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Sample records for activation product c5a

  1. Complement activation product C5a is a selective suppressor of TLR4-induced, but not TLR3-induced, production of IL-27(p28) from macrophages

    PubMed Central

    Bosmann, Markus; Haggadone, Mikel D.; Hemmila, Mark R.; Zetoune, Firas S.; Sarma, J. Vidya; Ward, Peter A.

    2012-01-01

    There is accumulating evidence that the complement activation product, C5a, can orchestrate cellular immune functions. IL-27 (p28/EBI3) is an emerging key player essential for regulating inflammatory responses and T cells. Here, we report that C5a robustly suppressed IL-27(p28) gene expression and release in peritoneal macrophages. These cells from C57BL/6J mice abundantly produced IL-27(p28) after engagement of either the TLR3 (Poly I:C) or TLR4 (LPS) receptor. Genetic deficiency of either TLR4 or LPS-binding protein (LBP) completely incapacitated the ability of macrophages to secrete IL-27(p28) in response to LPS. IL-27(p28) producing macrophages also expressed the C5aR receptor, thus displaying an IL-27(p28)+F4/80+C5aR+ phenotype. C5a suppressed IL-27(p28) in LPS-stimulated macrophages via interactions with the C5aR receptor, rather than the C5L2 receptor. C5aR−/− mice after endotoxemia displayed higher plasma levels of IL-27(p28) when compared to C57BL/6J mice. C5a did not affect the release of IL-27(p28) or frequency of IL-27(p28)+F4/80+ macrophages after engagement of TLR3. Mechanistically, LPS activated both NFκB and the PI3K-Akt pathways, whereas C5a activated only the PI3K-Akt pathway. Engagement of PI3K-Akt was inhibitory for IL-27(p28) production, since PI3K-Akt pharmacologic blockade resulted in increased amounts of IL-27(p28) and reversed the suppressive effects of C5a. Blockade of PI3K-Akt in endotoxemic C57BL/6J mice resulted in higher generation of IL-27(p28). In contrast, for TLR3-mediated release of IL-27(p28), the PI3K-Akt pathway was not involved. These data provide new evidence on how complement activation may selectively interfere with production of T cell regulatory cytokines by antigen-presenting cells in the varying contexts of either bacterial (TLR4-pathway) or viral (TLR3-pathway) infection. PMID:22491257

  2. The Novel Receptor C5aR2 Is Required for C5a-Mediated Human Mast Cell Adhesion, Migration, and Proinflammatory Mediator Production.

    PubMed

    Pundir, Priyanka; MacDonald, Clayton A; Kulka, Marianna

    2015-09-15

    C5a generated during complement activation possesses proinflammatory and immunoregulatory properties critical for the development and modulation of allergic immune responses. In immune cells, C5a mediates its effects through binding to two G protein-coupled receptors, C5aR1 and C5aR2. Mast cells are key effectors in allergic reactions, and decades of research have suggested that the majority of C5a effects on mast cells are mediated through C5aR1, whereas the expression and function of C5aR2 have not been explored. We demonstrated that the human mast cell line Laboratory of Allergic Diseases 2 (LAD2) expresses surface C5aR2 but not C5aR1, whereas CD34(+) cell-derived primary mast cells do not express surface C5aR1 or C5aR2. Stem cell factor and IL-4 upregulated C5aR2 expression on LAD2 cells. Furthermore, C5a caused internalization of LAD2 cell-surface C5aR2. We therefore used LAD2 cells as a model to study C5a/C5aR2-induced biological responses and signaling in human mast cells. We found that whereas C5a was unable to induce degranulation, it stimulated GM-CSF, TNF, CXCL10, and CCL2 production. C5a caused ERK phosphorylation, a signaling molecule important in cytokine and chemokine generation. In addition, C5a stimulated adhesion and chemotaxis of mast cells. Wortmannin, an inhibitor of PI3K, and small interfering RNA against β-arrestin-2 blocked C5a-induced adhesion. Silencing of C5aR2 using lentiviral short hairpin RNA rendered the cells unresponsive to C5a-induced adhesion, chemotaxis, and mediator release, as well as ERK phosphorylation. Overall, this study reveals a novel role for C5aR2 in C5a-mediated activation of mast cells and demonstrates that C5aR2 ligation initiates a β-arrestin-2-, PI3K-, and ERK-dependent signaling pathway in these cells.

  3. The effect of nuclear factor of activated T-cells (NFAT) in kidney I/R mediated by C5a/C5aR.

    PubMed

    Zhang, Ze-Ying; Wu, Yang-Qian; Luo, Heng; Liu, Dong-Xu

    2015-01-01

    To investigate the relationship between NFAT and C5a/C5aR in C5a/C5aR-mediated kidney Ischemia/reperfusion (I/R) injury, the rats' NRK-52E cell line was used in this study and was distributed into 4 groups, I: the normal control (NC), II: the ischemia/reperfusion (I/R) injury cell model (MG), III: the ischemia/reperfusion (I/R) injury cell model treated with C5a (50 nmol/l) (MG + C5a), IV: the ischemia/reperfusion (I/R) injury cell model treated with C5aR antagonist (2.5 μmol/l) (MG + anti-C5aR). Reverse transcription polymerase chain reaction (RT-PCR), western blot, immunofluorescence and flow cytometry were performed. Nuclear Factor Activated T Cell (NFAT), tumor necrosis factor-α (TNF-α) and interleukin (IL-6) were detected in this study. The results of immunofluorescence showed that NFAT had a nuclear translocation phenomenon during the study. The RT-PCR and WB data indicated that the expression of TNF-α and IL-6 in group III were higher than any other groups. Apoptosis in group III was much serious than other groups. All the results in this study showed that NFAT plays an important role in ischemia/reperfusion injury, it can be induced to up-regulate the inflammatory factor TNF-α and IL-6 by the complement system member C5a/C5aR.

  4. The role of the complement system and the activation fragment C5a in the central nervous system.

    PubMed

    Woodruff, Trent M; Ager, Rahasson R; Tenner, Andrea J; Noakes, Peter G; Taylor, Stephen M

    2010-06-01

    The complement system is a pivotal component of the innate immune system which protects the host from infection and injury. Complement proteins can be induced in all cell types within the central nervous system (CNS), where the pathway seems to play similar roles in host defense. Complement activation produces the C5 cleavage fragment C5a, a potent inflammatory mediator, which recruits and activates immune cells. The primary cellular receptor for C5a, the C5a receptor (CD88), has been reported to be on all CNS cells, including neurons and glia, suggesting a functional role for C5a in the CNS. A second receptor for C5a, the C5a-like receptor 2 (C5L2), is also expressed on these cells; however, little is currently known about its potential role in the CNS. The potent immune and inflammatory actions of complement activation are necessary for host defense. However, if over-activated, or left unchecked it promotes tissue injury and contributes to brain disease pathology. Thus, complement activation, and subsequent C5a generation, is thought to play a significant role in the progression of CNS disease. Paradoxically, complement may also exert a neuroprotective role in these diseases by aiding in the elimination of aggregated and toxic proteins and debris which are a principal hallmark of many of these diseases. This review will discuss the expression and known roles for complement in the CNS, with a particular focus on the pro-inflammatory end-product, C5a. The possible overarching role for C5a in diseases of the CNS is reviewed, and the therapeutic potential of blocking C5a/CD88 interaction is evaluated.

  5. Peptidyl arginine deiminase from Porphyromonas gingivalis abolishes anaphylatoxin C5a activity.

    PubMed

    Bielecka, Ewa; Scavenius, Carsten; Kantyka, Tomasz; Jusko, Monika; Mizgalska, Danuta; Szmigielski, Borys; Potempa, Barbara; Enghild, Jan J; Prossnitz, Eric R; Blom, Anna M; Potempa, Jan

    2014-11-21

    Evasion of killing by the complement system, a crucial part of innate immunity, is a key evolutionary strategy of many human pathogens. A major etiological agent of chronic periodontitis, the Gram-negative bacterium Porphyromonas gingivalis, produces a vast arsenal of virulence factors that compromise human defense mechanisms. One of these is peptidylarginine deiminase (PPAD), an enzyme unique to P. gingivalis among bacteria, which converts Arg residues in polypeptide chains into citrulline. Here, we report that PPAD citrullination of a critical C-terminal arginine of the anaphylatoxin C5a disabled the protein function. Treatment of C5a with PPAD in vitro resulted in decreased chemotaxis of human neutrophils and diminished calcium signaling in monocytic cell line U937 transfected with the C5a receptor (C5aR) and loaded with a fluorescent intracellular calcium probe: Fura-2 AM. Moreover, a low degree of citrullination of internal arginine residues by PPAD was also detected using mass spectrometry. Further, after treatment of C5 with outer membrane vesicles naturally shed by P. gingivalis, we observed generation of C5a totally citrullinated at the C-terminal Arg-74 residue (Arg74Cit). In stark contrast, only native C5a was detected after treatment with PPAD-null outer membrane vesicles. Our study suggests reduced antibacterial and proinflammatory capacity of citrullinated C5a, achieved via lower level of chemotactic potential of the modified molecule, and weaker cell activation. In the context of previous studies, which showed crosstalk between C5aR and Toll-like receptors, as well as enhanced arthritis development in mice infected with PPAD-expressing P. gingivalis, our findings support a crucial role of PPAD in the virulence of P. gingivalis. PMID:25324545

  6. New insights for C5a and C5a receptors in sepsis

    PubMed Central

    Yan, Chunguang; Gao, Hongwei

    2012-01-01

    The complement system plays a central role in inflammation and immunity. Among the complement activation products, C5a is one of the most potent inflammatory peptides with a broad spectrum of functions. There is strong evidence for complement activation including elevated plasma level of C5a in humans and animals with sepsis. C5a exerts its effects through the C5a receptors. Of the two receptors that bind C5a, the C5aR (CD88) is known to mediate signaling activity, whereas the function of another C5a binding receptor, C5L2, remains largely unknown. Here, we review the critical role of C5a in sepsis and summarize evidence indicating that both C5aR and C5L2 act as regulating receptors for C5a during sepsis. PMID:23233853

  7. Cofactor Regulation of C5a Chemotactic Activity in Physiological Fluids. Requirement for the Vitamin D Binding Protein, Thrombospondin-1 and its Receptors

    PubMed Central

    Trujillo, Glenda; Zhang, Jianhua; Habiel, David M.; Ge, Lingyin; Ramadass, Mahalakshmi; Ghebrehiwet, Berhane; Kew, Richard R.

    2011-01-01

    Factors in physiological fluids that regulate the chemotactic activity of complement activation peptides C5a and C5a des Arg are not well understood. The vitamin D binding protein (DBP) has been shown to significantly enhance chemotaxis to C5a/C5a des Arg. More recently, platelet-derived thrombospondin-1 (TSP-1) has been shown to facilitate the augmentation of C5a-induced chemotaxis by DBP. The objective of this study was to better characterize these chemotactic cofactors and investigate the role that cell surface TSP-1 receptors CD36 and CD47 may play in this process. The chemotactic activity in C-activated normal serum, citrated plasma, DBP-depleted serum or C5 depleted serum was determined for both normal human neutrophils and U937 cell line transfected with the C5a receptor (U937-C5aR). In addition, levels of C5a des Arg, DBP and TSP-1 in these fluids were measured by RIA or ELISA. Results show that there is a clear hierarchy with C5a being the essential primary signal (DBP or TSP-1 will not function in the absence of C5a), DBP the necessary cofactor and TSP-1 a dependent tertiary factor, since it cannot function to enhance chemotaxis to C5a without DBP. Measurement of the C5a-induced intracellular calcium flux confirmed the same hierarchy observed with chemotaxis. Moreover, analysis of bronchoalveolar lavage fluid (BALF) from patients with the adult respiratory distress syndrome (ARDS) demonstrated that C5a-dependent chemotactic activity is significantly decreased after anti-DBP treatment. Finally, results show that TSP-1 utilizes cell surface receptors CD36 and CD47 to augment chemotaxis, but DBP does not bind to TSP-1, CD36 or CD47. The results clearly demonstrate that C5a/C5a des Arg needs both DBP and TSP-1 for maximal chemotactic activity and suggest that the regulation of C5a chemotactic activity in physiological fluids is more complex than previously thought. PMID:22014686

  8. Critical role of the C5a-activated neutrophils in high-fat diet-induced vascular inflammation

    PubMed Central

    Osaka, Mizuko; Ito, Shunsuke; Honda, Masaki; Inomata, Yukihiro; Egashira, Kensuke; Yoshida, Masayuki

    2016-01-01

    Exceed and chronic high-fat diet (HFD) contributes to the diagnosis and development of atherosclerosis, obesity, and metabolic syndrome. However, the key molecular component(s) triggered by HFD responsible for initiating vascular inflammation remain unknown. We observed that feeding HFD for 4 weeks is sufficient to induce leukocyte recruitment in the femoral artery of wild-type mice. Neutrophil- and monocyte-depletion analyses confirmed the preferential recruitment of neutrophils in these mice. Protein analysis of sera from HFD-fed mice revealed a marked elevation of complement component C5a levels. Exogenous C5a alone induced leukocyte recruitment, which was abolished by a C5a-receptor antagonist. We also examined the role of neutrophil-derived MCP-1 in accumulation of leukocytes in the artery. These results demonstrated a previously unrecognized role for C5a and neutrophils in the early onset of HFD-induced vascular inflammation. Further study may help in elucidating a novel regulatory pathway to control diet-induced inflammation such as that in case of atherosclerosis. PMID:26893238

  9. Molecular analysis of the bovine anaphylatoxin C5a receptor

    PubMed Central

    Nemali, Sailasree; Siemsen, Daniel W.; Nelson, Laura K.; Bunger, Peggy L.; Faulkner, Craig L.; Rainard, Pascal; Gauss, Katherine A.; Jutila, Mark A.; Quinn, Mark T.

    2008-01-01

    Recruitment of phagocytes to inflammatory sites involves the coordinated action of several chemoattractants, including the anaphylatoxin C5a. While the C5a receptor (C5aR) has been well characterized in humans and rodents, little is known about the bovine C5aR. Here, we report cloning of bovine C5R1, the gene encoding bovine C5aR. We also analyzed genomic sequence upstream of the C5R1 translation start site. Although the bovine C5aR amino acid sequence was well conserved among species, significant differences in conserved features were found, including major differences in the N terminus, intracellular loop 3, and transmembrane domain VII. Analysis of C5aR expression by flow cytometry and confocal microscopy demonstrated high levels of C5aR on all bovine neutrophils and a subset of bovine monocytes. C5aR was not expressed on resting or activated bovine lymphocytes, although C5aR message was present in these cells. C5aR was also expressed on a small subset of bovine mammary epithelial cells. Pharmacological analysis of bovine C5aR-mediated responses showed that bovine C5a and C5adesArg both induced dose-dependent calcium fluxes and chemotaxis in bovine neutrophils, with similar efficacy for both agonists. Treatment of bovine neutrophils with C5a or C5adesArg resulted in homologous desensitization of bovine C5aR and cross-desensitization to interleukin 8 (IL-8) and platelet-activating factor (PAF); whereas, treatment with IL-8 or PAF did not cross-desensitize the cells to C5a or C5adesArg. Overall, these studies provide important information regarding distinct structural and functional features that may contribute to the unique pharmacological properties of bovine C5aR. PMID:18480166

  10. Bidirectional Crosstalk between C5a Receptors and the NLRP3 Inflammasome in Macrophages and Monocytes

    PubMed Central

    Haggadone, Mikel D.; Grailer, Jamison J.; Fattahi, Fatemeh; Zetoune, Firas S.; Ward, Peter A.

    2016-01-01

    C5a is an inflammatory mediator generated by complement activation that positively regulates various arms of immune defense, including Toll-like receptor 4 (TLR4) signaling. The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome is activated by pathogen products and cellular/tissue damage products and is a major contributor of IL-1β. In this study, we investigate whether C5a modulates lipopolysaccharide- (LPS-) induced NLRP3 inflammasome activation in myeloid cells. Appearance of plasma IL-1β during endotoxemia was reduced in C5aR1−/− mice when compared to wild-type mice. In vitro, C5a significantly enhanced LPS-induced production of IL-1β in bone marrow Ly6C-high inflammatory monocytes, accompanied by augmented intracellular pro-IL-1β expression. This effect was abolished during p38 blockade by SB 203580 and in the absence of C5aR1. Conversely, C5a suppressed LPS-induced macrophage production of IL-1β, which was accompanied by attenuated levels of pro-IL-1β, NLRP3, and caspase-1 expression. C5a's suppressive effects were negated during phosphoinositide 3-kinase (PI3K) inhibition by wortmannin but were largely preserved in the absence of C5aR1. Thus, C5a bidirectionally amplifies TLR4-mediated NLRP3 inflammasome activation in monocytes while suppressing this pathway in macrophages. However, as C5aR1 deficiency attenuates the IL-1β response to LPS challenge in vivo, our results suggest overall that C5a augments physiologic inflammasome responses. PMID:27382187

  11. A Novel Role for the Receptor of the Complement Cleavage Fragment C5a, C5aR1, in CCR5-Mediated Entry of HIV into Macrophages.

    PubMed

    Moreno-Fernandez, Maria E; Aliberti, Julio; Groeneweg, Sander; Köhl, Jörg; Chougnet, Claire A

    2016-04-01

    The complement system is an ancient pattern recognition system that becomes activated during all stages of HIV infection. Previous studies have shown that C5a can enhance the infection of monocyte-derived macrophages and T cells indirectly through the production of interleukin (IL)-6 and tumor necrosis factor (TNF)-α and the attraction of dendritic cells. C5a exerts its multiple biologic functions mainly through activation of C5a receptor 1 (C5aR1). Here, we assessed the role of C5aR1 as an enhancer of CCR5-mediated HIV infection. We determined CCR5 and C5aR1 heterodimer formation in myeloid cells and the impact of C5aR1 blockade on HIV entry and genomic integration. C5aR1/CCR5 heterodimer formation was identified by immunoprecipitation and western blotting. THP-1 cells and monocyte-derived macrophages (MDM) were infected by R5 laboratory strains or HIV pseudotyped for the vesicular stomatitis virus (VSV) envelope. Levels of integrated HIV were measured by quantitative PCR after targeting of C5aR1 by a C5aR antagonist, neutralizing C5aR1 monoclonal antibody (mAb) or hC5a. C5aR1 was also silenced by specific siRNA prior to viral entry. We found that C5aR1 forms heterodimers with the HIV coreceptor CCR5 in myeloid cells. Targeting C5aR1 significantly decreased integration by R5 viruses but not by VSV-pseudotyped viruses, suggesting that C5aR1 is critical for viral entry. The level of inhibition achieved with C5aR1-blocking reagents was comparable to that of CCR5 antagonists. Mechanistically, C5aR1 targeting decreased CCR5 expression. MDM from CCR5Δ32 homozygous subjects expressed levels of C5aR1 similar to CCR5 WT individuals, suggesting that mere C5aR1 expression is not sufficient for HIV infection. HIV appeared to preferentially enter THP-1 cells expressing high levels of both C5aR1 and CCR5. Targeted reduction of C5aR1 expression in such cells reduced HIV infection by ~50%. Our data thus suggest that C5aR1 acts as an enhancer of CCR5-mediated HIV entry into

  12. The complement component C5a receptor mediates pain and inflammation in a postsurgical pain model.

    PubMed

    Liang, De-Yong; Li, XiangQi; Shi, Xiaoyu; Sun, Yuan; Sahbaie, Peyman; Li, Wen-Wu; Clark, J David

    2012-02-01

    The complement system is an important part of innate immunity. Complement activation generates a set of effector molecules with diverse biological functions. C5a is a crucial terminal component of the complement cascade. Several reports suggest that C5a can support nociceptive sensitization and inflammation in various models, including models of incisional pain. However, information concerning the differential effects of C5a on specific modalities of nociception, the role of C5a in supporting neutrophil infiltration, secondary nociceptive mediator generation, and the location of the relevant populations of C5a receptors supporting incisional sensitization are needed. In these studies we utilized C5a receptor-null mice (C5aR(-/-)) and matched controls to study nociceptive changes after hind paw incision. Heat hyperalgesia and mechanical allodynia were measured for 4 days after incision. We also followed hind paw edema, wound area neutrophil infiltration using the myeloperoxidase assay, and interleukin-1β and nerve growth factor levels using both enzyme-linked immunosorbent assay and immunohistochemical techniques. The main findings were: (1) Heat vs mechanical nociceptive sensitization after incision were differentially reduced in C5aR(-/-) mice, with thermal sensitization affected throughout the postincisional period but mechanical sensitization affected only at later time points; (2) Edema developed after incision in wild-type mice but only slightly and transiently in C5aR(-/-) mice, and (3) Deletion of C5aR blocked interleukin-1β and nerve growth factor production near the wound site. These findings demonstrate that the complement system component C5a is a novel biomarker and mediator associated with postsurgical nociceptive processing. C5aR may provide a novel target for the control of pain and inflammation after surgery.

  13. Effective suppression of C5a-induced proinflammatory response using anti-human C5a repebody.

    PubMed

    Hwang, Da-Eun; Choi, Jung-Min; Yang, Chul-Su; Lee, Joong-Jae; Heu, Woosung; Jo, Eun-Kyeong; Kim, Hak-Sung

    2016-09-01

    The strongest anaphylatoxin, C5a, plays a critical role in the proinflammatory responses, causing the pathogenesis of a number of inflammatory diseases including sepsis, asthma, and rheumatoid arthritis. Inhibitors of C5a thus have great potential as therapeutics for various inflammatory disorders. Herein, we present the development of a high-affinity repebody against human C5a (hC5a), which effectively suppresses the proinflammatory response. A repebody scaffold composed of leucine-rich repeat (LRR) modules was previously developed as an alternative protein scaffold. A repebody specifically binding to hC5a was selected through a phage display, and its affinity was increased up to 5 nM using modular engineering. The repebody was shown to effectively inhibit the production of C5a-induced proinflammatory cytokines by human monocytes. To obtain insight into a mode of action by the repebody, we determined its crystal structure in complex with hC5a. A structural analysis revealed that the repebody binds to the D1 and D3 regions of hC5a, overlapping several epitope residues with the hC5a receptor (hC5aR). It is thus likely that the repebody suppresses the hC5a-mediated immune response in monocytes by blocking the binding of hC5a to its receptor. The anti-hC5a repebody can be developed as a potential therapeutic for C5a-involved inflammatory diseases. PMID:27416759

  14. Inhibition of C5a receptor alleviates experimental CNS lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Bai, Tao; Brorson, James R; Quigg, Richard J; Alexander, Jessy J

    2010-04-15

    To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF-alpha and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK, pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/lpr brains. MRL/lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus.

  15. Inhibition of C5a receptor alleviates experimental CNS lupus

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Bai, Tao; Brorson, James R.; Quigg, Richard J.; Alexander, Jessy J.

    2010-01-01

    To investigate the role of C5a generated on complement activation in brain, the lupus model, MRL/lpr mice were treated with C5a receptor(R) antagonist (ant). Neutrophil infiltration, ICAM, TNF-α and iNOS mRNA expression, neuronal apoptosis and the expression of p-JNK, pSTAT1 and p-Erk were reduced and p-Akt increased on C5aR inhibition in MRL/lpr brains. MRL/lpr serum caused increased apoptosis in neurons showing that lupus had a direct effect on these cells. C5aRant pretreatment prevented the lupus serum induced loss of neuronal cells. Our findings demonstrate for the first time that C5a/C5aR signaling plays an important role in the pathogenesis of CNS lupus. PMID:20207017

  16. Anaphylatoxin C5a fails to promote prostacyclin release from cultured human endothelial cells

    SciTech Connect

    Lunberg, C.; Marceau, F.; Huey, R.; Hugli, T.E.

    1986-03-01

    A predominantly relaxing effect of C5a on isolated blood vessels has been reported, which is associated with prostacyclin release from the vessel wall. Further, the well known hypothensive effect of C5a, also associated with increased prostacyclin output and preventable by indomethacin, indicates an involvement of endothelial cells in this reaction. In this study the authors characterized the response to C5a of cultured human endothelial cells from umbilical vein as measured by prostacyclin release. Prostacyclin was quantitated by radioimmunoassay as 6-keto-PGF/sub 1..cap alpha../. Subcultured cells respond to histamine and mellitin with increased prostacyclin production, but do not respond to leukotriene C4 (LTC/sub 4/). Primary cultures, on the other hand, respond to LTC/sub 4/ and the histamine response is 7-fold greater for these cells than for subcultured cells. However, neither primary nor subcultured cells release prostacyclin following application of either human C5a (100 nM) or C3a (1 ..mu..M). Also, these cells fail to show specific binding sites for /sup 125/I-C5a. In contrast, endothelial cells in the presence of human PMNs challenged with C5a release prostacyclin. These data suggest that C5a has no direct effect on the endothelial cell, but rather activates this cell indirectly via mediators from other cells known to respond to C5a.

  17. C5a alters blood-brain barrier integrity in experimental lupus

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G. N.; Quigg, Richard J.; Alexander, Jessy J.

    2010-01-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6lpr (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL+/+ mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases

  18. Expression and Subcellular Targeting of Human Complement Factor C5a in Nicotiana species

    PubMed Central

    Nausch, Henrik; Mischofsky, Heike; Koslowski, Roswitha; Meyer, Udo; Broer, Inge; Huckauf, Jana

    2012-01-01

    We evaluated transgenic tobacco plants as an alternative to Escherichia coli for the production of recombinant human complement factor 5a (C5a). C5a has not been expressed in plants before and is highly unstable in vivo in its native form, so it was necessary to establish the most suitable subcellular targeting strategy. We used the strong and constitutive CaMV 35S promoter to drive transgene expression and compared three different subcellular compartments. The yields of C5a in the T0 transgenic plants were low in terms of the proportion of total soluble protein (TSP) when targeted to the apoplast (0.0002% TSP) or endoplasmic reticulum (0.0003% TSP) but was one order of magnitude higher when targeted to the vacuole (0.001% TSP). The yields could be increased by conventional breeding (up to 0.014% TSP in the T2 generation). C5a accumulated to the same level in seeds and leaves when targeted to the apoplast but was up to 1.7-fold more abundant in the seeds when targeted to the ER or vacuole, although this difference was less striking in the better-performing lines. When yields were calculated as an amount per gram fresh weight of transgenic plant tissue, the vacuole targeting strategy was clearly more efficient in seeds, reaching 35.8 µg C5a per gram of fresh seed weight compared to 10.62 µg C5a per gram fresh weight of leaves. Transient expression of C5aER and C5aVac in N. benthamiana, using MagnICON vectors, reached up to 0.2% and 0.7% of TSP, respectively, but was accompanied by cytotoxic effects and induced leaf senescence. Western blot of the plant extracts revealed a band matching the corresponding glycosylated native protein and the bioassay demonstrated that recombinant C5a was biologically active. PMID:23285250

  19. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  20. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases

  1. Brief report: complement C5a promotes human embryonic stem cell pluripotency in the absence of FGF2.

    PubMed

    Hawksworth, Owen A; Coulthard, Liam G; Taylor, Stephen M; Wolvetang, Ernst J; Woodruff, Trent M

    2014-12-01

    The complement activation product, C5a, is a pivotal member of the innate immune response; however, a diverse number of nonimmune functions are now being ascribed to C5a signaling, including roles during embryonic development. Here, we identify the expression of the C5a precursor protein, C5, as well as the C5a receptors, C5aR and C5L2, in both human embryonic stem cells and human-induced pluripotent stem cells. We show that administration of a physiologically relevant dose of purified human C5a (1 nM) stimulates activation of ERK1/2 and AKT signaling pathways, and is able to promote maintenance of the pluripotent state in the absence of FGF2. C5a also reduced cell loss following dissociation of human pluripotent stem cells. Our results reveal that complement C5a signaling supports human stem cell pluripotency and survival, and thus may play a key role in shaping early human embryonic development.

  2. Streptococcal C5a peptidase is a highly specific endopeptidase.

    PubMed Central

    Cleary, P P; Prahbu, U; Dale, J B; Wexler, D E; Handley, J

    1992-01-01

    Compositional analysis of streptococcal C5a peptidase (SCPA) cleavage products from a synthetic peptide corresponding to the 20 C-terminal residues of C5a demonstrated that the target cleavage site is His-Lys rather than Lys-Asp, as previously suggested. A C5a peptide analog with Lys replaced by Gln was also subject to cleavage by SCPA. This confirmed that His-Lys rather than Lys-Asp is the scissile bond. Cleavage at histidine is unusual but is the same as that suggested for a peptidase produced by group B streptococci. Native C5 protein was also resistant to SCPA, suggesting that the His-Lys bond is inaccessible prior to proteolytic cleavage by C5 convertase. These experiments showed that the streptococcal C5a peptidase is highly specific for C5a and suggest that its function is not merely to process protein for metabolic consumption but to act primarily to eliminate this chemotactic signal from inflammatory foci. Images PMID:1452354

  3. Complement C5a induces PD-L1 expression and acts in synergy with LPS through Erk1/2 and JNK signaling pathways.

    PubMed

    An, Ling-Ling; Gorman, Jacob V; Stephens, Geoffrey; Swerdlow, Bonnie; Warrener, Paul; Bonnell, Jessica; Mustelin, Tomas; Fung, Michael; Kolbeck, Roland

    2016-01-01

    Severe bacterial infection results in both uncontrolled inflammation and immune suppression in septic patients. Although there is ample evidence that complement activation provokes overwhelming pro-inflammatory responses, whether or not it plays a role in immune suppression in this case is unclear. Here, we identify that complement C5a directly participates in negative regulation of immune responses to bacteria-induced inflammation in an ex vivo model of human whole blood. Challenge of whole blood with heat-killed Pseudomonas aeruginosa induces PD-L1 expression on monocytes and the production of IL-10 and TGF-β, which we show to be inhibited by C5a blockade. The induction of PD-L1 expression by C5a is via C5aR1but not C5aR2. Furthermore, C5a synergises with P. aeruginosa LPS in both PD-L1 expression and the production of IL-10 and TGF-β. Mechanistically, C5a contributes to the synergy in PD-L1 expression by specifically activating Erk1/2 and JNK signaling pathways. Our study reveals a new role for C5a in directly promoting immunosuppressive responses. Therefore, aberrant production of complement C5a during bacterial infection could have broader effect on compromising host defense including the induction of immune suppression. PMID:27624143

  4. Complement C5a induces PD-L1 expression and acts in synergy with LPS through Erk1/2 and JNK signaling pathways

    PubMed Central

    An, Ling-Ling; Gorman, Jacob V.; Stephens, Geoffrey; Swerdlow, Bonnie; Warrener, Paul; Bonnell, Jessica; Mustelin, Tomas; Fung, Michael; Kolbeck, Roland

    2016-01-01

    Severe bacterial infection results in both uncontrolled inflammation and immune suppression in septic patients. Although there is ample evidence that complement activation provokes overwhelming pro-inflammatory responses, whether or not it plays a role in immune suppression in this case is unclear. Here, we identify that complement C5a directly participates in negative regulation of immune responses to bacteria-induced inflammation in an ex vivo model of human whole blood. Challenge of whole blood with heat-killed Pseudomonas aeruginosa induces PD-L1 expression on monocytes and the production of IL-10 and TGF-β, which we show to be inhibited by C5a blockade. The induction of PD-L1 expression by C5a is via C5aR1but not C5aR2. Furthermore, C5a synergises with P. aeruginosa LPS in both PD-L1 expression and the production of IL-10 and TGF-β. Mechanistically, C5a contributes to the synergy in PD-L1 expression by specifically activating Erk1/2 and JNK signaling pathways. Our study reveals a new role for C5a in directly promoting immunosuppressive responses. Therefore, aberrant production of complement C5a during bacterial infection could have broader effect on compromising host defense including the induction of immune suppression. PMID:27624143

  5. The complement factor C5a receptor is upregulated in NFL-/- mouse motor neurons.

    PubMed

    Humayun, Saima; Gohar, May; Volkening, Kathryn; Moisse, Katie; Leystra-Lantz, Cheryl; Mepham, Jennifer; McLean, Jesse; Strong, Michael J

    2009-05-29

    In NFL-/- mice, a model of motor neuron degeneration in ALS, degenerating spinal motor neurons express high levels of the receptor for the C5a anaphylatoxin (C5aR) early in the disease process. C5a is a potent in vitro neurotoxin for both Neuro2A and NGF-differentiated PC12 cells. While no interaction was observed between glutamate and C5a, both C5a and kainate upregulated the expression of activated C5aR. C5aR expression was increased in motor neurons in ALS. This data suggests that the early upregulation of C5aR may contribute to motor neuron damage that potentiates excitotoxicity in ALS.

  6. Nociceptive sensitization by complement C5a and C3a in mouse

    PubMed Central

    Jang, Jun Ho; Clark, J. David; Li, Xiangqi; Yorek, Matthew S.; Usachev, Yuriy M.; Brennan, Timothy J.

    2009-01-01

    Activation of the complement system by injury increases inflammation by producing complement fragments C5a and C3a which are able to recruit and activate immune cells. Complement activation may contribute to pain after inflammation and injury. In the present study, we examined whether C5a and C3a elicit nociception when injected into mouse hind paws in vivo, and whether C5a and C3a activate and/or sensitize mechanosensitive nociceptors when applied on peripheral terminals in vitro. We also examined the dorsal root ganglia (DRG) for C5a receptor (C5aR) mRNA and effects of C5a and C3a on intracellular Ca2+ concentration ([Ca2+]i) using Ca2+ imaging. Heat hyperalgesia was elicited by intraplantar injection of C5a, and mechanical hyperalgesia by C5a and C3a. After exposure to either C5a or C3a, C-nociceptors were sensitized to heat as evidenced by an increased proportion of heat responsive fibers, lowered response threshold to heat and increased action potentials during and after heat stimulation. A-nociceptors were activated by complement. However, no change was observed in mechanical responses of A- and C- nociceptors after C5a and C3a application. The presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated [Ca2+]i and facilitated capsaicin-induced [Ca2+]i responses in DRG neurons. The results suggest a potential role for complement fragments C5a and C3a in nociception by activating and sensitizing cutaneous nociceptors. PMID:20031321

  7. Structural and functional characterization of human and murine C5a anaphylatoxins

    SciTech Connect

    Schatz-Jakobsen, Janus Asbjørn; Yatime, Laure Larsen, Casper; Petersen, Steen Vang; Klos, Andreas; Andersen, Gregers Rom

    2014-06-01

    The structure of the human C5aR antagonist, C5a-A8, reveals a three-helix bundle conformation similar to that observed for human C5a-desArg, whereas murine C5a and C5a-desArg both form the canonical four-helix bundle. These conformational differences are discussed in light of the differential C5aR activation properties observed for the human and murine complement anaphylatoxins across species. Complement is an ancient part of the innate immune system that plays a pivotal role in protection against invading pathogens and helps to clear apoptotic and necrotic cells. Upon complement activation, a cascade of proteolytic events generates the complement effectors, including the anaphylatoxins C3a and C5a. Signalling through their cognate G-protein coupled receptors, C3aR and C5aR, leads to a wide range of biological events promoting inflammation at the site of complement activation. The function of anaphylatoxins is regulated by circulating carboxypeptidases that remove their C-terminal arginine residue, yielding C3a-desArg and C5a-desArg. Whereas human C3a and C3a-desArg adopt a canonical four-helix bundle fold, the conformation of human C5a-desArg has recently been described as a three-helix bundle. Here, the crystal structures of an antagonist version of human C5a, A8{sup Δ71–73}, and of murine C5a and C5a-desArg are reported. Whereas A8{sup Δ71–73} adopts a three-helix bundle conformation similar to human C5a-desArg, the two murine proteins form a four-helix bundle. A cell-based functional assay reveals that murine C5a-desArg, in contrast to its human counterpart, exerts the same level of activition as murine C5a on its cognate receptor. The role of the different C5a conformations is discussed in relation to the differential activation of C5a receptors across species.

  8. C5a Induces the Synthesis of IL-6 and TNF-α in Rat Glomerular Mesangial Cells through MAPK Signaling Pathways

    PubMed Central

    Ji, Mingde; Lu, Yanlai; Zhao, Chenhui; Gao, Wenxing; He, Fengxia; Zhang, Jing; Zhao, Dan; Qiu, Wen; Wang, Yingwei

    2016-01-01

    Inflammatory response has been reported to contribute to the renal lesions in rat Thy-1 nephritis (Thy-1N) as an animal model of human mesangioproliferative glomerulonephritis (MsPGN). Besides C5b-9 complex, C5a is also a potent pro-inflammatory mediator and correlated to severity of various nephritic diseases. However, the role of C5a in mediating pro-inflammatory cytokine production in rats with Thy-1N is poorly defined. In the present studies, the levels of C5a, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were first determined in the renal tissues of rats with Thy-1N. Then, the expression of IL-6 and TNF-α was detected in rat glomerular mesangial cells (GMC) stimulated with our recombinant rat C5a in vitro. Subsequently, the activation of mitogen-activated protein kinase (MAPK) signaling pathways (p38 MAPK, ERK1/2 and JNK) and their roles in the regulation of IL-6 and TNF-α production were examined in the GMC induced by C5a. The results showed that the levels of C5a, IL-6 and TNF-α were markedly increased in the renal tissues of Thy-1N rats. Rat C5a stimulation in vitro could up-regulate the expression of IL-6 and TNF-α in rat GMC, and the activation of MAPK signaling pathways was involved in the induction of IL-6 and TNF-α. Mechanically, p38 MAPK activation promoted IL-6 production, while either ERK1/2 or JNK activation promoted TNF-α production in the GMC with exposure to C5a. Taken together, these data implicate that C5a induces the synthesis of IL-6 and TNF-α in rat GMC through the activation of MAPK signaling pathways. PMID:27583546

  9. Differential effects of the complement peptides, C5a and C5a des Arg on human basophil and lung mast cell histamine release.

    PubMed Central

    Schulman, E S; Post, T J; Henson, P M; Giclas, P C

    1988-01-01

    The ability of purified anaphylatoxins to induce human lung mast cell mediator release was investigated. In eight anti-IgE responsive (histamine release = 22 +/- 5%, mean +/- SEM) mast cell preparations of 1-96% purity, C5a and C5a des Arg (0.55 pg/ml to 55 micrograms/ml), failed to elicit or potentiate histamine release; lung fragments were similarly unresponsive. The related peptide C3a was also inactive. All anaphylatoxins failed to induce mast cell leukotriene C4 (LTC4) and prostaglandin D2 (PGD2) release. LTC4 release was also negligible from basophils where C5a was a potent histamine release stimulus. Supernatants from C5a-challenged mast cells remained fully active on basophils, excluding carboxypeptidase inactivation of C5a as an explanation for the lung mast cell results. In contrast to lung, skin mast cells were C5a-responsive (histamine release = 8 +/- 1%, at 55 micrograms/ml, n = 2). We conclude that C5a, though devoid of activity on the human lung mast cell, is a human basophil and skin mast cell secretagogue. These findings demonstrate significant organ-specific heterogeneity in mast cell responsiveness. PMID:2449462

  10. C5A Protects Macaques from Vaginal Simian-Human Immunodeficiency Virus Challenge

    PubMed Central

    Veazey, Ronald S.; Chatterji, Udayan; Bobardt, Michael; Russell-Lodrigue, Kasi E.; Li, Jian; Wang, Xiaolei

    2015-01-01

    A safe and effective vaginal microbicide could decrease human immunodeficiency virus (HIV) transmission in women. Here, we evaluated the safety and microbicidal efficacy of a short amphipathic peptide, C5A, in a rhesus macaque model. We found that a vaginal application of C5A protects 89% of the macaques from a simian-human immunodeficiency virus (SHIV-162P3) challenge. We observed no signs of lesions or inflammation in animals vaginally treated with repeated C5A applications. With its noncellular cytotoxic activity and rare mechanism of action, C5A represents an attractive microbicidal candidate. PMID:26552985

  11. Properdin provides protection from Citrobacter rodentium-induced intestinal inflammation in a C5a/IL-6-dependent manner.

    PubMed

    Jain, Umang; Cao, Qi; Thomas, Nikhil A; Woodruff, Trent M; Schwaeble, Wilhelm J; Stover, Cordula M; Stadnyk, Andrew W

    2015-04-01

    Citrobacter rodentium is an attaching and effacing mouse pathogen that models enteropathogenic and enterohemorrhagic Escherichia coli in humans. The complement system is an important innate defense mechanism; however, only scant information is available about the role of complement proteins during enteric infections. In this study, we examined the impact of the lack of properdin, a positive regulator of complement, in C. rodentium-induced colitis. Following infection, properdin knockout (P(KO)) mice had increased diarrhea and exacerbated inflammation combined with defective epithelial cell-derived IL-6 and greater numbers of colonizing bacteria. The defect in the mucosal response was reversed by administering exogenous properdin to P(KO) mice. Then, using in vitro and in vivo approaches, we show that the mechanism behind the exacerbated inflammation of P(KO) mice is due to a failure to increase local C5a levels. We show that C5a directly stimulates IL-6 production from colonic epithelial cells and that inhibiting C5a in infected wild-type mice resulted in defective epithelial IL-6 production and exacerbated inflammation. These outcomes position properdin early in the response to an infectious challenge in the colon, leading to complement activation and C5a, which in turn provides protection through IL-6 expression by the epithelium. Our results unveil a previously unappreciated mechanism of intestinal homeostasis involving complement, C5a, and IL-6 during bacteria-triggered epithelial injury.

  12. The Complement Anaphylatoxin C5a Induces Apoptosis in Adrenomedullary Cells during Experimental Sepsis

    PubMed Central

    Flierl, Michael A.; Rittirsch, Daniel; Chen, Anthony J.; Nadeau, Brian A.; Day, Danielle E.; Sarma, J. Vidya; Huber-Lang, Markus S.; Ward, Peter A.

    2008-01-01

    Sepsis remains a poorly understood, enigmatic disease. One of the cascades crucially involved in its pathogenesis is the complement system. Especially the anaphylatoxin C5a has been shown to have numerous harmful effects during sepsis. We have investigated the impact of high levels of C5a on the adrenal medulla following cecal ligation and puncture (CLP)-induced sepsis in rats as well as the role of C5a on catecholamine production from pheochromocytoma-derived PC12 cells. There was significant apoptosis of adrenal medulla cells in rats 24 hrs after CLP, as assessed by the TUNEL technique. These effects could be reversed by dual-blockade of the C5a receptors, C5aR and C5L2. When rats were subjected to CLP, levels of C5a and norepinephrine were found to be antipodal as a function of time. PC12 cell production of norepinephrine and dopamine was significantly blunted following exposure to recombinant rat C5a in a time-dependent and dose-dependent manner. This impaired production could be related to C5a-induced initiation of apoptosis as defined by binding of Annexin V and Propidium Iodine to PC12 cells. Collectively, we describe a C5a-dependent induction of apoptotic events in cells of adrenal medulla in vivo and pheochromocytoma PC12 cells in vitro. These data suggest that experimental sepsis induces apoptosis of adrenomedullary cells, which are responsible for the bulk of endogenous catecholamines. Septic shock may be linked to these events. Since blockade of both C5a receptors virtually abolished adrenomedullary apoptosis in vivo, C5aR and C5L2 become promising targets with implications on future complement-blocking strategies in the clinical setting of sepsis. PMID:18648551

  13. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway

    PubMed Central

    McDonald, Chloë R.; Cahill, Lindsay S.; Ho, Keith T.; Yang, Jimmy; Kim, Hani; Silver, Karlee L.; Ward, Peter A.; Mount, Howard T.; Liles, W. Conrad; Sled, John G.; Kain, Kevin C.

    2015-01-01

    The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention. PMID:26402732

  14. Experimental Malaria in Pregnancy Induces Neurocognitive Injury in Uninfected Offspring via a C5a-C5a Receptor Dependent Pathway.

    PubMed

    McDonald, Chloë R; Cahill, Lindsay S; Ho, Keith T; Yang, Jimmy; Kim, Hani; Silver, Karlee L; Ward, Peter A; Mount, Howard T; Liles, W Conrad; Sled, John G; Kain, Kevin C

    2015-09-01

    The in utero environment profoundly impacts childhood neurodevelopment and behaviour. A substantial proportion of pregnancies in Africa are at risk of malaria in pregnancy (MIP) however the impact of in utero exposure to MIP on fetal neurodevelopment is unknown. Complement activation, in particular C5a, may contribute to neuropathology and adverse outcomes during MIP. We used an experimental model of MIP and standardized neurocognitive testing, MRI, micro-CT and HPLC analysis of neurotransmitter levels, to test the hypothesis that in utero exposure to malaria alters neurodevelopment through a C5a-C5aR dependent pathway. We show that malaria-exposed offspring have persistent neurocognitive deficits in memory and affective-like behaviour compared to unexposed controls. These deficits were associated with reduced regional brain levels of major biogenic amines and BDNF that were rescued by disruption of C5a-C5aR signaling using genetic and functional approaches. Our results demonstrate that experimental MIP induces neurocognitive deficits in offspring and suggest novel targets for intervention. PMID:26402732

  15. Synthesis of C-5a-chain extended derivatives of 4-epi-isofagomine: Powerful β-galactosidase inhibitors and low concentration activators of GM1-gangliosidosis-related human lysosomal β-galactosidase.

    PubMed

    Thonhofer, Martin; Weber, Patrick; Santana, Andres Gonzalez; Fischer, Roland; Pabst, Bettina M; Paschke, Eduard; Schalli, Michael; Stütz, Arnold E; Tschernutter, Marion; Windischhofer, Werner; Withers, Stephen G

    2016-03-01

    From an easily available partially protected formal derivative of 1-deoxymannojirimycin, by hydroxymethyl chain-branching and further elaboration, lipophilic analogs of the powerful β-d-galactosidase inhibitor 4-epi-isofagomine have become available. New compounds exhibit improved inhibitory activities comparable to benchmark compound NOEV (N-octyl-epi-valienamine) and may serve as leads towards improved and more selective pharmacological chaperones for GM1-gangliosidosis.

  16. Regulation of human mast cell and basophil function by anaphylatoxins C3a and C5a

    PubMed Central

    Ali, Hydar

    2009-01-01

    Allergic diseases such as asthma result from inappropriate immunologic responses to common environmental allergens in genetically susceptible individuals. Following allergen exposure, interaction of dendritic cells (DC) with CD4+ T cells leads to the production of Th2 cytokines, which induce B cells to synthesize IgE molecules (sensitization phase). These IgE molecules bind to their high affinity receptors (FcεRI) on the surface of mast cells and basophils and their subsequent cross-linking by allergen results in the release of preformed and newly synthesized mediators, which cause bronchoconstriction, lung inflammation and airway hyperresponsiveness (AHR) in asthma (effector phase). The complement components C3a and C5a levels are increased in the lungs of patients with asthma and are likely generated via the actions of both allergen and mast cell proteases. In vivo studies with rodents have shown that while C3a facilitates allergen sensitization in some models C5a inhibits this response. Despite this difference, both anaphylatoxins promote lung inflammation and AHR in vivo indicating that cells other than DC and T cells likely mediate the functional effects of C3a and C5a in asthma. This review focuses on the contribution of C3a and C5a in the pathogenesis of asthma with a particular emphasis on mast cells and basophils. It discusses the mechanisms by which anaphylatoxins activate mast cells and basophils and the associated signaling pathways via which their receptors are regulated by priming and desensitization. PMID:19895849

  17. Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a.

    PubMed

    Taylor, Lewis; Brodermann, Maximillian Hugo; McCaffary, David; Iqbal, Asif Jilani; Greaves, David R

    2016-01-01

    Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with netrin-1 inhibited their chemotaxis towards C5a, as measured using two different real-time methods. This inhibitory effect was found to be dependent on netrin-1 receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1 inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no effect on C5aR1 proximal signalling events, as surface C5aR1 expression, internalisation and intracellular Ca2+ release following C5aR1 ligation remained unaffected after netrin-1 exposure. We next examined receptor distal events that occur following C5aR1 activation, but found that netrin-1 was unable to inhibit C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM cytoskeletal rearrangement following C5a stimulation as determined by microscopy and real-time electrical impedance sensing. Taken together these data highlight that netrin-1 inhibits monocyte and macrophage cell migration, but that the mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its cognate receptors warrant further investigation as they may represent a potential avenue for the development of

  18. Netrin-1 Reduces Monocyte and Macrophage Chemotaxis towards the Complement Component C5a

    PubMed Central

    McCaffary, David; Iqbal, Asif Jilani; Greaves, David R.

    2016-01-01

    Netrin-1, acting at its cognate receptor UNC5b, has been previously demonstrated to inhibit CC chemokine-induced immune cell migration. In line with this, we found that netrin-1 was able to inhibit CCL2-induced migration of bone marrow derived macrophages (BMDMs). However, whether netrin-1 is capable of inhibiting chemotaxis to a broader range of chemoattractants remains largely unexplored. As our initial experiments demonstrated that RAW264.7 and BMDMs expressed high levels of C5a receptor 1 (C5aR1) on their surface, we aimed to determine the effect of netrin-1 exposure on monocyte/macrophage cell migration induced by C5a, a complement peptide that plays a major role in multiple inflammatory pathologies. Treatment of RAW264.7 macrophages, BMDMs and human monocytes with netrin-1 inhibited their chemotaxis towards C5a, as measured using two different real-time methods. This inhibitory effect was found to be dependent on netrin-1 receptor signalling, as an UNC5b blocking antibody was able to reverse netrin-1 inhibition of C5a induced BMDM migration. Treatment of BMDMs with netrin-1 had no effect on C5aR1 proximal signalling events, as surface C5aR1 expression, internalisation and intracellular Ca2+ release following C5aR1 ligation remained unaffected after netrin-1 exposure. We next examined receptor distal events that occur following C5aR1 activation, but found that netrin-1 was unable to inhibit C5a induced phosphorylation of ERK1/2, Akt and p38, pathways important for cellular migration. Furthermore, netrin-1 treatment had no effect on BMDM cytoskeletal rearrangement following C5a stimulation as determined by microscopy and real-time electrical impedance sensing. Taken together these data highlight that netrin-1 inhibits monocyte and macrophage cell migration, but that the mechanism behind this effect remains unresolved. Nevertheless, netrin-1 and its cognate receptors warrant further investigation as they may represent a potential avenue for the development of

  19. Protective effects of anti-C5a in sepsis-induced thymocyte apoptosis

    PubMed Central

    Guo, Ren-Feng; Huber-Lang, Markus; Wang, Xin; Sarma, Vidya; Padgaonkar, Vaishalee A.; Craig, Ronald A.; Riedemann, Niels C.; McClintock, Shannon D.; Hlaing, Tommy; Shi, Michael M.; Ward, Peter A.

    2000-01-01

    Multiorgan apoptosis occurs during sepsis. Following cecal ligation and puncture (CLP) in rats, thymocytes underwent apoptosis in a time-dependent manner. C5a blockade dramatically reduced thymocyte apoptosis as measured by thymic weight, binding of annexin V to thymocytes, and laddering of thymocyte DNA. When C5a was generated in vivo by infusion of purified cobra venom factor (CVF), thymocyte apoptosis was significantly increased. Similar results were found when CVF was injected in vivo during the early stages of CLP. In animals 12 hours after induction of CLP, there was an increase in the activities of caspase-3, -6, and -9, but not caspase-1 and -8. Cytosolic cytochrome c levels increased by twofold, whereas mitochondrial levels showed a 50% decrease. Western blot analysis revealed that the content of Bcl-XL (but not of Bcl-2, BAX, Bad, and Bim) significantly decreased in thymocytes after CLP. C5a blockade in the sepsis model almost completely inhibited caspase-3, -6, and -9 activation, significantly preserved cytochrome c in the mitochondrial fraction, and restored Bcl-XL expression. These data suggest that systemic activation of complement induces C5a-dependent apoptosis of thymocytes and that the blockade of C5a during sepsis rescues thymocytes from apoptosis. PMID:11086028

  20. Cloning, expression, cellular distribution, and role in chemotaxis of a C5a receptor in rainbow trout: the first identification of a C5a receptor in a nonmammalian species

    USGS Publications Warehouse

    Boshra, Hani; Li, Jun; Peters, Rodney; Hansen, John; Matlapudi, Anjan; Sunyer, J. Oriol

    2004-01-01

    C3a, C4a, and C5a anaphylatoxins generated during complement activation play a key role in inflammation. C5a is the most potent of the three anaphylatoxins in eliciting biological responses. The effects of C5a are mediated by its binding to C5a receptor (C5aR, CD88). To date, C5aR has only been identified and cloned in mammalian species, and its evolutionary history remains ill-defined. To gain insights into the evolution, conserved structural domains, and functions of C5aR, we have cloned and characterized a C5aR in rainbow trout, a teleost fish. The isolated cDNA encoded a 350-aa protein that showed the highest sequence similarity to C5aR from other species. Genomic analysis revealed the presence of one continuous exon encoding the entire open reading frame. Northern blot analysis showed significant expression of the trout C5a receptor (TC5aR) message in PBLs and kidney. Flow cytometric analysis showed that two Abs generated against two different areas of the extracellular N-terminal region of TC5aR positively stained the same leukocyte populations from PBLs. B lymphocytes and granulocytes comprised the majority of cells recognized by the anti-TC5aR. More importantly, these Abs inhibited chemotaxis of PBLs toward a chemoattractant fraction purified from complement-activated trout serum. Our data suggest that the split between C5aR and C3aR from a common ancestral molecule occurred before the emergence of teleost fish. Moreover, we demonstrate that the overall structure of C5aR as well as its role in chemotaxis have remained conserved for >300 million years.

  1. Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer

    NASA Astrophysics Data System (ADS)

    Yatime, Laure; Maasch, Christian; Hoehlig, Kai; Klussmann, Sven; Andersen, Gregers R.; Vater, Axel

    2015-04-01

    L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the first crystallographic structures of an active Spiegelmer, NOX-D20, bound to its physiological targets, mouse C5a and C5a-desArg. The structures reveal a complex 3D architecture for the L-aptamer that wraps around C5a, including an intramolecular G-quadruplex stabilized by a central Ca2+ ion. Functional validation of the observed L-aptamer:C5a binding mode through mutational studies also rationalizes the specificity of NOX-D20 for mouse and human C5a against macaque and rat C5a. Finally, our structural model provides the molecular basis for the Spiegelmer affinity improvement through positional L-ribonucleotide to L-deoxyribonucleotide exchanges and for its inhibition of the C5a:C5aR interaction.

  2. Structural basis for the targeting of complement anaphylatoxin C5a using a mixed L-RNA/L-DNA aptamer

    PubMed Central

    Yatime, Laure; Maasch, Christian; Hoehlig, Kai; Klussmann, Sven; Andersen, Gregers R.; Vater, Axel

    2015-01-01

    L-Oligonucleotide aptamers (Spiegelmers) consist of non-natural L-configured nucleotides and are of particular therapeutic interest due to their high resistance to plasma nucleases. The anaphylatoxin C5a, a potent inflammatory mediator generated during complement activation that has been implicated with organ damage, can be efficiently targeted by Spiegelmers. Here, we present the first crystallographic structures of an active Spiegelmer, NOX-D20, bound to its physiological targets, mouse C5a and C5a-desArg. The structures reveal a complex 3D architecture for the L-aptamer that wraps around C5a, including an intramolecular G-quadruplex stabilized by a central Ca2+ ion. Functional validation of the observed L-aptamer:C5a binding mode through mutational studies also rationalizes the specificity of NOX-D20 for mouse and human C5a against macaque and rat C5a. Finally, our structural model provides the molecular basis for the Spiegelmer affinity improvement through positional L-ribonucleotide to L-deoxyribonucleotide exchanges and for its inhibition of the C5a:C5aR interaction. PMID:25901944

  3. Structural complexes of the agonist, inverse agonist and antagonist bound C5a receptor: insights into pharmacology and signaling.

    PubMed

    Rana, Soumendra; Sahoo, Amita Rani; Majhi, Bharat Kumar

    2016-04-26

    The C5a receptor (C5aR) is a pharmacologically important G-protein coupled receptor (GPCR) that interacts with (h)C5a, by recruiting both the "orthosteric" sites (site1 at the N-terminus and site2 at the ECS, extra cellular surface) on C5aR in a two site-binding model. However, the complex pharmacological landscape and the distinguishing chemistry operating either at the "orthosteric" site1 or at the functionally important "orthosteric" site2 of C5aR are still not clear, which greatly limits the understanding of C5aR pharmacology. One of the major bottlenecks is the lack of an experimental structure or a refined model structure of C5aR with appropriately defined active sites. The study attempts to understand the pharmacology at the "orthosteric" site2 of C5aR rationally by generating a highly refined full-blown model structure of C5aR through advanced molecular modeling techniques, and further subjecting it to automated docking and molecular dynamics (MD) studies in the POPC bilayer. The first series of structural complexes of C5aR respectively bound to a linear native peptide agonist ((h)C5a-CT), a small molecule inverse agonist (NDT) and a cyclic peptide antagonist (PMX53) are reported, apparently establishing the unique pharmacological landscape of the "orthosteric" site2, which also illustrates an energetically distinct but coherent competitive chemistry ("cation-π" vs. "π-π" interactions) involved in distinguishing the established ligands known for targeting the "orthosteric" site2 of C5aR. Over a total of 1 μs molecular dynamics (MD) simulation in the POPC bilayer, it is evidenced that while the agonist prefers a "cation-π" interaction, the inverse agonist prefers a "cogwheel/L-shaped" interaction in contrast to the "edge-to-face/T-shaped" type π-π interactions demonstrated by the antagonist by engaging the F275(7.28) of the C5aR. In the absence of a NMR or crystallographically guided model structure of C5aR, the computational model complexes not only

  4. Abrogation of immune complex glomerulonephritis by native carboxypeptidase and pharmacological antagonism of the C5a receptor

    PubMed Central

    Alexander, Jessy J.; Chaves, Lee D.; Chang, Anthony; Dighe, Shruti; Jacob, Alexander; Quigg, Richard J.

    2016-01-01

    Activation of complement generates C5a which leads to signaling through C5aR1. This is tightly controlled, including by the plasma proteins factor H (FH) and carboxypeptidase N. Here we studied a chronic serum sickness (CSS) model of glomerulonephritis (GN) in which there is an active humoral immune response, formation of glomerular immune complexes (ICs), and resulting glomerular inflammation. The antibody response, glomerular IC deposition, the degree of GN, and consequent renal functional insufficiency in CSS were all worse in FH−/− mice compared to wild-type FH+/+ animals. This was ameliorated in the former by giving a C5aR1 antagonist for the final 3 weeks of the 5-week protocol. In contrast, blocking CP-mediated inactivation of C5a increased these disease measures. Thus, complement regulation by both plasma FH and CP to limit the quantity of active C5a is important in conditions where the humoral immune response is directed to a continuously present foreign antigen. Signaling through C5aR1 enhances the humoral immune response as well as the inflammatory response to ICs that have formed in glomeruli. Both effects are relevant even after disease has begun. Thus, pharmacological targeting of C5a in IC-mediated GN has potential clinical relevance. PMID:26166765

  5. Interleukin 3-dependent mediator release in basophils triggered by C5a

    PubMed Central

    1989-01-01

    The anaphylatoxin C5a is a potent trigger for basophil degranulations, but in contrast to IgE-dependent basophil activation, it does not result in the synthesis of sulfidoleukotrienes (leukotriene C4/D4/E4). Thus, degranulation and the generation of lipid mediators are separately regulated cellular responses. Exposure of human blood basophils to the cytokine IL-3 alone does not induce the release of histamine in cells from most donors and never leads to the generation of LTC4, indicating that IL-3 is not a direct agonist for basophil mediator release. However, preincubation of basophils with IL-3 enhances the degranulation response to C5a. Most importantly, IL-3 "primes" basophils to release large amounts of leukotriene C4 after challenge with C5a (mean of 50 gp LTC4 per nanograms cellular histamine), while neither peptide alone is capable of inducing the formation of bioactive lipids. This effect is dose dependent, occurring at IL-3 concentrations considerably lower than are required to stimulate the growth of bone marrow progenitor cells. IL-3 affects the extent but not the time course of basophil degranulation, and leukotriene release of cells sequentially exposed to IL-3 and C5a occurs very rapidly concomitant with degranulation. A preincubation of the basophils with IL-3 is strictly required for C5a-induced LTC4 synthesis, but not for an enhancement of degranulation. Priming for C5a- induced lipid mediator generation occurs rapidly after exposure of the cells to IL-3, starting at 1 min and reaching maximal effects at 5 min, but this altered state of responsiveness is relatively long lasting. Cell fractionation studies indicate that the basophil is the source of lipid mediators and that IL-3 affects the basophil response directly. This study demonstrates that IL-3 is a potent modifier of effector functions of mature basophils; this is possibly of greater in vivo significance than its growth factor properties. The large amounts of LTC4 formed after triggering of

  6. Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth.

    PubMed

    Chmilewsky, Fanny; Ayaz, Warda; Appiah, James; About, Imad; Chung, Seung-Hyuk

    2016-01-01

    Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation. PMID:27539194

  7. Nerve Growth Factor Secretion From Pulp Fibroblasts is Modulated by Complement C5a Receptor and Implied in Neurite Outgrowth

    PubMed Central

    Chmilewsky, Fanny; Ayaz, Warda; Appiah, James; About, Imad; Chung, Seung-Hyuk

    2016-01-01

    Given the importance of sensory innervation in tooth vitality, the identification of signals that control nerve regeneration and the cellular events they induce is essential. Previous studies demonstrated that the complement system, a major component of innate immunity and inflammation, is activated at the injured site of human carious teeth and plays an important role in dental-pulp regeneration via interaction of the active Complement C5a fragment with pulp progenitor cells. In this study, we further determined the role of the active fragment complement C5a receptor (C5aR) in dental nerve regeneration in regards to local secretion of nerve growth factor (NGF) upon carious injury. Using ELISA and AXIS co-culture systems, we demonstrate that C5aR is critically implicated in the modulation of NGF secretion by LTA-stimulated pulp fibroblasts. The NGF secretion by LTA-stimulated pulp fibroblasts, which is negatively regulated by C5aR activation, has a role in the control of the neurite outgrowth length in our axon regeneration analysis. Our data provide a scientific step forward that can guide development of future therapeutic tools for innovative and incipient interventions targeting the dentin-pulp regeneration process by linking the neurite outgrowth to human pulp fibroblast through complement system activation. PMID:27539194

  8. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.

    PubMed

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-09-01

    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  9. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

    PubMed Central

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-01-01

    Blood–brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

  10. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

    PubMed

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-11-01

    Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings.

  11. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

    PubMed

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-11-01

    Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

  12. CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a

    PubMed Central

    Vaivoda, Rachel; Vaine, Christine; Boerstler, Cassandra; Galloway, Kristy; Christmas, Peter

    2015-01-01

    CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4). CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9–2.25-fold in knockout cells compared to wild-type (P < 0.01). This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies. PMID:26613087

  13. CYP4F18-Deficient Neutrophils Exhibit Increased Chemotaxis to Complement Component C5a.

    PubMed

    Vaivoda, Rachel; Vaine, Christine; Boerstler, Cassandra; Galloway, Kristy; Christmas, Peter

    2015-01-01

    CYP4Fs were first identified as enzymes that catalyze hydroxylation of leukotriene B4 (LTB4). CYP4F18 has an unusual expression in neutrophils and was predicted to play a role in regulating LTB4-dependent inflammation. We compared chemotaxis of wild-type and Cyp4f18 knockout neutrophils using an in vitro assay. There was no significant difference in the chemotactic response to LTB4, but the response to complement component C5a increased 1.9-2.25-fold in knockout cells compared to wild-type (P < 0.01). This increase was still observed when neutrophils were treated with inhibitors of eicosanoid synthesis. There were no changes in expression of other CYP4 enzymes in knockout neutrophils that might compensate for loss of CYP4F18 or lead to differences in activity. A mouse model of dextran sodium sulfate colitis was used to investigate the consequences of increased C5a-dependent chemotaxis in vivo, but there was no significant difference in weight loss, disease activity, or colonic tissue myeloperoxidase between wild-type and Cyp4f18 knockout mice. This study demonstrates the limitations of inferring CYP4F function based on an ability to use LTB4 as a substrate, points to expanding roles for CYP4F enzymes in immune regulation, and underscores the in vivo challenges of CYP knockout studies.

  14. Silencing of C5a receptor gene with siRNA for protection from Gram-negative bacterial lipopolysaccharide-induced vascular permeability.

    PubMed

    Liu, Zi-ming; Zhu, Shi-ming; Qin, Xiang-jing; Cheng, Zhi-de; Liu, Meng-yuan; Zhang, Hai-mou; Liu, Dong-xu

    2010-03-01

    Endothelial barrier dysfunction leading to increased permeability and vascular leakage is an underlying cause of several pathological conditions. Whereas these changes have been shown to be associated with activation of the complement system, leading to the release of C5a and interaction of C5a-C5a receptor (C5aR), the role of C5aR in endothelial cells remain(s) ill-defined. Here, we report an essential role of C5aR in endothelial cell injury and vascular permeability through silencing of the C5aR gene using siRNA. In the cultured mouse dermal microvascular endothelial cells (MEMECs) monolayer transfected with C5aR-siRNA, endotoxin-induced cell injury by evaluated as transendothelial flux, cell detachment, and cytoskeletal disorganization was inhibited. Upregulation of vascular cell adhesion molecule-1 (VCAM-1) was also suppressed. Studies exploring the underlying mechanism of siRNA-mediated suppression in VCAM-1 expression were related to reduction of NF-kappaB activation and nuclear localization of both p50 and p65. The effect was associated with inhibition in activation of protein kinase Cdelta(PKC-delta) and induction of PKC-mediated mitogen-activated protein kinase phosphatases-1 (MKP-1) leading to the increased activity of p42/p44 mitogen-activated protein (MAP) kinase cascade. In the model of mice administrated with C5aR-siRNA, endotoxin-induced plasma leakage was inhibited in local abdominal skin. Systemic administration of endotoxin to mice resulted in increased microvascular permeability in multiple organs was reduced. These studies demonstrate that the C5aR responsible for vascular endothelial cell injury and plasma permeability is an important factor, and that blockade of C5aR may be useful therapeutic targets for the prevention of vascular permeability in pathogenic condition.

  15. Inhibition of inflammation and fibrosis by a complement C5a receptor antagonist in DOCA-salt hypertensive rats.

    PubMed

    Iyer, Abishek; Woodruff, Trent M; Wu, Mike C L; Stylianou, Con; Reid, Robert C; Fairlie, David P; Taylor, Stephen M; Brown, Lindsay

    2011-11-01

    The anaphylatoxin C5a generated by activation of the innate immunity complement system is a potent inflammatory peptide mediator through the G-protein-coupled receptor C5aR (CD88) present in immune-inflammatory cells, including monocytes, macrophages, neutrophils, T cells, and mast cells. Inflammatory cells infiltrate and initiate the development of fibrosis in the chronically hypertensive heart. In this study, we have investigated whether treatment with a selective C5aR antagonist prevents cardiovascular remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Control and DOCA-salt rats were treated with PMX53 (AcF-[OPdChaWR], 1 mg·kg·d oral gavage) for 32 days; structural and functional changes in cardiovascular system were determined. DOCA-salt hypertension increased leukocyte extravasation into ventricular tissue, increasing collagen deposition and ventricular stiffness; PMX53 treatment attenuated these changes, thereby improving cardiac function. Further, treatment with PMX53 suppressed an increased expression of C5aR in the left ventricle from DOCA-salt rats, consistent with the reduced infiltration of inflammatory cells. Vascular endothelial dysfunction in thoracic aortic rings was attenuated by PMX53 treatment, but systolic blood pressure was unchanged in DOCA-salt rats. In the heart, PMX53 treatment attenuated inflammatory cell infiltration, fibrosis, and ventricular stiffness, indicating that C5aR is critically involved in ventricular remodeling by regulating inflammatory responses in the hypertensive heart. PMID:21753735

  16. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection.

    PubMed

    Hung, Chiung-Yu; Hurtgen, Brady J; Bellecourt, Michael; Sanderson, Sam D; Morgan, Edward L; Cole, Garry T

    2012-06-29

    Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical vaccine exists. In this study we evaluated a novel vaccine adjuvant referred to as EP67, which is a peptide agonist of the biologically active C-terminal region of human complement component C5a. The EP67 peptide was conjugated to live spores of an attenuated vaccine strain (ΔT) of Coccidioides posadasii. The non-conjugated ΔT vaccine provided partial protection to BALB/c mice against coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67 vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67 vaccine also revealed enhanced expression of MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4(+) T cells. Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides antigen-specific IgG1 and IgG2a were detected in mice immunized with the EP67-conjugated versus the non-conjugated vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to Coccidioides infection.

  17. An agonist of human complement fragment C5a enhances vaccine immunity against Coccidioides infection

    PubMed Central

    Hung, Chiung-Yu; Hurtgen, Brady J.; Bellecourt, Michael; Sanderson, Sam D.; Morgan, Edward L.; Cole, Garry T.

    2012-01-01

    Coccidioides is a fungal pathogen and causative agent of a human respiratory disease against which no clinical vaccine exists. In this study we evaluated a novel vaccine adjuvant referred to as EP67, which is a peptide agonist of the biologically active C-terminal region of human complement component C5a. The EP67 peptide was conjugated to live spores of an attenuated vaccine strain (ΔT) of C. posadasii. The non-conjugated ΔT vaccine provided partial protection to BALB/c mice against coccidioidomycosis. In this report we compared the protective efficacy of the ΔT-EP67 conjugate to the ΔT vaccine in BALB/c mice. Animals immunized subcutaneously with the ΔT-EP67 vaccine showed significant increase in survival and decrease in fungal burden over 75 days postchallenge. Increased pulmonary infiltration of dendritic cells and macrophages was observed on day 7 postchallenge but marked decrease in neutrophil numbers had occurred by 11 days. The reduced influx of neutrophils may have contributed to the observed reduction of inflammatory pathology. Mice immunized with the ΔT-EP67 vaccine also revealed enhanced expression of MHC II molecules on the surface of antigen presenting cells, and in vitro recall assays of immune splenocytes showed elevated Th1- and Th17-type cytokine production. The latter correlated with a marked increase in lung infiltration of IFN-γ- and IL-17-producing CD4+ T cells. Elevated expression of T-bet and RORc transcription factors in ΔT-EP67-vaccinated mice indicated the promotion of Th1 and Th17 cell differentiation. Higher titers of Coccidioides antigen-specific IgG1 and IgG2a were detected in mice immunized with the EP67- conjugated versus the non-conjugated vaccine. These combined results suggest that the EP67 adjuvant enhances protective efficacy of the live vaccine by augmentation of T-cell immunity, especially through Th1- and Th17-mediated responses to Coccidioides infection. PMID:22575167

  18. Role of the complement anaphylatoxin C5a-receptor pathway in atopic dermatitis in mice

    PubMed Central

    DANG, LIN; HE, LEI; WANG, YAN; XIONG, JIKUI; BAI, BINGXUE; LI, YUZHEN

    2015-01-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease with a genetic background. The C5a-receptor (C5aR) pathway has been reported to be involved in AD; however, the precise pathogenesis remains to be elucidated. In the present study, the contribution of the C5aR pathway to AD in mice was investigated. A BALB/c mouse model of AD was induced by application of 2,4-dinitrochlorobenzene (DNCB) onto hairless dorsal skin. Following DNCB application for 2 weeks, C5aR expression in skin tissue was assessed by reverse transcription quantitative polymerase chain reaction. C5aR expression in skin tissue was significantly increased in mice with AD. In an additional experiment, C5aR antagonist (C5aRA) intracutaneously injected in combination with DNCB treatment. The skin-fold thickness, number of total infiltrating leukocytes and mast cells infiltrating in skin tissue were measured. Interleukin-4 (IL-4) and interferon-γ (IFN-γ) levels in skin tissue and IL-4, IFN-γ, histamine and immunoglobulin E (IgE) levels in serum were measured using ELISA. The skin-fold thickness, numbers of total infiltrating leukocytes and mast cells in skin tissue, as well as levels of IL-4, IFN-γ, histamine and IgE were significantly increased in mice with AD. However, simultaneous treatment with C5aRA significantly attenuated increases in skin fold thickness and the numbers of total infiltrating leukocytes and mast cells in skin tissue. Treatment with C5aRA also decreased IL-4 and IFN-γ levels in skin tissue, as well as the levels of IL-4, IFN-γ, histamine and IgE in the serum. In conclusion, C5aRA inhibited AD in mice, possibly through suppression of the C5aR-mediated cascade action of mast cells. PMID:25650554

  19. Combined Yeast β-Glucan and Antitumor Monoclonal Antibody Therapy Requires C5a-Mediated Neutrophil Chemotaxis via Regulation of Decay-Accelerating Factor CD55

    PubMed Central

    Li, Bing; Allendorf, Daniel J.; Hansen, Richard; Marroquin, Jose; Cramer, Daniel E.; Harris, Claire L.; Yan, Jun

    2008-01-01

    Administration of a combination of yeast-derived β-glucan with antitumor monoclonal antibodies (mAb) has significant therapeutic efficacy in a variety of syngeneic murine tumor models. We have now tested this strategy using human carcinomas implanted in immunocompromised severe combined immunodeficient mice. Combined immunotherapy was therapeutically effective in vivo against NCI-H23 human non–small-cell lung carcinomas, but this modality was surprisingly ineffective against SKOV-3 human ovarian carcinomas. Whereas NCI-H23 tumors responded to this combination therapy with increased intratumoral neutrophil infiltration and C5a production, these responses were lacking in treated SKOV-3 tumors. Further results suggested that SKOV-3 tumors were protected by up-regulation of the membrane complement regulatory protein CD55 (decay-accelerating factor). Blockade of CD55 in vitro led to enhanced deposition of C activation product C3b and increased cytotoxicity mediated by β-glucan–primed neutrophils. In vivo, administration of anti-CD55 mAb along with β-glucan and anti–Her-2/neu mAb caused tumor regression and greatly improved long-term survival in animals bearing the previously resistant SKOV-3 tumors. This was accompanied by increased intratumoral neutrophil accumulation and C5a production. We conclude that CD55 suppresses tumor killing by antitumor mAb plus β-glucan therapy (and, perhaps, in other circumstances). These results suggest a critical role for CD55 to regulate iC3b and C5a release and in turn to influence the recruitment of β-glucan–primed neutrophils eliciting killing activity. PMID:17671212

  20. C5L2: a controversial receptor of complement anaphylatoxin, C5a.

    PubMed

    Li, Rui; Coulthard, Liam G; Wu, M C L; Taylor, Stephen M; Woodruff, Trent M

    2013-03-01

    C5a is the paramount proinflammatory mediator of the complement cascade, and has been previously thought to act only through a single, G-protein-coupled, C5a receptor (C5aR; also termed CD88). In 2000, a second C5a receptor, C5L2 (previously known as GPR77), was discovered; yet, despite 12 yr of intensive research, its biological, or pathophysiological, function is both enigmatic and controversial. Unlike C5aR, this receptor does not couple to G proteins, and early studies promoted the hypothesis that C5L2 functions as a decoy receptor. However, recent data have provided other evidence for more complicated and conflicting interactions between C5L2 and other inflammatory mediators. C5L2 has been recently demonstrated to physically interact with both C5aR and β-arrestin to negatively regulate C5aR signaling toward an anti-inflammatory manner, and to reduce pathology, in several disease models in vivo. In direct contrast, other groups have demonstrated that C5L2 stimulation caused release of HMGB1 both in vitro and in vivo, and enhanced pathology in sepsis models, suggesting a clear proinflammatory signaling role. These astoundingly contradictory data challenge our precepts and complicate the foundational bases for the possible targeting of C5L2 as a therapeutic option in inflammatory disease. C5L2 may be the great masquerader in complement biology; its function dependent on the cell type, species, and disease context. Because of these unusual and unforeseen complexities, we present the current state of knowledge on C5L2 structure, expression and, most controversially, its putative functions.-Li, R., Coulthard, L.G., Wu, M. C. L., Taylor, S. M., Woodruff, T. M. C5L2: a controversial receptor of complement anaphylatoxin, C5a. PMID:23239822

  1. *C5a/CD88 signaling alters blood-brain barrier integrity in lupus through NFκb

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Chen, Peili; Quigg, Richard J.; Alexander, Jessy J.

    2011-01-01

    Inflammation is a key factor in a number of neurodegenerative diseases including systemic lupus erythematosus (SLE). The complement system is an important mechanism in initiating and amplifying inflammation. Our recent studies demonstrate that C5a, a protein fragment generated during complement activation could alter the blood-brain barrier (BBB) integrity, and thereby disturb the brain microenvironment. To understand the mechanism by which this occurs, we examined the effects of C5a on apoptosis, translocation of nuclear factor-κB (NFκb) and the expression of Iκbα, MAPK, CREB and TJ protein, zona occludens (ZO-1) in mouse brain endothelial cells. Apoptosis was examined by DNA laddering and caspase-3 activity and the distribution of the ZO-1 and the p65 subunit of NFκB were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NFκb into the nucleus, altered ZO-1 at the interfaces of neighboring cells, decreased caspase-3 activity and prevented apoptosis in these cells. Our results indicate that signaling through CD88 regulates the BBB in a NFκb dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NFκb signaling cascades in inflammatory settings. PMID:21929539

  2. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  3. Spontaneous abortion is associated with elevated systemic C5a and reduced mRNA of complement inhibitory proteins in placenta.

    PubMed

    Banadakoppa, M; Chauhan, M S; Havemann, D; Balakrishnan, M; Dominic, J S; Yallampalli, C

    2014-09-01

    Spontaneous abortion in early pregnancy due to unknown reasons is a common problem. The excess complement activation and consequent placental inflammation and anti-angiogenic milieu is emerging as an important associated factor in many pregnancy-related complications. In the present study we sought to examine the expression of complement inhibitory proteins at the feto-maternal interface and levels of complement split products in the circulation to understand their role in spontaneous abortion. Consenting pregnant women who either underwent elective abortion due to non-clinical reasons (n = 13) or suffered miscarriage (n = 14) were recruited for the study. Systemic levels of complement factors C3a and C5a were measured by enzyme-linked immunosorbent assay (ELISA). Plasma C5 and C3 protein levels were examined by Western blot. Expressions of complement regulatory proteins such as CD46 and CD55 in the decidua were investigated by quantitative polymerase chain reaction (PCR) and Western blot. The median of plasma C3a level was 82·83 ng/ml and 66·17 ng/ml in elective and spontaneous abortion patients, respectively. Medians of plasma C5a levels in elective and spontaneous abortion patients were 0·96 ng/ml and 1·14 ng/ml, respectively. Only plasma C5a levels but not C3a levels showed significant elevation in spontaneous abortion patients compared to elective abortion patients. Further, there was a threefold decrease in the mRNA expressions of complement inhibitory proteins CD46 and CD55 in the decidua obtained from spontaneous abortion patients compared to that of elective abortion patients. These data suggested that dysregulated complement cascade may be associated with spontaneous abortion.

  4. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    NASA Astrophysics Data System (ADS)

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-04-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1–3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents.

  5. Receptor residence time trumps drug-likeness and oral bioavailability in determining efficacy of complement C5a antagonists

    PubMed Central

    Seow, Vernon; Lim, Junxian; Cotterell, Adam J.; Yau, Mei-Kwan; Xu, Weijun; Lohman, Rink-Jan; Kok, W. Mei; Stoermer, Martin J.; Sweet, Matthew J.; Reid, Robert C.; Suen, Jacky Y.; Fairlie, David P.

    2016-01-01

    Drug discovery and translation are normally based on optimizing efficacy by increasing receptor affinity, functional potency, drug-likeness (rule-of-five compliance) and oral bioavailability. Here we demonstrate that residence time of a compound on its receptor has an overriding influence on efficacy, exemplified for antagonists of inflammatory protein complement C5a that activates immune cells and promotes disease. Three equipotent antagonists (3D53, W54011, JJ47) of inflammatory responses to C5a (3nM) were compared for drug-likeness, receptor affinity and antagonist potency in human macrophages, and anti-inflammatory efficacy in rats. Only the least drug-like antagonist (3D53) maintained potency in cells against higher C5a concentrations and had a much longer duration of action (t1/2 ~ 20 h) than W54011 or JJ47 (t1/2 ~ 1–3 h) in inhibiting macrophage responses. The unusually long residence time of 3D53 on its receptor was mechanistically probed by molecular dynamics simulations, which revealed long-lasting interactions that trap the antagonist within the receptor. Despite negligible oral bioavailability, 3D53 was much more orally efficacious than W54011 or JJ47 in preventing repeated agonist insults to induce rat paw oedema over 24 h. Thus, residence time on a receptor can trump drug-likeness in determining efficacy, even oral efficacy, of pharmacological agents. PMID:27094554

  6. A Novel C5a-neutralizing Mirror-image (l-)Aptamer Prevents Organ Failure and Improves Survival in Experimental Sepsis

    PubMed Central

    Hoehlig, Kai; Maasch, Christian; Shushakova, Nelli; Buchner, Klaus; Huber-Lang, Markus; Purschke, Werner G; Vater, Axel; Klussmann, Sven

    2013-01-01

    Complement factor C5a is a potent proinflammatory mediator that contributes to the pathogenesis of numerous inflammatory diseases. Here, we describe the discovery of NOX-D20, a PEGylated biostable mirror-image mixed (l-)RNA/DNA aptamer (Spiegelmer) that binds to mouse and human C5a with picomolar affinity. In vitro, NOX-D20 inhibited C5a-induced chemotaxis of a CD88-expressing cell line and efficiently antagonized the activation of primary human polymorphonuclear leukocytes (PMN) by C5a. Binding of NOX-D20 to the C5a moiety of human C5 did not interfere with the formation of the terminal membrane attack complex (MAC). In sepsis, for which a specific interventional therapy is currently lacking, complement activation and elevated levels of C5a are suggested to contribute to multiorgan failure and mortality. In the model of polymicrobial sepsis induced by cecal ligation and puncture (CLP), NOX-D20 attenuated inflammation and organ damage, prevented the breakdown of the vascular endothelial barrier, and improved survival. Our study suggests NOX-D20 as a new therapeutic candidate for the treatment of sepsis. PMID:23887360

  7. C5a Receptor Signaling Prevents Folate Deficiency-Induced Neural Tube Defects in Mice

    PubMed Central

    Denny, Kerina J; Coulthard, Liam G; Jeanes, Angela; Lisgo, Steven; Simmons, David G; Callaway, Leonie K; Wlodarczyk, Bogdan; Finnell, Richard H; Woodruff, Trent M; Taylor, Stephen M

    2013-01-01

    The complement system is involved in a range of diverse developmental processes including cell survival, growth, differentiation, and regeneration. However, little is known about the role of complement in embryogenesis. Herein we demonstrate a novel role for the canonical complement 5a receptor (C5aR) in the development of the mammalian neural tube under conditions of maternal dietary folic acid deficiency. Specifically, we found C5aR and C5 to be expressed throughout the period of neurulation in wildtype mice and localized the expression to the cephalic regions of the developing neural tube. C5aR was also found to be expressed in the neuroepithelium of early human embryos. Ablation of the C5ar1 gene or the administration of a specific C5aR peptide antagonist to folic acid-deficient pregnant mice resulted in a high prevalence of severe anterior neural tube defect-associated congenital malformations. These findings provide a new and compelling insight into the role of the complement system during mammalian embryonic development. PMID:23420882

  8. C5a alters blood–brain barrier integrity in a human in vitro model of systemic lupus erythematosus

    PubMed Central

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-01-01

    The blood–brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5–50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases. PMID:26059553

  9. Deletion of the complement C5a receptor alleviates the severity of acute pneumococcal otitis media following influenza A virus infection in mice.

    PubMed

    Tong, Hua Hua; Lambert, Garrett; Li, Yong Xing; Thurman, Joshua M; Stahl, Gregory L; Douthitt, Kelsey; Clancy, Caitlin; He, Yujuan; Bowman, Andrew S

    2014-01-01

    There is considerable evidence that influenza A virus (IAV) promotes adherence, colonization, and superinfection by S. pneumoniae (Spn) and contributes to the pathogenesis of otitis media (OM). The complement system is a critical innate immune defense against both pathogens. To assess the role of the complement system in the host defense and the pathogenesis of acute pneumococcal OM following IAV infection, we employed a well-established transtympanically-induced mouse model of acute pneumococcal OM. We found that antecedent IAV infection enhanced the severity of acute pneumococcal OM. Mice deficient in complement C1qa (C1qa-/-) or factor B (Bf -/-) exhibited delayed viral and bacterial clearance from the middle ear and developed significant mucosal damage in the eustachian tube and middle ear. This indicates that both the classical and alternative complement pathways are critical for the oto-immune defense against acute pneumococcal OM following influenza infection. We also found that Spn increased complement activation following IAV infection. This was characterized by sustained increased levels of anaphylatoxins C3a and C5a in serum and middle ear lavage samples. In contrast, mice deficient in the complement C5a receptor (C5aR) demonstrated enhanced bacterial clearance and reduced severity of OM. Our data support the concept that C5a-C5aR interactions play a significant role in the pathogenesis of acute pneumococcal OM following IAV infection. It is possible that targeting the C5a-C5aR axis might prove useful in attenuating acute pneumococcal OM in patients with influenza infection.

  10. Complement component C5a Promotes Expression of IL-22 and IL-17 from Human T cells and its Implication in Age-related Macular Degeneration

    PubMed Central

    2011-01-01

    Background Age related macular degeneration (AMD) is the leading cause of irreversible blindness in elderly populations worldwide. Inflammation, among many factors, has been suggested to play an important role in AMD pathogenesis. Recent studies have demonstrated a strong genetic association between AMD and complement factor H (CFH), the down-regulatory factor of complement activation. Elevated levels of complement activating molecules including complement component 5a (C5a) have been found in the serum of AMD patients. Our aim is to study whether C5a can impact human T cells and its implication in AMD. Methods Human peripheral blood mononuclear cells (PBMCs) were isolated from the blood of exudative form of AMD patients using a Ficoll gradient centrifugation protocol. Intracellular staining and enzyme-linked immunosorbent assays were used to measure protein expression. Apoptotic cells were detected by staining of cells with the annexin-V and TUNEL technology and analyzed by a FACS Caliber flow cytometer. SNP genotyping was analyzed by TaqMan genotyping assay using the Real-time PCR system 7500. Results We show that C5a promotes interleukin (IL)-22 and IL-17 expression by human CD4+ T cells. This effect is dependent on B7, IL-1β and IL-6 expression from monocytes. We have also found that C5a could protect human CD4+ cells from undergoing apoptosis. Importantly, consistent with a role of C5a in promoting IL-22 and IL-17 expression, significant elevation in IL-22 and IL-17 levels was found in AMD patients as compared to non-AMD controls. Conclusions Our results support the notion that C5a may be one of the factors contributing to the elevated serum IL-22 and IL-17 levels in AMD patients. The possible involvement of IL-22 and IL-17 in the inflammation that contributes to AMD may herald a new approach to treat AMD. PMID:21762495

  11. Expression of the anaphylatoxin C5a receptor in gastric cancer: implications for vascular invasion and patient outcomes.

    PubMed

    Nitta, Hidetoshi; Shimose, Takayuki; Emi, Yasunori; Imamura, Takahisa; Ohnishi, Koji; Kusumoto, Tetsuya; Yamamoto, Manabu; Fukuzawa, Kengo; Takahashi, Ikuo; Higashi, Hidefumi; Tsuji, Akihito; Akagi, Yoshito; Oki, Eiji; Maehara, Yoshihiko; Baba, Hideo

    2016-11-01

    The C5a receptor (C5aR) expressed in various types of cancers is involved in C5a-induced cancer cell invasion. However, its role in gastric cancer has not yet been fully elucidated. Therefore, we studied the clinical significance of C5aR expression in gastric cancer. The association of C5aR expression in gastric cancer, determined by immunostaining using the anti-C5aR antibody, with clinicopathological parameters and outcomes was evaluated in 148 patients. Further, the association of C5aR expression in liver metastatic sites with clinicopathological parameters was investigated in a separate cohort of 58 patients who underwent hepatectomy. High tumoral C5aR expression (n = 45, 30.4 %) was significantly related to tumor location, cancer invasion depth, vascular and lymphatic invasion, and tumor stage. The 5-year recurrence-free and overall survival rates of patients with high tumoral C5aR expression were significantly lower than those of patients with low tumoral C5aR expression (50.9 vs. 84.2 %, P = 0.002 and 58.8 vs. 86.1 %, P = 0.007, respectively). The incidence of liver metastasis was significantly higher in patients with high tumoral C5aR expression (13.3 %) than in those with low tumoral C5aR expression (3.9 %; P = 0.04). C5aR expression at liver metastatic sites was associated with the C5aR expression status at the primary site (P = 0.0004), vascular invasion at the primary site (P = 0.04), and tumor size at the metastatic site (P = 0.01). C5aR expression in gastric cancer was associated with cancer progression, liver metastasis, and poor prognosis. Therefore, C5aR may represent a prognostic factor and therapeutic target in gastric cancer. PMID:27688239

  12. Commercial Product Activation Using RFID

    NASA Technical Reports Server (NTRS)

    Jedrey, Thomas

    2008-01-01

    Radio-frequency identification (RFID) would be used for commercial product activation, according to a proposal. What is new here is the concept of combining RFID with activation - more specifically, using RFID for activating commercial products (principally, electronic ones) and for performing such ancillary functions as tracking individual product units on production lines, tracking shipments, and updating inventories. According to the proposal, an RFID chip would be embedded in each product. The information encoded in the chip would include a unique number for identifying the product. An RFID reader at the point of sale would record the number of the product and would write digital information to the RFID chip for either immediate activation of the product or for later interrogation and processing. To be practical, an RFID product-activation system should satisfy a number of key requirements: the system should be designed to be integrable into the inventory-tracking and the data-processing and -communication infrastructures of businesses along the entire supply chain from manufacture to retail; the system should be resistant to sophisticated hacking; activation codes should be made sufficiently complexity to minimize the probability of activating stolen products; RFID activation equipment at points of sale must be capable to two-way RF communication for the purposes of reading information from, and writing information to, embedded RFID chips; the equipment at points of sale should be easily operable by sales clerks with little or no training; the point-of-sale equipment should verify activation and provide visible and/or audible signals indicating verification or lack thereof; and, the system should be able to handle millions of products per year with minimal human intervention, among other requirements.

  13. Validation of a flow cytometry-based assay to assess C5aR receptor occupancy on neutrophils and monocytes for use in drug development.

    PubMed

    Quadrini, Karen J; Hegelund, Anne Charlotte; Cortes, Kasia E; Xue, Chengsen; Kennelly, Susan M; Ji, Hong; Högerkorp, Carl-Magnus; Mc Closkey, Thomas W

    2016-03-01

    The C5a/C5a receptor (C5aR) pathway, a key component in the proinflammatory immune response, is an attractive therapeutic target since its dysregulation is implicated in a variety of autoimmune and inflammatory disorders. The objective of the present study was to validate a receptor occupancy (RO) assay for a human anti-C5aR monoclonal antibody drug candidate, NNC0215-0384 (NN0384). This flow cytometry-based assay measures the percentage (%), median fluorescence intensity (MFI), and molecules of equivalent soluble fluorochrome (MESF) of NN0384 binding to its target cells, neutrophils and monocytes, in whole blood from normal healthy donors and rheumatoid arthritis (RA) patients with clinically active disease. The validation parameters assessed included postcollection and postprocessing sample stability, intra- and interassay precision, an analyst-to-analyst comparison, a comparison of normal healthy donor and RA patient sample postcollection stability, and a laboratory-to-laboratory comparison and assay transfer. The cumulative results indicate that the assay was reproducible, met the clearly defined acceptance criteria for the validation parameters tested, and was transferable to another laboratory. In conclusion, this RO assay is suitable for use to accrue pharmacodynamic biomarker data in a multicenter, global clinical trial. PMID:26084468

  14. Efficacy of polymeric encapsulated C5a peptidase–based group B streptococcus vaccines in a murine model

    PubMed Central

    SANTILLAN, Donna A.; RAI, Karishma K.; SANTILLAN, Mark K.; KRISHNAMACHARI, Yogita; SALEM, Aliasger K.; HUNTER, Stephen K.

    2011-01-01

    Objectives The purpose was to examine in mice the efficacy of various polymeric encapsulated C5a peptidase vaccine formulations in eliciting a long-term immune response and preventing Group B Streptococci infection. Study Design C5a peptidase was encapsulated in semi-permeable microspheres of poly(lactide-co-glycolide) (PLGA). Female ICR mice were immunized with 0, 10, or 30ug of encapsulated C5a peptidase within 2 different formulations of PLGA polymers. Booster doses were given at weeks 4 and 8. Antibody responses were measured by ELISA at weeks 4, 8, 11, and 40. Vaginal challenge with GBS types 1a, III, and V were performed at week 12. Results 30ug doses of the 75:25 and 50:50 PLGA formulations generate the highest and most sustained C5a peptidase specific immune responses. Mice that received encapsulated C5a peptidase were significantly protected from vaginal colonization compared to mice that receive empty microspheres. Conclusion Encapsulated C5a peptidase elicited significant immune responses and protection against GBS challenge. C5a peptidase microsphere encapsulation has potential as a GBS vaccine. PMID:21802065

  15. Inhibition of complement C5a prevents breakdown of the blood-brain barrier and pituitary dysfunction in experimental sepsis

    PubMed Central

    Flierl, Michael A; Stahel, Philip F; Rittirsch, Daniel; Huber-Lang, Markus; Niederbichler, Andreas D; Hoesel, L Marco; Touban, Basel M; Morgan, Steven J; Smith, Wade R; Ward, Peter A; Ipaktchi, Kyros

    2009-01-01

    Introduction Septic encephalopathy secondary to a breakdown of the blood-brain barrier (BBB) is a known complication of sepsis. However, its pathophysiology remains unclear. The present study investigated the effect of complement C5a blockade in preventing BBB damage and pituitary dysfunction during experimental sepsis. Methods Using the standardised caecal ligation and puncture (CLP) model, Sprague-Dawley rats were treated with either neutralising anti-C5a antibody or pre-immune immunoglobulin (Ig) G as a placebo. Sham-operated animals served as internal controls. Results Placebo-treated septic rats showed severe BBB dysfunction within 24 hours, accompanied by a significant upregulation of pituitary C5a receptor and pro-inflammatory cytokine expression, although gene levels of growth hormone were significantly attenuated. The pathophysiological changes in placebo-treated septic rats were restored by administration of neutralising anti-C5a antibody to the normal levels of BBB and pituitary function seen in the sham-operated group. Conclusions Collectively, the neutralisation of C5a greatly ameliorated pathophysiological changes associated with septic encephalopathy, implying a further rationale for the concept of pharmacological C5a inhibition in sepsis. PMID:19196477

  16. C5a/CD88 signaling alters blood-brain barrier integrity in lupus through nuclear factor-κB.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chen, Peili; Quigg, Richard J; Alexander, Jessy J

    2011-12-01

    Inflammation is a key factor in a number of neurodegenerative diseases including systemic lupus erythematosus. The complement system is an important mechanism in initiating and amplifying inflammation. Our recent studies demonstrate that C5a, a protein fragment generated during complement activation could alter the blood-brain barrier integrity, and thereby disturb the brain microenvironment. To understand the mechanism by which this occurs, we examined the effects of C5a on apoptosis, translocation of nuclear factor-κB (NF-κb) and the expression of Iκbα, MAPK, CREB and TJ protein, zona occludens (ZO-1) in mouse brain endothelial cells. Apoptosis was examined by DNA laddering and caspase 3 activity and the distribution of the ZO-1 and the p65 subunit of NF-κB were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NF-κb into the nucleus, altered ZO-1 at the interfaces of neighboring cells, decreased caspase 3 activity and prevented apoptosis in these cells. Our results indicate that signaling through CD88 regulates the blood-brain barrier in a NF-κb-dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NF-κb-signaling cascades in inflammatory settings.

  17. Selective steroid oxyfunctionalisation by CYP154C5, a bacterial cytochrome P450

    PubMed Central

    2013-01-01

    Background Cytochrome P450 monooxygenases – able to regio- and stereoselectively hydroxylate non-activated carbon atoms – are important enzymes for the synthesis of valuable intermediates in the production of steroid hormones in the pharmaceutical industry. However, up to now only a few bacterial enzymes able to hydroxylate steroids have been reported. CYP154C5 from Nocardia farcinica IFM 10152, a bacterial P450 monooxygenase, was previously shown to convert testosterone to 16α-hydroxytestosterone. Since the hydroxylation at 16α-position is of special interest for the pharmaceutical industry, we have studied this enzyme in more detail to investigate its activity and selectivity in bioconversions of further steroids. Results CYP154C5 was coexpressed in Escherichia coli together with putidaredoxin and putidaredoxin reductase from Pseudomonas putida as redox partners for electron transfer and applied in bioconversions of various pregnanes and androstanes [pregnenolone (1), dehydroepiandrosterone (2), progesterone (3), androstenedione (4), testosterone (5) and nandrolone (6)]. Structure elucidation of the formed products revealed an exclusive regio- and stereoselectivity of CYP154C5, always yielding the corresponding 16α-hydroxylated steroids. Application of whole cells expressing the three components, P450, Pdx and PdR, in steroid biotransformations resulted in significantly higher conversions and total turnover numbers (TTN) compared to reactions using cell-free extracts. Additionally, considerably higher substrate loads (up to 15 mM) were tolerated by the whole-cell system. Furthermore, turnover numbers (TON) were determined for the six different steroids using whole cells. Thus, testosterone was found to be the worst substrate with a TON of only 0.8 μmol substrate consumed min-1 μmol-1 CYP154C5, while progesterone and pregnenolone were converted the fastest resulting in TON of 3.3 μmol substrate consumed min-1 μmol-1 CYP154C5. Conclusion CYP154C5

  18. Characterization of Cracking and Crack Growth Properties of the C5A Aircraft Tie-Box Forging

    NASA Technical Reports Server (NTRS)

    Piascik, Robert S.; Smith, Stephen W.; Newman, John A.; Willard, Scott A.

    2003-01-01

    Detailed destructive examinations were conducted to characterize the integrity and material properties of two aluminum alloy (7075-T6) horizontal stabilizer tie box forgings removed.from US. Air Force C5A and C5B transport aircraft. The C5B tie box forging was,found to contain no evidence of cracking. Thirteen cracks were found in the CSA,forging. All but one of the cracks observed in the C5A component were located along the top cap region (one crack was located in the bottom cap region). The cracks in the C5A component initiated at fastener holes and propagated along a highly tunneled intergranular crack path. The tunneled crack growth configuration is a likelv result of surface compressive stress produced during peening of the .forging suijace. The tie box forging ,fatigue crack growth, fracture and stress corrosion cracking (SCC) properties were characterized. Reported herein are the results of laboratory air ,fatigue crack growth tests and 95% relative humidity SCC tests conducted using specimens machined from the C5A ,forging. SCC test results revealed that the C5A ,forging material was susceptible to intergranular environmental assisted cracking: the C5A forging material exhibited a SCC crack-tip stress-intensity factor threshold of less than 6 MPadn. Fracture toughness tests revealed that the C5A forging material exhibited a fracture toughness that was 25% less than the C5B forging. The C5A forging exhibited rapid laboratory air fatigue crack growth rates having a threshold crack-tip stress-intensity factor range of less than 0.8 MPa sup m. Detailed fractographic examinations revealed that the ,fatigue crack intergranular growth crack path was similar to the cracking observed in the C5A tie box forging. Because both fatigue crack propagation and SCC exhibit similar intergranular crack path behavior, the damage mechanism resulting in multi-site cracking of tie box forgings cannot be determined unless local cyclic stresses can be quantified.

  19. Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells

    PubMed Central

    Coughlin, Beth; Schnabolk, Gloriane; Joseph, Kusumam; Raikwar, Himanshu; Kunchithapautham, Kannan; Johnson, Krista; Moore, Kristi; Wang, Yi; Rohrer, Bärbel

    2016-01-01

    Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment. PMID:27029558

  20. CME Productivity of Active Regions.

    NASA Astrophysics Data System (ADS)

    Liu, L.; Wang, Y.; Wang, J.; Shen, C.; Ye, P.; Zhang, Q.; Liu, R.; Wang, S.

    2015-12-01

    Solar active regions (ARs) are the major sources of two kinds of the most violent solar eruptions, namely flares and coronal mass ejections (CMEs). Although they are believed to be two phenomena in the same eruptive process, the productivity of them could be quiet different for various ARs. Why is an AR productive? And why is a flare-rich AR CME-poor? To answer these questions, we compared the recent super flare-rich but CME-poor AR 12192, with other four ARs; two were productive in both flares and CMEs and the other two were inert to produce any M-class or intenser flares or CMEs. By investigating the photospheric parameters based on the SDO/HMI vector magnetogram, we find the three productive ARs have larger magnetic flux, current and free magnetic energy than the inert ARs. Furthermore, the two ARs productive in both flares and CMEs contain higher current helicity, concentrating along both sides of the flaring neutral lines, indicating the presence of a seed magnetic structure( that is highly sheared or twisted) of a CME; they also have higher decay index in the low corona, showing weak constraint. The results suggest that productive ARs are always large and have strong current system and sufficient free energy to power flares, and more importantly whether or not a flare is accompanied by a CME is seemingly related to (1) if there is significant sheared or twisted core field serving as the seed of the CME and (2) if the constraint of the overlying arcades is weak enough. Moreover, some productive ARs may frequently produce more than one CME. How does this happen? We do a statistical investigation of waiting times of quasi-homologous CMEs ( CME ssuccessive originating from the same ARs within short intervals) from super ARs in solar cycle 23 to answer this question. The waiting times of quasi-homologous CMEs have a two-component distribution with a separation at about 18 hours, the first component peaks at 7 hours. The correlation analysis among CME waiting times

  1. Neutrophil Recruitment to the Lung in both C5a and CXCL1-Induced Alveolitis is Impaired in Vitamin D Binding Protein Deficient Mice

    PubMed Central

    Trujillo, Glenda; Habiel, David M.; Ge, Lingyin; Ramadass, Mahalakshmi; Cooke, Nancy E.; Kew, Richard R.

    2013-01-01

    Knowledge of how neutrophils respond to chemotactic signals in a complex inflammatory environment is not completely understood. Moreover, even less is known about factors in physiological fluids that regulate the activity of chemoattractants. The vitamin D binding protein (DBP) has been shown to significantly enhance chemotaxis to complement activation peptide C5a using purified proteins in vitro, and by ex vivo depletion of DBP in physiological fluids, but this function has not been determined in vivo. DBP null (-/-) mice were used to investigate how a systemic absence of this plasma protein affects leukocyte recruitment in alveolitis models of lung inflammation. DBP-/- mice had significantly reduced (~50%) neutrophil recruitment to the lungs compared to their wild-type DBP+/+ counterparts in three different alveolitis models, two acute and one chronic. The histology of DBP-/- mouse lungs also showed significantly less injury than wild-type animals. The chemotactic cofactor function of DBP appears to be selective for neutrophil recruitment, but in contrast to previous in vitro results, in vivo DBP can enhance the activity of other chemoattractants including CXCL1. The reduced neutrophil response in DBP-/- mice could be rescued to wild-type levels by administering exogenous DBP. Finally, in inflammatory fluids DBP binds to G-actin released from damaged cells and this complex may be the active chemotactic cofactor. Results show for the first time that DBP is a significant chemotactic cofactor in vivo and not specific for C5a, suggesting that this ubiquitous plasma protein may have a more significant role in neutrophil recruitment than previously recognized. PMID:23752613

  2. Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model

    PubMed Central

    Andersson, C; Wenander, C S; Usher, P A; Hebsgaard, J B; Sondergaard, B-C; Rønø, B; Mackay, C; Friedrichsen, B; Chang, C; Tang, R; Hornum, L

    2014-01-01

    Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR. PMID:24665841

  3. Rapid-onset clinical and mechanistic effects of anti-C5aR treatment in the mouse collagen-induced arthritis model.

    PubMed

    Andersson, C; Wenander, C S; Usher, P A; Hebsgaard, J B; Sondergaard, B-C; Rønø, B; Mackay, C; Friedrichsen, B; Chang, C; Tang, R; Hornum, L

    2014-07-01

    Preclinical evidence supports targeting the C5a receptor (C5aR) in rheumatoid arthritis (RA). To support ongoing clinical development of an anti-C5aR monoclonal antibody, we have investigated for the first time the mechanism of action and the pharmacodynamics of a blocking anti-murine C5aR (anti-mC5aR) surrogate antibody in mouse collagen-induced arthritis (CIA). First, efficacy was demonstrated in a multiple-dose treatment study. Almost complete inhibition of clinical disease progression was obtained, including reduced bone and cartilage destruction in anti-mC5aR-treated mice. Then, the mechanism of action was examined by looking for early effects of anti-mC5aR treatment in single-dose treatment studies. We found that 48 h after single-dose treatment with anti-mC5aR, the neutrophil and macrophage infiltration into the paws was already reduced. In addition, several inflammatory markers, including tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-17A were reduced locally in the paws, indicating reduction of local inflammation. Furthermore, dose-setting experiments supported a beneficial clinical effect of dosing above the C5aR saturation level. In conclusion, these preclinical data demonstrated rapid onset effects of antibody blockade of C5aR. The data have translational value in supporting the Novo Nordisk clinical trials of an anti-C5aR antibody in rheumatoid arthritis patients, by identifying potential biomarkers of treatment effects as well as by providing information on pharmacodynamics and novel insights into the mechanism of action of monoclonal antibody blockade of C5aR.

  4. Glycosylation and Activities of Natural Products.

    PubMed

    Huang, Gangliang; Lv, Meijiao; Hu, Jinchuan; Huang, Kunlin; Xu, Hong

    2016-01-01

    Natural products are widely found in nature, their number and variety are numerous, the structures are complex and diverse. These natural products have many physiological and pharmacological activities. Glycosylation can increase the diversity of structure and function of natural product, it has become the focus of drug research and development. The impacts of glycosylation of natural products to water solubility, pharmacological activities, bioavailability, or others were described in this review, which provides a reference for the development and application of glycosylated natural products. PMID:27499190

  5. Targeting the minor pocket of C5aR for the rational design of an oral allosteric inhibitor for inflammatory and neuropathic pain relief

    PubMed Central

    Moriconi, Alessio; Cunha, Thiago M.; Souza, Guilherme R.; Lopes, Alexandre H.; Cunha, Fernando Q.; Carneiro, Victor L.; Pinto, Larissa G.; Brandolini, Laura; Aramini, Andrea; Bizzarri, Cinzia; Bianchini, Gianluca; Beccari, Andrea R.; Fanton, Marco; Bruno, Agostino; Costantino, Gabriele; Bertini, Riccardo; Galliera, Emanuela; Locati, Massimo; Ferreira, Sérgio H.; Teixeira, Mauro M.; Allegretti, Marcello

    2014-01-01

    Chronic pain resulting from inflammatory and neuropathic disorders causes considerable economic and social burden. Pharmacological therapies currently available for certain types of pain are only partially effective and may cause severe adverse side effects. The C5a anaphylatoxin acting on its cognate G protein-coupled receptor (GPCR), C5aR, is a potent pronociceptive mediator in several models of inflammatory and neuropathic pain. Although there has long been interest in the identification of C5aR inhibitors, their development has been complicated, as for many peptidomimetic drugs, mostly by poor drug-like properties. Herein, we report the de novo design of a potent and selective C5aR noncompetitive allosteric inhibitor, DF2593A, guided by the hypothesis that an allosteric site, the “minor pocket,” previously characterized in CXC chemokine receptors-1 and -2, is functionally conserved in the GPCR class. In vitro, DF2593A potently inhibited C5a-induced migration of human and rodent neutrophils. In vivo, oral administration of DF2593A effectively reduced mechanical hyperalgesia in several models of acute and chronic inflammatory and neuropathic pain, without any apparent side effects. Mechanical hyperalgesia after spared nerve injury was also reduced in C5aR−/− mice compared with WT mice. Furthermore, treatment of C5aR−/− mice with DF2593A did not produce any further antinociceptive effect compared with C5aR−/− mice treated with vehicle. The successful medicinal chemistry strategy confirms that a conserved minor pocket is amenable for the rational design of selective inhibitors and the pharmacological results support that the allosteric blockade of the C5aR represents a highly promising therapeutic approach to control chronic inflammatory and neuropathic pain. PMID:25385614

  6. Enhancement of human polymorphonuclear leukocyte adherence to plastic and endothelium by phorbol myristate acetate. Comparison with human C5a.

    PubMed Central

    Webster, R. O.; Wysolmerski, R. B.; Lagunoff, D.

    1986-01-01

    The adherence of circulating neutrophils to vascular endothelium represents a necessary step in the chemotactic emigration of neutrophils to extravascular inflammatory sites. Studies of neutrophil adherence induced by phorbol myristate acetate (PMA) were undertaken to determine the ability of a nonchemotactic neutrophil stimulus to provoke increased adherence. The authors found that the adherence of human neutrophils to plastic surfaces or confluent monolayers of endothelial cells is enhanced in a concentration-dependent fashion by exposure of neutrophils to PMA. The effect of PMA concentration (0.1-5.0 ng/ml) on increased neutrophil adherence parallels that observed for superoxide anion generation and release of lysosomal enzymes from specific granules. Whereas complement C5a-treated neutrophils exhibited a fourfold to fivefold increase in adherence to endothelial cells, PMA-treated neutrophils showed a 10-fold to 20-fold increase. The ability of PMA to cause increased neutrophil adherence to endothelium appeared to be directed primarily at the neutrophil. Pretreatment of neutrophils with PMA was as effective as coincubation in causing increased adherence to plastic surfaces or confluent cultured endothelial cells, but pretreatment of endothelial cells with PMA failed to promote neutrophil adherence. Alteration of neutrophil cytoskeletal structures by cytochalasin B treatment did not prevent subsequent PMA-stimulated neutrophil adherence. These results demonstrate that increased neutrophil adherence to surfaces can be induced by a nonchemotactic stimulus and that neutrophil adherence is independent of organized microfilaments. Images Figure 4 Figure 6 PMID:3789092

  7. Complement Activation in Arterial and Venous Thrombosis is Mediated by Plasmin

    PubMed Central

    Foley, Jonathan H.; Walton, Bethany L.; Aleman, Maria M.; O'Byrne, Alice M.; Lei, Victor; Harrasser, Micaela; Foley, Kimberley A.; Wolberg, Alisa S.; Conway, Edward M.

    2016-01-01

    Thrombus formation leading to vaso-occlusive events is a major cause of death, and involves complex interactions between coagulation, fibrinolytic and innate immune systems. Leukocyte recruitment is a key step, mediated partly by chemotactic complement activation factors C3a and C5a. However, mechanisms mediating C3a/C5a generation during thrombosis have not been studied. In a murine venous thrombosis model, levels of thrombin–antithrombin complexes poorly correlated with C3a and C5a, excluding a central role for thrombin in C3a/C5a production. However, clot weight strongly correlated with C5a, suggesting processes triggered during thrombosis promote C5a generation. Since thrombosis elicits fibrinolysis, we hypothesized that plasmin activates C5 during thrombosis. In vitro, the catalytic efficiency of plasmin-mediated C5a generation greatly exceeded that of thrombin or factor Xa, but was similar to the recognized complement C5 convertases. Plasmin-activated C5 yielded a functional membrane attack complex (MAC). In an arterial thrombosis model, plasminogen activator administration increased C5a levels. Overall, these findings suggest plasmin bridges thrombosis and the immune response by liberating C5a and inducing MAC assembly. These new insights may lead to the development of strategies to limit thrombus formation and/or enhance resolution. PMID:27077125

  8. Suomi NPP VIIRS active fire product status

    NASA Astrophysics Data System (ADS)

    Ellicott, E. A.; Csiszar, I. A.; Schroeder, W.; Giglio, L.; Wind, B.; Justice, C. O.

    2012-12-01

    We provide an overview of the evaluation and development of the Active Fires product derived from the Visible Infrared Imager Radiometer Suite (VIIRS) sensor on the Suomi National Polar-orbiting Partnership (SNPP) satellite during the first year of on-orbit data. Results from the initial evaluation of the standard SNPP Active Fires product, generated by the SNPP Interface Data Processing System (IDPS), supported the stabilization of the VIIRS Sensor Data Record (SDR) product. This activity focused in particular on the processing of the dual-gain 4 micron VIIRS M13 radiometric measurements into 750m aggregated data, which are fundamental for active fire detection. Following the VIIRS SDR product's Beta maturity status in April 2012, correlative analysis between VIIRS and near-simultaneous fire detections from the Moderate Resolution Imaging Spectroradiometer (MODIS) on the NASA Earth Observing System Aqua satellite confirmed the expected relative detection rates driven primarily by sensor differences. The VIIRS Active Fires Product Development and Validation Team also developed a science code that is based on the latest MODIS Collection 6 algorithm and provides a full spatially explicit fire mask to replace the sparse array output of fire locations from a MODIS Collection 4 equivalent algorithm in the current IDPS product. The Algorithm Development Library (ADL) was used to support the planning for the transition of the science code into IDPS operations in the future. Product evaluation and user outreach was facilitated by a product website that provided end user access to fire data in user-friendly format over North America as well as examples of VIIRS-MODIS comparisons. The VIIRS fire team also developed an experimental product based on 375m VIIRS Imagery band measurements and provided high quality imagery of major fire events in US. By August 2012 the IDPS product achieved Beta maturity, with some known and documented shortfalls related to the processing of

  9. Improvements in neuroelectrophysiological and rear limb functions in rats with spinal cord injury after Schwann cell transplantation in combination with a C5a receptor antagonist.

    PubMed

    Zhang, S-Q; Wu, M-F; Peng, C-G; Lv, Y; Wu, D-K; Liu, J; Yang, Q

    2015-01-01

    We measured the effect of Schwann cell transplantation and complement factor 5a (C5a) receptor antagonist on nerve function recovery in rats with spinal cord injury. Experimental spinal cord injury was induced in eighty Wistar rats and these were randomly divided into four treatment groups: culture medium and saline injection (control group), Schwann cell injection (cell transplantation group), C5a receptor antagonist injection (C5a receptor antagonist group), and both Schwann cell and C5a receptor antagonist injections (combination group). Rear limb functional recovery was assessed 1, 2, 4, 6, and 8 weeks after the spinal cord injury with the tilt table test and the Basso, Beattie, Bresnahan scale. Sex-determining region Y (SRY) gene expression was measured at week 4 and horseradish peroxidase (HRP) labeling was used at week 8 to further assess the recovery of neuroelectrophysiological functions. The rear limb functional assessment showed that the combination group had better outcomes than the cell transplantation and C5a receptor antagonist groups. All treatment groups had better outcomes than control. Only the cell transplantation and combination groups showed SRY expression. The number of HRP-positive nerve fibers in the different groups ranked as follows: combination group > cell transplantation and C5a receptor antagonist > control. The refractory period and amplitude of the induced potential in the combination group were significantly greater than in the other three groups. These results suggest that the combination of Schwann cell transplantation and the C5a receptor antagonist enhances the regeneration of injured synapses and improves limb function and electrophysiology. PMID:26634479

  10. Sum Product Networks for Activity Recognition.

    PubMed

    Amer, Mohamed R; Todorovic, Sinisa

    2016-04-01

    This paper addresses detection and localization of human activities in videos. We focus on activities that may have variable spatiotemporal arrangements of parts, and numbers of actors. Such activities are represented by a sum-product network (SPN). A product node in SPN represents a particular arrangement of parts, and a sum node represents alternative arrangements. The sums and products are hierarchically organized, and grounded onto space-time windows covering the video. The windows provide evidence about the activity classes based on the Counting Grid (CG) model of visual words. This evidence is propagated bottom-up and top-down to parse the SPN graph for the explanation of the video. The node connectivity and model parameters of SPN and CG are jointly learned under two settings, weakly supervised, and supervised. For evaluation, we use our new Volleyball dataset, along with the benchmark datasets VIRAT, UT-Interactions, KTH, and TRECVID MED 2011. Our video classification and activity localization are superior to those of the state of the art on these datasets.

  11. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2003-10-28

    A process for the selective production and isolation of high specific activity Cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  12. Production Of High Specific Activity Copper-67

    DOEpatents

    Jamriska, Sr., David J.; Taylor, Wayne A.; Ott, Martin A.; Fowler, Malcolm; Heaton, Richard C.

    2002-12-03

    A process for the selective production and isolation of high specific activity cu.sup.67 from proton-irradiated enriched Zn.sup.70 target comprises target fabrication, target irradiation with low energy (<25 MeV) protons, chemical separation of the Cu.sup.67 product from the target material and radioactive impurities of gallium, cobalt, iron, and stable aluminum via electrochemical methods or ion exchange using both anion and cation organic ion exchangers, chemical recovery of the enriched Zn.sup.70 target material, and fabrication of new targets for re-irradiation is disclosed.

  13. Production of high specific activity silicon-32

    SciTech Connect

    Phillips, D.R.; Brzezinski, M.A.

    1998-12-31

    This is the final report of a three-year, Laboratory Directed Research and Development Project (LDRD) at Los Alamos National Laboratory (LANL). There were two primary objectives for the work performed under this project. The first was to take advantage of capabilities and facilities at Los Alamos to produce the radionuclide {sup 32}Si in unusually high specific activity. The second was to combine the radioanalytical expertise at Los Alamos with the expertise at the University of California to develop methods for the application of {sup 32}Si in biological oceanographic research related to global climate modeling. The first objective was met by developing targetry for proton spallation production of {sup 32}Si in KCl targets and chemistry for its recovery in very high specific activity. The second objective was met by developing a validated field-useable, radioanalytical technique, based upon gas-flow proportional counting, to measure the dynamics of silicon uptake by naturally occurring diatoms.

  14. Production of high specific activity silicon-32

    DOEpatents

    Phillips, Dennis R.; Brzezinski, Mark A.

    1994-01-01

    A process for preparation of silicon-32 is provide and includes contacting an irradiated potassium chloride target, including spallation products from a prior irradiation, with sufficient water, hydrochloric acid or potassium hydroxide to form a solution, filtering the solution, adjusting pH of the solution to from about 5.5 to about 7.5, admixing sufficient molybdate-reagent to the solution to adjust the pH of the solution to about 1.5 and to form a silicon-molybdate complex, contacting the solution including the silicon-molybdate complex with a dextran-based material, washing the dextran-based material to remove residual contaminants such as sodium-22, separating the silicon-molybdate complex from the dextran-based material as another solution, adding sufficient hydrochloric acid and hydrogen peroxide to the solution to prevent reformation of the silicon-molybdate complex and to yield an oxidization state of the molybdate adapted for subsequent separation by an anion exchange material, contacting the solution with an anion exchange material whereby the molybdate is retained by the anion exchange material and the silicon remains in solution, and optionally adding sufficient alkali metal hydroxide to adjust the pH of the solution to about 12 to 13. Additionally, a high specific activity silicon-32 product having a high purity is provided.

  15. Monascus secondary metabolites: production and biological activity.

    PubMed

    Patakova, Petra

    2013-02-01

    The genus Monascus, comprising nine species, can reproduce either vegetatively with filaments and conidia or sexually by the formation of ascospores. The most well-known species of genus Monascus, namely, M. purpureus, M. ruber and M. pilosus, are often used for rice fermentation to produce red yeast rice, a special product used either for food coloring or as a food supplement with positive effects on human health. The colored appearance (red, orange or yellow) of Monascus-fermented substrates is produced by a mixture of oligoketide pigments that are synthesized by a combination of polyketide and fatty acid synthases. The major pigments consist of pairs of yellow (ankaflavin and monascin), orange (rubropunctatin and monascorubrin) and red (rubropunctamine and monascorubramine) compounds; however, more than 20 other colored products have recently been isolated from fermented rice or culture media. In addition to pigments, a group of monacolin substances and the mycotoxin citrinin can be produced by Monascus. Various non-specific biological activities (antimicrobial, antitumor, immunomodulative and others) of these pigmented compounds are, at least partly, ascribed to their reaction with amino group-containing compounds, i.e. amino acids, proteins or nucleic acids. Monacolins, in the form of β-hydroxy acids, inhibit hydroxymethylglutaryl-coenzyme A reductase, a key enzyme in cholesterol biosynthesis in animals and humans.

  16. Selected demonstration and educational products/activities

    SciTech Connect

    Williams, R.J.; Mann, H.C.

    1992-07-01

    The information in this paper was assembled for several informal presentations to a variety of visitor groups during the summer of 1992. A number of staff members at TVA`s National Fertilizer and Environmental Research Center (NFERC) found it useful as a quick overview for their use and for their sharing with external colleagues and customers. The paper is not meant to be an exhaustive list or explanation of all products and services available from NFERC. However, the authors believe it will give a flavor and tenor of some of the ongoing activities of the Center, especially those activities relating to the retail fertilizer dealer. Programs over the years have focused on key aspects of nutrient efficiency and management. TVA is uniquely positioned to assist the fertilizer industry and US agriculture in protecting the environment from potential adverse environmental impacts of agriculture, especially for fertilizer and the attendant agrichemicals. TVA has the technical base and an ongoing working relationship with the fertilizer industry in technology development and introduction. Dealer education is very important in TVA programs in two aspects: (1) education for the dealer in meeting new environmental stewardship challenges from an operational perspective; and (2) education for the dealer in meeting the site-specific information needs of the farmer.

  17. Production of activated carbon from TCR char

    NASA Astrophysics Data System (ADS)

    Stenzel, Fabian; Heberlein, Markus; Klinner, Tobias; Hornung, Andreas

    2016-04-01

    The utilization of char for adsorptive purposes is known since the 18th century. At that time the char was made of wood or bones and used for decoloration of fluids. In the 20th century the production of activated carbon in an industrial scale was started. The today's raw materials for activated carbon production are hard coal, peat, wood or coconut shells. All these materials entail costs especially the latter. Thus, the utilization of carbon rich residues (biomass) is an interesting economic opportunity because it is available for no costs or even can create income. The char is produced by thermo-catalytic reforming (TCR®). This process is a combination of an intermediate pyrolysis and subsequently a reforming step. During the pyrolysis step the material is decomposed in a vapor and a solid carbon enriched phase. In the second step the vapor and the solid phase get in an intensive contact and the quality of both materials is improved via the reforming process. Subsequently, the condensables are precipitated from the vapor phase and a permanent gas as well as oil is obtained. Both are suitable for heat and power production which is a clear advantage of the TCR® process. The obtained biochar from the TCR® process has special properties. This material has a very low hydrogen and oxygen content. Its stability is comparable to hard coal or anthracite. Therefore it consists almost only of carbon and ash. The latter depends from input material. Furthermore the surface structure and area can be influenced during the reforming step. Depending from temperature and residence time the number of micro pores and the surface area can be increased. Preliminary investigations with methylene blue solution have shown that a TCR® char made of digestate from anaerobic digestion has adsorptive properties. The decoloration of the solution was achieved. A further influencing factor of the adsorption performance is the particle size. Based on the results of the preliminary tests a

  18. Pulp Fibroblasts Control Nerve Regeneration through Complement Activation.

    PubMed

    Chmilewsky, F; About, I; Chung, S-H

    2016-07-01

    Dentin-pulp regeneration is closely linked to the presence of nerve fibers in the pulp and to the healing mechanism by sprouting of the nerve fiber's terminal branches beneath the carious injury site. However, little is known about the initial mechanisms regulating this process in carious teeth. It has been recently demonstrated that the complement system activation, which is one of the first immune responses, contributes to tissue regeneration through the local production of anaphylatoxins such as C5a. While few pulp fibroblasts in intact teeth and in untreated fibroblast cultures express the C5a receptor (C5aR), here we show that all dental pulp fibroblasts, localized beneath the carious injury site, do express this receptor. This observation is consistent with our in vitro results, which showed expression of C5aR in lipoteichoic acid-stimulated pulp fibroblasts. The interaction of C5a, produced after complement synthesis and activation from pulp fibroblasts, with the C5aR of these cells mediated the local brain-derived neurotropic factor (BDNF) secretion. Overall, this activation guided the neuronal growth toward the lipoteichoic acid-stimulated fibroblasts. Thus, our findings highlight a new mechanism in one of the initial steps of the dentin-pulp regeneration process, linking pulp fibroblasts to the nerve sprouting through the complement system activation. This may provide a useful future therapeutic tool in targeting the fibroblasts in the dentin-pulp regeneration process. PMID:27053117

  19. Collagenase Production by Endotoxin-Activated Macrophages

    PubMed Central

    Wahl, Larry M.; Wahl, Sharon M.; Mergenhagen, Stephan E.; Martin, George R.

    1974-01-01

    Peritoneal exudate macrophages, when exposed to bacterial lipopolysaccharide in culture, were found to produce collagenase (EC 3.4.24.3). This enzyme was not detected in extracts of the macrophages or in media from nonstimulated macrophage cultures. Lipidcontaining fractions of the lipopolysaccharide, including a glycolipid from the rough mutant of Salmonella minnesota (R595) and lipid A, were potent stimulators of collagenase production. The lipid-free polysaccharide fraction had no effect. Cycloheximide prevented the production of collagenase by endotoxin-treated macrophages, suggesting that it was newly synthesized. Images PMID:4372628

  20. Microbial production of sensory-active miraculin.

    PubMed

    Ito, Keisuke; Asakura, Tomiko; Morita, Yuji; Nakajima, Ken-ichiro; Koizumi, Ayako; Shimizu-Ibuka, Akiko; Masuda, Katsuyoshi; Ishiguro, Masaji; Terada, Tohru; Maruyama, Jun-ichi; Kitamoto, Katsuhiko; Misaka, Takumi; Abe, Keiko

    2007-08-24

    Miraculin (MCL), a tropical fruit protein, is unique in that it has taste-modifying activity to convert sourness to sweetness, though flat in taste at neutral pH. To obtain a sufficient amount of MCL to examine the mechanism involved in this sensory event at the molecular level, we transformed Aspergillus oryzae by introducing the MCL gene. Transformants were expressed and secreted a sensory-active form of MCL yielding 2 mg/L. Recombinant MCL resembled native MCL in the secondary structure and the taste-modifying activity to generate sweetness at acidic pH. Since the observed pH-sweetness relation seemed to reflect the imidazole titration curve, suggesting that histidine residues might be involved in the taste-modifying activity. H30A and H30,60A mutants were generated using the A. oryzae-mediated expression system. Both mutants found to have lost the taste-modifying activity. The result suggests that the histidine-30 residue is important for the taste-modifying activity of MCL. PMID:17592723

  1. Mutagenic activity of disinfection by-products.

    PubMed

    Cognet, L; Courtois, Y; Mallevialle, J

    1986-11-01

    Data on raw water quality, disinfection treatment practices, and the resulting mutagenic properties of the treated water were compiled from pilot- and full-scale treatment experiments to evaluate that parameter which might produce variability in the results of a mutagenic study. Analysis of the data and comparison of treatment practices indicated that the measured mutagenic activity is strongly related to the characteristics of the organic matter in the raw water, the methodology used to sample and detect mutagens, the scale of the study both in terms of treatment flow and period of study, and the point at which and the conditions under which oxidants are added during treatment. Conclusions regarding disinfection systems in full-scale water treatment plants include the following: When raw water is pretreated and high concentrations of organics are present in the raw water, both ozonation and chlorination increased mutagenic activity. However, no significant difference in mutagenicity was found between the two oxidants. Both in the case of a nitrified groundwater and a clarified surface water, the mutagenic activity of the water after ozonation was related to its mutagenic activity before ozonation. With ozonation, mutagenic activity decreased after granular activated carbon (GAC) filtration. Thus, when GAC filtration follows ozone disinfection, early addition of oxidants may not be deleterious to the finished water quality. When chlorine or chlorine dioxide is added after GAC filtration, chlorine dioxide was found to produce a less mutagenic water than chlorine. Although these conclusions suggest means of controlling mutagenic activity during treatment, it must be stressed that the measurement of mutagenicity is a presumptive index of contamination level.

  2. Active PZT fibers: a commercial production process

    NASA Astrophysics Data System (ADS)

    Strock, Harold B.; Pascucci, Marina R.; Parish, Mark V.; Bent, Aaron A.; Shrout, Thomas R.

    1999-07-01

    Lead Zirconate Titanate (PZT) active fibers, from 80 to 250 micrometers in diameter, are produced for the AFOSR/DARPA funded Active Fiber Composites Consortium (AFCC) Program and commercial customers. CeraNova has developed a proprietary ceramics-based technology to produce PZT mono-filaments of the required purity, composition, straightness, and piezoelectric properties for use in active fiber composite structures. CeraNova's process begins with the extrusion of continuous lengths of mono-filament precursor fiber from a plasticized mix of PZT-5A powder. The care that must be taken to avoid mix contamination is described using illustrations form problems experiences with extruder wear and metallic contamination. Corrective actions are described and example microstructures are shown. The consequences of inadequate lead control are also shown. Sintered mono- filament mechanical strength and piezoelectric properties data approach bulk values but the validity of such a benchmark is questioned based on variable correlation with composite performance measures. Comb-like ceramic preform structures are shown that are being developed to minimize process and handling costs while maintaining the required mono-filament straightness necessary for composite fabrication. Lastly, actuation performance data are presented for composite structures fabricated and tested by Continuum Control Corporation. Free strain actuation in excess of 2000 microstrain are observed.

  3. Extracellular enzyme activities during cassava fermentation for 'fufu' production.

    PubMed

    Oyewole, O B; Odunfa, S A

    1992-01-01

    Amylase and pectin methyl esterase activities increased rapidly during the early period of the fermentation of cassava for 'fufu' production, attaining their peak activities after 12 and 24h, respectively. Cellulase activity was lower and approximately constant for most of the fermentation period.

  4. RBSE: Product development team research activity deliverables

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The GHG Functions and Extensions to be added to the NASA Electronic Library System (NELS) 1.1 product are described. These functions will implement the 'output request' capability within the Object Browser. The functions will be implemented in two parts. The first part is a code to be added to the Object Browser (X version) to implement menus allowing the user to request that objects be copied to specific media, or that objects be downloaded to the user's system following a specific protocol, or that the object be printed to one of the printers attached to the host system. The second part is shell scripts which support the various menu selections. Additional scripts to support functions within the GHG shell (X version) will also be created along with the X version of the GHG Shell as initial capability for the 27 Mar. prototype. The scripts will be composed of C shell routines that will accept parameters (primary file pathways). Certain limitations in functionality will invoke Mail instead of Oracle Mail since that has yet to be delivered and the NELS invocation will default to the X-Windows version instead of the ASCII version.

  5. Total synthesis and biological activity of natural product Urukthapelstatin A.

    PubMed

    Lin, Chun-Chieh; Tantisantisom, Worawan; McAlpine, Shelli R

    2013-07-19

    Herein we report the first total synthesis of the natural product Urkuthaplestatin A (Ustat A) utilizing a convergent synthetic strategy. The characterization and biological activity match those of the previously published natural product. Interestingly, several intermediates, including the linear and serine cyclized precursors, show a 100-fold decrease in cytotoxicity, with IC50's in the low micromolar range. These data indicate that the rigidity and the consecutive aromatic heterocyclic system are responsible for the biological activity. PMID:23819711

  6. Which Words Are Activated during Bilingual Word Production?

    ERIC Educational Resources Information Center

    Colome, Angels; Miozzo, Michele

    2010-01-01

    Whether words are or are not activated within the lexicon of the nonused language is an important question for accounts of bilingual word production. Prior studies have not led to conclusive results, either because alternative accounts could be proposed for their findings or because activation could have been artificially induced by the…

  7. [Cytogenetic activity of the butylcaptax defoliant transformation product].

    PubMed

    Vesmanova, O Ia; Semykina, E E; Koblov, R K; Ergashev

    1989-01-01

    Cytogenetical activity of the product of metabolitic butylcaptax transformations in cells of cotton plants G. barbadense has been studied. It is shown that butylcaptax, with a significant mutagenicity, looses its mutagenic activity, metabolizing in low mutagenic 2-oxyamylthiobenzthiazole. Low water solubility prevents its concentration to exceed 0.005% in tissue liquids and to exert a mutagenic action on cotton plants. PMID:2773061

  8. [Cytogenetic activity of the butylcaptax defoliant transformation product].

    PubMed

    Vesmanova, O Ia; Semykina, E E; Koblov, R K; Ergashev

    1989-01-01

    Cytogenetical activity of the product of metabolitic butylcaptax transformations in cells of cotton plants G. barbadense has been studied. It is shown that butylcaptax, with a significant mutagenicity, looses its mutagenic activity, metabolizing in low mutagenic 2-oxyamylthiobenzthiazole. Low water solubility prevents its concentration to exceed 0.005% in tissue liquids and to exert a mutagenic action on cotton plants.

  9. Assessment of activation products in the Savannah River Site environment

    SciTech Connect

    Carlton, W.H.; Denham, M.

    1996-07-01

    This document assesses the impact of radioactive activation products released from SRS facilities since the first reactor became operational late in 1953. The isotopes reported here are those whose release resulted in the highest dose to people living near SRS: {sup 32}P, {sup 51}Cr, {sup 60}C, and {sup 65}Zn. Release pathways, emission control features, and annual releases to the aqueous and atmospheric environments are discussed. No single incident has resulted in a major acute release of activation products to the environment. The releases were the result of normal operations of the reactors and separations facilities. Releases declined over the years as better controls were established and production was reduced. The overall radiological impact of SRS activation product atmospheric releases from 1954 through 1994 on the offsite maximally exposed individual can be characterized by a total dose of 0.76 mrem. During the same period, such an individual received a total dose of 14,400 mrem from non-SRS sources of ionizing radiation present in the environment. SRS activation product aqueous releases between 1954 and 1994 resulted in a total dose of 54 mrem to the offsite maximally exposed individual. The impact of SRS activation product releases on offsite populations also has been evaluated.

  10. Milk kefir: composition, microbial cultures, biological activities, and related products.

    PubMed

    Prado, Maria R; Blandón, Lina Marcela; Vandenberghe, Luciana P S; Rodrigues, Cristine; Castro, Guillermo R; Thomaz-Soccol, Vanete; Soccol, Carlos R

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir's exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir's microflora and the importance of kefiran as a beneficial health substance.

  11. Milk kefir: composition, microbial cultures, biological activities, and related products

    PubMed Central

    Prado, Maria R.; Blandón, Lina Marcela; Vandenberghe, Luciana P. S.; Rodrigues, Cristine; Castro, Guillermo R.; Thomaz-Soccol, Vanete; Soccol, Carlos R.

    2015-01-01

    In recent years, there has been a strong focus on beneficial foods with probiotic microorganisms and functional organic substances. In this context, there is an increasing interest in the commercial use of kefir, since it can be marketed as a natural beverage that has health promoting bacteria. There are numerous commercially available kefir based-products. Kefir may act as a matrix in the effective delivery of probiotic microorganisms in different types of products. Also, the presence of kefir’s exopolysaccharides, known as kefiran, which has biological activity, certainly adds value to products. Kefiran can also be used separately in other food products and as a coating film for various food and pharmaceutical products. This article aims to update the information about kefir and its microbiological composition, biological activity of the kefir’s microflora and the importance of kefiran as a beneficial health substance. PMID:26579086

  12. Superoxide Anion Production by Human Neutrophils Activated by Trichomonas vaginalis

    PubMed Central

    Song, Hyun-Ouk

    2013-01-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2.-) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis. PMID:24039294

  13. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    PubMed

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis. PMID:24039294

  14. Superoxide anion production by human neutrophils activated by Trichomonas vaginalis.

    PubMed

    Song, Hyun-Ouk; Ryu, Jae-Sook

    2013-08-01

    Neutrophils are the predominant inflammatory cells found in vaginal discharges of patients infected with Trichomonas vaginalis. In this study, we examined superoxide anion (O2 (.-)) production by neutrophils activated by T. vaginalis. Human neutrophils produced superoxide anions when stimulated with either a lysate of T. vaginalis, its membrane component (MC), or excretory-secretory product (ESP). To assess the role of trichomonad protease in production of superoxide anions by neutrophils, T. vaginalis lysate, ESP, and MC were each pretreated with a protease inhibitor cocktail before incubation with neutrophils. Superoxide anion production was significantly decreased by this treatment. Trichomonad growth was inhibited by preincubation with supernatants of neutrophils incubated for 3 hr with T. vaginalis lysate. Furthermore, myeloperoxidase (MPO) production by neutrophils was stimulated by live trichomonads. These results indicate that the production of superoxide anions and MPO by neutrophils stimulated with T. vaginalis may be a part of defense mechanisms of neutrophils in trichomoniasis.

  15. Charged fusion product loss measurements using nuclear activation

    SciTech Connect

    Bonheure, G.; Hult, M.; Gonzalez de Orduna, R.; Wieslander, E.; Arnold, D.; Dombrowski, H.; Laubenstein, M.; Murari, A.; Collaboration: JET-EFDA Contributors

    2010-10-15

    In ITER, {alpha} particle loss measurements will be required in order to understand the alpha particle physics. Techniques capable of operating in a fusion reactor environment need further development. Recent experimental studies on JET demonstrated the potential of nuclear activation to measure the flux of escaping MeV ions. New results from MeV ion induced activation of metallic, ceramic, and crystal samples placed near the plasma edge are reported. Activation products were measured as function of orientation with respect to the magnetic field as well as function of the distance to the plasma. Sample activity was measured using ultralow-level gamma-ray spectrometry. Distribution of 14.68 MeV fusion proton induced activation products is strongly anisotropic in agreement with simulations and falls off sharply with increasing distance to the plasma. Prospects for using the technique in ITER are discussed.

  16. Enriching step-based product information models to support product life-cycle activities

    NASA Astrophysics Data System (ADS)

    Sarigecili, Mehmet Ilteris

    The representation and management of product information in its life-cycle requires standardized data exchange protocols. Standard for Exchange of Product Model Data (STEP) is such a standard that has been used widely by the industries. Even though STEP-based product models are well defined and syntactically correct, populating product data according to these models is not easy because they are too big and disorganized. Data exchange specifications (DEXs) and templates provide re-organized information models required in data exchange of specific activities for various businesses. DEXs show us it would be possible to organize STEP-based product models in order to support different engineering activities at various stages of product life-cycle. In this study, STEP-based models are enriched and organized to support two engineering activities: materials information declaration and tolerance analysis. Due to new environmental regulations, the substance and materials information in products have to be screened closely by manufacturing industries. This requires a fast, unambiguous and complete product information exchange between the members of a supply chain. Tolerance analysis activity, on the other hand, is used to verify the functional requirements of an assembly considering the worst case (i.e., maximum and minimum) conditions for the part/assembly dimensions. Another issue with STEP-based product models is that the semantics of product data are represented implicitly. Hence, it is difficult to interpret the semantics of data for different product life-cycle phases for various application domains. OntoSTEP, developed at NIST, provides semantically enriched product models in OWL. In this thesis, we would like to present how to interpret the GD & T specifications in STEP for tolerance analysis by utilizing OntoSTEP.

  17. Novel condensation products having high activity to insolubilize proteins and protein-insolubilized products

    SciTech Connect

    Krasnobajew, V.; Boeniger, R.

    1980-01-01

    According to the invention a substantially more active product with respect to the fixing or insolubilization pf proteins, including enzymes, is obtained when 1,3 phenylenediamine is condensed with glutardialdehyde. One application of the process is the enzymatic hydrolysis of lactose in milk products by lactase.

  18. Production of activated carbon from rice husk Vietnam

    NASA Astrophysics Data System (ADS)

    Korobochkin, V. V.; Tu, N. V.; Hieu, N. M.

    2016-09-01

    This work is dedicated to the production of activated carbon from rice husk from Delta of the Red River in Viet Nam. At the first stage, carbonization of a rice husk was carried out to obtain material containing 43.1% carbon and 25 % silica with a specific surface area of 51.5 m2/g. After separating of silica (the second stage), the specific surface area of the product increased to 204 m2/g and the silica content decreased to 1.23% by weight as well. The most important stage in the formation of the porous structure of the material is the activation. The products with the high specific surface area in the range of 800-1345 m2/g were obtained by activation of carbonized product with water vapour or carbon dioxide at temperatures of 700 °C and 850 °C, with varying the flow rate of the activating agent and activation time. The best results were achieved by activation of carbon material with water vapour at the flow rate of 0.08 dm3/min per 500 g of material and the temperature of 850 °C.

  19. Review of the anticancer activities of bee products

    PubMed Central

    Premratanachai, Pongsathon; Chanchao, Chanpen

    2014-01-01

    Bee products have long been used in traditional medicine. The raw materials, crude extracts and purified active compounds from them have been found to exhibit interesting bioactivities, such as antimicrobial, anti-inflammatory and antioxidant activities. In addition, they have been widely used in the treatment of many immune-related diseases, as well as in recent times in the treatment of tumors. Bee product peptides induce apoptotic cell death in vitro in several transformed (cancer) human cell lines, including those derived from renal, lung, liver, prostate, bladder and lymphoid cancers. These bioactive natural products may, therefore, prove to be useful as part of a novel targeted therapy for some types of cancer, such as prostate and breast cancer. This review summarizes the current knowledge regarding the in vivo and in vitro potential of selective bee products against tumor cells. PMID:25182716

  20. Effects of dietary carbohydrates on mutacin production and activity.

    PubMed

    Morency, H; Lavoie, M C

    1991-01-01

    Although mutacins (bacteriocins produced by Streptococcus mutans) were shown to be active in vivo, their ecological role in the oral cavity is still controversial. In the present paper, the effect of dietary carbohydrates, one of the ecological parameters which influences oral bacterial populations, on the activity and the production of mutacins from four S. mutans strains (C67-1, Ny257, Ny266 and T8) is described. Results obtained by the deferred antagonism test in solid media and by the mixed cultivation of the mutacinogenic strains with a sensitive indicator strain in liquid batch cultures, indicate that a minimal fermentable sugar concentration is needed for mutacin production. Among all the fermentable carbohydrates tested (fructose, glucose, lactose, mannitol and sucrose), none significantly affected the production and the activity of the four mutacinogenic strains used, in concentrations up to 5%. Although the results do not discount the possibility of mutacin inactivation in vivo, they indicate that they are not affected by dietary carbohydrates.

  1. Suppression of Active-Region CME Production by the Presence of Other Active Regions

    NASA Technical Reports Server (NTRS)

    Falconer, David; Moore, Ron; Barghouty, Abdulnasser; Khazanov, Igor

    2009-01-01

    From the SOHO mission s data base of MDI full-disk magnetograms spanning solar cycle 23, we have obtained a set of 40,000 magnetograms of 1,300 active regions, tracking each active region across the 30 degree central solar disk. Each active region magnetogram is cropped from the full-disk magnetogram by an automated code. The cadence is 96 minutes. From each active-region magnetogram, we have measured two whole-active-region magnetic quantities: (1) the magnetic size of the active region (the active region s total magnetic flux), and (2) a gauge of the active region s free magnetic energy (part of the free energy is released in the production of a flare and/or CME eruption). From NOAA Flare/CME catalogs, we have obtained the event (Flare/CME/SEP event) production history of each active region. Using all these data, we find that for each type of eruptive event, an active region s expected rate of event production increases as a power law of our gauge of active-region free magnetic energy. We have also found that, among active regions having nearly the same free energy, the rate of the CME production is less when there are many other active regions on the disk than when there are few or none, but there is no significant discernible suppression of the rate of flare production. This indicates that the presence of other active regions somehow tends to inhibit an active region s flare-producing magnetic explosions from becoming CMEs, contrary to the expectation from the breakout model for the production of CMEs.

  2. Isobutyraldehyde production from Escherichia coli by removing aldehyde reductase activity

    PubMed Central

    2012-01-01

    Background Increasing global demand and reliance on petroleum-derived chemicals will necessitate alternative sources for chemical feedstocks. Currently, 99% of chemical feedstocks are derived from petroleum and natural gas. Renewable methods for producing important chemical feedstocks largely remain unaddressed. Synthetic biology enables the renewable production of various chemicals from microorganisms by constructing unique metabolic pathways. Here, we engineer Escherichia coli for the production of isobutyraldehyde, which can be readily converted to various hydrocarbons currently derived from petroleum such as isobutyric acid, acetal, oxime and imine using existing chemical catalysis. Isobutyraldehyde can be readily stripped from cultures during production, which reduces toxic effects of isobutyraldehyde. Results We adopted the isobutanol pathway previously constructed in E. coli, neglecting the last step in the pathway where isobutyraldehyde is converted to isobutanol. However, this strain still overwhelmingly produced isobutanol (1.5 g/L/OD600 (isobutanol) vs 0.14 g/L/OD600 (isobutyraldehyde)). Next, we deleted yqhD which encodes a broad-substrate range aldehyde reductase known to be active toward isobutyraldehyde. This strain produced isobutanol and isobutyraldehyde at a near 1:1 ratio, indicating further native isobutyraldehyde reductase (IBR) activity in E. coli. To further eliminate isobutanol formation, we set out to identify and remove the remaining IBRs from the E. coli genome. We identified 7 annotated genes coding for IBRs that could be active toward isobutyraldehyde: adhP, eutG, yiaY, yjgB, betA, fucO, eutE. Individual deletions of the genes yielded only marginal improvements. Therefore, we sequentially deleted all seven of the genes and assessed production. The combined deletions greatly increased isobutyraldehyde production (1.5 g/L/OD600) and decreased isobutanol production (0.4 g/L/OD600). By assessing production by overexpression of each

  3. Polyhydroxyalkanoate production potential of heterotrophic bacteria in activated sludge.

    PubMed

    Inoue, Daisuke; Suzuki, Yuta; Uchida, Takahiro; Morohoshi, Jota; Sei, Kazunari

    2016-01-01

    This study was conducted to evaluate the polyhydroxyalkanoate (PHA) production potential of cultivable heterotrophic bacteria in activated sludge by genotypic and phenotypic characterizations. A total of 114 bacterial strains were isolated from four activated sludge samples taken from a lab-scale sequencing batch reactor and three wastewater treatment processes of two municipal wastewater treatment plants. PCR detection of the phaC genes encoding class I and II PHA synthase revealed that 15% of the total isolates possessed phaC genes, all of which had the closest similarities to known phaC genes of α- and β-Proteobacteria and Actinobacteria. PHA production experiments under aerobic and nitrogen-limited conditions showed that 68% of the total isolates were capable of producing PHA from at least one of the six substrates used (acetate, propionate, lactate, butyrate, glucose and glycerol). Genotypic and phenotypic characterizations revealed that 75% of the activated sludge bacteria had PHA production potential. Our results also indicated that short-chain fatty acids would be the preferable substrates for PHA production by activated sludge bacteria, and that there might be a variety of unidentified phaC genes in activated sludge.

  4. Long-lived activation products in reactor materials

    SciTech Connect

    Evans, J.C.; Lepel, E.L.; Sanders, R.W.; Wilkerson, C.L.; Silker, W.; Thomas, C.W.; Abel, K.H.; Robertson, D.R.

    1984-08-01

    The purpose of this program was to assess the problems posed to reactor decommissioning by long-lived activation products in reactor construction materials. Samples of stainless steel, vessel steel, concrete, and concrete ingredients were analyzed for up to 52 elements in order to develop a data base of activatable major, minor, and trace elements. Large compositional variations were noted for some elements. Cobalt and niobium concentrations in stainless steel, for example, were found to vary by more than an order of magnitude. A thorough evaluation was made of all possible nuclear reactions that could lead to long lived activation products. It was concluded that all major activation products have been satisfactorily accounted for in decommissioning planning studies completed to date. A detailed series of calculations was carried out using average values of the measured compositions of the appropriate materials to predict the levels of activation products expected in reactor internals, vessel walls, and bioshield materials for PWR and BWR geometries. A comparison is made between calculated activation levels and regulatory guidelines for shallow land disposal according to 10 CFR 61. This analysis shows that PWR and BWR shroud material exceeds the Class C limits and is, therefore, generally unsuitable for near-surface disposal. The PWR core barrel material approaches the Class C limits. Most of the remaining massive components qualify as either Class A or B waste with the bioshield clearly Class A, even at the highest point of activation. Selected samples of activated steel and concrete were subjected to a limited radiochemical analysis program as a verification of the computer model. Reasonably good agreement with the calculations was obtained where comparison was possible. In particular, the presence of /sup 94/Nb in activated stainless steel at or somewhat above expected levels was confirmed.

  5. Review: Production and functionality of active peptides from milk.

    PubMed

    Muro Urista, C; Álvarez Fernández, R; Riera Rodriguez, F; Arana Cuenca, A; Téllez Jurado, A

    2011-08-01

    In recent years, research on the production of active peptides obtained from milk and their potential functionality has grown, to a great extent. Bioactive peptides have been defined as specific protein fragments that have a positive impact on body functions or conditions, and they may ultimately have an influence on health. Individual proteins of casein or milk-derived products such as cheese and yogurt have been used as a protein source to study the isolation and activity of peptides with several applications. Currently, the milk whey waste obtained in the production of cheese also represents a protein source from which active peptides could be isolated with potential industrial applications. The active properties of milk peptides and the results found with regard to their physiological effects have led to the classification of peptides as belonging to the group of ingredients of protein nature, appropriate for use in functional foods or pharmaceutical formulations. In this study, the main peptides obtained from milk protein and the past research studies about its production and biological activities will be explained. Second, an analysis will be made on the methods to determinate the biological activities, the separation of bioactive peptides and its structure identification. All of these form the base required to obtain synthetic peptides. Finally, we explain the experimental animal and human trials done in the past years. Nevertheless, more research is required on the design and implementation of equipment for the industrial production and separation of peptides. In addition, different authors suggest that more emphasis should therefore be given to preclinical studies, proving that results are consistent and that effects are demonstrated repeatedly by several research human groups.

  6. Eliciting Production of L2 Target Structures through Priming Activities

    ERIC Educational Resources Information Center

    McDonough, Kim; Trofimovich, Pavel; Neumann, Heike

    2015-01-01

    This study focuses on the pedagogical applications of structural priming research in an English for academic purposes (EAP) context, investigating whether priming activities are an effective tool for eliciting production of target grammatical structures. University students across four EAP classes carried out a total of 6 information-exchange…

  7. Biological Activity of Recently Discovered Halogenated Marine Natural Products

    PubMed Central

    Gribble, Gordon W.

    2015-01-01

    This review presents the biological activity—antibacterial, antifungal, anti-parasitic, antiviral, antitumor, antiinflammatory, antioxidant, and enzymatic activity—of halogenated marine natural products discovered in the past five years. Newly discovered examples that do not report biological activity are not included. PMID:26133553

  8. DEVELOPMENT OF ACTIVATED CARBONS FROM COAL COMBUSTION BY-PRODUCTS

    SciTech Connect

    Harold H. Schobert; M. Mercedes Maroto-Valer; Zhe Lu

    2003-09-30

    The increasing role of coal as a source of energy in the 21st century will demand environmental and cost-effective strategies for the use of coal combustion by-products (CCBPs), mainly unburned carbon in fly ash. Unburned carbon is nowadays regarded as a waste product and its fate is mainly disposal, due to the present lack of efficient routes for its utilization. However, unburned carbon is a potential precursor for the production of adsorbent carbons, since it has gone through a devolatilization process while in the combustor, and therefore, only requires to be activated. Accordingly, the principal objective of this work was to characterize and utilize the unburned carbon in fly ash for the production of activated carbons. The unburned carbon samples were collected from different combustion systems, including pulverized utility boilers, a utility cyclone, a stoker, and a fluidized bed combustor. LOI (loss-on-ignition), proximate, ultimate, and petrographic analyses were conducted, and the surface areas of the samples were characterized by N2 adsorption isotherms at 77K. The LOIs of the unburned carbon samples varied between 21.79-84.52%. The proximate analyses showed that all the samples had very low moisture contents (0.17 to 3.39 wt %), while the volatile matter contents varied between 0.45 to 24.82 wt%. The elemental analyses show that all the unburned carbon samples consist mainly of carbon with very little hydrogen, nitrogen, sulfur and oxygen In addition, the potential use of unburned carbon as precursor for activated carbon (AC) was investigated. Activated carbons with specific surface area up to 1075m{sup 2}/g were produced from the unburned carbon. The porosity of the resultant activated carbons was related to the properties of the unburned carbon feedstock and the activation conditions used. It was found that not all the unburned carbon samples are equally suited for activation, and furthermore, their potential as activated carbons precursors could be

  9. Can aquatic worms enhance methane production from waste activated sludge?

    PubMed

    Serrano, Antonio; Hendrickx, Tim L G; Elissen, Hellen H J; Laarhoven, Bob; Buisman, Cees J N; Temmink, Hardy

    2016-07-01

    Although literature suggests that aquatic worms can help to enhance the methane production from excess activated sludge, clear evidence for this is missing. Therefore, anaerobic digestion tests were performed at 20 and at 30°C with sludge from a high-loaded membrane bioreactor, the aquatic worm Lumbriculus variegatus, feces from these worms and with mixtures of these substrates. A significant synergistic effect of the worms or their feces on methane production from the high-loaded sludge or on its digestion rate was not observed. However, a positive effect on low-loaded activated sludge, which generally has a lower anaerobic biodegradability, cannot be excluded. The results furthermore showed that the high-loaded sludge provides an excellent feed for L. variegatus, which is promising for concepts where worm biomass is considered a resource for technical grade products such as coatings and glues.

  10. Prediction of Active-Region CME Productivity from Magnetograms

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Gary, G. A.

    2004-01-01

    We report results of an expanded evaluation of whole-active-region magnetic measures as predictors of active-region coronal mass ejection (CME) productivity. Previously, in a sample of 17 vector magnetograms of 12 bipolar active regions observed by the Marshall Space Flight Center (MSFC) vector magnetograph, from each magnetogram we extracted a measure of the size of the active region (the active region s total magnetic flux a) and four measures of the nonpotentiality of the active region: the strong-shear length L(sub SS), the strong-gradient length L(sub SG), the net vertical electric current I(sub N), and the net-current magnetic twist parameter alpha (sub IN). This sample size allowed us to show that each of the four nonpotentiality measures was statistically significantly correlated with active-region CME productivity in time windows of a few days centered on the day of the magnetogram. We have now added a fifth measure of active-region nonpotentiality (the best-constant-alpha magnetic twist parameter (alpha sub BC)), and have expanded the sample to 36 MSFC vector magnetograms of 31 bipolar active regions. This larger sample allows us to demonstrate statistically significant correlations of each of the five nonpotentiality measures with future CME productivity, in time windows of a few days starting from the day of the magnetogram. The two magnetic twist parameters (alpha (sub 1N) and alpha (sub BC)) are normalized measures of an active region s nonpotentially in that they do not depend directly on the size of the active region, while the other three nonpotentiality measures (L(sub SS), L(sub SG), and I(sub N)) are non-normalized measures in that they do depend directly on active-region size. We find (1) Each of the five nonpotentiality measures is statistically significantly correlated (correlation confidence level greater than 95%) with future CME productivity and has a CME prediction success rate of approximately 80%. (2) None of the nonpotentiality

  11. JV Task 90 - Activated Carbon Production from North Dakota Lignite

    SciTech Connect

    Steven Benson; Charlene Crocker; Rokan Zaman; Mark Musich; Edwin Olson

    2008-03-31

    The Energy & Environmental Research Center (EERC) has pursued a research program for producing activated carbon from North Dakota lignite that can be competitive with commercial-grade activated carbon. As part of this effort, small-scale production of activated carbon was produced from Fort Union lignite. A conceptual design of a commercial activated carbon production plant was drawn, and a market assessment was performed to determine likely revenue streams for the produced carbon. Activated carbon was produced from lignite coal in both laboratory-scale fixed-bed reactors and in a small pilot-scale rotary kiln. The EERC was successfully able to upgrade the laboratory-scale activated carbon production system to a pilot-scale rotary kiln system. The activated carbon produced from North Dakota lignite was superior to commercial grade DARCO{reg_sign} FGD and Rheinbraun's HOK activated coke product with respect to iodine number. The iodine number of North Dakota lignite-derived activated carbon was between 600 and 800 mg I{sub 2}/g, whereas the iodine number of DARCO FGD was between 500 and 600 mg I{sub 2}/g, and the iodine number of Rheinbraun's HOK activated coke product was around 275 mg I{sub 2}/g. The EERC performed both bench-scale and pilot-scale mercury capture tests using the activated carbon made under various optimization process conditions. For comparison, the mercury capture capability of commercial DARCO FGD was also tested. The lab-scale apparatus is a thin fixed-bed mercury-screening system, which has been used by the EERC for many mercury capture screen tests. The pilot-scale systems included two combustion units, both equipped with an electrostatic precipitator (ESP). Activated carbons were also tested in a slipstream baghouse at a Texas power plant. The results indicated that the activated carbon produced from North Dakota lignite coal is capable of removing mercury from flue gas. The tests showed that activated carbon with the greatest iodine number

  12. Ecological and Pharmacological Activities of Antarctic Marine Natural Products.

    PubMed

    Avila, Conxita

    2016-06-01

    Antarctic benthic communities are regulated by abundant interactions of different types among organisms, such as predation, competition, etc. Predators are usually sea stars, with omnivorous habits, as well as other invertebrates. Against this strong predation pressure, many organisms have developed all sorts of defensive strategies, including chemical defenses. Natural products are thus quite common in Antarctic organisms with an important ecological and pharmacological potential. In this paper, the chemical defenses of the Antarctic organisms studied during the ECOQUIM and ACTIQUIM projects, as well as their pharmacological potential, are reviewed. For the ecological defenses, predation against the sea star Odontaster validus is analyzed and evaluated along depth gradients as well as considering the lifestyle of the organisms. For the pharmacological activity, the anticancer, anti-inflammatory, and antibacterial activities tested are evaluated here. Very often, only crude extracts or fractions have been tested so far, and therefore, the natural products responsible for such activities remain yet to be identified. Even if the sampling efforts are not uniform along depth, most ecologically active organisms are found between 200 and 500 m depth. Also, from the samples studied, about four times more sessile organisms possess chemical defenses against the sea star than the vagile ones; these represent 50 % of sessile organisms and 35 % of the vagile ones, out of the total tested, being active. Pharmacological activity has not been tested uniformly in all groups, but the results show that relevant activity is found in different phyla, especially in Porifera, Cnidaria, Bryozoa, and Tunicata, but also in others. No relationship between depth and pharmacological activity can be established with the samples tested so far. More studies are needed in order to better understand the ecological relationships among Antarctic invertebrates mediated by natural products and

  13. Ecological and Pharmacological Activities of Antarctic Marine Natural Products.

    PubMed

    Avila, Conxita

    2016-06-01

    Antarctic benthic communities are regulated by abundant interactions of different types among organisms, such as predation, competition, etc. Predators are usually sea stars, with omnivorous habits, as well as other invertebrates. Against this strong predation pressure, many organisms have developed all sorts of defensive strategies, including chemical defenses. Natural products are thus quite common in Antarctic organisms with an important ecological and pharmacological potential. In this paper, the chemical defenses of the Antarctic organisms studied during the ECOQUIM and ACTIQUIM projects, as well as their pharmacological potential, are reviewed. For the ecological defenses, predation against the sea star Odontaster validus is analyzed and evaluated along depth gradients as well as considering the lifestyle of the organisms. For the pharmacological activity, the anticancer, anti-inflammatory, and antibacterial activities tested are evaluated here. Very often, only crude extracts or fractions have been tested so far, and therefore, the natural products responsible for such activities remain yet to be identified. Even if the sampling efforts are not uniform along depth, most ecologically active organisms are found between 200 and 500 m depth. Also, from the samples studied, about four times more sessile organisms possess chemical defenses against the sea star than the vagile ones; these represent 50 % of sessile organisms and 35 % of the vagile ones, out of the total tested, being active. Pharmacological activity has not been tested uniformly in all groups, but the results show that relevant activity is found in different phyla, especially in Porifera, Cnidaria, Bryozoa, and Tunicata, but also in others. No relationship between depth and pharmacological activity can be established with the samples tested so far. More studies are needed in order to better understand the ecological relationships among Antarctic invertebrates mediated by natural products and

  14. Deoxygedunin, a natural product with potent neurotrophic activity in mice.

    PubMed

    Jang, Sung-Wuk; Liu, Xia; Chan, Chi Bun; France, Stefan A; Sayeed, Iqbal; Tang, Wenxue; Lin, Xi; Xiao, Ge; Andero, Raul; Chang, Qiang; Ressler, Kerry J; Ye, Keqiang

    2010-01-01

    Gedunin, a family of natural products from the Indian neem tree, possess a variety of biological activities. Here we report the discovery of deoxygedunin, which activates the mouse TrkB receptor and its downstream signaling cascades. Deoxygedunin is orally available and activates TrkB in mouse brain in a BDNF-independent way. Strikingly, it prevents the degeneration of vestibular ganglion in BDNF -/- pups. Moreover, deoxygedunin robustly protects rat neurons from cell death in a TrkB-dependent manner. Further, administration of deoxygedunin into mice displays potent neuroprotective, anti-depressant and learning enhancement effects, all of which are mediated by the TrkB receptor. Hence, deoxygedunin imitates BDNF's biological activities through activating TrkB, providing a powerful therapeutic tool for treatment of various neurological diseases. PMID:20644624

  15. Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

    PubMed

    Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Raza Ali, Syed; Kunkel, Maya T; Lin, Ann E; Forli, Stefano; Newton, Alexandra C; Kumar, Geetha B; Nair, Bipin G; Perry, J Jefferson P; Nizet, Victor

    2016-07-01

    Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound. PMID:27226531

  16. Natural Product Anacardic Acid from Cashew Nut Shells Stimulates Neutrophil Extracellular Trap Production and Bactericidal Activity.

    PubMed

    Hollands, Andrew; Corriden, Ross; Gysler, Gabriela; Dahesh, Samira; Olson, Joshua; Raza Ali, Syed; Kunkel, Maya T; Lin, Ann E; Forli, Stefano; Newton, Alexandra C; Kumar, Geetha B; Nair, Bipin G; Perry, J Jefferson P; Nizet, Victor

    2016-07-01

    Emerging antibiotic resistance among pathogenic bacteria is an issue of great clinical importance, and new approaches to therapy are urgently needed. Anacardic acid, the primary active component of cashew nut shell extract, is a natural product used in the treatment of a variety of medical conditions, including infectious abscesses. Here, we investigate the effects of this natural product on the function of human neutrophils. We find that anacardic acid stimulates the production of reactive oxygen species and neutrophil extracellular traps, two mechanisms utilized by neutrophils to kill invading bacteria. Molecular modeling and pharmacological inhibitor studies suggest anacardic acid stimulation of neutrophils occurs in a PI3K-dependent manner through activation of surface-expressed G protein-coupled sphingosine-1-phosphate receptors. Neutrophil extracellular traps produced in response to anacardic acid are bactericidal and complement select direct antimicrobial activities of the compound.

  17. Aerobic activated sludge transformation of methotrexate: identification of biotransformation products.

    PubMed

    Kosjek, Tina; Negreira, Noelia; de Alda, Miren López; Barceló, Damià

    2015-01-01

    This study describes the biotransformation of cytostatic and immunosuppressive pharmaceutical methotrexate. Its susceptibility to microbiological breakdown was studied in a batch biotransformation system, in presence or absence of carbon source and at two activated sludge concentrations. The primary focus of the present study are methotrexate biotransformation products, which were tentatively identified by the ultra-high performance liquid chromatography-quadrupole--Orbitrap-MS. Data-dependent experiments, combining full-scan MS data with product ion spectra were acquired, in order to identify the molecular ions of methotrexate transformation products, to propose the molecular formulae and to elucidate their chemical structures. Among the identified transformation products 2,4-diamino-N10-methyl-pteroic acid is most abundant and persistent. Other biotransformation reactions involve demethylation, oxidative cleavage of amine, cleavage of C-N bond, aldehyde to carboxylate transformation and hydroxylation. Finally, a breakdown pathway is proposed, which shows that most of methotrexate breakdown products retain the diaminopteridine structural segment. In total we propose nine transformation products, among them eight are described as methotrexate transformation products for the first time.

  18. ACTIVITY OF NATURAL PRODUCTS AGAINST SOME PHYTOPATHOGENIC FUNGI.

    PubMed

    La Torre, A; Caradonia, F; Gianferro, M; Molinu, M G; Battaglia, V

    2014-01-01

    The requirement of environmental protection and food safety is perceived with always major interest by public opinion and it is consistent with European Union legislation on the sustainable use of pesticides (Directive 2009/128/EC). This directive requires member states to promote low pesticide-input, giving priority to non-chemical methods and low risk plant protection products. In order to contribute to the achievement of these objectives antifungal activity of natural substances, characterized by a good toxicological and ecotoxicological profile, was tested. Essential oil of Melaleuca alternifolia, essential oil of Syzygium aromaticum and extract from Mimosa tenuiflora were tested against Alternaria alternata, Botrytis cinerea and Fusarium oxysporum f. sp. lycopersici (races 1 and 2). In vitro tests involved determination of radial growth of the colonies of fungi in the presence of varying concentrations of tested products in agar media and determination of germination percentage in the presence of tested product at various concentrations. The products based on essential oil of M. alternifolia were also tested in vivo on tomato fruits wounded and artificially inoculated with A. alternata or with B. cinerea. The in vitro tests showed the antifungal activity of both essential oils instead the extract from M. tenuiflora exhibited poor antifungal activity and only against A. alternata and B. cinerea. The results on tomato fruits showed inhibition of grey mould and black mould by essential oil of M. alternifolia. The antifungal activity increased with increasing concentrations. In conclusion, the obtained results in the present study showed promising prospects for the utilisation of investigated products to reduce the using of antifungal chemicals and to achieve a more sustainable use of pesticides. PMID:26080478

  19. Phospholipid Ozonation Products Activate the 5-Lipoxygenase Pathway in Macrophages.

    PubMed

    Zemski Berry, Karin A; Murphy, Robert C

    2016-08-15

    Ozone is a highly reactive environmental toxicant that can react with the double bonds of lipids in pulmonary surfactant. This study was undertaken to investigate the proinflammatory properties of the major lipid-ozone product in pulmonary surfactant, 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (16:0/9al-PC), with respect to eicosanoid production. A dose-dependent increase in the formation of 5-lipoxygenase (5-LO) products was observed in murine resident peritoneal macrophages (RPM) and alveolar macrophages (AM) upon treatment with 16:0/9al-PC. In contrast, the production of cyclooxygenase (COX) derived eicosanoids did not change from basal levels in the presence of 16:0/9al-PC. When 16:0/9al-PC and the TLR2 ligand, zymosan, were added to RPM or AM, an enhancement of 5-LO product formation along with a concomitant decrease in COX product formation was observed. Neither intracellular calcium levels nor arachidonic acid release was influenced by the addition of 16:0/9al-PC to RPM. Results from mitogen-activated protein kinase (MAPK) inhibitor studies and direct measurement of phosphorylation of MAPKs revealed that 16:0/9al-PC activates the p38 MAPK pathway in RPM, which results in the activation of 5-LO. Our results indicate that 16:0/9al-PC has a profound effect on the eicosanoid pathway, which may have implications in inflammatory pulmonary disease states where eicosanoids have been shown to play a role. PMID:27448436

  20. Active Desiccant-Based Preconditioning Market Analysis and Product Development

    SciTech Connect

    Fischer, J.

    2001-01-11

    The Phase 1 report (ORNL/Sub/94-SVO44/1), completed earlier in this program, involved a comprehensive field survey and market analysis comparing various specialized outdoor air handling units. This initial investigation included conventional cooling and reheat, conventional cooling with sensible recovery, total energy recovery systems (passive desiccant technology) and various active desiccant systems. The report concluded that several markets do promise a significant sales opportunity for a Climate Changer-based active desiccant system offering. (Climate Changer is a registered trademark of Trane Company.) This initial market analysis defined the wants and needs of the end customers (design engineers and building owners), which, along with subsequent information included in this report, have been used to guide the determination of the most promising active desiccant system configurations. This Phase 2 report begins with a summary of a more thorough investigation of those specific markets identified as most promising for active desiccant systems. Table 1 estimates the annual sales potential for a cost-effective product line of active desiccant systems, such as that built from Climate Changer modules. The Product Development Strategy section describes the active desiccant system configurations chosen to best fit the needs of the marketplace while minimizing system options. Key design objectives based on market research are listed in this report for these active desiccant systems. Corresponding performance goals for the dehumidification wheel required to meet the overall system design objectives are also defined. The Performance Modeling section describes the strategy used by SEMCO to design the dehumidification wheels integrated into the prototype systems currently being tested as part of the U.S. Department of Energy's Advanced Desiccant Technology Program. Actual performance data from wheel testing was used to revise the system performance and energy analysis

  1. Patterns of plasminogen activator production in cultured normal embryonic cells

    PubMed Central

    1977-01-01

    Cultured normal low-passage embryo fibroblasts, from a number of species, and two untransformed clones of a Balb/3T3 line elaborate increasing amounts of plasminogen activator (PA) as they approach confluence; the low-passage cells then lose this PA activity after reaching confluence, while the 3T3 cells retain it indefinitely. Even at their peaks, however, the PA activities of the low-passage cells remain well below those of the corresponding virally or spontaneously transformed cells. The PA increases in normal cells are probably a result of PA production rather than of adsorption of secreted PA to the cell surface, or of changes in cell-associated protease inhibitors. The elaboration of PA by normal cells is dependent upon their metabolic activity, such that the level of serum supplementation and the growth phase of the culture directly influence the level of cell-associated PA observed. In addition, there may be a component of serum which exerts a negative control on PA production and which is not an acid-labile protease inhibitor. PMID:21193

  2. 75 FR 6386 - Pesticide Products; Registration Applications for a New Active Ingredient Chemical; Demiditraz

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ... register pesticide products containing active ingredients not included in any previously registered pesticide products. Pursuant to the provisions of section 3(c)(4) of the Federal Insecticide, Fungicide, and... AGENCY Pesticide Products; Registration Applications for a New Active Ingredient Chemical;...

  3. [Activity of hydrogen sulfide production enzymes in kidneys of rats].

    PubMed

    Mel'nyk, A V; Pentiuk, O O

    2009-01-01

    An experimental research of activity and kinetic descriptions of enzymes participating in formation of hydrogen sulfide in the kidney of rats has been carried out. It was established that cystein, homocystein and thiosulphate are the basic substrates for hydrogen sulfide synthesis. The higest activity for hydrogen sulfide production belongs to thiosulfate-dithiolsulfurtransferase and cysteine aminotransferase, less activity is characteristic of cystathionine beta-synthase and cystathio-nine gamma-lyase. The highest affinity to substrate is registered for thiosulfate-dithiolsulfurtransferase and cystathionine gamma-lyase. It is discovered that the substrate inhibition is typical of all hydrogen sulfide formation enzymes, although this characteristic is the most expressed thiosulfat-dithiolsulfurtransferase. PMID:20387629

  4. Production and characterization of activated carbons from cereal grains

    SciTech Connect

    Venkatraman, A.; Walawender, W.P.; Fan, L.T.

    1996-12-31

    The term, activated carbon, is a generic name for a family of carbonaceous materials with well-developed porosities and consequently, large adsorptive capacities. Activated carbons are increasingly being consumed worldwide for environmental applications such as separation of volatiles from bulk gases and purification of water and waste-water streams. The global annual production is estimated to be around 300 million kilograms, with a rate of increase of 7% each year. Activated carbons can be prepared from a variety of raw materials. Approximately, 60% of the activated carbons generated in the United States is produced from coal; 20%, from coconut shells; and the remaining 20% from wood and other sources of biomass. The pore structure and properties of activated carbons are influenced by the nature of the starting material and the initial physical and chemical conditioning as well as the process conditions involved in its manufacture. The porous structures of charcoals and activated carbons obtained by the carbonization of kernels have been characterized.

  5. Which words are activated during bilingual word production?

    PubMed

    Colomé, Angels; Miozzo, Michele

    2010-01-01

    Whether words are or are not activated within the lexicon of the nonused language is an important question for accounts of bilingual word production. Prior studies have not led to conclusive results, either because alternative accounts could be proposed for their findings or because activation could have been artificially induced by the experimental paradigms. Moreover, previous data only involved target translations, and nothing is known about the activation of nontarget words in the nonused language. The picture-picture interference paradigm was used here, since it allowed the activation of nontarget words to be determined without showing stimuli that could artificially activate the nonused language. Proficient Spanish-Catalan speakers were presented with pairs of partially overlapping colored pictures and were instructed to name the green picture and ignore the red picture. In Experiment 1, distractor pictures with cognate names interfered more than distractor pictures with noncognate names. In Experiment 2, facilitation was observed when the names of the distractor pictures in the nonused language were phonologically related to the names of the target pictures. Overall, these results indicate that nontarget words are activated in the nonused language, at least in the case of proficient bilingual speakers. These results help researchers to constrain theories of bilingual lexical access. (PsycINFO Database Record (c) 2009 APA, all rights reserved). PMID:20053047

  6. Galectin-3 binds highly galactosylated IgG1 and is crucial for the IgG1 complex mediated inhibition of C5aReceptor induced immune responses.

    PubMed

    Heyl, Kerstin A; Karsten, Christian M; Slevogt, Hortense

    2016-10-01

    Changes in the glycosylation of immunoglobulins have been shown to modulate immune homeostasis and disease pathology. In this sense it has been shown that highly galactosylated but not agalactosylated IgG1 immune complexes (ICs) inhibit C5aR-mediated pro-inflammatory immune responses via the assembly of FcγRIIB-Dectin-1 receptor complexes. In this study we demonstrated that Galectin-3, a galactose-binding lectin that is known to cross-link proteins on cell-surfaces via binding their N-glycans, bound to highly-galactosylated, but not agalactosylated IgG1. Further, Galectin-3 was essential for the IC-mediated inhibition of C5a-induced neutrophil chemotaxis in vitro. Taken together our results indicate that Galectin-3 mediates the interaction of ICs with the FcγRIIB-Dectin-1 receptor complex for delivering immunoregulatory signals to inhibit C5aR-mediated immune responses. PMID:27620493

  7. Production of charcoal and activated carbon at elevated pressure

    SciTech Connect

    Dai, Xiangfeng; Norberg, N.; Antal, M.J. Jr.

    1995-12-31

    With its wide range of properties, charcoal finds many commercial applications for domestic cooking, refining of metals (steel, copper, bronze, nickel, aluminum and electro-manganese), production of chemicals (carbon disulfide, calcium carbide, silicon carbide, sodium cyanide, carbon black, fireworks, gaseous chemicals, absorbents, soil conditioners and pharmaceuticals), as well as production of activated carbon and synthesis gas. In 1991, the world production of charcoal was 22.8 million cubic meters (3.8 million metric tons) as shown in Table 1. Brazil is the world`s largest charcoal producer --- 5.9 million cubic meters or one million metric tons was produced in 1991, most of which is used in steel and iron industry. African countries produced 45% of the world total amount of charcoal, where 86% of the wood-based energy is for domestic use, most of which is inefficiently used. Charcoal is produced commercially in kilns with a 25% to 30% yield by mass on a 7 to 12 day operating cycle. Until recently, the highest yield of good quality charcoal reported in the literature was 38%. In this paper, and ASME code rated experimental system is presented for producing charcoal and activated carbon from biomass.

  8. Production of carboxylates from high rate activated sludge through fermentation.

    PubMed

    Cagnetta, C; Coma, M; Vlaeminck, S E; Rabaey, K

    2016-10-01

    The aim of this work was to study the key parameters affecting fermentation of high rate activated A-sludge to carboxylates, including pH, temperature, inoculum, sludge composition and iron content. The maximum volatile fatty acids production was 141mgCg(-1) VSSfed, at pH 7. Subsequently the potential for carboxylate and methane production for A-sludge from four different plants at pH 7 and 35°C were compared. Initial BOD of the sludge appeared to be key determining carboxylate yield from A-sludge. Whereas methanogenesis could be correlated linearly to the quantity of ferric used for coagulation, fermentation did not show a dependency on iron presence. This difference may enable a strategy whereby A-stage sludge is separated to achieve fermentation, and iron dosing for phosphate removal is only implemented at the B-stage. PMID:27020399

  9. Land processes distributed active archive center product lifecycle plan

    USGS Publications Warehouse

    Daucsavage, John C.; Bennett, Stacie D.

    2014-01-01

    The U.S. Geological Survey (USGS) Earth Resources Observation and Science (EROS) Center and the National Aeronautics and Space Administration (NASA) Earth Science Data System Program worked together to establish, develop, and operate the Land Processes (LP) Distributed Active Archive Center (DAAC) to provide stewardship for NASA’s land processes science data. These data are critical science assets that serve the land processes science community with potential value beyond any immediate research use, and therefore need to be accounted for and properly managed throughout their lifecycle. A fundamental LP DAAC objective is to enable permanent preservation of these data and information products. The LP DAAC accomplishes this by bridging data producers and permanent archival resources while providing intermediate archive services for data and information products.

  10. Natural Product Compounds with Aromatase Inhibitory Activity: An Update

    PubMed Central

    Balunas, Marcy J.; Kinghorn, A. Douglas

    2010-01-01

    Several synthetic aromatase inhibitors are currently in clinical use for the treatment of postmenopausal women with hormone-receptor positive breast cancer. However, these treatments may lead to untoward side effects and so a search for new aromatase inhibitors continues, especially those for which the activity is promoter-specific, targeting the breast-specific promoters I.3 and II. Recently, numerous natural product compounds have been found to inhibit aromatase in non-cellular, cellular, and in vivo studies. These investigations, covering the last two years, as well as additional studies that have focused on the evaluation of natural product compounds as promoter-specific aromatase inhibitors or as aromatase inducers, are described in this review. PMID:20635310

  11. Turbokon scientific and production implementation company—25 years of activity

    NASA Astrophysics Data System (ADS)

    Favorskii, O. N.; Leont'ev, A. I.; Milman, O. O.

    2016-05-01

    The main results of studies performed at ZAO Turbokon NPVP in cooperation with leading Russian scientific organizations during 25 years of its activity in the field of development of unique ecologically clean electric power and heat production technologies are described. They include the development and experimental verification using prototypes and full-scale models of highly efficient air-cooled condensers for steam turbines, a high temperature gas steam turbine for stationary and transport power engineering, a nonfuel technology of electric power production using steam turbine installations with a unit power of 4-20 MW at gas-main pipelines and industrial boiler houses and heat stations. The results of efforts in the field of reducing vibroactivity of power equipment for transport installations are given. Basic directions of further research for increasing the efficiency and ecological safety of home power engineering are discussed.

  12. 78 FR 68814 - Subzone 41L; Authorization of Production Activity; Broan-NuTone, LLC (Home Ventilation Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... Foreign-Trade Zones Board Subzone 41L; Authorization of Production Activity; Broan-NuTone, LLC (Home Ventilation Products and Heaters); Hartford, Wisconsin On June 26, 2013, Broan-NuTone LLC submitted a notification of proposed production activity to the Foreign-Trade Zones (FTZ) Board for its facility...

  13. Digital Wave Processor Products in the Cluster Active Archive

    NASA Astrophysics Data System (ADS)

    Yearby, K. H.; Alleyne, H. St. C.; Walker, S. N.; Bates, I.; Gough, M. P.; Buckley, A.; Carozzi, T. D.

    The Digital Wave Processor (DWP) is the central control and data processing instrument for the Cluster Wave Experiment Consortium. DWP products in the Cluster Active Archive (CAA) provide a mainly supporting function for the rest of the consortium. This includes a time correction dataset which allows the standard timing accuracy of 2 ms to be improved to around 20 μs, and experiment command and status datasets which show what commands have been sent to the experiments, and the resulting status. DWP also contains a particle correlator experiment that computes the auto-correlation of electron counts received by the PEACE electron experiment via an inter-experiment link.

  14. Hanford Immobilized Low-Activity Waste Product Acceptance Test Plan

    SciTech Connect

    Peeler, D.

    1999-06-22

    'The Hanford Site has been used to produce nuclear materials for the U.S. Department of Energy (DOE) and its predecessors. A large inventory of radioactive and mixed waste, largely generated during Pu production, exists in 177 underground single- and double-shell tanks. These wastes are to be retrieved and separated into low-activity waste (LAW) and high-level waste (HLW) fractions. The DOE is proceeding with an approach to privatize the treatment and immobilization of Handord''s LAW and HLW.'

  15. Neutron Activation Analysis and Product Isotope Inventory Code System.

    1990-10-31

    Version 00 NAC was designed to predict the neutron-induced gamma-ray radioactivity for a wide variety of composite materials. The NAC output includes the input data, a list of all reactions for each constituent element, and the end-of-irradiation disintegration rates for each reaction. NAC also compiles a product isotope inventory containing the isotope name, the disintegration rate, the gamma-ray source strength, and the absorbed dose rate at 1 meter from an unshielded point source. The inducedmore » activity is calculated as a function of irradiation and decay times; the effect of cyclic irradiation can also be calculated.« less

  16. T helper 1 immunity requires complement-driven NLRP3 inflammasome activity in CD4⁺ T cells.

    PubMed

    Arbore, Giuseppina; West, Erin E; Spolski, Rosanne; Robertson, Avril A B; Klos, Andreas; Rheinheimer, Claudia; Dutow, Pavel; Woodruff, Trent M; Yu, Zu Xi; O'Neill, Luke A; Coll, Rebecca C; Sher, Alan; Leonard, Warren J; Köhl, Jörg; Monk, Pete; Cooper, Matthew A; Arno, Matthew; Afzali, Behdad; Lachmann, Helen J; Cope, Andrew P; Mayer-Barber, Katrin D; Kemper, Claudia

    2016-06-17

    The NLRP3 inflammasome controls interleukin-1β maturation in antigen-presenting cells, but a direct role for NLRP3 in human adaptive immune cells has not been described. We found that the NLRP3 inflammasome assembles in human CD4(+) T cells and initiates caspase-1-dependent interleukin-1β secretion, thereby promoting interferon-γ production and T helper 1 (T(H)1) differentiation in an autocrine fashion. NLRP3 assembly requires intracellular C5 activation and stimulation of C5a receptor 1 (C5aR1), which is negatively regulated by surface-expressed C5aR2. Aberrant NLRP3 activity in T cells affects inflammatory responses in human autoinflammatory disease and in mouse models of inflammation and infection. Our results demonstrate that NLRP3 inflammasome activity is not confined to "innate immune cells" but is an integral component of normal adaptive T(H)1 responses. PMID:27313051

  17. Conformation-Activity Relationships of Polyketide Natural Products

    PubMed Central

    Larsen, Erik M.; Wilson, Matthew R.; Taylor, Richard E.

    2015-01-01

    Polyketides represent an important class of secondary metabolites that interact with biological targets connected to a variety of disease-associated pathways. Remarkably, nature’s assembly lines, polyketide synthases, manufacture these privileged structures through a combinatorial mixture of just a few structural units. This review highlights the role of these structural elements in shaping a polyketide’s conformational preferences, the use of computer-based molecular modeling and solution NMR studies in the identification of low-energy conformers, and the importance of conformational analogues in probing the bound conformation. In particular, this review covers several examples wherein conformational analysis complements classic structure-activity relationships in the design of biologically active natural product analogues. PMID:25974024

  18. Natural Product Nitric Oxide Chemistry: New Activity of Old Medicines

    PubMed Central

    Jiang, Hong; Torregrossa, Ashley C.; Parthasarathy, Deepa K.; Bryan, Nathan S.

    2012-01-01

    The use of complementary and alternative medicine (CAM) as a therapy and preventative care measure for cardiovascular diseases (CVD) may prove to be beneficial when used in conjunction with or in place of conventional medicine. However, the lack of understanding of a mechanism of action of many CAMs limits their use and acceptance in western medicine. We have recently recognized and characterized specific nitric oxide (NO) activity of select alternative and herbal medicines that may account for many of their reported health benefits. The ability of certain CAM to restore NO homeostasis both through enhancing endothelial production of NO and by providing a system for reducing nitrate and nitrite to NO as a compensatory pathway for repleting NO bioavailability may prove to be a safe and cost-effective strategy for combating CVD. We will review the current state of science behind NO activity of herbal medicines and their effects on CVD. PMID:22548122

  19. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Active ingredients for deodorant drug products for... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following...

  20. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Active ingredients for deodorant drug products for... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following...

  1. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Active ingredients for deodorant drug products for... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant drug products for internal use. The active ingredient of the product consists of either of the following...

  2. An Update on Natural Products with Carbonic Anhydrase Inhibitory Activity.

    PubMed

    Karioti, Anastasia; Carta, Fabrizio; Supuran, Claudiu T

    2016-01-01

    Carbonic anhydrases (CAs, EC 4.2.1.1) catalyze the fundamental reaction of CO2 hydration in all living organisms, being actively involved in the regulation of a plethora of patho/physiological processes. They represent a typical example of enzyme convergent evolution, as six genetically unrelated families of such enzymes were described so far. It is more than 70 years that synthetic compounds, mainly sulfonamides, have been used in clinical practice as diuretics and systemic acting antiglaucoma drugs. Recent studies using natural product libraries and isolated constituents from natural sources (such as fungi and plants) have disclosed novel chemotypes possessing carbonic anhydrase inhibition activities. These natural sources offer new opportunities in the search for new and more effective carbonic anhydrase inhibitors, and may serve as new leads for the design and development of future drugs. This review will discuss the most recent advances in the search of naturally occurring products and their synthetic derivatives that inhibit the CAs and their mechanisms of action at molecular level. Plant extracts are not considered in the present review. PMID:26654592

  3. Structure-activity relationship of caffeoylquinic acids on the accelerating activity on ATP production.

    PubMed

    Miyamae, Yusaku; Kurisu, Manami; Han, Junkyu; Isoda, Hiroko; Shigemori, Hideyuki

    2011-01-01

    Caffeoylquinic acid (CQA) is one of the phenylpropanoids which have various bioactivities such as antioxidant, antibacterial, anticancer, antihistamic, and other biological effects. We previously reported that 3,5-di-O-caffeoylquinic acid inhibited amyloid β(1-42)-induced cellular toxicity on human neuroblastoma SH-SY5Y cells and increased the mRNA expression level of glycolytic enzymes and the intracellular ATP level. To investigate structure-activity relationship on the accelerating activity on ATP production, we synthesized 1,4,5-tri-O-caffeoylquinic acid, 4,5-di-O-caffeoylquinic acid, 3,4,5-tri-O-caffeoylquinic acid, and other derivatives. Additionally, we evaluated intracellular ATP level in SH-SY5Y treated with each CQA derivative. As a result, 3,4,5-tri-O-caffeoylquinic acid showed the highest accelerating activity on ATP production among tested compounds. It was suggested that caffeoyl groups bound to quinic acid are important for activity and the more caffeoyl groups are bound to quinic acid, the higher accelerating activity on ATP production exhibits.

  4. DEVELOPMENT OF ACTIVATED CARBONS FROM COAL COMBUSTION BY-PRODUCTS

    SciTech Connect

    Prof. Harold H. Schobert; Dr. M. Mercedes Maroto-Valer; Ms. Zhe Lu

    2001-09-29

    The implementation of increasingly stringent Clean Air Act Regulations by the coal utility industry has resulted in an increase in the concentration of unburned carbon in coal combustion fly ash. In 1999, around 6 million tons of unburned carbon were disposed in the US, due to the present lack of efficient routes for its utilization. However, unburned carbon is a potential precursor for the production of adsorbent carbons, since it has gone through a devolatilization process while in the combustor, and therefore, only requires to be activated. Accordingly, this report evaluates and compares several routes for the production of activated carbons from unburned carbon, including physical activation with steam or CO{sub 2}, and chemical activation using KOH pretreatment. During the present reporting period (June 30, 2000--June 29, 2001), Task 1 ''Procurement and characterization of CCBPs'' was concluded, including samples from pulverized utility boilers, a utility cyclone unit equipped with a beneficiation technology, a suspension-fired research boiler, and a class C fly ash. The characterization studies showed that the samples collected have significantly different carbon contents, as determined by the ASTM C114 procedure, with the sample from the cyclone unit containing the highest carbon content (LOI of {approx} 80%), since this unit has been retrofitted with a technology to separate the unburned carbon from the fly ash. The porosity of the samples assembled was characterized by N{sub 2} adsorption isotherms at 77K. The surface areas of the class F fly ash samples from pulverized coal combustors are between 30-40 m{sup 2}/g, while the samples from the suspension-fired research boiler had surface area around 115 m{sup 2}/g. As expected, the surface areas of the class C ash is much higher than that of the class F ashes, with values up to 390 m{sup 2}/g. In addition, during the current reporting period, also Task 2 ''Development of activated carbons'' and Task 3

  5. Sustainable production of biologically active molecules of marine based origin.

    PubMed

    Murray, Patrick M; Moane, Siobhan; Collins, Catherine; Beletskaya, Tanya; Thomas, Olivier P; Duarte, Alysson W F; Nobre, Fernando S; Owoyemi, Ifeloju O; Pagnocca, Fernando C; Sette, L D; McHugh, Edward; Causse, Eric; Pérez-López, Paula; Feijoo, Gumersindo; Moreira, Ma T; Rubiolo, Juan; Leirós, Marta; Botana, Luis M; Pinteus, Susete; Alves, Celso; Horta, André; Pedrosa, Rui; Jeffryes, Clayton; Agathos, Spiros N; Allewaert, Celine; Verween, Annick; Vyverman, Wim; Laptev, Ivan; Sineoky, Sergei; Bisio, Angela; Manconi, Renata; Ledda, Fabio; Marchi, Mario; Pronzato, Roberto; Walsh, Daniel J

    2013-09-25

    The marine environment offers both economic and scientific potential which are relatively untapped from a biotechnological point of view. These environments whilst harsh are ironically fragile and dependent on a harmonious life form balance. Exploitation of natural resources by exhaustive wild harvesting has obvious negative environmental consequences. From a European industry perspective marine organisms are a largely underutilised resource. This is not due to lack of interest but due to a lack of choice the industry faces for cost competitive, sustainable and environmentally conscientious product alternatives. Knowledge of the biotechnological potential of marine organisms together with the development of sustainable systems for their cultivation, processing and utilisation are essential. In 2010, the European Commission recognised this need and funded a collaborative RTD/SME project under the Framework 7-Knowledge Based Bio-Economy (KBBE) Theme 2 Programme 'Sustainable culture of marine microorganisms, algae and/or invertebrates for high value added products'. The scope of that project entitled 'Sustainable Production of Biologically Active Molecules of Marine Based Origin' (BAMMBO) is outlined. Although the Union is a global leader in many technologies, it faces increasing competition from traditional rivals and emerging economies alike and must therefore improve its innovation performance. For this reason innovation is placed at the heart of a European Horizon 2020 Strategy wherein the challenge is to connect economic performance to eco performance. This article provides a synopsis of the research activities of the BAMMBO project as they fit within the wider scope of sustainable environmentally conscientious marine resource exploitation for high-value biomolecules.

  6. Structure activity relationship study of Mezzettiasides natural products and their four new disaccharide analogues for anticancer/antibacterial activity

    PubMed Central

    Bajaj, Sumit O.; Shi, Pei

    2014-01-01

    Ten members of the mezzettiaside family of natural products were synthesized and evaluated for anticancer and antibacterial activity. Complete anticancer (H460) and antibacterial (B. subtilis) activities for the ten natural products and four new analogues were found. Comparison to the cleistrioside and cleistetroside classes of natural products were made. PMID:25729554

  7. Centennial Scale Variations in Lake Productivity Linked to Solar Activity

    NASA Astrophysics Data System (ADS)

    Englebrecht, A.; Bhattacharyya, S.; Guilderson, T. P.; Ingram, L.; Byrne, R.

    2012-12-01

    Solar variations on both decadal and centennial timescales have been associated with climate phenomena (van Loon et al., 2004; Hodell et al., 2001; White et al., 1997). The energy received by the Earth at the peak of the solar cycle increases by <0.1%; so the question has remained of how this could be amplified to produce an observable climate response. Recent modeling shows that the response of the Earth's climate system to the 11-year solar cycle may be amplified through stratosphere and ocean feedbacks and has the potential to impact climate variability on a multidecadal to centennial timescales (Meehl et al., 2009). Here, we report a 1000-year record of changes in the stratigraphy and carbon isotope composition of varved lake sediment from Isla Isabela (22°N, 106°W) in the subtropical northeast Pacific. Stable carbon isotopes and carbonate stratigraphy can be used to infer surface productivity in the lake. Our analysis shows variations in primary productivity on centennial timescales and suggests that solar activity may be an important component of Pacific climate variability. A possible response during solar maxima acts to keep the eastern equatorial Pacific cooler and drier than usual, producing conditions similar to a La Niña event. In the region around Isla Isabela peak solar years were characterized by decreased surface temperatures and suppressed precipitation (Meehl et al., 2009), which enhance productivity at Isabela (Kienel et al. 2011). In the future, we plan to analyze the data using advanced time series analysis techniques like the wavelets together with techniques to handle irregularly spaced time series data. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-571672

  8. Plans for the Sentinel-3 SLSTR Active Fire Product

    NASA Astrophysics Data System (ADS)

    Wooster, Martin; Xu, Weidong

    2010-05-01

    The Sea and Land Surface Temperature Radiometer (SLSTR) will fly on the ESA Sentinel-3 satellites as a follow-on to the highly successful ERS/ENVISAR (A)ATSR series of imaging radiometers. SLSTR has been designed to offer a series of new capabilities over and above those of the forunner instruments (including an increased number of spectral channels, a much wider swath width, and an increased revisit frequency) whist still maintaining the key characteristics of dual-view, high accuracy and high precision radiometry. Included in the SLSTR-design are two dedicated "fire channels" that will allow unsaturated thermal spectral radiance observations over even high intensity and/or large open vegetation fires. Data from these and the other spectral channels will be used to generate an operational near real-time SLSTR active fire detection and fire radiative power product, to be used for both scientific studies on wildfire causes, behaviour and effects, and also operational applications involved with forecasting the short-term atmospheric impact of wildfire smoke. This work will present the plans for the SLSTR fire product, including details of the algorithm design and performance analysis, and an evaluation of the ver1 algorithm using MODIS data of global fire events.

  9. 78 FR 49254 - Foreign-Trade Zone 158-Vicksburg/Jackson, Mississippi; Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... Production Activity; Extension of Production Authority; Bauhaus USA, Inc. (Upholstered Furniture); Saltillo... comment (78 FR 20889, 4-8-2013). The FTZ Board has determined that no further review of the activity...

  10. 78 FR 10167 - Pesticide Products; Registration Applications for a New Active Ingredient

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... include: Crop production (NAICS code 111). Animal production (NAICS code 112). Food manufacturing (NAICS... AGENCY Pesticide Products; Registration Applications for a New Active Ingredient AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: EPA has received applications to register...

  11. Natural products as a resource for biologically active compounds

    SciTech Connect

    Hanke, F.J.

    1986-01-01

    The goal of this study was to investigate various sources of biologically active natural products in an effort to identify the active pesticidal compounds involved. The study is divided into several parts. Chapter 1 contains a discussion of several new compounds from plant and animal sources. Chapter 2 introduces a new NMR technique. In section 2.1 a new technique for better utilizing the lanthanide relaxation agent Gd(fod)/sub 3/ is presented which allows the predictable removal of resonances without line broadening. Section 2.2 discusses a variation of this technique for use in an aqueous solvent by applying this technique towards identifying the binding sites of metals of biological interest. Section 2.3 presents an unambiguous /sup 13/C NMR assignment of melibiose. Chapter 3 deals with work relating to the molting hormone of most arthropods, 20-hydroxyecdysone. Section 3.1 discusses the use of two-dimensional NMR (2D NMR) to assign the /sup 1/H NMR spectrum of this biologically important compound. Section 3.2 presents a new application for Droplet countercurrent chromatography (DCCC). Chapter 4 presents a basic improvement to the commercial DCCC instrument that is currently being applied to future commercial instruments. Chapter 5 discusses a curious observation of the effects that two previously known compounds, nagilactone C and (-)-epicatechin, have on lettuce and rice and suggest a possible new role for the ubiquitous flavanol (-)-epicatechin in plants.

  12. 78 FR 28190 - Foreign-Trade Zone (FTZ) 134-Chattanooga, Tennessee; Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ... Production Activity; Komatsu America Corporation (Construction and Forestry Equipment Production... of proposed production activity to the FTZ Board on behalf of Komatsu America Corporation (Komatsu... located within Site 14 of FTZ 134 (S-38- 2013, 4-2-2013). The facility is used for the production...

  13. Activation product safety in the ARIES-I reactor design

    SciTech Connect

    Herring, J.S. ); Sze, D.K. ); Wong, C.; Cheng, E.T. ); Grotz, S.P. )

    1990-01-01

    The ARIES design effort has sought to maximize the environmental and safety advantages of fusion through careful selection of materials and careful design. Three goals are that the reactor achieve inherent or passive safety, that no public evacuation plan be necessary and that the waste be disposable as 10CFR61 Class C waste. The ARIES-I reactor consists of a SiC composite structure for the first wall and blanket, cooled by 10 MPa He. The breeder is Li{sub 2}ZrO{sub 3}, although Li{sub 2}O and Li{sub 4}SiO{sub 4} were also considered. The divertor consists of SiC composite tubes coated with 2 mm of tungsten. Due to the minimal afterheat of this blanket design, LOCA calculations indicate maximum temperatures will not cause damage if the plasma is promptly extinguished. Two primary safety issues are the zirconium in the breeder and tungsten on the divertor. Li{sub 2}ZrO{sub 3} was chosen because of its demonstrated high-temperature stability. The other breeders have lower afterheat and activation. Use of zirconium in the breeder will necessitate isotopic tailoring to remove {sup 90}Zr and {sup 94}Zr. The 5.8 tonnes of W on the divertor would also have to be tailored to remove {sup 186}W and/or to concentrate {sup 183}W. Thus the ARIES-I design achieves the passive safety and low-level waste disposal criteria with respect to activation products. Development of low activation materials to replace zirconium and tungsten is needed to avoid requiring an evacuation plan.

  14. Production Scale-Up or Activated Carbons for Ultracapacitors

    SciTech Connect

    Dr. Steven D. Dietz

    2007-01-10

    Transportation use accounts for 67% of the petroleum consumption in the US. Electric and hybrid vehicles are promising technologies for decreasing our dependence on petroleum, and this is the objective of the FreedomCAR & Vehicle Technologies Program. Inexpensive and efficient energy storage devices are needed for electric and hybrid vehicle to be economically viable, and ultracapacitors are a leading energy storage technology being investigated by the FreedomCAR program. The most important parameter in determining the power and energy density of a carbon-based ultracapacitor is the amount of surface area accessible to the electrolyte, which is primarily determined by the pore size distribution. The major problems with current carbons are that their pore size distribution is not optimized for liquid electrolytes and the best carbons are very expensive. TDA Research, Inc. (TDA) has developed methods to prepare porous carbons with tunable pore size distributions from inexpensive carbohydrate based precursors. The use of low-cost feedstocks and processing steps greatly lowers the production costs. During this project with the assistance of Maxwell Technologies, we found that an impurity was limiting the performance of our carbon and the major impurity found was sulfur. A new carbon with low sulfur content was made and found that the performance of the carbon was greatly improved. We also scaled-up the process to pre-production levels and we are currently able to produce 0.25 tons/year of activated carbon. We could easily double this amount by purchasing a second rotary kiln. More importantly, we are working with MeadWestvaco on a Joint Development Agreement to scale-up the process to produce hundreds of tons of high quality, inexpensive carbon per year based on our processes.

  15. Actinide, Activation Product and Fission Product Decay Data for Reactor-based Applications

    SciTech Connect

    Perry, R.J.; Dean, C.J.; Nichols, A.L.

    2014-06-15

    The UK Activation Product Decay Data Library was first released in September 1977 as UK-PADD1, to be followed by regular improvements on an almost yearly basis up to the assembly of UKPADD6.12 in March 2013. Similarly, the UK Heavy Element and Actinide Decay Data Library followed in December 1981 as UKHEDD1, with the implementation of various modifications leading to UKHEDD2.6, February 2008. Both the data content and evaluation procedures are defined, and the most recent evaluations are described in terms of specific radionuclides and the resulting consistency of their recommended decay-data files. New versions of the UKPADD and UKHEDD libraries are regularly submitted to the NEA Data Bank for possible inclusion in the JEFF library.

  16. Microbial Community Dynamics and Activity Link to Indigo Production from Indole in Bioaugmented Activated Sludge Systems

    PubMed Central

    Deng, Jie; Deng, Ye; Van Nostrand, Joy D.; Wu, Liyou; He, Zhili; Qin, Yujia; Zhou, Jiti; Zhou, Jizhong

    2015-01-01

    Biosynthesis of the popular dyestuff indigo from indole has been comprehensively studied using pure cultures, but less has been done to characterize the indigo production by microbial communities. In our previous studies, a wild strain Comamonas sp. MQ was isolated from activated sludge and the recombinant Escherichia coli nagAc carrying the naphthalene dioxygenase gene (nag) from strain MQ was constructed, both of which were capable of producing indigo from indole. Herein, three activated sludge systems, G1 (non-augmented control), G2 (augmented with Comamonas sp. MQ), and G3 (augmented with recombinant E. coli nagAc), were constructed to investigate indigo production. After 132-day operation, G3 produced the highest yields of indigo (99.5 ± 3.0 mg/l), followed by G2 (27.3 ± 1.3 mg/l) and G1 (19.2 ± 1.2 mg/l). The microbial community dynamics and activities associated with indigo production were analyzed by Illumina Miseq sequencing of 16S rRNA gene amplicons. The inoculated strain MQ survived for at least 30 days, whereas E. coli nagAc was undetectable shortly after inoculation. Quantitative real-time PCR analysis suggested the abundance of naphthalene dioxygenase gene (nagAc) from both inoculated strains was strongly correlated with indigo yields in early stages (0–30 days) (P < 0.001) but not in later stages (30–132 days) (P > 0.10) of operation. Based on detrended correspondence analysis (DCA) and dissimilarity test results, the communities underwent a noticeable shift during the operation. Among the four major genera (> 1% on average), the commonly reported indigo-producing populations Comamonas and Pseudomonas showed no positive relationship with indigo yields (P > 0.05) based on Pearson correlation test, while Alcaligenes and Aquamicrobium, rarely reported for indigo production, were positively correlated with indigo yields (P < 0.05). This study should provide new insights into our understanding of indigo bio-production by microbial communities

  17. Lexical Activation in Bilinguals' Speech Production Is Dynamic: How Language Ambiguous Words Can Affect Cross-Language Activation

    ERIC Educational Resources Information Center

    Hermans, Daan; Ormel, E.; van Besselaar, Ria; van Hell, Janet

    2011-01-01

    Is the bilingual language production system a dynamic system that can operate in different language activation states? Three experiments investigated to what extent cross-language phonological co-activation effects in language production are sensitive to the composition of the stimulus list. L1 Dutch-L2 English bilinguals decided whether or not a…

  18. 78 FR 42930 - Foreign-Trade Zone (FTZ) 114-Peoria, Illinois; Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-18

    ... Production Activity, Easton-Bell Sports, Inc. (Sports Equipment), Rantoul, Illinois Easton-Bell Sports, Inc. (Easton-Bell Sports) submitted a notification of proposed production activity to the FTZ Board for its... FTZ Board. Production under FTZ procedures could exempt Easton-Bell Sports from customs duty...

  19. A Study on Situated Cognition: Product Dissection's Effect on Redesign Activities

    ERIC Educational Resources Information Center

    Grantham, Katie; Okudan Kremer, Gül E.; Simpson, Timothy W.; Ashour, Omar

    2013-01-01

    Situated cognition theory describes the context of a learning activity's effect on learner's cognition. In this paper, we use situated cognition theory to examine the effect of product dissection on product redesign activities. Two specific research questions are addressed: 1) Does situated cognition, in the form of product dissection, improve…

  20. 15 CFR 400.37 - Procedure for notification of proposed production activity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... production activity. 400.37 Section 400.37 Commerce and Foreign Trade Regulations Relating to Commerce and... of proposed production activity. (a) Submission of notification. A notification for production... Secretary and to CBP (as well as to the grantee of the zone, if the grantee is not the party making...

  1. 15 CFR 400.37 - Procedure for notification of proposed production activity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... production activity. 400.37 Section 400.37 Commerce and Foreign Trade Regulations Relating to Commerce and... of proposed production activity. (a) Submission of notification. A notification for production... Secretary and to CBP (as well as to the grantee of the zone, if the grantee is not the party making...

  2. Production of polyhydroxyalcanoates (PHAs) using milk whey and dairy wastewater activated sludge production of bioplastics using dairy residues.

    PubMed

    Bosco, Francesca; Chiampo, Fulvia

    2010-04-01

    The production of polyhydroxyalcanoates (PHAs), which are biodegradable plastics, was studied using milk whey and dairy wastewater activated sludge to define a suitable C/N ratio, the pre-treatments required to reduce the protein content, and the effect of pH correction. The results show good production of PHAs at a C/N=50 and without pH correction. The use of dairy wastewater activated sludge has the advantage of not requiring aseptic conditions. PMID:20226388

  3. High Activity catalysts for Polyols Production From C-6 Sugars

    SciTech Connect

    Todd Werpy; Alan Zacher; John Frye; Keith Peterson; Gary Neuenschwander; Eric Alderson; Daniel Muzatko; Jim White

    2003-05-06

    Over the course of this project, many significant discoveries have been made in the process for the conversion of sorbitol to value added products. The object was developing a process for the production of propylene glycol (PG), ethylene glycol (EG), and glycerol from sorbitol.

  4. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis

    PubMed Central

    Crane, Erika A.

    2016-01-01

    Abstract Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody–drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products. PMID:26833854

  5. Capturing Biological Activity in Natural Product Fragments by Chemical Synthesis.

    PubMed

    Crane, Erika A; Gademann, Karl

    2016-03-14

    Natural products have had an immense influence on science and have directly led to the introduction of many drugs. Organic chemistry, and its unique ability to tailor natural products through synthesis, provides an extraordinary approach to unlock the full potential of natural products. In this Review, an approach based on natural product derived fragments is presented that can successfully address some of the current challenges in drug discovery. These fragments often display significantly reduced molecular weights, reduced structural complexity, a reduced number of synthetic steps, while retaining or even improving key biological parameters such as potency or selectivity. Examples from various stages of the drug development process up to the clinic are presented. In addition, this process can be leveraged by recent developments such as genome mining, antibody-drug conjugates, and computational approaches. All these concepts have the potential to identify the next generation of drug candidates inspired by natural products.

  6. 78 FR 49254 - Foreign-Trade Zone 158-Vicksburg/Jackson, Mississippi; Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... Production Activity; Extension of Production Authority; H.M. Richards, Inc. (Upholstered Furniture); Guntown... comment (78 FR 20889-20890, 4-8-2013). The FTZ Board has determined that no further review of the...

  7. 77 FR 22602 - Information Collection Activities: Well Control and Production Safety Training, Submitted for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-16

    ... paperwork requirements in the regulations under Subpart O, ``Well Control and Production Safety Training... Bureau of Safety and Environmental Enforcement (BSEE) Information Collection Activities: Well Control and Production Safety Training, Submitted for Office of Management and Budget (OMB) Review; Comment...

  8. 78 FR 68027 - Notification of Proposed Production Activity, Revlon Consumer Products Corporation, Subzone 93G...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... Corporation, Subzone 93G, (Cosmetics and Personal Care Products), Oxford, North Carolina Revlon Consumer... currently has authority to produce certain cosmetics and personal care products under FTZ procedures using... sulfate, cosmetic wax, oligopeptide, cetearyl alcohol polysorbate, calcium aluminum...

  9. Alcohol production from Jerusalem artichoke using yeasts with inulinase activity

    SciTech Connect

    Guiraud, J.P.; Daurelles, J.; Galzy, P.

    1981-07-01

    The purpose of this article is to show that yeasts with inulinase activity can be used to produce ethanol from the Jerusalem artichoke (Helianthus tuberosus L.). The results show that a fermentable extract can be easily obtained from the Jerusalem artichoke even under cold conditions. Yeasts with inulinase activity can be used to produce ethanol with good profitability. 19 refs.

  10. Effects of Age, Animacy and Activation Order on Sentence Production

    ERIC Educational Resources Information Center

    Altmann, Lori J. P.; Kemper, Susan

    2006-01-01

    The current study examines whether young and older adults have similar preferences for animate-subject and active sentences, and for using the order of activation of a verb's arguments to determine sentence structure. Ninety-six participants produced sentences in response to three-word stimuli that included a verb and two nouns differing in…

  11. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils.

    PubMed Central

    Camussi, G; Aglietta, M; Coda, R; Bussolino, F; Piacibello, W; Tetta, C

    1981-01-01

    The origin of platelet activating factor (PAF) from human leucocytes was investigated. Purified monocytes release PAF passively at pH 10.6, when challenged with Ionophore A 23187 or under phagocytic stimuli. Pure preparations of polymorphonuclear neutrophils liberate PAF passively, when challenged with C5a, neutrophil cationic proteins (CP), their carboxypeptidase B derived products (C5a des Arg, CP des Arg) or under phagocytic stimuli. Basophil rich buffy coat cells release PAF when challenged with C5a, CP, anti-IgE (in low amount) or Synacthen concomitantly with basophil degranulation and histamine release. Electron microscopy studies, carried out on Synacthen-stimulated basophil rich buffy coat, provide morphological evidence for platelet-basophil interaction. In conclusion our data demonstrate that PAF can be released from different leucocyte populations. However, the stimuli able to trigger such release appear to have some specificity for the cell target. Images Figure 5 PMID:6161885

  12. Complement activation in the context of stem cells and tissue repair

    PubMed Central

    Schraufstatter, Ingrid U; Khaldoyanidi, Sophia K; DiScipio, Richard G

    2015-01-01

    The complement pathway is best known for its role in immune surveillance and inflammation. However, its ability of opsonizing and removing not only pathogens, but also necrotic and apoptotic cells, is a phylogenetically ancient means of initiating tissue repair. The means and mechanisms of complement-mediated tissue repair are discussed in this review. There is increasing evidence that complement activation contributes to tissue repair at several levels. These range from the chemo-attraction of stem and progenitor cells to areas of complement activation, to increased survival of various cell types in the presence of split products of complement, and to the production of trophic factors by cells activated by the anaphylatoxins C3a and C5a. This repair aspect of complement biology has not found sufficient appreciation until recently. The following will examine this aspect of complement biology with an emphasis on the anaphylatoxins C3a and C5a. PMID:26435769

  13. Performance improvement: an active life cycle product management

    NASA Astrophysics Data System (ADS)

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

    2010-03-01

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

  14. The macrophage chemotactic activity of Edwardsiella tarda extracellular products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The chemoattractant capabilities of Edwardsiella tarda extracellular products (ECP) were investigated from two isolates, the virulent FL6-60 parent and less virulent RET-04 mutant. Chemotaxis and chemokinesis were assayed in vitro using blind well chambers with peritoneal macrophages obtained from ...

  15. Production of microbial glycolipid biosurfactants and their antimicrobial activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Microbial glycolipids produced by bacteria or yeast as secondary metabolites, such as sophorolipids (SLs), rhamnolipids (RLs) and mannosylerythritol lipids (MELs) are “green” biosurfactants desirable in a bioeconomy. High cost of production is a major hurdle toward widespread commercial use of bios...

  16. Activities and Products at IVS combination center at BKG

    NASA Astrophysics Data System (ADS)

    Bachmann, S.; Lösler, M.

    2013-08-01

    The IVS combination center is primarily responsible to provide rapid EOP products based on observation campaigns twice a week and a long-term EOP series which is updated four times a year. Besides EOP products, methods and analysis of combined station coordinates and source positions are evolving and new products are developed in order to expand the range of combined VLBI products. Within the last year the combination center continuously worked on several improvements and refinements of the combination procedure: outlier test have been improved, the detection of unsuitable sessions in order to improve the stability of the results, the modeling of station coordinates of the reference frame generation and the data presentation on the combination centers website. Besides the routine combination of 24h VLBI sessions, several other projects have been developed, e.g. the preparation of the latest VLBI reference frame (VTRF) including the calculation of station height variations and baseline lengths generation derived by the combination of station coordinates. The combination center is furthermore intensely working on the combination of source coordinates and on providing user friendly online analysis tools on the combination centers website in order to meet the user requirements.

  17. 78 FR 14963 - Foreign-Trade Zone 163-Ponce, Puerto Rico; Authorization of Production Activity; Zimmer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-08

    ... Foreign-Trade Zones Board Foreign-Trade Zone 163--Ponce, Puerto Rico; Authorization of Production Activity; Zimmer Manufacturing BV (Medical Devices); Ponce, Puerto Rico On November 1, 2012, CODEZOL, C.D., grantee of FTZ 163, submitted a notification of proposed production activity to the Foreign-Trade Zones...

  18. 78 FR 52759 - Foreign-Trade Zone 265-Conroe, Texas: Authorization of Production Activity; Bauer Manufacturing...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-26

    ... Foreign-Trade Zones Board Foreign-Trade Zone 265--Conroe, Texas: Authorization of Production Activity; Bauer Manufacturing Inc. (Foundation Casings and Tools/Accessories for Pile Drivers and Boring Machinery... of proposed production activity to the Foreign-Trade Zones (FTZ) Board on behalf of...

  19. An Active Learning Exercise for Product Design from an Operations Perspective

    ERIC Educational Resources Information Center

    Hill, Stephen; Baker, Elizabeth

    2016-01-01

    Product design is a topic that is regularly covered in introductory operations management courses. However, a pedagogical challenge exists related to the presentation of introductory-level product design in a way that promotes active learning. The hands-on exercise presented in this article provides instructors with an activity that gives students…

  20. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  1. 21 CFR 357.810 - Active ingredients for deodorant drug products for internal use.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Active ingredients for deodorant drug products for internal use. 357.810 Section 357.810 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... HUMAN USE Deodorant Drug Products for Internal Use § 357.810 Active ingredients for deodorant...

  2. Learner Uptake and Acquisition in Three Grammar-Oriented Production Activities

    ERIC Educational Resources Information Center

    Reinders, Hayo

    2009-01-01

    This study investigates the effects of three types of production activities on uptake (operationalized as correct suppliance of the target structure during the treatment) and acquisition of negative adverbs in English. It also investigates the relationship between uptake and acquisition. The three production activities included a dictation, an…

  3. Microsomal activation of constituents of white snakeroot (Eupatorium rugosum Houtt) to form toxic products.

    PubMed

    Beier, R C; Norman, J O; Irvin, T R; Witzel, D A

    1987-04-01

    Components of white snakeroot, a plant toxic to livestock and human beings, were activated by Aroclor 1254-induced rat liver microsomes. The toxic products of microsomal activation were evaluated in murine melanoma (B16F1) cell cultures. Toxic products in white snakeroot were inactive in cell culture systems without microsomal activation. This activation system revealed that at least 2 fractions of white snakeroot were metabolically activated to cytotoxic agents. The autocatalytic inactivator of cytochrome P-450, 1-aminobenzotriazole, inhibited activation of white snakeroot constituents by rat liver microsomes. PMID:3592355

  4. 78 FR 15682 - Notification of Proposed Production Activity TTI, Inc.; Subzone 196A (Electromechanical and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-12

    ... production equipment. The components and materials sourced from abroad include: Rubber and plastic gaskets... Foreign-Trade Zones Board Notification of Proposed Production Activity TTI, Inc.; Subzone 196A (Electromechanical and Circuit Protection Devices Production/ Kitting); Fort Worth, TX TTI, Inc. (TTI), operator...

  5. 77 FR 48519 - Registration Applications for Pesticide Products Containing New Active Ingredients

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-14

    .... israelensis, Strain SUM-6218 at 100.0%. Product Type: microbial insecticide. Proposed Use: Manufacturing use..., Kalamazoo, MI 49008. Active Ingredient: GS-U-ACTX-Hv1a-SEQ2 at 30.00%. Product Type: Insecticide. Proposed...%. Product Type: Insecticide. Proposed Uses: For use on ornamental plants, turf, vegetables, fruits,...

  6. BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF THE GENUS CALLICARPA.

    PubMed

    Jones, William P; Kinghorn, A Douglas

    2008-06-01

    About 20 species from Callicarpa have reported ethnobotanical and ethnomedical uses, and several members of this genus are well known in the traditional medical systems of China and South Asia. Ethnomedical reports indicate their use in the treatment of hepatitis, rheumatism, fever, headache, indigestion, and other ailments. Several species of Callicarpa have been reported to be used against cancer (e.g., Callicarpa americana root to treat skin cancer and Callicarpa rubella bark to treat tumors of the large intestine). Extracts from about 14 species in this genus have been evaluated for biological activity, including antibacterial, antifungal, anti-insect growth, cytotoxic, and phytotoxic activities. In addition to amino acids, benzenoids, simple carbohydrates, and lipids, numerous diterpenes, flavonoids, phenylpropanoids, phytosterols, sesquiterpenes, and triterpenes have been detected in or isolated from the genus Callicarpa. The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species (and C. japonica) were identified as contributing to the mosquito bite-deterrent activity that was first indicated by folkloric usage. Recent bioassay-guided investigations of C. americana extracts have resulted in the isolation of several active compounds, mainly of the clerodane diterpene structural type. PMID:19830264

  7. BIOLOGICALLY ACTIVE NATURAL PRODUCTS OF THE GENUS CALLICARPA⊥

    PubMed Central

    JONES, WILLIAM P.; KINGHORN, A. DOUGLAS

    2009-01-01

    About 20 species from Callicarpa have reported ethnobotanical and ethnomedical uses, and several members of this genus are well known in the traditional medical systems of China and South Asia. Ethnomedical reports indicate their use in the treatment of hepatitis, rheumatism, fever, headache, indigestion, and other ailments. Several species of Callicarpa have been reported to be used against cancer (e.g., Callicarpa americana root to treat skin cancer and Callicarpa rubella bark to treat tumors of the large intestine). Extracts from about 14 species in this genus have been evaluated for biological activity, including antibacterial, antifungal, anti-insect growth, cytotoxic, and phytotoxic activities. In addition to amino acids, benzenoids, simple carbohydrates, and lipids, numerous diterpenes, flavonoids, phenylpropanoids, phytosterols, sesquiterpenes, and triterpenes have been detected in or isolated from the genus Callicarpa. The essential oils of Callicarpa americana have recently been reported to have antialgal and phytotoxic activities, and several isolates from this species (and C. japonica) were identified as contributing to the mosquito bite-deterrent activity that was first indicated by folkloric usage. Recent bioassay-guided investigations of C. americana extracts have resulted in the isolation of several active compounds, mainly of the clerodane diterpene structural type. PMID:19830264

  8. Xenicane Natural Products: Biological Activity and Total Synthesis.

    PubMed

    Betschart, Leo; Altmann, Karl-Heinz

    2015-01-01

    The xenicanes are a large class of mostly bicyclic marine diterpenoids featuring a cyclononane ring as a common structural denominator. After a brief introduction into the characteristic structural features of xenicanes and some biogenetic considerations, the major focus of this review will be on the various biological activities that have been reported for xenicanes and on efforts towards the total synthesis of these structures. Several xenicanes have been shown to be potent antiproliferative agents in vitro, but activities have also been reported in relation to inflammatory processes. However, so far, data on the possible in vivo activity of xenicanes are lacking. The major challenge in the total synthesis of xenicanes is the construction of the nine-membered ring. Different strategies have been pursued to establish this crucial substructure, including Grob fragmentation, ring-closing olefin metathesis, or Suzuki cross coupling as the enabling transformations. PMID:26429717

  9. Characterization of surface active materials derived from farm products

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Surface active materials obtained by chemical modification of plant protein isolates (lupin, barley, oat), corn starches (dextrin, normal, high amylose, and waxy) and soybean oil (soybean oil based polysoaps, SOPS) were investigated for their surface and interfacial properties using axisymmetric dro...

  10. 78 FR 30270 - Foreign-Trade Zone (FTZ) 61-San Juan, Puerto Rico, Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-22

    ...-counter pharmaceutical products, including: Anti-cancer; anti-diabetic and immunosuppressive medicaments... Production Activity, Janssen Ortho LLC (Pharmaceutical Products Production), Gurabo, Puerto Rico The Puerto Rico Trade and Export Company, grantee of FTZ 61, submitted a notification of proposed...

  11. Lipoteichoic Acid-Induced Nitric Oxide Production Depends on the Activation of Platelet-Activating Factor Receptor and Jak21

    PubMed Central

    Han, Seung Hyun; Kim, Je Hak; Seo, Ho Seong; Martin, Michael H.; Chung, Gook-Hyun; Michalek, Suzanne M.; Nahm, Moon H.

    2006-01-01

    NO production by macrophages in response to lipoteichoic acid (LTA) and a synthetic lipopeptide (Pam3CSK4) was investigated. LTA and Pam3CSK4 induced the production of both TNF-α and NO. Inhibitors of platelet-activating factor receptor (PAFR) blocked LTA- or Pam3CSK4-induced production of NO but not TNF-α. Jak2 tyrosine kinase blocked LTA-induced production of NO but not TNF-α. PAFR inhibition blocked phosphorylation of Jak2 and STAT1, a key factor for expressing inducible NO synthase. In addition, LTA did not induce IFN-β expression, and p38 mitogen-activated protein serine kinase was necessary for LTA-induced NO production but not for TNF-α production. These findings suggest that Gram-positive bacteria induce NO production using a PAFR signaling pathway to activate STAT1 via Jak2. This PAFR/Jak2/STAT1 signaling pathway resembles the IFN-β, type I IFNR/Jak/STAT1 pathway described for LPS. Consequently, Gram-positive and Gram-negative bacteria appear to have different but analogous mechanisms for NO production. PMID:16365452

  12. Antioxidant activity of a Mediterranean food product: "fig syrup".

    PubMed

    Puoci, Francesco; Iemma, Francesca; Spizzirri, Umile G; Restuccia, Donatella; Pezzi, Vincenzo; Sirianni, Rosa; Manganaro, Lillo; Curcio, Manuela; Parisi, Ortensia I; Cirillo, Giuseppe; Picci, Nevio

    2011-03-01

    In this work, the efficacy of fig syrup, a Mediterranean fig derivative, as a nutraceutical supplement, was demonstrated. Fig syrup is a fruit concentrate used as a common ingredient in the preparation of typical foods, and particularly in cakes. In vitro assays were performed to determine the amount of nutraceutical ingredients, such as phenolic compounds (3.92 mg equivalent of gallic acid per g) and flavonoids (0.35 mg equivalent of catechin per g), while HPLC analyses provided specific information about the composition of antioxidants in the syrup. Furthermore, total antioxidant activity, scavenging properties against DPPH and peroxyl radicals, and the anticholinesterase activity, clearly showed the efficacy of the syrup in preventing damage induced by free radicals and, thus, the applicability of this food derivative as a nutraceutical supplement.

  13. Production of hydroxyl radical by redox active flavonoids

    SciTech Connect

    Kalyanaraman, B.; Hodnick, W.F.; Pardini, R.S.

    1986-05-01

    The authors have previously shown that flavonoids autoxidize and generate superoxide (O/sub 2//sup -/) and hydrogen peroxide (H/sub 2/O/sub 2/), suggesting that hydroxyl radical (OH) could be formed via the metal-ion catalyzed Haber-Weiss reaction. In the presence of ethylenediamine tetraacetic acid (EDTA) and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO), myricetin, quercetagetin and quercetin gave an ESR signal for the DMPO-OH spin adduct, and the DMPO-Eto adduct in the presence of excess ethanol, indicating the production of free OH. The addition of FeCl/sub 3/ to the reaction mixture resulted in a dramatic increase in the DMPO-OH signal. Without chelator (EDTA) there was no signal and the presence of diethylenetriamine-pentaacetic acid (DETAPAC) greatly diminished the signal. The presence of superoxide dismutase (SOD) had no effect on the signal while catalase completely abrogated the signal. The addition of Fe (III)-EDTA to flavonoid solutions under anaerobic conditions produced time dependent auxochromic shifts in their absorption spectra and resulted in the reduction of Fe (III) to Fe (II). These data suggest that the flavonoids autoxidize to produce O/sub 2//sup -/ and H/sub 2/O/sub 2/ by dismutation and in the presence of Fe (III)-EDTA the flavonoid can directly reduce the Fe (III) to Fe (II) resulting in the production of OH through Fenton chemistry.

  14. Soft gamma-ray production in active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Sikora, M.; Zbyszewska, M.

    1985-02-01

    Recent studies by Lightman (1982), Svensson (1984), an others on the pair-equilibrium states of mildly relativistic thermal plasma, including magnetic fields and optical sources are considered. Resulting constraints on luminosities and proton densities together with observational data permit the selection of an accretion scenario in which a high-energy spectrum, similar to that of NGC 4151, is produced. It is shown that soft gamma-ray production via thermal bremsstrahlung can occur in the central region of the two-temperature, geometrically thick part of the disc. On the other hand, the power-law X-ray spectrum is expected to be generated in the intermediate region due to Comptonization of optical photons coming from an outer, geometrically thin part of the disc. Implications for the relation between quasars and Seyfert galaxies are discussed.

  15. 76 FR 81508 - Communications and Activities Related to Off-Label Uses of Marketed Products and Use of Products...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-12-28

    ... investigational products. For example, in the Federal Register of May 22, 1987 (52 FR 19466), the Agency published....'' (52 FR 19466 at 19475). II. FDA Is Seeking Comments on Communications and Activities Related to Off... ``commercialization'' of the drug (see 74 FR 40872 at 40890, August 13, 2009; 52 FR 19466 at 19467). What...

  16. Design Strategies for Redox Active Metalloenzymes: Applications in Hydrogen Production.

    PubMed

    Alcala-Torano, R; Sommer, D J; Bahrami Dizicheh, Z; Ghirlanda, G

    2016-01-01

    The last decades have seen an increased interest in finding alternative means to produce renewable fuels in order to satisfy the growing energy demands and to minimize environmental impact. Nature can serve as an inspiration for development of these methodologies, as enzymes are able to carry out a wide variety of redox processes at high efficiency, employing a wide array of earth-abundant transition metals to do so. While it is well recognized that the protein environment plays an important role in tuning the properties of the different metal centers, the structure/function relationships between amino acids and catalytic centers are not well resolved. One specific approach to study the role of proteins in both electron and proton transfer is the biomimetic design of redox active peptides, binding organometallic clusters in well-understood protein environments. Here we discuss different strategies for the design of peptides incorporating redox active FeS clusters, [FeFe]-hydrogenase organometallic mimics, and porphyrin centers into different peptide and protein environments in order to understand natural redox enzymes. PMID:27586342

  17. Production of the Ramoplanin Activity Analogue by Double Gene Inactivation

    PubMed Central

    Han, Jungang; Chen, Junsheng; Shao, Lei; Zhang, Junliang; Dong, Xiaojing; Liu, Pengyu; Chen, Daijie

    2016-01-01

    Glycopeptides such as vancomycin and telavancin are essential for treating infections caused by Gram-positive bacteria. But the dwindling availability of new antibiotics and the emergence of resistant bacteria are making effective antibiotic treatment increasingly difficult. Ramoplanin, an inhibitor of bacterial cell wall biosynthesis, is a highly effective antibiotic against a wide range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus, vancomycin-intermediate resistant Clostridium difficile and vancomycin-resistant Enterococcus sp. Here, two tailoring enzyme genes in the biosynthesis of ramoplanin were deleted by double in-frame gene knockouts to produce new ramoplanin derivatives. The deschlororamoplanin A2 aglycone was purified and its structure was identified with LC-MS/MS. Deschlororamoplanin A2 aglycone and ramoplanin aglycone showed similar activity to ramoplanin A2. The results showed that α-1,2-dimannosyl disaccharide at Hpg11 and chlorination at Chp17 in the ramoplanin structure are not essential for its antimicrobial activity. This work provides new precursor compounds for the semisynthetic modification of ramoplanin. PMID:27149627

  18. Cluster Wideband Data Products in the Cluster Active Archive

    NASA Astrophysics Data System (ADS)

    Pickett, J. S.; Seeberger, J. M.; Christopher, I. W.; Santolík, O.; Sigsbee, K. M.

    Cluster Wideband Data (WBD) plasma wave receivers are mounted on all four of the Cluster spacecraft providing approximately 4-7% orbit coverage since mission operations began in February 2001. Data obtained by the WBD instruments are downlinked in real time to various Deep Space Network (DSN) and Panska Ves (PV) ground stations. The strengths of the WBD instruments lie in their high time and frequency resolution data, which allow analysis of the wave fine structure in order to more accurately investigate the linear and nonlinear nature of the waves, and in their use in carrying out Very Long Baseline Interferometry (VLBI) investigations to locate and characterize remote wave sources and their characteristics. The WBD team has already archived at the Cluster Active Archive (CAA) the documentation, software and data plots required for carrying on an independent scientific investigation. A document on interpretation issues has also been archived to help ensure that signals which are not naturally in the plasma are not misinterpreted. The WBD team also plans to archive digital, calibrated data files for the entire mission in cdf format at NASA's CDAWeb and submit these files for conversion to the Cluster standard cef format and archiving at the CAA. In order to ensure that the calibration of the WBD data has been done properly, WBD has taken part in Cluster cross calibration activities with the other wave instruments with regard to wave amplitudes in the time and frequency domains and with the PEACE instruments with regard to low density measurements.

  19. Functional and Behavioral Product Information Representation and Consistency Validation for Collaboration in Product Lifecycle Activities

    ERIC Educational Resources Information Center

    Baysal, Mehmet Murat

    2012-01-01

    Information models that represent the function, assembly and behavior of artifacts are critical in the conceptual development of a product and its evaluation. Much research has been conducted in this area; however, existing models do not relate function, behavior and structure in a comprehensive and consistent way. In this work, NIST's Core…

  20. Plan now to make your retirement active, productive.

    PubMed

    Schlepp, S

    1989-12-01

    In his book Planning to the Years Ahead, Lester I. Tenney, PhD, professor emeritus at Arizona State University, Tempe, links Abraham Maslow's hierarchy of needs to retirement planning. According to Maslow, economic and security needs can be achieved through a family environment (eg, food clothing, shelter), and social acceptance, self-worth, and self-satisfaction can be achieved from social interaction, work, or leisure activities. After the basic needs of food, clothing, and shelter have been achieved, people are able to move to the next level of achieving safety and security. The level of dependency that people have on satisfying these needs through work will determine how well they are at adapting to retirement. The more people depend on work alone, the harder will be the adjustment; people who are less dependent on work will find retirement easier to accept.

  1. Lignite slime as activator in production of oxidized asphalts

    SciTech Connect

    Gureev, A.A.; Gorlov, E.G.; Leont'eva, O.B.; Zotova, O.V.

    1988-03-01

    The possibility of activation of the oxidation of straight-run resids to asphalts by the addition of lignite slimes obtained in the liquefaction of coals of the Kansk-Achinsk basin was studied on the basis of a hypothesis formulated with due regard for the principles of physicochemical mechanics of petroleum disperse systems. A reduction of the air bubble size in the oxidizing vessel should lead to an increase in the total surface of oxidation and hence to a shortening of the time required for oxidation of the feed. A straight-run vacuum resid from mixed West Siberian and Ukhta crudes was used. The resid was oxidized with and without the addition of slime.

  2. Key role for transketolase activity in erythritol production by Trichosporonoides megachiliensis SN-G42.

    PubMed

    Sawada, Katsuhiko; Taki, Arihiro; Yamakawa, Takashi; Seki, Minoru

    2009-11-01

    Erythritol is an important sugar alcohol industrially produced only by fermentation. The highly osmophilic yeast-like fungi, Trichosporonoides megachiliensis SN-G42, enables commercial production of erythritol with a high conversion from glucose to erythritol of more than 47%. However, the microbial production pathway of erythritol remains unclear. In the present study, the activities of enzymes in the pentose phosphate pathway of Trichosporonoides megachiliensis SN-G42 used for industrial erythritol production were measured under various culture conditions to examine the production mechanism and the key-enzymes. As a result, the various enzyme activities of this organism are revealed in the pentose phosphate pathway, i.e., those of hexokinase, glucose-6-phosphate dehydrogenase, gluconate dehydrogenase, transketolase, transaldolase, and erythrose reductase. In the cultures in which erythritol was produced after completion of cell growth, the enzyme activities of the pentose phosphate pathway were higher than those of the TCA cycle. In particular, transketolase activity was correlated with erythritol productivity under various production cultures with different agitation speeds and thiamine concentrations. These results suggest that erythritol may be produced mainly through the pentose phosphate pathway. In addition, the high activity of transketolase is required to produce abundant intermediates, which results in high erythritol productivity. As such, transketolase appears to be a key-enzyme for erythritol production in the organism studied.

  3. Identification of biotransformation products of citalopram formed in activated sludge.

    PubMed

    Beretsou, Vasiliki G; Psoma, Aikaterini K; Gago-Ferrero, Pablo; Aalizadeh, Reza; Fenner, Kathrin; Thomaidis, Nikolaos S

    2016-10-15

    Citalopram (CTR) is a worldwide highly consumed antidepressant which has demonstrated incomplete removal by conventional wastewater treatment. Despite its global ubiquitous presence in different environmental compartments, little is known about its behaviour and transformation processes during wastewater treatment. The present study aims to expand the knowledge on fate and transformation of CTR during the biological treatment process. For this purpose, batch reactors were set up to assess biotic, abiotic and sorption losses of this compound. One of the main objectives of the study was the identification of the formed transformation products (TPs) by applying suspect and non-target strategies based on liquid chromatography quadrupole-time-of-flight mass spectrometry (LC-QTOF-MS). The complementary use of reversed phase liquid chromatography (RPLC) and hydrophilic interaction liquid chromatography (HILIC) for the identification of polar TPs, and the application of in-house developed quantitative structure-retention relationship (QSRR) prediction models, in addition to the comprehensive evaluation of the obtained MS/MS spectra, provided valuable information to support identification. In total, fourteen TPs were detected and thirteen of them were tentatively identified. Four compounds were confirmed (N-desmethylCTR, CTR amide, CTR carboxylic acid and 3-oxo-CTR) through the purchase of the corresponding reference standard. Probable structures based on diagnostic evidence were proposed for the additional nine TPs. Eleven TPs are reported for the first time. A transformation pathway for the biotransformation of CTR was proposed. The presence of the identified TPs was assessed in real wastewater samples through retrospective analysis, resulting in the detection of five compounds. Finally, the potential ecotoxicological risk posed by CTR and its TPs to different trophic levels of aquatic organisms was evaluated by means of risk quotients. PMID:27459150

  4. Influence of External Nitrogen on Nitrogenase Enzyme Activity and Auxin Production in Herbaspirillum seropedicae (Z78)

    PubMed Central

    Yin, Tan Tzy; Pin, Ui Li; Ghazali, Amir Hamzah Ahmad

    2015-01-01

    The production of nitrogenase enzyme and auxins by free living diazotrophs has the potential to influence the growth of host plants. In this study, diazotrophs were grown in the presence of various concentrations of nitogen (N) to determine the optimal concentration of N for microbial growth stimulation, promotion of gaseous N (N2) fixation, and phytohormone production. Therefore, we investigate whether different levels of N supplied to Herbaspirillum seropedicae (Z78) have significant effects on nitrogenase activity and auxin production. The highest nitrogenase activity and the lowest auxin production of H. seropedicae (Z78) were both recorded at 0 gL−1 of NH4Cl. Higher levels of external N caused a significant decrease in the nitrogenase activity and an increased production of auxins. In a subsequent test, two different inoculum sizes of Z78 (106 and 1012 cfu/ml) were used to study the effect of different percentages of acetylene on nitrogenase activity of the inoculum via the acetylene reduction assay (ARA). The results showed that the optimal amount of acetylene required for nitrogenase enzyme activity was 5% for the 106 cfu/ml inoculum, whereas the higher inoculum size (1012 cfu/ml) required at least 10% of acetylene for optimal nitrogenase activity. These findings provide a clearer understanding of the effects of N levels on diazotrophic nitrogenase activity and auxin production, which are important factors influencing plant growth. PMID:26868594

  5. Lipoprotein lipase activity is required for cardiac lipid droplet production.

    PubMed

    Trent, Chad M; Yu, Shuiqing; Hu, Yunying; Skoller, Nathan; Huggins, Lesley A; Homma, Shunichi; Goldberg, Ira J

    2014-04-01

    The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice.

  6. Production of diagnostic pigment by phenoloxidase activity of cryptococcus neoformans.

    PubMed

    Shaw, C E; Kapica, L

    1972-11-01

    Cryptococcus neoformans produces brown pigmented colonies when grown on agar media made from an extract of potatoes and carrots, broad beans (Vicia faba), or Guizotia abyssinica seeds. Since other yeasts do not produce the pigment, these media are useful as differential isolation media for C. neoformans. Similar specific pigment was produced by C. neoformans on chemically defined agar media which contained six different substrates of phenoloxidase (o-diphenol: oxygen oxidoreductase EC 1.10.3.1) an enzyme which catalyses the oxidation of o-diphenols to melanin. Substrates were incorporated singly into the media and included L-3, 4-dihydroxyphenylalanine (L-DOPA), chlorogenic acid, protocatechuic acid, catechol, norepinephrine, and 3-hydroxytyramine hydrochloride (dopamine). No pigment was produced on media without substrate. Phenoloxidase activity in (NH(4))(2)SO(4) precipitates of C. neoformans cell-free extract was assayed by measuring increases in absorbance at 480 nm produced in solutions of L-DOPA. This reaction showed oxygen uptake and was effectively inhibited by copper chelators, but not by catalase. The enzyme also oxidized the five other substrates which induced pigment formation. Electron micrographs of cells incubated in L-DOPA showed deposition of the pigment in the cell wall. PMID:4118328

  7. Lipoprotein lipase activity is required for cardiac lipid droplet production.

    PubMed

    Trent, Chad M; Yu, Shuiqing; Hu, Yunying; Skoller, Nathan; Huggins, Lesley A; Homma, Shunichi; Goldberg, Ira J

    2014-04-01

    The rodent heart accumulates TGs and lipid droplets during fasting. The sources of heart lipids could be either FFAs liberated from adipose tissue or FAs from lipoprotein-associated TGs via the action of lipoprotein lipase (LpL). Because circulating levels of FFAs increase during fasting, it has been assumed that albumin transported FFAs are the source of lipids within heart lipid droplets. We studied mice with three genetic mutations: peroxisomal proliferator-activated receptor α deficiency, cluster of differentiation 36 (CD36) deficiency, and heart-specific LpL deletion. All three genetically altered groups of mice had defective accumulation of lipid droplet TGs. Moreover, hearts from mice treated with poloxamer 407, an inhibitor of lipoprotein TG lipolysis, also failed to accumulate TGs, despite increased uptake of FFAs. TG storage did not impair maximal cardiac function as measured by stress echocardiography. Thus, LpL hydrolysis of circulating lipoproteins is required for the accumulation of lipids in the heart of fasting mice. PMID:24493834

  8. Production of activated carbon from coconut shell char in a fluidized bed reactor

    SciTech Connect

    Sai, P.M.S.; Ahmed, J.; Krishnaiah, K.

    1997-09-01

    Activated carbon is produced from coconut shell char using steam or carbon dioxide as the reacting gas in a 100 mm diameter fluidized bed reactor. The effect of process parameters such as reaction time, fluidizing velocity, particle size, static bed height, temperature of activation, fluidizing medium, and solid raw material on activation is studied. The product is characterized by determination of iodine number and BET surface area. The product obtained in the fluidized bed reactor is much superior in quality to the activated carbons produced by conventional processes. Based on the experimental observations, the optimum values of process parameters are identified.

  9. Dynamics of locomotor activity and heat production in rats after acute stress.

    PubMed

    Pertsov, S S; Alekseeva, I V; Koplik, E V; Sharanova, N E; Kirbaeva, N V; Gapparov, M M G

    2014-05-01

    The dynamics of locomotor activity and heat production were studied in rats demonstrating passive and active behavior in the open field test at different time after exposure to acute emotional stress caused by 12-h immobilization during dark hours. The most pronounced changes in behavior and heat production followed by disturbances in circadian rhythms of these parameters were detected within the first 2 days after stress. In contrast to behaviorally active rats, the most significant decrease in locomotor activity and heat production of passive animals subjected to emotional stress was observed during dark hours. Circadian rhythms of behavior and heat production in rats tended to recover on day 3 after immobilization stress. These data illustrate the specificity of metabolic and behavioral changes reflecting the shift of endogenous biological rhythms in individuals with different prognostic resistance to stress at different terms after exposure to negative emotiogenic stimuli. PMID:24906959

  10. PHARMACEUTICAL AND PERSONAL CARE PRODUCTS AS UBIQUITOUS POLLUTANTS FROM PERSONAL USE AND ACTIVITIES

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environment. In...

  11. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS AS UBIQUITOUS POLLUTANTS FROM PERSONAL USE AND ACTIVITIES

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environment. In...

  12. Reductions in Northeast Refining Activity: Potential Implications for Petroleum Product Markets

    EIA Publications

    2011-01-01

    This report is the Energy Information Administration's (EIA) initial effort to provide information and analysis on the potential impacts on petroleum product markets from reductions in Northeast petroleum refining activity.

  13. POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS: PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPs) in the environment highlights the immediate, intimate, and inseparable connection between the personal activities of individual citizens and their environ...

  14. 77 FR 26737 - Foreign-Trade Zone 235-Lakewood, NJ: Notification of Proposed Production Activity; Cosmetic...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-07

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Foreign-Trade Zone 235--Lakewood, NJ: Notification of Proposed Production Activity; Cosmetic Essence Innovations, LLC (Fragrance Bottling); Holmdel, NJ Cosmetic Essence...

  15. 78 FR 37203 - Authorization of Production Activity; Subzone 196A; TTI, Inc. (Electromechanical and Circuit...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-20

    ... comment (78 FR 15683, 03-12-2013). The FTZ Board has determined that no further review of the activity is... and Circuit Protection Devices Production/Kitting); Fort Worth, Texas On February 13, 2013, TTI,...

  16. POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS: PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT

    EPA Science Inventory

    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the personal activities of individual citizens and their environ...

  17. [The effect of physiologically active compounds on the production of ethylene and the activity of polygalacturonase inhibiting protein in fruits].

    PubMed

    Bulantseva, E A; Protsenko, M A; Toropkina, A S; Korableva, N P

    2011-01-01

    The treatment of apple and banana fruits with 2-CEFA and ethacyde induced the production of ethylene and accelerated the ripening and accumulation of ACC in apple fruits. Inhibitors AOA, AVG, and CoCl2 acted at the different steps of ethylene biosynthesis, inhibited the physiological aging process and increased storage longevity. Treatment with astaxantine and BOA delayed the pick of ethylene production by fruits. The content of PGIP was correlated with intensity of ethylene production. The infection of fruits with phytopathogenic microorganisms lowered as the result of the inhibition of pathogen PG. The dynamics of PGIP activity in fruits suggests its important role in the processes of ripening.

  18. [The effect of physiologically active compounds on the production of ethylene and the activity of polygalacturonase inhibiting protein in fruits].

    PubMed

    Bulantseva, E A; Protsenko, M A; Toropkina, A S; Korableva, N P

    2011-01-01

    The treatment of apple and banana fruits with 2-CEFA and ethacyde induced the production of ethylene and accelerated the ripening and accumulation of ACC in apple fruits. Inhibitors AOA, AVG, and CoCl2 acted at the different steps of ethylene biosynthesis, inhibited the physiological aging process and increased storage longevity. Treatment with astaxantine and BOA delayed the pick of ethylene production by fruits. The content of PGIP was correlated with intensity of ethylene production. The infection of fruits with phytopathogenic microorganisms lowered as the result of the inhibition of pathogen PG. The dynamics of PGIP activity in fruits suggests its important role in the processes of ripening. PMID:22808745

  19. Antioxidant activity, cytotoxic activity and metabolic profiling of juices obtained from saffron (Crocus sativus L.) floral by-products.

    PubMed

    Tuberoso, Carlo I G; Rosa, Antonella; Montoro, Paola; Fenu, Maurizio Antonio; Pizza, Cosimo

    2016-05-15

    Juices obtained from cold-pressed saffron (Crocus sativus L.) floral by-products were evaluated as a potential source of compounds with antioxidant and cytotoxic activities. Floral by-products were split in two batches for extraction 24 and 48h after flower harvesting, respectively. The in vitro anti-oxidant activity of these extracts was tested using the FRAP and DPPH assays, and two biological models of lipid oxidation (activity in preventing cholesterol degradation and protection against Cu(2+)-mediated degradation of the liposomal unsaturated fatty acids). The cytotoxic activity was evaluated using the MTT assay. The results show that extracts obtained 48h post-harvest contained higher levels of total polar phenols and had the highest antioxidant activity in all of the performed assays. The LC-DAD and LC-ESI-(HR)MS(n) metabolic profiles showed high levels of kaempferol derivatives and anthocyanins. This study suggests that juices from saffron floral by-products could potentially be used to develop new products for the food and health industry. PMID:26775939

  20. Antioxidant activity, cytotoxic activity and metabolic profiling of juices obtained from saffron (Crocus sativus L.) floral by-products.

    PubMed

    Tuberoso, Carlo I G; Rosa, Antonella; Montoro, Paola; Fenu, Maurizio Antonio; Pizza, Cosimo

    2016-05-15

    Juices obtained from cold-pressed saffron (Crocus sativus L.) floral by-products were evaluated as a potential source of compounds with antioxidant and cytotoxic activities. Floral by-products were split in two batches for extraction 24 and 48h after flower harvesting, respectively. The in vitro anti-oxidant activity of these extracts was tested using the FRAP and DPPH assays, and two biological models of lipid oxidation (activity in preventing cholesterol degradation and protection against Cu(2+)-mediated degradation of the liposomal unsaturated fatty acids). The cytotoxic activity was evaluated using the MTT assay. The results show that extracts obtained 48h post-harvest contained higher levels of total polar phenols and had the highest antioxidant activity in all of the performed assays. The LC-DAD and LC-ESI-(HR)MS(n) metabolic profiles showed high levels of kaempferol derivatives and anthocyanins. This study suggests that juices from saffron floral by-products could potentially be used to develop new products for the food and health industry.

  1. Potential Impacts of Reductions in Refinery Activity on Northeast Petroleum Product Markets

    EIA Publications

    2012-01-01

    Potential Impacts of Reductions in Refinery Activity on Northeast Petroleum Product Markets is an update to a previous Energy Information Administration (EIA) report, Reductions in Northeast Refining Activity: Potential Implications for Petroleum Product Markets, released in December 2011. This update analyzes possible market responses and impacts in the event Sunoco's Philadelphia refinery closes this summer, in addition to the recently idled refineries on the East Coast and in the U.S. Virgin Islands.

  2. 78 FR 68026 - Foreign-Trade Zone (FTZ) 99-Wilmington, Delaware, Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-13

    ... Section 400.38 of the FTZ Board's regulations. The facility is used for the production of a pharmaceutical... Production Activity, Noramco, Inc., (Pharmaceutical Intermediate), Wilmington, Delaware The Delaware Economic... to the requirements of the regulations of the FTZ Board (15 CFR 400.22) was received on November...

  3. 78 FR 49255 - Foreign-Trade Zone 158-Vicksburg/Jackson, Mississippi; Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-13

    ... Production Activity; Extension of Production Authority; Lane Furniture Industries, Inc. (Upholstered Furniture); Belden, Saltillo, and Verona, Mississippi On February 28, 2013, the Greater Mississippi Foreign... Foreign-Trade Zones (FTZ) Board on behalf of Lane Furniture Industries, Inc., in Belden, Saltillo,...

  4. The Chemistry of Self-Heating Food Products: An Activity for Classroom Engagement

    ERIC Educational Resources Information Center

    Oliver-Hoyo, Maria T.; Pinto, Gabriel; Llorens-Molina, Juan Antonio

    2009-01-01

    Two commercial self-heating food products have been used to apply chemical concepts such as stoichiometry, enthalpies of reactions and solutions, and heat transfer in a classroom activity. These products are the self-heating beverages sold in Europe and the Meals, Ready to Eat or MREs used primarily by the military in the United States. The main…

  5. NASA Astrophysics Education and Public Outreach Forum: Product and Activity Analysis

    NASA Astrophysics Data System (ADS)

    Ryer, Holly; Eisenhamer, B.; Knisely, L.; McCallister, D.; Smith, D. A.

    2013-01-01

    The NASA Science Education and Public Outreach Forums (SEPOFs) have been working together to conduct a detailed analysis of SMD E/PO products and activities. The goal of this effort is to characterize individual SMD E/PO products and the collection as a whole, while identifying gaps in the SMD E/PO portfolio. The Astrophysics Forum has undertaken the task of analyzing the astrophysics portfolio of formal, informal, and outreach products and programs. The astrophysics analysis team has been characterizing products based upon AAAS Project 2061 benchmarks addressed, target audience, instructional strategies used, and types of assessments included. All formal education activities that have been analyzed to date have been compiled into a populated database that includes analyzed activities from all four SEPOFs. The database will be used to inform the development of a product and resources catalog. It also will be used to begin a gap analysis for SMD products and activities. Ultimately, we hope to help end users easily find resources, we hope to identify progressions and connections between SMD E/PO resources and programming, and we hope to provide guidance to the E/PO community in developing materials that will help bridge gaps for both NASA SMD and target audiences. This poster highlights the astrophysics product analysis process, and the preliminary findings and results of product analysis to date.

  6. 78 FR 22843 - Foreign-Trade Zone 33-Pittsburgh, Pennsylvania, Authorization of Export Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-17

    ... 400), including notice in the Federal Register inviting public comment (77 FR 77016, 12-31-2012). The... Production Activity, Tsudis Chocolate Company (Chocolate Confectionery Bars), Pittsburgh, Pennsylvania On December 4, 2012, Tsudis Chocolate Company, submitted a notification of proposed export production...

  7. Technology Transfer Activities of NASA/MSFC: Enhancing the Southeast Region's Production Capabilities

    NASA Technical Reports Server (NTRS)

    Trivoli, George W.

    1998-01-01

    The researcher was charged with the task of developing a simplified model to illustrate the impact of how NASA/MSFC technology transfer activities contribute to shifting outward the Southeast region's and the nation's productive capacity. The report is a background of the impact of technological growth on the nation's production possibility frontier (ppf).

  8. Antimicrobial and antioxidant activities of lignin from residue of corn stover to ethanol production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To improve the economic viability of the biofuel production from biomass resource, a value-added lignin byproduct from this process is increasingly interested. Antioxidant and antimicrobial activities of lignin extracted from residue of corn stover to ethanol production were investigated. The lignin...

  9. 77 FR 65856 - Foreign-Trade Subzone 93G-Oxford, NC; Notification of Proposed Production Activity Revlon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-31

    ... granted subzone authority in 2006 (Board Order 1433, 71 FR 4112, 1/26/06) for the production of certain cosmetics and personal care products (hair products, fragrances, and skincare products). Revlon is now... Activity Revlon Consumer Products Corporation (Cosmetics and Personal Care Products) Revlon...

  10. Inhibition of Th2 cytokine production in T cells by monascin via PPAR-γ activation.

    PubMed

    Hsu, Wei-Hsuan; Lee, Bao-Hong; Hsu, Ya-Wen; Pan, Tzu-Ming

    2013-08-28

    Yellow pigment monascin (MS) is a secondary metabolite isolated from Monascus -fermented products and has numerous physiological activities. However, the potential use of MS for immunomodulation remains unclear. We showed that MS and the synthetic peroxisome proliferator-activated receptor (PPAR)-γ ligand rosiglitazone (RG) significantly inhibited the production of Th2 cytokines, including IL-4, IL-5, and IL-13, in PMA/ionomycin-activated mouse EL-4 T cells. Moreover, we showed that this was due to cellular PPAR-γ translocation. These results indicate that MS and RG promote PPAR-γ-DNA interactions and suggest that the regulatory effects of MS and RG on Th2 cytokine production could be abolished with PPAR-γ antagonist treatment. MS and RG also suppressed Th2 transcription factor translocation (e.g., GATA-3 and nuclear factor of activated T cells) by preventing the phosphorylation of protein kinase C and signal transducer and activator of transcription 6. PMID:23848565

  11. ImuVert activation of natural killer cytotoxicity and interferon gamma production via CD16 triggering.

    PubMed

    Cunningham-Rundles, S; Pearson, F C

    1990-01-01

    The effect and mechanism of action of ImuVert, a new biological response modifier consisting of ribosomes and natural membrane vesicles of Serratia marcescens, on endogenous natural killer (NK) cells and activated NK activity has been analyzed. The studies showed that endogenous NK activity of peripheral blood mononuclear cells (PBMC) from normal cell donors was significantly increased (P less than 0.03) against K562, U937, and Molt-4 target cells. PBMC from cord blood of newborn infants lacking NK activity were upregulated (1.5-4 fold over endogenous NK activity) by ImuVert. Other studies showed that the abnormal NK activity of PBMC from patients with the human immunodeficiency virus (HIV) infection was significantly augmented in vitro (P less than 0.01) by ImuVert. ImuVert strongly stimulated interferon gamma production and in combination with interleukin 2 produced synergistically enhanced interferon gamma production and greater cytotoxicity than that induced by either alone. Studies on lymphocyte differentiation antigen expression following treatment with ImuVert indicated that ImuVert triggers interferon gamma production through binding the low affinity IgG Fc receptor, type III, CD16. The studies suggest that ImuVert may trigger interferon gamma production by binding to the Fc receptor and that the amplitude of the ensuing reaction and the ability of ImuVert to induce cytotoxicity in a setting where this activity has been down regulated is based on the absence of suppressor activation or direct contra suppressor activity.

  12. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production.

    PubMed

    Furukawa, Tomohiro; Iimura, Kurin; Kimura, Taichi; Yamamoto, Toshiyoshi; Sakuda, Shohei

    2016-06-07

    Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control.

  13. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production.

    PubMed

    Furukawa, Tomohiro; Iimura, Kurin; Kimura, Taichi; Yamamoto, Toshiyoshi; Sakuda, Shohei

    2016-01-01

    Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control. PMID:27338472

  14. Inhibitory Activities of Alkyl Syringates and Related Compounds on Aflatoxin Production

    PubMed Central

    Furukawa, Tomohiro; Iimura, Kurin; Kimura, Taichi; Yamamoto, Toshiyoshi; Sakuda, Shohei

    2016-01-01

    Inhibitors of aflatoxin production of aflatoxigenic fungi are useful for preventing aflatoxin contamination in crops. As methyl syringate weakly inhibits aflatoxin production, aflatoxin production inhibitory activities of additional alkyl syringates with alkyl chains from ethyl to octyl were examined. Inhibitory activity toward aflatoxin production of Aspergillus flavus became stronger as the length of the alkyl chains on the esters became longer. Pentyl, hexyl, heptyl, and octyl syringates showed strong activity at 0.05 mM. Heptyl and octyl parabens, and octyl gallate also inhibited aflatoxin production as strongly as octyl syringate. Alkyl parabens and alkyl gallates inhibit the complex II activity of the mitochondrial respiration chain; thus, whether alkyl syringates inhibit complex II activity was examined. Inhibitory activities of alkyl syringates toward complex II also became stronger as the length of the alkyl chains increased. The complex II inhibitory activity of octyl syringate was comparable to that of octyl paraben and octyl gallate. These results suggest that alkyl syringates, alkyl parabens, and alkyl gallates, including commonly used food additives, are useful for aflatoxin control. PMID:27338472

  15. 78 FR 24158 - Foreign-Trade Zone (FTZ) 75-Phoenix, Arizona; Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... Production Activity; Orbital Sciences Corporation (Satellites and Spacecraft Launch Vehicles); Gilbert... satellites and spacecraft launch vehicles. Pursuant to 15 CFR 400.14(b), FTZ activity would be limited to the... procedures that applies to satellites and spacecraft launch vehicles (free) for the foreign status...

  16. 78 FR 68814 - Subzone 183B; Authorization of Production Activity; Samsung Austin Semiconductor, LLC...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-15

    ... (78 FR 40427, 7-5-2013). The FTZ Board has determined that no further review of the activity is... Foreign-Trade Zones Board Subzone 183B; Authorization of Production Activity; Samsung Austin Semiconductor, LLC (Semiconductors); Austin, Texas On June 26, 2013, Samsung Austin Semiconductor, LLC submitted...

  17. Production of activated carbons from waste tire--process design and economical analysis.

    PubMed

    Ko, Danny C K; Mui, Edward L K; Lau, Ken S T; McKay, Gordon

    2004-01-01

    The process design and economic analysis of process plants to produce activated carbons from waste tires and coal have been performed. The potential range of products from each process has been considered, namely for waste tire--pyro-gas, active carbon, carbon black and pyro-oil; for coal--pyro-gas and active carbons. Sensitivity analyses have been carried out on the main process factors; these are product price, production capacity, total production cost, capital investment and the tipping fee. Net present values for the two plants at various discount factors have been determined and the internal rates of return have been determined as 27.4% and 18.9% for the waste tire plant and the coal plant, respectively.

  18. Marine natural products with anti-HIV activities in the last decade.

    PubMed

    Zhou, Xuefeng; Liu, Juan; Yang, Bin; Lin, Xiuping; Yang, Xian-Wen; Liu, Yonghong

    2013-01-01

    Marine organisms have been proven to be excellent sources of biologically active compounds against HIV. This review gives an overview of 132 natural products from marine sources obtained during the last decade (2002-2011), which exhibit anti-HIV activity toward different biological targets. Sponges contribute more than half of all anti-HIV natural products from marine organisms, mainly as alkaloids and cyclic depsipeptides. In addition, some macromolecules are considered as potential anti-HIV agents, including lectins from algae and marine invertebrates, as well as sulfated polysaccharides from algae. In the reviewed marine natural products, many active ingredients act as HIV entry inhibitors, one class of new anti-HIV agents, and may be regarded as potential candidates for the development of novel anti-HIV agents. The other features of development in the marine original anti-HIV natural products in this ten years are also discussed.

  19. Viral pseudo-enzymes activate RIG-I via deamidation to evade cytokine production.

    PubMed

    He, Shanping; Zhao, Jun; Song, Shanshan; He, Xiaojing; Minassian, Arlet; Zhou, Yu; Zhang, Junjie; Brulois, Kevin; Wang, Yuqi; Cabo, Jackson; Zandi, Ebrahim; Liang, Chengyu; Jung, Jae U; Zhang, Xuewu; Feng, Pinghui

    2015-04-01

    RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here, we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologs of phosphoribosylformylglycinamidine synthetase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homolog thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme. PMID:25752576

  20. Viral Pseudo Enzymes Activate RIG-I via Deamidation to Evade Cytokine Production

    PubMed Central

    He, Shanping; Zhao, Jun; Song, Shanshan; He, Xiaojing; Minassian, Arlet; Zhou, Yu; Zhang, Junjie; Brulois, Kevin; Wang, Yuqi; Cabo, Jackson; Zandi, Ebrahim; Liang, Chengyu; Jung, Jae U; Zhang, Xuewu; Feng, Pinghui

    2015-01-01

    SUMMARY RIG-I is a pattern recognition receptor that senses viral RNA and is crucial for host innate immune defense. Here we describe a mechanism of RIG-I activation through amidotransferase-mediated deamidation. We show that viral homologues of phosphoribosylformyglycinamide synthase (PFAS), although lacking intrinsic enzyme activity, recruit cellular PFAS to deamidate and activate RIG-I. Accordingly, depletion and biochemical inhibition of PFAS impair RIG-I deamidation and concomitant activation. Purified PFAS and viral homologue thereof deamidate RIG-I in vitro. Ultimately, herpesvirus hijacks activated RIG-I to avoid antiviral cytokine production; loss of RIG-I or inhibition of RIG-I deamidation results in elevated cytokine production. Together, these findings demonstrate a surprising mechanism of RIG-I activation that is mediated by an enzyme. PMID:25752576

  1. Auxin-induced reactive oxygen species production requires the activation of phosphatidylinositol 3-kinase.

    PubMed

    Joo, Jung Hee; Yoo, Ho Jung; Hwang, Inhwan; Lee, June Seung; Nam, Kyoung Hee; Bae, Yun Soo

    2005-02-14

    We recently reported that production of reactive oxygen species (ROS) is essential for auxin-induced gravitropic signaling. Here, we investigated the role of phosphatidylinositol 3-kinase and its product, PtdIns(3)P, in auxin-mediated ROS production and the root gravitropic response. Pretreatment with LY294002, an inhibitor of PtdIns 3-kinase activity, blocked auxin-mediated ROS generation, and reduced the sensitivity of root tissue to gravistimulation. The amount of PtdIns(3)P increased in response to auxin, and this effect was abolished by pretreatment with LY294002. In addition, sequestration of PtdIns(3)P by transient expression of the endosome binding domain in protoplasts abrogated IAA-induced ROS accumulation. These results indicate that activation of PtdIns 3-kinase and its product PtdIns(3)P are required for auxin-induced production of ROS and root gravitropism. PMID:15710420

  2. Antifeedant activity of xanthohumol and supercritical carbon dioxide extract of spent hops against stored product pests.

    PubMed

    Jackowski, J; Hurej, M; Rój, E; Popłoński, J; Kośny, L; Huszcza, E

    2015-08-01

    Xanthohumol, a prenylated flavonoid from hops, and a supercritical carbon dioxide extract of spent hops were studied for their antifeedant activity against stored product insect pests: Sitophilus granarius L., Tribolium confusum Duv. and Trogoderma granarium Everts. Xanthohumol exhibited medium deterrent activity against the adults of S. granarius L. and larvae of T. confusum Duv. The spent hops extract was more active than xanthohumol towards the adults of T. confusum Duv. The potential application of the crude spent hops extract as a feeding deterrent against the stored product pests is proposed.

  3. Larvicidal activity of a botanical natural product, AkseBio2, against Culex pipiens.

    PubMed

    Cetin, H; Erler, F; Yanikoglu, A

    2004-12-01

    A botanical natural product, AkseBio2, was evaluated for its larvicidal effect against Culex pipiens under laboratory conditions. The product exhibited strong larvicidal activity and caused >90% mortalities in both the young (first-second) and the older (third-fourth) larval stages of the species at 24 h at the doses of 25 and 50 ppm. However, it was determined that the young larval stages were more susceptible to the product in comparison with the older larval stages. The results suggest that the product is promising as a larvicide against C. pipiens and could be useful in the search of new larvicidal natural compounds.

  4. Sclerotiamide: The First Non-Peptide-Based Natural Product Activator of Bacterial Caseinolytic Protease P.

    PubMed

    Lavey, Nathan P; Coker, Jesse A; Ruben, Eliza A; Duerfeldt, Adam S

    2016-04-22

    Caseinolytic protease P (ClpP) maintains essential roles in bacterial homeostasis. As such, both the inhibition and activation of this enzyme result in bactericidal activity, making ClpP a promising target for antibacterial drug development. Herein, we report the results of a fluorescence-based screen of ∼450 structurally diverse fungal and bacterial secondary metabolites. Sclerotiamide (1), a paraherquamide-related indolinone, was identified as the first non-peptide-based natural product activator of ClpP. Structure-activity relationships arising from the initial screen, preliminary biochemical evaluation of 1, and rationale for the exploitation of this chemotype to develop novel ClpP activators are presented.

  5. 78 FR 33052 - Foreign-Trade Zone (FTZ) 267-Fargo, North Dakota; Notification of Proposed Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ... Production Activity; CNH America, LLC (Construction and Agricultural Equipment Production); Fargo, North... production activity to the FTZ Board on behalf of CNH America, LLC (CNH), located in Fargo, North Dakota. The.... Production under FTZ procedures could exempt CNH from customs duty payments on the foreign status...

  6. Population based study of social and productive activities as predictors of survival among elderly Americans

    PubMed Central

    Glass, Thomas A; de Leon, Carlos Mendes; Marottoli, Richard A; Berkman, Lisa F

    1999-01-01

    Objectives To examine any association between social, productive, and physical activity and 13 year survival in older people. Design Prospective cohort study with annual mortality follow up. Activity and other measures were assessed by structured interviews at baseline in the participants’ homes. Proportional hazards models were used to model survival from time of initial interview. Setting City of New Haven, Connecticut, United States. Participants 2761 men and women from a random population sample of 2812 people aged 65 and older. Main outcome measure Mortality from all causes during 13 years of follow up. Results All three types of activity were independently associated with survival after age, sex, race/ethnicity, marital status, income, body mass index, smoking, functional disability, and history of cancer, diabetes, stroke, and myocardial infarction were controlled for. Conclusions Social and productive activities that involve little or no enhancement of fitness lower the risk of all cause mortality as much as fitness activities do. This suggests that in addition to increased cardiopulmonary fitness, activity may confer survival benefits through psychosocial pathways. Social and productive activities that require less physical exertion may complement exercise programmes and may constitute alternative interventions for frail elderly people. Key messagesLittle is known about predictors of survival among elderly peoplePhysical activity is clearly good for health, but the potential benefits of social activities have not been studiedSocial and productive activities are as effective as fitness activities in lowering the risk of deathEnhanced social activities may help to increase the quality and length of life PMID:10454399

  7. Listening to Puns Elicits the Co-Activation of Alternative Homophone Meanings during Language Production.

    PubMed

    Rose, Sebastian Benjamin; Spalek, Katharina; Rahman, Rasha Abdel

    2015-01-01

    Recent evidence suggests that lexical-semantic activation spread during language production can be dynamically shaped by contextual factors. In this study we investigated whether semantic processing modes can also affect lexical-semantic activation during word production. Specifically, we tested whether the processing of linguistic ambiguities, presented in the form of puns, has an influence on the co-activation of unrelated meanings of homophones in a subsequent language production task. In a picture-word interference paradigm with word distractors that were semantically related or unrelated to the non-depicted meanings of homophones we found facilitation induced by related words only when participants listened to puns before object naming, but not when they heard jokes with unambiguous linguistic stimuli. This finding suggests that a semantic processing mode of ambiguity perception can induce the co-activation of alternative homophone meanings during speech planning. PMID:26114942

  8. The Antibacterial Activity of Chitosan Products Blended with Monoterpenes and Their Biofilms against Plant Pathogenic Bacteria.

    PubMed

    Badawy, Mohamed E I; Rabea, Entsar I; Taktak, Nehad E M; El-Nouby, Mahmoud A M

    2016-01-01

    This study focuses on the biological activities of eleven chitosan products with a viscosity-average molecular weight ranging from 22 to 846 kDa in combination with the most active monoterpenes (geraniol and thymol), out of 10 tested, against four plant pathogenic bacteria, Agrobacterium tumefaciens, Erwinia carotovora, Corynebacterium fascians, and Pseudomonas solanacearum. The antibacterial activity was evaluated in vitro by the agar dilution technique as a minimum inhibitory concentration (MIC) that was found to be dependent on the type of the microorganism tested. The most active product of chitosan was used for biofilm production enriched with geraniol and thymol (0.1 and 0.5%) and the films were also evaluated against the tested bacteria. The biological bioactivities summarized here may provide novel insights into the functions of chitosan and some monoterpenes and potentially allow their use for food protection from microbial attack. PMID:27127676

  9. Listening to Puns Elicits the Co-Activation of Alternative Homophone Meanings during Language Production.

    PubMed

    Rose, Sebastian Benjamin; Spalek, Katharina; Rahman, Rasha Abdel

    2015-01-01

    Recent evidence suggests that lexical-semantic activation spread during language production can be dynamically shaped by contextual factors. In this study we investigated whether semantic processing modes can also affect lexical-semantic activation during word production. Specifically, we tested whether the processing of linguistic ambiguities, presented in the form of puns, has an influence on the co-activation of unrelated meanings of homophones in a subsequent language production task. In a picture-word interference paradigm with word distractors that were semantically related or unrelated to the non-depicted meanings of homophones we found facilitation induced by related words only when participants listened to puns before object naming, but not when they heard jokes with unambiguous linguistic stimuli. This finding suggests that a semantic processing mode of ambiguity perception can induce the co-activation of alternative homophone meanings during speech planning.

  10. The Antibacterial Activity of Chitosan Products Blended with Monoterpenes and Their Biofilms against Plant Pathogenic Bacteria

    PubMed Central

    Badawy, Mohamed E. I.; Rabea, Entsar I.; Taktak, Nehad E. M.; El-Nouby, Mahmoud A. M.

    2016-01-01

    This study focuses on the biological activities of eleven chitosan products with a viscosity-average molecular weight ranging from 22 to 846 kDa in combination with the most active monoterpenes (geraniol and thymol), out of 10 tested, against four plant pathogenic bacteria, Agrobacterium tumefaciens, Erwinia carotovora, Corynebacterium fascians, and Pseudomonas solanacearum. The antibacterial activity was evaluated in vitro by the agar dilution technique as a minimum inhibitory concentration (MIC) that was found to be dependent on the type of the microorganism tested. The most active product of chitosan was used for biofilm production enriched with geraniol and thymol (0.1 and 0.5%) and the films were also evaluated against the tested bacteria. The biological bioactivities summarized here may provide novel insights into the functions of chitosan and some monoterpenes and potentially allow their use for food protection from microbial attack. PMID:27127676

  11. Listening to Puns Elicits the Co-Activation of Alternative Homophone Meanings during Language Production

    PubMed Central

    Rose, Sebastian Benjamin; Spalek, Katharina; Rahman, Rasha Abdel

    2015-01-01

    Recent evidence suggests that lexical-semantic activation spread during language production can be dynamically shaped by contextual factors. In this study we investigated whether semantic processing modes can also affect lexical-semantic activation during word production. Specifically, we tested whether the processing of linguistic ambiguities, presented in the form of puns, has an influence on the co-activation of unrelated meanings of homophones in a subsequent language production task. In a picture-word interference paradigm with word distractors that were semantically related or unrelated to the non-depicted meanings of homophones we found facilitation induced by related words only when participants listened to puns before object naming, but not when they heard jokes with unambiguous linguistic stimuli. This finding suggests that a semantic processing mode of ambiguity perception can induce the co-activation of alternative homophone meanings during speech planning. PMID:26114942

  12. 78 FR 60826 - Foreign-Trade Zone 155-Calhoun/Victoria Counties, Texas; Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-02

    ... (78 FR 35604, 06/13/2013). The FTZ Board has determined that no further review of the activity is... Production Activity; Caterpillar, Inc. (Excavator and Frame Assembly Production); Victoria, Texas On May 29... proposed production activity to the Foreign-Trade Zones (FTZ) Board on behalf of Caterpillar, Inc.,...

  13. Lipoxygenase activity and sanguinarine production in cell suspension cultures of California poppy (Eschscholtzia californica CHAM.).

    PubMed

    Kollárová, R; Oblozinský, M; Kováciková, V; Holková, I; Balazová, A; Pekárová, M; Hoffman, P; Bezáková, L

    2014-08-01

    In this study we investigated the influence of biotic elicitor (phytopathogenic fungus Botrytis cinerea) and abiotic elicitors (methyljasmonate [MJ] and salicylic acid [SA]) on lipoxygenase (LOX) activity and sanguinarine production in cell suspension cultures of California poppy (Eschscholtzia californica CHAM.). We have observed different time effects of elicitors (10, 24, 48 and 72 h) on LOX activity and production of sanguinarine in in vitro cultures. All elicitors used in the experiments evidently increased the LOX activity and sanguinarine production in contrast to control samples. The highest LOX activities were determined in samples elicitated by MJ after 48 h and 72 h and the lowest LOX activities (in contrast to control samples) were detected after biotic elicitation by Botrytis cinerea. These activities showed about 50% lower level against the activities after MJ elicitation. The maximal amount of sanguinarine was observed after 48 h in MJ treated cultures (429.91 mg/g DCW) in comparision with control samples. Although all elicitors affect the sanguinarine production, effect of SA and biotic elicitor on sanguinarine accumulation in in vitrocultures was not so significant than after MJ elicitation.

  14. Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production

    PubMed Central

    Wolverton, Jay E.; Al-Hassani, Mohammed; Yao, Yongxue; Zhang, Qiwei; Travers, Jeffrey B.

    2010-01-01

    Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. PMID:19769579

  15. Activation of peripheral blood mononuclear cells in bronchoalveolar lavage fluid from patients with sarcoidosis: visualisation of single cell activation products.

    PubMed Central

    Pantelidis, P.; Southcott, A. M.; Cambrey, A. D.; Laurent, G. J.; du Bois, R. M.

    1994-01-01

    BACKGROUND--Interstitial lung diseases are characterised by the recruitment of mononuclear cells to disease sites where maturation occurs and activation products, including lysozyme (LZM), are released. Analysis of in vitro cell culture supernatants for activation products masks the functional heterogeneity of cell populations. It is therefore necessary to examine the secretion of activation products by single cells to assess whether the activation of newly recruited mononuclear phagocytes at the sites of disease in the lung is uniform and controlled by the local microenvironment. METHODS--The reverse haemolytic plaque assay was used to evaluate, at a single cell level, the ability of bronchoalveolar lavage (BAL) fluid from seven patients with sarcoidosis to activate Ficoll-Hypaque-separated peripheral blood mononuclear cells by comparison with BAL fluid from six normal volunteers and nine patients with systemic sclerosis. Monolayers of peripheral blood mononuclear cells and sheep red blood cells were cultured either alone or in the presence of 20% (v/v) BAL fluid with a polyclonal anti-LZM antibody. LZM/anti-LZM complexes bound to red blood cells surrounding the secreting cells were disclosed following complement lysis of red blood cells and quantification of plaque dimensions using microscopy and image analysis. RESULTS--Bronchoalveolar lavage fluid from all the patients with sarcoidosis increased LZM secretion by peripheral blood mononuclear cells compared with unstimulated mononuclear cells. By contrast, BAL fluid from the other individuals had no effect on LZM secretion. CONCLUSIONS--Single cells activated by BAL fluid can be evaluated by the reverse haemolytic plaque assay. BAL fluid from patients with sarcoidosis, but not from patients with systemic sclerosis or normal individuals, contains components capable of activating mononuclear phagocytes to secrete lysozyme. Images PMID:7831632

  16. Identification of Triclosan-O-Sulfate and other transformation products of Triclosan formed by activated sludge.

    PubMed

    Chen, Xijuan; Casas, Mònica Escolà; Nielsen, Jeppe Lund; Wimmer, Reinhard; Bester, Kai

    2015-02-01

    Aerobic degradation experiments of Triclosan were performed in activated sludge to identify possible transformation products for this compound. During 7 days, the formation of biotransformation products such as 2,4-Dichlorophenol, 4-Chlorocatechol, 5-Hydroxy-Triclosan and other Monohydroxy-Triclosan derivatives as well as Dihydroxy-Triclosan-derivatives were observed. The structure of 5-Hydroxy-Triclosan was elucidated by NMR data for the first time in sludge degradation experiments. Additionally the production of a hitherto unknown transformation product in sludge, i.e., Triclosan-O-Sulfate was detected. During the incubations, the concentrations of this transformation product changed from zero to 330 μg L(-1). Based on the analysis of the biodegradation products, three types of reactions were identified: 1) chemical scission of ether bond to form phenols and catechols, 2) addition of OH moieties to the aromatic ring, and 3) adding of methyl or sulfate groups to the original hydroxyl group.

  17. Effect of azithromycin on enhancement of methane production from waste activated sludge.

    PubMed

    Nguyen, Minh Tuan; Maeda, Toshinari; Mohd Yusoff, Mohd Zulkhairi; Ogawa, Hiroaki I

    2014-07-01

    In the methane production from waste activated sludge (WAS), complex bacterial interactions in WAS have been known as a major contribution to methane production. Therefore, the influence of bacterial community changes toward methane production from WAS was investigated by an application of antibiotics as a simple means for it. In this study, azithromycin (Azm) as an antibiotic was mainly used to observe the effect on microbial changes that influence methane production from WAS. The results showed that at the end of fermentation, Azm enhanced methane production about twofold compared to control. Azm fostered the growth of acid-producing bacterial communities, which synthesized more precursors for methane formation. DGGE result showed that the hydrolysis as well as acetogenesis stage was improved by the dominant of B1, B2 and B3 strains, which are Clostridium species. In the presence of Azm, the total population of archaeal group was increased, resulting in higher methane productivity achievement.

  18. Nanocapsular dispersion of cinnamaldehyde for enhanced inhibitory activity against aflatoxin production by Aspergillus flavus.

    PubMed

    Li, Hongbo; Shen, Qingshan; Zhou, Wei; Mo, Haizhen; Pan, Daodong; Hu, Liangbin

    2015-01-01

    Cinnamaldehyde (CA) is marginally soluble in water, making it challenging to evenly disperse it in foods, and resulting in lowered anti-A. flavus efficacy. In the present study, nano-dispersed CA (nano-CA) was prepared to increase its aqueous solubility. Free and nano-dispersed CA were compared in terms of their inhibitory activity against fungal growth and aflatoxin production of A. flavus both in Sabouraud Dextrose (SD) culture and in peanut butter. Our results indicated that free CA inhibited the mycelia growth and aflatoxin production of A. flavus with a minimal inhibitory concentration (MIC) value of 1.0 mM, but promoted the aflatoxin production at some concentrations lower than the MIC. Nano-CA had a lower MIC value of 0.8 mM against A. flavus, and also showed improved activity against aflatoxin production without the promotion at lower dose. The solidity of peanut butter had an adverse impact on the antifungal activity of free CA, whereas nano-dispersed CA showed more than 2-fold improved activity against the growth of A. flavus. Free CA still promoted AFB1 production at the concentration of 0.25 mM, whereas nano-CA showed more efficient inhibition of AFB1 production in the butter. PMID:25853318

  19. Increased riboflavin production from activated bleaching earth by a mutant strain of Ashbya gossypii.

    PubMed

    Tajima, Satoshi; Itoh, Yoko; Sugimoto, Takashi; Kato, Tatsuya; Park, Enoch Y

    2009-10-01

    The production of riboflavin from vegetable oil was increased using a mutant strain of Ashbya gossypii. This mutant was generated by treating the wild-type strain with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Riboflavin production was 10-fold higher in the mutant compared to the wild-type strain. The specific intracellular catalase activity after 3 d of culture was 6-fold higher in the mutant than in the wild-type strain. For the mutant, riboflavin production in the presence of 40 mM hydrogen peroxide was 16% less than that in the absence of hydrogen peroxide, whereas it was 56% less for the wild-type strain. The isocitrate lyase (ICL) activity of the mutant was 0.26 mU/mg of protein during the active riboflavin production phase, which was 2.6-fold higher than the wild-type strain. These data indicate that the mutant utilizes the carbon flux from the TCA cycle to the glyoxylate cycle more efficiently than the wild-type strain, resulting in enhanced riboflavin production. This novel mutant has the potential to be of use for industrial-scale riboflavin production from waste-activated bleaching earth (ABE), thereby transforming a useless material into a valuable bioproduct. PMID:19716523

  20. Enhancing methane production from waste activated sludge using a novel indigenous iron activated peroxidation pre-treatment process.

    PubMed

    Zhou, Xu; Wang, Qilin; Jiang, Guangming

    2015-04-01

    Methane production from anaerobic digestion of waste activated sludge (WAS) is limited by the slow hydrolysis rate and/or poor methane potential of WAS. This study presents a novel pre-treatment strategy based on indigenous iron (in WAS) activated peroxidation to enhance methane production from WAS. Pre-treatment of WAS for 30 min at 50mg H2O2/g total solids (dry weight) and pH 2.0 (iron concentration in WAS was 7 mg/g TS) substantially enhanced WAS solubilization. Biochemical methane potential tests demonstrated that methane production was improved by 10% at a digestion time of 16d after incorporating the indigenous iron activated peroxidation pre-treatment. Model-based analysis indicated that indigenous iron activated peroxidation pre-treatment improved the methane potential by 13%, whereas the hydrolysis rate was not significantly affected. The economic analysis showed that the proposed pre-treatment method can save the cost by $112,000 per year in a treatment plant with a population equivalent of 300,000.

  1. Evaluation of the oxidation of enrofloxacin by permanganate and the antimicrobial activity of the products.

    PubMed

    Xu, Yongpeng; Liu, Shiyao; Guo, Fang; Zhang, Bo

    2016-02-01

    Permanganate [Mn(VII)] oxidation of the fluoroquinolone (FQ) antibiotic enrofloxacin (ENR) was investigated with respect to kinetics and mechanisms, and the products were evaluated for residual antibacterial activity. The degradation of ENR by Mn(VII) obeyed second-order kinetics. A modern liquid chromatography coupled to a hybrid quadrupole time-of-flight mass spectrometer (LC-Q-TOF) was used to determine the accurate mass of the measured degradation products. The structures of nine oxidation products were identified at a neutral pH, one of which was an N-oxide product formed from the oxidation of tertiary amines. One proposed plausible reaction pathway was that the oxidation occurred on the piperazine ring; the C-H adjacent to the amine group was attacked by Mn(VII). The identified products from ENR arose through four pathways involving two mechanisms of N-dealkylation, C-hydroxylation and the reactions of amine oxides. The quinolone core remained intact for all of the products. The residual antibacterial activity of the oxidative reaction byproducts against the nonresistant Escherichia coli (G(-)) reference strain DH5ɑ was evaluated by quantifying the bacterial colonies. The oxidation products exhibited reduced antibacterial activity compared with their parent compound.

  2. The size of active bubbles for the production of hydrogen in sonochemical reaction field.

    PubMed

    Merouani, Slimane; Hamdaoui, Oualid

    2016-09-01

    The sonication of aqueous solution generates microscopic cavitation bubbles that may growth and violently collapse to produce highly reactive species (i.e. OH, HO2 and H2O2), hydrogen and emit light, sonoluminescence. The bubble size is a key parameter that influences the chemical activity of the system. This wok aims to study theoretically the size of active bubbles for the production of hydrogen in ultrasonic cavitation field in water using a single bubble sonochemistry model. The effect of several parameters such as frequency of ultrasound, acoustic intensity and liquid temperature on the range of sonochemically active bubbles for the production of hydrogen was clarified. The numerical simulation results showed that the size of active bubbles is an interval which includes an optimum value at which the production rate of H2 is maximal. It was shown that the range of ambient radius for an active bubble as well as the optimum bubble radius for the production of hydrogen increased with increasing acoustic intensity and decreased with increasing ultrasound frequency and bulk liquid temperature. It was found that the range of ambient bubble radius dependence of the operational conditions followed the same trend as those reported experimentally for sonoluminescing bubbles. Comparison with literature data showed a good agreement between the theoretical determined optimum bubble sizes for the production of hydrogen and the experimental reported sizes for sonoluminescing bubbles. PMID:27150777

  3. The size of active bubbles for the production of hydrogen in sonochemical reaction field.

    PubMed

    Merouani, Slimane; Hamdaoui, Oualid

    2016-09-01

    The sonication of aqueous solution generates microscopic cavitation bubbles that may growth and violently collapse to produce highly reactive species (i.e. OH, HO2 and H2O2), hydrogen and emit light, sonoluminescence. The bubble size is a key parameter that influences the chemical activity of the system. This wok aims to study theoretically the size of active bubbles for the production of hydrogen in ultrasonic cavitation field in water using a single bubble sonochemistry model. The effect of several parameters such as frequency of ultrasound, acoustic intensity and liquid temperature on the range of sonochemically active bubbles for the production of hydrogen was clarified. The numerical simulation results showed that the size of active bubbles is an interval which includes an optimum value at which the production rate of H2 is maximal. It was shown that the range of ambient radius for an active bubble as well as the optimum bubble radius for the production of hydrogen increased with increasing acoustic intensity and decreased with increasing ultrasound frequency and bulk liquid temperature. It was found that the range of ambient bubble radius dependence of the operational conditions followed the same trend as those reported experimentally for sonoluminescing bubbles. Comparison with literature data showed a good agreement between the theoretical determined optimum bubble sizes for the production of hydrogen and the experimental reported sizes for sonoluminescing bubbles.

  4. Analysis of inducers of xylanase and cellulase activities production by Ganoderma applanatum LPB MR-56.

    PubMed

    Salmon, Denise Naomi Xavier; Spier, Michele Rigon; Soccol, Carlos Ricardo; Vandenberghe, Luciana Porto de Souza; Weingartner Montibeller, Valesca; Bier, Mário César Jucoski; Faraco, Vincenza

    2014-08-01

    This manuscript describes the analysis of the effect of cellulose, carboxymethylcellulose (CMC), xylan, and xylose as inducers of cellulase and xylanase activity production by Ganoderma applanatum MR-56 and the optimization of their production in liquid cultures by statistical methods. The Plackett-Burman screening design was applied to identify the most significant inducers of xylanase and cellulase activities production by G. applanatum MR-56. The most significant effect on xylanase and cellulase activities production was exercised by cellulose, even if xylose and CMC were also effective at some times. The combined effect of cellulose, yeast extract, and pH was analyzed by a 2(3) factorial experimental design with four central points that showed that the maximum tested cellulose (1 % w/v) and yeast extract (5 g L(-1)) concentrations gave the maximum production of xylanase (8.24 U mL(-1)) and cellulase (3.29 U mL(-1)) activity at pH 6 and 4, respectively. These values achieved for cellulase and xylanase activity represent 12-25 fold and 36 fold higher values than the maximum so far reported for other strains of G. applanatum, respectively.

  5. Production of Cold-Active Bacterial Lipases through Semisolid State Fermentation Using Oil Cakes.

    PubMed

    Joseph, Babu; Upadhyaya, Supriya; Ramteke, Pramod

    2011-01-01

    Production of cold active lipase by semisolid state fermentation involves the use of agroindustrial residues. In the present study, semisolid state fermentation was carried out for the production of cold active lipase using Micrococcus roseus, isolated from soil samples of Gangotri glaciers, Western Himalayas. Among various substrate tested, groundnut oil cake (GOC) favored maximal yield of lipases at 15 ± 1°C within 48 h. Supplementation of glucose 1% (w/v) as additional carbon source and ammonium nitrate 2% (w/v) as additional nitrogen source enhanced production of lipase. Addition of triglycerides 0.5% (v/v) tends to repress the lipase production. Further mixed preparation of groundnut oil cake (GOC) along with mustard oil cake (MOC) in the ratio of 1 : 1, and its optimization resulted in improved production of cold active lipase. The enzyme exhibited maximum activity at 10-15°C and was stable at temperatures lower than 30°C. The lipase exhibited optimum activity at pH 8 and showed more than 60% stability at pH 9. Semisolid state fermentation process by utilizing agroindustrial wastes will direct to large-scale commercialization of lipase catalyzed process in cost-effective systems.

  6. Grazing-Activated Production of Dimethyl Sulfide (DMS) by two clones of Emiliania huxleyi

    NASA Technical Reports Server (NTRS)

    Wolfe, Gordon V.; Steinke, Michael

    1996-01-01

    Emiliania huxleyi clones CCMP 370 and CCMP 373 produced similar amounts of dimethylsulfoniopropionate (DMSP) during axenic exponential growth, averaging 109 mM internal DMSP. Both clones had detectable DMSP lyase activity, as measured by production of dimethyl sulfide (DMS) during in vitro assays of crude cell preparations, but activities and conditions differed considerably between clones. Clone 373 had high activity; clone 370 had low activity and required chloride. For both strains, enzyme activity per cell was constant during exponential growth, but little DMS was produced by healthy cells. Rather, DMS production was activated when cells were subjected to physical or chemical stresses that caused cell lysis. We propose that DMSP lyase and DMSP are segregated within these cells and re-action only under conditions that result in cell stress or damage. Such activation occurs during microzooplankton grazing. When these clones were grazed by the dinoflagellate Oxyrrhis marina, DMS was produced; ungrazed cells, as well as those exposed to grazer exudates and associated bacteria, generated no DMS. Grazing of clone 373 produced much more DMS than grazing of clone 370, consistent with their relative in vitro DMSP lyase activities. DMS was only generated when cells were actually being grazed, indicating that ingested cells were responsible for the DMS formation. We suggest that even low levels of grazing can greatly accelerate DMS production.

  7. Protectin DX, a double lipoxygenase product of DHA, inhibits both ROS production in human neutrophils and cyclooxygenase activities

    PubMed Central

    Liu, Miao; Boussetta, Tarek; Makni-Maalej, Karama; Fay, Michèle; Driss, Fathi; El-Benna, Jamel; Lagarde, Michel; Guichardant, Michel

    2014-01-01

    Neutrophils play a major role in inflammation by releasing large amounts of reactive oxygen species (ROS) produced by NADPH oxidase (NOX) and myeloperoxidase (MPO). This ROS overproduction is mediated by phosphorylation of the NOX subunits with an uncontrolled manner. Therefore, targeting neutrophil subunits would represent a promising strategy to moderate NOX activity, lower ROS, and other inflammatory agents, such as cytokines and leukotrienes, produced by neutrophils. For this purpose, we investigated the effects of protectin DX (PDX) - a docosahexaenoic acid (DHA) di-hydroxylated product which inhibits blood platelet aggregation - on neutrophil activation in vitro. We found that PDX decreases ROS production, inhibits NOX activation and MPO release from neutrophils. We also confirm, that PDX is an anti-aggregatory and anti-inflammatory agent by inhibiting both cyclooxygenase-1 and -2 (COX-1 and COX-2, E.C. 1.14.99.1) as well as COX-2 in lipopolysaccharides (LPS)-treated human neutrophils. However, PDX has no effect on the 5-lipoxygenase pathway that produces the chemotactic agent leukotriene B4 (LTB4). Taken together, our results suggest that PDX could be a protective agent against neutrophil invasion in chronic inflammatory diseases. PMID:24254970

  8. Cascading activation from lexical processing to letter-level processing in written word production.

    PubMed

    Buchwald, Adam; Falconer, Carolyn

    2014-01-01

    Descriptions of language production have identified processes involved in producing language and the presence and type of interaction among those processes. In the case of spoken language production, consensus has emerged that there is interaction among lexical selection processes and phoneme-level processing. This issue has received less attention in written language production. In this paper, we present a novel analysis of the writing-to-dictation performance of an individual with acquired dysgraphia revealing cascading activation from lexical processing to letter-level processing. The individual produced frequent lexical-semantic errors (e.g., chipmunk → SQUIRREL) as well as letter errors (e.g., inhibit → INBHITI) and had a profile consistent with impairment affecting both lexical processing and letter-level processing. The presence of cascading activation is suggested by lower letter accuracy on words that are more weakly activated during lexical selection than on those that are more strongly activated. We operationalize weakly activated lexemes as those lexemes that are produced as lexical-semantic errors (e.g., lethal in deadly → LETAHL) compared to strongly activated lexemes where the intended target word (e.g., lethal) is the lexeme selected for production. PMID:25163539

  9. Production of activated carbons from waste tyres for low temperature NOx control.

    PubMed

    Al-Rahbi, Amal S; Williams, Paul T

    2016-03-01

    Waste tyres were pyrolysed in a bench scale reactor and the product chars were chemically activated with alkali chemical agents, KOH, K2CO3, NaOH and Na2CO3 to produce waste tyre derived activated carbons. The activated carbon products were then examined in terms of their ability to adsorb NOx (NO) at low temperature (25°C) from a simulated industrial process flue gas. This study investigates the influence of surface area and porosity of the carbons produced with the different alkali chemical activating agents on NO capture from the simulated flue gas. The influence of varying the chemical activation conditions on the porous texture and corresponding NO removal from the flue gas was studied. The activated carbon sorbents were characterized in relation to BET surface area, micropore and mesopore volumes and chemical composition. The highest NO removal efficiency for the waste tyre derived activated carbons was ∼75% which was obtained with the adsorbent treated with KOH which correlated with both the highest BET surface area and largest micropore volume. In contrast, the waste tyre derived activated carbons prepared using K2CO3, NaOH and Na2CO3 alkali activating agents appeared to have little influence on NO removal from the flue gases. The results suggest problematic waste tyres, have the potential to be converted to activated carbons with NOx removal efficiency comparable with conventionally produced carbons.

  10. Modeling and production of 240Am by deuteron-induced activation of a 240Pu target

    SciTech Connect

    Finn, Erin C.; McNamara, Bruce K.; Greenwood, Lawrence R.; Wittman, Richard S.; Soderquist, Chuck Z.; Woods, Vincent T.; VanDevender, Brent A.; Metz, Lori A.; Friese, Judah I.

    2015-02-01

    A novel reaction pathway for production of 240Am is reported. Models of reaction cross-sections in EMPIRE II suggests that deuteron-induced activation of a 240Pu target produces maximum yields of 240Am from 11.5 MeV incident deuterons. This activation had not been previously reported in the literature. A 240Pu target was activated under the modeled optimum conditions to produce 240Am. The modeled cross-section for the 240Pu(d, 2n)240Am reaction is on the order of 20-30 mbarn, but the experimentally estimated value is 5.3 ± 0.2 mbarn. We discuss reasons for the discrepancy as well as production of other Am isotopes that contaminate the final product.

  11. Gamma irradiation induced disintegration of waste activated sludge for biological hydrogen production

    NASA Astrophysics Data System (ADS)

    Yin, Yanan; Wang, Jianlong

    2016-04-01

    In this paper, gamma irradiation was applied for the disintegration and dissolution of waste activated sludge produced during the biological wastewater treatment, and the solubilized sludge was used as substrate for bio-hydrogen production. The experimental results showed that the solubilization of waste activated sludge was 53.7% at 20 kGy and pH=12, and the SCOD, polysaccharides, protein, TN and TP contents in the irradiated sludge solutions was 3789.6 mg/L, 268.3 mg/L, 1881.5 mg/L, 132.3 mg/L and 80.4 mg/L, respectively. The irradiated sludge was used for fermentative hydrogen production, and the hydrogen yield was 10.5±0.7 mL/g SCODconsumed. It can be concluded that the irradiated waste activated sludge could be used as a low-cost substrate for fermentative hydrogen production.

  12. The role of degradant profiling in active pharmaceutical ingredients and drug products.

    PubMed

    Alsante, Karen M; Ando, Akemi; Brown, Roland; Ensing, Janice; Hatajik, Todd D; Kong, Wei; Tsuda, Yoshiko

    2007-01-10

    Forced degradation studies are used to facilitate the development of analytical methodology, to gain a better understanding of active pharmaceutical ingredient (API) and drug product (DP) stability, and to provide information about degradation pathways and degradation products. In order to fulfill development and regulatory needs, this publication provides a roadmap for when and how to perform studies, helpful tools in designing rugged scientific studies, and guidance on how to record and communicate results. PMID:17187892

  13. An Approach to the Commercial Production of Highly Active Pharmaceutical Ingredients.

    PubMed

    Beyeler, Andreas; Wilhelm, Roland; Brodbeck, Bernd

    2016-01-01

    To meet the requirements for production of highly active pharmaceutical ingredients (API) new approaches and technical solutions are required. Prior to the design and construction of a new multipurpose manufacturing facility, a process study was performed to clarify the future needs. During the planning phase, concepts were defined and elaborated to meet production, cleaning, health and safety standards. The ideas were taken into account and a small-scale manufacturing facility was designed and realized accordingly. PMID:27646539

  14. Integrated separation scheme for measuring a suite of fission and activation products from a fresh mixed fission and activation product sample

    SciTech Connect

    Morley, Shannon M.; Seiner, Brienne N.; Finn, Erin C.; Greenwood, Lawrence R.; Smith, Steven C.; Gregory, Stephanie J.; Haney, Morgan M.; Lucas, Dawn D.; Arrigo, Leah M.; Beacham, Tere A.; Swearingen, Kevin J.; Friese, Judah I.; Douglas, Matthew; Metz, Lori A.

    2015-05-01

    Mixed fission and activation materials resulting from various nuclear processes and events contain a wide range of isotopes for analysis spanning almost the entire periodic table. In some applications such as environmental monitoring, nuclear waste management, and national security a very limited amount of material is available for analysis and characterization so an integrated analysis scheme is needed to measure multiple radionuclides from one sample. This work describes the production of a complex synthetic sample containing fission products, activation products, and irradiated soil and determines the percent recovery of select isotopes through the integrated chemical separation scheme. Results were determined using gamma energy analysis of separated fractions and demonstrate high yields of Ag (76 ± 6%), Au (94 ± 7%), Cd (59 ± 2%), Co (93 ± 5%), Cs (88 ± 3%), Fe (62 ± 1%), Mn (70 ± 7%), Np (65 ± 5%), Sr (73 ± 2%) and Zn (72 ± 3%). Lower yields (< 25%) were measured for Ga, Ir, Sc, and W. Based on the results of this experiment, a complex synthetic sample can be prepared with low atom/fission ratios and isotopes of interest accurately and precisely measured following an integrated chemical separation method.

  15. Screening of Bacterial Strains for Polygalacturonase Activity: Its Production by Bacillus sphaericus (MTCC 7542).

    PubMed

    Jayani, Ranveer Singh; Shukla, Surendra Kumar; Gupta, Reena

    2010-10-31

    At present almost all the pectinolytic enzymes used for industrial applications are produced by fungi. There are a few reports of pectinase production by bacterial strains. Therefore, in the present study, seventy-four bacterial strains, isolated from soil and rotten vegetable samples, were screened for polygalacturonase production. The strain PG-31, which gave maximum activity, was identified as Bacillus sphaericus (MTCC 7542). Maximal quantities of polygalacturonase were produced when a 16-hours-old inoculum was used at 7.5% (v/v) in production medium and incubated in shaking conditions (160 rpm) for 72 hours. The optimal temperature and pH for bacterial growth and polygalacturonase production were found to be 30°C and 6.8, respectively. Maximum enzyme production resulted when citrus pectin was used as the carbon source at a concentration of 1.25% (w/v), whereas other carbon sources led to a decrease (30%-70%) in enzyme production. Casein hydrolysate and yeast extract used together as organic nitrogen source gave best results, and ammonium chloride was found to be the most suitable inorganic nitrogen source. The supplementation of media with 0.9% (w/v) D-galacturonic acid led to a 23% increase in activity. Bacillus sphaericus, a bacterium isolated from soil, produced good amount of polygalacturonase activity at neutral pH; hence, it would be potentially useful to increase the yield of banana, grape, or apple juice.

  16. SIGNR1 ligation on murine peritoneal macrophages induces IL-12 production through NFkappaB activation.

    PubMed

    Kato, Chiaki; Kojima, Naoya

    2010-07-01

    We have previously shown that murine resident peritoneal macrophages (PEMs) are activated in response to uptake of oligomannose-coated liposomes (OMLs), leading to production of interleukin (IL)-12. To understand the mechanism of activation of PEMs by OMLs, in the present study we investigated the role of a mannose-binding C-type lectin receptor, SIGNR1, in production of proinflammatory cytokines by PEMs, in which SIGNR1 acts as a physiological receptor for OMLs. Engagement of SIGNR1 on PEMs with an anti-SIGNR1-specific rat IgM antibody, ERTR9, induced production of IL-12 and tumor necrosis factor (TNF)-alpha from PEMs, while secretion of IL-6 and IL-1beta was not detected with the same treatment. The level of phosphorylated IkappaB kinase in PEMs also increased in response to ERTR9 treatment of the cells. Treatment of PEMs with a specific nuclear factor kappa-B (NFkappaB) inhibitor, BAY11-7082, reduced ERTR9-dependent IL-12 production. Intraperitoneal treatment with BAY11-7082 also led to reduction of subsequent OML-induced IL-12 production from PEMs. These results indicate that SIGNR1-mediated intercellular signaling may induce production of cytokines such as IL-12 through NFkappaB activation.

  17. Serratia marcescens Quinoprotein Glucose Dehydrogenase Activity Mediates Medium Acidification and Inhibition of Prodigiosin Production by Glucose

    PubMed Central

    Fender, James E.; Bender, Cody M.; Stella, Nicholas A.; Lahr, Roni M.; Kalivoda, Eric J.

    2012-01-01

    Serratia marcescens is a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed that d-glucono-1,5-lactone and d-gluconic acid, but not d-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation of d-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites. PMID:22752173

  18. Enhancement of anaerobic biohydrogen/methane production from cellulose using heat-treated activated sludge.

    PubMed

    Lay, C H; Chang, F Y; Chu, C Y; Chen, C C; Chi, Y C; Hsieh, T T; Huang, H H; Lin, C Y

    2011-01-01

    Anaerobic digestion is an effective technology to convert cellulosic wastes to methane and hydrogen. Heat-treatment is a well known method to inhibit hydrogen-consuming bacteria in using anaerobic mixed cultures for seeding. This study aims to investigate the effects of heat-treatment temperature and time on activated sludge for fermentative hydrogen production from alpha-cellulose by response surface methodology. Hydrogen and methane production was evaluated based on the production rate and yield (the ability of converting cellulose into hydrogen and methane) with heat-treated sludge as the seed at various temperatures (60-97 degrees C) and times (20-60 min). Batch experiments were conducted at 55 degrees C and initial pH of 8.0. The results indicate that hydrogen and methane production yields peaked at 4.3 mmol H2/g cellulose and 11.6 mmol CH4/g cellulose using the seed activated sludge that was thermally treated at 60 degrees C for 40 min. These parameter values are higher than those of no-treatment seed (HY 3.6 mmol H2/g cellulose and MY 10.4 mmol CH4/g cellulose). The maximum hydrogen production rate of 26.0 mmol H2/L/d and methane production rate of 23.2 mmol CH4/L/d were obtained for the seed activated sludge that was thermally treated at 70 degrees C for 50 min and 60 degrees C for 40 min, respectively.

  19. Serratia marcescens quinoprotein glucose dehydrogenase activity mediates medium acidification and inhibition of prodigiosin production by glucose.

    PubMed

    Fender, James E; Bender, Cody M; Stella, Nicholas A; Lahr, Roni M; Kalivoda, Eric J; Shanks, Robert M Q

    2012-09-01

    Serratia marcescens is a model organism for the study of secondary metabolites. The biologically active pigment prodigiosin (2-methyl-3-pentyl-6-methoxyprodiginine), like many other secondary metabolites, is inhibited by growth in glucose-rich medium. Whereas previous studies indicated that this inhibitory effect was pH dependent and did not require cyclic AMP (cAMP), there is no information on the genes involved in mediating this phenomenon. Here we used transposon mutagenesis to identify genes involved in the inhibition of prodigiosin by glucose. Multiple genetic loci involved in quinoprotein glucose dehydrogenase (GDH) activity were found to be required for glucose inhibition of prodigiosin production, including pyrroloquinoline quinone and ubiquinone biosynthetic genes. Upon assessing whether the enzymatic products of GDH activity were involved in the inhibitory effect, we observed that d-glucono-1,5-lactone and d-gluconic acid, but not d-gluconate, were able to inhibit prodigiosin production. These data support a model in which the oxidation of d-glucose by quinoprotein GDH initiates a reduction in pH that inhibits prodigiosin production through transcriptional control of the prodigiosin biosynthetic operon, providing new insight into the genetic pathways that control prodigiosin production. Strains generated in this report may be useful in large-scale production of secondary metabolites.

  20. Event-related potential evidence for parallel activation of two languages in bilingual speech production.

    PubMed

    Guo, Taomei; Peng, Danling

    2006-11-27

    The cross-language identity effect refers to the benefit of processing a translation distractor in the cross-language picture-word interference task. The first event-related-potential evidence for this effect was obtained in a picture-naming priming task using Chinese-English bilinguals of languages with distinct scripts. The results indicated that parallel activation of both languages is a universal phenomenon in bilingual speech production. Furthermore, the present study revealed that the temporal course and magnitude of activation of the nontarget language during target language production was modulated by the relative proficiency in the two languages.

  1. Heterologous production of active ribonuclease inhibitor in Escherichia coli by redox state control and chaperonin coexpression

    PubMed Central

    2011-01-01

    Background Eukaryotic Ribonuclease inhibitor (RI), belonging to the RNH1 family, is distinguished by unique features - a high sensitivity to oxidation due to the large number of reduced cysteins and a high hydrophobicity, which made most production approaches so far unsuccessful or resulted in very low yields. In this work efficient in vivo folding of native RI in the Escherichia coli cytoplasm was obtained by external addition of a reducing agent in tandem with oxygen limitation and overproduction of a molecular chaperonin. After optimisation of the production conditions in the shake flask scale the process was scaled up to high cell densities by applying a glucose limited fed-batch procedure. Results RI production in a T7 RNA polymerase based system results in accumulation of aggregated inactive product in inclusion bodies. Combination of addition of the reductant DTT, low production temperature and coexpression of the chaperonin GroELS resulted in high level production of approximately 25 mg g-1 CDW active RI in E. coli ER2566 pET21b, corresponding to approximately 800 kU g-1 cell wet weight. Further conditional screening under fed-batch-like conditions with the EnBase® technology and scale up into the bioreactor scale resulted in an efficient high cell density glucose and oxygen limited fed-batch process with a final cell dry weight of 25 g L-1 and a total RI yield of app. 625 mg L-1 (volumetric activity of 80,000 kU L-1). The E. coli based production constructs showed a very high robustness. The recombinant culture maintained its productivity despite the combination of the toxic growth conditions, the substrate limited production mode in tandem with a high level expression of several recombinant proteins, the set of molecular chaperonins and the target protein (RI). Conclusions High level production of active RI in E. coli in a T7 RNA polymerase expression system depends on the following factors: (i) addition of a reducing agent, (ii) low production

  2. Soil Moisture Active Passive (SMAP) Mission Level 4 Carbon (L4_C) Product Specification Document

    NASA Technical Reports Server (NTRS)

    Glassy, Joe; Kimball, John S.; Jones, Lucas; Reichle, Rolf H.; Ardizzone, Joseph V.; Kim, Gi-Kong; Lucchesi, Robert A.; Smith, Edmond B.; Weiss, Barry H.

    2015-01-01

    This is the Product Specification Document (PSD) for Level 4 Surface and Root Zone Soil Moisture (L4_SM) data for the Science Data System (SDS) of the Soil Moisture Active Passive (SMAP) project. The L4_SM data product provides estimates of land surface conditions based on the assimilation of SMAP observations into a customized version of the NASA Goddard Earth Observing System, Version 5 (GEOS-5) land data assimilation system (LDAS). This document applies to any standard L4_SM data product generated by the SMAP Project.

  3. Entropy production by active particles: Coupling of odd and even functions of velocity

    NASA Astrophysics Data System (ADS)

    Chaudhuri, Debasish

    2016-09-01

    Nonequilibrium stochastic dynamics of several active Brownian systems are modeled in terms of nonlinear velocity dependent force. In general, this force may consist of both even and odd functions of velocity. We derive the expression for total entropy production in such systems using the Fokker-Planck equation. The result is consistent with the expression for stochastic entropy production in the reservoir that we obtain from probabilities of time-forward and time-reversed trajectories, leading to fluctuation theorems. Numerical simulation is used to find probability distribution of entropy production, which shows good agreement with the detailed fluctuation theorem.

  4. Sphingomyelinase promotes oxidant production and skeletal muscle contractile dysfunction through activation of NADPH oxidase

    PubMed Central

    Loehr, James A.; Abo-Zahrah, Reem; Pal, Rituraj; Rodney, George G.

    2015-01-01

    Elevated concentrations of sphingomyelinase (SMase) have been detected in a variety of diseases. SMase has been shown to increase muscle derived oxidants and decrease skeletal muscle force; however, the sub-cellular site of oxidant production has not been elucidated. Using redox sensitive biosensors targeted to the mitochondria and NADPH oxidase (Nox2), we demonstrate that SMase increased Nox2-dependent ROS and had no effect on mitochondrial ROS in isolated FDB fibers. Pharmacological inhibition and genetic knockdown of Nox2 activity prevented SMase induced ROS production and provided protection against decreased force production in the diaphragm. In contrast, genetic overexpression of superoxide dismutase within the mitochondria did not prevent increased ROS production and offered no protection against decreased diaphragm function in response to SMase. Our study shows that SMase induced ROS production occurs in specific sub-cellular regions of skeletal muscle; however, the increased ROS does not completely account for the decrease in muscle function. PMID:25653619

  5. Relation of osteoclast activating factor production to extent of bone disease in multiple myeloma.

    PubMed

    Durie, B G; Salmon, S E; Mundy, G R

    1981-01-01

    Measurements of total body myeloma cell number and osteoclast activating factor (OAF) production by bone marrow myeloma cells in vitro were made in 33 patients with plasma cell myeloma. There was a highly significant correlation (P < 0.001) between the amount of OAF produced by bone marrow myeloma cells and the extent of skeletal destruction. Serial studies indicated reduction of OAF production with remission induction and high OAF production at the time of relapse with new bone destruction. Although hypercalcaemia occurred only in patients with the most extensive bone lesions, there was no direct relationship between OAF production and the serum calcium concentration. These data suggest that measurement of OAF production in multiple myeloma may predict those patients at risk for development of extensive skeletal destruction due to this neoplasm.

  6. Process engineering for bioflavour production with metabolically active yeasts - a mini-review.

    PubMed

    Carlquist, Magnus; Gibson, Brian; Karagul Yuceer, Yonca; Paraskevopoulou, Adamantini; Sandell, Mari; Angelov, Angel I; Gotcheva, Velitchka; Angelov, Angel D; Etschmann, Marlene; de Billerbeck, Gustavo M; Lidén, Gunnar

    2015-01-01

    Flavours are biologically active molecules of large commercial interest in the food, cosmetics, detergent and pharmaceutical industries. The production of flavours can take place by either extraction from plant materials, chemical synthesis, biological conversion of precursor molecules or de novo biosynthesis. The latter alternatives are gaining importance through the rapidly growing fields of systems biology and metabolic engineering, giving efficient production hosts for the so-called 'bioflavours', which are natural flavour and/or fragrance compounds obtained with cell factories or enzymatic systems. Yeasts are potential production hosts for bioflavours. In this mini-review, we give an overview of bioflavour production in yeasts from the process-engineering perspective. Two specific examples, production of 2-phenylethanol and vanillin, are used to illustrate the process challenges and strategies used.

  7. A Maillard reaction product enhances eNOS activity in human endothelial cells.

    PubMed

    Schmitt, Christoph A; Heiss, Elke H; Schachner, Daniel; Aristei, Yasmin; Severin, Theodor; Dirsch, Verena M

    2010-07-01

    Nitric oxide (NO) produced by the endothelial nitric oxide synthase (eNOS) is an important signaling molecule in the cardiovascular system. Although dietary factors can modulate eNOS activity, putative effects of processed food are barely investigated. We aimed to examine whether the model Maillard reaction product 3-hydroxy-2-methyl-1-propyl-4(1H)-pyridone (HMPP), formed from maltol or starch and propylamine, affects the eNOS system. Incubation of EA.hy926 endothelial cells with 30-300 microM HMPP for 18 h enhanced endothelial NO release measured with the fluorescent probe diaminofluorescein-2 and eNOS activity determined by the [14C]L-arginine-[14C]L-citrulline conversion assay. HMPP increased NO production also in two different types of primary human endothelial cells. Protein levels of eNOS and inducible NO synthase remained unaltered by HMPP. HMPP inhibited eNOS activity within the first 2-4 h, whereas it potently increased eNOS activity after 12-24 h. Levels of eNOS phosphorylation, expression of heat-shock protein 90, caveolin-1 and various antioxidant enzymes were not affected. Intracellular reactive oxygen species remained unchanged by HMPP. This is the first study to demonstrate positive effects of a Maillard reaction product on eNOS activity and endothelial NO production, which is considered favourable for cardiovascular protection. PMID:20112298

  8. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products.

    PubMed

    Myers, Sharon L; Yang, Chun Z; Bittner, George D; Witt, Kristine L; Tice, Raymond R; Baird, Donna D

    2015-05-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. PMID:24849798

  9. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products

    PubMed Central

    Myers, Sharon L.; Yang, Chun Z.; Bittner, George D.; Witt, Kristine L.; Tice, Raymond R.; Baird, Donna D.

    2014-01-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products. PMID:24849798

  10. Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

    PubMed

    Ticehurst, Martyn David; Marziano, Ivan

    2015-06-01

    This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery.

  11. Developmental changes in brain activation involved in the production of novel speech sounds in children.

    PubMed

    Hashizume, Hiroshi; Taki, Yasuyuki; Sassa, Yuko; Thyreau, Benjamin; Asano, Michiko; Asano, Kohei; Takeuchi, Hikaru; Nouchi, Rui; Kotozaki, Yuka; Jeong, Hyeonjeong; Sugiura, Motoaki; Kawashima, Ryuta

    2014-08-01

    Older children are more successful at producing unfamiliar, non-native speech sounds than younger children during the initial stages of learning. To reveal the neuronal underpinning of the age-related increase in the accuracy of non-native speech production, we examined the developmental changes in activation involved in the production of novel speech sounds using functional magnetic resonance imaging. Healthy right-handed children (aged 6-18 years) were scanned while performing an overt repetition task and a perceptual task involving aurally presented non-native and native syllables. Productions of non-native speech sounds were recorded and evaluated by native speakers. The mouth regions in the bilateral primary sensorimotor areas were activated more significantly during the repetition task relative to the perceptual task. The hemodynamic response in the left inferior frontal gyrus pars opercularis (IFG pOp) specific to non-native speech sound production (defined by prior hypothesis) increased with age. Additionally, the accuracy of non-native speech sound production increased with age. These results provide the first evidence of developmental changes in the neural processes underlying the production of novel speech sounds. Our data further suggest that the recruitment of the left IFG pOp during the production of novel speech sounds was possibly enhanced due to the maturation of the neuronal circuits needed for speech motor planning. This, in turn, would lead to improvement in the ability to immediately imitate non-native speech.

  12. Estrogenic and anti-estrogenic activity of off-the-shelf hair and skin care products.

    PubMed

    Myers, Sharon L; Yang, Chun Z; Bittner, George D; Witt, Kristine L; Tice, Raymond R; Baird, Donna D

    2015-05-01

    Use of personal care products is widespread in the United States but tends to be greater among African Americans than whites. Of special concern is the possible hazard of absorption of chemicals with estrogenic activity (EA) or anti-EA (AEA) in these products. Such exposure may have adverse health effects, especially when it occurs during developmental windows (e.g., prepubertally) when estrogen levels are low. We assessed the ethanol extracts of eight commonly used hair and skin products popular among African Americans for EA and AEA using a cell proliferation assay with the estrogen sensitive MCF-7:WS8 cell line derived from a human breast cancer. Four of the eight personal care products tested (Oil Hair Lotion, Extra-dry Skin Lotion, Intensive Skin Lotion, Petroleum Jelly) demonstrated detectable EA, whereas three (Placenta Hair Conditioner, Tea-Tree Hair Conditioner, Cocoa Butter Skin Cream) exhibited AEA. Our data indicate that hair and skin care products can have EA or AEA, and suggest that laboratory studies are warranted to investigate the in vivo activity of such products under chronic exposure conditions as well as epidemiologic studies to investigate potential adverse health effects that might be associated with use of such products.

  13. Discovery of New Compounds Active against Plasmodium falciparum by High Throughput Screening of Microbial Natural Products

    PubMed Central

    Pérez-Moreno, Guiomar; Cantizani, Juan; Sánchez-Carrasco, Paula; Ruiz-Pérez, Luis Miguel; Martín, Jesús; el Aouad, Noureddine; Pérez-Victoria, Ignacio; Tormo, José Rubén; González-Menendez, Víctor; González, Ignacio; de Pedro, Nuria; Reyes, Fernando; Genilloud, Olga; Vicente, Francisca; González-Pacanowska, Dolores

    2016-01-01

    Due to the low structural diversity within the set of antimalarial drugs currently available in the clinic and the increasing number of cases of resistance, there is an urgent need to find new compounds with novel modes of action to treat the disease. Microbial natural products are characterized by their large diversity provided in terms of the chemical complexity of the compounds and the novelty of structures. Microbial natural products extracts have been underexplored in the search for new antiparasitic drugs and even more so in the discovery of new antimalarials. Our objective was to find new druggable natural products with antimalarial properties from the MEDINA natural products collection, one of the largest natural product libraries harboring more than 130,000 microbial extracts. In this work, we describe the optimization process and the results of a phenotypic high throughput screen (HTS) based on measurements of Plasmodium lactate dehydrogenase. A subset of more than 20,000 extracts from the MEDINA microbial products collection has been explored, leading to the discovery of 3 new compounds with antimalarial activity. In addition, we report on the novel antiplasmodial activity of 4 previously described natural products. PMID:26735308

  14. Activity, life time and effect of hydrolytic enzymes for enhanced biogas production from sludge anaerobic digestion.

    PubMed

    Odnell, Anna; Recktenwald, Michael; Stensén, Katarina; Jonsson, Bengt-Harald; Karlsson, Martin

    2016-10-15

    As an alternative to energy intensive physical methods, enzymatic treatment of sludge produced at wastewater treatment plants for increased hydrolysis and biogas production was investigated. Several hydrolytic enzymes were assessed with a focus on how enzyme activity and life time was influenced by sludge environments. It could be concluded that the activity life time of added enzymes was limited (<24 h) in both waste activated sludge and anaerobic digester sludge environments and that this was, for the majority of enzymes, due to endogenous protease activity. In biogas in situ experiments, subtilisin at a 1% mixture on basis of volatile solids, was the only enzyme providing a significantly increased biomethane production of 37%. However, even at this high concentration, subtilisin could not hydrolyze all available substrate within the life time of the enzyme. Thus, for large scale implementation, enzymes better suited to the sludge environments are needed. PMID:27498254

  15. Activity, life time and effect of hydrolytic enzymes for enhanced biogas production from sludge anaerobic digestion.

    PubMed

    Odnell, Anna; Recktenwald, Michael; Stensén, Katarina; Jonsson, Bengt-Harald; Karlsson, Martin

    2016-10-15

    As an alternative to energy intensive physical methods, enzymatic treatment of sludge produced at wastewater treatment plants for increased hydrolysis and biogas production was investigated. Several hydrolytic enzymes were assessed with a focus on how enzyme activity and life time was influenced by sludge environments. It could be concluded that the activity life time of added enzymes was limited (<24 h) in both waste activated sludge and anaerobic digester sludge environments and that this was, for the majority of enzymes, due to endogenous protease activity. In biogas in situ experiments, subtilisin at a 1% mixture on basis of volatile solids, was the only enzyme providing a significantly increased biomethane production of 37%. However, even at this high concentration, subtilisin could not hydrolyze all available substrate within the life time of the enzyme. Thus, for large scale implementation, enzymes better suited to the sludge environments are needed.

  16. Cyclotron production of ``very high specific activity'' platinum radiotracers in No Carrier Added form

    NASA Astrophysics Data System (ADS)

    Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.; Gallorini, M.; Sabbioni, E.; Stroosnijder, M. F.

    2001-12-01

    At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, several production and quality assurance methods for short-lived and high specific activity radionuclides, have been developed. Presently, the irradiations are carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community, while both chemical purity and specific activity determination are carried out at the TRIGA MARK II research reactor of University of Pavia and at LASA itself. In order to optimize the irradiation conditions for platinum radiotracer production, both thin- and thick-target excitation function of natOs(α,xn) nuclear reactions were measured. A very selective radiochemical separation to obtain Pt radiotracers in No Carrier Added form, has been developed. Both real specific activity and chemical purity of radiotracer, have been determined by neutron activation analysis and atomic absorption spectrometry. An Isotopic Dilution Factor (IDF) of the order of 50 is achieved.

  17. MAG4 Versus Alternative Techniques for Forecasting Active-Region Flare Productivity

    NASA Technical Reports Server (NTRS)

    Falconer, David A.; Moore, Ronald L.; Barghouty, Abdulnasser F.; Khazanov, Igor

    2014-01-01

    MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free-magnetic-energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region's major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the "Present MAG4" technique and each of three alternative techniques, called "McIntosh Active-Region Class," "Total Magnetic Flux," and "Next MAG4." We do this by using (1) the MAG4 database of magnetograms and major-flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique-performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4).

  18. Fluency-dependent cortical activation associated with speech production and comprehension in second language learners.

    PubMed

    Shimada, K; Hirotani, M; Yokokawa, H; Yoshida, H; Makita, K; Yamazaki-Murase, M; Tanabe, H C; Sadato, N

    2015-08-01

    This functional magnetic resonance imaging (fMRI) study investigated the brain regions underlying language task performance in adult second language (L2) learners. Specifically, we identified brain regions where the level of activation was associated with L2 fluency levels. Thirty Japanese-speaking adults participated in the study. All participants were L2 learners of English and had achieved varying levels of fluency, as determined by a standardized L2 English proficiency test, the Versant English Test (Pearson Education Inc., 2011). When participants performed the oral sentence building task from the production tasks administered, the dorsal part of the left inferior frontal gyrus (dIFG) showed activation patterns that differed depending on the L2 fluency levels: The more fluent the participants were, the more dIFG activation decreased. This decreased activation of the dIFG might reflect the increased automaticity of a syntactic building process. In contrast, when participants performed an oral story comprehension task, the left posterior superior temporal gyrus (pSTG) showed increased activation with higher fluency levels. This suggests that the learners with higher L2 fluency were actively engaged in post-syntactic integration processing supported by the left pSTG. These data imply that L2 fluency predicts neural resource allocation during language comprehension tasks as well as in production tasks. This study sheds light on the neural underpinnings of L2 learning by identifying the brain regions recruited during different language tasks across different modalities (production vs. comprehension). PMID:26026679

  19. Fluency-dependent cortical activation associated with speech production and comprehension in second language learners.

    PubMed

    Shimada, K; Hirotani, M; Yokokawa, H; Yoshida, H; Makita, K; Yamazaki-Murase, M; Tanabe, H C; Sadato, N

    2015-08-01

    This functional magnetic resonance imaging (fMRI) study investigated the brain regions underlying language task performance in adult second language (L2) learners. Specifically, we identified brain regions where the level of activation was associated with L2 fluency levels. Thirty Japanese-speaking adults participated in the study. All participants were L2 learners of English and had achieved varying levels of fluency, as determined by a standardized L2 English proficiency test, the Versant English Test (Pearson Education Inc., 2011). When participants performed the oral sentence building task from the production tasks administered, the dorsal part of the left inferior frontal gyrus (dIFG) showed activation patterns that differed depending on the L2 fluency levels: The more fluent the participants were, the more dIFG activation decreased. This decreased activation of the dIFG might reflect the increased automaticity of a syntactic building process. In contrast, when participants performed an oral story comprehension task, the left posterior superior temporal gyrus (pSTG) showed increased activation with higher fluency levels. This suggests that the learners with higher L2 fluency were actively engaged in post-syntactic integration processing supported by the left pSTG. These data imply that L2 fluency predicts neural resource allocation during language comprehension tasks as well as in production tasks. This study sheds light on the neural underpinnings of L2 learning by identifying the brain regions recruited during different language tasks across different modalities (production vs. comprehension).

  20. Consensus Modeling for Prediction of Estrogenic Activity of Ingredients Commonly Used in Sunscreen Products

    PubMed Central

    Hong, Huixiao; Rua, Diego; Sakkiah, Sugunadevi; Selvaraj, Chandrabose; Ge, Weigong; Tong, Weida

    2016-01-01

    Sunscreen products are predominantly regulated as over-the-counter (OTC) drugs by the US FDA. The “active” ingredients function as ultraviolet filters. Once a sunscreen product is generally recognized as safe and effective (GRASE) via an OTC drug review process, new formulations using these ingredients do not require FDA review and approval, however, the majority of ingredients have never been tested to uncover any potential endocrine activity and their ability to interact with the estrogen receptor (ER) is unknown, despite the fact that this is a very extensively studied target related to endocrine activity. Consequently, we have developed an in silico model to prioritize single ingredient estrogen receptor activity for use when actual animal data are inadequate, equivocal, or absent. It relies on consensus modeling to qualitatively and quantitatively predict ER binding activity. As proof of concept, the model was applied to ingredients commonly used in sunscreen products worldwide and a few reference chemicals. Of the 32 chemicals with unknown ER binding activity that were evaluated, seven were predicted to be active estrogenic compounds. Five of the seven were confirmed by the published data. Further experimental data is needed to confirm the other two predictions. PMID:27690075

  1. Electron transport chain inhibitors induce microglia activation through enhancing mitochondrial reactive oxygen species production.

    PubMed

    Ye, Junli; Jiang, Zhongxin; Chen, Xuehong; Liu, Mengyang; Li, Jing; Liu, Na

    2016-01-15

    Reactive oxygen species (ROS) are believed to be mediators of excessive microglial activation, yet the resources and mechanism are not fully understood. Here we stimulated murine microglial BV-2 cells and primary microglial cells with different inhibitors of electron transport chain (ETC), rotenone, thenoyltrifluoroacetone (TTFA), antimycin A, and NaN3 to induce mitochondrial ROS production and we observed the role of mitochondrial ROS in microglial activation. Our results showed that ETC inhibitors resulted in significant changes in cell viability, microglial morphology, cell cycle arrest and mitochondrial ROS production in a dose-dependent manner in both primary cultural microglia and BV-2 cell lines. Moreover, ETC inhibitors, especially rotenone and antimycin A stimulated secretion of interleukin 1β (IL-1β), interleukin 6 (IL-6), interleukin 12 (IL-12) and tumor necrosis factor α (TNF-α) by microglia with marked activation of mitogen-activated proteinkinases (MAPKs) and nuclear factor κB (NF-κB), which could be blocked by specific inhibitors of MAPK and NF-κB and mitochondrial antioxidants, Mito-TEMPO. Taken together, our results demonstrated that inhibition of mitochondrial respiratory chain in microglia led to production of mitochondrial ROS and therefore may activate MAPK/NF-кB dependent inflammatory cytokines release in microglia, which indicated that mitochondrial-derived ROS were contributed to microglial activation.

  2. New approaches to estimation of peat deposits for production of biologically active compounds

    NASA Astrophysics Data System (ADS)

    Stepchenko, L. M.; Yurchenko, V. I.; Krasnik, V. G.; Syedykh, N. J.

    2009-04-01

    It is known, that biologically active preparations from peat increase animals productivity as well as resistance against stress-factors and have adaptogeneous, antioxidant, immunomodulative properties. Optymal choice of peat deposits for the production of biologically active preparations supposes the detailed comparative analysis of peat properties from different deposits. For this the cadastre of peat of Ukraine is developed in the humic substances laboratory named after prof. Khristeva L.A. (Dnipropetrovsk Agrarian University, Ukraine). It based on the research of its physical and chemical properties, toxicity and biological activity, and called Biocadastre. The Biocadastre is based on the set of parameters, including the descriptions of physical and chemical properties (active acidity, degree of decomposition, botanical composition etc.), toxicity estimation (by parabyotyc, infusorial, inhibitor and other tests), biological activity indexes (growth-promoting, antioxidative, adaptogeneous, immunomodulative antistress and other actions). The blocks of Biocadastre indexes are differentiated, taking into account their use for creation the preparations for vegetable, animals and microorganisms. The Biocadastre will allow to choose the peat deposits, most suitable for the production of different biologically active preparations, both wide directed and narrow spectrum of action, depending on application fields (medicine, agriculture, veterinary medicine, microbiological industry, balneology, cosmetology).

  3. YC-1 potentiates cAMP-induced CREB activation and nitric oxide production in alveolar macrophages

    SciTech Connect

    Hwang, Tsong-Long; Tang, Ming-Chi; Kuo, Liang-Mou; Chang, Wen-De; Chung, Pei-Jen; Chang, Ya-Wen; Fang, Yao-Ching

    2012-04-15

    Alveolar macrophages play significant roles in the pathogenesis of several inflammatory lung diseases. Increases in exhaled nitric oxide (NO) are well documented to reflect disease severity in the airway. In this study, we investigated the effect of 3-(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole (YC-1), a known activator of soluble guanylyl cyclase, on prostaglandin (PG)E{sub 1} (a stable PGE{sub 2} analogue) and forskolin (a adenylate cyclase activator) induced NO production and inducible NO synthase (iNOS) expression in rat alveolar macrophages (NR8383). YC-1 did not directly cause NO production or iNOS expression, but drastically potentiated PGE{sub 1}- or forskolin-induced NO production and iNOS expression in NR8383 alveolar macrophages. Combination treatment with YC-1 and PGE{sub 1} significantly increased phosphorylation of the cAMP response element-binding protein (CREB), but not nuclear factor (NF)-κB activation. The combined effect on NO production, iNOS expression, and CREB phosphorylation was reversed by a protein kinase (PK)A inhibitor (H89), suggesting that the potentiating functions were mediated through a cAMP/PKA signaling pathway. Consistent with this, cAMP analogues, but not the cGMP analogue, caused NO release, iNOS expression, and CREB activation. YC-1 treatment induced an increase in PGE{sub 1}-induced cAMP formation, which occurred through the inhibition of cAMP-specific phosphodiesterase (PDE) activity. Furthermore, the combination of rolipram (an inhibitor of PDE4), but not milronone (an inhibitor of PDE3), and PGE{sub 1} also triggered NO production and iNOS expression. In summary, YC-1 potentiates PGE{sub 1}-induced NO production and iNOS expression in alveolar macrophages through inhibition of cAMP PDE activity and activation of the cAMP/PKA/CREB signaling pathway. Highlights: ► YC-1 potentiated PGE1-induced iNOS expression in alveolar macrophages. ► The combination of YC-1 and PGE1 increased CREB but not NFκB activation.

  4. Realizing the full potential of Remotely Sensed Active Layer Thickness (ReSALT) Products

    NASA Astrophysics Data System (ADS)

    Schaefer, K. M.; Chen, A.; Liu, L.; Parsekian, A.; Jafarov, E. E.; Panda, S. K.; Zebker, H. A.

    2015-12-01

    The Remotely Sensed Active Layer Thickness (ReSALT) product uses the Interferometric Synthetic Aperture Radar (InSAR) technique to measure ground subsidence, active layer thickness (ALT), and thermokarst activity in permafrost regions. ReSALT supports research for the Arctic-Boreal Vulnerability Experiment (ABoVE) field campaign in Alaska and northwest Canada and is a precursor for a potential Nasa-Isro Synthetic Aperture Radar (NISAR) product. ALT is a critical parameter for monitoring the status of permafrost and thermokarst activity is one of the key drivers of change in permafrost regions. The ReSALT product currently includes 1) long-term subsidence trends resulting from the melting and subsequent drainage of excess ground ice in permafrost-affected soils, 2) seasonal subsidence resulting from the expansion of soil water into ice as the active layer freezes and thaws, and 3) ALT estimated from the seasonal subsidence assuming a vertical profile of water within the soil column. ReSALT includes uncertainties for all parameters and is validated against in situ measurements from the Circumpolar Active Layer Monitoring (CALM) network, Ground Penetrating Radar and mechanical probe measurements. We present high resolution ReSALT products on the North Slope of Alaska: Prudhoe Bay, Barrow, Toolik Lake, Happy Valley, and the Anaktuvuk fire zone. We believe that the ReSALT product could be expanded to include maps of individual thermokarst features identified as spatial anomalies in the subsidence trends, with quantified expansion rates. We illustrate the technique with multiple examples of thermokarst features on the North Slope of Alaska. Knowing the locations and expansion rates for individual features allows us to evaluate risks to human infrastructure. Our results highlight the untapped potential of the InSAR technique to remotely sense ALT and thermokarst dynamics over large areas of the Arctic.

  5. Genetic Characterization of the Homeodomain-Independent Activity of the Drosophila Fushi Tarazu Gene Product

    PubMed Central

    Hyduk, D.; Percival-Smith, A.

    1996-01-01

    The gene product of fushi tarazu (FTZ) has a homeodomain (HD)-independent activity. Ectopic expression of a FTZ protein that lacks half the HD in embryos results in the anti-ftz phenotype. We have characterized this FTZ HD-independent activity further. Ectopic expression of the HD-independent FTZ activity, in the absence of FTZ activity expressed from the endogenous ftz gene, was sufficient to result in the anti-ftz phenotype. Since the anti-ftz phenotype is a first instar larvae composed nearly entirely of FTZ-dependent cuticular structures derived from the even-numbered parasegments, this result suggests that expression of the HD-independent FTZ activity is sufficient to establish FTZ-dependent cuticle. Activation of FTZ-dependent Engrailed (EN) expression and activation of the ftz enhancer were HD-independent. The ftz enhancer element, AE-1, was activated by the HD-independent FTZ activity; however, the ftz enhancer element, AE-BS2CCC, which is the same as AE-1 except for the inactivation of two FTZ HD DNA-binding sites, was not. Activation of the ftz enhancer by ectopic expression of FTZ activity was effective only during gastrulation and germ band extension. In the discussion, we propose an explanation for these results. PMID:8852847

  6. TRPV4 activation mediates flow-induced nitric oxide production in the rat thick ascending limb

    PubMed Central

    Garvin, Jeffrey L.

    2014-01-01

    Nitric oxide (NO) regulates renal function. Luminal flow stimulates NO production in the thick ascending limb (TAL). Transient receptor potential vanilloid 4 (TRPV4) is a mechano-sensitive channel activated by luminal flow in different types of cells. We hypothesized that TRPV4 mediates flow-induced NO production in the rat TAL. We measured NO production in isolated, perfused rat TALs using the fluorescent dye DAF FM. Increasing luminal flow from 0 to 20 nl/min stimulated NO from 8 ± 3 to 45 ± 12 arbitrary units (AU)/min (n = 5; P < 0.05). The TRPV4 antagonists, ruthenium red (15 μmol/l) and RN 1734 (10 μmol/l), blocked flow-induced NO production. Also, luminal flow did not increase NO production in the absence of extracellular calcium. We also studied the effect of luminal flow on NO production in TALs transduced with a TRPV4shRNA. In nontransduced TALs luminal flow increased NO production by 47 ± 17 AU/min (P < 0.05; n = 5). Similar to nontransduced TALs, luminal flow increased NO production by 39 ± 11 AU/min (P < 0.03; n = 5) in TALs transduced with a control negative sequence-shRNA while in TRPV4shRNA-transduced TALs, luminal flow did not increase NO production (Δ10 ± 15 AU/min; n = 5). We then tested the effect of two different TRPV4 agonists on NO production in the absence of luminal flow. 4α-Phorbol 12,13-didecanoate (1 μmol/l) enhanced NO production by 60 ± 11 AU/min (P < 0.002; n = 7) and GSK1016790A (10 ηmol/l) increased NO production by 52 ± 15 AU/min (P < 0.03; n = 5). GSK1016790A (10 ηmol/l) did not stimulate NO production in TRPV4shRNA-transduced TALs. We conclude that activation of TRPV4 channels mediates flow-induced NO production in the rat TAL. PMID:24966090

  7. Production of activated carbon and its catalytic application for oxidation of hydrogen sulphide

    NASA Astrophysics Data System (ADS)

    Azargohar, Ramin

    Hydrogen sulphide is an environmentally hazardous gas which is present in many gas streams associated with oil and gas industry. Oxidation of H 2S to sulphur in air produces no bulky or waste material and requires no further purification. Activated carbon is known as a catalyst for this reaction. In this research, a coal-based precursor (luscar char) and a biomass-based precursor (biochar) were used for production of activated carbons by two common methods of activation: physical and chemical activation in which steam and potassium hydroxide (KOH), respectively, were used. Experiments were designed by the statistical central composite design method. Two models were developed for the BET surface area and reaction yield of each activation process. These models showed the effects of operating conditions, such as activation temperature, mass ratio of activating agent to precursor, activation time, and nitrogen flowrate on the BET surface area and reaction yield for each activation method for each precursor. The optimum operating conditions were calculated using these models to produce activated carbons with relatively large BET surface area (> 500 m2/g) and high reaction yield (> 50 wt %). The BET surface area and reaction yield for activated carbons produced at optimum operating conditions showed maximum 7 and 7.4% difference, respectively, comparing to the values predicted by models. The activated carbons produced at optimum operating conditions were used as the base catalysts for the direct oxidation of 1 mol % hydrogen sulphide in nitrogen to sulphur at the temperature range of 160-205°C and pressure of 700 kPa. Originally activated carbons showed a good potential for oxidation of hydrogen sulphide by their selectivity for sulphur product and low amount of sulphur dioxide production. To improve the performance of steam-activated carbons, the catalysts were modified by acid-treatment followed by thermal desorption. This method increased the break-through times for

  8. Activated carbon from pyrolysis of brewer's spent grain: Production and adsorption properties.

    PubMed

    Vanreppelen, Kenny; Vanderheyden, Sara; Kuppens, Tom; Schreurs, Sonja; Yperman, Jan; Carleer, Robert

    2014-06-20

    Brewer's spent grain is a low cost residue generated by the brewing industry. Its chemical composition (high nitrogen content 4.35 wt.%, fibres, etc.) makes it very useful for the production of added value in situ nitrogenised activated carbon. The composition of brewer's spent grain revealed high amounts of cellulose (20.8 wt.%), hemicellulose (48.78 wt.%) and lignin (11.3 wt.%). The fat, ethanol extractives and ash accounted for 8.17 wt.%, 4.7 wt.% and 3.2 wt.%, respectively. Different activated carbons were produced in a lab-scale pyrolysis/activation reactor by applying several heat and steam activation profiles on brewer's spent grain. Activated carbon yields from 16.1 to 23.6 wt.% with high N-contents (> 2 wt.%) were obtained. The efficiency of the prepared activated carbons for phenol adsorption was studied as a function of different parameters: pH, contact time and carbon dosage relative to two commercial activated carbons. The equilibrium isotherms were described by the non-linear Langmuir and Freundlich models, and the kinetic results were fitted using the pseudo-first-order model and the pseudo-second-order model. The feasibility of an activated carbon production facility (onsite and offsite) that processes brewer's spent grain for different input feeds is evaluated based on a techno-economic model for estimating the net present value. Even though the model assumptions start from a rather pessimistic scenario, encouraging results for a profitable production of activated carbon using brewer's spent grain are obtained. PMID:25012859

  9. Activated carbon from pyrolysis of brewer's spent grain: Production and adsorption properties.

    PubMed

    Vanreppelen, Kenny; Vanderheyden, Sara; Kuppens, Tom; Schreurs, Sonja; Yperman, Jan; Carleer, Robert

    2014-07-01

    Brewer's spent grain is a low cost residue generated by the brewing industry. Its chemical composition (high nitrogen content 4.35 wt.%, fibres, etc.) makes it very useful for the production of added value in situ nitrogenised activated carbon. The composition of brewer's spent grain revealed high amounts of cellulose (20.8 wt.%), hemicellulose (48.78 wt.%) and lignin (11.3 wt.%). The fat, ethanol extractives and ash accounted for 8.17 wt.%, 4.7 wt.% and 3.2 wt.%, respectively. Different activated carbons were produced in a lab-scale pyrolysis/activation reactor by applying several heat and steam activation profiles on brewer's spent grain. Activated carbon yields from 16.1 to 23.6 wt.% with high N-contents (> 2 wt.%) were obtained. The efficiency of the prepared activated carbons for phenol adsorption was studied as a function of different parameters: pH, contact time and carbon dosage relative to two commercial activated carbons. The equilibrium isotherms were described by the non-linear Langmuir and Freundlich models, and the kinetic results were fitted using the pseudo-first-order model and the pseudo-second-order model. The feasibility of an activated carbon production facility (onsite and offsite) that processes brewer's spent grain for different input feeds is evaluated based on a techno-economic model for estimating the net present value. Even though the model assumptions start from a rather pessimistic scenario, encouraging results for a profitable production of activated carbon using brewer's spent grain are obtained.

  10. EGFR activation suppresses respiratory virus-induced IRF1-dependent CXCL10 production.

    PubMed

    Kalinowski, April; Ueki, Iris; Min-Oo, Gundula; Ballon-Landa, Eric; Knoff, David; Galen, Benjamin; Lanier, Lewis L; Nadel, Jay A; Koff, Jonathan L

    2014-07-15

    Airway epithelial cells are the primary cell type involved in respiratory viral infection. Upon infection, airway epithelium plays a critical role in host defense against viral infection by contributing to innate and adaptive immune responses. Influenza A virus, rhinovirus, and respiratory syncytial virus (RSV) represent a broad range of human viral pathogens that cause viral pneumonia and induce exacerbations of asthma and chronic obstructive pulmonary disease. These respiratory viruses induce airway epithelial production of IL-8, which involves epidermal growth factor receptor (EGFR) activation. EGFR activation involves an integrated signaling pathway that includes NADPH oxidase activation of metalloproteinase, and EGFR proligand release that activates EGFR. Because respiratory viruses have been shown to activate EGFR via this signaling pathway in airway epithelium, we investigated the effect of virus-induced EGFR activation on airway epithelial antiviral responses. CXCL10, a chemokine produced by airway epithelial cells in response to respiratory viral infection, contributes to the recruitment of lymphocytes to target and kill virus-infected cells. While respiratory viruses activate EGFR, the interaction between CXCL10 and EGFR signaling pathways is unclear, and the potential for EGFR signaling to suppress CXCL10 has not been explored. Here, we report that respiratory virus-induced EGFR activation suppresses CXCL10 production. We found that influenza virus-, rhinovirus-, and RSV-induced EGFR activation suppressed IFN regulatory factor (IRF) 1-dependent CXCL10 production. In addition, inhibition of EGFR during viral infection augmented IRF1 and CXCL10. These findings describe a novel mechanism that viruses use to suppress endogenous antiviral defenses, and provide potential targets for future therapies.

  11. Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Sams, Clarence F.

    2001-01-01

    An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing

  12. Sphingosine kinase 1 activation enhances epidermal innate immunity through sphingosine-1-phosphate stimulation of cathelicidin production

    PubMed Central

    Jeong, Se Kyoo; Kim, Young Il; Shin, Kyong-Oh; Kim, Bong-Woo; Lee, Sin Hee; Jeon, Jeong Eun; Kim, Hyun Jong; Lee, Yong-Moon; Mauro, Theodora M.; Elias, Peter M.; Uchida, Yoshikazu; Park, Kyungho

    2015-01-01

    Background The ceramide metabolite, sphingosine-1-phosphate (S1P), regulates multiple cellular functions in keratinocytes (KC). We recently discovered that production of a key innate immune element, cathelicidin antimicrobial peptide (CAMP), is stimulated via a NF-κB-dependent mechanism that is activated by S1P when S1P is generated by sphingosine kinase (SPHK) 1. Objective We investigated whether pharmacological modulation of SPHK1 activity, using a novel synthetic SPHK1 activator, (S)-Methyl 2-(hexanamide)-3-(4-hydroxyphenyl) propanoate (MHP), stimulates CAMP expression. Methods MHP-mediated changes in both S1P and CAMP downstream mediators were analyzed in normal cultured human KC by qRT-PCR, Western immunoblot, ELISA, confocal microscopy for immunohistochemistry, HPLC and ESI-LC/MS/MS, and microbial pathogen invasion/colonization in a human epidermal organotypic model. Results Treatment with MHP directly activated SPHK1 and increased cellular S1P content in normal cultured human KC. Because MHP did not inhibit S1P lyase activity, which hydrolyses S1P, augumented S1P levels could be attributed to increased synthesis rather than blockade of S1P degradation. Next, we found that exogenous MHP significantly stimulated CAMP mRNA and protein production in KC, increases that were significantly suppressed by siRNA directed against SPHK1, but not by a scrambled control siRNA. NF-κB activation, assessed by nuclear translocation of NF-κB, occurred in cells following incubation with MHP. Conversely, pretreatment with a specific inhibitor of SPHK1 decreased MHP-induced nuclear translocation of NF-κB, and significantly attenuated the MHP-mediated increase in CAMP production. Finally, topical MHP significantly suppressed invasion of the virulent Staphylococcus aureus into murine skin explants. Conclusion MHP activation of SPHK1, a target enzyme of CAMP production, can stimulate innate immunity. PMID:26113114

  13. Activated human valvular interstitial cells sustain interleukin-17 production to recruit neutrophils in infective endocarditis.

    PubMed

    Yeh, Chiou-Yueh; Shun, Chia-Tung; Kuo, Yu-Min; Jung, Chiau-Jing; Hsieh, Song-Chou; Chiu, Yen-Ling; Chen, Jeng-Wei; Hsu, Ron-Bin; Yang, Chia-Ju; Chia, Jean-San

    2015-06-01

    The mechanisms that underlie valvular inflammation in streptococcus-induced infective endocarditis (IE) remain unclear. We previously demonstrated that streptococcal glucosyltransferases (GTFs) can activate human heart valvular interstitial cells (VIC) to secrete interleukin-6 (IL-6), a cytokine involved in T helper 17 (Th17) cell differentiation. Here, we tested the hypothesis that activated VIC can enhance neutrophil infiltration through sustained IL-17 production, leading to valvular damage. To monitor cytokine and chemokine production, leukocyte recruitment, and the induction or expansion of CD4(+) CD45RA(-) CD25(-) CCR6(+) Th17 cells, primary human VIC were cultured in vitro and activated by GTFs. Serum cytokine levels were measured using an enzyme-linked immunosorbent assay (ELISA), and neutrophils and Th17 cells were detected by immunohistochemistry in infected valves from patients with IE. The expression of IL-21, IL-23, IL-17, and retinoic acid receptor-related orphan receptor C (Rorc) was upregulated in GTF-activated VIC, which may enhance the proliferation of memory Th17 cells in an IL-6-dependent manner. Many chemokines, including chemokine (C-X-C motif) ligand 1 (CXCL1), were upregulated in GTF-activated VIC, which might recruit neutrophils and CD4(+) T cells. Moreover, CXCL1 production in VIC was induced in a dose-dependent manner by IL-17 to enhance neutrophil chemotaxis. CXCL1-expressing VIC and infiltrating neutrophils could be detected in infected valves, and serum concentrations of IL-17, IL-21, and IL-23 were increased in patients with IE compared to healthy donors. Furthermore, elevated serum IL-21 levels have been significantly associated with severe valvular damage, including rupture of chordae tendineae, in IE patients. Our findings suggest that VIC are activated by bacterial modulins to recruit neutrophils and that such activities might be further enhanced by the production of Th17-associated cytokines. Together, these factors can amplify

  14. Lecturers' Perception of Research Activities for Knowledge Production in Universities in Cross River State, Nigeria

    ERIC Educational Resources Information Center

    Uchendu, C. C.; Osim, R. O.; Odigwe, F. N.; Alade, F. N.

    2014-01-01

    This study examined lecturers' perception of research activities for knowledge production in universities in Cross River State, Nigeria. Two hypotheses were isolated to give direction to this investigation. 240 university lecturers were sampled from a population of 1,868 from the two universities in Cross River State, using stratified random…

  15. Contribution of activation products to occupational exposure following treatment using high-energy photons in radiotherapy.

    PubMed

    Petrović, Nina; Krestić-Vesović, Jelena; Stojanović, Darko; Ciraj-Bjelac, Olivera; Lazarević, Dorde; Kovacević, Milojko

    2011-01-01

    When high-energy photon beams are used for irradiation in radiotherapy, neutrons that are the result of photonuclear reactions create activation products that affect the occupational dose of radiotherapy staff. For the assessment of activation products in situ gamma spectroscopy was performed parallel to dose-rate measurements following irradiation, by using a high-energy photon beam from a linear accelerator Elekta Precise (Elekta, Stockholm, Sweden) used in radiotherapy. The major identified activation products were the following radioisotopes: (28)Al, (24)Na, (56)Mn, (54)Mn, (187)W, (64)Cu and (62)Cu. Based on the typical workload and dose-rate measurement, the assessed additional annual occupational dose ranged from 1.7 to 0.25 mSv. As the measured dose rate arising from the activation products rapidly decreases as a function of time, the assessed additional dose is negligible after 10 min following irradiation. To keep the occupational dose as low as reasonably achievable, it is recommended to delay entrance to the therapy room at least 2-4 min, when high-energy photons are used. This would reduce the effective dose by 30%.

  16. Production-on-the-Go Practice: Storyboarding as a Retrospective and Redundant School Literacy Activity

    ERIC Educational Resources Information Center

    Tan, Lynde

    2013-01-01

    Storyboarding is one common strategy used in teaching young people digital media. This paper argues that in adolescents' literacy practices, they engage in production on the go. The metaphor is described in this paper to put forward the argument that storyboarding can be a retrospective and redundant literacy activity in adolescents'…

  17. Single crystalline tantalum oxychloride microcubes: controllable synthesis, formation mechanism and enhanced photocatalytic hydrogen production activity.

    PubMed

    Tu, Hao; Xu, Leilei; Mou, Fangzhi; Guan, Jianguo

    2015-08-11

    Single crystalline microcubes of a new tantalum compound, tantalum oxychloride (TaO2.18Cl0.64), have been fabricated hydrothermally in a concentrated aqueous solution of hydrochloric acid and acetic acid. They contain a superstructure and exhibit remarkably enhanced photocatalytic activities for hydrogen production due to the improved light harvest and facilitated charge transport.

  18. Learning as the Construction and Re-Mediation of Activity Systems: Environmental Management in Biogas Production

    ERIC Educational Resources Information Center

    Pereira Querol, Marco A.; Suutari, Timo; Seppanen, Laura

    2010-01-01

    The purpose of this paper is to present theoretical tools for understanding the dynamics of change and learning during the emergence and development of environmental management activities. The methodology consists of a historical analysis of a case of biogas production that took place in the Southwest region of Finland. The theoretical tools used…

  19. PHARMACEUTICALS AND PERSONAL CARE PRODUCTS IN THE ENVIRONMENT: POLLUTION FROM PERSONAL ACTIONS, ACTIVITIES, AND BEHAVIORS

    EPA Science Inventory



    Perhaps more so than with any other class of pollutants, the occurrence of pharmaceuticals and personal care products (PPCPS) in the environment highlights the immediate, intimate, and inseparable connection between the individual activities of consumers and their environ...

  20. Nobiletin metabolites: synthesis and inhibitory activity against matrix metalloproteinase-9 production.

    PubMed

    Oshitari, Tetsuta; Okuyama, Yuji; Miyata, Yoshiki; Kosano, Hiroshi; Takahashi, Hideyo; Natsugari, Hideaki

    2011-08-01

    A divergent synthesis of nobiletin metabolites was developed through highly oxygenated acetophenone derivative. We used commercially available methyl 3,4,5-trimethoxybenzoate as a starting material for concise preparation of the key intermediate, 2'-hydroxy-3',4',5',6'-tetramethoxyacetophenone (I). These metabolites showed strong inhibitory activity against matrix metalloproteinase-9 production in human lens epithelial cells.

  1. 78 FR 20091 - Foreign-Trade Zone 26-Atlanta, Georgia, Authorization of Production Activity, Perkins Shibaura...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Foreign-Trade Zone 26--Atlanta, Georgia, Authorization of Production Activity, Perkins Shibaura Engines, LLC (Diesel Engines), Griffin, Georgia On November 29, 2012, Georgia Foreign-Trade Zone, Inc., grantee of FTZ 26,...

  2. 78 FR 16247 - Foreign-Trade Zone 38-Spartanburg County, South Carolina; Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-14

    ... Production Activity; ZF Transmissions Gray Court, LLC (Automatic Transmissions); Gray Court, South Carolina... Transmissions Gray Court, LLC, within FTZ 38--Site 20, in Gray Court, South Carolina. The notification was... Federal Register inviting public comment (77 FR 70992-70993, 11-28-2012). The FTZ Board has...

  3. Textile and Apparel Production, Management, and Services. Reference Book [and] Student Activity Book.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Curriculum Center for Family and Consumer Sciences.

    This student activity book and reference book, which are part of a family and consumer sciences education series focusing on a broad range of employment opportunities, are intended for use in 1- and 2-year textile and apparel production, management, and services programs for Texas high school students. The reference book provides information…

  4. Food Production, Management, and Services. Reference Book [and] Student Activity Book.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Curriculum Center for Family and Consumer Sciences.

    This student activity book and reference book, which are part of a family and consumer sciences education series focusing on a broad range of employment opportunities, are intended for use in one- and two-year food production, management, and services programs for Texas high school students. The reference book provides information needed by…

  5. Cross-Language Activation in Children's Speech Production: Evidence from Second Language Learners, Bilinguals, and Trilinguals

    ERIC Educational Resources Information Center

    Poarch, Gregory J.; van Hell, Janet G.

    2012-01-01

    In five experiments, we examined cross-language activation during speech production in various groups of bilinguals and trilinguals who differed in nonnative language proficiency, language learning background, and age. In Experiments 1, 2, 3, and 5, German 5- to 8-year-old second language learners of English, German-English bilinguals,…

  6. Task-Dependent Modulations of Prefrontal and Hippocampal Activity during Intrinsic Word Production

    ERIC Educational Resources Information Center

    Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

    2009-01-01

    Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on…

  7. 77 FR 48127 - Foreign-Trade Zone 20-Suffolk, VA; Notification of Proposed Production Activity, Usui...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-13

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Foreign-Trade Zone 20--Suffolk, VA; Notification of Proposed Production Activity, Usui International Corporation, (Diesel Engine Fuel Lines), Chesapeake, VA The Virginia Port Authority, grantee of FTZ 20, submitted a...

  8. 78 FR 31517 - Notification of Proposed Production Activity; Vestas Nacelles America, Inc.; Subzone 123E (Wind...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-24

    ... From the Federal Register Online via the Government Publishing Office ] DEPARTMENT OF COMMERCE Foreign-Trade Zones Board Notification of Proposed Production Activity; Vestas Nacelles America, Inc.; Subzone 123E (Wind Turbines); Brighton, Denver, Pueblo, and Windsor, Colorado Vestas Nacelles America, Inc. (Vestas), operator of Subzone...

  9. 75 FR 27574 - Agency Information Collection Activities: Comment Request for the Production Estimate, Quarterly...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-17

    ... Comments On October 9, 2009, we published a Federal Register notice (74 FR 52254) announcing that we would..., Minerals Information Team, U.S. Geological Survey. FR Doc. 2010-11617 Filed 5-14-10; 8:45 am] BILLING CODE... Geological Survey Agency Information Collection Activities: Comment Request for the Production...

  10. Synthesis and antifungal activity of natural product-based 6-alkyl-2 3 4 5-tetrahydropyridines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seven 6-alkyl-2,3,4,5-tetrahydropyridines (5a–5g) that mimic the natural products piperideines that were recently identified in the fire ant venom have been synthesized. Compounds 5c–5g with the C-6 alkyl chain lengths from C14 to C18 showed varying degrees of antifungal activities, with 5e (6-hexa...

  11. 78 FR 13857 - Foreign-Trade Zone 84-Houston, TX; Notification of Proposed Production Activity; Toshiba...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-01

    ...; Toshiba International Corporation (Hybrid Electric Vehicle Motors and Generators Production) The Port of... generators for hybrid electric vehicles (HEV). Pursuant to 15 CFR 400.14(b), FTZ activity would be limited to... customs entry procedures that apply to electric motors and generators (duty rates range from free to...

  12. 78 FR 28801 - Foreign-Trade Zone 117-Orange, TX, Authorization of Production Activity, Signal International...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-16

    ... notice in the Federal Register inviting public comment (78 FR 4383, 1-22-2013). The FTZ Board has... Foreign-Trade Zones Board Foreign-Trade Zone 117--Orange, TX, Authorization of Production Activity, Signal International Texas GP, LLC (Shipbuilding), Orange, TX On January 10, 2013, the Foreign Trade Zone of...

  13. Formation of distinct soluble microbial products by activated sludge: kinetic analysis and quantitative determination.

    PubMed

    Ni, Bing-Jie; Fang, Fang; Xie, Wen-Ming; Xu, Juan; Yu, Han-Qing

    2012-02-01

    Soluble microbial products (SMP) released by microorganisms in bioreactors are classified into two distinct groups according to their different chemical and degradation kinetics: utilization-associated products (UAP) and biomass-associated products (BAP). SMP are responsible for effluent chemical oxygen demand or for membrane fouling of membrane bioreactor. Here an effective and convenient approach, other than the complicated chemical methods or complex models, is developed to quantify the formation of UAP and BAP together with their kinetics in activated sludge process. In this approach, an integrated substrate utilization equation is developed and used to determine UAP and their production kinetics. On the basis of total SMP measurements, BAP formation is determined with an integrated BAP formation equation. The fraction of substrate electrons diverted to UAP, and the content of BAP derived from biomass can then be calculated. Dynamic quantification data are obtained for UAP and BAP separately and conveniently. The obtained kinetic parameters are found to be reasonable as they are generally bounded and comparable to the literature values. The validity of this approach is confirmed by independent SMP production tests in six different activated sludge systems, which demonstrates its applicability in a wide range of engineered system regarding SMP production. This work provides a widely applied approach to determine the formation of UAP and BAP conveniently, which may offer engineers with basis to optimize bioreactor operation to avoid a high effluent soluble organics from SMP or SMP-based membrane fouling in membrane bioreactors. PMID:22185635

  14. MS/MS analysis of the products of toluene photooxidation and measurement of their mutagenic activity

    SciTech Connect

    Dumdel, B.E.; Kenny, D.V.; Shepson, P.B.; Kleindienst, T.E.; Nero, C.M.; Cupitt, L.T.; Claxton, L.D.

    1988-12-01

    Products of the photooxidation of toluene from an irradiated 5.1 ppm toluene/0.9 ppm NO/sub x/ mixture were identified by use of a triple-quadrupole MS/MS operated in an atmospheric pressure ionization mode. The reaction was carried out in a flow-mode 22.7-m/sup 3/ Telfon smog chamber. The steady-state reactant and product mixture was continuously transferred to the mass spectrometer inlet at 144 L/min. By using structurally similar standards, semiquantitative MS/MS analyses for many of the ring fragmentation products were conducted. Quantitative analyses by chromatographic methods and semiquantitative analyses by MS/MS were conducted for a variety of ring fragmentation products. The following products were found with yields of 1% (C/C) or greater: methylglyoxal, glyoxal, benzaldehyde, methylbutenedial, hydroxy-methylbutenedial, peroxyacetyl nitrate, oxoheptadienal, CH/sub 3/COOH, HCHO, hexadienal, and hydroxyoxo-heptadienal. The mutagenic activity of the steady-state product mixture was measured by using the Ames assay Salmonella typhimurium strain TA 100. The mutagenic activity data are discussed relative to our earlier findings that resulted from different reaction conditions.

  15. Structural transitions of complement component C3 and its activation products

    PubMed Central

    Nishida, Noritaka; Walz, Thomas; Springer, Timothy A.

    2006-01-01

    Complement sensitizes pathogens for phagocytosis and lysis. We use electron microscopy to examine the structural transitions in the activation of the pivotal protein in the complement pathway, C3. In the cleavage product C3b, the position of the thioester domain moves ≈100 Å, which becomes covalently coupled to antigenic surfaces. In the iC3b fragment, cleavage in an intervening domain creates a long flexible linker between the thioester domain and the macroglobulin domain ring of C3. Studies on two products of nucleophile addition to C3 reveal a structural intermediate in activation, and a final product, in which the anaphylatoxin domain has undergone a remarkable movement through the macroglobulin ring. PMID:17172439

  16. Enhancement of sludge reduction and methane production by removing extracellular polymeric substances from waste activated sludge.

    PubMed

    Nguyen, Minh Tuan; Mohd Yasin, Nazlina Haiza; Miyazaki, Toshiki; Maeda, Toshinari

    2014-12-01

    The management of waste activated sludge (WAS) recycling is a concern that affects the development of the future low-carbon society, particularly sludge reduction and biomass utilization. In this study, we investigated the effect of removing extracellular polymeric substances (EPS), which play important roles in the adhesion and flocculation of WAS, on increased sludge disintegration, thereby enhancing sludge reduction and methane production by anaerobic digestion. EPS removal from WAS by ethylenediaminetetraacetic acid (EDTA) significantly enhanced sludge reduction, i.e., 49 ± 5% compared with 27 ± 1% of the control at the end the digestion process. Methane production was also improved in WAS without EPS by 8881 ± 109 CH4 μmol g(-1) dry-weight of sludge. Microbial activity was determined by denaturing gradient gel electrophoresis and real-time polymerase chain reaction, which showed that the hydrolysis and acetogenesis stages were enhanced by pretreatment with 2% EDTA, with a larger methanogenic community and better methane production.

  17. The regulation of work activity and the new labor and production contexts.

    PubMed

    Silva, Elaine Cristina; Bento, Paulo Eduardo Gomes

    2012-01-01

    In recent decades, there has been a rise in the use o lean production model techniques. Through this approach, companies become more flexible, a fact that increases the interest in studies regarding the introduction of this model in businesses and its impacts on working conditions. Important observations concerning ergonomics, such as the theme of work activity regulation, have been highlighted in such studies. This article aims to discuss strategies and regulations adopted by the workers on assembly lines that are considered flexible. The article presents the results of a study in a company that adopts some lean production techniques. The study was analyzed using the activity analysis as one of the premises of the Ergonomic Work Analysis (EWA). Many aspects of the traditional assembly line remain present in the scenario that was studied, however a new language was employed and aspects in the nature of regulations demonstrate that the relation with lean production techniques influence the operators' operational modes.

  18. Factor Xa stimulates fibroblast procollagen production, proliferation, and calcium signaling via PAR{sub 1} activation

    SciTech Connect

    Blanc-Brude, Olivier P. . E-mail: olivier.blanc-brude@larib.inserm.fr; Archer, Fabienne; Leoni, Patricia; Derian, Claudia; Bolsover, Steven; Laurent, Geoffrey J.; Chambers, Rachel C.

    2005-03-10

    Fibroblast proliferation and procollagen production are central features of tissue repair and fibrosis. In addition to its role in blood clotting, the coagulation cascade proteinase thrombin can contribute to tissue repair by stimulating fibroblasts via proteolytic activation of proteinase-activated receptor-1 (PAR{sub 1}). During hemostasis, the coagulation cascade proteinase factor X is converted into factor Xa. We have previously shown that factor Xa upregulates fibroblast proliferation via production of autocrine PDGF. In this study, we further examined the effects of factor Xa on fibroblast function and aimed to identify its signaling receptor. We showed that factor Xa stimulates procollagen promoter activity and protein production by human and mouse fibroblasts. This effect was independent of PDGF and thrombin production, but dependent on factor Xa proteolytic activity. We also showed that PAR{sub 1}-deficient mouse fibroblasts did not upregulate procollagen production, mobilize cytosolic calcium, or proliferate in response to factor Xa. Desensitization techniques and PAR{sub 1}-specific agonists and inhibitors were used to demonstrate that PAR{sub 1} mediates factor Xa signaling in human fibroblasts. This is the first report that factor Xa stimulates extracellular matrix production. In contrast with endothelial cells and vascular smooth muscle cells, fibroblasts appear to be the only cell type in which the effects of factor Xa are mediated mainly via PAR{sub 1} and not PAR{sub 2}. These findings are critical for our understanding of tissue repair and fibrotic mechanisms, and for the design of novel approaches to inhibit the profibrotic effects of the coagulation cascade without compromising blood hemostasis.

  19. Activity and biological effects of neem products against arthropods of medical and veterinary importance.

    PubMed

    Mulla, M S; Su, T

    1999-06-01

    Botanical insecticides are relatively safe and degradable, and are readily available sources of biopesticides. The most prominent phytochemical pesticides in recent years are those derived from neem trees, which have been studied extensively in the fields of entomology and phytochemistry, and have uses for medicinal and cosmetic purposes. The neem products have been obtained from several species of neem trees in the family Meliaceae. Six species in this family have been the subject of botanical pesticide research. They are Azadirachta indica A. Juss, Azadirachta excelsa Jack, Azadirachta siamens Valeton, Melia azedarach L., Melia toosendan Sieb. and Zucc., and Melia volkensii Gürke. The Meliaceae, especially A. indica (Indian neem tree), contains at least 35 biologically active principles. Azadirachtin is the predominant insecticidal active ingredient in the seed, leaves, and other parts of the neem tree. Azadirachtin and other compounds in neem products exhibit various modes of action against insects such as antifeedancy, growth regulation, fecundity suppression and sterilization, oviposition repellency or attractancy, changes in biological fitness, and blocking development of vector-borne pathogens. Some of these bioactivity parameters of neem products have been investigated at least in some species of insects of medical and veterinary importance, such as mosquitoes, flies, triatomines, cockroaches, fleas, lice, and others. Here we review, synthesize, and analyze published information on the activity, modes of action, and other biological effects of neem products against arthropods of medical and veterinary importance. The amount of information on the activity, use, and application of neem products for the control of disease vectors and human and animal pests is limited. Additional research is needed to determine the potential usefulness of neem products in vector control programs. PMID:10412110

  20. Common Commercial and Consumer Products Contain Activators of the Aryl Hydrocarbon (Dioxin) Receptor

    PubMed Central

    Zhao, Bin; Bohonowych, Jessica E. S.; Timme-Laragy, Alicia; Jung, Dawoon; Affatato, Alessandra A.; Rice, Robert H.; Di Giulio, Richard T.; Denison, Michael S.

    2013-01-01

    Activation of the Ah receptor (AhR) by halogenated aromatic hydrocarbons (HAHs), such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, dioxin), can produce a wide variety of toxic and biological effects. While recent studies have shown that the AhR can bind and be activated by structurally diverse chemicals, how widespread of these AhR agonists are in environmental, biological and synthetic materials remains to be determined. Using AhR-based assays, we demonstrate the presence of potent AhR agonists in a variety of common commercial and consumer items. Solvent extracts of paper, rubber and plastic products contain chemicals that can bind to and stimulate AhR DNA binding and/or AhR-dependent gene expression in hepatic cytosol, cultured cell lines, human epidermis and zebrafish embryos. In contrast to TCDD and other persistent dioxin-like HAHs, activation of AhR-dependent gene expression by these extracts was transient, suggesting that the agonists are metabolically labile. Solvent extracts of rubber products produce AhR-dependent developmental toxicity in zebrafish in vivo, and inhibition of expression of the metabolic enzyme CYP1A, significantly increased their toxic potency. Although the identity of the responsible AhR-active chemicals and their toxicological impact remain to be determined, our data demonstrate that AhR active chemicals are widely distributed in everyday products. PMID:23441220

  1. 31 CFR 542.529 - Policy on activities related to petroleum and petroleum products of Syrian origin for the benefit...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... petroleum and petroleum products of Syrian origin for the benefit of the National Coalition of Syrian... activities related to petroleum and petroleum products of Syrian origin for the benefit of the National... the purchase, trade, export, import, or production of petroleum or petroleum products of Syrian...

  2. A review on plant-derived natural products and their analogs with anti-tumor activity

    PubMed Central

    Dholwani, K.K.; Saluja, A.K.; Gupta, A.R.; Shah, D.R.

    2008-01-01

    Traditional medicines, including Chinese herbal formulations, can serve as the source of potential new drugs, and initial research focuses on the isolation of bioactive lead compound(s). The development of novel plant-derived natural products and their analogs for anticancer activity details efforts to synthesize new derivatives based on bioactivity- and mechanism of action-directed isolation and characterization coupled with rational drug design - based modification. Also, the anticancer activity of certain natural products and their analogs can be enhanced by synthesizing new derivatives based on active pharmacophore models; drug resistance and solubility and metabolic limitations can be overcome by appropriate molecular modifications; and new biological properties or mechanisms of action can be added by combining other functional groups or molecules. Preclinical screening for in vitro human cell line panels and selected in vivo xenograft testing then identifies the most promising drug development targets. PMID:21279166

  3. Reactive oxygen species production and antioxidant enzyme activity during epididymal sperm maturation in Corynorhinus mexicanus bats.

    PubMed

    Arenas-Ríos, Edith; Rosado García, Adolfo; Cortés-Barberena, Edith; Königsberg, Mina; Arteaga-Silva, Marcela; Rodríguez-Tobón, Ahiezer; Fuentes-Mascorro, Gisela; León-Galván, Miguel Angel

    2016-03-01

    Prolonged sperm storage in the epididymis of Corynorhinus mexicanus bats after testicular regression has been associated with epididymal sperm maturation in the caudal region, although the precise factors linked with this phenomenon are unknown. The aim of this work is to determine the role of reactive oxygen species (ROS) and changes in antioxidant enzymatic activity occurring in the spermatozoa and epididymal fluid over time, in sperm maturation and storage in the caput, corpus and cauda of the bat epididymis. Our data showed that an increment in ROS production coincided with an increase in superoxide dismutase (SOD) activity in epididymal fluid and with a decrease in glutathione peroxidase (GPX) activity in the spermatozoa in at different time points and epididymal regions. The increase in ROS production was not associated with oxidative damage measured by lipid peroxidation. The results of the current study suggest the existence of a shift in the redox balance, which might be associated with sperm maturation and storage.

  4. The Influence of Consumer Goals and Marketing Activities on Product Bundling

    NASA Astrophysics Data System (ADS)

    Haijun, Wang

    Upon entering a store, consumers are faced with the questions of whether to buy, what to buy, and how much to buy. Consumers include products from different categories in their decision process. Product categories can be related in different ways. Product bundling is a process that involves the choice of at least two non-substitutable items. In this research, the consumers' explicit product bundling activity at the point of sale is focused. We focuses on the retailers' perspective and therefore leaves out consumers' brand choice decisions, concentrating on purchase incidence and quantity. At the base of the current model of the exist researches, we integrate behavioural choice analysis and predictive choice modelling through the underlying behavioural models, called random utility maximization (RUM) models. The methodological contribution of this research lies therein to combine a nested logit choice model with a latent variable factor model. We point out several limitations for both theory and practice at the end.

  5. Cash transfer programme, productive activities and labour supply: Evidence from randomized experiment in Kenya

    PubMed Central

    Asfaw, Solomon; Davis, Benjamin; Dewbre, Josh; Handa, Sudhanshu; Winters, Paul

    2015-01-01

    This paper reports analysis of the impact of Kenya’s Cash Transfer for Orphans and Vulnerable Children Programme on the household decisions on productive activities using data from a randomized experimental design. Results show that the programme had a positive and significant impact on food consumption coming from home production, accumulation of productive assets, especially on the ownership of small livestock and on formation of nonfarm enterprise, especially for females. The programme has provided more flexibility to families in terms of labour allocation decisions, particularly for those who are geographically isolated. The programme was also found to have reduced child labour, an important objective of the programme. However we find very little impact of the programme on direct indicators of crop production. PMID:25663712

  6. Identification and steroid receptor activity of products formed from the bromination of technical nonylphenol.

    PubMed

    Hill, Elizabeth M; Smith, Michael D

    2006-09-01

    Alkylphenols are commonly present in wastewater effluents and may contribute to the total hormonal loading of receiving waters due to their weakly estrogenic properties. However the presence of reactive bromine species in some treated wastewaters can result in the formation of brominated alkylphenols which may also possess steroid receptor activity. In this study, the products of bromination of technical nonylphenol (NP) were identified, purified and tested in vitro in recombinant yeast steroid receptor transcription assays. Bromination of NP in the presence of acetic acid resulted in the formation of one major product which was identified as 2-bromo-4-nonylphenol (NPBr). In the presence of methanol/water, bromination of NP resulted in the formation 2,6-dibromo-4-nonylphenol (NPBr2) as well as a number of other minor polybrominated products. The EC50 of NPBr in the yeast estrogen receptor transcription (YES) assay was 6.7x10(-6) M, which was 48 fold less active than NP and 86,000 fold less active than the estrogen agonist 17beta-estradiol NPBr2 was not active in the YES assay. NP, NPBr and NPBr2 were all weakly androgenic in the yeast androgen receptor transcription assay but at concentrations which were 100,000 fold less active than the androgen receptor agonist dihydrotestosterone. Neither NP, NPBr or NPBr2 exhibited appreciable anti-estrogenic or anti-androgenic activity in the yeast receptor transcription assays. This study suggests that bromination of NP markedly reduces its estrogen receptor transcription activity but has no effect on the weak androgen receptor transcription activity of the alkylphenol. PMID:16473392

  7. Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production

    PubMed Central

    Colin, Sophie; Briand, Olivier; Touche, Véronique; Wouters, Kristiaan; Baron, Morgane; Pattou, François; Hanf, Rémy; Tailleux, Anne; Chinetti, Giulia; Staels, Bart; Lestavel, Sophie

    2013-01-01

    Aims Peroxisome Proliferator-Activated Receptor (PPAR) α is a transcription factor controlling lipid metabolism in liver, heart, muscle and macrophages. PPARα-activation increases plasma HDL-cholesterol and exerts hypotriglyceridemic actions via the liver. However, the intestine expresses PPARα, produces HDL and chylomicrons and is exposed to diet-derived PPARα ligands. Therefore, we examined the effects of PPARα-activation on intestinal lipid and lipoprotein metabolism. Methods and Results The impact of PPARα-activation was evaluated in term of HDL-related gene expression in mice, ex-vivo in human jejunal biopsies and in Caco-2/TC7 cells. ApoAI/HDL secretion, cholesterol esterification and trafficking were also studied in-vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty-acid-oxidation genes, treatment with the dual PPARα/δ-ligand GFT505 resulted in a more pronounced increase of plasma HDL compared to fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL-production genes such as apolipoprotein-AI and ATP-Binding-Cassette-A1 transporter in murine intestines. A similar increase was observed upon PPARα-activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPARα-activation decreased the cholesterol-esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking and reduced apolipoprotein-B secretion. Conclusions PPARα-activation reduces cholesterol esterification, suppresses chylomicron- and increases HDL-secretion by enterocytes. These results identify the intestine as a target organ of PPARα-ligands with entero-hepatic tropism to reduce atherogenic dyslipidemia. PMID:22843443

  8. 78 FR 39254 - Notification of Proposed Production Activity; Subzone 7G; Schering-Plough Products, L.L.C...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... Products, L.L.C. (Pharmaceutical Products); Las Piedras, Puerto Rico Schering-Plough Products, L.L.C...-Plough currently has authority to produce certain pharmaceutical products and their intermediates within Subzone 7G. The current request would add the production of suvorexant pharmaceutical tablets for...

  9. Toward aldehyde and alkane production by removing aldehyde reductase activity in Escherichia coli

    PubMed Central

    Rodriguez, Gabriel M.; Atsumi, Shota

    2015-01-01

    Advances in synthetic biology and metabolic engineering have enabled the construction of novel biological routes to valuable chemicals using suitable microbial hosts. Aldehydes serve as chemical feedstocks in the synthesis of rubbers, plastics, and other larger molecules. Microbial production of alkanes is dependent on the formation of a fatty aldehyde intermediate which is converted to an alkane by an aldehyde deformylating oxygenase (ADO). However, microbial hosts such as Escherichia coli are plagued by many highly active endogenous aldehyde reductases (ALRs) that convert aldehydes to alcohols, which greatly complicates strain engineering for aldehyde and alkane production. It has been shown that the endogenous ALR activity outcompetes the ADO enzyme for fatty aldehyde substrate. The large degree of ALR redundancy coupled with an incomplete database of ALRs represents a significant obstacle in engineering E. coli for either aldehyde or alkane production. In this study, we identified 44 ALR candidates encoded in the E. coli genome using bioinformatics tools, and undertook a comprehensive screening by measuring the ability of these enzymes to produce isobutanol. From the pool of 44 candidates, we found five new ALRs using this screening method (YahK, DkgA, GldA, YbbO, and YghA). Combined deletions of all 13 known ALRs resulted in a 90–99% reduction in endogenous ALR activity for a wide range of aldehyde substrates (C2–C12). Elucidation of the ALRs found in E. coli could guide one in reducing competing alcohol formation during alkane or aldehyde production. PMID:25108218

  10. Cell-specific production and antimicrobial activity of naphthoquinones in roots of lithospermum erythrorhizon

    PubMed

    Brigham; Michaels; Flores

    1999-02-01

    Pigmented naphthoquinone derivatives of shikonin are produced at specific times and in specific cells of Lithospermum erythrorhizon roots. Normal pigment development is limited to root hairs and root border cells in hairy roots grown on "noninducing" medium, whereas induction of additional pigment production by abiotic (CuSO4) or biotic (fungal elicitor) factors increases the amount of total pigment, changes the ratios of derivatives produced, and initiates production of pigment de novo in epidermal cells. When the biological activity of these compounds was tested against soil-borne bacteria and fungi, a wide range of sensitivity was recorded. Acetyl-shikonin and beta-hydroxyisovaleryl-shikonin, the two most abundant derivatives in both Agrobacterium rhizogenes-transformed "hairy-root" cultures and greenhouse-grown plant roots, were the most biologically active of the seven compounds tested. Hyphae of the pathogenic fungi Rhizoctonia solani, Pythium aphanidermatum, and Nectria hematococca induced localized pigment production upon contact with the roots. Challenge by R. solani crude elicitor increased shikonin derivative production 30-fold. We have studied the regulation of this suite of related, differentially produced, differentially active compounds to understand their role(s) in plant defense at the cellular level in the rhizosphere.

  11. Deposition of fission and activation products after the Fukushima Dai-ichi nuclear power plant accident.

    PubMed

    Shozugawa, Katsumi; Nogawa, Norio; Matsuo, Motoyuki

    2012-04-01

    The Great Eastern Japan Earthquake on March 11, 2011, damaged reactor cooling systems at Fukushima Dai-ichi nuclear power plant. The subsequent venting operation and hydrogen explosion resulted in a large radioactive nuclide emission from reactor containers into the environment. Here, we collected environmental samples such as soil, plant species, and water on April 10, 2011, in front of the power plant main gate as well as 35 km away in Iitate village, and observed gamma-rays with a Ge(Li) semiconductor detector. We observed activation products ((239)Np and (59)Fe) and fission products ((131)I, (134)Cs ((133)Cs), (137)Cs, (110m)Ag ((109)Ag), (132)Te, (132)I, (140)Ba, (140)La, (91)Sr, (91)Y, (95)Zr, and (95)Nb). (239)Np is the parent nuclide of (239)Pu; (59)Fe are presumably activation products of (58)Fe obtained by corrosion of cooling pipes. The results show that these activation and fission products, diffused within a month of the accident.

  12. Antioxidant, Anti-Tyrosinase and Anti-Inflammatory Activities of Oil Production Residues from Camellia tenuifloria.

    PubMed

    Chiou, Shu-Yuan; Ha, Choi-Lan; Wu, Pei-Shan; Yeh, Chiu-Ling; Su, Ying-Shan; Li, Man-Po; Wu, Ming-Jiuan

    2015-12-10

    Camellia tenuifloria is an indigenous Camellia species used for the production of camellia oil in Taiwan. This study investigated for the first time the potential antioxidant, anti-tyrosinase and anti-inflammatory activities of oil production byproducts, specifically those of the fruit shell, seed shell, and seed pomace from C. tenuifloria. It was found that the crude ethanol extract of the seed shell had the strongest DPPH scavenging and mushroom tyrosinase inhibitory activities, followed by the fruit shell, while seed pomace was the weakest. The IC50 values of crude extracts and fractions on monophenolase were smaller than diphenolase. The phenolic-rich methanol fraction of seed shell (SM) reduced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It also repressed the expression of IL-1β, and secretion of prostaglandin E₂ (PGE₂) and IL-6 in response to LPS. SM strongly stimulated heme oxygenase 1 (HO-1) expression and addition of zinc protoporphyrin (ZnPP), a HO-1 competitive inhibitor, reversed the inhibition of NO production, indicating the involvement of HO-1 in its anti-inflammatory activity. The effects observed in this study provide evidence for the reuse of residues from C. tenuifloria in the food additive, medicine and cosmetic industries.

  13. Antioxidant, Anti-Tyrosinase and Anti-Inflammatory Activities of Oil Production Residues from Camellia tenuifloria

    PubMed Central

    Chiou, Shu-Yuan; Ha, Choi-Lan; Wu, Pei-Shan; Yeh, Chiu-Ling; Su, Ying-Shan; Li, Man-Po; Wu, Ming-Jiuan

    2015-01-01

    Camellia tenuifloria is an indigenous Camellia species used for the production of camellia oil in Taiwan. This study investigated for the first time the potential antioxidant, anti-tyrosinase and anti-inflammatory activities of oil production byproducts, specifically those of the fruit shell, seed shell, and seed pomace from C. tenuifloria. It was found that the crude ethanol extract of the seed shell had the strongest DPPH scavenging and mushroom tyrosinase inhibitory activities, followed by the fruit shell, while seed pomace was the weakest. The IC50 values of crude extracts and fractions on monophenolase were smaller than diphenolase. The phenolic-rich methanol fraction of seed shell (SM) reduced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It also repressed the expression of IL-1β, and secretion of prostaglandin E2 (PGE2) and IL-6 in response to LPS. SM strongly stimulated heme oxygenase 1 (HO-1) expression and addition of zinc protoporphyrin (ZnPP), a HO-1 competitive inhibitor, reversed the inhibition of NO production, indicating the involvement of HO-1 in its anti-inflammatory activity. The effects observed in this study provide evidence for the reuse of residues from C. tenuifloria in the food additive, medicine and cosmetic industries. PMID:26690417

  14. Phosphoribosyl pyrophosphate synthetase activity affects growth and riboflavin production in Ashbya gossypii

    PubMed Central

    Jiménez, Alberto; Santos, María A; Revuelta, José L

    2008-01-01

    Background Phosphoribosyl pyrophosphate (PRPP) is a central compound for cellular metabolism and may be considered as a link between carbon and nitrogen metabolism. PRPP is directly involved in the de novo and salvage biosynthesis of GTP, which is the immediate precursor of riboflavin. The industrial production of this vitamin using the fungus Ashbya gossypii is an important biotechnological process that is strongly influenced by substrate availability. Results Here we describe the characterization and manipulation of two genes of A. gossypii encoding PRPP synthetase (AGR371C and AGL080C). We show that the AGR371C and AGL080C gene products participate in PRPP synthesis and exhibit inhibition by ADP. We also observed a major contribution of AGL080C to total PRPP synthetase activity, which was confirmed by an evident growth defect of the Δagl080c strain. Moreover, we report the overexpression of wild-type and mutant deregulated isoforms of Agr371cp and Agl080cp that significantly enhanced the production of riboflavin in the engineered A. gossypii strains. Conclusion It is shown that alterations in PRPP synthetase activity have pleiotropic effects on the fungal growth pattern and that an increase in PRPP synthetase enzymatic activity can be used to enhance riboflavin production in A. gossypii. PMID:18782443

  15. Advances in the analysis of non-allowed pharmacologically active substances in cosmetic products.

    PubMed

    Pellegrini, Manuela; Marchei, Emilia; Pacifici, Roberta; Rotolo, Maria Concetta; Pichini, Simona

    2011-06-25

    The state-of-the art analysis of non-allowed pharmacologically active substances in cosmetic products is here presented and a new methodology developed for this type of analysis is proposed. Cosmetic products released on the market should not cause damage to human health when applied under normal conditions of use. With respect to this condition, the definition of "cosmetic product" is reported according to the international and region specific regulatory requirements for the manufacturing and marketing and that of non-allowed substances with particular reference to pharmacologically active substances, with therapeutic indication. The existing methodologies for the analysis of non-allowed products in cosmetic preparations generally include some sort of sample treatment and/or extraction before the analytical step, which always include a separation by liquid chromatography (LC) at ambient temperature followed by detection with ultraviolet spectrophotometric detection or mass spectrometry. A systematic high throughput analysis of non-allowed pharmacologically active substances is finally proposed together with the results of such an analysis performed in the "Drug abuse and doping" Unit of the National Institute of Health in Rome.

  16. Deposition of fission and activation products after the Fukushima Dai-ichi nuclear power plant accident.

    PubMed

    Shozugawa, Katsumi; Nogawa, Norio; Matsuo, Motoyuki

    2012-04-01

    The Great Eastern Japan Earthquake on March 11, 2011, damaged reactor cooling systems at Fukushima Dai-ichi nuclear power plant. The subsequent venting operation and hydrogen explosion resulted in a large radioactive nuclide emission from reactor containers into the environment. Here, we collected environmental samples such as soil, plant species, and water on April 10, 2011, in front of the power plant main gate as well as 35 km away in Iitate village, and observed gamma-rays with a Ge(Li) semiconductor detector. We observed activation products ((239)Np and (59)Fe) and fission products ((131)I, (134)Cs ((133)Cs), (137)Cs, (110m)Ag ((109)Ag), (132)Te, (132)I, (140)Ba, (140)La, (91)Sr, (91)Y, (95)Zr, and (95)Nb). (239)Np is the parent nuclide of (239)Pu; (59)Fe are presumably activation products of (58)Fe obtained by corrosion of cooling pipes. The results show that these activation and fission products, diffused within a month of the accident. PMID:22266366

  17. Penrose pair production as a power source of quasars and active galactic nuclei. [black hole mechanisms

    NASA Technical Reports Server (NTRS)

    Kafatos, M.; Leiter, D.

    1979-01-01

    Penrose pair production in massive canonical Kerr black holes (those with a/M equal to 0.998) is proposed as a way to explain the nature of the vast fluctuating energy production associated with active galactic nuclei and quasars. It is assumed that a Kerr black hole with a mass of the order of 100 million solar masses lies at the center of an active nucleus and that an accretion disk is formed. Penrose pair production in the inner ergosphere of such a massive canonical Kerr black hole is analyzed. The results indicate that: (1) particle pairs are ejected within a 40 deg angle relative to the equator; (2) the particle energy is of the order of 1 GeV per pair; (3) the pressure of the electron-positron relativistic gas is proportional to the electron-positron number density; (4) pair production may occur in bursts; and (5) the overall lifetime of an active nucleus would depend on the time required to exhaust the disk of its matter content. A test of the theory is suggested which involves observation of the 0.5-MeV pair-annihilation gamma rays that would be generated by annihilating particle pairs.

  18. Antioxidant, Anti-Tyrosinase and Anti-Inflammatory Activities of Oil Production Residues from Camellia tenuifloria.

    PubMed

    Chiou, Shu-Yuan; Ha, Choi-Lan; Wu, Pei-Shan; Yeh, Chiu-Ling; Su, Ying-Shan; Li, Man-Po; Wu, Ming-Jiuan

    2015-01-01

    Camellia tenuifloria is an indigenous Camellia species used for the production of camellia oil in Taiwan. This study investigated for the first time the potential antioxidant, anti-tyrosinase and anti-inflammatory activities of oil production byproducts, specifically those of the fruit shell, seed shell, and seed pomace from C. tenuifloria. It was found that the crude ethanol extract of the seed shell had the strongest DPPH scavenging and mushroom tyrosinase inhibitory activities, followed by the fruit shell, while seed pomace was the weakest. The IC50 values of crude extracts and fractions on monophenolase were smaller than diphenolase. The phenolic-rich methanol fraction of seed shell (SM) reduced nitric oxide (NO) production, and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. It also repressed the expression of IL-1β, and secretion of prostaglandin E₂ (PGE₂) and IL-6 in response to LPS. SM strongly stimulated heme oxygenase 1 (HO-1) expression and addition of zinc protoporphyrin (ZnPP), a HO-1 competitive inhibitor, reversed the inhibition of NO production, indicating the involvement of HO-1 in its anti-inflammatory activity. The effects observed in this study provide evidence for the reuse of residues from C. tenuifloria in the food additive, medicine and cosmetic industries. PMID:26690417

  19. Prenylated flavonoids from Artocarpus altilis: antioxidant activities and inhibitory effects on melanin production.

    PubMed

    Lan, Wen-Chun; Tzeng, Cheng-Wei; Lin, Chun-Ching; Yen, Feng-Lin; Ko, Horng-Huey

    2013-05-01

    Flavonoids, 10-oxoartogomezianone (1), 8-geranyl-3-(hydroxyprenyl)isoetin (2), hydroxyartoflavone A (3), isocycloartobiloxanthone (4), and furanocyclocommunin (5), together with 12 known compounds, were isolated from heartwood and cortex of Artocarpus altilis, and their structures were identified by comparing their spectra with those of similar compounds. To identify natural antioxidants and whitening agents, the ability of these prenylated flavonoids was assessed to scavenge the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH), the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+·)) radical cation, and the superoxide anion (O2(-·)), and their abilities to inhibit tyrosinase and melanin production. It was found that compounds 3, 4, and artoflavone A (15) had moderate DPPH(·)-scavenging activity, whereas compound 4 exhibited significant ABTS(+·)-scavenging activity, and that norartocarpetin (7) and artogomezianone (8) exhibited moderate ABTS(+·)-scavenging activity, with compounds 2, 7, and artocarpin (6) displaying good superoxide anion-scavenging activity. In addition, compounds 7, 8, cudraflavone A (14), and artonin M (17), inhibited melanin production by strongly suppressing tyrosinase activity. Compound 6 reduced the melanin content without inhibiting tyrosinase activity. These results suggest that flavonoids isolated from A. altilis may be candidate antioxidants and/or skin-whitening agents. However, further investigations are required to determine their mechanisms of action.

  20. Radon decay products in realistic living rooms and their activity distributions in human respiratory system.

    PubMed

    Mohery, M; Abdallah, A M; Baz, S S; Al-Amoudi, Z M

    2014-12-01

    In this study, the individual activity concentrations of attached short-lived radon decay products ((218)Po, (214)Pb and (214)Po) in aerosol particles were measured in ten poorly ventilated realistic living rooms. Using standard methodologies, the samples were collected using a filter holder technique connected with alpha-spectrometric. The mean value of air activity concentration of these radionuclides was found to be 5.3±0.8, 4.5±0.5 and 3.9±0.4 Bq m(-3), respectively. Based on the physical properties of the attached decay products and physiological parameters of light work activity for an adult human male recommended by ICRP 66 and considering the parameters of activity size distribution (AMD = 0.25 μm and σ(g) = 2.5) given by NRC, the total and regional deposition fractions in each airway generation could be evaluated. Moreover, the total and regional equivalent doses in the human respiratory tract could be estimated. In addition, the surface activity distribution per generation is calculated for the bronchial region (BB) and the bronchiolar region (bb) of the respiratory system. The maximum values of these activities were found in the upper bronchial airway generations.

  1. Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide

    PubMed Central

    TOHYAMA, M.; KAWAKAMI, K.; FUTENMA, M.; SAITO, A.

    1996-01-01

    We examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-γ)-induced cryptococcostatic activity of murine peritoneal macrophages using NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of RNI synthesis, and superoxide dismutase (SOD) and catalase, oxygen radical scavengers. IFN-γ-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant. IFN-γ also enhanced the suppressive effect on cryptococcal growth in a similar dose-dependent manner. The induction of killing activity and NO production by an optimal dose of IFN-γ (100 U/ml) was virtually suppressed by 500 μM L-NMMA. These results confirmed the importance of the RNI-mediated effector mechanism in anticryptococcal activity of macrophages. SOD and catalase significantly enhanced the cryptococcostatic activity of macrophages induced by a suboptimal dose of IFN-γ (20 U/ml). The augmenting effect of these reagents was mediated by NO, since they potentiated the production of NO by macrophages and their effects were totally blocked by L-NMMA. Our results indicate that the IFN-γ-induced anticryptococcal activity of macrophages is dependent mostly on RNI, and suggest that the ROI system down-regulates the effector mechanism for cryptococcostasis by suppressing the RNI system. PMID:8608643

  2. Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products.

    PubMed

    Ozaki, Hitomi; Sugihara, Kazumi; Watanabe, Yoko; Ohta, Shigeru; Kitamura, Shigeyuki

    2016-01-01

    The in vitro cytochrome P450 (CYP)-inhibitory effects of 11 parabens and 7 phthalates used in consumer products, as well as their hydrolytic metabolites, were investigated, using rat liver microsomes as an enzyme source. The effects on individual CYP isozymes were evaluated by assaying inhibition of activities towards specific substrates, i.e., ethoxyresorufin O-dealkylase (EROD), methoxyresorufin O-dealkylase (MROD), pentoxyresorufin O-dealkylase (PROD), 7-benzyloxy-4-trifluoromethylcoumarin dealkylase (BFCD), 7-methoxy-4-trifluoromethylcoumarin dealkylase (MFCD) and 7-ethoxy-4-trifluoromethylcoumarin dealkylase (EFCD) activities. These activities were dose-dependently inhibited, most potently by medium-side-chain parabens (C6-9) and phthalates (C4-6), and less potently by shorter- and longer-side-chain esters. The hydrolytic product of parabens, 4-hydroxybenzoic acid, was not inhibitory, while those of phthalates, phthalic acid monoesters, showed lower inhibitory activity than the parent phthalates. Parabens showed relatively potent inhibition of MFCD activity, considered to be mainly due to CYP2C, and phthalates showed relatively potent inhibition of PROD activity, considered to be mainly due to CYP2B. PMID:27432241

  3. Hyperthyroidism increases the uncoupled ATPase activity and heat production by the sarcoplasmic reticulum Ca2+-ATPase.

    PubMed Central

    Arruda, Ana Paula; Da-Silva, Wagner S; Carvalho, Denise P; De Meis, Leopoldo

    2003-01-01

    The sarcoplasmic reticulum Ca2+-ATPase is able to modulate the distribution of energy released during ATP hydrolysis, so that a portion of energy is used for Ca2+ transport (coupled ATPase activity) and a portion is converted into heat (uncoupled ATPase activity). In this report it is shown that T4 administration to rabbits promotes an increase in the rates of both the uncoupled ATPase activity and heat production in sarcoplasmic reticulum vesicles, and that the degree of activation varies depending on the muscle type used. In white muscles hyperthyroidism promotes a 0.8-fold increase of the uncoupled ATPase activity and in red muscle a 4-fold increase. The yield of vesicles from hyperthyroid muscles is 3-4-fold larger than that obtained from normal muscles; thus the rate of heat production by the Ca2+-ATPase expressed in terms of g of muscle in hyperthyroidism is increased by a factor of 3.6 in white muscles and 12.0 in red muscles. The data presented suggest that the Ca2+-ATPase uncoupled activity may represent one of the heat sources that contributes to the enhanced thermogenesis noted in hyperthyroidism. PMID:12887329

  4. Cytochrome P450-inhibitory activity of parabens and phthalates used in consumer products.

    PubMed

    Ozaki, Hitomi; Sugihara, Kazumi; Watanabe, Yoko; Ohta, Shigeru; Kitamura, Shigeyuki

    2016-01-01

    The in vitro cytochrome P450 (CYP)-inhibitory effects of 11 parabens and 7 phthalates used in consumer products, as well as their hydrolytic metabolites, were investigated, using rat liver microsomes as an enzyme source. The effects on individual CYP isozymes were evaluated by assaying inhibition of activities towards specific substrates, i.e., ethoxyresorufin O-dealkylase (EROD), methoxyresorufin O-dealkylase (MROD), pentoxyresorufin O-dealkylase (PROD), 7-benzyloxy-4-trifluoromethylcoumarin dealkylase (BFCD), 7-methoxy-4-trifluoromethylcoumarin dealkylase (MFCD) and 7-ethoxy-4-trifluoromethylcoumarin dealkylase (EFCD) activities. These activities were dose-dependently inhibited, most potently by medium-side-chain parabens (C6-9) and phthalates (C4-6), and less potently by shorter- and longer-side-chain esters. The hydrolytic product of parabens, 4-hydroxybenzoic acid, was not inhibitory, while those of phthalates, phthalic acid monoesters, showed lower inhibitory activity than the parent phthalates. Parabens showed relatively potent inhibition of MFCD activity, considered to be mainly due to CYP2C, and phthalates showed relatively potent inhibition of PROD activity, considered to be mainly due to CYP2B.

  5. Microbial Activation of Wooden Vats Used for Traditional Cheese Production and Evolution of Neoformed Biofilms.

    PubMed

    Gaglio, Raimondo; Cruciata, Margherita; Di Gerlando, Rosalia; Scatassa, Maria Luisa; Cardamone, Cinzia; Mancuso, Isabella; Sardina, Maria Teresa; Moschetti, Giancarlo; Portolano, Baldassare; Settanni, Luca

    2015-11-06

    Three Lactococcus lactis subsp. cremoris strains were used to develop ad hoc biofilms on the surfaces of virgin wooden vats used for cheese production. Two vats (TZ) were tested under controlled conditions (pilot plant), and two vats (TA) were tested under uncontrolled conditions (industrial plant). In each plant, one vat (TA1 and TZ1) was used for the control, traditional production of PDO Vastedda della Valle del Belìce (Vastedda) cheese, and one (TA2 and TZ2) was used for experimental production performed after lactococcal biofilm activation and the daily addition of a natural whey starter culture (NWSC). Microbiological and scanning electron microscopy analyses showed differences in terms of microbial levels and composition of the neoformed biofilms. The levels of the microbial groups investigated during cheese production showed significant differences between the control trials and between the control and experimental trials, but the differences were not particularly marked between the TA2 and TZ2 productions, which showed the largest numbers of mesophilic lactic acid bacterium (LAB) cocci. LAB populations were characterized phenotypically and genotypically, and 44 dominant strains belonging to 10 species were identified. Direct comparison of the polymorphic profiles of the LAB collected during cheese making showed that the addition of the NWSC reduced their biodiversity. Sensory evaluation showed that the microbial activation of the wooden vats with the multistrain Lactococcus culture generated cheeses with sensory attributes comparable to those of commercial cheese. Thus, neoformed biofilms enable a reduction of microbial variability and stabilize the sensorial attributes of Vastedda cheese.

  6. Relationship between Active Oxygen Species, Lipid Peroxidation, Necrosis, and Phytoalexin Production Induced by Elicitins in Nicotiana.

    PubMed Central

    Rusterucci, C.; Stallaert, V.; Milat, M. L.; Pugin, A.; Ricci, P.; Blein, J. P.

    1996-01-01

    Excised leaves of Nicotiana tabacum var Xanthi and Nicotiana rustica were treated with cryptogein and capsicein, basic and acidic elicitins, respectively. Both compounds induced leaf necrosis, the intensity of which depended on concentration and duration of treatment. N. tabacum var Xanthi was the most sensitive species and cryptogein was the most active elicitin. Lipid peroxidation in elicitin-treated Nicotiana leaves was closely correlated with the appearance of necrosis. Elicitin treatments induced a rapid and transient burst of active oxygen species (AOS) in cell cultures of both Nicotiana species, with the production by Xanthi cells being 6-fold greater than that by N. rustica. Similar maximum AOS production levels were observed with both elicitins, but capsicein required 10-fold higher concentrations than those of cryptogein. Phytoalexin production was lower in response to both elicitins in N. tabacum var Xanthi cells than in N. rustica cells, and capsicein was the most efficient elicitor of this response. In cryptogein-treated cell suspensions, phytoalexin synthesis was unaffected by diphenyleneiodonium, which inhibited AOS generation, nor was it affected by tiron or catalase, which suppressed AOS accumulation in the extracellular medium. These results suggest that AOS production, lipid peroxidation, and necrosis are directly related, whereas phytoalexin production depends on neither the presence nor the intensity of these responses. PMID:12226334

  7. Soluble microbial products (SMPs) release in activated sludge systems: a review

    PubMed Central

    2012-01-01

    This review discusses the characterization, production and implications of soluble microbial products (SMPs) in biological wastewater treatment. The precise definition of SMPs is open to talk about, but is currently regarded as “the pool of organic compounds that are released into solution from substrate metabolism and biomass decay”'. Some of the SMPs have been identified as humic acids, polysaccharides, proteins, amino acids, antibiotics, extracellular enzymes and structural components of cells and products of energy metabolism. They adversely affect the kinetic activity, flocculating and settling properties of sludge. This review outlines some important findings with regard to biodegradability and treatability of SMPs and also the effect of process parameters on their production. As SMPs are produced during biological treatment process, their trace amounts normally remain in the effluent that defines the highest COD removal efficiency. Their presence in effluent represents a high potential risk of toxic by-product formation during chlorine disinfection. Studies have indicated that among all wastewater post-treatment processes, the adsorption by granular activated carbon combined with biologically induced degradation is the most effective method for removal of SMPs. However, it may be concludes that the knowledge regarding SMPs is still under progress and more work is required to fully understand their contribution to the treatment process. PMID:23369231

  8. Effect of polyhydroxyalkanoates on dark fermentative hydrogen production from waste activated sludge.

    PubMed

    Wang, Dongbo; Zeng, Guangming; Chen, Yinguang; Li, Xiaoming

    2015-04-15

    Polyhydroxyalkanoates (PHA), an intracellular energy and carbon storage polymer, can be accumulated in activated sludge in substantial quantities under wastewater dynamic treatment (i.e., substrate feast-famine) conditions. However, its influence on hydrogen production has never been investigated before. This study therefore evaluated the influences of PHA level and composition in waste activated sludge (WAS) on hydrogen production. The results showed that with the increase of sludge PHA content from 25 to 178 mg per gram volatile suspended solids (VSS) hydrogen production from WAS alkaline anaerobic fermentation increased from 26.5 to 58.7 mL/g VSS. The composition of PHA was also found to affect hydrogen production. When the dominant composition shifted from polyhydroxybutyrate (PHB) to polyhydroxyvalerate (PHV), the amount of generated hydrogen decreased from 51.2 to 41.1 mL/g VSS even under the same PHA level (around 130 mg/g VSS). The mechanism studies exhibited that the increased PHA content accelerated both the cell solubilization and the hydrolysis process of solubilized substrates. Compared with the PHB-dominant sludge, the increased PHV fraction not only slowed the hydrolysis process but also caused more propionic acid production, with less theoretical hydrogen generation in this fermentation type. It was also found that the increased PHA content enhanced the soluble protein conversion of non-PHA biomass. Further investigations with enzyme analyses showed that both the key hydrolytic enzyme activities and hydrogen-forming enzyme activities were in the sequence of the PHB-dominant sludge > the PHV-dominant sludge > the low PHA sludge, which was in accord with the observed order of hydrogen yield.

  9. Activating transhydrogenase and NAD kinase in combination for improving isobutanol production.

    PubMed

    Shi, Aiqin; Zhu, Xinna; Lu, Jiao; Zhang, Xueli; Ma, Yanhe

    2013-03-01

    Isobutanol is an excellent alternative biofuel. Fermentative production of isobutanol had been realized in several microorganisms by combining branched-chain amino acids synthetic pathway and Ehrlich pathway. In contrast to using plasmid overexpression and inducible promoters, genetically stable Escherichia coli strains for isobutanol production were constructed in this work by integrating essential genes into chromosome. A chromosome-based markerless gene modulation method was then developed for fine-tuning gene expression with multiple regulatory parts to improve isobutanol production. There was also a cofactor imbalance problem for anaerobic isobutanol synthesis. NADPH is the reducing equivalent required for isobutanol production, while the common reducing equivalent under anaerobic condition is NADH. Two strategies were used to modulate expression of transhydrogenase (pntAB) and NAD kinase (yfjB) genes to increase NADPH supply for improving isobutanol production. Plasmid overexpression of pntAB and yfjB genes either individually or in combination had little effect on isobutanol production. In contrast, modulating pntAB and yfjB gene expression in chromosome with multiple regulatory parts identified optimal modulators under aerobic and anaerobic conditions, respectively, and improved isobutanol production. Modulating pntAB gene alone led to 20% and 8% increase of anaerobic isobutanol titer and yield. Although modulating yfjB gene alone had nearly no effect, modulating pntAB and yfjB genes in combination led to 50% and 30% increase of isobutanol titer and yield in comparison with modulating pntAB gene alone. It was also found that increasing pntAB gene expression alone had a threshold for improving anaerobic isobutanol production, while activating NAD kinase could break through this threshold, leading to a yield of 0.92mol/mol. Our results suggested that transhydrogenase and NAD kinase had a synergistic effect on increasing NADPH supply and improving anaerobic

  10. Nitric oxide synthase expression, enzyme activity and NO production during angiogenesis in the chick chorioallantoic membrane

    PubMed Central

    Pipili-Synetos, Eva; Kritikou, Sosanna; Papadimitriou, Evangelia; Athanassiadou, Aglaia; Flordellis, C; Maragoudakis, M E

    2000-01-01

    In order to elucidate further the role of nitric oxide (NO) as an endogenous antiangiogenic mediator, mRNA expression of inducible nitric oxide synthase (iNOS), enzyme activity and production of NO were determined in the chick chorioallantoic membrane (CAM), an in vivo model of angiogenesis. In this model, maximum angiogenesis is reached between days 9–12 of chick embryo development. After that period, vascular density remains constant. Inducible NO synthase (iNOS) mRNA expression, determined by reverse transcriptase polymerase chain reaction (RT–PCR), increased from the 8th day reaching a maximum (70% increase) at days 10–11. NO synthase activity, determined as citrulline formation in the presence of calcium, also increased from day 8 reaching a maximum around day 10 (100% increase). Similar results were obtained in the absence of calcium suggesting that the NOS determined was the inducible form. Nitric oxide production, determined as nitrites, increased from day 8 reaching a maximum around day 10 (64% increase) and remaining stable at day 13. Finally, the bacterial lipopolysaccharide LPS (which activates transcriptionally iNOS), inhibited dose dependently angiogenesis in the CAM. These results in connection with previous findings from this laboratory, showing that NO inhibits angiogenesis in the CAM, suggest that increases in iNOS expression, enzyme activity and NO production closely parallel the progression of angiogenesis in the CAM, thus providing an endogenous brake to control this process. PMID:10694222

  11. Antibacterial and Antidiarrheal Activities of Plant Products against Enterotoxinogenic Escherichia coli

    PubMed Central

    Dubreuil, J. Daniel

    2013-01-01

    Enterotoxigenic Escherichia coli (ETEC) produces two types of enterotoxins: heat-labile (LT) and heat-stable (STa and STb). These molecules are involved in the induction of secretory diarrhea in animals including humans. This condition is currently treated using a fluid replacement therapy and antibiotics. This treatment is often not available to people in developing countries, and several die from the condition provoke by ETEC. Over the years, plants and plant extracts have been use as traditional medicine to treat various gastrointestinal ailments including diarrhea. Many of these plant products have been claimed to be active against diarrhea, however few have been extensively studied. The main objective of this review was to gather the scattered information on the antidiarrheal activities reported for various plant products on ETEC. This includes two major effects: (1) The inhibitory effect on bacterial growth or viability and (2) The interference with ETEC enterotoxins activity upon the intestinal epithelium. We will focus on plant products and extracts for which we have major indications of their biological activity against ETEC and their enterotoxins. Because Vibrio cholerae toxin (CT) is structurally, antigenically and mechanistically related to LT, it will also be discussed in this review. PMID:24212181

  12. Improved Production of Active Streptomyces griseus Trypsin with a Novel Auto-Catalyzed Strategy

    PubMed Central

    Zhang, Yunfeng; Ling, Zhenmin; Du, Guocheng; Chen, Jian; Kang, Zhen

    2016-01-01

    N-terminal sequences play crucial roles in regulating expression, translation, activation and enzymatic properties of proteins. To reduce cell toxicity of intracellular trypsin and increase secretory expression, we developed a novel auto-catalyzed strategy to produce recombinant trypsin by engineering the N-terminus of mature Streptomyces griseus trypsin (SGT). The engineered N-terminal peptide of SGT was composed of the thioredoxin, glycine-serine linker, His6-tag and the partial bovine trypsinogen pro-peptide (DDDDK). Furthermore, we constructed a variant TLEI with insertion of the artificial peptide at N-terminus and site-directed mutagenesis of the autolysis residue R145. In fed-batch fermentation, the production of extracellular trypsin activity was significantly improved to 47.4 ± 1.2 U·ml−1 (amidase activity, 8532 ± 142.2 U·ml−1 BAEE activity) with a productivity of 0.49 U·ml−1·h−1, which was 329% greater than that of parent strain Pichia pastoris GS115-SGT. This work has significant potential to be scaled-up for microbial production of SGT. In addition, the N-terminal peptide engineering strategy can be extended to improve heterologous expression of other toxic enzymes. PMID:26983398

  13. Production of Plasminogen Activator in Cultures of Superior Cervical Ganglia and Isolated Schwann Cells

    NASA Astrophysics Data System (ADS)

    Alvarez-Buylla, Arturo; Valinsky, Jay E.

    1985-05-01

    Plasminogen activator has been implicated in tissue remodeling and cell migration during embryogenesis. In the developing nervous system, these processes are evident in the migration of neurons, axonal extension, Schwann cell migration, and the ensheathment and myelination of nerves. We have studied the production of plasminogen activator in cultures of superior cervical ganglia under conditions in which both neurons and glia are present. We have found that a principal source of the enzyme in these cultures is the glial cells and that the enzyme could not be detected at the growing tips of neurites. Plasminogen activator is also produced by Schwann cells isolated from neonatal rat sciatic nerve. The production of the enzyme by these cells is stimulated 6- to 10-fold by cholera toxin. Isolated Schwann cells and glial cells in the ganglion explant cultures produce the tissue form of plasminogen activator, a form of the enzyme not often found in nonmalignant cells. Preliminary experiments suggest that neuronal-glial interactions may regulate enzyme production by Schwann cells.

  14. Impacts of Climate Change/Variability and Human Activities on Contemporary Vegetation Productivity across Africa

    NASA Astrophysics Data System (ADS)

    Ugbaje, S. U.; Odeh, I. A.; Bishop, T.

    2015-12-01

    Vegetation productivity is increasingly being impacted upon by climate change/variability and anthropogenic activities, especially in developing countries, where many livelihoods depend on the natural resource base. Despite these impacts, the individual and combined roles of climate and anthropogenic factors on vegetation dynamics have rarely been quantified in many ecosystems and regions of the world. This paper analyzes recent trend in vegetation productivity across Africa and quantified the relative roles of climate change/variability and human activities in driving this trend over 2000-2014 using net primary productivity (NPP) as an indicator. The relative roles of these factors to vegetation productivity change were quantified by comparing the trend slope (p<0.1) and total change in interannual actual NPP (NPPA), potential NPP (NPPP), and human appropriated NPP (NPPH). NPP significantly increased across Africa relative to NPP decline, though the extent of NPP decline is also quite appreciable. Whereas estimated NPP declined by 207 Tg C over 140 X 104 km of land area, vegetation productivity was estimated to improve by 1415 Tg C over 786 X 104 km of land area. NPP improvement is largely concentrated in equatorial and northern hemispheric Africa, while subequatorial Africa exhibited the most NPP decline. Generally, anthropogenic activities dominated climate change/variability in improving or degrading vegetation productivity. Of the estimated total NPP gained over the study period, 32.6, 8.8, and 58.6 % were due to individual human, climate and combined impacts respectively. The contributions of the factors to NPP decline in the same order are: 50.7, 16.0 and 33.3 %. The Central Africa region is where human activities had the greatest impact on NPP improvement; whereas the Sahel and the coastlines of west northern Africa are areas associated with the greatest influence of climate-driven NPP gain. Areas with humans dominating NPP degradation include eastern

  15. The GEOGLAM Rangelands and Pasture Productivity Activity: Recent Progress and Future Directions

    NASA Astrophysics Data System (ADS)

    Guerschman, J. P.; Held, A. A.; Donohue, R. J.; Renzullo, L. J.; Sims, N.; Kerblat, F.; Grundy, M.

    2015-12-01

    Rangelands and pastures cover about a third of the world's land area and support livestock production which represents ~40% of global agricultural gross domestic product. The global consumption of animal protein shows a clear increasing trend, driven by both total population and per capita income increases, putting a growing pressure on the sustainability of grazing lands worldwide. Despite their relevance, rangelands have received less attention than croplands regarding global monitoring of the resource productivity and condition. The Rangelands and Pasture Productivity (RaPP) activity is a component within the Global Agricultural Monitoring initiative established under the Group on Earth Observations (GEOGLAM) in 2013. GEOGLAM RaPP is aimed at providing the global community with the means to monitor the world's rangelands and pastures on a routine basis, and the capacity to produce animal protein in real-time, at global, regional and national levels. Since its launch two years ago GEOGLAM RAPP has made progress in the four implementation elements. These include: 1- the establishment of community of practice; 2- the development of a global monitoring system for rangeland condition; 3- the establishment of pilot sites in main rangeland systems for satellite data products validation and model testing; and 4- integration with livestock production models. Three international workshops have been held building the community of practice. A prototype monitoring system that provides global visualisations and querying capability of vegetation cover data and anomalies has been established. Pilot sites, mostly in areas with long records of field measurements of rangeland condition and productivity have been proposed for nine countries. The link to global livestock models, including physical and economic components, have been established. Future challenges for GEOGLAM RaPP have also been identified and include: better representation of the areas occupied by rangelands

  16. [Screening of phagocyte activators in plants; enhancement of TNF production by flavonoids].

    PubMed

    Kunizane, H; Ueda, H; Yamazaki, M

    1995-09-01

    The tumor necrosis factor (TNF) was first discovered as a substance that induced necrosis of transplanted tumors. Recently, TNF has been recognized as an important and endogenous mediator in host defense mechanisms. To prove the fact that plant foods contain substances which activate the host defense mechanisms, we first examined if the administration of flavonoids could induce TNF production in mice. Some selected flavonoids such as naringin, apiin, poncirin and rutin were shown to amplify TNF release from murine macrophages in vivo in response to OK-432 as a second stimulus. However, their aglycone forms were not effective. The differences in the saccharide-chain of flavonoids induced the variety of TNF production.

  17. Effect of process variables on the production of Polyhydroxyalkanoates by activated sludge

    PubMed Central

    2012-01-01

    Polyhydroxyalkanoates are known to be temporarily stored by microorganisms in activated sludge, especially in anaerobic-aerobic processes. Due to the problems resulted from the disposals of plastic wastes and excess sludge of wastewater treatment plants, the production of polyhydroxyalkanoates by treating activated sludge and determining the effect of process variables were the main issues of this paper. In this research, an anaerobic-aerobic sequencing batch reactor was used to make microorganism adapted and a batch aerobic reactor was used for enriching them. The variables affecting polyhydroxyalkanoates production including aeration time, sludge retention time, and volatile fatty acids concentration of the influent in sequencing batch reactor, and also carbon to nitrogen ratio and cultivation time in polymer production reactor, were investigated using Taguchi statistical approach to determine optimum conditions. The maximum polymer production of 29% was achieved at sludge retention time of 5–10 days, aeration time of 2 hours, supplementation of 40% of volatile fatty acids in the influent and increasing of carbon to nitrogen ratio of polymer production reactor to above 25 g/g. Based on the results, in optimum conditions, the volatile fatty acids concentration which increased the production of polyhydroxyalkanoates up to 49% was the most effective variable. Carbon to nitrogen ratio, sludge retention time and aeration time were ranked as the next affecting parameters. Although the polyhydroxyalkanoates content achieved in present study is much lower than that by pure culture, but the proposed method may still serve well as an environmental friendly means to convert waste into valuable product. PMID:23369512

  18. Myeloperoxidase deficiency induces MIP-2 production via ERK activation in zymosan-stimulated mouse neutrophils.

    PubMed

    Tateno, N; Matsumoto, N; Motowaki, T; Suzuki, K; Aratani, Y

    2013-05-01

    Myeloperoxidase (MPO), a major constituent of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion. We have previously reported that MPO-deficient (MPO(-/-)) neutrophils produce greater amount of macrophage inflammatory protein-2 (MIP-2) in vitro than do wild type when stimulated with zymosan. In this study, we investigated the molecular mechanisms governing the up-regulation of MIP-2 production in the mutant neutrophils. Interestingly, we found that zymosan-induced production of MIP-2 was blocked by pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK), and with BAY11-7082, an inhibitor of nuclear factor (NF)-κB. Western blot analysis indicated that U0126 also inhibited the phosphorylation of p65 subunit of NF-κB (p65), indicating that MIP-2 was produced via the ERK/NF-κB pathway. Intriguingly, we found that ERK1/2, p65, and alpha subunit of inhibitor of κB (IκBα) in the MPO(-/-) neutrophils were phosphorylated more strongly than in the wild type when stimulated with zymosan. Exogenous H2O2 treatment in addition to zymosan stimulation enhanced the phosphorylation of ERK1/2 without affecting the zymosan-induced MIP-2 production. In contrast, exogenous HOCl inhibited the production of MIP-2 as well as IκBα phosphorylation without affecting ERK activity. The zymosan-induced production of MIP-2 in the wild-type neutrophils was enhanced by pre-treatment of the MPO inhibitor 4-aminobenzoic acid hydrazide. Collectively, these results strongly suggest that both lack of HOCl and accumulation of H2O2 due to MPO deficiency contribute to the up-regulation of MIP-2 production in mouse neutrophils stimulated with zymosan.

  19. Myeloperoxidase deficiency induces MIP-2 production via ERK activation in zymosan-stimulated mouse neutrophils.

    PubMed

    Tateno, N; Matsumoto, N; Motowaki, T; Suzuki, K; Aratani, Y

    2013-05-01

    Myeloperoxidase (MPO), a major constituent of neutrophils, catalyzes the production of hypochlorous acid (HOCl) from hydrogen peroxide (H2O2) and chloride anion. We have previously reported that MPO-deficient (MPO(-/-)) neutrophils produce greater amount of macrophage inflammatory protein-2 (MIP-2) in vitro than do wild type when stimulated with zymosan. In this study, we investigated the molecular mechanisms governing the up-regulation of MIP-2 production in the mutant neutrophils. Interestingly, we found that zymosan-induced production of MIP-2 was blocked by pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK), and with BAY11-7082, an inhibitor of nuclear factor (NF)-κB. Western blot analysis indicated that U0126 also inhibited the phosphorylation of p65 subunit of NF-κB (p65), indicating that MIP-2 was produced via the ERK/NF-κB pathway. Intriguingly, we found that ERK1/2, p65, and alpha subunit of inhibitor of κB (IκBα) in the MPO(-/-) neutrophils were phosphorylated more strongly than in the wild type when stimulated with zymosan. Exogenous H2O2 treatment in addition to zymosan stimulation enhanced the phosphorylation of ERK1/2 without affecting the zymosan-induced MIP-2 production. In contrast, exogenous HOCl inhibited the production of MIP-2 as well as IκBα phosphorylation without affecting ERK activity. The zymosan-induced production of MIP-2 in the wild-type neutrophils was enhanced by pre-treatment of the MPO inhibitor 4-aminobenzoic acid hydrazide. Collectively, these results strongly suggest that both lack of HOCl and accumulation of H2O2 due to MPO deficiency contribute to the up-regulation of MIP-2 production in mouse neutrophils stimulated with zymosan. PMID:23438680

  20. Influence of Environmental Factors on the Active Substance Production and Antioxidant Activity in Potentilla fruticosa L. and Its Quality Assessment.

    PubMed

    Liu, Wei; Yin, Dongxue; Li, Na; Hou, Xiaogai; Wang, Dongmei; Li, Dengwu; Liu, Jianjun

    2016-01-01

    Environmental factors may influence types and contents of active substances. This study investigated the influence of environmental factors on the active substance contents and antioxidant activity of Potentilla fruticosa L. from different regions of China. Also, HPLC fingerprint similarity analysis (SA) coupled with hierarchical cluster analysis (HCA) and discriminant analysis (DA) were further introduced for the accurate classification and quality assessment of P. fruticosa. The results showed that altitude was significantly and negatively correlated to the content of tannin (P < 0.05). Annual sunshine duration and altitude were significantly and positively correlated to the flavonoids content, rutin content and antioxidant activity (P < 0.05). Annual mean temperature was significantly and negatively correlated to the content of total phenolics, while altitude was significantly and positively correlated to the content of total phenolics (P < 0.05). Eight samples were unambiguously separated into three groups. Two types of discriminant functions with a 100% discrimination ratio were constructed. All data consistently supported the conclusion that P. fruticosa produced from Kangding, Sichuan Province had high quality among all samples, therefore, Kangding in Sichuan Province with favorable environmental conditions is recommended as a preferable production location. PMID:27373366

  1. Influence of Environmental Factors on the Active Substance Production and Antioxidant Activity in Potentilla fruticosa L. and Its Quality Assessment

    PubMed Central

    Liu, Wei; Yin, Dongxue; Li, Na; Hou, Xiaogai; Wang, Dongmei; Li, Dengwu; Liu, Jianjun

    2016-01-01

    Environmental factors may influence types and contents of active substances. This study investigated the influence of environmental factors on the active substance contents and antioxidant activity of Potentilla fruticosa L. from different regions of China. Also, HPLC fingerprint similarity analysis (SA) coupled with hierarchical cluster analysis (HCA) and discriminant analysis (DA) were further introduced for the accurate classification and quality assessment of P. fruticosa. The results showed that altitude was significantly and negatively correlated to the content of tannin (P < 0.05). Annual sunshine duration and altitude were significantly and positively correlated to the flavonoids content, rutin content and antioxidant activity (P < 0.05). Annual mean temperature was significantly and negatively correlated to the content of total phenolics, while altitude was significantly and positively correlated to the content of total phenolics (P < 0.05). Eight samples were unambiguously separated into three groups. Two types of discriminant functions with a 100% discrimination ratio were constructed. All data consistently supported the conclusion that P. fruticosa produced from Kangding, Sichuan Province had high quality among all samples, therefore, Kangding in Sichuan Province with favorable environmental conditions is recommended as a preferable production location. PMID:27373366

  2. Productivity, absorbed photosynthetically active radiation, and light use efficiency in crops: implications for remote sensing of crop primary production.

    PubMed

    Gitelson, Anatoly A; Peng, Yi; Arkebauer, Timothy J; Suyker, Andrew E

    2015-04-01

    Vegetation productivity metrics such as gross primary production (GPP) at the canopy scale are greatly affected by the efficiency of using absorbed radiation for photosynthesis, or light use efficiency (LUE). Thus, close investigation of the relationships between canopy GPP and photosynthetically active radiation absorbed by vegetation is the basis for quantification of LUE. We used multiyear observations over irrigated and rainfed contrasting C3 (soybean) and C4 (maize) crops having different physiology, leaf structure, and canopy architecture to establish the relationships between canopy GPP and radiation absorbed by vegetation and quantify LUE. Although multiple LUE definitions are reported in the literature, we used a definition of efficiency of light use by photosynthetically active "green" vegetation (LUE(green)) based on radiation absorbed by "green" photosynthetically active vegetation on a daily basis. We quantified, irreversible slowly changing seasonal (constitutive) and rapidly day-to-day changing (facultative) LUE(green), as well as sensitivity of LUE(green) to the magnitude of incident radiation and drought events. Large (2-3-fold) variation of daily LUE(green) over the course of a growing season that is governed by crop physiological and phenological status was observed. The day-to-day variations of LUE(green) oscillated with magnitude 10-15% around the seasonal LUE(green) trend and appeared to be closely related to day-to-day variations of magnitude and composition of incident radiation. Our results show the high variability of LUE(green) between C3 and C4 crop species (1.43 g C/MJ vs. 2.24 g C/MJ, respectively), as well as within single crop species (i.e., maize or soybean). This implies that assuming LUE(green) as a constant value in GPP models is not warranted for the crops studied, and brings unpredictable uncertainties of remote GPP estimation, which should be accounted for in LUE models. The uncertainty of GPP estimation due to facultative and

  3. 77 FR 63290 - Foreign-Trade Zone 61-San Juan, Puerto Rico; Authorization of Production Activity, Pfizer...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-16

    ... comment (77 FR 36997, 6/20/2012). The FTZ Board has determined that no further review of the activity is... Activity, Pfizer Pharmaceuticals, LLC (Subzone 61A), (Ibuprofen Pharmaceutical Products), Guayama,...

  4. Production of activated carbons from pyrolysis of waste tires impregnated with potassium hydroxide.

    PubMed

    Teng, H; Lin, Y C; Hsu, L Y

    2000-11-01

    Activated carbons were produced from waste tires using a chemical activation method. The carbon production process consisted of potassium hydroxide (KOH) impregnation followed by pyrolysis in N2 at 600-900 degrees C for 0-2 hr. The activation method can produce carbons with a surface area (SA) and total pore volume as high as 470 m2/g and 0.57 cm3/g, respectively. The influence of different parameters during chemical activation, such as pyrolysis temperature, holding time, and KOH/tire ratio, on the carbon yield and the surface characteristics was explored, and the optimum preparation conditions were recommended. The pore volume of the resulting carbons generally increases with the extent of carbon gasified by KOH and its derivatives, whereas the SA increases with degree of gasification to reach a maximum value, and then decreases upon further gasification. PMID:11111338

  5. Enhanced Xylitol Production by Mutant Kluyveromyces marxianus 36907-FMEL1 Due to Improved Xylose Reductase Activity.

    PubMed

    Kim, Jin-Seong; Park, Jae-Bum; Jang, Seung-Won; Ha, Suk-Jin

    2015-08-01

    A directed evolution and random mutagenesis were carried out with thermotolerant yeast Kluyveromyces marxianus ATCC 36907 for efficient xylitol production. The final selected strain, K. marxianus 36907-FMEL1, exhibited 120 and 39 % improvements of xylitol concentration and xylitol yield, respectively, as compared to the parental strain, K. marxianus ATCC 36907. According to enzymatic assays for xylose reductase (XR) activities, XR activity from K. marxianus 36907-FMEL1 was around twofold higher than that from the parental strain. Interestingly, the ratios of NADH-linked and NADPH-linked XR activities were highly changed from 1.92 to 1.30 when K. marxianus ATCC 36907 and K. marxianus 36907-FMEL1 were compared. As results of KmXYL1 genes sequencing, it was found that cysteine was substituted to tyrosine at position 36 after strain development which might cause enhanced XR activity from K. marxianus 36907-FMEL1.

  6. Proposed new reactor-activated positron source for intense slow e + beam production

    NASA Astrophysics Data System (ADS)

    Skalsey, M.; Van House, J.

    1988-03-01

    A novel method is suggested for producing a new positron (e +) emitting isotope in a nuclear reactor with application to slow e + beams. The initial radiated sample is 124Xe which is transformed to 126I by two neutron absorptions and an intermediate decay. Over 25 Ci of positrons with a specific activity of 25 {Ci}/{gm} can be produced by this technique, allowing the generation of a slow e + beam of over 4 × 10 7{e +}/{cm 2} -s. As discussed in the conclusion, specific activities approaching 200 {Ci}/{gm} should be for activation cells are presented, one with Xe in the gas phase, the other with solid Xe. Both designs allow the easy separation of the 126I from other contaminants, permitting the production of a pure, high specific activity source.

  7. Mass Spectrometric Collisional Activation and Product Ion Mobility of Human Serum Neutral Lipid Extracts

    PubMed Central

    Hankin, Joseph A.; Barkley, Robert M.; Zemski-Berry, Karin; Deng, Yiming; Murphy, Robert C.

    2016-01-01

    A novel method for lipid analysis called CTS (collisional activation and traveling wave mass spectrometry) involving tandem mass spectrometry of all precursor ions with ion mobility determinations of all product ions was applied to a sample of human serum. The resulting four dimensional data set (precursor ion, product ion, ion mobility values, and intensity) was found to be useful for characterization of lipids as classes as well as identification of specific species. Utilization of ion mobility measurements of the product ions is a novel approach for lipid analysis. The trends and patterns of product mobility values when visually displayed yield information on lipid classes and specific species independent of mass determination. The collection of a comprehensive set of data that incorporates all precursor-product relationships combined with ion mobility measurements of all products enables data analysis where different molecular properties can be juxtaposed and analyzed to assist with class and species identification. Overall, CTS is powerful, specific, and comprehensive method for lipid analysis. PMID:27213895

  8. Biologically active amines in fermented and non-fermented commercial soybean products from the Spanish market.

    PubMed

    Toro-Funes, N; Bosch-Fuste, J; Latorre-Moratalla, M L; Veciana-Nogués, M T; Vidal-Carou, M C

    2015-04-15

    Biologically active amines were determined in commercial soybean products. The antioxidant polyamines were found in both non-fermented and fermented soybean products. Natto and tempeh showed the highest content of polyamines (75-124 and 11-24 mg/kg of spermidine and spermine, respectively). On the other hand, the bacterial-related biogenic amines, tyramine, histamine, tryptamine and β-phenylethylamine, were detected in practically all fermented products with a high variability. The highest contents were found in sufu, tamari and soybean paste. Extremely high tyramine and histamine contents, 1700 and 700 mg/kg, respectively, found in some sufu samples could be unhealthy. However, biogenic amines observed in the other soybean products should not be a risk for healthy consumers. However, individuals who take monoamine and diamine oxidase inhibitors drugs should be strongly recommended to avoid this kind of products in order to suffer no adverse health effects. These biogenic amines were not detected in non-fermented soybean products.

  9. Enhanced volatile fatty acids production of waste activated sludge under salinity conditions: Performance and mechanisms.

    PubMed

    Su, Gaoqiang; Wang, Shuying; Yuan, Zhiguo; Peng, Yongzhen

    2016-03-01

    Volatile fatty acids (VFAs) are essential for removing biological nitrogen and phosphorus in wastewater treatment plants. The purpose of this work was to investigate whether and how the addition of NaCl could improve the production of VFAs from waste activated sludge (WAS). Sludge solubilization was efficiently improved by the addition of NaCl. Both protein and carbohydrate in the fermentation liquid increased with the dosage of NaCl, and it provided a larger amount of organic compounds for the production of the VFAs. NaCl had inhibitory effects on the production of methane and a high dosage of NaCl could severely suppress the growth of methanogens, which decreased the consumption of the VFAs. Consequently, the production of VFAs was significantly enhanced by the addition of NaCl. The maximum production of VFAs was achieved with the highest dosage of NaCl (3316 mg (COD)/L at the NaCl dosage 0.5 mol/L; 783 mg (COD)/L without the addition of NaCl). Therefore, this study indicates that using NaCl could be an efficient method for improving the production of VFAs from WAS. PMID:26320405

  10. Danger signal-dependent activation of human dendritic cells by plasma-derived factor VIII products.

    PubMed

    Miller, L; Weissmüller, S; Ringler, E; Crauwels, P; van Zandbergen, G; Seitz, R; Waibler, Z

    2015-08-01

    Treatment of haemophilia A by infusions of the clotting factor VIII (FVIII) results in the development of inhibitors/anti-drug antibodies in up to 25 % of patients. Mechanisms leading to immunogenicity of FVIII products are not yet fully understood. Amongst other factors, danger signals as elicited upon infection or surgery have been proposed to play a role. In the present study, we focused on effects of danger signals on maturation and activation of dendritic cells (DC) in the context of FVIII application. Human monocyte-derived DC were treated with FVIII alone, with a danger signal alone or a combination of both. By testing more than 60 different healthy donors, we show that FVIII and the bacterial danger signal lipopolysaccharide synergise in increasing DC activation, as characterised by increased expression of co-stimulatory molecules and secretion of pro-inflammatory cytokines. The degree and frequency of this synergistic activation correlate with CD86 expression levels on immature DC prior to stimulation. In our assay system, plasma-derived but not recombinant FVIII products activate human DC in a danger signal-dependent manner. Further tested danger signals, such as R848 also induced DC activation in combination with FVIII, albeit not in every tested donor. In our hands, human DC but not human B cells or macrophages could be activated by FVIII in a danger signal-dependent manner. Our results suggest that immunogenicity of FVIII is a result of multiple factors including the presence of danger, predisposition of the patient, and the choice of a FVIII product for treatment.

  11. HARPs: Tracked Active Region Patch Data Product from SDO/HMI

    NASA Astrophysics Data System (ADS)

    Turmon, M.; Hoeksema, J. T.; Sun, X.; Bobra, M.

    2012-12-01

    We describe an HMI data product consisting of tracked magnetic features on the scale of solar active regions, abbreviated HARPs (HMI Active Region Patches). The HARP data series has been helpful for subsetting individual active regions, for development of near-real-time (NRT) space weather indices for individual active regions, and for defining closed magnetic structures for computationally-intensive algorithms like vector field disambiguation. The data series builds upon the 720s cadence activity masks, which identify large-scale instantaneously-observed magnetic features. Using these masks as a starting point, large spatially-coherent structures are identified using convolution with a longitudinally-extended kernel on a spherical domain. The resulting set of identified regions is then tracked from image to image. The metric for inter-image association is area of overlap between the best current estimate of AR location, as predicted by temporally extrapolating each currently tracked object, and the set of instantaneously-observed magnetic structures. Once completed tracks have been extracted, they are made into a standardized HARP data series by finding the smallest constant-angular-velocity box, of constant width in latitude and longitude, that encompasses all appearances of the active region. This data product is currently available, in definitive and near-real-time forms, with accompanying region-strength, location, and NOAA-AR metadata, on HMI's Joint Science Operations Center (JSOC) data portal.; HARP outlines for three days (2001 February 14, 15, and 16, 00:00 TAI, flipped N-S, selected from the 12-minute cadence original data product). HARPs are shown in the same color (some colors repeated) with a thin white box surrounding each HARP. HARPs are tracked and associated from image to image. HARPs, such as the yellow one in the images above, need not be connected regions. Merges and splits, such as the light blue region, are accounted for automatically.

  12. Enrichment of specific electro-active microorganisms and enhancement of methane production by adding granular activated carbon in anaerobic reactors.

    PubMed

    Lee, Jung-Yeol; Lee, Sang-Hoon; Park, Hee-Deung

    2016-04-01

    Direct interspecies electron transfer (DIET) via conductive materials can provide significant benefits to anaerobic methane formation in terms of production amount and rate. Although granular activated carbon (GAC) demonstrated its applicability in facilitating DIET in methanogenesis, DIET in continuous flow anaerobic reactors has not been verified. Here, evidences of DIET via GAC were explored. The reactor supplemented with GAC showed 1.8-fold higher methane production rate than that without GAC (35.7 versus 20.1±7.1mL-CH4/d). Around 34% of methane formation was attributed to the biomass attached to GAC. Pyrosequencing of 16S rRNA gene demonstrated the enrichment of exoelectrogens (e.g. Geobacter) and hydrogenotrophic methanogens (e.g. Methanospirillum and Methanolinea) from the biomass attached to GAC. Furthermore, anodic and cathodic currents generation was observed in an electrochemical cell containing GAC biomass. Taken together, GAC supplementation created an environment for enriching the microorganisms involved in DIET, which increased the methane production rate. PMID:26836607

  13. 'Syntactic Perturbation' During Production Activates the Right IFG, but not Broca's Area or the ATL.

    PubMed

    Matchin, William; Hickok, Gregory

    2016-01-01

    Research on the neural organization of syntax - the core structure-building component of language - has focused on Broca's area and the anterior temporal lobe (ATL) as the chief candidates for syntactic processing. However, these proposals have received considerable challenges. In order to better understand the neural basis of syntactic processing, we performed a functional magnetic resonance imaging experiment using a constrained sentence production task. We examined the BOLD response to sentence production for active and passive sentences, unstructured word lists, and syntactic perturbation. Perturbation involved cued restructuring of the planned syntax of a sentence mid utterance. Perturbation was designed to capture the effects of syntactic violations previously studied in sentence comprehension. Our experiment showed that Broca's area and the ATL did not exhibit response profiles consistent with syntactic operations - we found no increase of activation in these areas for sentences > lists or for perturbation. Syntactic perturbation activated a cortical-subcortical network including robust activation of the right inferior frontal gyrus (RIFG). This network is similar to one previously shown to be involved in motor response inhibition. We hypothesize that RIFG activation in our study and in previous studies of sentence comprehension is due to an inhibition mechanism that may facilitate efficient syntactic restructuring. PMID:26941692

  14. Antifungal activity and identification of Lactobacilli, isolated from traditional dairy product "katak".

    PubMed

    Tropcheva, Rositsa; Nikolova, Dilyana; Evstatieva, Yana; Danova, Svetla

    2014-08-01

    Filamentous moulds are the main spoilage microorganisms, responsible for significant economic losses and several healthy risks in human food chain. The lactic acid bacteria (LAB), especially lactobacilli could be a natural antagonist of these dangerous organisms. In Bulgaria, a very limited data exists on the antifungal activity of LAB microbiota of fermented dairy products. In the present study, four active strains were isolated from traditional fermented curd/yogurt-like product "katak", produced in Bulgaria from centuries. The new isolates KR3, KR4, KR51 and KR53 were identified by API 50 CH biochemical test and different molecular methods (species-specific PCR, RAPD-PCR and 16S rDNA sequence analysis) as Lactobacillus brevis. According to our knowledge, this is the first data on the molecular characterization of the Lactobacillus microbiota of "katak". A broad spectrum of antifungal activity of the four L. brevis KR strains against test-cultures representatives of carcinogenic, toxigenic, deteriorative and allergenic fungi from the genera Aspergillus, Fusarium, Penicillium and Trichoderma was estimated. Strains L. brevis KR3, KR4 and KR51 completely suppress the growth of Penicillium claviforme, Aspergillus awamori and Aspergillus niger. With regard to Aspergillus flavus and Trichoderma viride, a lower and strain-specific inhibitory activity was observed. The antifungal activity of our new L. brevis isolates seems to be a promising advantage of these four strains, suggesting their potential applications in different food technologies as bio-preservative agents against moulds. PMID:24887637

  15. Low water activity induces the production of bioactive metabolites in halophilic and halotolerant fungi.

    PubMed

    Sepcic, Kristina; Zalar, Polona; Gunde-Cimerman, Nina

    2010-12-27

    The aim of the present study was to investigate indigenous fungal communities isolated from extreme environments (hypersaline waters of solar salterns and subglacial ice), for the production of metabolic compounds with selected biological activities: hemolysis, antibacterial, and acetylcholinesterase inhibition. In their natural habitats, the selected fungi are exposed to environmental extremes, and therefore the production of bioactive metabolites was tested under both standard growth conditions for mesophilic microorganisms, and at high NaCl and sugar concentrations and low growth temperatures. The results indicate that selected halotolerant and halophilic species synthesize specific bioactive metabolites under conditions that represent stress for non-adapted species. Furthermore, adaptation at the level of the chemical nature of the solute lowering the water activity of the medium was observed. Increased salt concentrations resulted in higher hemolytic activity, particularly within species dominating the salterns. The appearance of antibacterial potential under stress conditions was seen in the similar pattern of fungal species as for hemolysis. The active extracts exclusively affected the growth of the Gram-positive bacterium tested, Bacillus subtilis. None of the extracts tested showed inhibition of acetylcholinesterase activity.

  16. 'Syntactic Perturbation' During Production Activates the Right IFG, but not Broca's Area or the ATL.

    PubMed

    Matchin, William; Hickok, Gregory

    2016-01-01

    Research on the neural organization of syntax - the core structure-building component of language - has focused on Broca's area and the anterior temporal lobe (ATL) as the chief candidates for syntactic processing. However, these proposals have received considerable challenges. In order to better understand the neural basis of syntactic processing, we performed a functional magnetic resonance imaging experiment using a constrained sentence production task. We examined the BOLD response to sentence production for active and passive sentences, unstructured word lists, and syntactic perturbation. Perturbation involved cued restructuring of the planned syntax of a sentence mid utterance. Perturbation was designed to capture the effects of syntactic violations previously studied in sentence comprehension. Our experiment showed that Broca's area and the ATL did not exhibit response profiles consistent with syntactic operations - we found no increase of activation in these areas for sentences > lists or for perturbation. Syntactic perturbation activated a cortical-subcortical network including robust activation of the right inferior frontal gyrus (RIFG). This network is similar to one previously shown to be involved in motor response inhibition. We hypothesize that RIFG activation in our study and in previous studies of sentence comprehension is due to an inhibition mechanism that may facilitate efficient syntactic restructuring.

  17. MAG4 versus Alternative Techniques for Forecasting Active-Region Flare Productivity

    NASA Astrophysics Data System (ADS)

    Falconer, David; Moore, Ronald L.; Barghouty, Abdulnasser F; Khazanov, Igor

    2014-06-01

    MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free-magnetic-energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region’s major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the “Present MAG4” technique and each of three alternative techniques, called “McIntosh Active-Region Class,” “Total Magnetic Flux,” and “Next MAG4.” We do this by using (1) the MAG4 database of magnetograms and major-flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique-performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4). Funding for this research came from NASA’s Game Changing Development Program, Johnson Space Center’s Space Radiation Analysis Group (SRAG), and AFOSR’s Multi-University Research Initiative. In particular, funding was facilitated by Dr. Dan Fry (NASA-JSC) and David Moore (NASA-LaRC).

  18. MAG4 versus alternative techniques for forecasting active region flare productivity

    PubMed Central

    Falconer, David A; Moore, Ronald L; Barghouty, Abdulnasser F; Khazanov, Igor

    2014-01-01

    MAG4 is a technique of forecasting an active region's rate of production of major flares in the coming few days from a free magnetic energy proxy. We present a statistical method of measuring the difference in performance between MAG4 and comparable alternative techniques that forecast an active region's major-flare productivity from alternative observed aspects of the active region. We demonstrate the method by measuring the difference in performance between the “Present MAG4” technique and each of three alternative techniques, called “McIntosh Active-Region Class,” “Total Magnetic Flux,” and “Next MAG4.” We do this by using (1) the MAG4 database of magnetograms and major flare histories of sunspot active regions, (2) the NOAA table of the major-flare productivity of each of 60 McIntosh active-region classes of sunspot active regions, and (3) five technique performance metrics (Heidke Skill Score, True Skill Score, Percent Correct, Probability of Detection, and False Alarm Rate) evaluated from 2000 random two-by-two contingency tables obtained from the databases. We find that (1) Present MAG4 far outperforms both McIntosh Active-Region Class and Total Magnetic Flux, (2) Next MAG4 significantly outperforms Present MAG4, (3) the performance of Next MAG4 is insensitive to the forward and backward temporal windows used, in the range of one to a few days, and (4) forecasting from the free-energy proxy in combination with either any broad category of McIntosh active-region classes or any Mount Wilson active-region class gives no significant performance improvement over forecasting from the free-energy proxy alone (Present MAG4). Key Points Quantitative comparison of performance of pairs of forecasting techniques Next MAG4 forecasts major flares more accurately than Present MAG4 Present MAG4 forecast outperforms McIntosh AR Class and total magnetic flux PMID:26213517

  19. Thigmomorphogenesis: the relationship of mechanical perturbation to elicitor-like activity and ethylene production

    NASA Technical Reports Server (NTRS)

    Takahashi, H.; Jaffe, M. J.

    1984-01-01

    An extracellular solution obtained from bean (Phaseolus vulgaris L. cv. Resistant Cherokee Wax) stems induced phytoalexin-like substance and ethylene production in a soybean [Glycine max (L.) Merr. cv. Wayne] cotyledon bioassay. The elicitor-like activity for phytoalexin formation and ethylene production was increased by mechanical perturbation of bean stems. Moreover, the application of extracted or known elicitors to bean plants mimicked the effect of mechanical perturbation (i.e., inhibition of stem elongation and enhancement of radial growth). The effects of extract when applied exogenously, on elicitor-like activity in the bioassay as well as stem thickening were decreased by aminoethoxyvinylglycine, an inhibitor of ethylene biosynthesis. These results suggest that elicitor-like substances which are formed in response to mechanical perturbation contribute to the thigmomorphogenesis.

  20. Migration status and investment in rural productive activities: evidence from Oyo State, Nigeria.

    PubMed

    Bankole, A

    1988-01-01

    "This paper presents an attempt to investigate the differential contributions of return migrants and non migrants [in Nigeria] to rural economy with respect to their level of investment in rural productive activities. The study is [a] sequel to the controversy generated by the selectivity theory which tends to suggest that return migrants are superior to, and more enterprising than non migrants. The relevant data were collected from 363 returnees and non migrants.... An examination of the differential characteristics of the two groups shows that returnees are slightly superior to their non migrant counterparts. The differential characteristics seem to translate to differences in investment level and the general conclusion is that return migrants are likely to invest more in rural productive activities than non migrants." (SUMMARY IN FRE AND ITA)

  1. Renewable phenols production by catalytic microwave pyrolysis of Douglas fir sawdust pellets with activated carbon catalysts.

    PubMed

    Bu, Quan; Lei, Hanwu; Wang, Lu; Wei, Yi; Zhu, Lei; Liu, Yupeng; Liang, Jing; Tang, Juming

    2013-08-01

    The effects of different activated carbon (AC) catalysts based on various carbon sources on products yield and chemical compositions of upgraded pyrolysis oils were investigated using microwave pyrolysis of Douglas fir sawdust pellets. Results showed that high amounts of phenols were obtained (74.61% and 74.77% in the upgraded bio-oils by DARCO MRX (wood based) and DARCO 830 (lignite coal based) activated carbons, respectively). The catalysts recycling test of the selected catalysts indicated that the carbon catalysts can be reused for at least 3-4 times and produced high concentrations of phenol and phenolic compounds. The chemical reaction mechanism for phenolics production during microwave pyrolysis of biomass was analyzed. PMID:23765005

  2. The Effect of Productive Activities on Depressive Symptoms Among Older Adults With Dual Sensory Loss.

    PubMed

    McDonnall, Michele Capella

    2011-05-01

    The purpose of this study was to evaluate the ability of three productive activities (paid employment, volunteer work, and informal helping) to mitigate the negative effects of dual sensory loss (DSL) on depressive symptoms among older adults. Multilevel modeling was used to analyze longitudinal data from the nationally representative Health and Retirement Study. The sample consisted of 2,688 persons: 1,380 who developed DSL during the study and 1,308 who did not. Although participation in each of the productive activities was associated with fewer depressive symptoms for older adults with DSL, volunteering was also the only variable that moderated the relationship between DSL and depressive symptoms. Persons with a DSL who volunteered exhibited a larger decrease in depressive symptoms compared to persons without sensory loss who volunteered. A volunteer intervention for older adults with DSL may be a viable option to help reduce depression in this population.

  3. Renewable phenols production by catalytic microwave pyrolysis of Douglas fir sawdust pellets with activated carbon catalysts.

    PubMed

    Bu, Quan; Lei, Hanwu; Wang, Lu; Wei, Yi; Zhu, Lei; Liu, Yupeng; Liang, Jing; Tang, Juming

    2013-08-01

    The effects of different activated carbon (AC) catalysts based on various carbon sources on products yield and chemical compositions of upgraded pyrolysis oils were investigated using microwave pyrolysis of Douglas fir sawdust pellets. Results showed that high amounts of phenols were obtained (74.61% and 74.77% in the upgraded bio-oils by DARCO MRX (wood based) and DARCO 830 (lignite coal based) activated carbons, respectively). The catalysts recycling test of the selected catalysts indicated that the carbon catalysts can be reused for at least 3-4 times and produced high concentrations of phenol and phenolic compounds. The chemical reaction mechanism for phenolics production during microwave pyrolysis of biomass was analyzed.

  4. Nutrient regulation of bacterial production and ectoenzyme activities in the subtropical North Pacific Ocean

    NASA Astrophysics Data System (ADS)

    Donachie, Stuart P.; Christian, James R.; Karl, David M.

    Interactions between Bacteria and dissolved organic matter (DOM) in the open ocean are poorly understood. While it is likely that particular compounds may disproportionately regulate heterotrophic activity, very little is known about the underlying processes. Through 10 cruises between December 1996 and April 1998 we investigated how heterotrophic (non-pigmented) Bacteria cell production, per cell α- and β-glucosidase and leucine aminopeptidase (LAPase) activities, and 14C-glucose uptake in 0.8 μm filtered seawater (fsw) cultures at Station ALOHA (22°45'N, 158°W) responded to organic and inorganic nutrient additions (glucose, single amino acids, NH 4+, NO 3-). Bacterial cell production did not change significantly in fsw with glucose (1 μM) or single exogenous N sources (1 μM N) compared to that in fsw alone. Furthermore, there was no significant difference in heterotrophic bacterial cell production in fsw amended with organic or inorganic N, nor between that in fsw with organic N and glucose, or inorganic N and glucose. Cell production did increase significantly, however, in fsw with exogenous glucose (0.38 μM) plus 1 μM inorganic N (NH 4+) relative to that in fsw only, in fsw with glucose, and in fsw with 1 μM N as amino acids (His, Tyr, Leu). There was no significant difference between heterotrophic bacterial cell production in fsw with glucose, glucose plus amino acids, and that in fsw alone. Cell-specific LAPase activity increased significantly relative to that in unamended fsw when exogenous glucose plus NH 4+ or NO 3- were provided, but amino acids, glucose, NH 4+ or NO 3- alone had little or no effect. α-Glucosidase activity tended to increase with exogenous His and Tyr additions. Our results suggest that heterotrophic activity at Station ALOHA can be regulated by the abundance of particular compounds, regardless of their total concentrations. It appears that auxotrophy and de novo synthesis of cell protein from glucose may coexist among Bacteria

  5. Enhanced photocatalytic H2-production activity of graphene-modified titania nanosheets

    NASA Astrophysics Data System (ADS)

    Xiang, Quanjun; Yu, Jiaguo; Jaroniec, Mietek

    2011-09-01

    Graphene-modified TiO2 nanosheets with exposed (001) facets (graphene/TiO2) were prepared by microwave-hydrothermal treatment of graphene oxide (GO) and hydrothermally synthesized TiO2 nanosheets with exposed (001) facets in an ethanol-water solvent. These nanocomposite samples showed high photocatalytic H2-production activity in aqueous solutions containing methanol, as sacrificial reagent, even without Pt co-catalyst. The optimal graphene content was found to be ~1.0 wt%, giving a H2-production rate of 736 μmol h-1 g-1 with a quantum efficiency (QE) of 3.1%, which exceeded the rate observed on pure TiO2 nanosheets by more than 41 times. This high photocatalytic H2-production activity is due to the deposition of TiO2 nanosheets on graphene sheets, which act as an electron acceptor to efficiently separate the photogenerated charge carriers. The observed enhancement in the photocatalytic activity is due to the lower absolute potential of graphene/graphene z.rad- (-0.08 V vs. SHE, pH = 0) in comparison to the conduction band (-0.24 V) of anatase TiO2, meanwhile the aforementioned absolute value is higher than the reduction potential of H+ (0 V), which favors the electron transfer from the conduction band (CB) of TiO2 to graphene sheets and the reduction of H+, thus enhancing photocatalytic H2-production activity. The proposed mechanism for the observed photocatalytic performance of TiO2 nanosheets, modified with a small amount of graphene, was further confirmed by photoluminescence spectroscopy and transient photocurrent response. This work not only shows a possibility for the utilization of low cost graphene sheets as a substitute for noble metals (such as Pt) in the photocatalytic H2-production but also for the first time shows a significant enhancement in the H2-production activity by using metal-free carbon material as an effective co-catalyst.

  6. Enhanced photocatalytic H₂-production activity of graphene-modified titania nanosheets.

    PubMed

    Xiang, Quanjun; Yu, Jiaguo; Jaroniec, Mietek

    2011-09-01

    Graphene-modified TiO(2) nanosheets with exposed (001) facets (graphene/TiO(2)) were prepared by microwave-hydrothermal treatment of graphene oxide (GO) and hydrothermally synthesized TiO(2) nanosheets with exposed (001) facets in an ethanol-water solvent. These nanocomposite samples showed high photocatalytic H(2)-production activity in aqueous solutions containing methanol, as sacrificial reagent, even without Pt co-catalyst. The optimal graphene content was found to be ∼1.0 wt%, giving a H(2)-production rate of 736 μmol h(-1) g(-1) with a quantum efficiency (QE) of 3.1%, which exceeded the rate observed on pure TiO(2) nanosheets by more than 41 times. This high photocatalytic H(2)-production activity is due to the deposition of TiO(2) nanosheets on graphene sheets, which act as an electron acceptor to efficiently separate the photogenerated charge carriers. The observed enhancement in the photocatalytic activity is due to the lower absolute potential of graphene/graphene˙(-) (-0.08 V vs. SHE, pH = 0) in comparison to the conduction band (-0.24 V) of anatase TiO(2), meanwhile the aforementioned absolute value is higher than the reduction potential of H(+) (0 V), which favors the electron transfer from the conduction band (CB) of TiO(2) to graphene sheets and the reduction of H(+), thus enhancing photocatalytic H(2)-production activity. The proposed mechanism for the observed photocatalytic performance of TiO(2) nanosheets, modified with a small amount of graphene, was further confirmed by photoluminescence spectroscopy and transient photocurrent response. This work not only shows a possibility for the utilization of low cost graphene sheets as a substitute for noble metals (such as Pt) in the photocatalytic H(2)-production but also for the first time shows a significant enhancement in the H(2)-production activity by using metal-free carbon material as an effective co-catalyst. PMID:21826308

  7. Growth of and fumitremorgin production by Neosartorya fischeri as affected by temperature, light, and water activity.

    PubMed Central

    Nielsen, P V; Beuchat, L R; Frisvad, J C

    1988-01-01

    The effects of temperature, light, and water activity (aw) on the growth and fumitremorgin production of a heat-resistant mold, Neosartorya fischeri, cultured on Czapek Yeast Autolysate agar (CYA) were studied for incubation periods of up to 74 days. Colonies were examined visually, and extracts of mycelia and CYA on which the mold was cultured were analyzed for mycotoxin content by high-performance liquid chromatography. Growth always resulted in the production of the tremorgenic mycotoxins verruculogen and fumitremorgins A and C. The optimum temperatures for the production of verruculogen and fumitremorgins A and C on CYA at pH 7.0 were 25, 30, and 37 degrees C, respectively. The production of fumitremorgin C by N. fischeri has not been previously reported. Fumitremorgin production was retarded at 15 degrees C, but an extension of the incubation period resulted in concentrations approaching those observed at 25 degrees C. Light clearly enhanced fumitremorgin production on CYA (pH 7.0, 25 degrees C), but not as dramatically as did the addition of glucose, fructose, or sucrose to CYA growth medium (pH 3.5, 25 degrees C). Growth and fumitremorgin production was greatest at aw of 0.980 on CYA supplemented with glucose or fructose and at aw of 0.990 on CYA supplemented with sucrose. Growth and fumitremorgin production were observed at aw as low as 0.925 on glucose-supplemented CYA but not at aw lower than 0.970 on CYA supplemented with sucrose. Verruculogen was produced in the highest amount on all test media, followed by fumitremorgin A and fumitremorgin C. PMID:3415223

  8. Growth of and fumitremorgin production by Neosartorya fischeri as affected by temperature, light, and water activity.

    PubMed

    Nielsen, P V; Beuchat, L R; Frisvad, J C

    1988-06-01

    The effects of temperature, light, and water activity (aw) on the growth and fumitremorgin production of a heat-resistant mold, Neosartorya fischeri, cultured on Czapek Yeast Autolysate agar (CYA) were studied for incubation periods of up to 74 days. Colonies were examined visually, and extracts of mycelia and CYA on which the mold was cultured were analyzed for mycotoxin content by high-performance liquid chromatography. Growth always resulted in the production of the tremorgenic mycotoxins verruculogen and fumitremorgins A and C. The optimum temperatures for the production of verruculogen and fumitremorgins A and C on CYA at pH 7.0 were 25, 30, and 37 degrees C, respectively. The production of fumitremorgin C by N. fischeri has not been previously reported. Fumitremorgin production was retarded at 15 degrees C, but an extension of the incubation period resulted in concentrations approaching those observed at 25 degrees C. Light clearly enhanced fumitremorgin production on CYA (pH 7.0, 25 degrees C), but not as dramatically as did the addition of glucose, fructose, or sucrose to CYA growth medium (pH 3.5, 25 degrees C). Growth and fumitremorgin production was greatest at aw of 0.980 on CYA supplemented with glucose or fructose and at aw of 0.990 on CYA supplemented with sucrose. Growth and fumitremorgin production were observed at aw as low as 0.925 on glucose-supplemented CYA but not at aw lower than 0.970 on CYA supplemented with sucrose. Verruculogen was produced in the highest amount on all test media, followed by fumitremorgin A and fumitremorgin C. PMID:3415223

  9. Brazilian Propolis: A Natural Product That Improved the Fungicidal Activity by Blood Phagocytes

    PubMed Central

    Possamai, Muryllo Mendes; Honorio-França, Adenilda Cristina; Reinaque, Ana Paula Barcelos; França, Eduardo Luzia; Souto, Paula Cristina de Souza

    2013-01-01

    Natural product incorporation into microcarriers increases the bioavailability of these compounds, consequently improving their therapeutic properties. Natural products, particularly those from bees such as propolis, are widely used in popular medicine. Propolis is a powerful treatment for several diseases. In this context, the present study evaluated the effect of propolis Scaptotrigona sp. and its fractions, alone or adsorbed to polyethylene glycol (PEG) microspheres, on the activity of human phagocytes against Candida albicans. The results show that propolis exerts a stimulatory effect on these cells to assist in combating the fungus, especially as the crude extract is compared with the fractions. However, when incorporated into microspheres, these properties were significantly potentiated. These results suggest that propolis adsorbed onto PEG microspheres has immunostimulatory effects on phagocytes in human blood. Therefore, propolis may potentially be an additional natural product that can be used for a variety of therapies. PMID:23509737

  10. Brazilian propolis: a natural product that improved the fungicidal activity by blood phagocytes.

    PubMed

    Possamai, Muryllo Mendes; Honorio-França, Adenilda Cristina; Reinaque, Ana Paula Barcelos; França, Eduardo Luzia; Souto, Paula Cristina de Souza

    2013-01-01

    Natural product incorporation into microcarriers increases the bioavailability of these compounds, consequently improving their therapeutic properties. Natural products, particularly those from bees such as propolis, are widely used in popular medicine. Propolis is a powerful treatment for several diseases. In this context, the present study evaluated the effect of propolis Scaptotrigona sp. and its fractions, alone or adsorbed to polyethylene glycol (PEG) microspheres, on the activity of human phagocytes against Candida albicans. The results show that propolis exerts a stimulatory effect on these cells to assist in combating the fungus, especially as the crude extract is compared with the fractions. However, when incorporated into microspheres, these properties were significantly potentiated. These results suggest that propolis adsorbed onto PEG microspheres has immunostimulatory effects on phagocytes in human blood. Therefore, propolis may potentially be an additional natural product that can be used for a variety of therapies.

  11. G protein-coupled estrogen receptor inhibits vascular prostanoid production and activity.

    PubMed

    Meyer, Matthias R; Fredette, Natalie C; Barton, Matthias; Prossnitz, Eric R

    2015-10-01

    Complications of atherosclerotic vascular disease, such as myocardial infarction and stroke, are the most common causes of death in postmenopausal women. Endogenous estrogens inhibit vascular inflammation-driven atherogenesis, a process that involves cyclooxygenase (COX)-derived vasoconstrictor prostanoids such as thromboxane A2. Here, we studied whether the G protein-coupled estrogen receptor (GPER) mediates estrogen-dependent inhibitory effects on prostanoid production and activity under pro-inflammatory conditions. Effects of estrogen on production of thromboxane A(2) were determined in human endothelial cells stimulated by the pro-inflammatory cytokine tumour necrosis factor alpha (TNF-α). Moreover, Gper-deficient (Gper(-/-)) and WT mice were fed a pro-inflammatory diet and underwent ovariectomy or sham surgery to unmask the role of endogenous estrogens. Thereafter, contractions to acetylcholine-stimulated endothelial vasoconstrictor prostanoids and the thromboxane-prostanoid receptor agonist U46619 were recorded in isolated carotid arteries. In endothelial cells, TNF-α-stimulated thromboxane A2 production was inhibited by estrogen, an effect blocked by the GPER-selective antagonist G36. In ovary-intact mice, deletion of Gper increased prostanoid-dependent contractions by twofold. Ovariectomy also augmented prostanoid-dependent contractions by twofold in WT mice but had no additional effect in Gper(-/-) mice. These contractions were blocked by the COX inhibitor meclofenamate and unaffected by the nitric oxide synthase inhibitor l-N(G)-nitroarginine methyl ester. Vasoconstrictor responses to U46619 did not differ between groups, indicating intact signaling downstream of thromboxane-prostanoid receptor activation. In summary, under pro-inflammatory conditions, estrogen inhibits vasoconstrictor prostanoid production in endothelial cells and activity in intact arteries through GPER. Selective activation of GPER may therefore be considered as a novel strategy to

  12. G protein-coupled estrogen receptor inhibits vascular prostanoid production and activity

    PubMed Central

    Meyer, Matthias R.; Fredette, Natalie C.; Barton, Matthias; Prossnitz, Eric R.

    2016-01-01

    Complications of atherosclerotic vascular disease, such as myocardial infarction and stroke, are the most common cause of death in postmenopausal women. Endogenous estrogens inhibit vascular inflammation-driven atherogenesis, a process that involves cyclooxygenase-derived vasoconstrictor prostanoids such as thromboxane A2. Here, we studied whether the G protein-coupled estrogen receptor (GPER) mediates estrogen-dependent inhibitory effects on prostanoid production and activity under pro-inflammatory conditions. Effects of estrogen on production of thromboxane A2 were determined in human endothelial cells stimulated by the pro-inflammatory cytokine TNF-α. Moreover, Gper-deficient (Gper−/−) and wild-type mice were fed a pro-inflammatory diet and underwent ovariectomy or sham surgery to unmask the role of endogenous estrogens. Thereafter, endothelium-dependent contractions to acetylcholine-stimulated vasoconstrictor prostanoids and the thromboxane-prostanoid receptor agonist U46619 were recorded in isolated carotid arteries. In endothelial cells, TNF-α-stimulated thromboxane A2 production was inhibited by estrogen, an effect blocked by the GPER-selective antagonist G36. In ovary-intact mice, deletion of Gper increased prostanoid-dependent contractions by 2-fold. Ovariectomy also augmented prostanoid-dependent contractions by 2-fold in wild-type mice, but had no additional effect in Gper−/− mice. These contractions were blocked by the cyclooxygenase inhibitor meclofenamate and unaffected by the nitric oxide synthase inhibitor L-NAME. Vasoconstrictor responses to U46619 did not differ between groups, indicating intact signaling downstream of thromboxane-prostanoid receptor activation. In summary, under pro-inflammatory conditions, estrogen inhibits vasoconstrictor prostanoid production in endothelial cells and activity in intact arteries through GPER. Selective activation of GPER may therefore be considered as a novel strategy to treat increased prostanoid

  13. Task-dependent Modulations of Prefrontal and Hippocampal Activity during Intrinsic Word Production

    PubMed Central

    Whitney, Carin; Weis, Susanne; Krings, Timo; Huber, Walter; Grossman, Murray; Kircher, Tilo

    2009-01-01

    Functional imaging studies of single word production have consistently reported activation of the lateral prefrontal and cingulate cortex. Its contribution has been shown to be sensitive to task demands, which can be manipulated by the degree of response specification. Compared with classical verbal fluency, free word association relies less on response restrictions but to a greater extent on associative binding processes, usually subserved by the hippocampus. To elucidate the relevance of the frontal and medial-temporal areas during verbal retrieval tasks, we applied varying degrees of response specification. During fMRI data acquisition, 18 subjects performed a free verbal association (FVA), a semantic verbal fluency (SVF) task, and a phonological verbal fluency (PVF) task. Externally guided word production served as a baseline condition to control for basic articulatory and reading processes. As expected, increased brain activity was observed in the left lateral and bilateral medial frontal cortices for SVF and PVF. The anterior cingulate gyrus was the only structure common to both fluency tasks in direct comparison to the less restricted FVA task. The hippocampus was engaged during associative and semantic retrieval. Interestingly, hippocampal activity was selectively evident during FVA in direct comparison to SVF when it was controlled for stimulus–response relations. The current data confirm the role of the left prefrontal–cingulate network in constrained word production. Hippocampal activity during spontaneous word production is a novel finding and seems to be dependent on the retrieval process (free vs. constrained) rather than the variety of stimulus–response relationships that is involved. PMID:18578599

  14. Energy recovery during advanced wastewater treatment: simultaneous estrogenic activity removal and hydrogen production through solar photocatalysis.

    PubMed

    Zhang, Wenlong; Li, Yi; Wang, Chao; Wang, Peifang; Wang, Qing

    2013-03-01

    Simultaneous estrogenic activity removal and hydrogen production from secondary effluent were successfully achieved using TiO(2) microspheres modified with both platinum nanoparticles and phosphates (P-TiO(2)/Pt) for the first time. The coexistence of platinum and phosphate on the surface of TiO(2) microspheres was confirmed by transmission electron microscope, energy-dispersive X-ray and X-ray photoelectron spectroscopy analyses. P-TiO(2)/Pt microspheres showed a significantly higher photocatalytic activity than TiO(2) microspheres and TiO(2) powders (P25) for the removal of estrogenic activity from secondary effluent with the removal ratio of 100%, 58.2% and 48.5% in 200 min, respectively. Moreover, the marked production of hydrogen (photonic efficiency: 3.23 × 10(-3)) was accompanied by the removal of estrogenic activity only with P-TiO(2)/Pt as photocatalysts. The hydrogen production rate was increasing with decreased DO concentration in secondary effluent. Results of reactive oxygen species (ROS) evaluation during P-TiO(2)/Pt photocatalytic process showed that O(2)(-)and OH were dominant ROS in aerobic phase, while OH was the most abundant ROS in anoxic phase. Changes of effluent organic matter (EfOM) during photocatalysis revealed that aromatic, hydrophobic, and high molecular weight fractions of EfOM were preferentially transformed into non-humic, hydrophilic, and low MW fractions (e.g. aldehydes and carboxylic acids), which were continuously utilized as electron donors in hydrogen production process. PMID:23269320

  15. Energy recovery during advanced wastewater treatment: simultaneous estrogenic activity removal and hydrogen production through solar photocatalysis.

    PubMed

    Zhang, Wenlong; Li, Yi; Wang, Chao; Wang, Peifang; Wang, Qing

    2013-03-01

    Simultaneous estrogenic activity removal and hydrogen production from secondary effluent were successfully achieved using TiO(2) microspheres modified with both platinum nanoparticles and phosphates (P-TiO(2)/Pt) for the first time. The coexistence of platinum and phosphate on the surface of TiO(2) microspheres was confirmed by transmission electron microscope, energy-dispersive X-ray and X-ray photoelectron spectroscopy analyses. P-TiO(2)/Pt microspheres showed a significantly higher photocatalytic activity than TiO(2) microspheres and TiO(2) powders (P25) for the removal of estrogenic activity from secondary effluent with the removal ratio of 100%, 58.2% and 48.5% in 200 min, respectively. Moreover, the marked production of hydrogen (photonic efficiency: 3.23 × 10(-3)) was accompanied by the removal of estrogenic activity only with P-TiO(2)/Pt as photocatalysts. The hydrogen production rate was increasing with decreased DO concentration in secondary effluent. Results of reactive oxygen species (ROS) evaluation during P-TiO(2)/Pt photocatalytic process showed that O(2)(-)and OH were dominant ROS in aerobic phase, while OH was the most abundant ROS in anoxic phase. Changes of effluent organic matter (EfOM) during photocatalysis revealed that aromatic, hydrophobic, and high molecular weight fractions of EfOM were preferentially transformed into non-humic, hydrophilic, and low MW fractions (e.g. aldehydes and carboxylic acids), which were continuously utilized as electron donors in hydrogen production process.

  16. Lymphokine-activated killer (LAK) cells can be focused at sites of tumor growth by products of macrophage activation

    SciTech Connect

    Migliori, R.J.; Gruber, S.A.; Sawyer, M.D.; Hoffman, R.; Ochoa, A.; Bach, F.H.; Simmons, R.L.

    1987-08-01

    Successful adoptive cancer immunotherapy presumably depends on the accumulation of tumoricidal leukocytes at the sites of tumor growth. Large numbers of lymphokine-activated killer (LAK) cells can be generated in vitro by growth in high concentrations of interleukin-2 (IL-2), but relatively few arrive at the tumor site after intravenous injection. We hypothesize that the delivery of LAK cells to tumor sites may be augmented by previously demonstrated lymphocyte-recruiting factors, including activated macrophage products such as interleukin-1 (IL-1) and tumor necrosis factor. /sup 111/Indium-labeled LAK cells were injected intravenously into syngeneic mice bearing the macrophage activator endotoxin (LPS) in one hind footpad, and saline solution was injected into the contralateral footpad. Significantly more activity was recovered from the LPS-bearing footpad at all times during a 96-hour period. Recombinant IL-1 also attracted more LAK cells after injection into tumor-free hind footpads. Furthermore, LAK cells preferentially homed to hind footpads that were bearing 3-day established sarcomas after intralesional injections of LPS, IL-1, or tumor necrosis factor when compared with contralateral tumor-bearing footpads injected with saline solution alone. In preliminary experiments, mice with hind-footpad tumors appeared to survive longer after combined systemic IL-2 and LAK therapy if intralesional LPS was administered. These studies demonstrate that macrophage activation factors that have been shown capable of attracting circulating normal lymphocytes can also effectively attract LAK cells from the circulation. By the stimulation of macrophages at the sites of tumor growth, more LAK cells can be attracted. It is hoped that by focusing the migration of LAK cells to tumors, LAK cells and IL-2 would effect tumor regression more efficiently and with less toxicity.

  17. Modeling of Geomechanical Performance of Sloping Oceanic Hydrate Deposits Subjected Production Activities

    NASA Astrophysics Data System (ADS)

    Rutqvist, J.; Moridis, G. J.

    2012-12-01

    Oceanic Hydrate-Bearing Sediments (HBS) subjected to production activities can induced strongly coupled fluid flow and geomechanical changes that may have adverse consequences on wellbore integrity, the HBS, and the bounding formations. For a sloping hydrate bearing system, the geomechanical changes could potentially be catastrophic if triggering large slides of the seafloor. Marine sediments adjacent to the seafloor as well as hydrate deposits that are suitable target for production often involves unconsolidated sediments of relatively high porosity that are usually characterized by limited shear strength. The dissociation of the solid hydrates (a strong cementing agent) during gas production can degrade the structural strength of the HBS and thereby undermine the stability of the seafloor. In this study we investigate two cases of coupled hydraulic, thermodynamic and geomechanical behavior of sloping oceanic HBS: 1) hydrate heating as warm fluids from deeper conventional reservoirs ascend to the ocean floor through uninsulated pipes intersecting an HBS adjacent to the seafloor, 2) system response during gas production from a hydrate deposit located 400 m below the seafloor. In the first case we consider a situation when a hydraulically confined hydrate layer near the ocean floor is dissociated by heating from the well with associated gas release and forced pressure increase, which could undermine the stability of the slope. In the second case, depressurization leads to hydrate dissociation over a large lateral distance that may provide a weakening potential slip surface along the sloping hydrate system. The results of our analysis indicate that although these production activities induces strongly coupled geomechanical responses that may adversely impact the production itself, they are unlikely to trigger large scale slides of the seafloor.

  18. A mechanistic study of limonene oxidation products and pathways following cleaning activities

    NASA Astrophysics Data System (ADS)

    Carslaw, Nicola

    2013-12-01

    Indoor air pollution has caused increasing concern since the 1970s, when the advent of stricter energy efficiency measures lead to increased reports of building related symptoms. Cleaning activities have been linked to adverse health effects indoors, although it is unclear which of the components of cleaning products cause these reported health effects. This paper uses a detailed chemical model for indoor air chemistry, to identify the species formed at the highest concentrations following use of a limonene-based cleaning product. The explicit nature of the chemical mechanism also permits the key pathways to their formation to be identified. The results show that the key species in terms of gas-phase concentration are multi-functional carbonyl species including limonaldehyde, 4-acetyl-1-methyl-1-cyclohexene and other dicarbonyl species. The particle-phase was dominated by peroxide species. The predicted gas-phase concentrations for three limonene-oxidation products were compared to recently published human reference values, but found not to be high enough to cause concern for typical indoor conditions, or under high indoor ozone conditions. However, cleaning products contain a range of terpenes other than limonene, which could also produce some of the secondary products identified here, as well as more common species such as formaldehyde, glyoxal and hydrogen peroxide. A mechanistic pathway analysis shows that the secondary products formed through limonene oxidation indoors depend critically on the competition between ozone and hydroxyl radicals, such that indoor pollutant concentrations and composition could vary widely in different locations for a nominally similar residence and indoor activities. Future studies should focus on aiming to measure multi-functional carbonyl species indoors to help validate models, whilst human reference values are needed for many more relevant species indoors.

  19. Production of Hydroxyl Radical via the Activation of Hydrogen Peroxide by Hydroxylamine.

    PubMed

    Chen, Liwei; Li, Xuchun; Zhang, Jing; Fang, Jingyun; Huang, Yanmin; Wang, Ping; Ma, Jun

    2015-09-01

    The production of the hydroxyl radical (HO·) is important in environmental chemistry. This study reports a new source of HO· generated solely from hydrogen peroxide (H2O2) activated by hydroxylamine (HA). Electron paramagnetic resonance analysis and the oxidation of a HO· probe, benzoic acid, were used to confirm the production of HO·. The production of HO· increased with increasing concentrations of either HA or H2O2 as well as decreasing pH. The second-order rate constant for the reaction was (2.2 ± 0.2) × 10(-4) M(-1) s(-1). HO· was probably produced in two steps: the activation of H2O2 by protonated HA and then reaction between the H2O2 and the intermediate protonated aminoxyl radical generated in the first step. Such a two-step oxidation can possibly be ascribed to the ionizable hydroxyl moiety in the molecular structure of HA, as is suggested by comparing the reactivity of a series of HA derivatives in HO· production. The results shed light on a previously unknown source of HO· formation, which broadens the understanding of its role in environmental processes.

  20. Utilization of molasses spentwash for production of bioplastics by waste activated sludge.

    PubMed

    Khardenavis, Anshuman A; Vaidya, Atul N; Kumar, M Suresh; Chakrabarti, Tapan

    2009-09-01

    Present study describes the treatment of molasses spentwash and its use as a potential low cost substrate for production of biopolymer polyhydroxybutyrate (PHB) by waste activated sludge. Fluorescence microscopy revealed the presence of PHB granules in sludge biomass which was further confirmed by fourier transform-infra-red spectroscopy (FT-IR) and (13)C nuclear magnetic resonance (NMR). The processing of molasses spentwash was carried out for attaining different ratios of carbon and nitrogen (C:N). Highest chemical oxygen demand (COD) removal and PHB accumulation of 60% and 31% respectively was achieved with raw molasses spentwash containing inorganic nitrogen (C:N ratio=28) followed by COD removal of 52% and PHB accumulation of 28% for filtered molasses containing inorganic nitrogen (C:N ratio=29). PHB production yield (Y(p/s)) was highest (0.184 g g(-1) COD consumed) for deproteinized spentwash supplemented with nitrogen. In contrast, the substrate consumption and product formation were higher in case of raw spentwash. Though COD removal was lowest from deproteinized spentwash, evaluation of kinetic parameters suggested higher rates of conversion of available carbon to biomass and PHB. Thus the process provided dual benefit of conversion of two wastes viz. waste activated sludge and molasses spentwash into value-added product-PHB. PMID:19500968

  1. Utilization of molasses spentwash for production of bioplastics by waste activated sludge

    SciTech Connect

    Khardenavis, Anshuman A. Vaidya, Atul N.; Kumar, M. Suresh; Chakrabarti, Tapan

    2009-09-15

    Present study describes the treatment of molasses spentwash and its use as a potential low cost substrate for production of biopolymer polyhydroxybutyrate (PHB) by waste activated sludge. Fluorescence microscopy revealed the presence of PHB granules in sludge biomass which was further confirmed by fourier transform-infra-red spectroscopy (FT-IR) and {sup 13}C nuclear magnetic resonance (NMR). The processing of molasses spentwash was carried out for attaining different ratios of carbon and nitrogen (C:N). Highest chemical oxygen demand (COD) removal and PHB accumulation of 60% and 31% respectively was achieved with raw molasses spentwash containing inorganic nitrogen (C:N ratio = 28) followed by COD removal of 52% and PHB accumulation of 28% for filtered molasses containing inorganic nitrogen (C:N ratio = 29). PHB production yield (Y{sub p/s}) was highest (0.184 g g{sup -1} COD consumed) for deproteinized spentwash supplemented with nitrogen. In contrast, the substrate consumption and product formation were higher in case of raw spentwash. Though COD removal was lowest from deproteinized spentwash, evaluation of kinetic parameters suggested higher rates of conversion of available carbon to biomass and PHB. Thus the process provided dual benefit of conversion of two wastes viz. waste activated sludge and molasses spentwash into value-added product-PHB.

  2. Evaluation of antioxidant activity and inhibitory effect on nitric oxide production of some common vegetables.

    PubMed

    Bor, Jung-Yi; Chen, Hui-Yin; Yen, Gow-Chin

    2006-03-01

    The objectives of this study were to study the antioxidant activities and nitric oxide (NO) scavenging effects of vegetables in vitro systems and to study the inhibitory effects of vegetables on the NO production and NO-induced DNA damage in RAW 264.7 macrophage. The results indicated that water extracts from Indian lotus, Jew's ear, shiitake, eggplant, and winter mushroom showed stronger antioxidant activity and free-radical-scavenging ability than that of other vegetable extracts. The scavenging effects of vegetable extracts on NO derived from sodium nitroprusside (SNP) were in decreasing order of water spinach > Indian lotus > eggplant and garland chrysanthemum. In the macrophage model system, the water extracts from fresh daylily flower, sponge gourd, pea sprout, and eggplant exhibited over 80% inhibition on NO generation stimulated by lipopolysaccharide. The extract from fresh daylily flower that expressed the strongest inhibition on NO production was attributed to the ability to reduce the inducible nitric oxide synthase (iNOS) induction. However, the extracts from pea sprout and eggplant suppressed the NO production by scavenging on NO and inactivating toward iNOS enzyme. In addition, the water extracts from fresh daylily flower, sponge gourd, pea sprout, and eggplant also showed over 40% inhibitory effect on DNA damage induced by SNP in RAW 264.7 macrophage. The data also indicated that eggplant and pea sprout extracts contained higher total phenolic compounds, anthocyanins, and ascorbic acids and appeared to be responsible for their antioxidant activities and scavenging effects on NO derived from SNP. PMID:16506819

  3. Photodegradation of fluorene in aqueous solution: Identification and biological activity testing of degradation products.

    PubMed

    Kinani, Said; Souissi, Yasmine; Kinani, Aziz; Vujović, Svetlana; Aït-Aïssa, Sélim; Bouchonnet, Stéphane

    2016-04-15

    Degradation of fluorene under UV-vis irradiation in water was investigated and structural elucidation of the main photoproducts was achieved using gas chromatography coupled with mass spectrometry. Twenty-six photoproducts were structurally identified, mainly on the basis of electron ionization mass spectra interpretation. The main generated transformation products are hydroxy derivatives. Some secondary photoproducts including fluorenone, hydroxy fluorenone, 2-biphenyl carboxylic acid, biphenylene, methanol fluorene congeners and hydroxy fluorene dimers were also observed. A photodegradation pathway was suggested on the basis of the chemical structures of photoproducts. Fluorene as well as its main photoproducts for which chemical standards were commercially available were tested for their ability to elicit cytotoxic, estrogenic and dioxin-like activity by using in vitro cell-based bioassays. None of the tested compounds was cytotoxic at concentrations up to 100 μM. However, 2-hydroxyfluorene and 3-hydroxyfluorene exerted significant estrogenic and dioxin-like activity on a concentration range of 3-30 μM, while fluorene and 9-hydroxyfluorene were weakly or not active, respectively, in our assays. This supports the view that photodegradation processes can generate by-products of higher toxicological concern than the parent compound and strengthens the need to further identify transformation products in the aquatic environment.

  4. Treatment of saline wastewaters from marine-products processing factories by activated sludge reactor.

    PubMed

    Khannous, L; Souissi, N; Ghorbel, B; Jarboui, R; Kallel, M; Nasri, M; Gharsallah, N

    2003-10-01

    An activated sludge reactor, operated at room temperature (20-30 degrees C) was used to treat saline wastewaters generated by marine-products industries. The system was operated continuously and the influence of the organic loading rates (OLRs), varying from 250 to 1000 mg COD l(-1) day(-1), on chemical oxygen demand (COD) removal was investigated. The system, inoculated with NaCl-acclimated culture, removed up to 98% and 88% of the influent COD concentrations at OLRs of 250 and 1000 mg COD L(-1) day(-1), respectively. Since the organic pollution is essentially composed of proteins, microorganisms, which produced proteolytic enzymes, were isolated from the activated sludge culture. One bacterium with the highest protease activity, identified as Bacillus cereus, was chosen for protease production in fishery wastewaters of different concentrations containing combined heads and viscera powder. Protease synthesis was strongly enhanced when cells were cultivated in two times diluted fishery wastewaters. The enhancement of protease synthesis could have been due to the presence in effluent of organic matters or salts, which stimulated the growth of the strain and protease production.

  5. Selective enrichment and production of highly urease active bacteria by non-sterile (open) chemostat culture.

    PubMed

    Cheng, Liang; Cord-Ruwisch, Ralf

    2013-10-01

    In general, bioprocesses can be subdivided into naturally occurring processes, not requiring sterility (e.g., beer brewing, wine making, lactic acid fermentation, or biogas digestion) and other processes (e.g., the production of enzymes and antibiotics) that typically require a high level of sterility to avoid contaminant microbes overgrowing the production strain. The current paper describes the sustainable, non-sterile production of an industrial enzyme using activated sludge as inoculum. By using selective conditions (high pH, high ammonia concentration, and presence of urea) for the target bacterium, highly active ureolytic bacteria, physiologically resembling Sporosarcina pasteurii were reproducibly enriched and then continuously produced via chemostat operation of the bioreactor. When using a pH of 10 and about 0.2 M urea in a yeast extract-based medium, ureolytic bacteria developed under aerobic chemostat operation at hydraulic retention times of about 10 h with urease levels of about 60 μmol min⁻¹ ml⁻¹ culture. For cost minimization at an industrial scale the costly protein-rich yeast extract medium could be replaced by commercial milk powder or by lysed activated sludge. Glutamate, molasses, or glucose-based media did not result in the enrichment of ureolytic bacteria by the chemostat. The concentration of intracellular urease was sufficiently high such that the produced raw effluent from the reactor could be used directly for biocementation in the field.

  6. Treatment of saline wastewaters from marine-products processing factories by activated sludge reactor.

    PubMed

    Khannous, L; Souissi, N; Ghorbel, B; Jarboui, R; Kallel, M; Nasri, M; Gharsallah, N

    2003-10-01

    An activated sludge reactor, operated at room temperature (20-30 degrees C) was used to treat saline wastewaters generated by marine-products industries. The system was operated continuously and the influence of the organic loading rates (OLRs), varying from 250 to 1000 mg COD l(-1) day(-1), on chemical oxygen demand (COD) removal was investigated. The system, inoculated with NaCl-acclimated culture, removed up to 98% and 88% of the influent COD concentrations at OLRs of 250 and 1000 mg COD L(-1) day(-1), respectively. Since the organic pollution is essentially composed of proteins, microorganisms, which produced proteolytic enzymes, were isolated from the activated sludge culture. One bacterium with the highest protease activity, identified as Bacillus cereus, was chosen for protease production in fishery wastewaters of different concentrations containing combined heads and viscera powder. Protease synthesis was strongly enhanced when cells were cultivated in two times diluted fishery wastewaters. The enhancement of protease synthesis could have been due to the presence in effluent of organic matters or salts, which stimulated the growth of the strain and protease production. PMID:14669806

  7. A tensor-product-kernel framework for multiscale neural activity decoding and control.

    PubMed

    Li, Lin; Brockmeier, Austin J; Choi, John S; Francis, Joseph T; Sanchez, Justin C; Príncipe, José C

    2014-01-01

    Brain machine interfaces (BMIs) have attracted intense attention as a promising technology for directly interfacing computers or prostheses with the brain's motor and sensory areas, thereby bypassing the body. The availability of multiscale neural recordings including spike trains and local field potentials (LFPs) brings potential opportunities to enhance computational modeling by enriching the characterization of the neural system state. However, heterogeneity on data type (spike timing versus continuous amplitude signals) and spatiotemporal scale complicates the model integration of multiscale neural activity. In this paper, we propose a tensor-product-kernel-based framework to integrate the multiscale activity and exploit the complementary information available in multiscale neural activity. This provides a common mathematical framework for incorporating signals from different domains. The approach is applied to the problem of neural decoding and control. For neural decoding, the framework is able to identify the nonlinear functional relationship between the multiscale neural responses and the stimuli using general purpose kernel adaptive filtering. In a sensory stimulation experiment, the tensor-product-kernel decoder outperforms decoders that use only a single neural data type. In addition, an adaptive inverse controller for delivering electrical microstimulation patterns that utilizes the tensor-product kernel achieves promising results in emulating the responses to natural stimulation. PMID:24829569

  8. Mutagenicity and DNA-damaging activity of decomposed products of food colours under UV irradiation.

    PubMed

    Ozaki, A; Kitano, M; Itoh, N; Kuroda, K; Furusawa, N; Masuda, T; Yamaguchi, H

    1998-01-01

    Five synthetic food colours Food Red Nos 3, 40 and 102 and Food Blue Nos 1 and 2, and their UV irradiated products were tested for mutagenic activity by means of the Ames test using Salmonella typhimurium strains TA98 and TA100. Food colours were irradiated with UV light for 14 days. Food Red Nos 3, 40 and 102 and Food Blue No. 1 were non-mutagenic before and after irradiation. UV irradiated products of Food Blue No. 2 were mutagenic in TA98 with or without S-9 mix. The mutagenic activity increased with increasing irradiation period, reached maximum potency on day 6, and then decreased. Moreover, Food Blue No. 2 showed DNA-damaging activity after 14 days of irradiation in rec-assay using Bacillus subtilis strains H17 and M45. The capillary electrophoresis was applied for the analysis of UV irradiated products of Food Blue No. 2. The original peak of Food Blue No. 2 was decomposed into seven peaks after UV irradiation.

  9. Nanocrystals of medium soluble actives--novel concept for improved dermal delivery and production strategy.

    PubMed

    Zhai, Xuezhen; Lademann, Jürgen; Keck, Cornelia M; Müller, Rainer H

    2014-08-15

    After use in oral pharmaceutical products, nanocrystals are meanwhile applied to improve the dermal penetration of cosmetic actives (e.g. rutin, hesperidin) and of drugs. By now, nanocrystals are only dermally applied made from poorly soluble actives. The novel concept is to formulate nanocrystals also from medium soluble actives, and to apply a dermal formulation containing additionally nanocrystals. The nanocrystals should act as fast dissolving depot, increase saturation solubility and especially accumulate in the hair follicles, to further increase skin penetration. Caffeine was used as model compound with relevance to market products, and a particular process was developed for the production of caffeine nanocrystals to overcome the supersaturation related effect of crystal growth and fiber formation - typical with medium soluble compounds. It is based on low energy milling (pearl milling) in combination with low dielectric constant dispersion media (water-ethanol or ethanol-propylene glycol mixtures) and optimal stabilizers. Most successful was Carbopol(®) 981 (e.g. 20% caffeine in ethanol-propylene glycol 3:7 with 2% Carbopol, w/w). Nanocrystals with varied sizes can now be produced in a controlled process e.g. 660 nm (optimal for hair follicle accumulation) to 250 nm (optimal for fast dissolution). The short term test proved stability over 2 months of the present formulation being sufficient to perform in vivo testing of the novel concept.

  10. Utilization of date stones for production of activated carbon using phosphoric acid

    SciTech Connect

    Haimour, N.M. . E-mail: nomanhaimour@hotmail.com; Emeish, S. . E-mail: s_emiesh@yahoo.com

    2006-07-01

    Date stone wastes have been utilized for production of activated carbon by chemical activation with phosphoric acid using a fluidized-bed reactor. The effects of the activation time, activation temperature, impregnation ratio, and particle size on the yield and the adsorptive capacity towards iodine were studied. The yield and the quality of the activated carbon prepared by using H{sub 3}PO{sub 4} were compared with that prepared from date stones using the same equipment, and under similar conditions by using ZnCl{sub 2} as an oxidizing agent. The maximum value of the iodine number of the activated carbon produced using H{sub 3}PO{sub 4} in this work was about 495 under the following conditions: impregnation ratio 0.4, activation time 60 min, activation temperature 800 deg. C, particle size 0.60 mm. The iodine number for the produced activated carbon was higher when phosphoric acid was used, compared to that when zinc chloride was used as impregnation reagent; however, the yield obtained when H{sub 3}PO{sub 4} was used was lower than the yield when ZnCl{sub 2} was used. The iodine number increases significantly with increasing the activation temperature. By increasing the impregnation ratio at the same temperature, the iodine number decreased sharply and an oscillation is noticed for all the cases but it was clearer at 800 deg. C. The average variation of the iodine number for the whole range of particle size used in this work is {+-}10%.

  11. Activities of amylase, proteinase, and lipase enzymes from Lactococcus chungangensis and its application in dairy products.

    PubMed

    Konkit, Maytiya; Kim, Wonyong

    2016-07-01

    Several enzymes are involved in the process of converting milk to lactic acid and coagulated milk to curd and, therefore, are important in dairy fermented products. Amylase, proteinase, and lipase are enzymes that play an important role in degrading milk into monomeric molecules such as oligosaccharides, amino acids, and fatty acids, which are the main molecules responsible for flavors in cheese. In the current study, we determined the amylase, proteinase, and lipase activities of Lactococcus chungangensis CAU 28(T), a bacterial strain of nondairy origin, and compared them with those of the reference strain, Lactococcus lactis ssp. lactis KCTC 3769(T), which is commonly used in the dairy industry. Lactococcus chungangensis CAU 28(T) and L. lactis ssp. lactis KCTC 3769(T) were both found to have amylase, proteinase, and lipase activities in broth culture, cream cheese, and yogurt. Notably, the proteinase and lipase activities of L. chungangensis CAU 28(T) were higher than those of L. lactis ssp. lactis KCTC 3769(T), with proteinase activity of 10.50 U/mL in tryptic soy broth and 8.64 U/mL in cream cheese, and lipase activity of 100 U/mL of tryptic soy broth, and 100 U/mL of cream cheese. In contrast, the amylase activity was low, with 5.28 U/mL in tryptic soy broth and 8.86 U/mL in cream cheese. These enzyme activities in L. chungangensis CAU 28(T) suggest that this strain has potential to be used for manufacturing dairy fermented products, even though the strain is of nondairy origin. PMID:27108177

  12. Detection rates of the MODIS active fire product in the United States

    USGS Publications Warehouse

    Hawbaker, T.J.; Radeloff, V.C.; Syphard, A.D.; Zhu, Z.; Stewart, S.I.

    2008-01-01

    MODIS active fire data offer new information about global fire patterns. However, uncertainties in detection rates can render satellite-derived fire statistics difficult to interpret. We evaluated the MODIS 1??km daily active fire product to quantify detection rates for both Terra and Aqua MODIS sensors, examined how cloud cover and fire size affected detection rates, and estimated how detection rates varied across the United States. MODIS active fire detections were compared to 361 reference fires (??? 18??ha) that had been delineated using pre- and post-fire Landsat imagery. Reference fires were considered detected if at least one MODIS active fire pixel occurred within 1??km of the edge of the fire. When active fire data from both Aqua and Terra were combined, 82% of all reference fires were found, but detection rates were less for Aqua and Terra individually (73% and 66% respectively). Fires not detected generally had more cloudy days, but not when the Aqua data were considered exclusively. MODIS detection rates decreased with fire size, and the size at which 50% of all fires were detected was 105??ha when combining Aqua and Terra (195??ha for Aqua and 334??ha for Terra alone). Across the United States, detection rates were greatest in the West, lower in the Great Plains, and lowest in the East. The MODIS active fire product captures large fires in the U.S. well, but may under-represent fires in areas with frequent cloud cover or rapidly burning, small, and low-intensity fires. We recommend that users of the MODIS active fire data perform individual validations to ensure that all relevant fires are included. ?? 2008 Elsevier Inc. All rights reserved.

  13. Antioxidant and nitric oxide production inhibitory activities of galacturonyl hydroxamic acid.

    PubMed

    Liu, Yuh-Hwa; Lin, Shyr-Yi; Lee, Chi-Ching; Hou, Wen-Chi

    2008-07-01

    The self-prepared pectin hydroxamic acid has been reported to have antioxidant activities [Yang, S. S., Cheng, K. D., Lin, Y. S., Liu, Y. W., & Hou, W. C. (2004). Pectin hydroxamic acids exhibit antioxidant activities in vitro. Journal of Agricultural and Food Chemistry, 52, 4270-4273]. In this study, the galacturonic acid (GalA), the monomer unit of the pectin polymer, was esterified with acidic methanol (1N HCl) at 4°C with gentle stirring for 5days to get galacturonic acid methyl ester which was further reacted with alkaline hydroxylamine to get galacturonyl hydroxamic acid (GalA-NHOH). The GalA-NHOH was used to test the antioxidant and antiradical activities in the comparison with GalA. The scavenging activities of GalA-NHOH against DPPH radicals (half-inhibition concentration, IC50, was 82μM), hydroxyl radicals detected by electron spin resonance (IC50 was 0.227nM in the comparison with Trolox of 0.433μM), superoxide radicals (IC50 was 830μM) were determined. The protection activities of GalA-NHOH against hydroxyl radicals-mediated calf thymus DNA damages, linoleic acid peroxidation and peroxynitrite-mediated dihydrorhodamine 123 oxidations were also investigated. It was found that the GalA-NHOH exhibited dose-dependently antioxidant activity and few or none was found in GalA. The GalA-NHOH was used to evaluate the suppressed activity of nitric oxide (NO) productions of RAW264.7 cells in the presence of lipopolysaccharide (LPS, 100ng/ml) as inducers. It was found that GalA-NHOH (0.02-0.1mg/ml) could dose-dependently suppress the NO productions (expressed as nitrite concentrations) in RAW264.7 cells without significant cytotoxicity.

  14. TRIM11 negatively regulates IFNβ production and antiviral activity by targeting TBK1.

    PubMed

    Lee, Younglang; Song, Byeongwoon; Park, Chankyu; Kwon, Ki-Sun

    2013-01-01

    The innate immune response is a host defense mechanism against infection by viruses and bacteria. Type I interferons (IFNα/β) play a crucial role in innate immunity. If not tightly regulated under normal conditions and during immune responses, IFN production can become aberrant, leading to inflammatory and autoimmune diseases. In this study, we identified TRIM11 (tripartite motif containing 11) as a novel negative regulator of IFNβ production. Ectopic expression of TRIM11 decreased IFNβ promoter activity induced by poly (I:C) stimulation or overexpression of RIG-I (retinoic acid-inducible gene-I) signaling cascade components RIG-IN (constitutively active form of RIG-I), MAVS (mitochondrial antiviral signaling protein), or TBK1 (TANK-binding kinase-1). Conversely, TRIM11 knockdown enhanced IFNβ promoter activity induced by these stimuli. Moreover, TRIM11 overexpression inhibited the phosphorylation and dimerization of IRF3 and expression of IFNβ mRNA. By contrast, TRIM11 knockdown increased the IRF3 phosphorylation and IFNβ mRNA expression. We also found that TRIM11 and TBK1, a key kinase that phosphorylates IRF3 in the RIG-I pathway, interacted with each other through CC and CC2 domain, respectively. This interaction was enhanced in the presence of the TBK1 adaptor proteins, NAP1 (NF-κB activating kinase-associated protein-1), SINTBAD (similar to NAP1 TBK1 adaptor) or TANK (TRAF family member-associated NF-κB activator). Consistent with its inhibitory role in RIG-I-mediated IFNβ signaling, TRIM11 overexpression enhanced viral infectivity, whereas TRIM11 knockdown produced the opposite effect. Collectively, our results suggest that TRIM11 inhibits RIG-I-mediated IFNβ production by targeting the TBK1 signaling complex. PMID:23675467

  15. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.

    PubMed

    Wang, Limei; Waltenberger, Birgit; Pferschy-Wenzig, Eva-Maria; Blunder, Martina; Liu, Xin; Malainer, Clemens; Blazevic, Tina; Schwaiger, Stefan; Rollinger, Judith M; Heiss, Elke H; Schuster, Daniela; Kopp, Brigitte; Bauer, Rudolf; Stuppner, Hermann; Dirsch, Verena M; Atanasov, Atanas G

    2014-11-01

    Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements.

  16. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review

    PubMed Central

    Wang, Limei; Waltenberger, Birgit; Pferschy-Wenzig, Eva-Maria; Blunder, Martina; Liu, Xin; Malainer, Clemens; Blazevic, Tina; Schwaiger, Stefan; Rollinger, Judith M.; Heiss, Elke H.; Schuster, Daniela; Kopp, Brigitte; Bauer, Rudolf; Stuppner, Hermann; Dirsch, Verena M.; Atanasov, Atanas G.

    2014-01-01

    Agonists of the nuclear receptor PPARγ are therapeutically used to combat hyperglycaemia associated with the metabolic syndrome and type 2 diabetes. In spite of being effective in normalization of blood glucose levels, the currently used PPARγ agonists from the thiazolidinedione type have serious side effects, making the discovery of novel ligands highly relevant. Natural products have proven historically to be a promising pool of structures for drug discovery, and a significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources. The majority of identified compounds are selective PPARγ modulators (SPPARMs), transactivating the expression of PPARγ-dependent reporter genes as partial agonists. Those natural PPARγ ligands have different binding modes to the receptor in comparison to the full thiazolidinedione agonists, and on some occasions activate in addition PPARα (e.g. genistein, biochanin A, sargaquinoic acid, sargahydroquinoic acid, resveratrol, amorphastilbol) or the PPARγ-dimer partner retinoid X receptor (RXR; e.g. the neolignans magnolol and honokiol). A number of in vivo studies suggest that some of the natural product activators of PPARγ (e.g. honokiol, amorfrutin 1, amorfrutin B, amorphastilbol) improve metabolic parameters in diabetic animal models, partly with reduced side effects in comparison to full thiazolidinedione agonists. The bioactivity pattern as well as the dietary use of several of the identified active compounds and plant extracts warrants future research regarding their therapeutic potential and the possibility to modulate PPARγ activation by dietary interventions or food supplements. PMID:25083916

  17. Soil Moisture Active Passive Mission L4_C Data Product Assessment (Version 2 Validated Release)

    NASA Technical Reports Server (NTRS)

    Kimball, John S.; Jones, Lucas A.; Glassy, Joseph; Stavros, E. Natasha; Madani, Nima; Reichle, Rolf H.; Jackson, Thomas; Colliander, Andreas

    2016-01-01

    underlying FT and soil moisture constraints to these processes, 2) documenting primary connections between terrestrial water, energy and carbon cycles, and 3) improving understanding of terrestrial carbon sink activity in northern ecosystems. There are no L1 science requirements for the L4_C product; however self-imposed requirements have been established focusing on NEE as the primary product field for validation, and on demonstrating L4_C accuracy and success in meeting product science requirements (Jackson et al. 2012). The other L4_C product fields also have strong utility for carbon science applications; however, analysis of these other fields is considered secondary relative to primary validation activities focusing on NEE. The L4_C targeted accuracy requirements are to meet or exceed a mean unbiased accuracy (ubRMSE) for NEE of 1.6 g C/sq m/d or 30 g C/sq m/yr, emphasizing northern (45N) boreal and arctic ecosystems; this is similar to the estimated accuracy level of in situ tower eddy covariance measurement-based observations (Baldocchi 2008).

  18. Cerivastatin activates endothelial calcium-activated potassium channels and thereby modulates endothelial nitric oxide production and cell proliferation.

    PubMed

    Kuhlmann, Christoph Rüdiger Wolfram; Gast, Christine; Li, Fang; Schäfer, Matthias; Tillmanns, Harald; Waldecker, Bernd; Wiecha, Johannes

    2004-04-01

    Statins are known to counteract the process of arteriosclerosis by exerting direct pleiotropic effects on vascular endothelium. The aim of this study was to investigate a possible effect of cerivastatin on endothelial Ca(2+)-activated K+ channels (BK(Ca)) and to assess their contribution to cerivastatin-mediated changes of endothelial nitric oxide (NO) production and proliferation. Membrane potential was measured using bis-1,3-dibutylbarbituric acid-trimethine oxonol-fluorescence imaging. Patch-clamp recordings of BK(Ca) were performed on cultured human umbilical vein endothelial cells. NO production was measured using 4,5-diaminofluorescein-fluorescence imaging and a [(3)H]cGMP RIA. Proliferation was analyzed by means of cell counts and [(3)H]thymidine incorporation (TI). Cerivastatin (0.001 to 0.05 micromol/L) caused a significant membrane hyperpolarization (n = 30; P < 0.05). This effect was abolished using the BK(Ca) inhibitor iberiotoxin (IBX; 100 nmol/L). The addition of mevalonate (500 micromol/L) blocked the BK(Ca) activation induced by cerivastatin (n = 19; P < 0.05). Endothelial cGMP level was increased by acetylcholine (ACh; 1 micromol/L). The combination of ACh and cerivastatin additionally increased cGMP levels, with a maximum at 0.03 micromol/L cerivastatin (84%; n = 10, P < 0.01). ACh-induced increase of cGMP-level was significantly reduced by IBX (n = 10, P < 0.01) as it was with all combined administrations of ACh and cerivastatin. 4,5-Diaminofluorescein-fluorescence measurements revealed a significant increase of NO levels by cerivastatin, which was abolished by IBX (n = 30; P < 0.05). Cell counts and TI demonstrated significant inhibition of human umbilical vein endothelial cell proliferation with a maximum at 0.03 micro mol/L (cell count, -32.2%; TI, -70%; n = 12; P < 0.01). These data show that cerivastatin activates endothelial BK(Ca), which plays an important role in the signaling of cerivastatin-mediated endothelial NO production and

  19. Increased per cell IFN-γ productivity indicates recent in vivo activation of T cells

    PubMed Central

    Schlingmann, Tobias R.; Shive, Carey L.; Targoni, Oleg S.; Tary-Lehmann, Magdalena; Lehmann, Paul V.

    2009-01-01

    Immunization with vaccinia virus causes long-term immunity. Efforts have been made to characterize the T cells responsible for this protection. Recently, T cell subsets were described that not only co-express multiple cytokines, but also show increased per cell cytokine productivity. These highly productive cells are often considered to be the most protective. We used ELISPOT assays to measure per cell IFN-γ productivity of vaccinia specific T cells in childhood immunized adults immediately before and at different time points after vaccinia re-vaccination. Apart from an increase in frequency, we found a marked increase of IFN-γ productivity following vaccinia re-vaccination. However, these changes were short-lived as both parameters quickly returned to baseline values within 22 days after re-vaccination. Therefore, increased per cell IFN-γ productivity seems to be a sign of recent in vivo T cell activation rather than a stable marker of a distinct T cell subset responsible for long-term immune protection. PMID:19427634

  20. Comparative in vitro study of the antimicrobial activities of different commercial antibiotic products of vancomycin

    PubMed Central

    2011-01-01

    Background One of the most critical problems about antimicrobial therapy is the increasing resistance to antibiotics. Previous studies have shown that there is a direct relation between erroneous prescription, dosage, route, duration of the therapy and the antibiotics resistance. Other important point is the uncertainty about the quality of the prescribed medicines. Some physicians believe that generic drugs are not as effective as innovator ones, so it is very important to have evidence that shows that all commercialized drugs are suitable for therapeutic use. Methods Microbial assays were used to establish the potency, the Minimal Inhibitory Concentrations (MICs), the Minimal Bactericidal Concentration (MBCs), the critical concentrations, and the production of spontaneous mutants that are resistant to vancomycin. Results The microbial assay was validated in order to determine the Vancomycin potency of the tasted samples. All the products showed that have potency values between 90 - 115% (USP requirement). The products behave similarly because the MICs, The MBCs, the critical concentrations, the critical concentrations ratios between standard and samples, and the production of spontaneous mutants don't have significant differences. Conclusions All products analyzed by microbiological tests, show that both trademarks and generics do not have statistical variability and the answer of antimicrobial activity Show also that they are pharmaceutical equivalents. PMID:21777438

  1. Activation of G proteins mediates flow-induced prostaglandin E2 production in osteoblasts

    NASA Technical Reports Server (NTRS)

    Reich, K. M.; McAllister, T. N.; Gudi, S.; Frangos, J. A.

    1997-01-01

    Interstitial fluid flow may play a role in load-induced bone remodeling. Previously, we have shown that fluid flow stimulates osteoblast production of cAMP inositol trisphosphate (IP3), and PGE2. Flow-induced increases in cAMP and IP3 were shown to be a result of PG production. Thus, PGE2 production appears to be an important component in fluid flow induced signal transduction. In the present study, we investigated the mechanism of flow-induced PGE2 synthesis. Flow-induced a 20-fold increase in PGE2 production in osteoblasts. Increases were also observed with ALF4-(10mM) (98-fold), an activator of guanidine nucleotide-binding proteins (G proteins), and calcium ionophore A23187 (2 microM) (100-fold) in stationary cells. We then investigated whether flow stimulation is mediated by G proteins and increases in intracellular calcium. Flow-induced PGE2 production was inhibited by the G protein inhibitors GDP beta S (100 microM) and pertussis toxin (1 microgram/ml) by 83% and 72%, respectively. Chelation of extracellular calcium by EGTA (2 mM) and intracellular calcium by quin-2/AM (30 microM) blocked flow stimulation by 87% and 67%, respectively. These results suggest that G proteins and calcium play an important role in mediating mechanochemical signal transduction in osteoblasts.

  2. Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production.

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2016-02-01

    Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin. PMID:26543157

  3. Susceptibility of Candida albicans biofilms to caspofungin and anidulafungin is not affected by metabolic activity or biomass production.

    PubMed

    Marcos-Zambrano, Laura Judith; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

    2016-02-01

    Micafungin is more active against biofilms with high metabolic activity; however, it is unknown whether this observation applies to caspofungin and anidulafungin and whether it is also dependent on the biomass production. We compare the antifungal activity of anidulafungin, caspofungin, and micafungin against preformed Candida albicans biofilms with different degrees of metabolic activity and biomass production from 301 isolates causing fungemia in patients admitted to Gregorio Marañon Hospital (January 2007 to September 2014). Biofilms were classified as having low, moderate, or high metabolic activity according XTT reduction assay or having low, moderate, or high biomass according to crystal violet assay. Echinocandin MICs for planktonic and sessile cells were measured using the EUCAST E.Def 7.2 procedure and XTT reduction assay, respectively. Micafungin showed the highest activity against biofilms classified according to the metabolic activity and biomass production (P < .001). The activity of caspofungin and anidulafungin was not dependent on the metabolic activity of the biofilm or the biomass production. These observations were confirmed by scanning electron microscopy. None of the echinocandins produced major changes in the structure of biofilms with low metabolic activity and biomass production when compared with the untreated biofilms. However, biofilm with high metabolic activity or high biomass production was considerably more susceptible to micafungin; this effect was not shown by caspofungin or anidulafungin.

  4. Optimization of culture conditions for production of a novel cold-active lipase from Pichia lynferdii NRRL Y-7723.

    PubMed

    Park, Sun-Young; Kim, Ji-Yeon; Bae, Jae-Han; Hou, Ching T; Kim, Hak-Ryul

    2013-01-30

    Lipases with abnormal properties such as thermostability, alkalinity, acidity, and cold activity receive industrial attention because of their usability under restricted reaction conditions. Most microbial cold-active lipases originate from psychrotrophic and psychrophilic microorganisms found in Antarctic regions, which has led to difficulties in the practical production of cold-active lipase. Recently, a mesophilic yeast, Pichia lynferdii NRRL Y-7723, was reported to produce a novel cold-active lipase. This study focused on optimization of environmental factors, while giving particular attention to the relationships between given factors and incubation time, to maximize the production of a novel cold-active lipase from P. lynferdii NRRL Y-7723. Maximum lipase production was highly dependent on the incubation time at a given environmental factor. Lipase production varied with incubation time at a given temperature, and 20 °C was selected as the optimum temperature for lipase production. Fructose was selected as the best carbon source, and maximum lipase production was obtained when it was present at 0.7% (w/v). Yeast extract was an efficient organic nitrogen source, with maximum lipase production occurring at 0.9% (w/v). Specifically, at the optimum yeast extract level the lipase production was >10 times higher than the productivity under standard conditions. All natural oils tested showed lipase production, but their maximum productivities varied according to incubation time and oil species. PMID:23305314

  5. Potassium humate inhibits complement activation and the production of inflammatory cytokines in vitro

    SciTech Connect

    van Rensburg, C.E.J.; Naude, P.J.

    2009-08-15

    The effects of brown coal derived potassium humate on lymphocyte proliferation, cytokine production and complement activation were investigated in vitro. Potassium humate increased lymphocyte proliferation of phytohaemaglutinin A (PHA) and pokeweed mitogen (PWM) stimulated mononuclear lymphocytes (MNL) in vitro from concentrations of 20 to 80 {mu} g/ml, in a dose dependant manner. On the other hand potassium humate, at 40 {mu} g/ml, significantly inhibited the release of TNF-alpha, IL-1 beta, IL-6 and IL-10 by PHA stimulated MNL. Regarding complement activation it was found that potassium humate inhibits the activation of both the alternative and classical pathways without affecting the stability of the red blood cell membranes. These results indicate that the anti-inflammatory potential of potassium humate could be partially due to the inhibition of pro-inflammatory cytokines responsible for the initiation of these reactions as well as inhibition of complement activation. The increased lymphocyte proliferation observed, might be due to increased IL-2 production as previously been documented.

  6. Fungi Isolated from Maize (Zea mays L.) Grains and Production of Associated Enzyme Activities.

    PubMed

    Abe, Camila Agnes Lumi; Faria, Carla Bertechini; de Castro, Fausto Fernandes; de Souza, Sandra Regina; dos Santos, Fabiane Cristina; da Silva, Cleiltan Novais; Tessmann, Dauri José; Barbosa-Tessmann, Ione Parra

    2015-07-07

    Filamentous fungi produce a great variety of enzymes, and research on their biotechnological potential has recently intensified. The objective of this work was to identify, at the species level, using DNA barcoding, 46 fungal isolates obtained from maize grains with rot symptoms. We also analyzed the production of extracellular amylases, cellulases, proteases and lipases of 33 of those fungal isolates. The enzymatic activities were evaluated by the formation of a clear halo or a white precipitate around the colonies in defined substrate media. The found fungi belong to the genera Talaromyces, Stenocarpella, Penicillium, Phlebiopsis, Cladosporium, Hyphopichia, Epicoccum, Trichoderma, Aspergillus, Irpex, Fusarium, Microdochium, Mucor and Sarocladium. In the genus Fusarium, the species Fusarium verticillioides was predominant and this genus presented the highest diversity, followed by the genera Aspergillus. The best genera for lipase production were Cladosporium and Penicillium; while Cladosporium, Aspergillus and Penicillium were best for cellulase activity; Hyphopichia, Aspergillus and Irpex for amylase activity; and Cladosporium and Sarocladium for proteases activity. In conclusion, a collection of fungi from maize seeds presenting rotten symptoms were obtained, among which exist important producers of hydrolases.

  7. Interleukin 1 stimulates platelet-activating factor production in cultured human endothelial cells.

    PubMed Central

    Bussolino, F; Breviario, F; Tetta, C; Aglietta, M; Mantovani, A; Dejana, E

    1986-01-01

    Monocyte-derived interleukin 1 (IL-1) was found to be a potent inducer of platelet-activating factor (PAF) in cultured human vascular endothelial cells (HEC). The product was identified as PAF by its behavior in chromatographic systems, its recovery of biological activity, and its physico-chemical properties and susceptibility to lipases. The response of HEC to IL-1 was concentration-dependent, took more than 2 h to become apparent, and decreased after 18 h of incubation. Most of the PAF produced was cell-associated and only a small amount (about 25% of the total) was released in the culture medium. To study the mechanism of IL-1-induced HEC-PAF production we tested the activity of 1-O-alkyl-sn-glycero-3-phosphocholine:acetyl/coenzyme A acetyltransferase in HEC. Acetyltransferase activity measured in IL-1-stimulated HEC lysates showed a three to five times greater maximum velocity, but the same Michaelis constant, as untreated cells. The regulation of PAF generation in HEC by IL-1 may be an important aspect of the two-way interaction between immunocompetent cells and vascular tissue. PMID:2872233

  8. Fungi Isolated from Maize (Zea mays L.) Grains and Production of Associated Enzyme Activities

    PubMed Central

    Lumi Abe, Camila Agnes; Bertechini Faria, Carla; Fernandes de Castro, Fausto; de Souza, Sandra Regina; dos Santos, Fabiane Cristina; Novais da Silva, Cleiltan; Tessmann, Dauri José; Barbosa-Tessmann, Ione Parra

    2015-01-01

    Filamentous fungi produce a great variety of enzymes, and research on their biotechnological potential has recently intensified. The objective of this work was to identify, at the species level, using DNA barcoding, 46 fungal isolates obtained from maize grains with rot symptoms. We also analyzed the production of extracellular amylases, cellulases, proteases and lipases of 33 of those fungal isolates. The enzymatic activities were evaluated by the formation of a clear halo or a white precipitate around the colonies in defined substrate media. The found fungi belong to the genera Talaromyces, Stenocarpella, Penicillium, Phlebiopsis, Cladosporium, Hyphopichia, Epicoccum, Trichoderma, Aspergillus, Irpex, Fusarium, Microdochium, Mucor and Sarocladium. In the genus Fusarium, the species Fusarium verticillioides was predominant and this genus presented the highest diversity, followed by the genera Aspergillus. The best genera for lipase production were Cladosporium and Penicillium; while Cladosporium, Aspergillus and Penicillium were best for cellulase activity; Hyphopichia, Aspergillus and Irpex for amylase activity; and Cladosporium and Sarocladium for proteases activity. In conclusion, a collection of fungi from maize seeds presenting rotten symptoms were obtained, among which exist important producers of hydrolases. PMID:26198227

  9. beta. -endorphin augments the cytolytic activity and interferon production of natural killer cells

    SciTech Connect

    Mandler, R.N.; Biddison, W.E.; Mandler, R.; Serrate, S.A.

    1986-02-01

    The in vitro effects of the neurohormone ..beta..-endorphin (b-end) on natural killer (NK) activity and interferon (IFN) production mediated by large granular lymphocytes (LGL) were investigated. LGL-enriched fractions from peripheral blood mononuclear cells (PBMC) from normal human volunteers were obtained by fractionation over discontinuous Percoll gradients. LGL were preincubated with or without various concentrations of b-end or the closely related peptides ..cap alpha..-endorphin (a-end), ..gamma..-endorphin (g-end), or D-ALA/sub 2/-..beta..-endorphin (D-ALA/sub 2/-b-end), a synthetic b-end analogue. NK activity was assayed on /sup 51/Cr-labeled K562 target cells. Preincubation of LGL effectors (but not K562 targets) for 2 to 18 hr with concentrations of b-end between 10/sup -7/ M and 10/sup -10/ M produced significant augmentation of NK cytolytic activity (mean percentage increase: 63%). The classic opiate antagonist naloxone blocked the enhancing effect when used at a 100-fold molar excess relative to b-end. These findings demonstrate that b-end enhances NK activity and IFN production of purified LGL, and suggests that b-end might bind to an opioid receptor on LGL that can be blocked by naloxone. These results lend support to the concepts of regulation of the immune response by neurohormones and the functional relationship between the nervous and immune systems.

  10. Antiadherent and Antibiofilm Activity of Humulus lupulus L. Derived Products: New Pharmacological Properties

    PubMed Central

    Micota, Bartlomiej; Sadowska, Beata; Jedrejek, Dariusz; Wieckowska-Szakiel, Marzena

    2013-01-01

    New antimicrobial properties of products derived from Humulus lupulus L. such as antiadherent and antibiofilm activities were evaluated. The growth of gram-positive but not gram-negative bacteria was inhibited to different extents by these compounds. An extract of hop cones containing 51% xanthohumol was slightly less active against S. aureus strains (MIC range 31.2–125.0 μg/mL) than pure xanthohumol (MIC range 15.6–62.5 μg/mL). The spent hop extract, free of xanthohumol, exhibited lower but still relevant activity (MIC range 1-2 mg/mL). There were positive coactions of hop cone, spent hop extracts, and xanthohumol with oxacillin against MSSA and with linezolid against MSSA and MRSA. Plant compounds in the culture medium at sub-MIC concentrations decreased the adhesion of Staphylococci to abiotic surfaces, which in turn caused inhibition of biofilm formation. The rate of mature biofilm eradication by these products was significant. The spent hop extract at MIC reduced biofilm viability by 42.8%, the hop cone extract by 74.8%, and pure xanthohumol by 86.5%. When the hop cone extract or xanthohumol concentration was increased, almost complete biofilm eradication was achieved (97–99%). This study reveals the potent antibiofilm activity of hop-derived compounds for the first time. PMID:24175280

  11. Secreted Thrombospondin-1 Regulates Macrophage Interleukin-1β Production and Activation through CD47

    PubMed Central

    Stein, Erica V.; Miller, Thomas W.; Ivins-O’Keefe, Kelly; Kaur, Sukhbir; Roberts, David D.

    2016-01-01

    Thrombospondin-1 regulates inflammation by engaging several cell surface receptors and by modulating activities of other secreted factors. We have uncovered a novel role of thrombospondin-1 in modulating production and activation of the proinflammatory cytokine IL-1β by human and murine macrophages. Physiological concentrations of thrombospondin-1 limit the induction by lipopolysaccharide of IL-1β mRNA and total protein production by human macrophages. This inhibition can be explained by the ability of thrombospondin-1 to disrupt the interaction between CD47 and CD14, thereby limiting activation of NFκB/AP-1 by lipopolysaccharide. Only the CD47-binding domain of thrombospondin-1 exhibits this activity. In contrast, CD47, CD36, and integrin-binding domains of thrombospondin-1 independently enhance the inflammasome-dependent maturation of IL-1β in human THP-1 monocyte-derived macrophages. Correspondingly, mouse bone marrow-derived macrophages that lack either thrombospondin-1 or CD47 exhibit diminished induction of mature IL-1β in response to lipopolysaccharide. Lack of CD47 also limits lipopolysaccharide induction of IL-1β, NLRP3, and caspase-1 mRNAs. These data demonstrate that thrombospondin-1 exerts CD47-dependent and -independent pro-and anti-inflammatory effects on the IL-1β pathway. Therefore, thrombospondin-1 and its receptor CD47 may be useful targets for limiting the pro-inflammatory effects of lipopolysaccharide and for treating endotoxemia. PMID:26813769

  12. Antiadherent and antibiofilm activity of Humulus lupulus L. derived products: new pharmacological properties.

    PubMed

    Rozalski, Marcin; Micota, Bartlomiej; Sadowska, Beata; Stochmal, Anna; Jedrejek, Dariusz; Wieckowska-Szakiel, Marzena; Rozalska, Barbara

    2013-01-01

    New antimicrobial properties of products derived from Humulus lupulus L. such as antiadherent and antibiofilm activities were evaluated. The growth of gram-positive but not gram-negative bacteria was inhibited to different extents by these compounds. An extract of hop cones containing 51% xanthohumol was slightly less active against S. aureus strains (MIC range 31.2-125.0  μg/mL) than pure xanthohumol (MIC range 15.6-62.5  μg/mL). The spent hop extract, free of xanthohumol, exhibited lower but still relevant activity (MIC range 1-2 mg/mL). There were positive coactions of hop cone, spent hop extracts, and xanthohumol with oxacillin against MSSA and with linezolid against MSSA and MRSA. Plant compounds in the culture medium at sub-MIC concentrations decreased the adhesion of Staphylococci to abiotic surfaces, which in turn caused inhibition of biofilm formation. The rate of mature biofilm eradication by these products was significant. The spent hop extract at MIC reduced biofilm viability by 42.8%, the hop cone extract by 74.8%, and pure xanthohumol by 86.5%. When the hop cone extract or xanthohumol concentration was increased, almost complete biofilm eradication was achieved (97-99%). This study reveals the potent antibiofilm activity of hop-derived compounds for the first time. PMID:24175280

  13. Staphylococcus simulans Recombinant Lysostaphin: Production, Purification, and Determination of Antistaphylococcal Activity.

    PubMed

    Boksha, I S; Lavrova, N V; Grishin, A V; Demidenko, A V; Lyashchuk, A M; Galushkina, Z M; Ovchinnikov, R S; Umyarov, A M; Avetisian, L R; Chernukha, M Iu; Shaginian, I A; Lunin, V G; Karyagina, A S

    2016-05-01

    Staphylococcus simulans lysostaphin is an endopeptidase lysing staphylococcus cell walls by cleaving pentaglycine cross-bridges in their peptidoglycan. A synthetic gene encoding S. simulans lysostaphin was cloned in Escherichia coli cells, and producer strains were designed. The level of produced biologically active lysostaphin comprised 6-30% of total E. coli cell protein (depending on E. coli M15 or BL21 producer) under batch cultivation conditions. New methods were developed for purification of lysostaphin without affinity domains and for testing its enzymatic activity. As judged by PAGE, the purified recombinant lysostaphin is of >97% purity. The produced lysostaphin lysed cells of Staphylococcus aureus and Staphylococcus haemolyticus clinical isolates. In vitro activity and general biochemical properties of purified recombinant lysostaphin produced by M15 or BL21 E. coli strains were identical to those of recombinant lysostaphin supplied by Sigma-Aldrich (USA) and used as reference in other known studies. The prepared recombinant lysostaphin represents a potential product for development of enzymatic preparation for medicine and veterinary due to the simple purification scheme enabling production of the enzyme of high purity and antistaphylococcal activity. PMID:27297900

  14. Antimycobacterial and nitric oxide production inhibitory activities of Ocotea notata from Brazilian restinga.

    PubMed

    Costa, Isabela Francisca Borges; Calixto, Sanderson Dias; Heggdorne de Araujo, Marlon; Konno, Tatiana Ungaretti Paleo; Tinoco, Luzineide Wanderley; Guimarães, Denise Oliveira; Lasunskaia, Elena B; Leal, Ivana Ramos Correa; Muzitano, Michelle Frazão

    2015-01-01

    The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti-inflammatory activity with inhibition of COX-1, COX-2, and LOX-5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid-liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively.

  15. Antimycobacterial and Nitric Oxide Production Inhibitory Activities of Ocotea notata from Brazilian Restinga

    PubMed Central

    Costa, Isabela Francisca Borges; Calixto, Sanderson Dias; Heggdorne de Araujo, Marlon; Konno, Tatiana Ungaretti Paleo; Tinoco, Luzineide Wanderley; Guimarães, Denise Oliveira; Lasunskaia, Elena B.; Leal, Ivana Ramos Correa; Muzitano, Michelle Frazão

    2015-01-01

    The genus Ocotea (Lauraceae) is distributed mainly in tropical and subtropical regions. Some species of this genus as O. puberula and O. quixos have been described in the literature, showing antibacterial activity. And Ocotea macrophylla showed anti-inflammatory activity with inhibition of COX-1, COX-2, and LOX-5. The purpose of this study was the phytochemical investigation of the plant species Ocotea notata from Restinga Jurubatiba National Park, Macaé, RJ, Brazil, and the search for antimycobacterial fractions and compounds. The crude extract was evaluated for antimycobacterial activity and presented 95.75 ± 2.53% of growth inhibition at 100 µg/mL. Then, it was subjected to a liquid-liquid partition and subsequently was chemically investigated by HPLC, revealing the major presence of flavonoids. In this process the partition fractions hexane, ethyl acetate, and butanol are shown to be promising in the antimycobacterial assay. In addition, ethyl acetate fraction was chromatographed and afforded two flavonoids identified by MS and NMR as afzelin and isoquercitrin. The isolated flavonoids afzelin and isoquercitrin were evaluated for their antimycobacterial activity and for their ability to inhibit NO production by macrophages stimulated by LPS; both flavonoids isoquercitrin (Acet22) and afzelin (Acet32) were able to inhibit the production of NO by macrophages. The calculated IC50 of Acet22 and Acet32 was 1.03 and 0.85 µg/mL, respectively. PMID:25789338

  16. 78 FR 45181 - Foreign-Trade Zone 230-Piedmont Triad Area, North Carolina, Authorization of Production Activity...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-26

    ... inviting public comment (78 FR 23220, 4-18-2013). The FTZ Board has determined that no further review of... Production Activity, Oracle Flexible Packaging, Inc., (Foil-Backed Paperboard), Winston-Salem, North Carolina... proposed production activity to the Foreign-Trade Zones (FTZ) Board on behalf of Oracle Flexible...

  17. 78 FR 33051 - Notification of Proposed Production Activity, The Gas Company, LLC dba Hawai'i Gas, Subzone 9F...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-03

    ... Foreign-Trade Zones Board Notification of Proposed Production Activity, The Gas Company, LLC dba Hawai'i Gas, Subzone 9F (Synthetic Natural Gas), Kapolei, Hawaii The Gas Company, LLC dba Hawai'i Gas (Hawai'i Gas), operator of Subzone 9F, submitted a notification of proposed production activity to the...

  18. 77 FR 39209 - Foreign-Trade Zone 74-Baltimore, MD, Notification of Proposed Production Activity, J.D. Neuhaus...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-02

    ... Activity, J.D. Neuhaus LP (Overhead Lifting Equipment Production) Sparks, MD The Baltimore Development Corporation, grantee of FTZ 74, submitted a notification of proposed production activity on behalf of J.D. Neuhaus LP (J.D. Neuhaus), located in Sparks, Maryland. The notification conforming to the requirements...

  19. Influence of thermal treatment on color, enzyme activities, and antioxidant capacity of innovative pastelike parsley products.

    PubMed

    Kaiser, Andrea; Brinkmann, Maike; Carle, Reinhold; Kammerer, Dietmar R

    2012-03-28

    Conventional spice powders are often characterized by low sensory quality and high microbial loads. Furthermore, genuine enzymes are only inhibited but not entirely inactivated upon drying, so that they may regain their activity upon rehydration of dried foods. To overcome these problems, initial heating was applied in the present study as the first process step for the production of innovative pastelike parsley products. For this purpose, fresh parsley was blanched (80, 90, and 100 °C for 1-10 min) and subsequently comminuted to form a paste. Alternatively, mincing was carried out prior to heat treatment. Regardless of temperature, the color of the latter product did not show any change after heating for 1 min. With progressing exposure time the green color turned to olive hues due to marked pheophytin formation. Inactivation of genuine peroxidase (POD) and polyphenol oxidase (PPO) was achieved at all temperature-time regimes applied. In contrast, the parsley products obtained after immediate water-blanching were characterized by brighter green colors and enhanced pigment retention. With the exception of the variants water-blanched at 80 °C, POD and PPO were completely inactivated at any of the thermal treatments. Furthermore, in water-blanched samples, antioxidant capacities as determined by the TEAC and FRAP assays were even enhanced compared to unheated parsley, whereas a decrease of phenolic contents could not be prevented. Consequently, the innovative process presented in this study allows the production of novel herb and spice products characterized by improved sensory quality as compared to conventional spice products.

  20. Improvement of erythrose reductase activity, deletion of by-products and statistical media optimization for enhanced erythritol production from Yarrowia lipolytica mutant 49.

    PubMed

    Ghezelbash, Gholam Reza; Nahvi, Iraj; Emamzadeh, Rahman

    2014-08-01

    The purpose of the present investigation was to produce erythritol by Yarrowia lipolytica mutant without any by-products. Mutants of Y. lipolytica were generated by ultra-violet for enhancing erythrose reductase (ER) activity and erythritol production. The mutants showing the highest ER activity were screened by triphenyl tetrazolium chloride agar plate assay. Productivity of samples was analyzed by thin-layer chromatography and high-performance liquid chromatography equipped with the refractive index detector. One of the mutants named as mutant 49 gave maximum erythritol production without any other by-products (particularly glycerol). Erythritol production and specific ER activity in mutant 49 increased to 1.65 and 1.47 times, respectively, in comparison with wild-type strain. The ER gene of wild and mutant strains was sequenced and analyzed. A general comparison of wild and mutant gene sequences showed the replacement of Asp(270) with Glu(270) in ER protein. In