRBC. Conjugate formation with target cells, however, was normal. These data provide strong evidence that GA plays an important role in the cytolytic cycle, and that the quantity of enzyme is a limiting factor in these cytolytic cells.

  9. Sulfate reducing bacteria and their activities in oil sands process-affected water biofilm

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hong; Yu, Tong, E-mail: tong.yu@ualberta.ca; Liu, Yang, E-mail: yang.liu@ualberta.ca

    2015-12-01

    Biofilm reactors were constructed to grow stratified multispecies biofilm in oil sands process-affected water (OSPW) supplemented with growth medium. The development of sulfate reducing bacteria (SRB) within the biofilm and the biofilm treatment of OSPW were evaluated. The community structure and potential activity of SRB in the biofilm were investigated with H{sub 2}S microsensor measurements, dsrB gene-based denaturing gradient gel electrophoresis (DGGE), and the real time quantitative polymerase chain reaction (qPCR). Multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H{sub 2}S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the stratified biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. The study expands current knowledge of biofilm treatment of OSPW and the function of anaerobic SRB in OSPW biofilm, and thus provides information for future bioreactor development in the reclamation of OSPW. - Graphical abstract: The development of sulfate reducing bacteria (SRB) within Oil Sands Process-affected Water (OSPW) biofilm and the biofilm treatment of OSPW were evaluated by Liu and coworkers. Combined microsensor and molecular biology techniques were utilized in this study. Their results demonstrated that multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H{sub 2}S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. - Highlights: • Biofilm in oil sands wastewater was developed on engineered biocarriers. • Bacterial community and in situ activity of SRB were studied in the

  10. Sulfate reducing bacteria and their activities in oil sands process-affected water biofilm

    International Nuclear Information System (INIS)

    Liu, Hong; Yu, Tong; Liu, Yang

    2015-01-01

    Biofilm reactors were constructed to grow stratified multispecies biofilm in oil sands process-affected water (OSPW) supplemented with growth medium. The development of sulfate reducing bacteria (SRB) within the biofilm and the biofilm treatment of OSPW were evaluated. The community structure and potential activity of SRB in the biofilm were investigated with H 2 S microsensor measurements, dsrB gene-based denaturing gradient gel electrophoresis (DGGE), and the real time quantitative polymerase chain reaction (qPCR). Multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H 2 S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the stratified biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. The study expands current knowledge of biofilm treatment of OSPW and the function of anaerobic SRB in OSPW biofilm, and thus provides information for future bioreactor development in the reclamation of OSPW. - Graphical abstract: The development of sulfate reducing bacteria (SRB) within Oil Sands Process-affected Water (OSPW) biofilm and the biofilm treatment of OSPW were evaluated by Liu and coworkers. Combined microsensor and molecular biology techniques were utilized in this study. Their results demonstrated that multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H 2 S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. - Highlights: • Biofilm in oil sands wastewater was developed on engineered biocarriers. • Bacterial community and in situ activity of SRB were studied in the biofilm.

  11. The use of active breathing control (ABC) to reduce margin for breathing motion

    International Nuclear Information System (INIS)

    Wong, John W.; Sharpe, Michael B.; Jaffray, David A.; Kini, Vijay R.; Robertson, John M.; Stromberg, Jannifer S.; Martinez, Alavro A.

    1999-01-01

    Purpose: For tumors in the thorax and abdomen, reducing the treatment margin for organ motion due to breathing reduces the volume of normal tissues that will be irradiated. A higher dose can be delivered to the target, provided that the risk of marginal misses is not increased. To ensure safe margin reduction, we investigated the feasibility of using active breathing control (ABC) to temporarily immobilize the patient's breathing. Treatment planning and delivery can then be performed at identical ABC conditions with minimal margin for breathing motion. Methods and Materials: An ABC apparatus is constructed consisting of 2 pairs of flow monitor and scissor valve, 1 each to control the inspiration and expiration paths to the patient. The patient breathes through a mouth-piece connected to the ABC apparatus. The respiratory signal is processed continuously, using a personal computer that displays the changing lung volume in real-time. After the patient's breathing pattern becomes stable, the operator activates ABC at a preselected phase in the breathing cycle. Both valves are then closed to immobilize breathing motion. Breathing motion of 12 patients were held with ABC to examine their acceptance of the procedure. The feasibility of applying ABC for treatment was tested in 5 patients by acquiring volumetric scans with a spiral computed tomography (CT) scanner during active breath-hold. Two patients had Hodgkin's disease, 2 had metastatic liver cancer, and 1 had lung cancer. Two intrafraction ABC scans were acquired at the same respiratory phase near the end of normal or deep inspiration. An additional ABC scan near the end of normal expiration was acquired for 2 patients. The ABC scans were also repeated 1 week later for a Hodgkin's patient. In 1 liver patient, ABC scans were acquired at 7 different phases of the breathing cycle to facilitate examination of the liver motion associated with ventilation. Contours of the lungs and livers were outlined when applicable

  12. Lysophosphatidic acid activates peroxisome proliferator activated receptor-γ in CHO cells that over-express glycerol 3-phosphate acyltransferase-1.

    Directory of Open Access Journals (Sweden)

    Cliona M Stapleton

    2011-04-01

    Full Text Available Lysophosphatidic acid (LPA is an agonist for peroxisome proliferator activated receptor-γ (PPARγ. Although glycerol-3-phosphate acyltransferase-1 (GPAT1 esterifies glycerol-3-phosphate to form LPA, an intermediate in the de novo synthesis of glycerolipids, it has been assumed that LPA synthesized by this route does not have a signaling role. The availability of Chinese Hamster Ovary (CHO cells that stably overexpress GPAT1, allowed us to analyze PPARγ activation in the presence of LPA produced as an intracellular intermediate. LPA levels in CHO-GPAT1 cells were 6-fold higher than in wild-type CHO cells, and the mRNA abundance of CD36, a PPARγ target, was 2-fold higher. Transactivation assays showed that PPARγ activity was higher in the cells that overexpressed GPAT1. PPARγ activity was enhanced further in CHO-GPAT1 cells treated with the PPARγ ligand troglitazone. Extracellular LPA, phosphatidic acid (PA or a membrane-permeable diacylglycerol had no effect, showing that PPARγ had been activated by LPA generated intracellularly. Transient transfection of a vector expressing 1-acylglycerol-3-phosphate acyltransferase-2, which converts endogenous LPA to PA, markedly reduced PPARγ activity, as did over-expressing diacylglycerol kinase, which converts DAG to PA, indicating that PA could be a potent inhibitor of PPARγ. These data suggest that LPA synthesized via the glycerol-3-phosphate pathway can activate PPARγ and that intermediates of de novo glycerolipid synthesis regulate gene expression.

  13. Deuterium retention and desorption behavior in an advanced reduced-activation alloy

    Energy Technology Data Exchange (ETDEWEB)

    Noh, S.J., E-mail: sjnoh@dankook.ac.kr [Department of Applied Physics, Dankook University, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of); Kim, H.S.; Byeon, W.J.; Shin, H.W. [Department of Applied Physics, Dankook University, Yongin-si, Gyeonggi-do 448-701 (Korea, Republic of); Lee, Cheol Eui [Department of Physics, Korea University, Seoul 136-713 (Korea, Republic of); Lee, S.K. [Nuclear Fusion Development Division, Korea Atomic Energy Research Institute, 989-111 Daedeok-daero, Yuseong-gu, Daejeon 305-353 (Korea, Republic of)

    2017-07-15

    We present the first experimental results of the deuterium retention and desorption behavior in an advanced reduced-activation alloy (ARAA) under development in Korea. For the in-situ measurement of desorbed gases from samples immediately after irradiation, a thermal desorption spectroscopy (TDS) system clustered with an inductively coupled plasma ion source has been built. Samples were and were not irradiated with helium ions at energies of 1.4, 3.5, and 5.0 keV and then continuously irradiated with 1.7-keV deuterium ions. TDS measurements were performed in situ immediately after deuterium irradiation and after exposure to air for one week. The amount of desorbed deuterium is the largest for the sample without helium irradiation from the TDS results measured in situ immediately after irradiation. Further, the amount of desorbed deuterium is significantly lowered when the helium energy is increased to 3.5 keV with no significant changes thereafter, indicating that the layer formed by implanted helium at near or deeper than the stopping range for 1.7-keV deuterium ions effectively acts as a barrier against deuterium diffusion into the depth. Because of the strong diffusivity of deuterium into the ambient atmosphere, the amounts of desorbed deuterium are greatly reduced for the samples without helium irradiation and with 1.4-keV helium irradiation after exposure to air for one week. In addition, our deuterium results for the ARAA are also compared with the results for F82H by other authors. - Highlights: •The first result of the deuterium retention and desorption in an ARAA is presented. •The ARAA was irradiated with helium and then continuously irradiated with deuterium. •TDS measurements were performed in situ immediately after deuterium irradiation. •TDS measurements were performed after exposure to air for one week. •The effects of helium irradiation and exposure to air were investigated.

  14. Study of chlordecone desorption from activated carbons and subsequent dechlorination by reduced cobalamin.

    Science.gov (United States)

    Ranguin, Ronald; Durimel, Axelle; Karioua, Reeka; Gaspard, Sarra

    2017-11-01

    Since 1972, the French departments of Guadeloupe and Martinique have intensively used organochlorinated pesticides such as chlordecone (CLD) and hexachlorocyclohexane (HCH) isomers to prevent the proliferation of banana weevil (Cosmopolite sordidus). These molecules are stable in the environment, leading to a continuous contamination of soils, water, and food chain in the banana-producing areas. In these polluted areas, water treatment plants are equipped with activated carbon (AC) filters. In order to improve treatment of CLD-contaminated waters by AC, CLD adsorption and desorption kinetic studies are carried out using different ACs produced from sugar cane bagasse as adsorbents and subsequent CLD degradation is performed using reduced vitamin B12 (VB12). A GC-MS method for CLD quantification is as well optimized. This study shows that bagasse ACs are able to capture the pollutant, leading to a CLD concentration decrease from 1 to 73 μg L -1 , with an adsorption capacity of 162 μg mg -1 . Adsorption capacity increase with the temperature indicates an endothermic process. Polar solvents favor CLD desorption from ACs, suggesting hydrogen bonding between CLD and surface groups of ACs, the best solvent for chemical desorption being ethanol. Subsequent degradation of CLD in ethanol is performed using vitamin B12 reduced by either 1,4-dithiotreitol (DTT) or zerovalent zinc, leading to 90% of CLD removal and to the molecule cage structure opening for formation of a pentachloroindene intermediate product, characterized by GC MS/MS. A pathway for pentachloroindene formation from CLD is proposed.

  15. Increasing ocean temperatures reduce activity patterns of a large commercially important coral reef fish.

    Science.gov (United States)

    Johansen, J L; Messmer, V; Coker, D J; Hoey, A S; Pratchett, M S

    2014-04-01

    Large-bodied fish are critical for sustaining coral reef fisheries, but little is known about the vulnerability of these fish to global warming. This study examined the effects of elevated temperatures on the movement and activity patterns of the common coral trout Plectropomus leopardus (Serranidae), which is an important fishery species in tropical Australia and throughout the Indo West-Pacific. Adult fish were collected from two locations on Australia's Great Barrier Reef (23°S and 14°S) and maintained at one of four temperatures (24, 27, 30, 33 °C). Following >4 weeks acclimation, the spontaneous swimming speeds and activity patterns of individuals were recorded over a period of 12 days. At 24-27 °C, spontaneous swimming speeds of common coral trout were 0.43-0.45 body lengths per second (bls(-1)), but dropped sharply to 0.29 bls(-1) at 30 °C and 0.25 bls(-1) at 33 °C. Concurrently, individuals spent 9.3-10.6% of their time resting motionless on the bottom at 24-27 °C, but this behaviour increased to 14.0% at 30 °C and 20.0% of the time at 33 °C (mean ± SE). The impact of temperature was greatest for smaller individuals (55 cm TL) were first affected by 30 °C and 33 °C, respectively. Importantly, there was some indication that populations can adapt to elevated temperature if presented with adequate time, as the high-latitude population decreased significantly in swimming speeds at both 30 °C and 33 °C, while the low-latitude population only showed significant reductions at 33 °C. Given that movement and activity patterns of large mobile species are directly related to prey encounter rates, ability to capture prey and avoid predators, any reductions in activity patterns are likely to reduce overall foraging and energy intake, limit the energy available for growth and reproduction, and affect the fitness and survival of individuals and populations. © 2013 John Wiley & Sons Ltd.

  16. Inhibition of coagulation and inflammation by activated protein C or antithrombin reduces intestinal ischemia/reperfusion injury in rats

    NARCIS (Netherlands)

    Schoots, Ivo G.; Levi, Marcel; van Vliet, Arlène K.; Maas, Adrie M.; Roossink, E. H. Paulina; van Gulik, Thomas M.

    2004-01-01

    Objective: To examine whether administration of activated protein C or antithrombin reduces local splanchnic derangement of coagulation and inflammation and attenuates intestinal dysfunction and injury following intestinal ischemia/reperfusion. Design: Randomized prospective animal study. Setting:

  17. Vacuum Plasma Spraying W-coated Reduced Activation Structural Steels for Fusion Plasma Facing Components

    Energy Technology Data Exchange (ETDEWEB)

    Noh, Sanghoon; Kim, Tae Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Tungsten (W) and its alloys are considered as candidate materials for plasma facing materials of the first wall and diverter components in fusion reactor systems because of high sputtering resistance and low tritium retention in a fusion environment. Therefore, it is considered that the joining between W and reduced activation structural steels, and its evaluation, are critical issues for the development of fusion reactors. However, the joining between these materials is a very challenging process because of significant differences in their physical properties, particularly the mismatch of coefficients of thermal expansion (CTE). For instance, the CTE of pure W is known to be about 4.3Χ10{sup -6}K{sup -1}; however, that of martensitic steels reaches over three times, about 12-14Χ10{sup -6}K{sup -1} at room temperature even up to 373K. Nevertheless, several joining techniques have been developed for joining between W and structural steels, such as a vapor deposition method, brazing and diffusion bonding. Meanwhile, vacuum plasma spraying (VPS) is supposed to be one of the prospective methods to fabricate a sufficient W layer on the steel substrates because of the coating of a large area with a relatively high fabricating rate. In this study, the VPS method of W powders on reduced activation steels was employed, and its microstructure and hardness distribution were investigated. ODS ferritic steels and F82H steel were coated by VPS-W, and the microstructure and hardness distribution were investigated. A microstructure analysis revealed that pure W was successfully coated on steel substrates by the VPS process without an intermediate layer, in spite of a mismatch of the CTE between dissimilar materials. After neutron irradiation, irradiation hardening significantly occurred in the VPSW. However, the hardening of VPS-W was lesser than that of bulk W irradiated HFIR at 773K. Substrate materials, ODS ferritic steels, and F82H steel, did not show irradiation hardening

  18. Lipoxin A4 inhibits microglial activation and reduces neuroinflammation and neuropathic pain after spinal cord hemisection.

    Science.gov (United States)

    Martini, Alessandra Cadete; Berta, Temugin; Forner, Stefânia; Chen, Gang; Bento, Allisson Freire; Ji, Ru-Rong; Rae, Giles Alexander

    2016-04-08

    Spinal cord injury (SCI) is a severe neurological disorder with many disabling consequences, including persistent neuropathic pain, which develops in about 40 % of SCI patients and is induced and sustained by excessive and uncontrolled spinal neuroinflammation. Here, we have evaluated the effects of lipoxin A4 (LXA4), a member of a unique class of endogenous lipid mediators with both anti-inflammatory and analgesic properties, on spinal neuroinflammation and chronic pain in an experimental model of SCI. Spinal hemisection at T10 was carried out in adult male CD1 mice and Wistar rats. To test if LXA4 can reduce neuroinflammation and neuropathic pain, each animal received two intrathecal injections of LXA4 (300 pmol) or vehicle at 4 and 24 h after SCI. Sensitivity to mechanical stimulation of the hind paws was evaluated using von Frey monofilaments, and neuroinflammation was tested by measuring the mRNA and/or protein expression levels of glial markers and cytokines in the spinal cord samples after SCI. Also, microglia cultures prepared from murine cortical tissue were used to assess the direct effects of LXA4 on microglial activation and release of pro-inflammatory TNF-α. LXA4 treatment caused significant reductions in the intensity of mechanical pain hypersensitivity and spinal expression levels of microglial markers and pro-inflammatory cytokines induced by SCI, when compared to rodents receiving control vehicle injections. Notably, the increased expressions of the microglial marker IBA-1 and of the pro-inflammatory cytokine TNF-α were the most affected by the LXA4 treatment. Furthermore, cortical microglial cultures expressed ALX/FPR2 receptors for LXA4 and displayed potentially anti-inflammatory responses upon challenge with LXA4. Collectively, our results suggest that LXA4 can effectively modulate microglial activation and TNF-α release through ALX/FPR2 receptors, ultimately reducing neuropathic pain in rodents after spinal cord hemisection. The dual anti

  19. Do walking strategies to increase physical activity reduce reported sitting in workplaces: a randomized control trial

    Directory of Open Access Journals (Sweden)

    Burton Nicola W

    2009-07-01

    Full Text Available Abstract Background Interventions designed to increase workplace physical activity may not automatically reduce high volumes of sitting, a behaviour independently linked to chronic diseases such as obesity and type II diabetes. This study compared the impact two different walking strategies had on step counts and reported sitting times. Methods Participants were white-collar university employees (n = 179; age 41.3 ± 10.1 years; 141 women, who volunteered and undertook a standardised ten-week intervention at three sites. Pre-intervention step counts (Yamax SW-200 and self-reported sitting times were measured over five consecutive workdays. Using pre-intervention step counts, employees at each site were randomly allocated to a control group (n = 60; maintain normal behaviour, a route-based walking group (n = 60; at least 10 minutes sustained walking each workday or an incidental walking group (n = 59; walking in workday tasks. Workday step counts and reported sitting times were re-assessed at the beginning, mid- and endpoint of intervention and group mean± SD steps/day and reported sitting times for pre-intervention and intervention measurement points compared using a mixed factorial ANOVA; paired sample-t-tests were used for follow-up, simple effect analyses. Results A significant interactive effect (F = 3.5; p t = 3.9, p t = 2.5, p Conclusion Compared to controls, both route and incidental walking increased physical activity in white-collar employees. Our data suggests that workplace walking, particularly through incidental movement, also has the potential to decrease employee sitting times, but there is a need for on-going research using concurrent and objective measures of sitting, standing and walking.

  20. Exposure of P. gingivalis to noradrenaline reduces bacterial growth and elevates ArgX protease activity.

    Science.gov (United States)

    Saito, Takayuki; Inagaki, Satoru; Sakurai, Kaoru; Okuda, Katsuji; Ishihara, Kazuyuki

    2011-03-01

    Periodontitis, an infectious disease caused by periodontopathic bacteria, including Porphyromonas gingivalis, is reported to be accelerated by stress, under which noradrenaline levels are increased in the bloodstream. The purpose of this study was to evaluate the effects of noradrenaline on P. gingivalis. P. gingivalis was incubated in the presence of 25μM, 50μM, or 100μM adrenaline or noradrenaline at 37°C for 12, 24 or 36h and growth was evaluated by OD(660). Auto-inducer-2 (AI-2) was measured by luminescence of Vibrio harveyi BB 170. Expression of P. gingivalis genes was evaluated using a microarray and RT-PCR. Rgp activity of arg-gingipainA and B (Rgp) was measured with a synthetic substrate. Growth of P. gingivalis FDC381 was inhibited by noradrenaline at 24 and 36h. Growth inhibition by noradrenaline increased dose-dependently. Inhibition of growth partially recovered with addition of propranolol. AI-2 production from P. gingivalis showed a marked decrease with addition of noradrenaline compared with peak production levels in the control group. Microarray analysis revealed an increase in expression in 18 genes and a decrease in expression in 2 genes. Amongst these genes, expression of the protease arg-gingipainB (RgpB) gene, a major virulence factor of P. gingivalis, was further analysed. Expression of rgpB showed a significant increase with addition of noradrenaline, which was partially reduced by addition of propranolol. Cell-associated Rgp activity also increased with addition of noradrenaline. These results suggest that stressors influence the expression of the virulence factors of P. gingivalis via noradrenaline. Copyright © 2010 Elsevier Ltd. All rights reserved.

  1. The loss of activating transcription factor 4 (ATF4) reduces bone toughness and fracture toughness.

    Science.gov (United States)

    Makowski, Alexander J; Uppuganti, Sasidhar; Wadeer, Sandra A; Whitehead, Jack M; Rowland, Barbara J; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S

    2014-05-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of these important factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4-/- littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4-/- mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective of age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4-/- mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also in maintaining bone toughness and fracture toughness. Published by Elsevier Inc.

  2. The Loss of Activating Transcription Factor 4 (ATF4) Reduces Bone Toughness and Fracture Toughness

    Science.gov (United States)

    Makowski, Alexander J.; Uppuganti, Sasidhar; Waader, Sandra A.; Whitehead, Jack M.; Rowland, Barbara J.; Granke, Mathilde; Mahadevan-Jansen, Anita; Yang, Xiangli; Nyman, Jeffry S.

    2014-01-01

    Even though age-related changes to bone tissue affecting fracture risk are well characterized, only a few matrix-related factors have been identified as important to maintaining fracture resistance. As a gene critical to osteoblast differentiation, activating transcription factor 4 (ATF4) is possibly one of the seimportant factors. To test the hypothesis that the loss of ATF4 affects the fracture resistance of bone beyond bone mass and structure, we harvested bones from Atf4+/+ and Atf4−/− littermates at 8 and 20 weeks of age (n≥9 per group) for bone assessment across several length scales. From whole bone mechanical tests in bending, femurs from Atf4−/− mice were found to be brittle with reduced toughness and fracture toughness compared to femurs from Atf4+/+ mice. However, there were no differences in material strength and in tissue hardness, as determined by nanoindentation, between the genotypes, irrespective age. Tissue mineral density of the cortex at the point of loading as determined by micro-computed tomography was also not significantly different. However, by analyzing local composition by Raman Spectroscopy (RS), bone tissue of Atf4−/− mice was found to have higher mineral to collagen ratio compared to wild-type tissue, primarily at 20 weeks of age. From RS analysis of intact femurs at 2 orthogonal orientations relative to the polarization axis of the laser, we also found that the organizational-sensitive peak ratio, ν1 Phosphate per Amide I, changed to a greater extent upon bone rotation for Atf4-deficient tissue, implying bone matrix organization may contribute to the brittleness phenotype. Target genes of ATF4 activity are not only important to osteoblast differentiation but also maintaining bone toughness and fracture toughness. PMID:24509412

  3. Biofeedback effectiveness to reduce upper limb muscle activity during computer work is muscle specific and time pressure dependent

    DEFF Research Database (Denmark)

    Vedsted, Pernille; Søgaard, Karen; Blangsted, Anne Katrine

    2011-01-01

    trapezius (TRA) can reduce bilateral TRA activity but not extensor digitorum communis (EDC) activity; (2) biofeedback from EDC can reduce activity in EDC but not in TRA; (3) biofeedback is more effective in no time constraint than in the time constraint working condition. Eleven healthy women performed......Continuous electromyographic (EMG) activity level is considered a risk factor in developing muscle disorders. EMG biofeedback is known to be useful in reducing EMG activity in working muscles during computer work. The purpose was to test the following hypotheses: (1) unilateral biofeedback from...... computer work during two different working conditions (time constraint/no time constraint) while receiving biofeedback. Biofeedback was given from right TRA or EDC through two modes (visual/auditory) by the use of EMG or mechanomyography as biofeedback source. During control sessions (no biofeedback), EMG...

  4. Efficiency of Worm Reactors in Reducing Sludge Volume in Activated Sludge Systems

    Directory of Open Access Journals (Sweden)

    Azam Naderi

    2017-01-01

    Full Text Available The activated sludge process is the most widely used on a global scale for the biological treatment of both domestic and industrial effluents. One problem associated with the process, however, is the high volume of sludge produced. Excess sludge treatment and disposal account for up to 60% of the total operating costs of urban wastewater treatment plants due to the stringent environmental regulations on excess sludge disposal. These strict requirements have encouraged a growing interest over the last few years in reducing sludge volumes produced at biological treatment plants and a number of physical, chemical, and mechanical methods have been accordingly developed for this purpose. The proposed methods are disadvantaged due to their rather high investment and operation costs. An alternative technology that avoids many of these limitations is the worm reactor. In this study, the characteristics of this technology are investigated while the related literature is reviewed to derive the optimal conditions for the operation of this process in different situations.

  5. Towards a reduced activation structural materials database for fusion DEMO reactors

    International Nuclear Information System (INIS)

    Moeslang, A.; Diegele, E.; Laesser, R.; Klimiankou, M.; Lindau, R.; Materna-Morris, E.; Rieth, M.; Lucon, E.; Petersen, C.; Schneider, H.-C.; Pippan, R.; Rensman, J.W.; Schaaf, B. van der; Tavassoli, F.

    2005-01-01

    The development of First Wall, Blanket and Divertor materials which are capable of withstanding many years the high neutron and heat fluxes, is a critical path to fusion power. Therefore, the timely availability of a sound materials database has become an indispensable element in international fusion road maps. In order to provide materials design data for short term needs of ITER Test Blanket Modules and for a DEMOnstration fusion reactor, a wealth of R and D results on the European reduced activation ferritic-martensitic steel EUROFER, and on oxide dispersion strengthened variants are being characterized, mainly in the temperature window 250-650 deg. C. The characterisation includes irradiations up to 15 dpa in the mixed spectrum reactor HFR and up to 75 dpa in the fast breeder reactor BOR60. Industrial EUROFER-batches of 3.5 and 7.5 tons have been produced with a variety of semi-finished, quality-assured product forms. To increase thermal efficiency of blankets, high temperature resistant SiC f /SiC channel inserts for liquid metal coolant tubes are also developed. Regarding radiation damage resistance, a broad based reactor irradiation programs counts several steps from ≤5dpa (ITER TBMs) up to 75 dpa (DEMO). For the European divertor designers, a materials data base is presently being set up for pure W and W alloys, and related reactor irradiations are foreseen with temperatures from 650-1000 deg. C. (author)

  6. Thermal and mechanical behaviour of the reduced-activation-ferritic-martensitic steel EUROFER

    International Nuclear Information System (INIS)

    Lindau, R.; Moeslang, A.; Schirra, M.

    2002-01-01

    Reduced activation ferritic/martensitic (RAFM) steels are being considered for structural application in potential fusion energy systems. Based on the substantial experience with RAFM developmental steels of OPTIFER type, an industrial 3.5 tons batch of a 9CrWVTa-RAFM steel, called EUROFER 97 had been specified and ordered. A characterisation programme has been launched to determine the relevant mechanical and physical-metallurgical properties in order to qualify the steel for fusion application. The hardening, tempering and transformation behaviour of EUROFER is in good agreement with that of other RAFM-steels like OPTIFER and the Japanese industrial scale heat F82H mod. Tensile tests, performed between RT and 750 deg. C, show comparable strength and ductility values that are not strongly affected by different heat treatments and ageing at 580 and 600 deg. C up to 3300 h. Impact bending tests indicate a superior ductile to brittle transition temperature (DBTT) of EUROFER in the as-received condition compared with that of F82H mod. Creep tests between 450 and 650 deg. C up to test times of 15000 h reveal a creep strength similar to other RAFM steels like OPTIFER and F82H mod. EUROFER shows a good low-cycle fatigue behaviour with longer lifetimes than F82H mod. The deformation and softening behaviour is similar

  7. Microstructural characterization of 5-9% chromium reduced-activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Jayaram, R. [Univ. of Pittsburgh, PA (United States); Klueh, R.L. [Oak Ridge National Lab., TN (United States)

    1997-08-01

    The microstructures of a 9Cr-2W-0.25-0.1C (9Cr-2WV), a 9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa), a 7Cr-2W-0.25V-0.07Ta-0.1C (7Cr-2WVTa), and a 5Cr-2W-0.25V-0.07Ta-0.1C (5Cr-2WVTa) steel (all compositions are in weight percent) have been characterized by Analytical Electron Microscopy (AEM) and Atom Probe Field Ion Microscopy (APFIM). The matrix in all four reduced-activation steels was 100% martensite. In the two 9Cr steels, the stable precipitates were blocky M{sub 23}C{sub 6} and small spherical MC. The two lower-chromium steels contained blocky M{sub 7}C{sub 3} and small needle-shaped carbonitrides in addition to M{sub 23}C{sub 6}. AEM and APFIM analysis revealed that in the steels containing tantalum, the majority of the tantalum was in solid solution. The experimental observations were in good agreement with phases and compositions predicted by phase equilibria calculations.

  8. Chemical compatibility study of lithium titanate with Indian reduced activation ferritic martensitic steel

    International Nuclear Information System (INIS)

    Sonak, Sagar; Jain, Uttam; Haldar, Rumu; Kumar, Sanjay

    2015-01-01

    Highlights: • Chemical compatibility between Li_2TiO_3 and Indian RAFM steel has been studied at ITER operating temperature. • The lithium titanate chemically reacted with ferritic martensitic steel to form a brittle and non-adherent oxide layer. • The layer grew in a parabolic manner as a function of heating time. • Diffusion of oxygen (from Li_2TiO_3) appears to be controlling the oxide layer. - Abstract: Chemical compatibility between lithium titanate and Indian reduced activation ferritic-martensitic steel (In-RAFMS) was studied for the first time under ITER operating temperature. Lithium titanate required for the study was synthesized in-house. Coupons of In-RAFMS were packed inside lithium titanate powder and heated at 550 °C up to 900 h under inert argon atmosphere. The lithium titanate chemically reacted with ferritic martensitic steel to form a brittle and non-adherent oxide layer. The layer grew in a parabolic manner as a function of heating time. Microstructural and phase evolution of this oxide layer was studied using XRD, SEM and EPMA. Iron and chromium enriched zones were found within the oxide layer. Diffusion of oxygen (from Li_2TiO_3) appears to be controlling the oxide layer.

  9. Delta ferrite in the weld metal of reduced activation ferritic martensitic steel

    Energy Technology Data Exchange (ETDEWEB)

    Sam, Shiju, E-mail: shiju@ipr.res.in [Institute for Plasma Research, Gandhinagar, Gujarat 382 428 (India); Das, C.R.; Ramasubbu, V.; Albert, S.K.; Bhaduri, A.K.; Jayakumar, T. [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Rajendra Kumar, E. [Institute for Plasma Research, Gandhinagar, Gujarat 382 428 (India)

    2014-12-15

    Formation of delta(δ)-ferrite in the weld metal, during autogenous bead-on-plate welding of Reduced Activation Ferritic Martensitic (RAFM) steel using Gas Tungsten Arc Welding (GTAW) process, has been studied. Composition of the alloy is such that delta-ferrite is not expected in the alloy; but examination of the weld metal revealed presence of delta-ferrite in the weld metal. Volume fraction of delta-ferrite is found to be higher in the weld interface than in the rest of the fusion zone. Decrease in the volume fraction of delta-ferrite, with an increase in preheat temperature or with an increase in heat input, is observed. Results indicate that the cooling rate experienced during welding affects the volume fraction of delta-ferrite retained in the weld metal and variation in the delta-ferrite content with cooling rate is explained with variation in the time that the weld metal spends in various temperature regimes in which delta-ferrite is stable for the alloy during its cooling from the liquid metal to the ambient temperature. This manuscript will discuss the effect of welding parameters on formation of delta-ferrite and its retention in the weld metal of RAFM steel.

  10. Fatigue life assessment based on crack growth behavior in reduced activation ferritic/martensitic steel

    International Nuclear Information System (INIS)

    Nogami, Shuhei; Sato, Yuki; Hasegawa, Akira

    2010-01-01

    Crack growth behavior under low cycle fatigue in reduced activation ferritic/martensitic steel, F82H IEA-heat (Fe-8Cr-2W-0.2V-0.02Ta), was investigated to improve the fatigue life assessment method of fusion reactor structural material. Low cycle fatigue test was carried out at room temperature in air at a total strain range of 0.4-1.5% using an hourglass-type miniature fatigue specimen. The relationship between the surface crack length and life fraction was described using one equation independent of the total strain range. Therefore, the fatigue life and residual life could be estimated using the surface crack length. Moreover, the microcrack initiation life could be estimated using the total strain range if there was a one-to-one correspondence between the total strain range and number of cycles to failure. The crack growth rate could be estimated using the total strain range and surface crack length by introducing the concept of the normalized crack growth rate. (author)

  11. Synthesis, Characterization and Photocatalytic Activity of Reduced Graphene Oxide-Ce/ZnO Composites

    International Nuclear Information System (INIS)

    Zhang, Wenjun; Zhao, Jinfeng; Zou, Xuefeng

    2016-01-01

    A series of Ce-doped ZnO (Ce/ZnO) nanostructures were fabricated using the co-precipitation method, then a simply nontoxic hydrothermal approach was proposed for preparation of reduced graphene oxide (rGO)-Ce/ZnO composites. The synthesized composites were investigated by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), photoluminescence spectroscopy (PL), electrochemical impedance spectroscopy (EIS), UV-vis diffuse reflectance spectroscopy (DRS) techniques and Raman pattern. The as-synthesized rGO-Ce/ZnO composites showed high photodecomposition efficiency in comparison with the rGO-ZnO, Ce/ZnO, pure ZnO under UV, visible-light and sunlight irradiation. The degradation of methylene blue (MB) (10 mg/L, 100ml) by 95.8% within 60 min by using rGO-2 (10 mg) under sunlight irradiation was observed. The repeated use of the rGO-2 was investigated, and the results showed almost no decay in the catalytic activity

  12. In situ treatment with activated carbon reduces bioaccumulation in aquatic food chains.

    Science.gov (United States)

    Kupryianchyk, D; Rakowska, M I; Roessink, I; Reichman, E P; Grotenhuis, J T C; Koelmans, A A

    2013-05-07

    In situ activated carbon (AC) amendment is a new direction in contaminated sediment management, yet its effectiveness and safety have never been tested on the level of entire food chains including fish. Here we tested the effects of three different AC treatments on hydrophobic organic chemical (HOC) concentrations in pore water, benthic invertebrates, zooplankton, and fish (Leuciscus idus melanotus). AC treatments were mixing with powdered AC (PAC), mixing with granular AC (GAC), and addition-removal of GAC (sediment stripping). The AC treatments resulted in a significant decrease in HOC concentrations in pore water, benthic invertebrates, zooplankton, macrophytes, and fish. In 6 months, PAC treatment caused a reduction of accumulation of polychlorobiphenyls (PCB) in fish by a factor of 20, bringing pollutant levels below toxic thresholds. All AC treatments supported growth of fish, but growth was inhibited in the PAC treatment, which was likely explained by reduced nutrient concentrations, resulting in lower zooplankton (i.e., food) densities for the fish. PAC treatment may be advised for sites where immediate ecosystem protection is required. GAC treatment may be equally effective in the longer term and may be adequate for vulnerable ecosystems where longer-term protection suffices.

  13. Reduced prefrontal dopaminergic activity in valproic acid-treated mouse autism model.

    Science.gov (United States)

    Hara, Yuta; Takuma, Kazuhiro; Takano, Erika; Katashiba, Keisuke; Taruta, Atsuki; Higashino, Kosuke; Hashimoto, Hitoshi; Ago, Yukio; Matsuda, Toshio

    2015-08-01

    Previous studies suggest that dysfunction of neurotransmitter systems is associated with the pathology of autism in humans and the disease model rodents, but the precise mechanism is not known. Rodent offspring exposed prenatally to VPA shows autism-related behavioral abnormalities. The present study examined the effect of prenatal VPA exposure on brain monoamine neurotransmitter systems in male and female mice. The prenatal VPA exposure did not affect the levels of dopamine (DA), noradrenaline (NA), serotonin (5-HT) and their metabolites in the prefrontal cortex and striatum, while it significantly reduced methamphetamine (METH) (1.0 mg/kg)-induced hyperlocomotion in male offspring. In vivo microdialysis study demonstrated that prenatal VPA exposure attenuated METH-induced increases in extracellular DA levels in the prefrontal cortex, while it did not affect those in extracellular NA and 5-HT levels. Prenatal VPA exposure also decreased METH-induced c-Fos expression in the prefrontal cortex and the mRNA levels of DA D1 and D2 receptors in the prefrontal cortex. These effects of VPA were not observed in the striatum. In contrast to male offspring, prenatal VPA exposure did not affect METH-induced increases in locomotor activity and prefrontal DA levels and the D1 and D2 receptor mRNA levels in the prefrontal cortex in female offspring. These findings suggest that prenatal VPA exposure causes hypofunction of prefrontal DA system in a sex-dependent way. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Optimum alloy compositions in reduced-activation martensitic 9Cr steels for fusion reactor

    International Nuclear Information System (INIS)

    Abe, F.; Noda, T.; Okada, M.

    1992-01-01

    In order to obtain potential reduced-activation ferritic steels suitable for fusion reactor structures, the effect of alloying elements W and V on the microstructural evolution, toughness, high-temperature creep and irradiation hardening behavior was investigated for simple 9Cr-W and 9Cr-V steels. The creep strength of the 9Cr-W steels increased but their toughness decreased with increasing W concentration. The 9Cr-V steels exhibited poor creep rupture strength, far below that of a conventional 9Cr-1MoVNb steel and poor toughness after aging at 873 K. It was also found that the Δ-ferrite should be avoided, because it degraded both the roughness and high-temperature creep strength. Based on the results on the simple steels, optimized martensitic 9Cr steels were alloy-designed from a standpoint of enough thoughness and high-temperature creep strength. Two kinds of optimized 9Cr steels with low and high levels of W were obtained; 9Cr-1WVTa and 9Cr-3WVTa. These steels indeed exhibited excellent toughness and creep strength, respectively. The 9Cr-1WVTa steel exhibiting an excellent roughness was shown to be the most promising for relatively low-temperature application below 500deg C, where irradiation embrittlement is significant. The 9Cr-3WVTa steel was the most promising for high temperature application above 500deg C from the standpoint of enough high-temperature strength. (orig.)

  15. Reduced activation ODS ferritic steel - recent development in high speed hot extrusion processing

    Energy Technology Data Exchange (ETDEWEB)

    Oksiuta, Zbigniew [Faculty of Mechanical Engineering, Bialystok Technical University (Poland); Lewandowska, Malgorzata; Kurzydlowski, Krzysztof [Faculty of Materials Science and Engineering, Warsaw University of Technology (Poland); Baluc, Nadine [Ecole Polytechnique Federale de Lausanne (EPFL), Centre de Recherches en Physique des Plasmas, Association Euratom-Confederation Suisse, Villigen PSI (Switzerland)

    2010-05-15

    The paper presents the microstructure and mechanical properties of an oxide dispersion strengthened (ODS), reduced activation, ferritic steel, namely the Fe-14Cr-2W-0.3Ti-0.3Y{sub 2}O{sub 3} alloy, which was fabricated by hot isostatic pressing followed by high speed hydrostatic extrusion (HSHE) and heat treatment HT at 1050 C. Transmission electron microscopy (TEM) observations revealed significant differences in the grain size and dislocation density between the as-HIPped and as-HSHE materials. It was also found that the microstructure of the steel is stable after HT. The HSHE process improves significantly the tensile and Charpy impact properties of the as-HIPped steel. The ultimate tensile strength at room temperature increases from 950 up to 1350 MPa, while the upper shelf energy increases from 3.0 up to 6.0 J. However, the ductile-to-brittle transition temperature (DBTT) remains relatively high (about 75 C).These results indicate that HSHE is a promising method for achieving grain refinement and thus improving the mechanical properties of ODS ferritic steels. (Abstract Copyright [2010], Wiley Periodicals, Inc.)

  16. Multiscale simulation of yield strength in reduced-activation ferritic/martensitic steel

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Chen Chong; Zhang, Chi; Yang, Zhigang [Key Laboratory of Advanced Materials of Ministry of Education, School of Materials Science and Engineering, Tsinghua University, Beijing (China); Zhao, Ji Jun [State Key Laboratory of Materials Modification by Laser, Electron, and Ion Beams, School of Physics and Optoelectronic Technology and College of Advanced Science and Technology, Dalian University of Technology, Dalian (China)

    2017-04-15

    One of the important requirements for the application of reduced-activation ferritic/martensitic (RAFM) steel is to retain proper mechanical properties under irradiation and high-temperature conditions. To simulate the yield strength and stress-strain curve of steels during high-temperature and irradiation conditions, a multiscale simulation method consisting of both microstructure and strengthening simulations was established. The simulation results of microstructure parameters were added to a superposition strengthening model, which consisted of constitutive models of different strengthening methods. Based on the simulation results, the strength contribution for different strengthening methods at both room temperature and high-temperature conditions was analyzed. The simulation results of the yield strength in irradiation and high-temperature conditions were mainly consistent with the experimental results. The optimal application field of this multiscale model was 9Cr series (7–9 wt.%Cr) RAFM steels in a condition characterized by 0.1–5 dpa (or 0 dpa) and a temperature range of 25–500°C.

  17. Microstructural characterization of 5-9% chromium reduced-activation steels

    International Nuclear Information System (INIS)

    Jayaram, R.; Klueh, R.L.

    1997-01-01

    The microstructures of a 9Cr-2W-0.25-0.1C (9Cr-2WV), a 9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa), a 7Cr-2W-0.25V-0.07Ta-0.1C (7Cr-2WVTa), and a 5Cr-2W-0.25V-0.07Ta-0.1C (5Cr-2WVTa) steel (all compositions are in weight percent) have been characterized by Analytical Electron Microscopy (AEM) and Atom Probe Field Ion Microscopy (APFIM). The matrix in all four reduced-activation steels was 100% martensite. In the two 9Cr steels, the stable precipitates were blocky M 23 C 6 and small spherical MC. The two lower-chromium steels contained blocky M 7 C 3 and small needle-shaped carbonitrides in addition to M 23 C 6 . AEM and APFIM analysis revealed that in the steels containing tantalum, the majority of the tantalum was in solid solution. The experimental observations were in good agreement with phases and compositions predicted by phase equilibria calculations

  18. Tensile and charpy impact properties of irradiated reduced-activation ferritic steels

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J. [Oak Ridge National Lab., TN (United States)

    1996-10-01

    Tensile tests were conducted on eight reduced-activation Cr-W steels after irradiation to 15-17 and 26-29 dpa, and Charpy impact tests were conducted on the steels irradiated to 26-29 dpa. Irradiation was in the Fast Flux Test Facility at 365{degrees}C on steels containing 2.25-12% Cr, varying amounts of W, V, and Ta, and 0.1%C. Previously, tensile specimens were irradiated to 6-8 dpa and Charpy specimens to 6-8, 15-17, and 20-24 dpa. Tensile and Charpy specimens were also thermally aged to 20000 h at 365{degrees}C. Thermal aging had little effect on the tensile behavior or the ductile-brittle transition temperature (DBTT), but several steels showed a slight increase in the upper-shelf energy (USE). After {approx}7 dpa, the strength of the steels increased and then remained relatively unchanged through 26-29 dpa (i.e., the strength saturated with fluence). Post-irradiation Charpy impact tests after 26-29 dpa showed that the loss of impact toughness, as measured by an increase in DBTT and a decrease in the USE, remained relatively unchanged from the values after 20-24 dpa, which had been relatively unchanged from the earlier irradiations. As before, the two 9Cr steels were the most irradiation resistant.

  19. Evaluation of mechanical properties of weldments for reduced activation ferritic/martensitic steel

    Energy Technology Data Exchange (ETDEWEB)

    Nakata, T. [Muroran Institute of Technology, Dept. of Materials Science and Engineeering, Muroran, Hokkaido (Japan); Tanigawa, H.; Ando, M. [Japan Atomic Energy Agency, Naga-gun, Ibaraki-ken (Japan); Komazaki, S.; Kohno, Y. [Muroran Institute of Technology, Muroran (Japan)

    2007-07-01

    Full text of publication follows: Reduced activation ferritic/martensitic steels are the first candidate material for fusion reactor, and will be used as the structural materials of ITER test blanket modules (TBM). TBM will be assembled by welding various parts, it is important to be clearly mechanical properties of weldments to qualify TBM structure. In this paper, unirradiated mechanical properties of weldments, which is consisted of weld metal, heat affected zone (HAZ) and base metal region, obtained from TIG and EB welded F82H IEA-heat were evaluated by tensile, Charpy impact and creep test. Charpy impact test revealed that impact properties of weld metal does not deteriorate compared with that of base metal. The creep tests were carried out at temperatures of 773-873 K and at stress levels of 130-280 MPa, with the specimens which include weld metal and HAZ region in the gage section. In these conditions, rupture time of weldments yield to about 100-1000 hours. In the high-stress range, creep lives of welded joint decreased about 40% of base metal. However, in the low-stress range, creep lives of welded joint decrease about 60 to 70% of base metal. The failure at fine grain HAZ region (Type IV failure) does not occur in these conditions. The mechanism of these properties deterioration will be discussed based on the detailed analyses on microstructure changes. (authors)

  20. Effect of helium on fatigue crack growth and life of reduced activation ferritic/martensitic steel

    International Nuclear Information System (INIS)

    Nogami, Shuhei; Takahashi, Manabu; Hasegawa, Akira; Yamazaki, Masanori

    2013-01-01

    The effects of helium on the fatigue life, micro-crack growth behavior up to final fatigue failure, and fracture mode under fatigue in the reduced activation ferritic/martensitic steel, F82H IEA-heat, were investigated by low cycle fatigue tests at room temperature in air at a total strain range of 0.6–1.5%. Significant reduction of the fatigue life due to helium implantation was observed for a total strain range of 1.0–1.5%, which might be attributable to an increase in the micro-crack propagation rate. However, the reduction of fatigue life due to helium implantation was not significant for a total strain range of 0.6–0.8%. A brittle fracture surface (an original point of micro-crack initiation) and a cleavage fracture surface were observed in the helium-implanted region of fracture surface. A striation pattern was observed in the non-implanted region. These fracture modes of the helium-implanted specimen were independent of the strain range

  1. Activation of murine pre-proglucagon-producing neurons reduces food intake and body weight.

    Science.gov (United States)

    Gaykema, Ronald P; Newmyer, Brandon A; Ottolini, Matteo; Raje, Vidisha; Warthen, Daniel M; Lambeth, Philip S; Niccum, Maria; Yao, Ting; Huang, Yiru; Schulman, Ira G; Harris, Thurl E; Patel, Manoj K; Williams, Kevin W; Scott, Michael M

    2017-03-01

    Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide-secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake-lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide-expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal.

  2. Activation of murine pre-proglucagon–producing neurons reduces food intake and body weight

    Science.gov (United States)

    Gaykema, Ronald P.; Newmyer, Brandon A.; Ottolini, Matteo; Warthen, Daniel M.; Lambeth, Philip S.; Niccum, Maria; Yao, Ting; Huang, Yiru; Schulman, Ira G.; Harris, Thurl E.; Patel, Manoj K.; Williams, Kevin W.

    2017-01-01

    Peptides derived from pre-proglucagon (GCG peptides) act in both the periphery and the CNS to change food intake, glucose homeostasis, and metabolic rate while playing a role in anxiety behaviors and physiological responses to stress. Although the actions of GCG peptides produced in the gut and pancreas are well described, the role of glutamatergic GGC peptide–secreting hindbrain neurons in regulating metabolic homeostasis has not been investigated. Here, we have shown that chemogenetic stimulation of GCG-producing neurons reduces metabolic rate and food intake in fed and fasted states and suppresses glucose production without an effect on glucose uptake. Stimulation of GCG neurons had no effect on corticosterone secretion, body weight, or conditioned taste aversion. In the diet-induced obese state, the effects of GCG neuronal stimulation on gluconeogenesis were lost, while the food intake–lowering effects remained, resulting in reductions in body weight and adiposity. Our work suggests that GCG peptide–expressing neurons can alter feeding, metabolic rate, and glucose production independent of their effects on hypothalamic pituitary-adrenal (HPA) axis activation, aversive conditioning, or insulin secretion. We conclude that GCG neurons likely stimulate separate populations of downstream cells to produce a change in food intake and glucose homeostasis and that these effects depend on the metabolic state of the animal. PMID:28218622

  3. Do evidence-based active-engagement courses reduce the gender gap in introductory physics?

    Science.gov (United States)

    Karim, Nafis I.; Maries, Alexandru; Singh, Chandralekha

    2018-03-01

    Prior research suggests that using evidence-based pedagogies can not only improve learning for all students, it can also reduce the gender gap. We describe the impact of physics education research-based pedagogical techniques in flipped and active-engagement non-flipped courses on the gender gap observed with validated conceptual surveys. We compare male and female students’ performance in courses which make significant use of evidence-based active-engagement (EBAE) strategies with courses that primarily use lecture-based (LB) instruction. All courses had large enrolment and often had more than 100 students. The analysis of data for validated conceptual surveys presented here includes data from two-semester sequences of algebra-based and calculus-based introductory physics courses. The conceptual surveys used to assess student learning in the first and second semester courses were the force concept inventory and the conceptual survey of electricity and magnetism, respectively. In the research discussed here, the performance of male and female students in EBAE courses at a particular level is compared with LB courses in two situations: (I) the same instructor taught two courses, one of which was an EBAE course and the other an LB course, while the homework, recitations and final exams were kept the same; (II) student performance in all of the EBAE courses taught by different instructors was averaged and compared with LB courses of the same type also averaged over different instructors. In all cases, on conceptual surveys we find that students in courses which make significant use of active-engagement strategies, on average, outperformed students in courses of the same type using primarily lecture-based instruction even though there was no statistically significant difference on the pre-test before instruction. However, the gender gap persisted even in courses using EBAE methods. We also discuss correlations between the performance of male and female students on

  4. Active travel co-benefits of travel demand management policies that reduce greenhouse gas emissions.

    Science.gov (United States)

    2014-04-01

    There is increasing evidence that improved health outcomes may be a significant co-benefit of land use plans and transport policies : that increase active transport (or active travel)walking, biking or other physical activity for the purpose...

  5. Kinetics of Indigenous Nitrate Reducing Sulfide Oxidizing Activity in Microaerophilic Wastewater Biofilms

    Science.gov (United States)

    Villahermosa, Desirée; Corzo, Alfonso; Garcia-Robledo, Emilio; González, Juan M.; Papaspyrou, Sokratis

    2016-01-01

    Nitrate decreases sulfide release in wastewater treatment plants (WWTP), but little is known on how it affects the microzonation and kinetics of related microbial processes within the biofilm. The effect of nitrate addition on these properties for sulfate reduction, sulfide oxidation, and oxygen respiration were studied with the use of microelectrodes in microaerophilic wastewater biofilms. Mass balance calaculations and community composition analysis were also performed. At basal WWTP conditions, the biofilm presented a double-layer system. The upper microaerophilic layer (~300 μm) showed low sulfide production (0.31 μmol cm-3 h-1) and oxygen consumption rates (0.01 μmol cm-3 h-1). The anoxic lower layer showed high sulfide production (2.7 μmol cm-3 h-1). Nitrate addition decreased net sulfide production rates, caused by an increase in sulfide oxidation rates (SOR) in the upper layer, rather than an inhibition of sulfate reducing bacteria (SRB). This suggests that the indigenous nitrate reducing-sulfide oxidizing bacteria (NR-SOB) were immediately activated by nitrate. The functional vertical structure of the biofilm changed to a triple-layer system, where the previously upper sulfide-producing layer in the absence of nitrate split into two new layers: 1) an upper sulfide-consuming layer, whose thickness is probably determined by the nitrate penetration depth within the biofilm, and 2) a middle layer producing sulfide at an even higher rate than in the absence of nitrate in some cases. Below these layers, the lower net sulfide-producing layer remained unaffected. Net SOR varied from 0.05 to 0.72 μmol cm-3 h-1 depending on nitrate and sulfate availability. Addition of low nitrate concentrations likely increased sulfate availability within the biofilm and resulted in an increase of both net sulfate reduction and net sulfide oxidation by overcoming sulfate diffusional limitation from the water phase and the strong coupling between SRB and NR-SOB syntrophic

  6. Kinetics of Indigenous Nitrate Reducing Sulfide Oxidizing Activity in Microaerophilic Wastewater Biofilms.

    Directory of Open Access Journals (Sweden)

    Desirée Villahermosa

    Full Text Available Nitrate decreases sulfide release in wastewater treatment plants (WWTP, but little is known on how it affects the microzonation and kinetics of related microbial processes within the biofilm. The effect of nitrate addition on these properties for sulfate reduction, sulfide oxidation, and oxygen respiration were studied with the use of microelectrodes in microaerophilic wastewater biofilms. Mass balance calaculations and community composition analysis were also performed. At basal WWTP conditions, the biofilm presented a double-layer system. The upper microaerophilic layer (~300 μm showed low sulfide production (0.31 μmol cm-3 h-1 and oxygen consumption rates (0.01 μmol cm-3 h-1. The anoxic lower layer showed high sulfide production (2.7 μmol cm-3 h-1. Nitrate addition decreased net sulfide production rates, caused by an increase in sulfide oxidation rates (SOR in the upper layer, rather than an inhibition of sulfate reducing bacteria (SRB. This suggests that the indigenous nitrate reducing-sulfide oxidizing bacteria (NR-SOB were immediately activated by nitrate. The functional vertical structure of the biofilm changed to a triple-layer system, where the previously upper sulfide-producing layer in the absence of nitrate split into two new layers: 1 an upper sulfide-consuming layer, whose thickness is probably determined by the nitrate penetration depth within the biofilm, and 2 a middle layer producing sulfide at an even higher rate than in the absence of nitrate in some cases. Below these layers, the lower net sulfide-producing layer remained unaffected. Net SOR varied from 0.05 to 0.72 μmol cm-3 h-1 depending on nitrate and sulfate availability. Addition of low nitrate concentrations likely increased sulfate availability within the biofilm and resulted in an increase of both net sulfate reduction and net sulfide oxidation by overcoming sulfate diffusional limitation from the water phase and the strong coupling between SRB and NR

  7. Annexin A5 binds to lipopolysaccharide and reduces its endotoxin activity.

    Science.gov (United States)

    Rand, Jacob H; Wu, Xiao-Xuan; Lin, Elaine Y; Griffel, Alexander; Gialanella, Philip; McKitrick, John C

    2012-01-01

    Annexin A5 (AnxA5) has a high affinity for phosphatidylserine. The protein is widely used to detect apoptotic cells because phosphatidylserine, a phospholipid that is normally present in the inner leaflets of cytoplasmic membranes, becomes translocated to the outer leaflets during programmed cell death. Here we report the novel observation that AnxA5 binds to Gram-negative bacteria via the lipid A domain of lipopolysaccharide (LPS). Binding of AnxA5 to bacteria was measured quantitatively, confirmed by fluorescence microscopy, and found to be inhibited by antibodies against lipid A. AnxA5 also bound to purified dot-blotted LPS and lipid A. Through ellipsometry, we found that the binding of AnxA5 to purified LPS was calcium dependent and rapid and showed a high affinity-characteristics similar to those of AnxA5 binding to phosphatidylserine. Initial functional studies indicated that AnxA5 can affect LPS activities. AnxA5 inhibited LPS-mediated gelation in the Limulus amebocyte lysate assay. Incubation of LPS with the protein reduced the quantity of tumor necrosis factor alpha (TNF-α) released by cultured monocytes compared to that released upon incubation with LPS alone. Initial in vivo experiments indicated that injection of mice with LPS preincubated with AnxA5 produced serum TNF-α levels lower than those seen after injection of LPS alone. These data demonstrate that AnxA5 binds to LPS and open paths to investigation of the potential biological and therapeutic implications of this interaction. AnxA5 is highly expressed in cells that have a barrier function-including, among others, vascular endothelium, placental trophoblasts, and epithelial cells lining bile ducts, renal tubules, mammary ducts, and nasal epithelium. The protein has been well characterized for its binding to phospholipid bilayers that contain phosphatidylserine. This report of a previously unrecognized activity of AnxA5 opens the door to investigation of the possibility that this binding may have

  8. Empowering Sedentary Adults to Reduce Sedentary Behavior and Increase Physical Activity Levels and Energy Expenditure: A Pilot Study

    OpenAIRE

    Barwais, Faisal A.; Cuddihy, Thomas F.

    2015-01-01

    Objective: The purpose of this study was to assess the effectiveness of a 4-week intervention in which an online personal activity monitor (Gruve-Technologies™) was used to reduce sedentary behavior among sedentary adults. Method: Eighteen, sedentary adult volunteers (12 men, six women, mean age 29 ± 4.0 years) were recruited to participate in the study. Time spent in sedentary activities and light-, moderate-, and vigorous-intensity physical activity and energy expenditure were assessed duri...

  9. Hyperpolarization-activated current (In is reduced in hippocampal neurons from Gabra5-/- mice.

    Directory of Open Access Journals (Sweden)

    Robert P Bonin

    Full Text Available Changes in the expression of γ-aminobutyric acid type A (GABAA receptors can either drive or mediate homeostatic alterations in neuronal excitability. A homeostatic relationship between α5 subunit-containing GABAA (α5GABAA receptors that generate a tonic inhibitory conductance, and HCN channels that generate a hyperpolarization-activated cation current (Ih was recently described for cortical neurons, where a reduction in Ih was accompanied by a reciprocal increase in the expression of α5GABAA receptors resulting in the preservation of dendritosomatic synaptic function. Here, we report that in mice that lack the α5 subunit gene (Gabra5-/-, cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a decrease in Ih current density (by 40% and 28%, respectively, compared with neurons from wild-type (WT mice. The resting membrane potential and membrane hyperpolarization induced by blockade of Ih with ZD-7288 were similar in cultured WT and Gabra5-/- neurons. In contrast, membrane hyperpolarization measured after a train of action potentials was lower in Gabra5-/- neurons than in WT neurons. Also, membrane impedance measured in response to low frequency stimulation was greater in cultured Gabra5-/- neurons. Finally, the expression of HCN1 protein that generates Ih was reduced by 41% in the hippocampus of Gabra5-/- mice. These data indicate that loss of a tonic GABAergic inhibitory conductance was followed by a compensatory reduction in Ih. The results further suggest that the maintenance of resting membrane potential is preferentially maintained in mature and immature hippocampal neurons through the homeostatic co-regulation of structurally and biophysically distinct cation and anion channels.

  10. The Abundance and Activity of Nitrate-Reducing Microbial Populations in Estuarine Sediments

    Science.gov (United States)

    Cardarelli, E.; Francis, C. A.

    2014-12-01

    Estuaries are productive ecosystems that ameliorate nutrient and metal contaminants from surficial water supplies. At the intersection of terrestrial and aquatic environments, estuarine sediments host major microbially-mediated geochemical transformations. These include denitrification (the conversion of nitrate to nitrous oxide and/or dinitrogen) and dissimilatory nitrate reduction to ammonium (DNRA). Denitrification has historically been seen as the predominant nitrate attenuation process and functions as an effective sink for nitrate. DNRA has previously been believed to be a minor nitrate reduction process and transforms nitrate within the ecosystem to ammonium, a more biologically available N species. Recent studies have compared the two processes in coastal environments and determined fluctuating environmental conditions may suppress denitrification, supporting an increased role for DNRA in the N cycle. Nitrate availability and salinity are factors thought to influence the membership of the microbial communities present, and the nitrate reduction process that predominates. The aim of this study is to investigate how nitrate concentration and salinity alter the transcript abundances of N cycling functional gene markers for denitrification (nirK, nirS) and DNRA (nrfA) in estuarine sediments at the mouth of the hypernutrified Old Salinas River, CA. Short-term whole core incubations amended with artificial freshwater/artificial seawater (2 psu, 35 psu) and with varying NO3- concentrations (200mM, 2000mM) were conducted to assess the activity as well as the abundance of the nitrate-reducing microbial populations present. Gene expression of nirK, nirS, and nrfA at the conclusion of the incubations was quantified using reverse transcription quantitative polymerase chain reaction (RT-qPCR). High abundances of nirK, nirS, and nrfA under particular conditions coupled with the resulting geochemical data ultimately provides insight onto how the aforementioned factors

  11. Reducing the activity and secretion of microbial antioxidants enhances the immunogenicity of BCG.

    Directory of Open Access Journals (Sweden)

    Shanmugalakshmi Sadagopal

    Full Text Available In early clinical studies, the live tuberculosis vaccine Mycobacterium bovis BCG exhibited 80% protective efficacy against pulmonary tuberculosis (TB. Although BCG still exhibits reliable protection against TB meningitis and miliary TB in early childhood it has become less reliable in protecting against pulmonary TB. During decades of in vitro cultivation BCG not only lost some genes due to deletions of regions of the chromosome but also underwent gene duplication and other mutations resulting in increased antioxidant production.To determine whether microbial antioxidants influence vaccine immunogenicity, we eliminated duplicated alleles encoding the oxidative stress sigma factor SigH in BCG Tice and reduced the activity and secretion of iron co-factored superoxide dismutase. We then used assays of gene expression and flow cytometry with intracellular cytokine staining to compare BCG-specific immune responses in mice after vaccination with BCG Tice or the modified BCG vaccine. Compared to BCG, the modified vaccine induced greater IL-12p40, RANTES, and IL-21 mRNA in the spleens of mice at three days post-immunization, more cytokine-producing CD8+ lymphocytes at the peak of the primary immune response, and more IL-2-producing CD4+ lymphocytes during the memory phase. The modified vaccine also induced stronger secondary CD4+ lymphocyte responses and greater clearance of challenge bacilli.We conclude that antioxidants produced by BCG suppress host immune responses. These findings challenge the hypothesis that the failure of extensively cultivated BCG vaccines to prevent pulmonary tuberculosis is due to over-attenuation and suggest instead a new model in which BCG evolved to produce more immunity-suppressing antioxidants. By targeting these antioxidants it may be possible to restore BCG's ability to protect against pulmonary TB.

  12. Context-dependent activation of reduced autobiographical memory specificity as an avoidant coping style.

    Science.gov (United States)

    Debeer, Elise; Raes, Filip; Williams, J Mark G; Hermans, Dirk

    2011-12-01

    According to the affect-regulation hypothesis (Williams et al., 2007), reduced autobiographical memory specificity (rAMS) or overgeneral memory (OGM) might be considered a cognitive avoidance strategy; that is, people learn to avoid the emotionally painful consequences associated with the retrieval of specific negative memories. Based on this hypothesis, one would predict significant negative associations between AMS and avoidant coping. However, studies investigating this prediction have led to equivocal results. In the present study we tested a possible explanation for these contradictory findings. It was hypothesized that rAMS (in part) reflects an avoidant coping strategy, which might only become apparent under certain conditions, that is, conditions that signal the possibility of 'danger.' To test this hypothesis, we assessed AMS and behavioral avoidance but experimentally manipulated the instructions. In the neutral condition, two parallel versions of the Autobiographical Memory Test (AMT) were presented under neutral instructions. In the threat condition, the first AMT was presented under neutral instructions, while the second AMT was presented under 'threat instructions.' Results showed no significant correlations between avoidance and OGM under neutral conditions but significant and markedly stronger correlations under threat conditions, with more avoidance being associated with fewer specific and more categoric memories. In addition, high avoiders showed a stronger reduction in AMS in the threat condition as compared with the neutral condition, while low avoiders showed no such difference between conditions. The data confirm that OGM can be considered as part of a broader avoidant coping style. However, more importantly, they show that, at least in nonclinical individuals, the activation of this coping style may depend on the context. (c) 2011 APA, all rights reserved.

  13. Development of an extensive database of mechanical properties for Reduced Activation Ferritic/Martensitic Steels

    International Nuclear Information System (INIS)

    Tanigawa, H.; Shiba, K.; Ando, M.; Wakai, E.; Jitsukawa, S.; Hirose, T.; Kasada, R.; Kimura, A.; Kohyama, A.; Kohno, Y.; Klueh, R.L.; Sokolov, M.; Stoller, R.; Zinklek, S.; Yamamoto, T.; Odette, G.; Kurtz, R.J.

    2007-01-01

    Full text of publication follows: Reduced activation ferritic/martensitic steels (RAFMs) are recognized as the primary candidate structural materials for fusion blanket systems, as they have been developed based on massive industrial experience of ferritic/martensitic steel replacing Mo and Nb of high chromium heat resistant martensitic steels (such as modified 9Cr-1Mo) with W and Ta, respectively. F82H (8Cr-2W-0.2V-0.04Ta-0.1C) and JLF-1 (9Cr-2W-0.2V-0.08Ta-0.1C) are RAFMs, which have been developed and studied in Japan and the various effects of irradiation were reported. F82H is designed with emphasis on high temperature property and weldablility, and was provided and evaluated in various countries as a part of the IEA fusion materials development collaboration. The Japan/US collaboration program also has been conducted with the emphasis on heavy irradiation effects of F82H, JLF-1 and ORNL9Cr2WVTa over the past two decades using Fast Flux Testing Facility (FFTF) of PNNL and High Flux Isotope Reactor (HFIR) of ORNL, and the irradiation condition of the irradiation capsules of those reactors were precisely controlled by the well matured capsule designing and instrumentation. Now, among the existing database for RAFMs the most extensive one is that for F82H. The objective of this paper is to review the database status of RAFMs, mainly on F82H, to identify the key issues for the future development of database. Tensile, fracture toughness, creep and fatigue properties and microstructural studies before and after irradiation are summarized. (authors)

  14. Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects

    Science.gov (United States)

    Carter, Jason R.; Ray, Chester A.; Downs, Emily M.; Cooke, William H.

    2003-01-01

    The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.

  15. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging

    Directory of Open Access Journals (Sweden)

    Zhuoran Yin

    2018-03-01

    Full Text Available Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD or low-fat diet (LFD during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS. Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32 in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  16. Low-Fat Diet With Caloric Restriction Reduces White Matter Microglia Activation During Aging.

    Science.gov (United States)

    Yin, Zhuoran; Raj, Divya D; Schaafsma, Wandert; van der Heijden, Roel A; Kooistra, Susanne M; Reijne, Aaffien C; Zhang, Xiaoming; Moser, Jill; Brouwer, Nieske; Heeringa, Peter; Yi, Chun-Xia; van Dijk, Gertjan; Laman, Jon D; Boddeke, Erik W G M; Eggen, Bart J L

    2018-01-01

    Rodent models of both aging and obesity are characterized by inflammation in specific brain regions, notably the corpus callosum, fornix, and hypothalamus. Microglia, the resident macrophages of the central nervous system, are important for brain development, neural support, and homeostasis. However, the effects of diet and lifestyle on microglia during aging are only partly understood. Here, we report alterations in microglia phenotype and functions in different brain regions of mice on a high-fat diet (HFD) or low-fat diet (LFD) during aging and in response to voluntary running wheel exercise. We compared the expression levels of genes involved in immune response, phagocytosis, and metabolism in the hypothalamus of 6-month-old HFD and LFD mice. We also compared the immune response of microglia from HFD or LFD mice to peripheral inflammation induced by intraperitoneal injection of lipopolysaccharide (LPS). Finally, we investigated the effect of diet, physical exercise, and caloric restriction (40% reduction compared to ad libitum intake) on microglia in 24-month-old HFD and LFD mice. Changes in diet caused morphological changes in microglia, but did not change the microglia response to LPS-induced systemic inflammation. Expression of phagocytic markers (i.e., Mac-2/Lgals3, Dectin-1/Clec7a, and CD16/CD32) in the white matter microglia of 24-month-old brain was markedly decreased in calorically restricted LFD mice. In conclusion, LFD resulted in reduced activation of microglia, which might be an underlying mechanism for the protective role of caloric restriction during aging-associated decline.

  17. Habituation of Salmonella spp. at Reduced Water Activity and Its Effect on Heat Tolerance

    Science.gov (United States)

    Mattick, K. L.; Jørgensen, F.; Legan, J. D.; Lappin-Scott, H. M.; Humphrey, T. J.

    2000-01-01

    The effect of habituation at reduced water activity (aw) on heat tolerance of Salmonella spp. was investigated. Stationary-phase cells were exposed to aw 0.95 in broths containing glucose-fructose, sodium chloride, or glycerol at 21°C for up to a week prior to heat challenge at 54°C. In addition, the effects of different aws and heat challenge temperatures were investigated. Habituation at aw 0.95 resulted in increased heat tolerance at 54°C with all solutes tested. The extent of the increase and the optimal habituation time depended on the solute used. Exposure to broths containing glucose-fructose (aw 0.95) for 12 h resulted in maximal heat tolerance, with more than a fourfold increase in D54 values. Cells held for more than 72 h in these conditions, however, became as heat sensitive as nonhabituated populations. Habituation in the presence of sodium chloride or glycerol gave rise to less pronounced but still significant increases in heat tolerance at 54°C, and a shorter incubation time was required to maximize tolerance. The increase in heat tolerance following habituation in broths containing glucose-fructose (aw 0.95) was RpoS independent. The presence of chloramphenicol or rifampin during habituation and inactivation did not affect the extent of heat tolerance achieved, suggesting that de novo protein synthesis was probably not necessary. These data highlight the importance of cell prehistory prior to heat inactivation and may have implications for food manufacturers using low-aw ingredients. PMID:11055944

  18. Current status of reduced-activation ferritic/martensitic steels R and D for fusion energy

    International Nuclear Information System (INIS)

    Kimura, Akihiko

    2005-01-01

    Reduced-activation ferritic/martensitic (RAF/M) steels have been considered to be the prime candidate for the fusion blanket structural material. The irradiation data obtained up to now indicates rather high feasibility of the steels for application to fusion reactors because of their high resistance to degradation of material performance caused by both the irradiation-induced displacement damage and transmutation helium atoms. The martensitic structure of RAF/M steels consists of a large number of lattice defects before the irradiation, which strongly retards the formation of displacement damage through absorption and annihilation of the point defects generated by irradiation. Transmutation helium can be also trapped at those defects in the martensitic structure so that the growth of helium bubbles at grain boundaries is suppressed. The major properties of the steels are well within our knowledge, and processing technologies are mostly developed for fusion application. RAF/M steels are now certainly ready to proceed to the next stage, that is, the construction of International Thermo-nuclear Experimental Reactor Test Blanket Modules (ITER-TBM). Oxide dispersion strengthening (ODS) steels have been developed for higher thermal efficiency of fusion power plants. Recent irradiation experiments indicated that the steels were quite highly resistant to neutron irradiation embrittlement, showing hardening accompanied by no loss of ductility. High-Cr ODS steels whose chromium concentration was in the range from 14 to 19 mass% showed high resistance to corrosion in supercritical pressurized water. It is shown that the 14Cr-ODS steel is susceptible to neither hydrogen nor helium embrittlement. A combined utilization of ODS steels with RAF/M steels will be effective to realize fusion power early at a reasonable thermal efficiency. (author)

  19. Materials design data for reduced activation martensitic steel type F82H

    Energy Technology Data Exchange (ETDEWEB)

    Tavassoli, A.-A.F. E-mail: tavassoli@cea.fr; Rensman, J.-W.; Schirra, M.; Shiba, K

    2002-11-01

    This paper presents materials data for design of ITER test blanket modules with the reduced activation ferritic martensitic steel type F82H as structural material. From the physical properties databases, variations of modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. Also reported are Poisson's ratio and magnetic properties. From the tension test results, nominal and minimum stress values of S{sub y} and S{sub u} are derived and used for calculation of allowable primary membrane stress intensity S{sub m}. Likewise, uniform and total elongations, as well as reduction of area data, are used for calculation of minimum and true ductility at rupture values. From the instrumented Charpy impact and fracture toughness test data, ductile to brittle transition temperature, toughness and behavior of material in different fracture modes are evaluated. The effect of specimen size and geometry are discussed but preference is given to standard size specimens. From the fatigue data, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves, using a reduction factor of 2 on strain and a reduction factor of 20 on number of cycles to failure. Cyclic hardening curves are also derived and compared with monotonic hardening curves. From the creep data, time dependent allowable stresses S{sub r} and S{sub t} are calculated. Combination of tension and creep results are used to deduce S{sub mt} and isochronus curves. Finally, irradiated and aged materials data are compared to insure that the safety margins incorporated in unirradiated design limits are not exceeded.

  20. Activation of temperature-sensitive TRPV1-like receptors in ARC POMC neurons reduces food intake.

    Directory of Open Access Journals (Sweden)

    Jae Hoon Jeong

    2018-04-01

    Full Text Available Proopiomelanocortin (POMC neurons in the arcuate nucleus of the hypothalamus (ARC respond to numerous hormonal and neural signals, resulting in changes in food intake. Here, we demonstrate that ARC POMC neurons express capsaicin-sensitive transient receptor potential vanilloid 1 receptor (TRPV1-like receptors. To show expression of TRPV1-like receptors in ARC POMC neurons, we use single-cell reverse transcription-polymerase chain reaction (RT-PCR, immunohistochemistry, electrophysiology, TRPV1 knock-out (KO, and TRPV1-Cre knock-in mice. A small elevation of temperature in the physiological range is enough to depolarize ARC POMC neurons. This depolarization is blocked by the TRPV1 receptor antagonist and by Trpv1 gene knockdown. Capsaicin-induced activation reduces food intake that is abolished by a melanocortin receptor antagonist. To selectively stimulate TRPV1-like receptor-expressing ARC POMC neurons in the ARC, we generate an adeno-associated virus serotype 5 (AAV5 carrying a Cre-dependent channelrhodopsin-2 (ChR2-enhanced yellow fluorescent protein (eYFP expression cassette under the control of the two neuronal POMC enhancers (nPEs. Optogenetic stimulation of TRPV1-like receptor-expressing POMC neurons decreases food intake. Hypothalamic temperature is rapidly elevated and reaches to approximately 39 °C during treadmill running. This elevation is associated with a reduction in food intake. Knockdown of the Trpv1 gene exclusively in ARC POMC neurons blocks the feeding inhibition produced by increased hypothalamic temperature. Taken together, our findings identify a melanocortinergic circuit that links acute elevations in hypothalamic temperature with acute reductions in food intake.

  1. Development of an extensive database of mechanical properties for Reduced Activation Ferritic/Martensitic Steels

    Energy Technology Data Exchange (ETDEWEB)

    Tanigawa, H.; Shiba, K.; Ando, M.; Wakai, E.; Jitsukawa, S. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Kasada, R.; Kimura, A.; Kohyama, A. [Kyoto Univ., lnstitute of Advanced Energy (Japan); Kohno, Y. [Muroran Institute of Technology, Muroran, Hokkaido (Japan); Klueh, R.L. [0ak Ridge Noational Laboratory, TN (United States); Sokolov, M.; Stoller, R.; Zinklek, S. [0ak Ridge Noational Laboratory, Materials Science and Technology Div., TN (United States); Yamamoto, T.; Odette, G. [UCSB, Dept. of Chemical Engineering UCSB, Santa-Barbara (United States); Kurtz, R.J. [Pacifie Northwest National Laboratory, Richland WA (United States)

    2007-07-01

    Full text of publication follows: Reduced activation ferritic/martensitic steels (RAFMs) are recognized as the primary candidate structural materials for fusion blanket systems, as they have been developed based on massive industrial experience of ferritic/martensitic steel replacing Mo and Nb of high chromium heat resistant martensitic steels (such as modified 9Cr-1Mo) with W and Ta, respectively. F82H (8Cr-2W-0.2V-0.04Ta-0.1C) and JLF-1 (9Cr-2W-0.2V-0.08Ta-0.1C) are RAFMs, which have been developed and studied in Japan and the various effects of irradiation were reported. F82H is designed with emphasis on high temperature property and weldablility, and was provided and evaluated in various countries as a part of the IEA fusion materials development collaboration. The Japan/US collaboration program also has been conducted with the emphasis on heavy irradiation effects of F82H, JLF-1 and ORNL9Cr2WVTa over the past two decades using Fast Flux Testing Facility (FFTF) of PNNL and High Flux Isotope Reactor (HFIR) of ORNL, and the irradiation condition of the irradiation capsules of those reactors were precisely controlled by the well matured capsule designing and instrumentation. Now, among the existing database for RAFMs the most extensive one is that for F82H. The objective of this paper is to review the database status of RAFMs, mainly on F82H, to identify the key issues for the future development of database. Tensile, fracture toughness, creep and fatigue properties and microstructural studies before and after irradiation are summarized. (authors)

  2. Hardening and embrittlement mechanisms of reduced activation ferritic/martensitic steels irradiated at 573 K

    Energy Technology Data Exchange (ETDEWEB)

    Tanigawa, H. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Klueh, R.L. [Oak Ridge Noational Laboratory, TN (United States); Hashimoto, N. [Hokkaido Univ., Materials Science and Engineering Div., Graduate School of Engineering, Sapporo (Japan); Sokolov, M. [Oak Ridge National Laboratory, Materials Science and Technology Div., TN (United States)

    2007-07-01

    Full text of publication follows: It has been reported that reduced-activation ferritic/martensitic steels (RAFMs), such as F82H, ORNL9Cr-2WVTa, and JLF-1, showed a variety of changes in ductile-brittle transition temperature and yield stress after irradiation at 573 K up to 5 dpa, and those differences could not be interpreted solely by the difference of dislocation microstructure induced by irradiation. To investigate the impact of other microstructural feature, i.e. precipitates, the precipitation behavior of F82H, ORNL 9Cr-2WVTa, and JLF-1 was examined. It was revealed that irradiation-induced precipitation and amorphization of precipitates partly occurred and caused the different precipitation on block, packet and prior austenitic grain boundaries. In addition to these phenomena, irradiation-induced nano-size precipitates were also observed in the matrix. It was also revealed that the chemical compositions of precipitates approached the calculated thermal equilibrium state of M{sub 23}C{sub 6} at an irradiation temperature of 573 K. The calculation also suggests the presence of Laves phase at 573 K, which is usually not observed at this temperature, but the ion irradiation on aged F82H with Laves phase suggests that Laves phase becomes amorphous and could not be stable under irradiation at 573 K. This observation indicates the possibility that the irradiation-induced nano-size precipitation could be the consequence of the conflict between precipitation and amorphization of Laves phase. Over all, these observations suggests that the variety of embrittlement and hardening of RAFMs observed at 573 K irradiation up to 5 dpa might be the consequence of the transition phenomena that occur as the microstructure approaches thermal equilibrium during irradiation at 573 K. (authors)

  3. Facile determination of the specific activity of carbonyl compounds reduced by tritiated borohydride

    Energy Technology Data Exchange (ETDEWEB)

    Avigad, G [Rutgers--the State Univ., Piscataway, NJ (USA)

    1979-12-01

    Three procedures are described for microliter samples of glucose 6-phosphate or lactose as model compounds. After the reduction with (/sup 3/H)-NaBH/sub 4/ and suitable treatment, specific activity is calculated from the ratios /sup 3/H activity/total phosphorus, /sup 3/H//sup 14/C activity, or /sup 3/H activity/galactoside concentration.

  4. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Qualtrough, David, E-mail: david.qualtrough@uwe.ac.uk [Department of Biological, Biomedical & Analytical Sciences, University of the West of England, Faculty of Health and Applied Sciences, University of the West of England, Frenchay, Bristol BS16 1QY (United Kingdom); Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos [School of Cellular & Molecular Medicine, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD (United Kingdom)

    2015-09-17

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  5. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    Directory of Open Access Journals (Sweden)

    David Qualtrough

    2015-09-01

    Full Text Available Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, Cancers 2015, 7 1886 these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer.

  6. The Hedgehog Inhibitor Cyclopamine Reduces β-Catenin-Tcf Transcriptional Activity, Induces E-Cadherin Expression, and Reduces Invasion in Colorectal Cancer Cells

    International Nuclear Information System (INIS)

    Qualtrough, David; Rees, Phil; Speight, Beverley; Williams, Ann C.; Paraskeva, Christos

    2015-01-01

    Colorectal cancer is a major global health problem resulting in over 600,000 deaths world-wide every year with the majority of these due to metastatic disease. Wnt signalling, and more specifically β-catenin-related transcription, has been shown to drive both tumorigenesis and the metastatic process in colorectal neoplasia, yet its complex interactions with other key signalling pathways, such as hedgehog, remain to be elucidated. We have previously shown that the Hedgehog (HH) signalling pathway is active in cells from colorectal tumours, and that inhibition of the pathway with cyclopamine induces apoptosis. We now show that cyclopamine treatment reduces β-catenin related transcription in colorectal cancer cell lines, and that this effect can be reversed by addition of Sonic Hedgehog protein. We also show that cyclopamine concomitantly induces expression of the tumour suppressor and prognostic indicator E-cadherin. Consistent with a role for HH in regulating the invasive potential we show that cyclopamine reduces the expression of transcription factors (Slug, Snail and Twist) associated with the epithelial-mesenchymal transition and reduces the invasiveness of colorectal cancer cells in vitro. Taken together, these data show that pharmacological inhibition of the hedgehog pathway has therapeutic potential in the treatment of colorectal cancer

  7. Evaluation of Structure, Chaperone-Like Activity and Allergenicity of Reduced Glycated Adduct of Bovine β-casein.

    Science.gov (United States)

    Yousefi, Reza; Ferdowsi, Leila; Tavaf, Zohreh; Sadeghian, Tanaz; Tamaddon, Ali M; Moghtaderi, Mozhgan; Pourpak, Zahra

    2017-01-01

    Milk has a potent reducing environment with an important quantity of sugar levels. In the current study β-casein was glycated in the presence of D-glucose and sodium cyanoborohydride as a reducing agent. Then, the reduced glucitol adduct of β-casein was used for the structural and functional analyses using different spectroscopic techniques. The results of fluorescence and far ultraviolet circular dichroism assessments suggest important structural alteration upon non-enzymatic glycation of β-casein. In addition, the chaperone activity, micellization properties and antioxidant activity of this protein were altered upon glucose modification. Also, as a result of reduced glycation, the allergenicity profile of this protein remained largely unchanged. Additional to its energetic and nutritional values, β-casein has important functional properties. The native structure of this protein is important to perform accurately its biological functions. Non-enzymatic glycation under reducing state was capable to alter both structural and functional aspects of β-casein. Due to effective reducing environment and significant quantity of reducing sugar of human milk, similar structural and functional alterations are most likely to occur upon reducing glycation of β-casein in vivo. Also, these changes might be even intensified during chronic hyperglycemia in diabetic mothers. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Leisure time physical activity is associated with a reduced risk of preterm delivery

    DEFF Research Database (Denmark)

    Hegaard, Hanne Kristine; Hedegaard, Morten; Damm, Peter

    2008-01-01

    This study was undertaken to study the association between the times spent on sports activities and leisure time physical activity in the first and early second trimester of pregnancy and the risk of preterm delivery.......This study was undertaken to study the association between the times spent on sports activities and leisure time physical activity in the first and early second trimester of pregnancy and the risk of preterm delivery....

  9. Activated platelets enhance IL-10 secretion and reduce TNF-α secretion by monocytes

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Hasselbalch, Hans C; Nielsen, Claus H

    2013-01-01

    ), Escherichia coli LPS, or intact Porphyromonas gingivalis. Addition of platelets activated by thrombin-receptor-activating peptide enhanced IL-10 production induced by LPS (p gingivalis (p ....05), and P. gingivalis (p gingivalis-stimulated cultures (p ... of activated platelets. Adherence of platelets increased TG- and TT-induced IL-10 secretion by monocytes (p gingivalis (p

  10. Acute fasting inhibits central caspase-1 activity reducing anxiety-like behavior and increasing novel object and object location recognition.

    Science.gov (United States)

    Towers, Albert E; Oelschlager, Maci L; Patel, Jay; Gainey, Stephen J; McCusker, Robert H; Freund, Gregory G

    2017-06-01

    Inflammation within the central nervous system (CNS) is frequently comorbid with anxiety. Importantly, the pro-inflammatory cytokine most commonly associated with anxiety is IL-1β. The bioavailability and activity of IL-1β are regulated by caspase-1-dependent proteolysis vis-a-vis the inflammasome. Thus, interventions regulating the activation or activity of caspase-1 should reduce anxiety especially in states that foster IL-1β maturation. Male C57BL/6j, C57BL/6j mice treated with the capase-1 inhibitor biotin-YVAD-cmk, caspase-1 knockout (KO) mice and IL-1R1 KO mice were fasted for 24h or allowed ad libitum access to food. Immediately after fasting, caspase-1 activity was measured in brain region homogenates while activated caspase-1 was localized in the brain by immunohistochemistry. Mouse anxiety-like behavior and cognition were tested using the elevated zero maze and novel object/object location tasks, respectively. A 24h fast in mice reduced the activity of caspase-1 in whole brain and in the prefrontal cortex, amygdala, hippocampus, and hypothalamus by 35%, 25%, 40%, 40%, and 40% respectively. A 24h fast also reduced anxiety-like behavior by 40% and increased novel object and object location recognition by 21% and 31%, respectively. IL-1β protein, however, was not reduced in the brain by fasting. ICV administration of YVAD decreased caspase-1 activity in the prefrontal cortex and amygdala by 55%, respectively leading to a 64% reduction in anxiety like behavior. Importantly, when caspase-1 KO or IL1-R1 KO mice are fasted, no fasting-dependent reduction in anxiety-like behavior was observed. Results indicate that fasting decrease anxiety-like behavior and improves memory by a mechanism tied to reducing caspase-1 activity throughout the brain. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Effects of irradiation on low cycle fatigue properties for reduced activation ferritic/martensitic steel

    International Nuclear Information System (INIS)

    Kim, S.W.; Tanigawa, H.; Hirose, T.; Kohyama, A.

    2007-01-01

    Full text of publication follows: In materials life decision for a commercial blanket, thermal fatigue property of materials is a particularly important. The loading of structural materials in fusion reactor is, besides the plasma surface interactions, a combined effect of high heat fluxes and neutron irradiation. Depending on the pulse lengths, the operating conditions, and the thermal conductivity, these oscillating temperature gradients will cause elastic and elastic-plastic cyclic deformation giving rise to (creep-) fatigue in structural first wall and blanket components. Especially, investigation of the fatigue property in Reduced Activation Ferritic/Martensitic (RAF/M) steel and establishment of the evaluation technology are demanded in particular immediately for design/manufacturing of ITER-TBM. And also, fatigue testing after irradiation will be carried out in hot cells with remote control system. Considering limited ability of specimen manipulation in the cells, the specimen and the test method need to be simple for operation. The existing data bases of RAF/M steel provide baseline data set including post-irradiation fatigue data. However, to perform the accurate fatigue lifetime assessment for ITER-TBM and beyond utilizing the existing data base, the mechanical understanding of fatigue fracture is mandatory. It has been previously reported by co-authors that dislocation cell structure was developed on low cycle fatigued RAF/M steel, and led the fatigue crack to develop along prior austenitic grain boundary. In this work, the effects of nuclear irradiation on low cycle fatigue properties for RAF/M steels and its fracture mechanisms were examined based on the flow stress analysis and detailed microstructure analysis. Fracture surfaces and crack initiation site were investigated by scanning electron microscope (SEM). Transmission electron microscopy (TEM) was also applied to clarify the microstructural features of fatigue behavior. It is also important to

  12. High Temperature Elastic Properties of Reduced Activation Ferritic-Martensitic (RAFM) Steel Using Impulse Excitation Technique

    Science.gov (United States)

    Tripathy, Haraprasanna; Raju, Subramanian; Hajra, Raj Narayan; Saibaba, Saroja

    2018-03-01

    The polycrystalline elastic constants of an indigenous variant of 9Cr-1W-based reduced activation ferritic-martensitic (RAFM) steel have been determined as a function of temperature from 298 K to 1323 K (25 °C to 1000 °C), using impulse excitation technique (IET). The three elastic constants namely, Young's modulus E, shear modulus G, and bulk modulus B, exhibited significant softening with increasing temperature, in a pronounced non-linear fashion. In addition, clearly marked discontinuities in their temperature variations are noticed in the region, where ferrite + carbides → austenite phase transformation occurred upon heating. Further, the incidence of austenite → martensite transformation upon cooling has also been marked by a step-like jump in both elastic E and shear moduli G. The martensite start M s and M f finish temperatures estimated from this study are, M s = 652 K (379 °C) and M f =580 K (307 °C). Similarly, the measured ferrite + carbide → austenite transformation onset ( Ac 1) and completion ( Ac 3) temperatures are found to be 1126 K and 1143 K (853 °C and 870 °C), respectively. The Poisson ratio μ exhibited distinct discontinuities at phase transformation temperatures; but however, is found to vary in the range 0.27 to 0.29. The room temperature estimates of E, G, and μ for normalized and tempered microstructure are found to be 219 GPa, 86.65 GPa, and 0.27, respectively. For the metastable austenite phase, the corresponding values are: 197 GPa, 76.5 GPa, and 0.29, respectively. The measured elastic properties as well as their temperature dependencies are found to be in good accord with reported estimates for other 9Cr-based ferritic-martensitic steel grades. Estimates of θ D el , the elastic Debye temperature and γ G, the thermal Grüneisen parameter obtained from measured bulk elastic properties are found to be θ D el = 465 K (192 °C) and γ G = 1.57.

  13. Stress Corrosion cracking susceptibility of reduced-activation martensitic steel F82H

    Energy Technology Data Exchange (ETDEWEB)

    Miwa, Y. [Nuclear Energy and Science Directorate, Japan Atomic Energy Agency, Tokai-mura, Ibaraki-ken (Japan); Jitsukawa, S.; Tsukada, T. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan)

    2007-07-01

    Full text of publication follows: For fusion power source in near future, supercritical water-cooled type blanket system was planned in Japan Atomic Energy Agency. The blankest system was designed by the present knowledge base and a reasonable extrapolation in material and design technology. Reduced-activation martensitic steel, F82H, is one of the blanket system structural materials. Therefore durability of the F82H for corrosion and stress corrosion cracking (SCC) is one of the concerns for this water-cooling concept of the blanket system. In this paper, SCC susceptibility of F82H was studied after heat treatments simulating post weld heat treatment (PWHT) or neutron-irradiation at 493 K to a dose level of 2.2 dpa. In order to evaluate SCC susceptibility of F82H, slow strain rate testing (SSRT) in high-purity, circulating water was conducted at 513-603 K in an autoclave. The strain rate was 1.0- 2.0x10{sup -7} s{sup -1}. Concentration of dissolved oxygen and hydrogen of the circulating water was controlled by bubbling with these gases. Specimens were heat treated after normalization at 1313 K for 40 min and water quenching. Some of the specimens were tempered at 873-1073 K for 1 h. Since the temperature control during PWHT in vacuum vessel by remote handling will be difficult, it is expected the tempering temperature will be different at place to place. Some specimens after tempering at 1033 K for 1 h were irradiated at 493 K to 2.2 dpa in Japan Research Reactor No.3 at Japan Atomic Energy Agency. The SSRT results showed the as-normalized specimens failed by IGSCC in oxygenated temperature water at 573 K. SSRT results of specimens with other tempering temperature conditions will be presented at conference. In irradiated specimen, IGSCC did not occur in oxygenated water at 5113-603 K. IGSCC also did not occur in hydrogenated water at 573 K. However TGSCC occurred in the irradiated specimen with a round notch (radius= {approx}0.2 mm) in oxygenated water at 573 K

  14. Effects of irradiation on low cycle fatigue properties for reduced activation ferritic/martensitic steel

    Energy Technology Data Exchange (ETDEWEB)

    Kim, S.W. [Kyoto Univ., Graduate School of Energy Science (Japan); Tanigawa, H. [Japan Atomic Energy Agency, Tokai-mura, Naga-gun, Ibaraki-ken (Japan); Hirose, T. [Blanket Engineering Group, Japan Atomic Energy Agency, Naka, Ibaraki (Japan); Kohyama, A. [Kyoto Univ., lnstitute of Advanced Energy (Japan)

    2007-07-01

    Full text of publication follows: In materials life decision for a commercial blanket, thermal fatigue property of materials is a particularly important. The loading of structural materials in fusion reactor is, besides the plasma surface interactions, a combined effect of high heat fluxes and neutron irradiation. Depending on the pulse lengths, the operating conditions, and the thermal conductivity, these oscillating temperature gradients will cause elastic and elastic-plastic cyclic deformation giving rise to (creep-) fatigue in structural first wall and blanket components. Especially, investigation of the fatigue property in Reduced Activation Ferritic/Martensitic (RAF/M) steel and establishment of the evaluation technology are demanded in particular immediately for design/manufacturing of ITER-TBM. And also, fatigue testing after irradiation will be carried out in hot cells with remote control system. Considering limited ability of specimen manipulation in the cells, the specimen and the test method need to be simple for operation. The existing data bases of RAF/M steel provide baseline data set including post-irradiation fatigue data. However, to perform the accurate fatigue lifetime assessment for ITER-TBM and beyond utilizing the existing data base, the mechanical understanding of fatigue fracture is mandatory. It has been previously reported by co-authors that dislocation cell structure was developed on low cycle fatigued RAF/M steel, and led the fatigue crack to develop along prior austenitic grain boundary. In this work, the effects of nuclear irradiation on low cycle fatigue properties for RAF/M steels and its fracture mechanisms were examined based on the flow stress analysis and detailed microstructure analysis. Fracture surfaces and crack initiation site were investigated by scanning electron microscope (SEM). Transmission electron microscopy (TEM) was also applied to clarify the microstructural features of fatigue behavior. It is also important to

  15. Activity-guided separation of Chromolaena odorata leaf extract reveals fractions with rice disease-reducing properties

    DEFF Research Database (Denmark)

    Rodriguez Algaba, Julian; Sørensen, Jens Christian; Sørensen, Hilmer

    2015-01-01

    with water and methanol and the extracts separated using a group separation system followed by analysis using capillary electrophoresis. The fractions from the extracts were tested in vitro and in planta using Bipolaris oryzae (cause of brown spot of rice) to test for their potential to reduce disease...... severity. Activity-guided separation of the C. odorata extracts indicated that compounds with activity could, at least partly, be isolated on a weakly acidic cation exchange column. Further purification yielded fractions with disease reducing effects of up to 72 % at 15 days after inoculation. Activity...... was found both in methanol and water extracts, indicating that the bioactive compound(s) are hydrophilic, low molecular weight compounds. The disease-reducing fractions did not display any direct antimicrobial effects, but data indicate that they protect the plants by induced resistance as evidenced from...

  16. Submaximal oxygen uptake kinetics, functional mobility, and physical activity in older adults with heart failure and reduced ejection fraction

    OpenAIRE

    Hummel, Scott L; Herald, John; Alpert, Craig; Gretebeck, Kimberlee A; Champoux, Wendy S; Dengel, Donald R; Vaitkevicius, Peter V; Alexander, Neil B

    2016-01-01

    Background Submaximal oxygen uptake measures are more feasible and may better predict clinical cardiac outcomes than maximal tests in older adults with heart failure (HF). We examined relationships between maximal oxygen uptake, submaximal oxygen kinetics, functional mobility, and physical activity in older adults with HF and reduced ejection fraction. Methods Older adults with HF and reduced ejection fraction (n = 25, age 75 ? 7 years) were compared to 25 healthy age- and gender-matched cont...

  17. Activation of biceps femoris long head reduces tibiofemoral anterior shear force and tibial internal rotation torque in healthy subjects.

    Science.gov (United States)

    Azmi, Nur Liyana; Ding, Ziyun; Xu, Rui; Bull, Anthony M J

    2018-01-01

    The anterior cruciate ligament (ACL) provides resistance to tibial internal rotation torque and anterior shear at the knee. ACL deficiency results in knee instability. Optimisation of muscle contraction through functional electrical stimulation (FES) offers the prospect of mitigating the destabilising effects of ACL deficiency. The hypothesis of this study is that activation of the biceps femoris long head (BFLH) reduces the tibial internal rotation torque and the anterior shear force at the knee. Gait data of twelve healthy subjects were measured with and without the application of FES and taken as inputs to a computational musculoskeletal model. The model was used to investigate the optimum levels of BFLH activation during FES gait in reducing the anterior shear force to zero. This study found that FES significantly reduced the tibial internal rotation torque at the knee during the stance phase of gait (p = 0.0322) and the computational musculoskeletal modelling revealed that a mean BFLH activation of 20.8% (±8.4%) could reduce the anterior shear force to zero. At the time frame when the anterior shear force was zero, the internal rotation torque was reduced by 0.023 ± 0.0167 Nm/BW, with a mean 188% reduction across subjects (p = 0.0002). In conclusion, activation of the BFLH is able to reduce the tibial internal rotation torque and the anterior shear force at the knee in healthy control subjects. This should be tested on ACL deficient subject to consider its effect in mitigating instability due to ligament deficiency. In future clinical practice, activating the BFLH may be used to protect ACL reconstructions during post-operative rehabilitation, assist with residual instabilities post reconstruction, and reduce the need for ACL reconstruction surgery in some cases.

  18. Histamine H3 Receptors Decrease Dopamine Release in the Ventral Striatum by Reducing the Activity of Striatal Cholinergic Interneurons.

    Science.gov (United States)

    Varaschin, Rafael Koerich; Osterstock, Guillaume; Ducrot, Charles; Leino, Sakari; Bourque, Marie-Josée; Prado, Marco A M; Prado, Vania Ferreira; Salminen, Outi; Rannanpää Née Nuutinen, Saara; Trudeau, Louis-Eric

    2018-04-15

    Histamine H 3 receptors are widely distributed G i -coupled receptors whose activation reduces neuronal activity and inhibits release of numerous neurotransmitters. Although these receptors are abundantly expressed in the striatum, their modulatory role on activity-dependent dopamine release is not well understood. Here, we observed that histamine H 3 receptor activation indirectly diminishes dopamine overflow in the ventral striatum by reducing cholinergic interneuron activity. Acute brain slices from C57BL/6 or channelrhodopsin-2-transfected DAT-cre mice were obtained, and dopamine transients evoked either electrically or optogenetically were measured by fast-scan cyclic voltammetry. The H 3 agonist α-methylhistamine significantly reduced electrically- evoked dopamine overflow, an effect blocked by the nicotinic acetylcholine receptor antagonist dihydro-β-erythroidine, suggesting involvement of cholinergic interneurons. None of the drug treatments targeting H 3 receptors affected optogenetically evoked dopamine overflow, indicating that direct H 3 -modulation of dopaminergic axons is unlikely. Next, we used qPCR and confirmed the expression of histamine H 3 receptor mRNA in cholinergic interneurons, both in ventral and dorsal striatum. Activation of H 3 receptors by α-methylhistamine reduced spontaneous firing of cholinergic interneurons in the ventral, but not in the dorsal striatum. Resting membrane potential and number of spontaneous action potentials in ventral-striatal cholinergic interneurons were significantly reduced by α-methylhistamine. Acetylcholine release from isolated striatal synaptosomes, however, was not altered by α-methylhistamine. Together, these results indicate that histamine H 3 receptors are important modulators of dopamine release, specifically in the ventral striatum, and that they do so by decreasing the firing rate of cholinergic neurons and, consequently, reducing cholinergic tone on dopaminergic axons. Copyright © 2018 IBRO

  19. Inhibition of transglutaminase 2 reduces efferocytosis in human macrophages: Role of CD14 and SR-AI receptors.

    Science.gov (United States)

    Eligini, S; Fiorelli, S; Tremoli, E; Colli, S

    2016-10-01

    Transglutaminase 2 (TGM2), a member of the transglutaminase family of enzymes, is a multifunctional protein involved in numerous events spanning from cell differentiation, to signal transduction, apoptosis, and wound healing. It is expressed in a variety of cells, macrophages included. Macrophage TGM2 promotes the clearance of apoptotic cells (efferocytosis) and emerging evidence suggests that defective efferocytosis contributes to the consequences of inflammation-associated diseases, including atherosclerotic lesion progression and its sequelae. Of interest, active TGM2 identified in human atherosclerotic lesions plays critical roles in plaque stability through effects on matrix cross-linking and TGFβ activity. This study explores the mechanisms by which TGM2 controls efferocytosis in human macrophages. Herein we show that TGM2 increases progressively during monocyte differentiation towards macrophages and controls their efferocytic potential as well as morphology and viability. Two experimental approaches that took advantage of the inhibition of TGM2 activity and protein silencing give proof that TGM2 reduction significantly impairs macrophage efferocytosis. Among the mechanisms involved we highlighted a role of the receptors CD14 and SR-AI whose levels were markedly reduced by TGM2 inhibition. Conversely, CD36 receptor and αvβ3 integrin levels were not influenced. Of note, lipid accumulation and IL-10 secretion were reduced in macrophages displaying defective efferocytosis. Overall, our data define a crucial role of TGM2 activity during macrophage differentiation via mechanisms involving CD14 and SR-AI receptors and show that TGM2 inhibition triggers a pro-inflammatory phenotype. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  20. Reduced Tonoplast Fast-Activating and Slow-Activating Channel Activity Is Essential for Conferring Salinity Tolerance in a Facultative Halophyte, Quinoa1[C][W][OA

    Science.gov (United States)

    Bonales-Alatorre, Edgar; Shabala, Sergey; Chen, Zhong-Hua; Pottosin, Igor

    2013-01-01

    Halophyte species implement a “salt-including” strategy, sequestering significant amounts of Na+ to cell vacuoles. This requires a reduction of passive Na+ leak from the vacuole. In this work, we used quinoa (Chenopodium quinoa) to investigate the ability of halophytes to regulate Na+-permeable slow-activating (SV) and fast-activating (FV) tonoplast channels, linking it with Na+ accumulation in mesophyll cells and salt bladders as well as leaf photosynthetic efficiency under salt stress. Our data indicate that young leaves rely on Na+ exclusion to salt bladders, whereas old ones, possessing far fewer salt bladders, depend almost exclusively on Na+ sequestration to mesophyll vacuoles. Moreover, although old leaves accumulate more Na+, this does not compromise their leaf photochemistry. FV and SV channels are slightly more permeable for K+ than for Na+, and vacuoles in young leaves express less FV current and with a density unchanged in plants subjected to high (400 mm NaCl) salinity. In old leaves, with an intrinsically lower density of the FV current, FV channel density decreases about 2-fold in plants grown under high salinity. In contrast, intrinsic activity of SV channels in vacuoles from young leaves is unchanged under salt stress. In vacuoles of old leaves, however, it is 2- and 7-fold lower in older compared with young leaves in control- and salt-grown plants, respectively. We conclude that the negative control of SV and FV tonoplast channel activity in old leaves reduces Na+ leak, thus enabling efficient sequestration of Na+ to their vacuoles. This enables optimal photosynthetic performance, conferring salinity tolerance in quinoa species. PMID:23624857

  1. Active Lubrication: Feasibility and Limitations on Reducing Vibration in Rotating Machinery

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2004-01-01

    of increasing their operational range. As a result, one achieves intelligent machines that are more flexible to operate in a fast-changing demand environment. Some limitations of the active lubrication are also discussed based on experimental data, where the response of the servo valves and the supply pressure...... play an important role: the eigenfrequency of the servo valves establishes the operational frequency range of the active lubrication, whereas the supply pressure establishes the amplitude of vibration reduction achieved with the active lubrication....

  2. VI. The role of physical activity in reducing barriers to learning in children with developmental disorders.

    Science.gov (United States)

    Pontifex, Matthew B; Fine, Jodene G; da Cruz, Katelin; Parks, Andrew C; Smith, Alan L

    2014-12-01

    Emerging research suggests that physical activity may be an effective non-pharmaceutical intervention approach for childhood developmental disorders. Findings indicate that both single bouts of activity and chronic physical activity associate with improved mental health and classroom performance in children with attention-deficit/hyperactivity disorder and children with autism spectrum disorders. This review describes the research in this area and identifies limitations and challenges to the translation of these findings to promote physical activity in clinical practice and educational policy. © 2014 The Society for Research in Child Development, Inc.

  3. A translational research intervention to reduce screen behaviours and promote physical activity among children: Switch-2-Activity

    NARCIS (Netherlands)

    Salmon, J.; Jorna, M.; Hume, C.; Arundell, L.; Chahine, N.; Tienstra, M.L.; Crawford, D.

    2011-01-01

    Translational or implementation research that assesses the effectiveness of strategies to promote health behaviours among children that have been previously tested under 'ideal' conditions is rarely reported. Switch-2-Activity aimed to examine the effectiveness of an abbreviated programme delivered

  4. Can an incentive-based intervention increase physical activity and reduce sitting among adults? the ACHIEVE (Active Choices IncEntiVE) feasibility study.

    Science.gov (United States)

    Ball, Kylie; Hunter, Ruth F; Maple, Jaimie-Lee; Moodie, Marj; Salmon, Jo; Ong, Kok-Leong; Stephens, Lena D; Jackson, Michelle; Crawford, David

    2017-03-21

    Despite recent interest in the potential of incentivisation as a strategy for motivating healthier behaviors, little remains known about the effectiveness of incentives in promoting physical activity and reducing sedentary behavior, and improving associated health outcomes. This pre-post-test design study investigated the feasibility, appeal and effects of providing non-financial incentives for promoting increased physical activity, reduced sedentary time, and reduced body mass index (BMI) and blood pressure among inactive middle-aged adults. Inactive men (n = 36) and women (n = 46) aged 40-65 years were recruited via a not-for-profit insurance fund and participated in a 4 month pre-post design intervention. Baseline and post-intervention data were collected on self-reported physical activity and sitting time (IPAQ-Long), BMI and blood pressure. Participants were encouraged to increase physical activity to 150 mins/week and reduce sedentary behavior by 150 mins/week in progressive increments. Incentives included clothing, recipe books, store gift vouchers, and a chance to win one of four Apple iPad Mini devices. The incentive component of the intervention was supported by an initial motivational interview and text messaging to encourage participants and provide strategies to increase physical activity and reduce sedentary behaviors. Only two participants withdrew during the program, demonstrating the feasibility of recruiting and retaining inactive middle-aged participants. While two-thirds of the sample qualified for the easiest physical activity incentive (by demonstrating 100 mins physical activity/week or 100 mins reduced sitting time/week), only one third qualified for the most challenging incentive. Goals to reduce sitting appeared more challenging, with 43% of participants qualifying for the first incentive, but only 20% for the last incentive. More men than women qualified for most incentives. Mean leisure-time physical activity increased by 252

  5. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  6. Activation of TRPV1 reduces vascular lipid accumulation and attenuates atherosclerosis

    DEFF Research Database (Denmark)

    Ma, Liqun; Zhong, Jian; Zhao, Zhigang

    2011-01-01

    Activation of transient receptor potential vanilloid type-1 (TRPV1) channels may affect lipid storage and the cellular inflammatory response. Now, we tested the hypothesis that activation of TRPV1 channels attenuates atherosclerosis in apolipoprotein E knockout mice (ApoE(-/-)) but not Apo...

  7. Personalized Strategies to Activate and Empower Patients in Health Care and Reduce Health Disparities

    Science.gov (United States)

    Chen, Jie; Mullins, C. Daniel; Novak, Priscilla; Thomas, Stephen B.

    2016-01-01

    Designing culturally sensitive personalized interventions is essential to sustain patients' involvement in their treatment and encourage patients to take an active role in their own health and health care. We consider patient activation and empowerment as a cyclical process defined through patient accumulation of knowledge, confidence, and…

  8. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease.

    Science.gov (United States)

    van der Valk, Eline S; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

    2016-09-01

    Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. The aim of this study was to investigate the quality of life in Dutch patients with Addison's disease particularly regarding the presence of fatigue and the ability to be physically active. In this cross-sectional study, a postal survey was performed among Dutch patients with Addison's disease on stable glucocorticoid replacement therapy with hydrocortisone or cortisone acetate. For quality of life and physical activity assessment, patients completed general and health-related quality of life and physical activity questionnaires, and scores were compared to Dutch controls. A total of 328 patients with Addison's disease were studied. In patients with Addison's disease, only 45·7% met the standard of physical activity (Combinorm) compared to 67·8% of Dutch controls (P < 0·01). Forty-eight per cent of patients showed abnormal fatigue, while 61% had severe fatigue. The CIS fatigue scores were significantly higher compared to controls (P < 0·01). We found reduced general subjective health-related QoL scores in both male and female patients, especially in younger patients <65 years of age. Physical activity is decreased in patients with Addison's disease, combined with a reduced subjective health-related QoL and increased fatigue. © 2016 John Wiley & Sons Ltd.

  9. Increasing atmospheric deposition nitrogen and ammonium reduced microbial activity and changed the bacterial community composition of red paddy soil.

    Science.gov (United States)

    Zhou, Fengwu; Cui, Jian; Zhou, Jing; Yang, John; Li, Yong; Leng, Qiangmei; Wang, Yangqing; He, Dongyi; Song, Liyan; Gao, Min; Zeng, Jun; Chan, Andy

    2018-03-27

    Atmospheric deposition nitrogen (ADN) increases the N content in soil and subsequently impacts microbial activity of soil. However, the effects of ADN on paddy soil microbial activity have not been well characterized. In this study, we studied how red paddy soil microbial activity responses to different contents of ADN through a 10-months ADN simulation on well managed pot experiments. Results showed that all tested contents of ADN fluxes (27, 55, and 82kgNha -1 when its ratio of NH 4 + /NO 3 - -N (R N ) was 2:1) enhanced the soil enzyme activity and microbial biomass carbon and nitrogen and 27kgNha -1 ADN had maximum effects while comparing with the fertilizer treatment. Generally, increasing of both ADN flux and R N (1:2, 1:1 and 2:1 with the ADN flux of 55kgNha -1 ) had similar reduced effects on microbial activity. Furthermore, both ADN flux and R N significantly reduced soil bacterial alpha diversity (pADN flux and R N were the main drivers in shaping paddy soil bacteria community. Overall, the results have indicated that increasing ADN flux and ammonium reduced soil microbial activity and changed the soil bacterial community. The finding highlights how paddy soil microbial community response to ADN and provides information for N management in paddy soil. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Major depression in mothers predicts reduced ventral striatum activation in adolescent female offspring with and without depression.

    Science.gov (United States)

    Sharp, Carla; Kim, Sohye; Herman, Levi; Pane, Heather; Reuter, Tyson; Strathearn, Lane

    2014-05-01

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder (MDD). However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for MDD. One way of studying vulnerability is through a high-risk design. Therefore, the aim of the current study was to determine whether reward-related activation of the ventral striatum is reduced in nondepressed daughters of mothers with a history of MDD (high-risk) similarly to currently depressed adolescent girls, compared with healthy controls. By directly comparing groups with a shared risk profile during differing states, we aimed to shed light on the endophenotypic nature of reduced reward processing for adolescent depression. We compared reward-related neural activity through functional magnetic resonance imaging (fMRI) between three groups of female biological offspring (N = 52) of mothers with differential MDD status: (a) currently depressed daughters of mothers with a history of MDD (MDD group; n = 14), (b) age- and socioeconomic status (SES)-matched never-depressed daughters of mothers with a history of MDD (high-risk group; n = 19), and (c) age- and SES-matched control daughters of mothers with no past or current psychopathology in either the mother or the daughter (healthy control group; n = 19). For the outcome phase of the reward task, right-sided ventral striatum activation was reduced for both currently depressed and high-risk girls compared with healthy controls. This ventral striatal activity correlated significantly with maternal depression scores. These findings provide further evidence of aberrant functioning for the United States Department of Health & Human Services, National Institutes of Health, National Institute of Mental Health (NIMH) Research Domain Criteria (RDoC)-defined domain of positive valence systems as a vulnerability factor for MDD and a

  11. Active Recovery between Interval Bouts Reduces Blood Lactate While Improving Subsequent Exercise Performance in Trained Men

    Directory of Open Access Journals (Sweden)

    Harutiun M. Nalbandian

    2017-06-01

    Full Text Available This study aimed to examine the blood lactate and blood pH kinetics during high-intensity interval training. Seventeen well-trained athletes exercised on two different occasions. Exercises consisted of three 30 s bouts at a constant intensity (90% of peak power with 4 min recovery between bouts followed by a Wingate test (WT. The recoveries were either active recovery (at 60% of the lactate threshold intensity or passive recovery (resting at sitting position. During the exercise, blood samples were taken to determine blood gasses, blood lactate, and blood pH, and peak and average power were calculated for the WT. When performing the active recovery trials, blood pH was significantly higher (p < 0.01 and blood lactate was significantly lower (p < 0.01 compared with the passive recovery trials. WT performance was significantly higher in the active recovery trials: peak power was 671 ± 88 and 715 ± 108 watts, and average power was 510 ± 70 and 548 ± 73 watts (passive and active respectively; p < 0.01. However, no statistically significant correlations were found between the increased pH and the increased performance in the active recovery trials. These results suggest that active recovery performed during high-intensity interval exercise favors the performance in a following WT. Moreover, the blood pH variations associated with active recovery did not explain the enhanced performance.

  12. Role of physical activity in reducing cognitive decline in older Mexican-American adults.

    Science.gov (United States)

    Ottenbacher, Allison J; Snih, Soham Al; Bindawas, Saad M; Markides, Kyriakos S; Graham, James E; Samper-Ternent, Rafael; Raji, Mukaila; Ottenbacher, Kenneth J

    2014-09-01

    The effect of physical activity on cognitive function in older adults from minority and disadvantaged populations is not well understood. This study examined the longitudinal association between physical activity and cognition in older Mexican Americans. The study methodology included a prospective cohort with longitudinal analysis of data from the Hispanic Established Populations for the Epidemiologic Study of the Elderly. General linear mixed models were used to assess the associations and interactions between physical activity and cognitive function over 14 years. Community-based assessments were performed in participants' homes. Physical activity was recorded for 1,669 older Mexican Americans using the Physical Activity Scale for the Elderly. Cognition was measured using the Mini-Mental State Examination (MMSE) and separated into memory and nonmemory components. A statistically significant positive association was observed between levels of physical activity and cognitive function after adjusting for age, sex, marital status, education, and comorbid health conditions. There was a statistically significant difference in MMSE scores over time between participants in the third (β = 0.11, standard error (SE) = 0.05) and fourth (β = 0.10, SE = 0.2) quartiles of physical activity and those in the first. The protective effect of physical activity on cognitive decline was evident for the memory component of the MMSE but not the nonmemory component after adjusting for covariates. Greater physical activity at baseline was associated with less cognitive decline over 14 years in older Mexican Americans. The reduction in cognitive decline appeared to be related to the memory components of cognitive function. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

  13. Low salinity and high-level UV-B radiation reduce single-cell activity in antarctic sea ice bacteria.

    Science.gov (United States)

    Martin, Andrew; Hall, Julie; Ryan, Ken

    2009-12-01

    Experiments simulating the sea ice cycle were conducted by exposing microbes from Antarctic fast ice to saline and irradiance regimens associated with the freeze-thaw process. In contrast to hypersaline conditions (ice formation), the simulated release of bacteria into hyposaline seawater combined with rapid exposure to increased UV-B radiation significantly reduced metabolic activity.

  14. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    van der Valk, Eline S.; Smans, Lisanne C C J; Hofstetter, Hedwig; Stubbe, Janine H.; de Vries, Marieke; Backx, Frank J G; Hermus, Ad R M M; Zelissen, Pierre M J

    BACKGROUND: Health related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to

  15. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    Valk, E.S. Van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M de; Backx, F.J.; Hermus, A.R.M.M.; Zelissen, P.M.J.

    2016-01-01

    BACKGROUND: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. OBJECTIVE: The aim of this study was to

  16. Decreased physical activity, reduced QoL and presence of debilitating fatigue in patients with Addison's disease

    NARCIS (Netherlands)

    Valk, E.S. van der; Smans, L.C.C.J.; Hofstetter, H.; Stubbe, J.H.; Vries, M. de; Backx, F.J.G.; Hermus, A.R.M.M.; Zelissen, P.M.J.

    2016-01-01

    Background: Health-related quality of life in patients with Addison's disease has been assessed in various European countries, indicating a reduced quality of life. However, no studies have addressed the impact of Addison's disease on physical activity. Objective: The aim of this study was to

  17. Gas-shell-encapsulation of activated carbon to reduce fouling and increase the efficacy of volatile organic compound removal

    NARCIS (Netherlands)

    Poortinga, A.T.; van Rijn, C.J.M.

    2017-01-01

    A method to encapsulate activated carbon particles is presented that reduces fouling of these particles with Natural Organic Matter (NOM) to preserve their adsorption capacity for Volatile Organic Compounds (VOCs) from water in the presence of NOM. The encapsulation method uses an oil-in-water

  18. Gas-shell-encapsulation of Activated Carbon to Reduce Fouling and Increase the Efficacy of Volatile Organic Compound Removal

    NARCIS (Netherlands)

    Poortinga, Albert T.; Rijn, van Cees J.M.

    2017-01-01

    A method to encapsulate activated carbon particles is presented that reduces fouling of these particles with Natural Organic Matter (NOM) to preserve their adsorption capacity for Volatile Organic Compounds (VOCs) from water in the presence of NOM. The encapsulation method uses an oil-in-water

  19. Reduced activation in the ventral striatum during probabilistic decision-making in patients in an at-risk mental state

    NARCIS (Netherlands)

    Rausch, Franziska; Mier, Daniela; Eifler, Sarah; Fenske, Sabri