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Sample records for scavenger receptor class

  1. The evolution of the class A scavenger receptors

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    Whelan Fiona J

    2012-11-01

    Full Text Available Abstract Background The class A scavenger receptors are a subclass of a diverse family of proteins defined based on their ability to bind modified lipoproteins. The 5 members of this family are strikingly variable in their protein structure and function, raising the question as to whether it is appropriate to group them as a family based on their ligand binding abilities. Results To investigate these relationships, we defined the domain architecture of each of the 5 members followed by collecting and annotating class A scavenger receptor mRNA and amino acid sequences from publicly available databases. Phylogenetic analyses, sequence alignments, and permutation tests revealed a common evolutionary ancestry of these proteins, indicating that they form a protein family. We postulate that 4 distinct gene duplication events and subsequent domain fusions, internal repeats, and deletions are responsible for the diverse protein structures and functions of this family. Despite variation in domain structure, there are highly conserved regions across all 5 members, indicating the possibility that these regions may represent key conserved functional motifs. Conclusions We have shown with significant evidence that the 5 members of the class A scavenger receptors form a protein family. We have indicated that these receptors have a common origin which may provide insight into future functional work with these proteins.

  2. The Evolution of the Scavenger Receptor Cysteine-Rich Domain of the Class A Scavenger Receptors

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    Nicholas eYap

    2015-07-01

    Full Text Available The class A Scavenger Receptor (cA-SR family is a group of five evolutionarily related innate immune receptors. The cA-SRs are known for their promiscuous ligand binding; as they have been shown to bind bacteria such as Streptococcus pneumoniae, and Escherichia coli, as well as different modified forms of low-density lipoprotein. Three of the five family members possess a Scavenger Receptor Cysteine Rich (SRCR domain while the remaining two receptors lack the domain. Previous work has suggested that the Macrophage Associated Receptor with COllagenous structure (MARCO shares a recent common ancestor with the non-SRCR-containing receptors; however the origin of the SRCR domain within the cA-SRs remains unknown. We hypothesize that the SRCR domains of the cA-SRs have a common origin that predates teleost fish. Using the newly available sequence data from sea lamprey and ghost shark genome projects, we have shown that MARCO shares a common ancestor with the SRCR-containing proteins. In addition, we explored the evolutionary relationships within the SRCR domain by reconstructing the ancestral SRCR domains of the cA-SRs. We identified a motif that is highly conserved between the cA-SR SRCR domains and the ancestral SRCR domain that consist of WGTVCDD. We also show that the GRAEVYY motif, a functionally important motif within MARCO, is poorly conserved in the other cA-SRs and in the reconstructed ancestral domain. Further, we identified three sites within MARCO’s SRCR domain which are under positive selection. Two of these sites lie adjacent to the conserved WGTVCDD motif, and may indicate a potential biological function for these sites. Together these findings indicate a common origin of the SRCR domain within the cA-SRs; however different selective pressures between the proteins may have caused MARCOs SRCR domain to evolve to contain different functional motifs when compared to the other SRCR-containing cA-SRs.

  3. Transgenic mouse models to study the role of the macrophage scavenger receptor class A in atherosclerosis

    NARCIS (Netherlands)

    de Winther, M. P.; Gijbels, M. J.; van Dijk, K. W.; Havekes, L. M.; Hofker, M. H.

    2000-01-01

    Several in vivo studies have been performed on the role of the macrophage scavenger receptor class A (SR-A) in atherosclerosis using SR-A knockout mice. The results indicate both an antiatherogenic and a proatherogenic role of SR-A, depending on the nature of the animal model serving as the

  4. Scavenger receptor classes A and B. Their roles in atherogenesis and the metabolism of modified LDL and HDL

    NARCIS (Netherlands)

    van Berkel, T. J.; van Eck, M.; Herijgers, N.; Fluiter, K.; Nion, S.

    2000-01-01

    Scavenger-receptor class A has been held responsible for the clearance of modified LDL from the blood circulation. However, in mice deficient in scavenger-receptor class A, the decay in vivo of acetylated LDL (t1/2 <2 min), as well as tissue distribution and liver uptake (at 5 min 77.4 +/- 4.6% of

  5. Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1

    NARCIS (Netherlands)

    Ljunggren, Stefan A.; Levels, Johannes H. M.; Hovingh, Kees; Holleboom, Adriaan G.; Vergeer, Menno; Argyri, Letta; Gkolfinopoulou, Christina; Chroni, Angeliki; Sierts, Jeroen A.; Kastelein, John J.; Kuivenhoven, Jan Albert; Lindahl, Mats; Karlsson, Helen

    2015-01-01

    The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1(P297S) mutation are characterized by increased HDL cholesterol

  6. Suppression of TLR4-mediated inflammatory response by macrophage class A scavenger receptor (CD204)

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    Ohnishi, Koji; Komohara, Yoshihiro; Fujiwara, Yukio; Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Lei, XiaoFeng [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Biochemistry, Showa University School of Medicine, Tokyo (Japan); Nakagawa, Takenobu [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan); Department of Human Pathology, Institute of Health Biosciences, The University of Tokushima, Tokushima (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Faculty of Life Sciences, Kumamoto University, Kumamoto (Japan)

    2011-08-05

    Highlights: {yields} We focused on the interaction between SR-A and TLR4 signaling in this study. {yields} SR-A deletion promoted NF{kappa}B activation in macrophages in septic model mouse. {yields} SR-A suppresses both MyD88-dependent and -independent TLR4 signaling in vitro. {yields} SR-A clears LPS binding to TLR4 which resulting in the suppression of TLR4 signals. -- Abstract: The class A scavenger receptor (SR-A, CD204), one of the principal receptors expressed on macrophages, has been found to regulate inflammatory response and attenuate septic endotoxemia. However, the detailed mechanism of this process has not yet been well characterized. To clarify the regulative mechanisms of lipopolysaccharide (LPS)-induced macrophage activation by SR-A, we evaluated the activation of Toll-like receptor 4 (TLR4)-mediated signaling molecules in SR-A-deficient (SR-A{sup -/-}) macrophages. In a septic shock model, the blood levels of tumor necrosis factor (TNF)-{alpha}, interleukin (IL)-6 and interferon (IFN)-{beta} were significantly increased in SR-A{sup -/-} mice compared to wild-type mice, and elevated nuclear factor kappa B (NF{kappa}B) activation was detected in SR-A{sup -/-} macrophages. SR-A deletion increased the production of pro-inflammatory cytokines, and the phosphorylation of mitogen-activated protein kinase (MAPK) and NF{kappa}B in vitro. SR-A deletion also promoted the nuclear translocation of NF{kappa}B and IFN regulatory factor (IRF)-3. In addition, a competitive binding assay with acetylated low-density lipoprotein, an SR-A-specific ligand, and anti-SR-A antibody induced significant activation of TLR4-mediated signaling molecules in wild-type macrophages but not in SR-A{sup -/-} macrophages. These results suggest that SR-A suppresses the macrophage activation by inhibiting the binding of LPS to TLR4 in a competitive manner and it plays a pivotal role in the regulation of the LPS-induced inflammatory response.

  7. Class A scavenger receptor promotes osteoclast differentiation via the enhanced expression of receptor activator of NF-{kappa}B (RANK)

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    Takemura, Kenichi [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Sakashita, Naomi; Fujiwara, Yukio; Komohara, Yoshihiro; Lei, XiaoFeng; Ohnishi, Koji [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan); Suzuki, Hiroshi [National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido (Japan); Kodama, Tatsuhiko [Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Mizuta, Hiroshi [Department of Orthopaedic and Neuro-Musculoskeletal Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto (Japan); Takeya, Motohiro, E-mail: takeya@kumamoto-u.ac.jp [Department of Cell Pathology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556 (Japan)

    2010-01-22

    Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, and their differentiation depends on macrophage colony-stimulating factor (M-CSF) and receptor activator nuclear factor kappa B (RANK) ligand. Class A scavenger receptor (SR-A) is one of the principal functional molecules of macrophages, and its level of expression declines during osteoclast differentiation. To investigate the role of SR-A in osteoclastogenesis, we examined pathological changes in femoral bone and the expression levels of osteoclastogenesis-related molecules in SR-A{sup -/-} mice. The femoral osseous density of SR-A{sup -/-} mice was higher than that of SR-A{sup +/+} mice, and the number of multinucleated osteoclasts was significantly decreased. An in vitro differentiation assay revealed that the differentiation of multinucleated osteoclasts from bone marrow-derived progenitor cells is impaired in SR-A{sup -/-} mice. Elimination of SR-A did not alter the expression level of the M-CSF receptor, c-fms; however, the expression levels of RANK and RANK-related osteoclast-differentiation molecules such as nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) and microphthalmia-associated transcription factor (MITF) significantly decreased. Furthermore, acetylated low-density lipoprotein (AcLDL), an SR-A ligand, significantly increased the expression level of RANK and MITF during osteoclast differentiation. These data indicate that SR-A promotes osteoclastogenesis via augmentation of the expression level of RANK and its related molecules.

  8. The dual role of scavenger receptor class A in development of diabetes in autoimmune NOD mice.

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    Mami Shimizu

    Full Text Available Human type 1 diabetes is an autoimmune disease that results from the autoreactive destruction of pancreatic β cells by T cells. Antigen presenting cells including dendritic cells and macrophages are required to activate and suppress antigen-specific T cells. It has been suggested that antigen uptake from live cells by dendritic cells via scavenger receptor class A (SR-A may be important. However, the role of SR-A in autoimmune disease is unknown. In this study, SR-A-/- nonobese diabetic (NOD mice showed significant attenuation of insulitis, lower levels of insulin autoantibodies, and suppression of diabetes development compared with NOD mice. We also found that diabetes progression in SR-A-/- NOD mice treated with low-dose polyinosinic-polycytidylic acid (poly(I:C was significantly accelerated compared with that in disease-resistant NOD mice treated with low-dose poly(I:C. In addition, injection of high-dose poly(I: C to mimic an acute RNA virus infection significantly accelerated diabetes development in young SR-A-/- NOD mice compared with untreated SR-A-/- NOD mice. Pathogenic cells including CD4+CD25+ activated T cells were increased more in SR-A-/- NOD mice treated with poly(I:C than in untreated SR-A-/- NOD mice. These results suggested that viral infection might accelerate diabetes development even in diabetes-resistant subjects. In conclusion, our studies demonstrated that diabetes progression was suppressed in SR-A-/- NOD mice and that acceleration of diabetes development could be induced in young mice by poly(I:C treatment even in SR-A-/- NOD mice. These results suggest that SR-A on antigen presenting cells such as dendritic cells may play an unfavorable role in the steady state and a protective role in a mild infection. Our findings imply that SR-A may be an important target for improving therapeutic strategies for type 1 diabetes.

  9. Scavenger Receptor Class B Type I Mediates Biliary Cholesterol Secretion Independent of ATP-Binding Cassette Transporter g5/g8 in Mice

    NARCIS (Netherlands)

    Wiersma, Harmen; Gatti, Alberto; Nijstad, Niels; Elferink, Ronald P. J. Oude; Kuipers, Folkert; Tietge, Uwe J. F.

    2009-01-01

    Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not dear, if this effect is direct or indirect. The aim of this study was to determine the impact

  10. Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on cholesterol levels and atherosclerosis in ApoE-deficient mice

    NARCIS (Netherlands)

    van Eck, M.; de Winther, M. P.; Herijgers, N.; Havekes, L. M.; Hofker, M. H.; Groot, P. H.; van Berkel, T. J.

    2000-01-01

    In the arterial wall, scavenger receptor class A (SRA) is implicated in pathological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified lipoproteins from the circulation, thereby protecting the body from their pathological action. The role of SRA on bone marrow-derived

  11. Effect of human scavenger receptor class A overexpression in bone marrow-derived cells on cholesterol levels and atherosclerosis in apoE-deficient mice

    NARCIS (Netherlands)

    Eck, M. van; Winther, M.P.J. de; Herijgers, N.; Havekes, L.M.; Hofker, M.H.; Groot, P.H.E.; Berkel, T.J.C. van

    2000-01-01

    In the arterial wall, scavenger receptor class A (SRA) is implicated in pathological lipid deposition. In contrast, in the liver, SRA is suggested to remove modified lipoproteins from the circulation, thereby protecting the body from their pathological action. The role of SRA on bone marrow-derived

  12. Scavenger receptor class B member 1 protein: hepatic regulation and its effects on lipids, reverse cholesterol transport, and atherosclerosis

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    Kent AP

    2011-04-01

    Full Text Available Anthony P Kent, Ioannis M StylianouDepartment of Medicine and Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA, USAAbstract: Scavenger receptor class B member 1 (SR-BI, also known as SCARB1 is the primary receptor for the selective uptake of cholesterol from high-density lipoprotein (HDL. SR-BI is present in several key tissues; however, its presence and function in the liver is deemed the most relevant for protection against atherosclerosis. Cholesterol is transferred from HDL via SR-BI to the liver, which ultimately results in the excretion of cholesterol via bile and feces in what is known as the reverse cholesterol transport pathway. Much of our knowledge of SR-BI hepatic function and regulation is derived from mouse models and in vitro characterization. Multiple independent regulatory mechanisms of SR-BI have been discovered that operate at the transcriptional and post-transcriptional levels. In this review we summarize the critical discoveries relating to hepatic SR-BI cholesterol metabolism, atherosclerosis, and regulation of SR-BI, as well as alternative functions that may indirectly affect atherosclerosis.Keywords: SR-BI, SCARB1, lipids, atherosclerosis, CAD, mouse models

  13. Structures of class A macrophage scavenger receptors. Electron microscopic study of flexible, multidomain, fibrous proteins and determination of the disulfide bond pattern of the scavenger receptor cysteine-rich domain.

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    Resnick, D; Chatterton, J E; Schwartz, K; Slayter, H; Krieger, M

    1996-10-25

    Structures of secreted forms of the human type I and II class A macrophage scavenger receptors were studied using biochemical and biophysical methods. Proteolytic analysis was used to determine the intramolecular disulfide bonds in the type I-specific scavenger receptor cysteine-rich (SRCR) domain: Cys2-Cys7, Cys3-Cys8, and Cys5-Cys6. This pattern is likely to be shared by the highly homologous domains in the many other members of the SRCR domain superfamily. Electron microscopy using rotary shadowing and negative staining showed that the type I and II receptors are extended molecules whose contour lengths are approximately 440 A. They comprised two adjacent fibrous segments, an alpha-helical coiled-coil ( approximately 230 A, including a contribution from the N-terminal spacer domain) and a collagenous triple helix ( approximately 210 A). The type I molecules also contained a C-terminal globular structure ( approximately 58 x 76 A) composed of three SRCR domains. The fibrous domains were joined by an extremely flexible hinge. The angle between these domains varied from 0 to 180 degrees and depended on the conditions of sample preparation. Unexpectedly, at physiologic pH, the prevalent angle seen using rotary shadowing was 0 degrees , resulting in a structure that is significantly more compact than previously suggested. The apparent juxtaposition of the fibrous domains at neutral pH provides a framework for future structure-function studies of these unusual multiligand receptors.

  14. Major Vault Protein Regulates Class A Scavenger Receptor-mediated Tumor Necrosis Factor-α Synthesis and Apoptosis in Macrophages*

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    Ben, Jingjing; Zhang, Yan; Zhou, Rongmei; Zhang, Haiyang; Zhu, Xudong; Li, Xiaoyu; Zhang, Hanwen; Li, Nan; Zhou, Xiaodan; Bai, Hui; Yang, Qing; Li, Donghai; Xu, Yong; Chen, Qi

    2013-01-01

    Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis. PMID:23703615

  15. Vertebrate scavenger receptor class B member 2 (SCARB2: comparative studies of a major lysosomal membrane glycoprotein

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    Roger Stephen Holmes

    2012-06-01

    Full Text Available Scavenger receptor class B member 2 (SCARB2 (also LIMP-2, CD36L2 or LGP85 is a major lysosomal membrane glycoprotein involved in endosomal and lysosomal biogenesis and maintenance. SCARB2 acts as a receptor for the lysosomal mannose-6-phosphate independent targeting of β-glucuronidase and enterovirus 71 and influences Parkinson’s disease and epilepsy. Genetic deficiency of this protein causes deafness and peripheral neuropathy in mice as well as myoclonic epilepsy and nephrotic syndrome in humans. Comparative SCARB2 amino acid sequences and structures and SCARB2 gene locations were examined using data from several vertebrate genome projects. Vertebrate SCARB2 sequences shared 43-100% identity as compared with 30-36% sequence identities with other CD36-like superfamily members, SCARB1 and CD36. At least 10 N-glycosylation sites were conserved among most vertebrate SCARB2 proteins examined. Sequence alignments, key amino acid residues and conserved predicted secondary structures were examined, including cytoplasmic, transmembrane and external lysosomal membrane sequences: cysteine disulfide residues, thrombospondin (THP1 binding sites and 16 proline and 20 glycine conserved residues, which may contribute to short loop formation within the exomembrane SCARB2 sequences. Vertebrate SCARB2 genes contained 12 coding exons. The human SCARB2 gene contained a CpG island (CpG100, ten microRNA-binding sites and several transcription factor binding sites (including PPARA which may contribute to a higher level (2.4 times average of gene expression. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate SCARB2 gene with vertebrate SCARB1 and CD36 genes. These suggested that SCARB2 originated from duplications of the CD36 gene in an ancestral genome forming three vertebrate CD36 gene family members: SCARB1, SCARB2 and CD36.

  16. Comparative studies of vertebrate scavenger receptor class B type 1: a high-density lipoprotein binding protein

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    Holmes RS

    2012-06-01

    Full Text Available Roger S Holmes,1,2 Laura A Cox11Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA; 2School of Biomolecular and Physical Sciences, Griffith University, Nathan, Queensland, AustraliaAbstract: Scavenger receptor class B type 1 protein (SCARB1 plays an essential role in cholesterol homeostasis and functions in binding high density lipoprotein cholesterol (HDL in liver and other tissues of the body. SCARB1 also functions in lymphocyte homeostasis and in the uptake of hepatitis C virus (HCV by the liver. A genetic deficiency of this protein results in autoimmune disorders and significant changes in blood cholesterol phenotype. Comparative SCARB1 amino acid sequences and structures and SCARB1 gene locations were examined using data from several vertebrate genome projects. Vertebrate SCARB1 sequences shared 50%–99% identity as compared with 28%–31% sequence identities with other CD36-like superfamily members, ie, SCARB2 and SCARB3 (also called CD36. At least eight N-glycosylation sites were conserved among most of the vertebrate SCARB1 proteins examined. Sequence alignments, key amino acid residues, and conserved predicted secondary structures were also studied, including: cytoplasmic, transmembrane, and exoplasmic sequences; conserved N-terminal and C-terminal transmembrane glycines which participate in oligomer formation; conserved cystine disulfides and a free SH residue which participates in lipid transport; carboxyl terminal PDZ-binding domain sequences (Ala507-Arg/Lys508-Leu509; and 30 conserved proline and 18 conserved glycine residues, which may contribute to short loop formation within the exoplasmic HDL-binding sequence. Vertebrate SCARB1 genes usually contained 12 coding exons. The human SCARB1 gene contained CpG islands, micro RNA binding sites, and several transcription factor binding sites (including PPARG which may contribute to the high level (13.7 times

  17. Investigation of genetic variation in scavenger receptor class B, member 1 (SCARB1) and association with serum carotenoids

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    McKay, Gareth J; Loane, Edward; Nolan, John M; Patterson, Christopher C; Meyers, Kristin J; Mares, Julie A; Yonova-Doing, Ekaterina; Hammond, Christopher J; Beatty, Stephen; Silvestri, Giuliana

    2013-01-01

    Objective To investigate association of scavenger receptor class B, member 1 (SCARB1) genetic variants with serum carotenoid levels of lutein (L) and zeaxanthin (Z) and macular pigment optical density (MPOD). Design A cross-sectional study of healthy adults aged 20-70. Participants 302 participants recruited following local advertisement. Methods MPOD was measured by customized heterochromatic flicker photometry. Fasting blood samples were taken for serum L and Z measurement by HPLC and lipoprotein analysis by spectrophotometric assay. Forty-seven single nucleotide polymorphisms (SNPs) across SCARB1 were genotyped using Sequenom technology. Association analyses were performed using PLINK to compare allele and haplotype means, with adjustment for potential confounding and correction for multiple comparisons by permutation testing. Replication analysis was performed in the TwinsUK and CAREDS cohorts. Main outcome measures Odds ratios (ORs) for macular pigment optical density area, serum lutein and zeaxanthin concentrations associated with genetic variations in SCARB1 and interactions between SCARB1 and sex. Results Following multiple regression analysis with adjustment for age, body mass index, sex, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc), triglycerides, smoking, dietary L and Z levels, 5 SNPs were significantly associated with serum L concentration and 1 SNP with MPOD (P<0.01). Only the association between rs11057841 and serum L withstood correction for multiple comparisons by permutation testing (P<0.01) and replicated in the TwinsUK cohort (P=0.014). Independent replication was also observed in the CAREDS cohort with rs10846744 (P=2×10−4), a SNP in high linkage disequilibrium with rs11057841 (r2=0.93). No significant interactions by sex were found. Haplotype analysis revealed no stronger association than obtained with single SNP analyses. Conclusions Our study has identified association between rs11057841 and

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

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    Zhili Ding

    2016-01-01

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

  19. Hemoglobin and heme scavenger receptors

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Møller, Holger Jon; Moestrup, Søren Kragh

    2010-01-01

    Heme, the functional group of hemoglobin, myoglobin, and other hemoproteins, is a highly toxic substance when it appears in the extracellular milieu. To circumvent potential harmful effects of heme from hemoproteins released during physiological or pathological cell damage (such as hemolysis...... and rhabdomyolysis), specific high capacity scavenging systems have evolved in the mammalian organism. Two major systems, which essentially function in a similar way by means of a circulating latent plasma carrier protein that upon ligand binding is recognized by a receptor, are represented by a) the hemoglobin...

  20. Scavenger receptor class B type I (SR-BI) in pig enterocytes: trafficking from the brush border to lipid droplets during fat absorption

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, Lise-Lotte W; Immerdal, Lissi

    2003-01-01

    BACKGROUND: Scavenger receptor class B type I (SR-BI) is known to mediate cellular uptake of cholesterol from high density lipoprotein particles and is particularly abundant in liver and steroidogenic tissues. In addition, SR-BI expression in the enterocyte brush border has also been reported...... but its role in the small intestine remains unclear. AIM AND METHODS: To gain insight into the possible function of pig SR-BI during uptake of dietary fat, its localisation in enterocytes was studied in the fasting state and during fat absorption by immunogold electron microscopy and subcellular...... fat, SR-BI is endocytosed from the enterocyte brush border and accumulates in cytoplasmic lipid droplets. Internalisation of the receptor occurs mainly by clathrin coated pits rather than by a caveolae/lipid raft based mechanism....

  1. Scavenger receptors in homeostasis and immunity.

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    Canton, Johnathan; Neculai, Dante; Grinstein, Sergio

    2013-09-01

    Scavenger receptors were originally identified by their ability to recognize and to remove modified lipoproteins; however, it is now appreciated that they carry out a striking range of functions, including pathogen clearance, lipid transport, the transport of cargo within the cell and even functioning as taste receptors. The large repertoire of ligands recognized by scavenger receptors and their broad range of functions are not only due to the wide range of receptors that constitute this family but also to their ability to partner with various co-receptors. The ability of individual scavenger receptors to associate with different co-receptors makes their responsiveness extremely versatile. This Review highlights recent insights into the structural features that determine the function of scavenger receptors and the emerging role that these receptors have in immune responses, notably in macrophage polarization and in the pathogenesis of diseases such as atherosclerosis and Alzheimer's disease.

  2. Lower Squalene Epoxidase and Higher Scavenger Receptor Class B Type 1 Protein Levels Are Involved in Reduced Serum Cholesterol Levels in Stroke-Prone Spontaneously Hypertensive Rats.

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    Michihara, Akihiro; Mido, Mayuko; Matsuoka, Hiroshi; Mizutani, Yurika

    2015-01-01

    A lower serum cholesterol level was recently shown to be one of the causes of stroke in an epidemiological study. Spontaneously hypertensive rats stroke-prone (SHRSP) have lower serum cholesterol levels than normotensive Wistar-Kyoto rats (WKY). To elucidate the mechanisms responsible for the lower serum cholesterol levels in SHRSP, we determined whether the amounts of cholesterol biosynthetic enzymes or the receptor and transporter involved in cholesterol uptake and efflux in the liver were altered in SHRSP. When the mRNA levels of seven cholesterol biosynthetic enzymes were measured using real-time polymerase chain reaction (PCR), farnesyl pyrophosphate synthase and squalene epoxidase (SQE) levels in the liver of SHRSP were significantly lower than those in WKY. SQE protein levels were significantly reduced in tissues other than the brain of SHRSP. No significant differences were observed in low-density lipoprotein (LDL) receptor (uptake of serum LDL-cholesterol) or ATP-binding cassette transporter A1 (efflux of cholesterol from the liver/formation of high-density lipoprotein (HDL)) protein levels in the liver and testis between SHRSP and WKY, whereas scavenger receptor class B type 1 (SRB1: uptake of serum HDL-cholesterol) protein levels were higher in the livers of SHRSP. These results indicated that the lower protein levels of SQE and higher protein levels of SRB1 in the liver were involved in the reduced serum cholesterol levels in SHRSP.

  3. TmSR-C, scavenger receptor class C, plays a pivotal role in antifungal and antibacterial immunity in the coleopteran insect Tenebrio molitor.

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    Kim, Soo Gon; Jo, Yong Hun; Seong, Jeong Hwan; Park, Ki Beom; Noh, Mi Young; Cho, Jun Ho; Ko, Hye Jin; Kim, Chang Eun; Tindwa, Hamisi; Patnaik, Bharat Bhusan; Bang, In Seok; Lee, Yong Seok; Han, Yeon Soo

    2017-10-01

    Scavenger receptors (SRs) constitute a family of membrane-bound receptors that bind to multiple ligands. The SR family of proteins is involved in removing cellular debris, oxidized low-density lipoproteins, and pathogens. Specifically, class C scavenger receptors (SR-C) have also been reported to be involved in phagocytosis of gram-positive and -negative bacteria in Drosophila and viruses in shrimp. However, reports are unavailable regarding the role of SR-C in antifungal immune mechanisms in insects. In this study, a full-length Tenebrio molitor SR-C (TmSR-C) sequence was obtained by 5'- and 3'-Rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The TmSR-C full-length cDNA comprised 1671 bp with 5'- and 3'-untranslated regions of 23- and 107-bp, respectively. TmSR-C encodes a putative protein of 556 amino acid residues that is constitutively expressed in all tissues of late instar larvae and 2-day-old adults, with the highest transcript levels observed in hemocytes of larvae and adults. TmSR-C mRNA showed a 2.5-fold and 3-fold increase at 24 and 6 h after infection with Candida albicans and β-glucan, respectively. Immunoassay with TmSR-C polyclonal antibody showed induction of the putative protein in the cytosols of hemocytes at 3 h after inoculation of C. albicans. RNA interference (RNAi)-based gene silencing and phagocytosis assays were used to understand the role of TmSR-C in antifungal immunity. Silencing of TmSR-C transcripts reduced the survivability of late instar larvae at 2 days post-inoculation of C. albicans, Escherichia coli, or Staphylococcus aureus. Furthermore, in TmSR-C-silenced larvae, there was a decline in the rate of microorganism phagocytosis. Taken together, results of this study suggest that TmSR-C plays a pivotal role in phagocytosing not only fungi but also gram-negative and -positive bacteria in T. molitor. Copyright © 2017. Published by Elsevier Ltd.

  4. Cholesterol trafficking and raft-like membrane domain composition mediate scavenger receptor class B type 1-dependent lipid sensing in intestinal epithelial cells.

    Science.gov (United States)

    Morel, Etienne; Ghezzal, Sara; Lucchi, Géraldine; Truntzer, Caroline; Pais de Barros, Jean-Paul; Simon-Plas, Françoise; Demignot, Sylvie; Mineo, Chieko; Shaul, Philip W; Leturque, Armelle; Rousset, Monique; Carrière, Véronique

    2018-02-01

    Scavenger receptor Class B type 1 (SR-B1) is a lipid transporter and sensor. In intestinal epithelial cells, SR-B1-dependent lipid sensing is associated with SR-B1 recruitment in raft-like/ detergent-resistant membrane domains and interaction of its C-terminal transmembrane domain with plasma membrane cholesterol. To clarify the initiating events occurring during lipid sensing by SR-B1, we analyzed cholesterol trafficking and raft-like domain composition in intestinal epithelial cells expressing wild-type SR-B1 or the mutated form SR-B1-Q445A, defective in membrane cholesterol binding and signal initiation. These features of SR-B1 were found to influence both apical cholesterol efflux and intracellular cholesterol trafficking from plasma membrane to lipid droplets, and the lipid composition of raft-like domains. Lipidomic analysis revealed likely participation of d18:0/16:0 sphingomyelin and 16:0/0:0 lysophosphatidylethanolamine in lipid sensing by SR-B1. Proteomic analysis identified proteins, whose abundance changed in raft-like domains during lipid sensing, and these included molecules linked to lipid raft dynamics and signal transduction. These findings provide new insights into the role of SR-B1 in cellular cholesterol homeostasis and suggest molecular links between SR-B1-dependent lipid sensing and cell cholesterol and lipid droplet dynamics. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Scavenger Receptor BI Plays a Role in Facilitating Chylomicron Metabolism

    NARCIS (Netherlands)

    Out, R.; Kruijt, J.K.; Rensen, P.C.N.; Hildebrand, R.B.; Vos, P. de; Eck, M. van; Berkel, T.J.C. van

    2004-01-01

    The function of scavenger receptor class B type I (SR-BI) in mediating the selective uptake of high density lipoprotein (HDL) cholesterol esters is well established. However, the potential role of SR-BI in chylomicron and chylomicron remnant metabolism is largely unknown. In the present

  6. Genetic Variant of the Scavenger Receptor BI in Humans

    NARCIS (Netherlands)

    Vergeer, Menno; Korporaal, Suzanne J. A.; Franssen, Remco; Meurs, Illiana; Out, Ruud; Hovingh, G. Kees; Hoekstra, Menno; Sierts, Jeroen A.; Dallinga-Thie, Geesje M.; Motazacker, Mohammad Mahdi; Holleboom, Adriaan G.; van Berkel, Theo J. C.; Kastelein, John J. P.; van Eck, Miranda; Kuivenhoven, Jan Albert

    2011-01-01

    BACKGROUND In mice, the scavenger receptor class B type I (SR-BI) is essential for the delivery of high-density lipoprotein (HDL) cholesterol to the liver and steroidogenic organs. Paradoxically, elevated HDL cholesterol levels are associated with increased atherosclerosis in SR-BI-knockout mice. It

  7. Genetic variant of the scavenger receptor BI in humans

    NARCIS (Netherlands)

    Vergeer, Menno; Korporaal, Suzanne J A; Franssen, Remco; Meurs, Illiana; Out, Ruud; Hovingh, G Kees; Hoekstra, Menno; Sierts, Jeroen A; Dallinga-Thie, Geesje M; Motazacker, Mohammad Mahdi; Holleboom, Adriaan G; Van Berkel, Theo J C; Kastelein, John J P; Van Eck, Miranda; Kuivenhoven, Jan Albert

    2011-01-01

    BACKGROUND: In mice, the scavenger receptor class B type I (SR-BI) is essential for the delivery of high-density lipoprotein (HDL) cholesterol to the liver and steroidogenic organs. Paradoxically, elevated HDL cholesterol levels are associated with increased atherosclerosis in SR-BI-knockout mice.

  8. The role of the class A scavenger receptors, SR-A and MARCO, in the immune system. Part 1. The structure of receptors, their ligand binding repertoires and ability to initiate intracellular signaling

    Directory of Open Access Journals (Sweden)

    Szczepan Józefowski

    2012-02-01

    Full Text Available  Recognition of pathogens by innate immune cells is mediated by pattern recognition receptors (PRR, which include scavenger receptors (SR. The class A SR, SR-A/CD204 and MARCO, are characterized by the presence of collagenous and SR cysteine-rich domains in their extracellular portions. Both receptors are expressed mainly on macrophages and dendritic cells. Thanks to their ability to bind to a wide range of polyanionic ligands, the class A SR may participate in numerous functions of these cells, such as endocytosis, and adhesion to extracellular matrix and to other cells. Among SR-A ligands are oxidized lipoproteins and β-amyloid fibrils, which link SR-A to the pathogenesis of arteriosclerosis and Alzheimer’s disease. Despite the demonstration of class A SR involvement in so many processes, the lack of selective ligands precluded reaching definite conclusions concerning their signaling abilities. Using specific receptor ligation with antibodies, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. Surprisingly, despite similarities in structure and ligand binding repertoires, SR-A and MARCO exert opposite effects on interleukin-12 (IL-12 production in macrophages. SR-A ligation also stimulated H2O2 and IL-10 production, but had no effect on the release of several other cytokines. These limited effects of specific SR-A ligation contrast with generalized enhancement of immune responses observed in SR-A-deficient mice. Recent studies have revealed that many of these effects of SR-A deficiency may be caused by compensatory changes in the expression of other receptors and/or disinhibition of signal transduction from receptors belonging to the Toll/IL-1R family, rather than by the loss of the receptor function of SR-A.

  9. Surfactant protein A (SP-A)-mediated clearance of Staphylococcus aureus involves binding of SP-A to the staphylococcal adhesin eap and the macrophage receptors SP-A receptor 210 and scavenger receptor class A.

    Science.gov (United States)

    Sever-Chroneos, Zvjezdana; Krupa, Agnieszka; Davis, Jeremy; Hasan, Misbah; Yang, Ching-Hui; Szeliga, Jacek; Herrmann, Mathias; Hussain, Muzafar; Geisbrecht, Brian V; Kobzik, Lester; Chroneos, Zissis C

    2011-02-11

    Staphylococcus aureus causes life-threatening pneumonia in hospitals and deadly superinfection during viral influenza. The current study investigated the role of surfactant protein A (SP-A) in opsonization and clearance of S. aureus. Previous studies showed that SP-A mediates phagocytosis via the SP-A receptor 210 (SP-R210). Here, we show that SP-R210 mediates binding and control of SP-A-opsonized S. aureus by macrophages. We determined that SP-A binds S. aureus through the extracellular adhesin Eap. Consequently, SP-A enhanced macrophage uptake of Eap-expressing (Eap(+)) but not Eap-deficient (Eap(-)) S. aureus. In a reciprocal fashion, SP-A failed to enhance uptake of Eap(+) S. aureus in peritoneal Raw264.7 macrophages with a dominant negative mutation (SP-R210(DN)) blocking surface expression of SP-R210. Accordingly, WT mice cleared infection with Eap(+) but succumbed to sublethal infection with Eap- S. aureus. However, SP-R210(DN) cells compensated by increasing non-opsonic phagocytosis of Eap(+) S. aureus via the scavenger receptor scavenger receptor class A (SR-A), while non-opsonic uptake of Eap(-) S. aureus was impaired. Macrophages express two isoforms: SP-R210(L) and SP-R210(S). The results show that WT alveolar macrophages are distinguished by expression of SP-R210(L), whereas SR-A(-/-) alveolar macrophages are deficient in SP-R210(L) expressing only SP-R210(S). Accordingly, SR-A(-/-) mice were highly susceptible to both Eap(+) and Eap(-) S. aureus. The lungs of susceptible mice generated abnormal inflammatory responses that were associated with impaired killing and persistence of S. aureus infection in the lung. In conclusion, alveolar macrophage SP-R210(L) mediates recognition and killing of SP-A-opsonized S. aureus in vivo, coordinating inflammatory responses and resolution of S. aureus pneumonia through interaction with SR-A.

  10. Increased DNA methylation of scavenger receptor class B type I contributes to inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and steroidogenesis in fetal adrenals

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Dong-Mei; He, Zheng; Ma, Liang-Peng; Wang, Lin-Long [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Ping, Jie, E-mail: pingjie@whu.edu.cn [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wang, Hui [Department of Pharmacology, Wuhan University School of Basic Medical Sciences, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Diseases, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

    2015-06-01

    Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial for fetal development. We have observed the inhibited fetal adrenal corticosterone synthesis and increased intrauterine growth retardation (IUGR) rate in rats under prenatal caffeine ingestion. The aim of this study is to evaluate the effects of prenatal caffeine ingestion on cholesterol supply in fetal adrenal steroidogenesis in rats and explore the underlying epigenetic mechanisms. Pregnant Wistar rats were treated with 60 mg/kg·d caffeine from gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and increased IUGR rates were observed in the caffeine group. There were significantly decreased steroid hormone contents and cholesterol supply in caffeine-treated fetal adrenals. Data from the gene expression array suggested that prenatal caffeine ingestion caused increased expression of genes related to DNA methylation and decreased expression of genes related to cholesterol uptake. The following conjoint analysis of DNA methylation array with these differentially expressed genes suggested that scavenger receptor class B type I (SR-BI) may play an important role in caffeine-induced cholesterol supply deficiency. Moreover, real-time RT-PCR and immunohistochemical detection certified the inhibitory effects of caffeine on both mRNA expression and protein expression of SR-BI in the fetal adrenal. And the increased DNA methylation frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation of the SR-BI promoter in the rat fetal adrenal. These effects may lead to decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis in the fetal adrenal. - Highlights: • Prenatal caffeine ingestion inhibits steroid hormone production in the fetal adrenal. • Prenatal caffeine ingestion inhibits cholesterol uptake in the fetal adrenal. • Prenatal caffeine

  11. Increased DNA methylation of scavenger receptor class B type I contributes to inhibitory effects of prenatal caffeine ingestion on cholesterol uptake and steroidogenesis in fetal adrenals

    International Nuclear Information System (INIS)

    Wu, Dong-Mei; He, Zheng; Ma, Liang-Peng; Wang, Lin-Long; Ping, Jie; Wang, Hui

    2015-01-01

    Steroid hormones synthesized from cholesterol in the fetal adrenal are crucial for fetal development. We have observed the inhibited fetal adrenal corticosterone synthesis and increased intrauterine growth retardation (IUGR) rate in rats under prenatal caffeine ingestion. The aim of this study is to evaluate the effects of prenatal caffeine ingestion on cholesterol supply in fetal adrenal steroidogenesis in rats and explore the underlying epigenetic mechanisms. Pregnant Wistar rats were treated with 60 mg/kg·d caffeine from gestational day (GD) 7 to GD17. Histological changes of fetal adrenals and increased IUGR rates were observed in the caffeine group. There were significantly decreased steroid hormone contents and cholesterol supply in caffeine-treated fetal adrenals. Data from the gene expression array suggested that prenatal caffeine ingestion caused increased expression of genes related to DNA methylation and decreased expression of genes related to cholesterol uptake. The following conjoint analysis of DNA methylation array with these differentially expressed genes suggested that scavenger receptor class B type I (SR-BI) may play an important role in caffeine-induced cholesterol supply deficiency. Moreover, real-time RT-PCR and immunohistochemical detection certified the inhibitory effects of caffeine on both mRNA expression and protein expression of SR-BI in the fetal adrenal. And the increased DNA methylation frequency in the proximal promoter of SR-BI was confirmed by bisulfite-sequencing PCR. In conclusion, prenatal caffeine ingestion can induce DNA hypermethylation of the SR-BI promoter in the rat fetal adrenal. These effects may lead to decreased SR-BI expression and cholesterol uptake, which inhibits steroidogenesis in the fetal adrenal. - Highlights: • Prenatal caffeine ingestion inhibits steroid hormone production in the fetal adrenal. • Prenatal caffeine ingestion inhibits cholesterol uptake in the fetal adrenal. • Prenatal caffeine

  12. Scavenger Receptors and Resistance to Inhaled Allergens

    Science.gov (United States)

    2010-02-01

    throughput manner which will enable future studies. We plan to continue two especially interesting aspects of these studies. First, the epigenetic control...directs mod- ified proteins to antigen presentation. Eur. J. Immunol. 29: 512–521. 30. Granucci, F., F. Petralia, M. Urbano , S. Citterio, F. Di Tota, L...11 Suppl:S32-6. 50. Granucci F, Petralia F, Urbano M, Citterio S, Di Tota F, Santambrogio L, Ricciardi-Castagnoli P: The scavenger receptor MARCO

  13. Scavenger Receptor Structure and Function in Health and Disease

    Directory of Open Access Journals (Sweden)

    Izma Abdul Zani

    2015-05-01

    Full Text Available Scavenger receptors (SRs are a ‘superfamily’ of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL, though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

  14. Scavenger Receptor CD163 and Its Biological Functions

    Directory of Open Access Journals (Sweden)

    Gabriela Onofre

    2009-01-01

    Full Text Available CD163 is a member of scavenger receptor super family class B of the first subgroup. It is mapped to the region p13 on chromosome 12. Five different isoforms of CD163 have been described, which differ in the structure of their cytoplasmic domains and putative phosporylation sites. This scavenger receptor is selectively expressed on cells of monocytes and macrophages lineage exclusively. CD163 immunological function is essentially homeostatic. It also has other functions because participates in adhesion to endothelial cells, in tolerance induction and tissues regeneration. Other very important function of CD163 is the clearance of hemoglobin in its cell-free form and participation in anti-inflammation in its soluble form, exhibiting cytokine-like functions. We review the biological functions of CD163 which have been discovered until now. It seems apparent from this review that CD163 scavenger receptor can be used as biomarker in different diseases and as a valuable diagnostic parameter for prognosis of many diseases especially inflammatory disorders and sepsis.

  15. The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria

    NARCIS (Netherlands)

    Fabriek, Babs O.; van Bruggen, Robin; Deng, Dong Mei; Ligtenberg, Antoon J. M.; Nazmi, Kamran; Schornagel, Karin; Vloet, Rianka P. M.; Dijkstra, Christine D.; van den Berg, Timo K.

    2009-01-01

    The plasma membrane glycoprotein receptor CD163 is a member of the scavenger receptor cystein-rich (SRCR) superfamily class B that is highly expressed on resident tissue macrophages in vivo. Previously, the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes and to

  16. In vitro and in vivo Analysis of the Binding of the C Terminus of the HDL Receptor Scavenger Receptor Class B type I (SR-BI) to the PDZ1 Domain of its Cytoplasmic Adaptor Protein PDZK1

    Energy Technology Data Exchange (ETDEWEB)

    O Kocher; G Birrane; K Tsukamoto; S Fenske; A Yesilaltay; R Pal; K Daniels; J Ladias; M Krieger

    2011-12-31

    The PDZ1 domain of the four PDZ domain-containing protein PDZK1 has been reported to bind the C terminus of the HDL receptor scavenger receptor class B, type I (SR-BI), and to control hepatic SR-BI expression and function. We generated wild-type (WT) and mutant murine PDZ1 domains, the mutants bearing single amino acid substitutions in their carboxylate binding loop (Lys(14)-Xaa(4)-Asn(19)-Tyr-Gly-Phe-Phe-Leu(24)), and measured their binding affinity for a 7-residue peptide corresponding to the C terminus of SR-BI ((503)VLQEAKL(509)). The Y20A and G21Y substitutions abrogated all binding activity. Surprisingly, binding affinities (K(d)) of the K14A and F22A mutants were 3.2 and 4.0 ?M, respectively, similar to 2.6 ?M measured for the WT PDZ1. To understand these findings, we determined the high resolution structure of WT PDZ1 bound to a 5-residue sequence from the C-terminal SR-BI ((505)QEAKL(509)) using x-ray crystallography. In addition, we incorporated the K14A and Y20A substitutions into full-length PDZK1 liver-specific transgenes and expressed them in WT and PDZK1 knock-out mice. In WT mice, the transgenes did not alter endogenous hepatic SR-BI protein expression (intracellular distribution or amount) or lipoprotein metabolism (total plasma cholesterol, lipoprotein size distribution). In PDZK1 knock-out mice, as expected, the K14A mutant behaved like wild-type PDZK1 and completely corrected their hepatic SR-BI and plasma lipoprotein abnormalities. Unexpectedly, the 10-20-fold overexpressed Y20A mutant also substantially, but not completely, corrected these abnormalities. The results suggest that there may be an additional site(s) within PDZK1 that bind(s) SR-BI and mediate(s) productive SR-BI-PDZK1 interaction previously attributed exclusively to the canonical binding of the C-terminal SR-BI to PDZ1.

  17. Novel mutations in scavenger receptor BI associated with high HDL cholesterol in humans

    NARCIS (Netherlands)

    Brunham, Liam R.; Tietjen, Ian; Bochem, Andrea E.; Singaraja, Roshni R.; Franchini, Patrick L.; Radomski, Chris; Mattice, Maryanne; Legendre, Annick; Hovingh, G. Kees; Kastelein, John J. P.; Hayden, Michael R.

    2011-01-01

    The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C).

  18. Scavenger

    DEFF Research Database (Denmark)

    2009-01-01

    Scavenger is one of the cyber foraging frameworks developed in the Locusts project. It has been released as open source software at http://code.google.com/p/scavenger-cf/......Scavenger is one of the cyber foraging frameworks developed in the Locusts project. It has been released as open source software at http://code.google.com/p/scavenger-cf/...

  19. Is the scavenger receptor MARCO a new immune checkpoint?

    Science.gov (United States)

    Arredouani, Mohamed S

    2014-11-01

    Whereas macrophages use the scavenger receptor MARCO primarily in antimicrobial immunity by interacting with both exogenous and endogenous environments, in dendritic cells (DCs) MARCO is believed to pleiotropically link innate to adaptive immunity. MARCO exerts a significant modulatory effect on TLR-induced DC activation, thus offering novel avenues in cancer immunotherapy.

  20. Scavenger receptor AI/II truncation, lung function and COPD

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjaerg-Hansen, A

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested whet...

  1. The macrophage scavenger receptor CD163

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Madsen, Mette; Møller, Holger J

    2006-01-01

    CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants are subs......CD163 is the monocyte/macrophage-specific receptor for haptoglobin-hemoglobin (Hp-Hb) complexes. The cytoplasmic tail of human CD163 exists as a short tail variant and two long tail variants. Reverse transcriptase-polymerase chain reaction analysis indicated that all three CD163 variants...

  2. High density lipoprotein stimulated migration of macrophages depends on the scavenger receptor class B, type I, PDZK1 and Akt1 and is blocked by sphingosine 1 phosphate receptor antagonists.

    Directory of Open Access Journals (Sweden)

    Aishah Al-Jarallah

    Full Text Available HDL carries biologically active lipids such as sphingosine-1-phosphate (S1P and stimulates a variety of cell signaling pathways in diverse cell types, which may contribute to its ability to protect against atherosclerosis. HDL and sphingosine-1-phosphate receptor agonists, FTY720 and SEW2871 triggered macrophage migration. HDL-, but not FTY720-stimulated migration was inhibited by an antibody against the HDL receptor, SR-BI, and an inhibitor of SR-BI mediated lipid transfer. HDL and FTY720-stimulated migration was also inhibited in macrophages lacking either SR-BI or PDZK1, an adaptor protein that binds to SR-BI's C-terminal cytoplasmic tail. Migration in response to HDL and S1P receptor agonists was inhibited by treatment of macrophages with sphingosine-1-phosphate receptor type 1 (S1PR1 antagonists and by pertussis toxin. S1PR1 activates signaling pathways including PI3K-Akt, PKC, p38 MAPK, ERK1/2 and Rho kinases. Using selective inhibitors or macrophages from gene targeted mice, we demonstrated the involvement of each of these pathways in HDL-dependent macrophage migration. These data suggest that HDL stimulates the migration of macrophages in a manner that requires the activities of the HDL receptor SR-BI as well as S1PR1 activity.

  3. Hypervariable region 1 deletion and required adaptive envelope mutations confer decreased dependency on scavenger receptor class B type I and low-density lipoprotein receptor for hepatitis C virus

    DEFF Research Database (Denmark)

    Prentoe, Jannick; Serre, Stéphanie B N; Ramirez, Santseharay

    2014-01-01

    -deleted viruses. Apolipoprotein E (ApoE)-specific HCV neutralization was similar for H77, J6, and S52 viruses with and without HVR1. In conclusion, HVR1 and HVR1-related adaptive envelope mutations appeared to be involved in LDLr and SR-BI dependency, respectively. Also, LDLr served Apo....../S733F), S52(ΔHVR1/A369V), and S52(A369V), but not for J6(ΔHVR1). Low-density lipoprotein receptor (LDLr) dependency was decreased for HVR1-deleted viruses, but not for H77(N476D/S733F) and S52(A369V). Soluble LDLr neutralization revealed strong inhibition of parental HCV but limited effect against HVR1...

  4. Innate scavenger receptor-A regulates adaptive T helper cell responses to pathogen infection

    Science.gov (United States)

    Xu, Zhipeng; Xu, Lei; Li, Wei; Jin, Xin; Song, Xian; Chen, Xiaojun; Zhu, Jifeng; Zhou, Sha; Li, Yong; Zhang, Weiwei; Dong, Xiaoxiao; Yang, Xiaowei; Liu, Feng; Bai, Hui; Chen, Qi; Su, Chuan

    2017-01-01

    The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction. Reduced abundance of nuclear IRF5 shifts macrophage polarization from M1 towards M2, which subsequently switches T-helper responses from type 1 to type 2. Our study identifies a role for SR-A as an innate PRR in regulating adaptive immune responses. PMID:28695899

  5. Scavenger Receptor C Mediates Phagocytosis of White Spot Syndrome Virus and Restricts Virus Proliferation in Shrimp

    Science.gov (United States)

    Yang, Ming-Chong; Shi, Xiu-Zhen; Yang, Hui-Ting; Sun, Jie-Jie; Xu, Ling; Wang, Xian-Wei; Zhao, Xiao-Fan

    2016-01-01

    Scavenger receptors are an important class of pattern recognition receptors that play several important roles in host defense against pathogens. The class C scavenger receptors (SRCs) have only been identified in a few invertebrates, and their role in the immune response against viruses is seldom studied. In this study, we firstly identified an SRC from kuruma shrimp, Marsupenaeus japonicus, designated MjSRC, which was significantly upregulated after white spot syndrome virus (WSSV) challenge at the mRNA and protein levels in hemocytes. The quantity of WSSV increased in shrimp after knockdown of MjSRC, compared with the controls. Furthermore, overexpression of MjSRC led to enhanced WSSV elimination via phagocytosis by hemocytes. Pull-down and co-immunoprecipitation assays demonstrated the interaction between MjSRC and the WSSV envelope protein. Electron microscopy observation indicated that the colloidal gold-labeled extracellular domain of MjSRC was located on the outer surface of WSSV. MjSRC formed a trimer and was internalized into the cytoplasm after WSSV challenge, and the internalization was strongly inhibited after knockdown of Mjβ-arrestin2. Further studies found that Mjβ-arrestin2 interacted with the intracellular domain of MjSRC and induced the internalization of WSSV in a clathrin-dependent manner. WSSV were co-localized with lysosomes in hemocytes and the WSSV quantity in shrimp increased after injection of lysosome inhibitor, chloroquine. Collectively, this study demonstrated that MjSRC recognized WSSV via its extracellular domain and invoked hemocyte phagocytosis to restrict WSSV systemic infection. This is the first study to report an SRC as a pattern recognition receptor promoting phagocytosis of a virus. PMID:28027319

  6. Scavenger Receptors and Their Potential as Therapeutic Targets in the Treatment of Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Sam L. Stephen

    2010-01-01

    Full Text Available Scavenger receptors act as membrane-bound and soluble proteins that bind to macromolecular complexes and pathogens. This diverse supergroup of proteins mediates binding to modified lipoprotein particles which regulate the initiation and progression of atherosclerotic plaques. In vascular tissues, scavenger receptors are implicated in regulating intracellular signaling, lipid accumulation, foam cell development, and cellular apoptosis or necrosis linked to the pathophysiology of atherosclerosis. One approach is using gene therapy to modulate scavenger receptor function in atherosclerosis. Ectopic expression of membrane-bound scavenger receptors using viral vectors can modify lipid profiles and reduce the incidence of atherosclerosis. Alternatively, expression of soluble scavenger receptors can also block plaque initiation and progression. Inhibition of scavenger receptor expression using a combined gene therapy and RNA interference strategy also holds promise for long-term therapy. Here we review our current understanding of the gene delivery by viral vectors to cells and tissues in gene therapy strategies and its application to the modulation of scavenger receptor function in atherosclerosis.

  7. Protection against inhaled oxidants through scavenging of oxidized lipids by macrophage receptors MARCO and SR-AI/II

    DEFF Research Database (Denmark)

    Dahl, Morten; Bauer, Alison K; Arredouani, Mohamed

    2007-01-01

    Alveolar macrophages (AMs) express the class A scavenger receptors (SRAs) macrophage receptor with collagenous structure (MARCO) and scavenger receptor AI/II (SRA-I/II), which recognize oxidized lipids and provide innate defense against inhaled pathogens and particles. Increased MARCO expression...... in lungs of ozone-resistant mice suggested an additional role protecting against inhaled oxidants. After ozone exposure, MARCO-/- mice showed greater lung injury than did MARCO+/+ mice. Ozone is known to generate oxidized, proinflammatory lipids in lung lining fluid, such as 5beta,6beta......-epoxycholesterol (beta-epoxide) and 1-palmitoyl-2-(9'-oxo-nonanoyl)-glycerophosphocholine (PON-GPC). Intratracheal instillation of either lipid caused substantial neutrophil influx in MARCO-/- mice, but had no effect in MARCO+/+ mice. Normal AMs showed greater uptake in vitro of beta-epoxide compared with MARCO-/- AMs...

  8. Human macrophage scavenger receptors: Primary structure, expression, and localization in atherosclerotic lesions

    International Nuclear Information System (INIS)

    Matsumoto, Akiyo; Itakura, Hiroshige; Kodama, Tatsuhiko; Naito, Makoto; Takahashi, Kiyoshi; Ikemoto, Shinji; Asaoka, Hitoshi; Hayakawa, Ikuho; Kanamori, Hiroshi; Takaku, Fumimaro; Aburatani, Hiroyuki; Suzuki, Hiroshi; Kobari, Yukage; Miyai, Tatsuya; Cohen, E.H.; Wydro, R.; Housman, D.E.

    1990-01-01

    Two types of cDNAs for human macrophage scavenger receptors were cloned from a cDNA library derived from the phorbol ester-treated human monocytic cell line THP-1. The type I and type II human scavenger receptors encoded by these cDNAs are homologous (73% and 71% amino acid identity) to their previously characterized bovine counterparts and consist of six domains: cytoplasmic (I), membrane-spanning (II), spacer (III), α-helical coiled-coil (IV), collagen-like (V), and a type-specific C-terminal (VI). The receptor gene is located on human chromosome 8. The human receptors expressed in CHO-K1 cells mediated endocytosis of modified low density lipoproteins. Two mRNAs, 4.0 and 3.2 kilobases, have been detected in human liver, placenta, and brain. Immunohistochemical studies using an anti-peptide antibody which recognizes human scavenger receptors indicated the presence of the scavenger receptors in the macrophages of lipid-rich atherosclerotic lesions, suggesting the involvement of scavenger receptors in atherogenesis

  9. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    Science.gov (United States)

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C l...

  10. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    DEFF Research Database (Denmark)

    Zanoni, Paolo; Khetarpal, Sumeet A; Larach, Daniel B

    2016-01-01

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-...

  11. The role of scavenger receptor B1 in infection with Mycobacterium tuberculosis in a murine model.

    Directory of Open Access Journals (Sweden)

    Georgia Schäfer

    2009-12-01

    Full Text Available The interaction between Mycobacterium tuberculosis (Mtb and host cells is complex and far from being understood. The role of the different receptor(s implicated in the recognition of Mtb in particular remains poorly defined, and those that have been found to have activity in vitro were subsequently shown to be redundant in vivo.To identify novel receptors involved in the recognition of Mtb, we screened a macrophage cDNA library and identified scavenger receptor B class 1 (SR-B1 as a receptor for mycobacteria. SR-B1 has been well-described as a lipoprotein receptor which mediates both the selective uptake of cholesteryl esters and the efflux of cholesterol, and has also recently been implicated in the recognition of other pathogens. We show here that mycobacteria can bind directly to SR-B1 on transfected cells, and that this interaction could be inhibited in the presence of a specific antibody to SR-B1, serum or LDL. We define a variety of macrophage populations, including alveolar macrophages, that express this receptor, however, no differences in the recognition and response to mycobacteria were observed in macrophages isolated from SR-B1(-/- or wild type mice in vitro. Moreover, when wild type and SR-B1(-/- animals were infected with a low dose of Mtb (100 CFU/mouse there were no alterations in survival, bacterial burdens, granuloma formation or cytokine production in the lung. However, significant reduction in the production of TNF, IFNgamma, and IL10 were observed in SR-B1(-/- mice following infection with a high dose of Mtb (1000 CFU/mouse, which marginally affected the size of inflammatory foci but did not influence bacterial burdens. Deficiency of SR-B1 also had no effect on resistance to disease under conditions of varying dietary cholesterol. We did observe, however, that the presence of high levels of cholesterol in the diet significantly enhanced the bacterial burdens in the lung, but this was independent of SR-B1.SR-B1 is involved in

  12. Identification of the receptor scavenging hemopexin-heme complexes

    DEFF Research Database (Denmark)

    Hvidberg, Vibeke; Maniecki, Maciej B; Jacobsen, Christian

    2005-01-01

    and is suggested to facilitate cellular heme metabolism. Using a ligand-affinity approach, we purified the human hemopexin-heme receptor and identified it as the low-density lipoprotein receptor-related protein (LRP)/CD91, a receptor expressed in several cell types including macrophages, hepatocytes, neurons......, and syncytiotrophoblasts. Binding experiments, including Biacore analysis, showed that hemopexin-heme complex formation elicits the high receptor affinity. Uptake studies of radio-labeled hemopexin-heme complex in LRP/CD91-expressing COS cells and confocal microscopy of the cellular processing of fluorescent hemopexin......-heme complexes are removed by a receptor-mediated pathway showing striking similarities to the CD163-mediated haptoglobin-hemoglobin clearance in macrophages. Furthermore, the data indicate a hitherto unknown role of LRP/CD91 in inflammation....

  13. Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI expression in liver and association with lipid levels in a population-based study

    Directory of Open Access Journals (Sweden)

    Barrett-Connor Elizabeth

    2010-01-01

    Full Text Available Abstract Background Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored. Methods We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII expression in 91 human liver tissues using quantitative real-time PCR. Results Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4 and triglycerides (p = 1.3 × 10-3 and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4. These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women Conclusions Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.

  14. Microglial Scavenger Receptors and Their Roles in the Pathogenesis of Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Kim Wilkinson

    2012-01-01

    Full Text Available Alzheimer’s disease (AD is increasing in prevalence with the aging population. Deposition of amyloid-β (Aβ in the brain of AD patients is a hallmark of the disease and is associated with increased microglial numbers and activation state. The interaction of microglia with Aβ appears to play a dichotomous role in AD pathogenesis. On one hand, microglia can phagocytose and clear Aβ, but binding of microglia to Aβ also increases their ability to produce inflammatory cytokines, chemokines, and neurotoxic reactive oxygen species (ROS. Scavenger receptors, a group of evolutionally conserved proteins expressed on the surface of microglia act as receptors for Aβ. Of particular interest are SCARA-1 (scavenger receptor A-1, CD36, and RAGE (receptor for advanced glycation end products. SCARA-1 appears to be involved in the clearance of Aβ, while CD36 and RAGE are involved in activation of microglia by Aβ. In this review, we discuss the roles of various scavenger receptors in the interaction of microglia with Aβ and propose that these receptors play complementary, nonredundant functions in the development of AD pathology. We also discuss potential therapeutic applications for these receptors in AD.

  15. Scavenger receptors in human airway epithelial cells: role in response to double-stranded RNA.

    Directory of Open Access Journals (Sweden)

    Audrey Dieudonné

    Full Text Available Scavenger receptors and Toll-like receptors (TLRs cooperate in response to danger signals to adjust the host immune response. The TLR3 agonist double stranded (dsRNA is an efficient activator of innate signalling in bronchial epithelial cells. In this study, we aimed at defining the role played by scavenger receptors expressed by bronchial epithelial cells in the control of the innate response to dsRNA both in vitro and in vivo. Expression of several scavenger receptor involved in pathogen recognition was first evaluated in human bronchial epithelial cells in steady-state and inflammatory conditions. Their implication in the uptake of dsRNA and the subsequent cell activation was evaluated in vitro by competition with ligand of scavenger receptors including maleylated ovalbumin and by RNA silencing. The capacity of maleylated ovalbumin to modulate lung inflammation induced by dsRNA was also investigated in mice. Exposure to tumor necrosis factor-α increased expression of the scavenger receptors LOX-1 and CXCL16 and the capacity to internalize maleylated ovalbumin, whereas activation by TLR ligands did not. In contrast, the expression of SR-B1 was not modulated in these conditions. Interestingly, supplementation with maleylated ovalbumin limited dsRNA uptake and inhibited subsequent activation of bronchial epithelial cells. RNA silencing of LOX-1 and SR-B1 strongly blocked the dsRNA-induced cytokine production. Finally, administration of maleylated ovalbumin in mice inhibited the dsRNA-induced infiltration and activation of inflammatory cells in bronchoalveolar spaces and lung draining lymph nodes. Together, our data characterize the function of SR-B1 and LOX-1 in bronchial epithelial cells and their implication in dsRNA-induced responses, a finding that might be relevant during respiratory viral infections.

  16. Proteolytic shedding of the macrophage scavenger receptor CD163 in multiple sclerosis

    DEFF Research Database (Denmark)

    Fabriek, Babs O; Møller, Holger J; Vloet, Rianka P M

    2007-01-01

    The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP...

  17. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets.

    Science.gov (United States)

    Mizejewski, G J

    2015-01-01

    Recent studies have demonstrated that the carboxyterminal third domain of alpha-fetoprotein (AFP-CD) binds with various ligands and receptors. Reports within the last decade have established that AFP-CD contains a large fragment of amino acids that interact with several different receptor types. Using computer software specifically designed to identify protein-to-protein interaction at amino acid sequence docking sites, the computer searches identified several types of scavenger-associated receptors and their amino acid sequence locations on the AFP-CD polypeptide chain. The scavenger receptors (SRs) identified were CD36, CD163, Stabilin, SSC5D, SRB1 and SREC; the SR-associated receptors included the mannose, low-density lipoprotein receptors, the asialoglycoprotein receptor, and the receptor for advanced glycation endproducts (RAGE). Interestingly, some SR interaction sites were localized on the AFP-derived Growth Inhibitory Peptide (GIP) segment at amino acids #480-500. Following the detection studies, a structural subdomain analysis of both the receptor and the AFP-CD revealed the presence of epidermal growth factor (EGF) repeats, extracellular matrix-like protein regions, amino acid-rich motifs and dimerization subdomains. For the first time, it was reported that EGF-like sequence repeats were identified on each of the three domains of AFP. Thereafter, the localization of receptors on specific cell types were reviewed and their functions were discussed.

  18. The macrophage scavenger receptor (CD163): a double-edged sword in treatment of malignant disease

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan

    2009-01-01

    of inflammatory processes. The receptor is expressed by circulatory monocytes and it is highly expressed on tissue-resident macrophages. CD163 is also expressed on leukemic blast cells of AML type M4/M5 and tumor cells in malignant melanoma and breast cancer. Although circumstantial evidence of the potential...... was investigated in biopsies from bladder cancer patients. We demonstrated that CD163 mRNA expression was significantly elevated in muscle invasive tumors (T2-T4) compared with superficial tumors (Ta), and that a high level of CD163 mRNA expression in tumor biopsies was significantly associated with poor 13-year......The hemoglobin scavenger receptor CD163 is a transmembrane glycoprotein belonging to the scavenger receptor cysteine-rich (SRCR) domain family. It mediates the clearance of hemoglobin released to the circulation during intravascular hemolysis, and it is also involved in the regulation...

  19. The LOX-1 Scavenger Receptor and Its Implications in the Treatment of Vascular Disease

    Directory of Open Access Journals (Sweden)

    M. W Twigg

    2012-01-01

    Full Text Available Cardiovascular disease is the leading cause of death. The disease is due to atherosclerosis which is characterized by lipid and fat accumulation in arterial blood vessel walls. A key causative event is the accumulation of oxidised low density lipoprotein particles within vascular cells, and this is mediated by scavenger receptors. One such molecule is the LOX-1 scavenger receptor that is expressed on endothelial, vascular smooth muscle, and lymphoid cells including macrophages. LOX-1 interaction with OxLDL particles stimulates atherosclerosis. LOX-1 mediates OxLDL endocytosis via a clathrin-independent internalization pathway. Transgenic animal model studies show that LOX-1 plays a significant role in atherosclerotic plaque initiation and progression. Administration of LOX-1 antibodies in cellular and animal models suggest that such intervention inhibits atherosclerosis. Antiatherogenic strategies that target LOX-1 function using gene therapy or small molecule inhibitors would be new ways to address the increasing incidence of vascular disease in many countries.

  20. Scavenger receptor AI/II truncation, lung function and COPD: a large population-based study

    DEFF Research Database (Denmark)

    Thomsen, M; Nordestgaard, B G; Tybjærg-Hansen, Anne

    2011-01-01

    The scavenger receptor A-I/II (SRA-I/II) on alveolar macrophages is involved in recognition and clearance of modified lipids and inhaled particulates. A rare variant of the SRA-I/II gene, Arg293X, truncates the distal collagen-like domain, which is essential for ligand recognition. We tested...... whether the Arg293X variant is associated with reduced lung function and risk of chronic obstructive pulmonary disease (COPD) in the general population....

  1. Pattern Recognition Scavenger Receptor A/CD204 Regulates Airway Inflammatory Homeostasis Following Organic Dust Extract Exposures

    Science.gov (United States)

    Poole, Jill A.; Anderson, Leigh; Gleason, Angela M.; West, William W.; Romberger, Debra J.; Wyatt, Todd A.

    2014-01-01

    Exposure to agriculture organic dusts, comprised of a diversity of pathogen-associated molecular patterns, results in chronic airway diseases. The multi-functional class A macrophage scavenger receptor (SRA)/CD204 has emerged as an important class of pattern recognition receptors with broad ligand binding ability. Our objective was to determine the role of SRA in mediating repetitive and post-inflammatory organic dust extract (ODE)-induced airway inflammation. Wild-type (WT) and SRA knockout (KO) mice were intra-nasally treated with ODE or saline daily for 3 wk and immediately euthanized or allowed to recover for 1 wk. Results show that lung histopathologic changes were increased in SRA KO mice as compared to WT following repetitive ODE exposures marked predominately by increased size and distribution of lymphoid aggregates. After a 1-wk recovery from daily ODE treatments, there was significant resolution of lung injury in WT mice, but not SRA KO animals. The increased lung histopathology induced by ODE treatment was associated with decreased accumulation of neutrophils, but greater accumulation of CD4+ T-cells. The lung cytokine milieu induced by ODE was consistent with a TH1/TH17 polarization in both WT and SRA KO mice. Overall, our data demonstrate that SRA/CD204 plays an important role in the normative inflammatory lung response to ODE as evidenced by the enhanced dust-mediated injury viewed in the absence of this receptor. PMID:24491035

  2. The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria

    NARCIS (Netherlands)

    Fabriek, B.O.; van Bruggen, R.; Deng, D.M.; Ligtenberg, A.J.M.; Nazmi, K.; Schornagel, K.; Vloet, R.P.M.; Dijkstra, C.D.; van den Berg, T.K.

    2009-01-01

    The plasma membrane glycoprotein re- ceptor CD163 is a member of the scaven- ger receptor cystein-rich (SRCR) super- family class B that is highly expressed on resident tissue macrophages in vivo. Pre- viously, the molecule has been shown to act as a receptor for hemoglobin- haptoglobin complexes

  3. Scavenger receptors mediate the role of SUMO and Ftz-f1 in Drosophila steroidogenesis.

    Directory of Open Access Journals (Sweden)

    Ana Talamillo

    2013-04-01

    Full Text Available SUMOylation participates in ecdysteroid biosynthesis at the onset of metamorphosis in Drosophila melanogaster. Silencing the Drosophila SUMO homologue smt3 in the prothoracic gland leads to reduced lipid content, low ecdysone titers, and a block in the larval-pupal transition. Here we show that the SR-BI family of Scavenger Receptors mediates SUMO functions. Reduced levels of Snmp1 compromise lipid uptake in the prothoracic gland. In addition, overexpression of Snmp1 is able to recover lipid droplet levels in the smt3 knockdown prothoracic gland cells. Snmp1 expression depends on Ftz-f1 (an NR5A-type orphan nuclear receptor, the expression of which, in turn, depends on SUMO. Furthermore, we show by in vitro and in vivo experiments that Ftz-f1 is SUMOylated. RNAi-mediated knockdown of ftz-f1 phenocopies that of smt3 at the larval to pupal transition, thus Ftz-f1 is an interesting candidate to mediate some of the functions of SUMO at the onset of metamorphosis. Additionally, we demonstrate that the role of SUMOylation, Ftz-f1, and the Scavenger Receptors in lipid capture and mobilization is conserved in other steroidogenic tissues such as the follicle cells of the ovary. smt3 knockdown, as well as ftz-f1 or Scavenger knockdown, depleted the lipid content of the follicle cells, which could be rescued by Snmp1 overexpression. Therefore, our data provide new insights into the regulation of metamorphosis via lipid homeostasis, showing that Drosophila Smt3, Ftz-f1, and SR-BIs are part of a general mechanism for uptake of lipids such as cholesterol, required during development in steroidogenic tissues.

  4. Identification of the hemoglobin scavenger receptor/CD163 as a natural soluble protein in plasma

    DEFF Research Database (Denmark)

    Møller, Holger Jon; Peterslund, Niels Anker; Graversen, Jonas Heilskov

    2002-01-01

    enabled identification of a soluble plasma form of HbSR (sHbSR) having an electrophoretic mobility equal to that of recombinant HbSR consisting of the extracellular domain (scavenger receptor cysteine-rich 1-9). A sandwich enzyme-linked immunosorbent assay was established and used to measure the s...... a level of sHbSR above the range of healthy persons. Patients with myelomonocytic leukemias and pneumonia/sepsis exhibited the highest levels (up to 67.3 mg/L). In conclusion, sHbSR is an abundant plasma protein potentially valuable in monitoring patients with infections and myelomonocytic leukemia....

  5. Design and synthesis of a stable oxidized phospholipid mimic with specific binding recognition for macrophage scavenger receptors

    DEFF Research Database (Denmark)

    Turner, William W; Hartvigsen, Karsten; Boullier, Agnes

    2012-01-01

    Macrophage scavenger receptors appear to play a major role in the clearance of oxidized phospholipid (OxPL) products. Discrete peptide-phospholipid conjugates with the phosphatidylcholine headgroup have been shown to exhibit binding affinity for these receptors. We report the preparation of a wat...

  6. Macrophage specific overexpression of the human macrophage scavenger receptor in transgenic mice, using a 180-kb yeast artificial chromosome, leads to enhanced foam cell formation of isolated peritoneal macrophages

    NARCIS (Netherlands)

    de Winther, M. P.; van Dijk, K. W.; van Vlijmen, B. J.; Gijbels, M. J.; Heus, J. J.; Wijers, E. R.; van den Bos, A. C.; Breuer, M.; Frants, R. R.; Havekes, L. M.; Hofker, M. H.

    1999-01-01

    Macrophage scavenger receptors class A (MSR) are thought to play an important role in atherogenesis by mediating the unrestricted uptake of modified lipoproteins by macrophages in the vessel wall leading to foam cell formation. To investigate the in vivo role of the MSR in this process, a transgenic

  7. In vitro photodynamic effects of scavenger receptor targeted-photoactivatable nanoagents on activated macrophages.

    Science.gov (United States)

    Yi, Bong Gu; Park, Ok Kyu; Jeong, Myeong Seon; Kwon, Seung Hae; Jung, Jae In; Lee, Seongsoo; Ryoo, Sungwoo; Kim, Sung Eun; Kim, Jin Won; Moon, Won-Jin; Park, Kyeongsoon

    2017-04-01

    Scavenger receptors (SRs) expressed on the activated macrophages in inflammation sites have been considered as the most interesting and important target biomarker for targeted drug delivery, imaging and therapy. In the present study, we fabricated the scavenger receptor-A (SR-A) targeted-photoactivatable nanoagents (termed as Ce6/DS-DOCA) by entrapping chlorin e6 (Ce6) into the amphiphilic dextran sulfate-deoxycholic acid (DS-DOCA) conjugates via physically hydrophobic interactions. Insoluble Ce6 was easily encapsulated into DS-DOCA nanoparticles by a dialysis method and the loading efficiency was approximately 51.7%. The Ce6/DS-DOCA formed nano-sized self-assembled aggregates (28.8±5.6nm in diameter), confirmed by transmission electron microscope, UV/Vis and fluorescence spectrophotometer. The Ce6/DS-DOCA nanoagents could generate highly reactive singlet oxygen under laser irradiation. Also, in vitro studies showed that they were more specifically taken up by lipopolysaccharide (LPS)-induced activated macrophages (RAW 264.7) via a SR-A-mediated endocytosis, relative to by non-activated macrophages, and notably induced cell death of activated macrophages under laser irradiation. Therefore, SR-A targetable and photoactivatable Ce6/DS-DOCA nanoagents with more selective targeting to the activated macrophages will have great potential for treatment of inflammatory diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The superoxide scavenger TEMPOL induces urokinase receptor (uPAR expression in human prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Francis Joseph

    2006-06-01

    Full Text Available Abstract There is little understanding of the effect that reactive oxygen metabolites have on cellular behavior during the processes of invasion and metastasis. These oxygen metabolites could interact with a number of targets modulating their function such as enzymes involved in basement membrane dissolution, adhesion molecules involved in motility or receptors involved in proliferation. We investigated the effect of increased scavenging of superoxide anions on the expression of the urokinase receptor (uPAR in PC-3M human prostate cancer cells. Urokinase receptor is a GPI-linked cell surface molecule which mediates multiple functions including adhesion, proliferation and pericellular proteolysis. Addition of the superoxide scavenger 4-hydroxy-2,2,6,6-tetramethylpiperidinyloxy (TEMPOL to PC-3M cultures stimulated expression of uPAR protein peaking between 48 and 72 hours. Cell surface expression of the uPAR was also increased. Surprisingly, uPAR transcript levels increased only slightly and this mild increase did not coincide with the striking degree of protein increase. This disparity indicates that the TEMPOL effect on uPAR occurs through a post-transcriptional mechanism. TEMPOL presence in PC-3M cultures reduced intracellular superoxide-type species by 75% as assayed by NBT dye conversion; however this reduction significantly diminished within hours following TEMPOL removal. The time gap between TEMPOL treatment and peak uPAR protein expression suggests that reduction of reactive oxygen metabolites in prostate cancer cells initiates a multistep pathway which requires several hours to culminate in uPAR induction. These findings reveal a novel pathway for uPAR regulation involving reactive oxygens such as superoxide anion.

  9. Uptake and metabolism of polymerized albumin by rat liver. Role of the scavenger receptor

    International Nuclear Information System (INIS)

    Wright, T.L.; Roll, F.J.; Jones, A.L.; Weisiger, R.A.

    1988-01-01

    Hepatitis B virus binds avidly to albumin polymers, which in turn may mediate viral attachment to liver cells. This hypothesis is critically dependent on prior results obtained using glutaraldehyde-polymerized human serum albumin as a model for naturally occurring albumin species. We used the perfused rat liver to characterize the uptake, cellular distribution, and metabolism of glutaraldehyde-polymerized human albumin. 125 I-glutaraldehyde-polymerized human albumin was efficiently removed from the perfusate by the liver (29% extraction). However, few autoradiographic grains were located over hepatic parenchymal cells (6%). Instead, most glutaraldehyde-polymerized human albumin appeared to be removed by endothelial (59%) or Kupffer (31%) cells. Hepatic uptake was strongly inhibited by formaldehyde-treated monomeric albumin, a known ligand of the endothelial scavenger receptor for chemically modified proteins. After uptake, most glutaraldehyde-polymerized human albumin was rapidly degraded and released into the perfusate (74% within 60 min). This process was blocked by chloroquine and leupeptin, suggesting that it involves lysosomal acid hydrolases. We conclude that glutaraldehyde-polymerized albumin is efficiently cleared and degraded by the endothelial scavenger pathway. Glutaraldehyde-polymerized albumin therefore appears to be a poor model for predicting the hepatic handling of naturally occurring albumin species bound to hepatitis B virions. Even if viral particles were to follow this pathway, few would enter parenchymal hepatocytes

  10. Alternative activation of macrophages and pulmonary fibrosis are modulated by scavenger receptor, macrophage receptor with collagenous structure.

    Science.gov (United States)

    Murthy, Shubha; Larson-Casey, Jennifer L; Ryan, Alan J; He, Chao; Kobzik, Lester; Carter, A Brent

    2015-08-01

    Alternative activation of alveolar macrophages is linked to fibrosis following exposure to asbestos. The scavenger receptor, macrophage receptor with collagenous structure (MARCO), provides innate immune defense against inhaled particles and pathogens; however, a receptor for asbestos has not been identified. We hypothesized that MARCO acts as an initial signaling receptor for asbestos, polarizes macrophages to a profibrotic M2 phenotype, and is required for the development of asbestos-induced fibrosis. Compared with normal subjects, alveolar macrophages isolated from patients with asbestosis express higher amounts of MARCO and have greater profibrotic polarization. Arginase 1 (40-fold) and IL-10 (265-fold) were higher in patients. In vivo, the genetic deletion of MARCO attenuated the profibrotic environment and pulmonary fibrosis in mice exposed to chrysotile. Moreover, alveolar macrophages from MARCO(-/-) mice polarize to an M1 phenotype, whereas wild-type mice have higher Ym1 (>3.0-fold) and nearly 7-fold more active TGF-β1 in bronchoalveolar lavage (BAL) fluid (BALF). Arg(432) and Arg(434) in domain V of MARCO are required for the polarization of macrophages to a profibrotic phenotype as mutation of these residues reduced FIZZ1 expression (17-fold) compared with cells expressing MARCO. These observations demonstrate that a macrophage membrane protein regulates the fibrotic response to lung injury and suggest a novel target for therapeutic intervention. © FASEB.

  11. Cloning and characterization of SCART1, a novel scavenger receptor cysteine-rich type I transmembrane molecule

    DEFF Research Database (Denmark)

    Holm, Dorte; Fink, Dorte Rosenbek; Grønlund, Jørn

    2009-01-01

    We have cloned and characterized a novel murine transmembrane molecule, mSCART1 belonging to the scavenger receptor cysteine-rich superfamily. The cDNA encodes a polypeptide chain of 989 amino acids, organized as a type I transmembrane protein that contains eight extracellular SRCR domains followed...

  12. A new class of free radical scavengers reducing adriamycin mitochondrial toxicity

    NARCIS (Netherlands)

    Praet, M.; Calderon, P. B.; Pollakis, G.; Roberfroid, M.; Ruysschaert, J. M.

    1988-01-01

    Beef heart mitochondria were incubated with ADM and NADH. An adriamycin semiquinone radical was detected using ESR spectroscopy. The semiquinone radical production rate is decreased upon addition of a scavenger (AD 20) in the reaction medium. NMRI mice were treated with AD 20 (70 mg/kg, i.p.) 15 min

  13. The scavenger receptor repertoire in six cnidarian species and its putative role in cnidarian-dinoflagellate symbiosis

    Directory of Open Access Journals (Sweden)

    Emilie F. Neubauer

    2016-11-01

    Full Text Available Many cnidarians engage in a mutualism with endosymbiotic photosynthetic dinoflagellates that forms the basis of the coral reef ecosystem. Interpartner interaction and regulation includes involvement of the host innate immune system. Basal metazoans, including cnidarians have diverse and complex innate immune repertoires that are just beginning to be described. Scavenger receptors (SR are a diverse superfamily of innate immunity genes that recognize a broad array of microbial ligands and participate in phagocytosis of invading microbes. The superfamily includes subclades named SR-A through SR-I that are categorized based on the arrangement of sequence domains including the scavenger receptor cysteine rich (SRCR, the C-type lectin (CTLD and the CD36 domains. Previous functional and gene expression studies on cnidarian-dinoflagellate symbiosis have implicated SR-like proteins in interpartner communication and regulation. In this study, we characterized the SR repertoire from a combination of genomic and transcriptomic resources from six cnidarian species in the Class Anthozoa. We combined these bioinformatic analyses with functional experiments using the SR inhibitor fucoidan to explore a role for SRs in cnidarian symbiosis and immunity. Bioinformatic searches revealed a large diversity of SR-like genes that resembled SR-As, SR-Bs, SR-Es and SR-Is. SRCRs, CTLDs and CD36 domains were identified in multiple sequences in combinations that were highly homologous to vertebrate SRs as well as in proteins with novel domain combinations. Phylogenetic analyses of CD36 domains of the SR-B-like sequences from a diversity of metazoans grouped cnidarian with bilaterian sequences separate from other basal metazoans. All cnidarian sequences grouped together with moderate support in a subclade separately from bilaterian sequences. Functional experiments were carried out on the sea anemone Aiptasia pallida that engages in a symbiosis with Symbiodinium minutum

  14. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Energy Technology Data Exchange (ETDEWEB)

    Aldossari, Abdullah A.; Shannahan, Jonathan H. [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States); Podila, Ramakrishna [Clemson University, Department of Physics and Astronomy (United States); Brown, Jared M., E-mail: jared.brown@ucdenver.edu [The University of Colorado Anschutz Medical Campus, Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences (United States)

    2015-07-15

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf-α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  15. Scavenger receptor B1 facilitates macrophage uptake of silver nanoparticles and cellular activation

    Science.gov (United States)

    Aldossari, Abdullah A.; Shannahan, Jonathan H.; Podila, Ramakrishna; Brown, Jared M.

    2015-07-01

    Due to increased use of silver nanoparticles (AgNPs) for their antimicrobial activity, concerns have risen regarding potential adverse human health effects. Scavenger receptor B1 (SR-B1), a major receptor for high-density lipoprotein (HDL), is expressed by macrophages and has also been reported to play a role in recognition of negatively charged particles. We, therefore, hypothesized that SR-B1 mediates macrophage uptake of AgNPs and inflammatory activation. To test this hypothesis, we exposed a mouse macrophage cell line RAW264.7 (RAW) and bone marrow-derived macrophages (BMDM) to 20 nm citrate-suspended AgNPs. To verify the role of the SR-B1 receptor, we utilized a SR-B1 inhibitor (Blt2). In vitro studies demonstrated uptake of AgNPs and HDL-coated AgNPs by macrophages which were significantly reduced following pretreatment with Blt2. Inflammatory cytokine arrays revealed that macrophages exposed to AgNPs up-regulated expression of Tnf- α, Oncostatin m (OSM), Ccl4, Il17f, Ccl7, and Ccl2, whereas Il16 was found to be down-regulated. Macrophage activation was observed following AgNP and HDL-coated AgNP exposure as measured by OSM protein production and increased surface expression of CD86. These markers of activation were reduced with Blt2 pretreatment. The in vitro findings were confirmed in vivo through pulmonary instillation of AgNPs in mice. Pulmonary instillation of AgNPs resulted in a recruitment of inflammatory cells that were reduced in SR-B1-deficient mice or following Blt2 pretreatment. This study suggests that SR-B1 plays a major role in cellular recognition of AgNPs and the induction of cell responses that could contribute to inflammation caused by AgNP exposure.

  16. Scavenger receptor-mediated recognition of maleyl bovine plasma albumin and the demaleylated protein in human monocyte macrophages

    International Nuclear Information System (INIS)

    Haberland, M.E.; Fogelman, A.M.

    1985-01-01

    Maleyl bovine plasma albumin competed on an equimolar basis with malondialdehyde low density lipoprotein (LDL) in suppressing the lysosomal hydrolysis of 125 I-labeled malondialdehyde LDL mediated by the scavenger receptor of human monocyte macrophages. Maleyl bovine plasma albumin, in which 94% of the amino groups were modified, exhibited an anodic mobility in agarose electrophoresis 1.7 times that of the native protein. Incubation of maleyl bovine plasma albumin at pH 3.5 regenerated the free amino groups and restored the protein to the same electrophoretic mobility as native albumin. Although ligands recognized by the scavenger receptor typically are anionic, the authors propose that addition of new negative charge achieved by maleylation, rather than directly forming the receptor binding site(s), induces conformational changes in albumin as a prerequisite to expression of the recognition domain(s). They conclude that the primary sequence of albumin, rather than addition of new negative charge, provides the recognition determinant(s) essential for interaction of maleyl bovine plasma albumin with the scavenger receptor

  17. Identification of Adenovirus Serotype 5 Hexon Regions That Interact with Scavenger Receptors

    Energy Technology Data Exchange (ETDEWEB)

    Khare, Reeti; Reddy, Vijay S.; Nemerow, Glen R.; Barry, Michael A. (Scripps); (Mayo)

    2012-05-04

    Most of an intravenous dose of species C adenovirus serotype 5 (Ad5) is destroyed by liver Kupffer cells. In contrast, another species C virus, Ad6, evades these cells to mediate more efficient liver gene delivery. Given that this difference in Kupffer cell interaction is mediated by the hypervariable (HVR) loops of the virus hexon protein, we genetically modified each of the seven HVRs of Ad5 with a cysteine residue to enable conditional blocking of these sites with polyethylene glycol (PEG). We show that these modifications do not affect in vitro virus transduction. In contrast, after intravenous injection, targeted PEGylation at HVRs 1, 2, 5, and 7 increased viral liver transduction up to 20-fold. Elimination or saturation of liver Kupffer cells did not significantly affect this increase in the liver transduction. In vitro, PEGylation blocked uptake of viruses via the Kupffer cell scavenger receptor SRA-II. These data suggest that HVRs 1, 2, 5, and 7 of Ad5 may be involved in Kupffer cell recognition and subsequent destruction. These data also demonstrate that this conditional genetic-chemical mutation strategy is a useful tool for investigating the interactions of viruses with host tissues.

  18. The scavenger receptor MARCO modulates TLR-induced responses in dendritic cells.

    Directory of Open Access Journals (Sweden)

    Haydn T Kissick

    Full Text Available The scavenger receptor MARCO mediates macrophage recognition and clearance of pathogens and their polyanionic ligands. However, recent studies demonstrate MARCO expression and function in dendritic cells, suggesting MARCO might serve to bridge innate and adaptive immunity. To gain additional insight into the role of MARCO in dendritic cell activation and function, we profiled transcriptomes of mouse splenic dendritic cells obtained from MARCO deficient mice and their wild type counterparts under resting and activating conditions. In silico analysis uncovered major alterations in gene expression in MARCO deficient dendritic cells resulting in dramatic alterations in key dendritic cell-specific pathways and functions. Specifically, changes in CD209, FCGR4 and Complement factors can have major consequences on DC-mediated innate responses. Notably, these perturbations were magnified following activation with the TLR-4 agonist lipopolysaccharide. To validate our in silico data, we challenged DC's with various agonists that recognize all mouse TLRs and assessed expression of a set of immune and inflammatory marker genes. This approach identified a differential contribution of MARCO to TLR activation and validated a major role for MARCO in mounting an inflammatory response. Together, our data demonstrate that MARCO differentially affects TLR-induced DC activation and suggest targeting of MARCO could lead to different outcomes that depend on the inflammatory context encountered by DC.

  19. Decreased immunostaining for macrophage scavenger receptor is associated with poor prognosis of prostate cancer.

    Science.gov (United States)

    Takayama, Hitoshi; Nonomura, Norio; Nishimura, Kazuo; Oka, Daizo; Shiba, Masahiro; Nakai, Yasutomo; Nakayama, Masashi; Tsujimura, Akira; Aozasa, Katsuyuki; Okuyama, Akihiko

    2009-02-01

    The aim of this study is to evaluate the expression of the macrophage scavenger receptor (MSR) in prostate needle biopsy specimens as a possible prognostic factor for prostate cancer. As MSR reportedly has a role in recognizing foreign pathogenic substances, MSR-positive inflammatory cells are often detected in solid tumours, and there is a correlation between the relative risk of prostate cancer and polymorphism of the MSR gene. MSR was evaluated by immunostaining in needle biopsies of the prostate from 135 patients who were confirmed to have prostate cancer. Among these men, 70 were treated by radical prostatectomy or by radiotherapy as definitive therapy; the other 65 were treated by hormonal therapy because of advanced disease or age. Needle-biopsy specimens were sectioned at 5 microm and immunostained with a monoclonal antibody against MSR. Six microscopic (x400) fields around the cancer foci were selected in each case for analysis. The median number of MSR-positive cells (MSR count) in each case was 24. There was an inverse correlation between the MSR count and Gleason score and clinical stage. The MSR count was lower in patients with biochemical (prostate-specific antigen, PSA) failure than that in those with no PSA failure (P or =24) than that in those with low MSR count (<24, P < 0.001). Moreover, for patients treated by definitive or hormonal therapy, the RFS rates in those with a higher MSR count were higher than in those with a lower MSR count (P < 0.001 and 0.014, respectively). Cox multivariate analysis showed that the MSR count was a prognostic factor for prostate cancer in addition to extraprostatic extension and Gleason score (P = 0.002, 0.038 and 0.011, respectively). The results of immunostaining of MSR in needle-biopsy specimens is a prognostic factor for prostate cancer.

  20. Activated human mast cells induce LOX-1-specific scavenger receptor expression in human monocyte-derived macrophages.

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    Mervi Alanne-Kinnunen

    Full Text Available Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs.Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1 mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α, and transforming growth factor beta (TGF-β1, which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell -induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages.Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis.

  1. Comparison of the effectiveness and safety between lymphocytes scavenger and IL-2 receptor blocking agent induction in living kidney transplantation

    Directory of Open Access Journals (Sweden)

    Ning-bo QIN

    2013-03-01

    Full Text Available Objective  To compare the safety of two antibody inductors, namely lymphocytes scavenger and IL-2 receptor blocking agent, in living kidney transplantation. Methods  The data of 191 patients, who received living kidney transplant in our hospital from Feb. 2007 to Jul. 2012, were retrospectively analyzed, and grouped according to the inductors they received as: a lymphocytes scavenger group (n=56, with rabbit antithymocyte immunoglobulin (rATG, 4 cases and porcine antihuman T-lymphocyte immunoglobulin (pATG, 52 cases served as the inductor; b IL -2 receptor blocking agent group (n=54, with basiliximab (40 cases and daclizumab (14 cases served as the inductor; and c control group (n=81. The incidence of rejection and infection, and the survival rate of patient/allograft within one year were then compared among the three groups. Results  Within one year after the transplantation, the incidence of acute rejection in lymphocytes scavenger group, IL-2 receptor blocking agent group and control group was 12.5%, 11.1% and 28.4%, respectively. There was a significant difference between the two inductor groups and control group (P=0.003, but no significant difference was found between the two inductor groups (P>0.05. The incidence of delayed graft function (DGF in the three groups was 8.9%, 7.4% and 13.6%, respectively, with no statistical significance (P>0.05. Also there was no significant difference among the three groups in the incidence of infection and the survival rate of patient/allograft within one year after transplantation (P>0.05. Conclusion  Both inductors may significantly reduce the incidence of acute rejection within one year without increasing the incidence of infection and other adverse events, nor affect the postoperative patient/graft survival, so they are both safe and effective.

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

    DEFF Research Database (Denmark)

    Handberg, Aase; Levin, Klaus; Højlund, Kurt

    2006-01-01

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

  3. Molecular and Functional Characterization of Mouse S5D-SRCRB: A New Group B Member of the Scavenger Receptor Cysteine-Rich Superfamily

    DEFF Research Database (Denmark)

    Miró-Julià, Cristina; Roselló, Sandra; Martínez, Vanesa G

    2011-01-01

    The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ∼100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which...... differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization...

  4. The scavenger receptor SSc5D physically interacts with bacteria through the SRCR-containing N-terminal domain

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    Catarina Bessa-Pereira

    2016-10-01

    Full Text Available The scavenger receptor cysteine-rich (SRCR family comprises a group of membrane-attached or secreted proteins that contain one or more modules/domains structurally similar to the membrane distal domain of type I macrophage scavenger receptor. Although no all-inclusive biological function has been ascribed to the SRCR family, some of these receptors have been shown to recognize pathogen-associated molecular patterns (PAMP of bacteria, fungi or other microbes. SSc5D is a recently described soluble SRCR receptor produced by monocytes/macrophages and T lymphocytes, consisting of an N-terminal portion which contains five SRCR modules, and a large C-terminal mucin-like domain. Towards establishing a global common role for SRCR domains, we interrogated whether the set of five SRCR domains of SSc5D displayed pattern recognition receptor (PRR properties. For that purpose, we have expressed in a mammalian expression system the N-terminal SRCR-containing moiety of SSC5D (N-SSc5D, thus excluding the mucin-like domain likely by nature to bind microorganisms, and tested the capacity of the SRCR functional groups to physically interact with bacteria. Using conventional protein-bacteria binding assays, we showed that N-SSc5D had a superior capacity to bind to E. coli strains RS218 and IHE3034 compared with that of the extracellular domains of the SRCR proteins CD5 and CD6 (sCD5 and sCD6, respectively, and similar E. coli-binding properties as Spα, a proven PRR of the SRCR family. We have further designed a more sensitive, real-time and label-free surface plasmon resonance (SPR-based assay, and examined the capacity of N-SSc5D, Spα, sCD5 and sCD6 to bind to different bacteria. We demonstrated that the N-SSc5D compares with Spα in the capacity to bind to E. coli and L. monocytogenes, and further that it can distinguish between pathogenic E. coli RS218 and IHE3034 strains and the non-pathogenic laboratory E. coli strain BL21(DE3. Our work thus advocates the

  5. CD163: a signal receptor scavenging haptoglobin-hemoglobin complexes from plasma

    DEFF Research Database (Denmark)

    Graversen, Jonas Heilskov; Madsen, Mette; Moestrup, Søren K

    2002-01-01

    as the endocytic receptor binding hemoglobin (Hb) in complex with the plasma protein haptoglobin (Hp). This specific receptor-ligand interaction leading to removal from plasma of the Hp-Hb complex-but not free Hp or Hb-now explains the depletion of circulating Hp in individuals with increased intravascular...

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

    Science.gov (United States)

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

    2014-02-01

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

  7. Molecular characterization of the haptoglobin.hemoglobin receptor CD163. Ligand binding properties of the scavenger receptor cysteine-rich domain region

    DEFF Research Database (Denmark)

    Madsen, Mette; Møller, Holger J; Nielsen, Marianne Jensby

    2004-01-01

    CD163 is the macrophage receptor for endocytosis of haptoglobin.hemoglobin complexes. The extracellular region consisting of nine scavenger receptor cysteine rich (SRCR) domains also circulates in plasma as a soluble protein. By ligand binding analysis of a broad spectrum of soluble CD163...... truncation variants, the amino-terminal third of the SRCR region was shown to be crucial for the binding of haptoglobin.hemoglobin complexes. By Western blotting of the CD163 variants, a panel of ten monoclonal antibodies was mapped to SRCR domains 1, 3, 4, 6, 7, and 9, respectively. Only the two antibodies...... to CD163 demonstrated that optimal ligand binding requires physiological plasma calcium concentrations, and an immediate ligand release occurs at the low calcium concentrations measured in acidifying endosomes. In conclusion, SRCR domain 3 of CD163 is an exposed domain and a critical determinant...

  8. Bacteria binding by DMBT1/SAG/gp-340 is confined to the VEVLXXXXW motif in its scavenger receptor cysteine-rich domains

    DEFF Research Database (Denmark)

    Bikker, Floris J; Ligtenberg, Antoon J M; End, Caroline

    2004-01-01

    The scavenger receptor cysteine-rich (SRCR) proteins form an archaic group of metazoan proteins characterized by the presence of SRCR domains. These proteins are classified in group A and B based on the number of conserved cysteine residues in their SRCR domains, i.e. six for group A and eight fo...

  9. In vivo regulation of scavenger receptor BI and the selective uptake of high density lipoprotein cholesteryl esters in rat liver parenchymal and Kupffer cells

    NARCIS (Netherlands)

    Fluiter, K.; van der Westhuijzen, D. R.; van Berkel, T. J.

    1998-01-01

    High density lipoprotein cholesteryl esters (HDL-CE) are selectively taken up by liver parenchymal cells without parallel apolipoprotein uptake. This selective uptake route forms an important step in the so-called reverse cholesterol transport. Scavenger receptor BI (SR-BI) is the only known HDL

  10. Scavenger receptor-mediated endocytosis by sinusoidal cells in rat bone marrow

    International Nuclear Information System (INIS)

    Geoffroy, J.S.

    1987-01-01

    Endocytosis of serum albumin by sinusoidal endothelial cells in rat bone marrow was investigated initially at the ultrastructural level with subsequent biochemical investigation of the specificity mediating this event. Bovine serum albumin adsorbed to 20nm colloidal gold particles (AuBSA) was chosen as the electron microscopic probe. Morphological data strongly suggested that a receptor was involved in uptake of AuBSA. Confirmation of receptor involvement in the uptake of AuBSA by marrow sinusoidal endothelial cells was achieved utilizing an in situ isolated hind limb perfusion protocol in conjunction with unlabeled, radiolabeled, and radio-/colloidal gold labeled probes. The major findings of competition and saturation experiments were: (1) endocytosis of AuBSA was mediated by a receptor for modified/treated serum albumin; (2) endocytosis of formaldehyde-treated serum albumin was mediated by a binding site which may be the same or closely related to the site responsible for the uptake of AuBSA; and (3) endocytosis of native untreated albumin was not mediated by receptor and probably represents fluid-phase pinocitosis

  11. Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages.

    Science.gov (United States)

    Maler, Mareike D; Nielsen, Peter J; Stichling, Nicole; Cohen, Idan; Ruzsics, Zsolt; Wood, Connor; Engelhard, Peggy; Suomalainen, Maarit; Gyory, Ildiko; Huber, Michael; Müller-Quernheim, Joachim; Schamel, Wolfgang W A; Gordon, Siamon; Jakob, Thilo; Martin, Stefan F; Jahnen-Dechent, Willi; Greber, Urs F; Freudenberg, Marina A; Fejer, György

    2017-08-01

    The scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responses in vivo Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors. IMPORTANCE Macrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responses in vitro and in vivo The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages

  12. Characterization of a novel human scavenger receptor cysteine-rich molecule SCART1 expressed by lymphocytes

    DEFF Research Database (Denmark)

    Holm, D.; Fink, D. R.; Steffensen, M. A.

    2013-01-01

    a member of the SRCR superfamily, mSCART1, which primarily is expressed on a large subset of γδ T cells in mice. Here we report the cloning and characterization of human SCART1 (hSCART1) mainly expressed by CD4(+) and CD8(+) T lymphocytes. The hSCART1 gene maps to chromosome 10, region q26.3, a region...... domain. Shorter splice forms have also been isolated. Quantitative real-time PCR analysis on human blood-fractions has shown that hSCART1 is expressed primarily by CD4(+) and CD8(+) T lymphocytes with either αβ or γδ T cell receptors, and real-time PCR on 22 different human tissues showed high expression...... that the protein plays a role in the immune system, perhaps as a co-receptor on αβ and γδ T cells....

  13. Conserved Bacterial-Binding Peptides of the Scavenger-Like Human Lymphocyte Receptor CD6 Protect From Mouse Experimental Sepsis

    Directory of Open Access Journals (Sweden)

    Mario Martínez-Florensa

    2018-04-01

    Full Text Available Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW. All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.

  14. Class I Cytokine Receptors: Structure and function in the Membrane

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard

    bilayer via structural characterizations of TMD representatives. To enable structural studies of these domains, an organic-extraction based strategy for efficient production of isotope-labeled TMDs with or without short intrinsically disordered regions was developed. This strategy successfully provided...... of these challenging domains. Supplemented by a review of the current collection of TMD structures from single-pass transmembrane receptors, the thesis as a whole provides important insights on the structure and function in the membrane as well as highlight the open questions to be addressed in the years to come.......Class I cytokine receptors are involved in important biological functions of both physiological and pathological nature in mammals. However, the molecular details of the cross-membrane signal transduction through these receptors remain obscure. One of the major reasons for this is the lack...

  15. Salivary agglutinin, which binds Streptococcus mutans and Helicobacter pylori, is the lung scavenger receptor cysteine-rich protein gp-340.

    Science.gov (United States)

    Prakobphol, A; Xu, F; Hoang, V M; Larsson, T; Bergstrom, J; Johansson, I; Frängsmyr, L; Holmskov, U; Leffler, H; Nilsson, C; Borén, T; Wright, J R; Strömberg, N; Fisher, S J

    2000-12-22

    Salivary agglutinin is a high molecular mass component of human saliva that binds Streptococcus mutans, an oral bacterium implicated in dental caries. To study its protein sequence, we isolated the agglutinin from human parotid saliva. After trypsin digestion, a portion was analyzed by matrix-assisted laser/desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), which gave the molecular mass of 14 unique peptides. The remainder of the digest was subjected to high performance liquid chromatography, and the separated peptides were analyzed by MALDI-TOF/post-source decay; the spectra gave the sequences of five peptides. The molecular mass and peptide sequence information showed that salivary agglutinin peptides were identical to sequences in lung (lavage) gp-340, a member of the scavenger receptor cysteine-rich protein family. Immunoblotting with antibodies that specifically recognized either lung gp-340 or the agglutinin confirmed that the salivary agglutinin was gp-340. Immunoblotting with an antibody specific to the sialyl Le(x) carbohydrate epitope detected expression on the salivary but not the lung glycoprotein, possible evidence of different glycoforms. The salivary agglutinin also interacted with Helicobacter pylori, implicated in gastritis and peptic ulcer disease, Streptococcus agalactiae, implicated in neonatal meningitis, and several oral commensal streptococci. These results identify the salivary agglutinin as gp-340 and suggest it binds bacteria that are important determinants of either the oral ecology or systemic diseases.

  16. Implication of scavenger receptors in the interactions between diesel exhaust particles and immature or mature dendritic cells

    Directory of Open Access Journals (Sweden)

    Lassalle Philippe

    2009-03-01

    Full Text Available Abstract Background The exposure to pollutants such as diesel exhaust particles (DEP is associated with an increased incidence of respiratory diseases. However, the mechanisms by which DEP have an effect on human health are not completely understood. In addition to their action on macrophages and airway epithelial cells, DEP also modulate the functions of dendritic cells (DC. These professional antigen-presenting cells are able to discriminate unmodified self from non-self thanks to pattern recognition receptors such as the Toll like Receptors (TLR and Scavenger Receptors (SR. SR were originally identified by their ability to bind and internalize modified lipoproteins and microorganisms but also particles and TLR agonists. In this study, we assessed the implication of SR in the effects of DEP associated or not with TLR agonists on monocyte-derived DC (MDDC. For this, we studied the regulation of CD36, CXCL16, LOX-1, SR-A1 and SR-B1 expression on MDDC treated with DEP associated or not with TLR2, 3 and 4 ligands. Then, the capacity of SR ligands (dextran sulfate and maleylated-ovalbumin to block the effects of DEP on the function of lipopolysaccharide (LPS-activated DC has been evaluated. Results Our data demonstrate that TLR2 agonists mainly augmented CXCL16, LOX-1 and SR-B1 expression whereas DEP alone had only a weak effect. Interestingly, DEP modulated the action of TLR2 and TLR4 ligands on the expression of LOX-1 and SR-B1. Pretreatment with the SR ligand maleylated-ovalbumin but not dextran sulfate inhibited the endocytosis of DEP by MDDC. Moreover, this SR ligand blocked the effect by DEP at low dose (1 μg/ml on MDDC phenotype (a decrease of CD86 and HLA-DR expression and on the secretion of CXCL10, IL-12 and TNF-α. In contrast, the decrease of IL-12 and CXCL10 secretion and the generation of oxygen metabolite induced by DEP at 10 μg/ml was not affected by SR ligands Conclusion Our results show for the first time that the modulation of

  17. The chemokine and scavenger receptor CXCL16/SR-PSOX is expressed in human vascular smooth muscle cells and is induced by interferon γ

    International Nuclear Information System (INIS)

    Wagsaeter, Dick; Olofsson, Peder S.; Norgren, Lars; Stenberg, Bjoern; Sirsjoe, Allan

    2004-01-01

    Atherosclerosis is an inflammatory disease that is characterised by the involvement of chemokines that are important for the recruitment of leukocytes and scavenger receptors that mediate foam cell formation. Several cytokines are involved in the regulation of chemokines and scavenger receptors in atherosclerosis. CXCL16 is a chemokine and scavenger receptor and found in macrophages in human atherosclerotic lesions. Using double-labelled immunohistochemistry, we identified that smooth muscle cells in human lesions express CXCL16. We then analysed the effects of IFN-γ, TNF-α, IL-12, IL-15, IL-18, and LPS on CXCL16 expression in cultured aortic smooth muscle cells. IFN-γ was the most potent CXCL16 inducer and increased mRNA, soluble form, membrane form, and total cellular levels of CXCL16. The IFN-γ induction of CXCL16 was also associated with increased uptake of oxLDL into these cells. Taken together, smooth muscle cells express CXCL16 in atherosclerotic lesions, which may play a role in the attraction of T cells to atherosclerotic lesions and contribute to the cellular internalisation of modified LDL

  18. Scavenger Receptor B1 is a Potential Biomarker of Human Nasopharyngeal Carcinoma and Its Growth is Inhibited by HDL-mimetic Nanoparticles

    Science.gov (United States)

    Zheng, Ying; Liu, Yanyan; Jin, Honglin; Pan, Shaotao; Qian, Yuan; Huang, Chuan; Zeng, Yixin; Luo, Qingming; Zeng, Musheng; Zhang, Zhihong

    2013-01-01

    Nasopharyngeal carcinoma (NPC) is a very regional malignant head and neck cancer that has attracted widespread attention for its unique etiology, epidemiology and therapeutic options. To achieve high cure rates in NPC patients, theranostic approaches are actively being pursued and improved efforts remain desirable in identifying novel biomarkers and establishing effective therapeutic approaches with low long-term toxicities. Here, we discovered that the scavenger receptor class B type I (SR-B1) was overexpressed in all investigated NPC cell lines and 75% of NPC biopsies, demonstrating that SR-B1 is a potential biomarker of NPC. Additional functional analysis showed that SR-B1 has great effect on cell motility while showing no significant impact on cell proliferation. As high-density lipoproteins (HDL) exhibit strong binding affinities to SR-B1 and HDL mimetic peptides are reportedly capable of inhibiting tumor growth, we further examined the SR-B1 targeting ability of a highly biocompatible HDL-mimicking peptide-phospholipid scaffold (HPPS) nanocarrier and investigated its therapeutic effect on NPC. Results show that NPC cells with higher SR-B1 expression have superior ability in taking up the core constituents of HPPS. Moreover, HPPS inhibited the motility and colony formation of 5-8F cells, and significantly suppressed the NPC cell growth in nude mice without inducing tumor cell necrosis or apoptosis. These results indicate that HPPS is not only a NPC-targeting nanocarrier but also an effective anti-NPC drug. Together, the identification of SR-B1 as a potential biomarker and the use of HPPS as an effective anti-NPC agent may shed new light on the diagnosis and therapeutics of NPC. PMID:23843895

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

    Directory of Open Access Journals (Sweden)

    Charlène Blanchet

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

  20. Function of macrophage scavenger receptor 1 gene polymorphisms in chronic obstructive pulmonary disease with and without lung cancer in China.

    Science.gov (United States)

    Xie, Liang; Chen, Wei; Dong, Ran; He, Bin; Zhao, Kaishun; Zhang, Li; Zhou, Min; He, Ping

    2018-05-01

    The present study assessed the association between the variants of macrophage scavenger receptor (MSR)1 and chronic obstructive pulmonary disease (COPD), with or without lung cancer in China. COPD and lung cancer were previously regarded as two separate diseases. However, it has since been reported that there are close associations between COPD and lung cancer. Lung cancer may be an outcome of COPD. COPD may also coexist with lung cancer, and patients with COPD with lung cancer tend to have increased mortality. It is important to have a better understanding of the pathogenesis of COPD and the reason why it develops into lung cancer. MSR1 serves a crucial function in phagocytosis, which may be associated with the pathogenesis of COPD and lung cancer in patients with COPD. From 1 July 2015 to 20 February 2016, 100 patients with COPD and lung cancer, 100 patients with COPD without lung cancer and 100 healthy smokers were enrolled at the Shanghai Ruijin Hospital (Shanghai, China) for the genotyping of eight single-nucleotide polymorphisms (SNPs; ex3P36A_C>G, ex3S41Y_C>A, ex4V113A_T>C, ex4P174Y_G>T, ex6P275A_C>G, ex6R293×_C>T, ex10G369S_G>A and ex11H441R_A>G) via gene sequencing. The genotype frequencies of these SNPs did not significantly differ between patients with COPD with and without lung cancer, and the healthy controls. However, during DNA sequencing, the SNP rs13306550 (IVS4+3A>G) was identified in the splice donor site and was significantly associated with an increased risk of COPD compared with the healthy smokers (P=0.0053). The present study demonstrated that the variant rs13306550 was a risk factor for COPD susceptibility, but that did not influence lung cancer pathogenesis in patients with COPD. However, the mechanisms underlying the influence of rs13306550 on COPD development and progression remain to be elucidated and require further study.

  1. Loss of Function of P2X7 Receptor Scavenger Activity in Aging Mice: A Novel Model for Investigating the Early Pathogenesis of Age-Related Macular Degeneration.

    Science.gov (United States)

    Vessey, Kirstan A; Gu, Ben J; Jobling, Andrew I; Phipps, Joanna A; Greferath, Ursula; Tran, Mai X; Dixon, Michael A; Baird, Paul N; Guymer, Robyn H; Wiley, James S; Fletcher, Erica L

    2017-08-01

    Age-related macular degeneration (AMD) is a leading cause of irreversible, severe vision loss in Western countries. Recently, we identified a novel pathway involving P2X7 receptor scavenger function expressed on ocular immune cells as a risk factor for advanced AMD. In this study, we investigate the effect of loss of P2X7 receptor function on retinal structure and function during aging. P2X7-null and wild-type C57bl6J mice were investigated at 4, 12, and 18 months of age for macrophage phagocytosis activity, ocular histological changes, and retinal function. Phagocytosis activity of blood-borne macrophages decreased with age at 18 months in the wild-type mouse. Lack of P2X7 receptor function reduced phagocytosis at all ages compared to wild-type mice. At 12 months of age, P2X7-null mice had thickening of Bruchs membrane and retinal pigment epithelium dysfunction. By 18 months of age, P2X7-null mice displayed phenotypic characteristics consistent with early AMD, including Bruchs membrane thickening, retinal pigment epithelium cell loss, retinal functional deficits, and signs of subretinal inflammation. Our present study shows that loss of function of the P2X7 receptor in mice induces retinal changes representing characteristics of early AMD, providing a valuable model for investigating the role of scavenger receptor function and the immune system in the development of this age-related disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  2. Identification of the bacteria-binding peptide domain on salivary agglutinin (gp-340/DMBT1), a member of the scavenger receptor cysteine-rich superfamily

    DEFF Research Database (Denmark)

    Bikker, Floris J; Ligtenberg, Antoon J M; Nazmi, Kamran

    2002-01-01

    Salivary agglutinin is encoded by DMBT1 and identical to gp-340, a member of the scavenger receptor cysteine-rich (SRCR) superfamily. Salivary agglutinin/DMBT1 is known for its Streptococcus mutans agglutinating properties. This 300-400 kDa glycoprotein is composed of conserved peptide motifs: 14...... containing exclusively SRCR and SID domains that binds to S. mutans. To define more closely the S. mutans-binding domain, consensus-based peptides of the SRCR domains and SIDs were designed and synthesized. Only one of the SRCR peptides, designated SRCRP2, and none of the SID peptides bound to S. mutans....... Strikingly, this peptide was also able to induce agglutination of S. mutans and a number of other bacteria. The repeated presence of this peptide in the native molecule endows agglutinin/DMBT1 with a general bacterial binding feature with a multivalent character. Moreover, our studies demonstrate...

  3. Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.

    2006-01-01

    We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung...

  4. Role of post-translational modifications on structure, function and pharmacology of class C G protein-coupled receptors

    DEFF Research Database (Denmark)

    Nørskov-Lauritsen, Lenea; Bräuner-Osborne, Hans

    2015-01-01

    taste receptors (T1R1-3), one calcium-sensing (CaS) receptor, one GPCR, class C, group 6, subtype A (GPRC6) receptor, and seven orphan receptors. G protein-coupled receptors undergo a number of post-translational modifications, which regulate their structure, function and/or pharmacology. Here, we...

  5. Host scavenger receptor SR-BI plays a dual role in the establishment of malaria parasite liver infection

    NARCIS (Netherlands)

    Rodrigues, Cristina D.; Hannus, Michael; Prudencio, Miguel; Martin, Cecilie; Goncalves, Ligia A.; Portugal, Silvia; Epiphanio, Sabrina; Akinc, Akin; Hadwiger, Philipp; Jahn-Hofmann, Kerstin; Roehl, Ingo; van Gemert, Geert-Jan; Franetich, Jean-Francois; Luty, Adrian J. F.; Sauerwein, Robert; Mazier, Dominique; Koteliansky, Victor; Vornlocher, Hans-Peter; Echeverri, Christophe J.; Mota, Maria M.

    2008-01-01

    An obligatory step of malaria parasite infection is Plasmodium sporozoite invasion of host hepatocytes, and host lipoprotein clearance pathways have been linked to Plasmodium liver infection. By using RNA interference to screen lipoprotein-related host factors, we show here that the class B, type I

  6. The Scavenger Receptor SSc5D Physically Interacts with Bacteria through the SRCR-Containing N-Terminal Domain

    Czech Academy of Sciences Publication Activity Database

    Pereira, C.B.; Bocková, Markéta; Santos, R.F.; Santos, A. M.; de Araujo, M.M.; Oliveira, L.; Homola, Jiří; Carmo, A.M.

    2016-01-01

    Roč. 7, October (2016), č. článku 416. ISSN 1664-3224 R&D Projects: GA ČR(CZ) GBP205/12/G118 Grant - others:AV ČR(CZ) AP1101 Program:Akademická prémie - Praemium Academiae Institutional support: RVO:67985882 Keywords : Pattern recognition receptors * Bacteria * Surface plasmon resonance Subject RIV: BH - Optics, Masers, Lasers Impact factor: 6.429, year: 2016

  7. Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

    Science.gov (United States)

    Khan, Muhammad Zahid; He, Ling

    2017-04-01

    In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

  8. Oxidised LDL internalisation by the LOX-1 scavenger receptor is dependent on a novel cytoplasmic motif and is regulated by dynamin-2.

    Science.gov (United States)

    Murphy, Jane E; Vohra, Ravinder S; Dunn, Sarah; Holloway, Zoe G; Monaco, Anthony P; Homer-Vanniasinkam, Shervanthi; Walker, John H; Ponnambalam, Sreenivasan

    2008-07-01

    The LOX-1 scavenger receptor recognises pro-atherogenic oxidised low-density lipoprotein (OxLDL) particles and is implicated in atherosclerotic plaque formation, but this mechanism is not well understood. Here we show evidence for a novel clathrin-independent and cytosolic-signal-dependent pathway that regulates LOX-1-mediated OxLDL internalisation. Cell surface labelling in the absence or presence of OxLDL ligand showed that LOX-1 is constitutively internalised from the plasma membrane and its half-life is not altered upon ligand binding and trafficking. We show that LOX-1-mediated OxLDL uptake is disrupted by overexpression of dominant-negative dynamin-2 but unaffected by CHC17 or mu2 (AP2) depletion. Site-directed mutagenesis revealed a conserved and novel cytoplasmic tripeptide motif (DDL) that regulates LOX-1-mediated endocytosis of OxLDL. Taken together, these findings indicate that LOX-1 is internalised by a clathrin-independent and dynamin-2-dependent pathway and is thus likely to mediate OxLDL trafficking in vascular tissues.

  9. Artesunate Reduces Serum Lipopolysaccharide in Cecal Ligation/Puncture Mice via Enhanced LPS Internalization by Macrophages through Increased mRNA Expression of Scavenger Receptors

    Directory of Open Access Journals (Sweden)

    Bin Li

    2014-01-01

    Full Text Available Innate immunity is the first line of defense in human beings against pathogen infection; monocytes/macrophages are the primary cells of the innate immune system. Recently, macrophages/monocytes have been discovered to participate in LPS clearance, and the clearance efficiency determines the magnitude of the inflammatory response and subsequent organ injury. Previously, we reported that artesunate (AS protected sepsis mice against heat-killed E. coli challenge. Herein, we further confirmed that AS protected cecal ligation/puncture (CLP sepsis mice. Its protection on sepsis mice was related to not only reduction of pro-inflammatory cytokines and serum LPS levels but also improvement of liver function. Based on the fact that AS did not directly bind and neutralize LPS, we hypothesized that the reduction of serum LPS level might be related to enhancement of LPS internalization and subsequent detoxification. Our results showed that AS increased FITC-LPS internalization by peritoneal macrophage and liver Kupffer cell, but enhancement of LPS internalization by AS was not related to the clathrin-dependent pathway. However, AS induced mRNA expression of important scavenger receptors (SRs; SR-A and MARCO mRNA expression was upregulated, suggesting that AS enhancement of LPS internalization and inhibition of pro-inflammatory cytokines was related to changes in mRNA expression of SRs.

  10. Extra-epitopic hepatitis C virus polymorphisms confer resistance to broadly neutralizing antibodies by modulating binding to scavenger receptor B1.

    Science.gov (United States)

    El-Diwany, Ramy; Cohen, Valerie J; Mankowski, Madeleine C; Wasilewski, Lisa N; Brady, Jillian K; Snider, Anna E; Osburn, William O; Murrell, Ben; Ray, Stuart C; Bailey, Justin R

    2017-02-01

    Broadly-neutralizing monoclonal antibodies (bNAbs) may guide vaccine development for highly variable viruses including hepatitis C virus (HCV), since they target conserved viral epitopes that could serve as vaccine antigens. However, HCV resistance to bNAbs could reduce the efficacy of a vaccine. HC33.4 and AR4A are two of the most potent anti-HCV human bNAbs characterized to date, binding to highly conserved epitopes near the amino- and carboxy-terminus of HCV envelope (E2) protein, respectively. Given their distinct epitopes, it was surprising that these bNAbs showed similar neutralization profiles across a panel of natural HCV isolates, suggesting that some viral polymorphisms may confer resistance to both bNAbs. To investigate this resistance, we developed a large, diverse panel of natural HCV envelope variants and a novel computational method to identify bNAb resistance polymorphisms in envelope proteins (E1 and E2). By measuring neutralization of a panel of HCV pseudoparticles by 10 μg/mL of each bNAb, we identified E1E2 variants with resistance to one or both bNAbs, despite 100% conservation of the AR4A binding epitope across the panel. We discovered polymorphisms outside of either binding epitope that modulate resistance to both bNAbs by altering E2 binding to the HCV co-receptor, scavenger receptor B1 (SR-B1). This study is focused on a mode of neutralization escape not addressed by conventional analysis of epitope conservation, highlighting the contribution of extra-epitopic polymorphisms to bNAb resistance and presenting a novel mechanism by which HCV might persist even in the face of an antibody response targeting multiple conserved epitopes.

  11. Structural–Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work

    Directory of Open Access Journals (Sweden)

    Gerd Krause

    2017-04-01

    Full Text Available The thyroid-stimulating hormone receptor (TSHR is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs. TSHR and its endogenous ligand thyrotropin (TSH are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016 concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other

  12. Structural-Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work.

    Science.gov (United States)

    Kleinau, Gunnar; Worth, Catherine L; Kreuchwig, Annika; Biebermann, Heike; Marcinkowski, Patrick; Scheerer, Patrick; Krause, Gerd

    2017-01-01

    The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to

  13. Structural–Functional Features of the Thyrotropin Receptor: A Class A G-Protein-Coupled Receptor at Work

    Science.gov (United States)

    Kleinau, Gunnar; Worth, Catherine L.; Kreuchwig, Annika; Biebermann, Heike; Marcinkowski, Patrick; Scheerer, Patrick; Krause, Gerd

    2017-01-01

    The thyroid-stimulating hormone receptor (TSHR) is a member of the glycoprotein hormone receptors, a sub-group of class A G-protein-coupled receptors (GPCRs). TSHR and its endogenous ligand thyrotropin (TSH) are of essential importance for growth and function of the thyroid gland and proper function of the TSH/TSHR system is pivotal for production and release of thyroid hormones. This receptor is also important with respect to pathophysiology, such as autoimmune (including ophthalmopathy) or non-autoimmune thyroid dysfunctions and cancer development. Pharmacological interventions directly targeting the TSHR should provide benefits to disease treatment compared to currently available therapies of dysfunctions associated with the TSHR or the thyroid gland. Upon TSHR activation, the molecular events conveying conformational changes from the extra- to the intracellular side of the cell across the membrane comprise reception, conversion, and amplification of the signal. These steps are highly dependent on structural features of this receptor and its intermolecular interaction partners, e.g., TSH, antibodies, small molecules, G-proteins, or arrestin. For better understanding of signal transduction, pathogenic mechanisms such as autoantibody action and mutational modifications or for developing new pharmacological strategies, it is essential to combine available structural data with functional information to generate homology models of the entire receptor. Although so far these insights are fragmental, in the past few decades essential contributions have been made to investigate in-depth the involved determinants, such as by structure determination via X-ray crystallography. This review summarizes available knowledge (as of December 2016) concerning the TSHR protein structure, associated functional aspects, and based on these insights we suggest several receptor complex models. Moreover, distinct TSHR properties will be highlighted in comparison to other class A GPCRs to

  14. Differential Requirement of the Extracellular Domain in Activation of Class B G Protein-coupled Receptors.

    Science.gov (United States)

    Zhao, Li-Hua; Yin, Yanting; Yang, Dehua; Liu, Bo; Hou, Li; Wang, Xiaoxi; Pal, Kuntal; Jiang, Yi; Feng, Yang; Cai, Xiaoqing; Dai, Antao; Liu, Mingyao; Wang, Ming-Wei; Melcher, Karsten; Xu, H Eric

    2016-07-15

    G protein-coupled receptors (GPCRs) from the secretin-like (class B) family are key players in hormonal homeostasis and are important drug targets for the treatment of metabolic disorders and neuronal diseases. They consist of a large N-terminal extracellular domain (ECD) and a transmembrane domain (TMD) with the GPCR signature of seven transmembrane helices. Class B GPCRs are activated by peptide hormones with their C termini bound to the receptor ECD and their N termini bound to the TMD. It is thought that the ECD functions as an affinity trap to bind and localize the hormone to the receptor. This in turn would allow the hormone N terminus to insert into the TMD and induce conformational changes of the TMD to activate downstream signaling. In contrast to this prevailing model, we demonstrate that human class B GPCRs vary widely in their requirement of the ECD for activation. In one group, represented by corticotrophin-releasing factor receptor 1 (CRF1R), parathyroid hormone receptor (PTH1R), and pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1R), the ECD requirement for high affinity hormone binding can be bypassed by induced proximity and mass action effects, whereas in the other group, represented by glucagon receptor (GCGR) and glucagon-like peptide-1 receptor (GLP-1R), the ECD is required for signaling even when the hormone is covalently linked to the TMD. Furthermore, the activation of GLP-1R by small molecules that interact with the intracellular side of the receptor is dependent on the presence of its ECD, suggesting a direct role of the ECD in GLP-1R activation. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. New insights into the structure of Class B G protein-coupled receptors

    NARCIS (Netherlands)

    Hollenstein, H.; de Graaf, C.; Bortolato, A.; Wang, M-W; Marshall, F.; Stevens, R.C.

    2014-01-01

    The secretin-like (class B) family of G protein-coupled receptors (GPCRs) are key players in hormonal homeostasis and are interesting drug targets for the treatment of several metabolic disorders (such as type 2 diabetes, osteoporosis, and obesity) and nervous system diseases (such as migraine,

  16. Low Density Lipoprotein Receptor Class A Repeats Are O-Glycosylated in Linker Regions

    DEFF Research Database (Denmark)

    Pedersen, Nis Borbye; Wang, Shengjun; Narimatsu, Yoshiki

    2014-01-01

    , which in wild-type CHO cells is glycosylated with the typical sialylated core 1 structure. The glycosites in linker regions of LDLR class A repeats are conserved in LDLR from man to Xenopus and found in other homologous receptors. O-Glycosylation is controlled by a large family of polypeptide Gal...

  17. The G protein-coupled receptor, class C, group 6, subtype A (GPRC6A) receptor

    DEFF Research Database (Denmark)

    Clemmensen, C; Smajilovic, S; Wellendorph, P

    2014-01-01

    the physiological concentration in most tissues. More recently, the peptide osteocalcin and the steroid testosterone have also been suggested to be endogenous GPRC6A agonists. The receptor is widely expressed in all three species which, along with the omnipresence of the amino acids and divalent cation ligands...

  18. The VPAC1 receptor: structure and function of a class B GPCR prototype

    Directory of Open Access Journals (Sweden)

    Alain eCouvineau

    2012-11-01

    Full Text Available The class B G protein-coupled receptors (GPCRs represents a small sub-family encompassing 15 members, and are very promising targets for the development of drugs to treat many diseases such as chronic inflammation, neurodegeneration, diabetes, stress and osteoporosis. The VPAC1 receptor which is an archetype of the class B GPCRs binds Vasoactive Intestinal Peptide (VIP, a neuropeptide widely distributed in central and peripheral nervous system modulating many physiological processes including regulation of exocrine secretions, hormone release, foetal development, immune response... VIP appears to exert beneficial effect in neuro-degenerative and inflammatory diseases. This article reviews the current knowledge regarding the structure and molecular pharmacology of VPAC1 receptors. Over the past decade, structure-function relationship studies have demonstrated that the N-terminal ectodomain (N-ted of VPAC1 plays a pivotal role in VIP recognition. The use of different approaches such as directed mutagenesis, photoaffinity labeling, Nuclear Magnetic Resonance (NMR, molecular modeling and molecular dynamic simulation has led to demonstrate that: i the central and C-terminal part of the VIP molecule interacts with the N-ted of VPAC1 receptor which is itself structured as a « Sushi » domain; ii the N-terminal end of the VIP molecule interacts with the first transmembrane domain of the receptor where three residues (K143, T144 and T147 play an important role in VPAC1 interaction with the first histidine residue of VIP.

  19. Peroxynitrite scavenging by flavonids.

    NARCIS (Netherlands)

    Haenen, G.R.M.M.; Paquay, J.B.G.; Korthouwer, R.E.M.; Bast, A.

    1997-01-01

    The peroxynitrite scavenging activity of a series of structurally related flavonoids was tested. It was found that flavonoids are excellent scavengers of peroxynitrite. Compared to the known peroxynitrite scavenger ebselen, the most active flavonoids proved to be 10 times more effective. Indications

  20. New functions and signaling mechanisms for the class of adhesion G protein-coupled receptors

    DEFF Research Database (Denmark)

    Liebscher, Ines; Ackley, Brian; Araç, Demet

    2014-01-01

    The class of adhesion G protein-coupled receptors (aGPCRs), with 33 human homologs, is the second largest family of GPCRs. In addition to a seven-transmembrane α-helix-a structural feature of all GPCRs-the class of aGPCRs is characterized by the presence of a large N-terminal extracellular region....... In addition, all aGPCRs but one (GPR123) contain a GPCR autoproteolysis-inducing (GAIN) domain that mediates autoproteolytic cleavage at the GPCR autoproteolysis site motif to generate N- and a C-terminal fragments (NTF and CTF, respectively) during protein maturation. Subsequently, the NTF and CTF...

  1. Serum levels of TWEAK and scavenger receptor CD163 in type 1 diabetes mellitus: relationship with cardiovascular risk factors. a case-control study.

    Directory of Open Access Journals (Sweden)

    Gemma Llauradó

    Full Text Available OBJECTIVE: To test the usefulness of serum concentrations of tumor necrosis factor-like weak inducer of apoptosis (sTWEAK and soluble scavenger receptor CD163 (sCD163 as markers of subtle inflammation in patients with type 1 diabetes mellitus (T1DM without clinical cardiovascular (CV disease and to evaluate their relationship with arterial stiffness (AS. METHODS: Sixty-eight patients with T1DM and 68 age and sex-matched, healthy subjects were evaluated. Anthropometrical variables and CV risk factors were recorded. Serum concentrations of sTWEAK and sCD163 were measured. AS was assessed by aortic pulse wave velocity (aPWV. All statistical analyses were stratified by gender. RESULTS: T1DM patients showed lower serum concentrations of sTWEAK (Men: 1636.5 (1146.3-3754.8 pg/mL vs. 765.9 (650.4-1097.1 pg/mL; p<0.001. Women: 1401.0 (788.0-2422.2 pg/mL vs. 830.1 (562.6-1175.9 pg/mL; p = 0.011 compared with their respective controls. Additionally, T1DM men had higher serum concentrations of sCD163 (285.0 (247.7-357.1 ng/mL vs. 224.8 (193.3-296.5 ng/mL; p = 0.012 compared with their respective controls. sTWEAK correlated negatively with aPWV in men (r = -0.443; p<0.001. However, this association disappeared after adjusting for potential confounders. In men, the best multiple linear regression model showed that the independent predictors of sTWEAK were T1DM and WHR (R(2 = 0.640; p<0.001. In women, T1DM and SBP were the independent predictors for sTWEAK (R(2 = 0.231; p = 0.001. CONCLUSION: sTWEAK is decreased in T1DM patients compared with age and sex-matched healthy subjects after adjusting for classic CV risk factors, although sTWEAK levels may be partially influenced by some of them. Additionally, T1DM men have higher serum concentrations of sCD163. These results point out an association between the inflammatory system and CV risk in T1DM.

  2. H pylori receptor MHC class II contributes to the dynamic gastric epithelial apoptotic response

    Science.gov (United States)

    Bland, David A; Suarez, Giovanni; Beswick, Ellen J; Sierra, Johanna C; Reyes, Victor E

    2006-01-01

    AIM: To investigate the role of MHC class II in the modulation of gastric epithelial cell apoptosis induced by H pylori infection. METHODS: After stimulating a human gastric epithelial cell line with bacteria or agonist antibodies specific for MHC class II and CD95, the quantitation of apoptotic and anti-apoptotic events, including caspase activation, BCL-2 activation, and FADD recruitment, was performed with a fluorometric assay, a cytometric bead array, and confocal microscopy, respectively. RESULTS: Pretreatment of N87 cells with the anti-MHC class II IgM antibody RFD1 resulted in a reduction in global caspase activation at 24 h of H pylori infection. When caspase 3 activation was specifically measured, crosslinking of MHC class II resulted in a marked reduced caspase activation, while simple ligation of MHC class II did not. Crosslinking of MHC class II also resulted in an increased activation of the anti-apoptosis molecule BCL-2 compared to simple ligation. Confocal microscope analysis demonstrated that the pretreatment of gastric epithelial cells with a crosslinking anti-MHC class II IgM blocked the recruitment of FADD to the cell surface. CONCLUSION: The results presented here demonstrate that the ability of MHC class II to modulate gastric epithelial apoptosis is at least partially dependent on its crosslinking. Furthermore, while previous research has demonstrated that MHC class II signaling can be pro-apoptotic during extended ligation, we have shown that the crosslinking of this molecule has anti-apoptotic effects during the earlier time points of H pylori infection. This effect is possibly mediated by the ability of MHC class II to modulate the activation of the pro-apoptotic receptor Fas by blocking the recruitment of the accessory molecule FADD, and this delay in apoptosis induction could allow for prolonged cytokine secretion by H pylori-infected gastric epithelial cells. PMID:16981259

  3. Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes.

    Directory of Open Access Journals (Sweden)

    Elise Courtot

    2015-12-01

    Full Text Available Acetylcholine receptors are pentameric ligand-gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, acr-26 and acr-27 that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, Haemonchus contortus, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in Xenopus laevis oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, Parascaris equorum, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In Caenorhabditis elegans, a free-living model nematode, we demonstrated that heterologous expression of the H. contortus and P. equorum receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in Xenopus oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR.

  4. Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes

    Science.gov (United States)

    Courtot, Elise; Charvet, Claude L.; Beech, Robin N.; Harmache, Abdallah; Wolstenholme, Adrian J.; Holden-Dye, Lindy; O’Connor, Vincent; Peineau, Nicolas; Woods, Debra J.; Neveu, Cedric

    2015-01-01

    Acetylcholine receptors are pentameric ligand–gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, acr-26 and acr-27 that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, Haemonchus contortus, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in Xenopus laevis oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, Parascaris equorum, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In Caenorhabditis elegans, a free-living model nematode, we demonstrated that heterologous expression of the H. contortus and P. equorum receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in Xenopus oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR. PMID:26625142

  5. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Directory of Open Access Journals (Sweden)

    Adam L Martin

    Full Text Available The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1 200% elevation over baseline reporter gene expression; 2 40% inhibition of baseline expression; and 3 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1 inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176; 2 no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119; 3 elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12; 4 elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65; and 5 no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87. Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40. This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65% than stimulation of expression (15%. Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  6. Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

    Science.gov (United States)

    Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

    2015-01-01

    The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.

  7. Differential effect on TCR:CD3 stimulation of a 90-kD glycoprotein (gp90/Mac-2BP), a member of the scavenger receptor cysteine-rich domain protein family

    DEFF Research Database (Denmark)

    Silvestri, B; Calderazzo, F; Coppola, V

    1998-01-01

    We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non-specific ......We studied the effects of a 90-kD glycoprotein (gp90/Mac-2BP) belonging to the scavenger receptor family, present in normal serum and at increased levels in inflammatory disease and cancer patients, on some T cell function parameters. Whereas the lymphocyte proliferative response to non......-specific mitogens such as phytohaemagglutinin (PHA) and concanavalin A (Con A), but not pokeweed mitogen (PWM), was strongly reduced, probably due to the lectin-binding properties of gp90/Mac-2BP, the response to T cell receptor (TCR) agonists such as superantigens and allogeneic cells was potentiated. When...... lymphocytes were stimulated with different anti-TCR:CD3 MoAbs, both in soluble and solid-phase form, gp90/Mac-2BP was able to down-regulate the proliferative response to anti-CD3 MoAb, whereas the response to anti-TCR alphabeta MoAb was enhanced. A similar differential effect was observed when a MoAb against...

  8. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    Science.gov (United States)

    Corin, Karolina; Baaske, Philipp; Ravel, Deepali B; Song, Junyao; Brown, Emily; Wang, Xiaoqiang; Wienken, Christoph J; Jerabek-Willemsen, Moran; Duhr, Stefan; Luo, Yuan; Braun, Dieter; Zhang, Shuguang

    2011-01-01

    A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  9. Designer lipid-like peptides: a class of detergents for studying functional olfactory receptors using commercial cell-free systems.

    Directory of Open Access Journals (Sweden)

    Karolina Corin

    Full Text Available A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.

  10. Leukocyte Ig-Like Receptors – a model for MHC class I disease associations

    Directory of Open Access Journals (Sweden)

    Rachel Louise Allen

    2016-07-01

    Full Text Available MHC class I (MHC-I polymorphisms are associated with the outcome of some viral infections and autoimmune diseases. MHC-I proteins present antigenic peptides and are recognised by receptors on Natural Killer cells and Cytotoxic T lymphocytes, thus enabling the immune system to detect self-antigens and eliminate targets lacking self or expressing foreign antigens. Recognition of MHC-I, however, extends beyond receptors on cytotoxic leukocytes. Members of the Leukocyte Ig-like receptor (LILR family are expressed on monocytic cells and can recognise both classical and non-classical MHC-I alleles. Despite their relatively broad specificity when compared to the T Cell Receptor or Killer Ig-like Receptors, variations in the strength of LILR binding between different MHC-I alleles have recently been shown to correlate with control of HIV infection. We suggest that LILR recognition may mediate MHC-I disease association in a manner that does not depend on a binary discrimination of self/non-self by cytotoxic cells. Instead, the effects of LILR activity following engagement by MHC-I may represent a degrees of self model, whereby strength of binding to different alleles determines the degree of influence exerted by these receptors on immune cell functions. LILR are expressed by myelomonocytic cells and lymphocytes, extending their influence across antigen presenting cell subsets including dendritic cells, macrophages and B cells. They have been identified as important players in the response to infection, inflammatory diseases and cancer, with recent literature to indicate that MHC-I recognition by these receptors and consequent allelic effects could extend an influence beyond the immune system.

  11. Probing natural killer cell education by Ly49 receptor expression analysis and computational modelling in single MHC class I mice.

    Directory of Open Access Journals (Sweden)

    Sofia Johansson

    Full Text Available Murine natural killer (NK cells express inhibitory Ly49 receptors for MHC class I molecules, which allows for "missing self" recognition of cells that downregulate MHC class I expression. During murine NK cell development, host MHC class I molecules impose an "educating impact" on the NK cell pool. As a result, mice with different MHC class I expression display different frequency distributions of Ly49 receptor combinations on NK cells. Two models have been put forward to explain this impact. The two-step selection model proposes a stochastic Ly49 receptor expression followed by selection for NK cells expressing appropriate receptor combinations. The sequential model, on the other hand, proposes that each NK cell sequentially expresses Ly49 receptors until an interaction of sufficient magnitude with self-class I MHC is reached for the NK cell to mature. With the aim to clarify which one of these models is most likely to reflect the actual biological process, we simulated the two educational schemes by mathematical modelling, and fitted the results to Ly49 expression patterns, which were analyzed in mice expressing single MHC class I molecules. Our results favour the two-step selection model over the sequential model. Furthermore, the MHC class I environment favoured maturation of NK cells expressing one or a few self receptors, suggesting a possible step of positive selection in NK cell education. Based on the predicted Ly49 binding preferences revealed by the model, we also propose, that Ly49 receptors are more promiscuous than previously thought in their interactions with MHC class I molecules, which was supported by functional studies of NK cell subsets expressing individual Ly49 receptors.

  12. Glucagon-like peptide-1 and its class B G Protein-coupled receptors: A long march to therapeutic successes.

    NARCIS (Netherlands)

    de Graaf, C.; Donnely, D.; Wootten, D.; Lau, J.; Sexton, P.M.; Miller, L.J.; Ahn, J.M.; Liao, J.; Fletcher, M.M.; Yang, D.; Brown, A.J.; Zhou, C.; Deng, J.; Wang, M.W.

    2016-01-01

    Theglucagon-likepeptide (GLP)-1receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secretedfromthreemajor tissues inhumans,enteroendocrine L cells in the distal intestine, a cells in the pancreas, and the central nervous system, which

  13. Botanical Scavenger Hunt

    Science.gov (United States)

    Walker-Livingston, Wendy

    2009-01-01

    Why not combine the use of technology with the excitement of a scavenger hunt that moves middle-level students out into the "wilds" of their school campus to classify plants? In the lesson plan described here, students embark on a botanical scavenger hunt and then document their findings using a digital camera. This project was designed to allow…

  14. The scavenger activity of the human P2X7 receptor differs from P2X7 pore function by insensitivity to antagonists, genetic variation and sodium concentration: Relevance to inflammatory brain diseases.

    Science.gov (United States)

    Ou, Amber; Gu, Ben J; Wiley, James S

    2018-04-01

    Activation of P2X7 receptors is widely recognised to initiate proinflammatory responses. However P2X7 also has a dual function as a scavenger receptor which is active in the absence of ATP and plasma proteins and may be important in central nervous system (CNS) diseases. Here, we investigated both P2X7 pore formation and its phagocytic function in fresh human monocytes (as a model of microglia) by measuring ATP-induced ethidium dye uptake and fluorescent bead uptake respectively. This was studied in monocytes expressing various polymorphic variants as well as in the presence of different P2X7 antagonists and ionic media. P2X7-mediated phagocytosis was found to account for about half of Latrunculin (or Cytochalasin D)-sensitive bead engulfment by fresh human monocytes. Monocytes harbouring P2X7 Ala348Thr or Glu496Ala polymorphic variants showed increase or loss of ethidium uptake respectively, but these changes in pore formation did not always correspond to the changes in phagocytosis of YG beads. Unlike pore function, P2X7-mediated phagocytosis was not affected by three potent selective P2X7 antagonists and remained identical in Na + and K + media. Taken together, our results show that P2X7 is a scavenger receptor with important function in the CNS but its phagocytic function has features distinct from its pore function. Both P2X7 pore formation and P2X7-mediated phagocytosis should be considered in the design of new P2X7 antagonists for the treatment of CNS diseases. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Representation Learning for Class C G Protein-Coupled Receptors Classification

    Directory of Open Access Journals (Sweden)

    Raúl Cruz-Barbosa

    2018-03-01

    Full Text Available G protein-coupled receptors (GPCRs are integral cell membrane proteins of relevance for pharmacology. The complete tertiary structure including both extracellular and transmembrane domains has not been determined for any member of class C GPCRs. An alternative way to work on GPCR structural models is the investigation of their functionality through the analysis of their primary structure. For this, sequence representation is a key factor for the GPCRs’ classification context, where usually, feature engineering is carried out. In this paper, we propose the use of representation learning to acquire the features that best represent the class C GPCR sequences and at the same time to obtain a model for classification automatically. Deep learning methods in conjunction with amino acid physicochemical property indices are then used for this purpose. Experimental results assessed by the classification accuracy, Matthews’ correlation coefficient and the balanced error rate show that using a hydrophobicity index and a restricted Boltzmann machine (RBM can achieve performance results (accuracy of 92.9% similar to those reported in the literature. As a second proposal, we combine two or more physicochemical property indices instead of only one as the input for a deep architecture in order to add information from the sequences. Experimental results show that using three hydrophobicity-related index combinations helps to improve the classification performance (accuracy of 94.1% of an RBM better than those reported in the literature for class C GPCRs without using feature selection methods.

  16. Blood Glutamate Scavenging: Insight into Neuroprotection

    Directory of Open Access Journals (Sweden)

    Alexander Zlotnik

    2012-08-01

    Full Text Available Brain insults are characterized by a multitude of complex processes, of which glutamate release plays a major role. Deleterious excess of glutamate in the brain’s extracellular fluids stimulates glutamate receptors, which in turn lead to cell swelling, apoptosis, and neuronal death. These exacerbate neurological outcome. Approaches aimed at antagonizing the astrocytic and glial glutamate receptors have failed to demonstrate clinical benefit. Alternatively, eliminating excess glutamate from brain interstitial fluids by making use of the naturally occurring brain-to-blood glutamate efflux has been shown to be effective in various animal studies. This is facilitated by gradient driven transport across brain capillary endothelial glutamate transporters. Blood glutamate scavengers enhance this naturally occurring mechanism by reducing the blood glutamate concentration, thus increasing the rate at which excess glutamate is cleared. Blood glutamate scavenging is achieved by several mechanisms including: catalyzation of the enzymatic process involved in glutamate metabolism, redistribution of glutamate into tissue, and acute stress response. Regardless of the mechanism involved, decreased blood glutamate concentration is associated with improved neurological outcome. This review focuses on the physiological, mechanistic and clinical roles of blood glutamate scavenging, particularly in the context of acute and chronic CNS injury. We discuss the details of brain-to-blood glutamate efflux, auto-regulation mechanisms of blood glutamate, natural and exogenous blood glutamate scavenging systems, and redistribution of glutamate. We then propose different applied methodologies to reduce blood and brain glutamate concentrations and discuss the neuroprotective role of blood glutamate scavenging.

  17. Cloning and expression of a cDNA coding for the human platelet-derived growth factor receptor: Evidence for more than one receptor class

    International Nuclear Information System (INIS)

    Gronwald, R.G.K.; Grant, F.J.; Haldeman, B.A.; Hart, C.E.; O'Hara, P.J.; Hagen, F.S.; Ross, R.; Bowen-Pope, D.F.; Murray, M.J.

    1988-01-01

    The complete nucleotide sequence of a cDNA encoding the human platelet-derived growth factor (PDGF) receptor is presented. The cDNA contains an open reading frame that codes for a protein of 1106 amino acids. Comparison to the mouse PDGF receptor reveals an overall amino acid sequence identity of 86%. This sequence identity rises to 98% in the cytoplasmic split tyrosine kinase domain. RNA blot hybridization analysis of poly(A) + RNA from human dermal fibroblasts detects a major and a minor transcript using the cDNA as a probe. Baby hamster kidney cells, transfected with an expression vector containing the receptor cDNA, express an ∼ 190-kDa cell surface protein that is recognized by an anti-human PDGF receptor antibody. The recombinant PDGF receptor is functional in the transfected baby hamster kidney cells as demonstrated by ligand-induced phosphorylation of the receptor. Binding properties of the recombinant PDGF receptor were also assessed with pure preparations of BB and AB isoforms of PDGF. Unlike human dermal fibroblasts, which bind both isoforms with high affinity, the transfected baby hamster kidney cells bind only the BB isoform of PDGF with high affinity. This observation is consistent with the existence of more than one PDGF receptor class

  18. Towards a Novel Class of Multitarget-Directed Ligands: Dual P2X7–NMDA Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Olga Karoutzou

    2018-01-01

    Full Text Available Multi-target-directed ligands (MTDLs offer new hope for the treatment of multifactorial complex diseases such as Alzheimer’s Disease (AD. Herein, we present compounds aimed at targeting the NMDA and the P2X7 receptors, which embody a different approach to AD therapy. On one hand, we are seeking to delay neurodegeneration targeting the glutamatergic NMDA receptors; on the other hand, we also aim to reduce neuroinflammation, targeting P2X7 receptors. Although the NMDA receptor is a widely recognized therapeutic target in treating AD, the P2X7 receptor remains largely unexplored for this purpose; therefore, the dual inhibitor presented herein—which is open to further optimization—represents the first member of a new class of MTDLs.

  19. Genetic Variation in the Scavenger Receptor MARCO and Its Association with Chronic Obstructive Pulmonary Disease and Lung Infection in 10,604 Individuals

    DEFF Research Database (Denmark)

    Thomsen, Mette; Nordestgaard, Børge G; Kobzik, Lester

    2013-01-01

    Background: MARCO (macrophage receptor with collagenous structure) is a dominant receptor for unopsonized particles and bacteria in the lungs. Reduced function of this receptor due to genetic variation may be associated with susceptibility to chronic obstructive pulmonary disease (COPD) and lung...... infection. Objectives: To identify novel genetic variants in MARCO that are associated with reduced lung function, or increased risk of COPD or lung infection. Methods: We first screened 760 individuals with extreme lung phenotypes in a large general population study to identify novel variants in the MARCO...... the entire cohort for these variants, we found low minor allele frequencies ranging from 0.005 to 5%. None of the individual MARCO genotypes were associated with reduced lung function, or risk of COPD or lung infection. H101Q heterozygotes had an increased odds ratio for sepsis of 2.2 (95% CI: 1...

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

  1. A Geospatial Scavenger Hunt

    Science.gov (United States)

    Martinez, Adriana E.; Williams, Nikki A.; Metoyer, Sandra K.; Morris, Jennifer N.; Berhane, Stephen A.

    2009-01-01

    With the use of technology such as Global Positioning System (GPS) units and Google Earth for a simple-machine scavenger hunt, you will transform a standard identification activity into an exciting learning experience that motivates students, incorporates practical skills in technology, and enhances students' spatial-thinking skills. In the…

  2. Association analysis of class II cytokine and receptor genes in vitiligo patients.

    Science.gov (United States)

    Traks, Tanel; Karelson, Maire; Reimann, Ene; Rätsep, Ranno; Silm, Helgi; Vasar, Eero; Kõks, Sulev; Kingo, Külli

    2016-05-01

    The loss of melanocytes in vitiligo is mainly attributed to defective autoimmune mechanisms and lately autoinflammatory mediators have become more emphasized. Among these, a number of class II cytokines and their receptors have displayed altered expression patterns in vitiligo. Thus, we selected 30 SNPs from the regions of respective genes to be genotyped in Estonian case-control sample (109 and 328 individuals, respectively). For more precise analyses, patients were divided into subgroups based on vitiligo progression activity, age of onset, sex, occurrence of vitiligo among relatives, extent of depigmented areas, appearance of Köbner's phenomenon, existence of halo nevi, occurrence of spontaneous repigmentation, and amount of thyroid peroxidase antibodies. No associations appeared in whole vitiligo group. In subgroups, several allelic and haplotype associations were found. The strongest involved SNPs rs12301088 (near IL26 gene), that was associated with familial vitiligo and existence of halo nevi, and rs2257167 (IFNAR1 gene), that was associated with female vitiligo. Additionally, haplotypes consisting of rs12301088 and rs12321603 alleles (IL26-IL22 genes), that were associated with familial vitiligo and existence of halo nevi. In conclusion, several genetic associations with vitiligo subphenotypes were revealed and functional explanations to these remain to be determined in respective studies. Copyright © 2016. Published by Elsevier Inc.

  3. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors

    Science.gov (United States)

    Yin, Yanting; de Waal, Parker W.; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H. Eric

    2017-01-01

    The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β2-adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. PMID:28356352

  4. Rearrangement of a polar core provides a conserved mechanism for constitutive activation of class B G protein-coupled receptors.

    Science.gov (United States)

    Yin, Yanting; de Waal, Parker W; He, Yuanzheng; Zhao, Li-Hua; Yang, Dehua; Cai, Xiaoqing; Jiang, Yi; Melcher, Karsten; Wang, Ming-Wei; Xu, H Eric

    2017-06-16

    The glucagon receptor (GCGR) belongs to the secretin-like (class B) family of G protein-coupled receptors (GPCRs) and is activated by the peptide hormone glucagon. The structures of an activated class B GPCR have remained unsolved, preventing a mechanistic understanding of how these receptors are activated. Using a combination of structural modeling and mutagenesis studies, we present here two modes of ligand-independent activation of GCGR. First, we identified a GCGR-specific hydrophobic lock comprising Met-338 and Phe-345 within the IC3 loop and transmembrane helix 6 (TM6) and found that this lock stabilizes the TM6 helix in the inactive conformation. Disruption of this hydrophobic lock led to constitutive G protein and arrestin signaling. Second, we discovered a polar core comprising conserved residues in TM2, TM3, TM6, and TM7, and mutations that disrupt this polar core led to constitutive GCGR activity. On the basis of these results, we propose a mechanistic model of GCGR activation in which TM6 is held in an inactive conformation by the conserved polar core and the hydrophobic lock. Mutations that disrupt these inhibitory elements allow TM6 to swing outward to adopt an active TM6 conformation similar to that of the canonical β 2 -adrenergic receptor complexed with G protein and to that of rhodopsin complexed with arrestin. Importantly, mutations in the corresponding polar core of several other members of class B GPCRs, including PTH1R, PAC1R, VIP1R, and CRFR1, also induce constitutive G protein signaling, suggesting that the rearrangement of the polar core is a conserved mechanism for class B GPCR activation. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Task-specific enhancement of short-term, but not long-term, memory by class I metabotropic glutamate receptor antagonist 1-aminoindan-1,5-dicarboxylic acid in rats

    DEFF Research Database (Denmark)

    Christoffersen, G.R.J.; Christensen, Lone H.; Harrington, Nicholas R.

    1999-01-01

    Metabotropic glutamate receptors; Class I antagonist; 1-aminoindan-1,5-dicarboxylic acid; spatial learning; contextual conditioning; rats......Metabotropic glutamate receptors; Class I antagonist; 1-aminoindan-1,5-dicarboxylic acid; spatial learning; contextual conditioning; rats...

  6. Getting from A to B-exploring the activation motifs of the class B adhesion G protein-coupled receptor subfamily G member 4/GPR112

    DEFF Research Database (Denmark)

    Cornelia Peeters, Miriam; Mos, Iris; Lenselink, Eelke B

    2016-01-01

    The adhesion G protein-coupled receptors (ADGRs/class B2 G protein-coupled receptors) constitute an ancient family of G protein-coupled receptors that have recently been demonstrated to play important roles in cellular and developmental processes. Here, we describe a first insight...... into the structure-function relationship of ADGRs using the family member ADGR subfamily G member 4 (ADGRG4)/GPR112 as a model receptor. In a bioinformatics approach, we compared conserved, functional elements of the well-characterized class A and class B1 secretin-like G protein-coupled receptors with the ADGRs. We...... identified several potential equivalent motifs and subjected those to mutational analysis. The importance of the mutated residues was evaluated by examining their effect on the high constitutive activity of the N-terminally truncated ADGRG4/GPR112 in a 1-receptor-1-G protein Saccharomyces cerevisiae...

  7. Glucagon-Like Peptide-1 and Its Class B G Protein–Coupled Receptors: A Long March to Therapeutic Successes

    Science.gov (United States)

    de Graaf, Chris; Donnelly, Dan; Wootten, Denise; Lau, Jesper; Sexton, Patrick M.; Miller, Laurence J.; Ahn, Jung-Mo; Liao, Jiayu; Fletcher, Madeleine M.; Brown, Alastair J. H.; Zhou, Caihong; Deng, Jiejie; Wang, Ming-Wei

    2016-01-01

    The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein–coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity. Physiologic and biochemical studies with truncated, chimeric, and mutated peptides and GLP-1R variants, together with ligand-bound crystal structures of the extracellular domain and the first three-dimensional structures of the 7-helical transmembrane domain of class B GPCRs, have provided the basis for a two-domain–binding mechanism of GLP-1 with its cognate receptor. Although efforts in discovering therapeutically viable nonpeptidic GLP-1R agonists have been hampered, small-molecule modulators offer complementary chemical tools to peptide analogs to investigate ligand-directed biased cellular signaling of GLP-1R. The integrated pharmacological and structural information of different GLP-1 analogs and homologous receptors give new insights into the molecular determinants of GLP-1R ligand selectivity and functional activity, thereby providing novel opportunities in the design and development of more efficacious agents to treat metabolic disorders. PMID:27630114

  8. Reduced soluble receptor for advanced glycation end-products (sRAGE) scavenger capacity precedes pre-eclampsia in Type 1 diabetes

    Science.gov (United States)

    Yu, Y; Hanssen, KF; Kalyanaraman, V; Chirindel, A; Jenkins, AJ; Nankervis, AJ; Torjesen, PA; Scholz, H; Henriksen, T; Lorentzen, B; Garg, SK; Menard, MK; Hammad, SM; Scardo, JA; Stanley, JR; Wu, M; Basu, A; Aston, CE; Lyons, TJ

    2014-01-01

    Objective Increased advanced glycation end-products (AGEs) and their soluble receptors (sRAGE) have been implicated in the pathogenesis of pre-eclampsia (PE). However, this association has not been elucidated in pregnancies complicated by diabetes. We aimed to investigate the serum levels of these factors in pregnant women with Type 1 diabetes mellitus (T1DM), a condition associated with a four-fold increase in PE. Design Prospective study in women with T1DM at 12.2 ± 1.9, 21.6 ± 1.5 and 31.5 ± 1.7 weeks of gestation [mean ± standard deviation (SD); no overlap] before PE onset. Setting Antenatal clinics. Population Pregnant women with T1DM (n = 118; 26 developed PE) and healthy nondiabetic pregnant controls (n = 21). Methods Maternal serum levels of sRAGE (total circulating pool), Nε-(carboxymethyl)lysine (CML), hydroimidazolone (methylglyoxal-modified proteins) and total AGEs were measured by immunoassays. Main outcome measures Serum sRAGE and AGEs in pregnant women with T1DM who subsequently developed PE (DM PE+) versus those who remained normotensive (DM PE–). Results In DM PE+ versus DM PE–, sRAGE was significantly lower in the first and second trimesters, prior to the clinical manifestation of PE (P diabetes, parity and mean arterial pressure as covariates. Conclusions In the early stages of pregnancy, lower circulating sRAGE levels, and the ratio of sRAGE to AGEs, may be associated with the subsequent development of PE in women with T1DM. PMID:22900949

  9. Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

    Science.gov (United States)

    Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

    2012-10-01

    In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.

  10. The scavenger endothelial cell: a new player in homeostasis and immunity.

    Science.gov (United States)

    Sørensen, Karen Kristine; McCourt, Peter; Berg, Trond; Crossley, Clive; Le Couteur, David; Wake, Kenjiro; Smedsrød, Bård

    2012-12-15

    To maintain homeostasis, the animal body is equipped with a powerful system to remove circulating waste. This review presents evidence that the scavenger endothelial cell (SEC) is responsible for the clearance of blood-borne waste macromolecules in vertebrates. SECs express pattern-recognition endocytosis receptors (mannose and scavenger receptors), and in mammals, the endocytic Fc gamma-receptor IIb2. This cell type has an endocytic machinery capable of super-efficient uptake and degradation of physiological and foreign waste material, including all major classes of biological macromolecules. In terrestrial vertebrates, most SECs line the wall of the liver sinusoid. In phylogenetically older vertebrates, SECs reside instead in heart, kidney, or gills. SECs, thus, by virtue of their efficient nonphagocytic elimination of physiological and microbial substances, play a critical role in the innate immunity of vertebrates. In major invertebrate phyla, including insects, the same function is carried out by nephrocytes. The concept of a dual-cell principle of waste clearance is introduced to emphasize that professional phagocytes (macrophages in vertebrates; hemocytes in invertebrates) eliminate larger particles (>0.5 μm) by phagocytosis, whereas soluble macromolecules and smaller particles are eliminated efficiently and preferentially by clathrin-mediated endocytosis in nonphagocytic SECs in vertebrates or nephrocytes in invertebrates. Including these cells as important players in immunology and physiology provides an additional basis for understanding host defense and tissue homeostasis.

  11. Organobasierter Sauerstoff-Scavenger/-Indikator

    OpenAIRE

    Langowski, H.C.; Wanner, T.

    2007-01-01

    WO 2007059901 A1 UPAB: 20070911 NOVELTY - Oxygen scavenger/indicator which contains at least one substance having combined scavenging and indicating functions for oxygen which is capable of absorbing oxygen under the effect of moisture in alkaline conditions, and at least one alkaline compound. The indicator effect is caused by a change in at least one physical property of the substance having combined scavenging and indicating function for oxygen, the change being initiated by the presence o...

  12. Identification of the haemoglobin scavenger receptor

    DEFF Research Database (Denmark)

    Kristiansen, M; Graversen, Jonas Heilskov; Jacobsen, C

    2001-01-01

    Intravascular haemolysis is a physiological phenomenon as well as a severe pathological complication when accelerated in various autoimmune, infectious (such as malaria) and inherited (such as sickle cell disease) disorders. Haemoglobin released into plasma is captured by the acute phase protein...

  13. The macrophage scavenger receptor CD163

    NARCIS (Netherlands)

    Fabriek, Babs O.; Dijkstra, Christine D.; van den Berg, Timo K.

    2005-01-01

    Mature tissue macrophages form a first line of defense to recognize and eliminate potential pathogens; these specialized cells are capable of phagocytosis, degradation of self and foreign materials, establishment of cell-cell interactions, and the production of inflammatory mediators. Mature tissue

  14. The discovery of the benzazepine class of histamine H3 receptor antagonists.

    Science.gov (United States)

    Wilson, David M; Apps, James; Bailey, Nicholas; Bamford, Mark J; Beresford, Isabel J; Briggs, Michael A; Calver, Andrew R; Crook, Barry; Davis, Robert P; Davis, Susannah; Dean, David K; Harris, Leanne; Heightman, Tom D; Panchal, Terry; Parr, Christopher A; Quashie, Nigel; Steadman, Jon G A; Schogger, Joanne; Sehmi, Sanjeet S; Stean, Tania O; Takle, Andrew K; Trail, Brenda K; White, Trevor; Witherington, Jason; Worby, Angela; Medhurst, Andrew D

    2013-12-15

    This Letter describes the discovery of a novel series of H3 receptor antagonists. The initial medicinal chemistry strategy focused on deconstructing and simplifying an early screening hit which rapidly led to the discovery of a novel series of H3 receptor antagonists based on the benzazepine core. Employing an H3 driven pharmacodynamic model, the series was then further optimised through to a lead compound that showed robust in vivo functional activity and possessed overall excellent developability properties. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Structure of the human glucagon class B G-protein-coupled receptor

    NARCIS (Netherlands)

    Siu, F.Y.; He, M.; de Graaf, C.; Yang, D; Zhang, Z.; Zhou, C.; Han, G.W.; Xu, Q.; Wacker, D.; Joseph, J.S.; Wei, Liu; Lau, J.F.; Cherezov, V.; Katritch, V; Wang, M.W.; Stevens, R.C.

    2013-01-01

    Binding of the glucagon peptide to the glucagon receptor (GCGR) triggers the release of glucose from the liver during fasting; thus GCGR plays an important role in glucose homeostasis. Here we report the crystal structure of the seven transmembrane helical domain of human GCGR at 3.4 Å resolution,

  16. Drug and cell type-specific regulation of genes with different classes of estrogen receptor beta-selective agonists.

    Directory of Open Access Journals (Sweden)

    Sreenivasan Paruthiyil

    2009-07-01

    Full Text Available Estrogens produce biological effects by interacting with two estrogen receptors, ERalpha and ERbeta. Drugs that selectively target ERalpha or ERbeta might be safer for conditions that have been traditionally treated with non-selective estrogens. Several synthetic and natural ERbeta-selective compounds have been identified. One class of ERbeta-selective agonists is represented by ERB-041 (WAY-202041 which binds to ERbeta much greater than ERalpha. A second class of ERbeta-selective agonists derived from plants include MF101, nyasol and liquiritigenin that bind similarly to both ERs, but only activate transcription with ERbeta. Diarylpropionitrile represents a third class of ERbeta-selective compounds because its selectivity is due to a combination of greater binding to ERbeta and transcriptional activity. However, it is unclear if these three classes of ERbeta-selective compounds produce similar biological activities. The goals of these studies were to determine the relative ERbeta selectivity and pattern of gene expression of these three classes of ERbeta-selective compounds compared to estradiol (E(2, which is a non-selective ER agonist. U2OS cells stably transfected with ERalpha or ERbeta were treated with E(2 or the ERbeta-selective compounds for 6 h. Microarray data demonstrated that ERB-041, MF101 and liquiritigenin were the most ERbeta-selective agonists compared to estradiol, followed by nyasol and then diarylpropionitrile. FRET analysis showed that all compounds induced a similar conformation of ERbeta, which is consistent with the finding that most genes regulated by the ERbeta-selective compounds were similar to each other and E(2. However, there were some classes of genes differentially regulated by the ERbeta agonists and E(2. Two ERbeta-selective compounds, MF101 and liquiritigenin had cell type-specific effects as they regulated different genes in HeLa, Caco-2 and Ishikawa cell lines expressing ERbeta. Our gene profiling studies

  17. Shared fine specificity between T-cell receptors and an antibody recognizing a peptide/major histocompatibility class I complex

    DEFF Research Database (Denmark)

    Stryhn, A; Andersen, P S; Pedersen, L O

    1996-01-01

    Cytotoxic T cells recognize mosaic structures consisting of target peptides embedded within self-major histocompatibility complex (MHC) class I molecules. This structure has been described in great detail for several peptide-MHC complexes. In contrast, how T-cell receptors recognize peptide...... each other showing that peptide residues 1, 3, 4, 6, and 7 were exposed on the MHC surface and recognized by the T cells. Thus, the majority, and perhaps all, of the side chains of the non-primary anchor residues may be available for T-cell recognition, and contribute to the stringent specificity of T...... cells. A striking similarity between the specificity of the T cells and that of the pSAN antibody was found and most of the peptide residues, which could be recognized by the T cells, could also be recognized by the antibody....

  18. 21 CFR 868.5430 - Gas-scavenging apparatus.

    Science.gov (United States)

    2010-04-01

    ...) Identification. A gas-scavenging apparatus is a device intended to collect excess anesthetic, analgesic, or trace gases or vapors from a patient's breathing system, ventilator, or extracorporeal pump-oxygenator, and to conduct these gases out of the area by means of an exhaust system. (b) Classification. Class II...

  19. Reward Your Students with an Online Scavenger Hunt!

    Science.gov (United States)

    Board, Keith

    2013-01-01

    Do you have a class of students who do excellent work and whom you would like to give an enjoyable reward? Try an "Internet scavenger hunt" for a fun and educational change of pace! This article shares how to run the activity.

  20. PI3K class II α regulates δ-opioid receptor export from the trans-Golgi network.

    Science.gov (United States)

    Shiwarski, Daniel J; Darr, Marlena; Telmer, Cheryl A; Bruchez, Marcel P; Puthenveedu, Manojkumar A

    2017-08-01

    The interplay between signaling and trafficking by G protein-coupled receptors (GPCRs) has focused mainly on endocytic trafficking. Whether and how surface delivery of newly synthesized GPCRs is regulated by extracellular signals is less understood. Here we define a signaling-regulated checkpoint at the trans -Golgi network (TGN) that controls the surface delivery of the delta opioid receptor (δR). In PC12 cells, inhibition of phosphoinositide-3 kinase (PI3K) activity blocked export of newly synthesized δR from the Golgi and delivery to the cell surface, similar to treatment with nerve growth factor (NGF). Depletion of class II phosphoinositide-3 kinase α (PI3K C2A), but not inhibition of class I PI3K, blocked δR export to comparable levels and attenuated δR-mediated cAMP inhibition. NGF treatment displaced PI3K C2A from the Golgi and optogenetic recruitment of the PI3K C2A kinase domain to the TGN-induced δR export downstream of NGF. Of importance, PI3K C2A expression promotes export of endogenous δR in primary trigeminal ganglion neurons. Taken together, our results identify PI3K C2A as being required and sufficient for δR export and surface delivery in neuronal cells and suggest that it could be a key modulator of a novel Golgi export checkpoint that coordinates GPCR delivery to the surface. © 2017 Shiwarski et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  1. Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by class B G-protein coupled receptors.

    Directory of Open Access Journals (Sweden)

    Shiva Kumar

    Full Text Available Pituitary adenylate cyclase activating polypeptide (PACAP is a member of the PACAP/glucagon family of peptide hormones, which controls many physiological functions in the immune, nervous, endocrine, and muscular systems. It activates adenylate cyclase by binding to its receptor, PAC1R, a member of class B G-protein coupled receptors (GPCR. Crystal structures of a number of Class B GPCR extracellular domains (ECD bound to their respective peptide hormones have revealed a consensus mechanism of hormone binding. However, the mechanism of how PACAP binds to its receptor remains controversial as an NMR structure of the PAC1R ECD/PACAP complex reveals a different topology of the ECD and a distinct mode of ligand recognition. Here we report a 1.9 Å crystal structure of the PAC1R ECD, which adopts the same fold as commonly observed for other members of Class B GPCR. Binding studies and cell-based assays with alanine-scanned peptides and mutated receptor support a model that PAC1R uses the same conserved fold of Class B GPCR ECD for PACAP binding, thus unifying the consensus mechanism of hormone binding for this family of receptors.

  2. MHC class I is functionally associated with antigen receptors in human T and B lymphomas

    DEFF Research Database (Denmark)

    Pedersen, Anders Elm; Jacoby, B F; Skov, S

    1996-01-01

    lines the increase in [Ca2+]i after MHC-I cross-linking caused upregulation of CD69, an early marker of activation. When studying the effect of MHC-I cross-linking on the TCR- and B cell antigen receptor (BCR)- mediated increase in [Ca2+]i, respectively, we observed that MHC-I had a costimulatory effect...... on the TCR-mediated increase in [Ca2+]i in Jurkat cells but not on the anti-IgM-mediated activity of Solubo cells. Studies of subpopulations of Jurkat and Solubo cells expressing different levels of MHC-I on their cell surfaces revealed that the TCR- and BCR-mediated increases in [Ca2+]i, respectively, were...

  3. Crystal structure of a Gammadelta T-cell Receptor Specific for the Human MHC class I Homolog MICA

    Energy Technology Data Exchange (ETDEWEB)

    B Xu; J Pizarro; M Holmes; C McBeth; V Groh; T Spies; R Strong

    2011-12-31

    {gamma}{delta} T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human {gamma}{delta} T cells of the V{sub {delta}}1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V{sub {delta}}1 {gamma}{delta} T-cell receptor (TCR) showed expected overall structural homology to antibodies, {alpha}{beta}, and other {gamma}{delta} TCRs, but complementary determining region conformations and conservation of V{sub {delta}}1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on {gamma}{delta} T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of {gamma}{delta} T-cell/target cell interfaces.

  4. Crystal structure of a gammadelta T-cell receptor specific for the human MHC class I homolog MICA.

    Science.gov (United States)

    Xu, Bin; Pizarro, Juan C; Holmes, Margaret A; McBeth, Christine; Groh, Veronika; Spies, Thomas; Strong, Roland K

    2011-02-08

    γδ T cells play important roles in bridging innate and adaptive immunity, but their recognition mechanisms remain poorly understood. Human γδ T cells of the V(δ)1 subset predominate in intestinal epithelia and respond to MICA and MICB (MHC class I chain-related, A and B; MIC) self-antigens, mediating responses to tumorigenesis or viral infection. The crystal structure of an MIC-reactive V(δ)1 γδ T-cell receptor (TCR) showed expected overall structural homology to antibodies, αβ, and other γδ TCRs, but complementary determining region conformations and conservation of V(δ)1 use revealed an uncharacteristically flat potential binding surface. MIC, likewise, serves as a ligand for the activating immunoreceptor natural killer group 2, D (NKG2D), also expressed on γδ T cells. Although MIC recognition drives both the TCR-dependent stimulatory and NKG2D-dependent costimulatory signals necessary for activation, interaction analyses showed that MIC binding by the two receptors was mutually exclusive. Analysis of relative binding kinetics suggested sequential recognition, defining constraints for the temporal organization of γδ T-cell/target cell interfaces.

  5. First-in-class inhibitor of the T cell receptor for the treatment of autoimmune diseases.

    Science.gov (United States)

    Borroto, Aldo; Reyes-Garau, Diana; Jiménez, M Angeles; Carrasco, Esther; Moreno, Beatriz; Martínez-Pasamar, Sara; Cortés, José R; Perona, Almudena; Abia, David; Blanco, Soledad; Fuentes, Manuel; Arellano, Irene; Lobo, Juan; Heidarieh, Haleh; Rueda, Javier; Esteve, Pilar; Cibrián, Danay; Martinez-Riaño, Ana; Mendoza, Pilar; Prieto, Cristina; Calleja, Enrique; Oeste, Clara L; Orfao, Alberto; Fresno, Manuel; Sánchez-Madrid, Francisco; Alcamí, Antonio; Bovolenta, Paola; Martín, Pilar; Villoslada, Pablo; Morreale, Antonio; Messeguer, Angel; Alarcon, Balbino

    2016-12-21

    Modulating T cell activation is critical for treating autoimmune diseases but requires avoiding concomitant opportunistic infections. Antigen binding to the T cell receptor (TCR) triggers the recruitment of the cytosolic adaptor protein Nck to a proline-rich sequence in the cytoplasmic tail of the TCR's CD3ε subunit. Through virtual screening and using combinatorial chemistry, we have generated an orally available, low-molecular weight inhibitor of the TCR-Nck interaction that selectively inhibits TCR-triggered T cell activation with an IC 50 (median inhibitory concentration) ~1 nM. By modulating TCR signaling, the inhibitor prevented the development of psoriasis and asthma and, furthermore, exerted a long-lasting therapeutic effect in a model of autoimmune encephalomyelitis. However, it did not prevent the generation of a protective memory response against a mouse pathogen, suggesting that the compound might not exert its effects through immunosuppression. These results suggest that inhibiting an immediate TCR signal has promise for treating a broad spectrum of human T cell-mediated autoimmune and inflammatory diseases. Copyright © 2016, American Association for the Advancement of Science.

  6. Atypical chemokine receptors in cancer: friends or foes?

    Science.gov (United States)

    Massara, Matteo; Bonavita, Ornella; Mantovani, Alberto; Locati, Massimo; Bonecchi, Raffaella

    2016-06-01

    The chemokine system is a fundamental component of cancer-related inflammation involved in all stages of cancer development. It controls not only leukocyte infiltration in primary tumors but also angiogenesis, cancer cell proliferation, and migration to metastatic sites. Atypical chemokine receptors are a new, emerging class of regulators of the chemokine system. They control chemokine bioavailability by scavenging, transporting, or storing chemokines. They can also regulate the activity of canonical chemokine receptors with which they share the ligands by forming heterodimers or by modulating their expression levels or signaling activity. Here, we summarize recent results about the role of these receptors (atypical chemokine receptor 1/Duffy antigen receptor for chemokine, atypical chemokine receptor 2/D6, atypical chemokine receptor 3/CXC-chemokine receptor 7, and atypical chemokine receptor 4/CC-chemokine receptor-like 1) on the tumorigenesis process, indicating that their effects are strictly dependent on the cell type on which they are expressed and on their coexpression with other chemokine receptors. Indeed, atypical chemokine receptors inhibit tumor growth and progression through their activity as negative regulators of chemokine bioavailability, whereas, on the contrary, they can promote tumorigenesis when they regulate the signaling of other chemokine receptors, such as CXC-chemokine receptor 4. Thus, atypical chemokine receptors are key components of the regulatory network of inflammation and immunity in cancer and may have a major effect on anti-inflammatory and immunotherapeutic strategies. © Society for Leukocyte Biology.

  7. Rain scavenging of radioactive particles

    International Nuclear Information System (INIS)

    Williams, A.L.

    1975-01-01

    An assessment is made of the rainout of airborne radioactive particles from a nuclear detonation with emphasis on the microphysical removal processes. For submicron particles the scavenging processes examined are Brownian and turbulent diffusion to cloud droplets. For particles larger than 1 μm radius, nucleation scavenging is examined. For various particle size and radioactivity distributions, it is found that from 27 to 99 percent of the radioactivity is attached to cloud droplets and subject to rapid removal by rain. (U.S.)

  8. Precipitation scavenging of aerosol particles

    International Nuclear Information System (INIS)

    Radke, L.F.; Eltgroth, M.W.; Hobbs, P.V.

    1978-01-01

    The paper presents the results of precipitation scavenging measurements of particles in the atmosphere and in plumes which were obtained using an airborne measuring system. Attention is given to the so-called 'Greenfield gap' and collection efficiencies for submicron particles

  9. Inhibition of Dengue Virus Replication by a Class of Small-Molecule Compounds That Antagonize Dopamine Receptor D4 and Downstream Mitogen-Activated Protein Kinase Signaling

    Science.gov (United States)

    Smith, Jessica L.; Stein, David A.; Shum, David; Fischer, Matthew A.; Radu, Constantin; Bhinder, Bhavneet; Djaballah, Hakim; Nelson, Jay A.; Früh, Klaus

    2014-01-01

    ABSTRACT Dengue viruses (DENV) are endemic pathogens of tropical and subtropical regions that cause significant morbidity and mortality worldwide. To date, no vaccines or antiviral therapeutics have been approved for combating DENV-associated disease. In this paper, we describe a class of tricyclic small-molecule compounds—dihydrodibenzothiepines (DHBTs), identified through high-throughput screening—with potent inhibitory activity against DENV serotype 2. SKI-417616, a highly active representative of this class, displayed activity against all four serotypes of DENV, as well as against a related flavivirus, West Nile virus (WNV), and an alphavirus, Sindbis virus (SINV). This compound was characterized to determine its mechanism of antiviral activity. Investigation of the stage of the viral life cycle affected revealed that an early event in the life cycle is inhibited. Due to the structural similarity of the DHBTs to known antagonists of the dopamine and serotonin receptors, we explored the roles of two of these receptors, serotonin receptor 2A (5HTR2A) and the D4 dopamine receptor (DRD4), in DENV infection. Antagonism of DRD4 and subsequent downstream phosphorylation of epidermal growth factor receptor (EGFR)-related kinase (ERK) were found to impact DENV infection negatively, and blockade of signaling through this network was confirmed as the mechanism of anti-DENV activity for this class of compounds. IMPORTANCE The dengue viruses are mosquito-borne, reemerging human pathogens that are the etiological agents of a spectrum of febrile diseases. Currently, there are no approved therapeutic treatments for dengue-associated disease, nor is there a vaccine. This study identifies a small molecule, SKI-417616, with potent anti-dengue virus activity. Further analysis revealed that SKI-417616 acts through antagonism of the host cell dopamine D4 receptor and subsequent repression of the ERK phosphorylation pathway. These results suggest that SKI-417616, or other

  10. Discovery of a New Class of Ionotropic Glutamate Receptor Antagonists by the Rational Design of (2S,3R)-3-(3-Carboxyphenyl)-pyrrolidine-2-carboxylic Acid

    DEFF Research Database (Denmark)

    Larsen, Ann Møller; Venskutonyte, Raminta; Valadés, Elena Antón

    2011-01-01

    The kainic acid (KA) receptors belong to the class of glutamate (Glu) receptors in the brain and constitute a promising target for the treatment of neurological and/ or psychiatric diseases such as schizophrenia, major depression, and epilepsy. Five KA subtypes have been identified and named GluK1......-5. In this article, we present the discovery of (2S,3R)-3-(3-carboxyphenyl)-pyrrolidine-2-carboxylic acid (1) based on a rational design process. Target compound 1 was synthesized by a stereoselective strategy in 10 steps from commercially available starting materials. Binding affinities of 1 at native ionotropic...

  11. 21 CFR 868.5590 - Scavenging mask.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Scavenging mask. 868.5590 Section 868.5590 Food... DEVICES ANESTHESIOLOGY DEVICES Therapeutic Devices § 868.5590 Scavenging mask. (a) Identification. A scavenging mask is a device positioned over a patient's nose to deliver anesthetic or analgesic gases to the...

  12. Scavenging in the genus Natrix

    Directory of Open Access Journals (Sweden)

    Cesar Ayres

    2012-07-01

    Full Text Available Scavenging is reported as an unusual behaviour of snakes. However, it is likely more common than is supposed. Here I report the use of dead newts as prey source by water snakes of the genus Natrix at a dam in north-western Spain. Juveniles and adults viperine snakes (Natrix maura, and also an adult grass snake (Natrix natrix were found feeding on newt carcasses.

  13. Class I Cytokine Receptors

    DEFF Research Database (Denmark)

    Steinocher, Helena

    , the minimal determinants for specificity between membrane spanning helices were investigated with small artificial low complexity peptides, prior found to activate the EPOR in cells. The placement of single methyl group in the so called transmembrane aptamers (traptamers) determined the stabilizing effect...... characteristics of membrane spanning helices, was designed and hGHR TMD and hEPOR TMD produced in sufficient amounts for spectroscopic investigations. The isolated hGHR TMD was revealed to associate in dimeric complexes in detergent micelles and first presumptions about the dimer interface could be made. Further...... the traptamers on the hEPOR TMD dimeric complex in detergent micelles. To gain a better understanding of hGHR regulation a point mutation in the hGHR intracellular domain (ICD), which has recently been linked to lung cancer, was characterized. The mutation was found to decrease binding of suppressor of cytokine...

  14. Changes in expression of Class 3 Semaphorins and their receptors during development of the rat retina and superior colliculus.

    Science.gov (United States)

    Sharma, Anil; LeVaillant, Chrisna J; Plant, Giles W; Harvey, Alan R

    2014-07-26

    Members of the Semaphorin 3 family (Sema3s) influence the development of the central nervous system, and some are implicated in regulating aspects of visual system development. However, we lack information about the timing of expression of the Sema3s with respect to different developmental epochs in the mammalian visual system. In this time-course study in the rat, we document for the first time changes in the expression of RNAs for the majority of Class 3 Semaphorins (Sema3s) and their receptor components during the development of the rat retina and superior colliculus (SC). During retinal development, transcript levels changed for all of the Sema3s examined, as well as Nrp2, Plxna2, Plxna3, and Plxna4a. In the SC there were also changes in transcript levels for all Sema3s tested, as well as Nrp1, Nrp2, Plxna1, Plxna2, Plxna3, and Plxna4a. These changes correlate with well-established epochs, and our data suggest that the Sema3s could influence retinal ganglion cell (RGC) apoptosis, patterning and connectivity in the maturing retina and SC, and perhaps guidance of RGC and cortical axons in the SC. Functionally we found that SEMA3A, SEMA3C, SEMA3E, and SEMA3F proteins collapsed purified postnatal day 1 RGC growth cones in vitro. Significantly this is a developmental stage when RGCs are growing into and within the SC and are exposed to Sema3 ligands. These new data describing the overall temporal regulation of Sema3 expression in the rat retina and SC provide a platform for further work characterising the functional impact of these proteins on the development and maturation of mammalian visual pathways.

  15. The Impact of HLA Class I-Specific Killer Cell Immunoglobulin-Like Receptors on Antibody-Dependent Natural Killer Cell-Mediated Cytotoxicity and Organ Allograft Rejection.

    Science.gov (United States)

    Rajalingam, Raja

    2016-01-01

    Natural killer (NK) cells of the innate immune system are cytotoxic lymphocytes that play an important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self-human leukocyte antigen (HLA) class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIRs) is involved in the calibration of NK cell effector capacities during the developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self-HLA class I (due to virus infection or tumor transformation) or HLA class I disparities (in the setting of allogeneic transplantation). NK cells expressing an inhibitory KIR-binding self-HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC), triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  16. The impact of HLA class I-specific killer cell immunoglobulin-like receptors on antibody-dependent natural killer cell-mediated cytotoxicity and organ allograft rejection

    Directory of Open Access Journals (Sweden)

    Raja Rajalingam

    2016-12-01

    Full Text Available Natural killer (NK cells of the innate immune system are cytotoxic lymphocytes that play important roles following transplantation of solid organs and hematopoietic stem cells. Recognition of self HLA class I molecules by inhibitory killer cell immunoglobulin-like receptors (KIR is involved in the calibration of NK cell effector capacities during a developmental stage, allowing the subsequent recognition and elimination of target cells with decreased expression of self HLA class I (due to virus infection or tumor transformation or HLA class I disparities (in the setting of allogeneic transplantation. NK cells expressing an inhibitory KIR binding self HLA can be activated when confronted with allografts lacking a ligand for the inhibitory receptor. Following the response of the adaptive immune system, NK cells can further destroy allograft endothelium by antibody-dependent cell-mediated cytotoxicity (ADCC, triggered through cross-linking of the CD16 Fc receptor by donor-specific antibodies bound to allograft. Upon recognizing allogeneic target cells, NK cells also secrete cytokines and chemokines that drive maturation of dendritic cells to promote cellular and humoral adaptive immune responses against the allograft. The cumulative activating and inhibitory signals generated by ligation of the receptors regulates mature NK cell killing of target cells and their production of cytokines and chemokines. This review summarizes the role of NK cells in allograft rejection and proposes mechanistic concepts that indicate a prominent role for KIR-HLA interactions in facilitating NK cells for Fc receptor-mediated ADCC effector function involved in antibody-mediated rejection of solid organ transplants.

  17. Improved pan-specific prediction of MHC class I peptide binding using a novel receptor clustering data partitioning strategy

    DEFF Research Database (Denmark)

    Mattsson, Andreas Holm; Kringelum, Jens Vindahl; Garde, C.

    2016-01-01

    Pan-specific prediction of receptor-ligand interaction is conventionally done using machine-learning methods that integrates information about both receptor and ligand primary sequences. To achieve optimal performance using machine learning, dealing with overfitting and data redundancy is critical....... Most often so-called ligand clustering methods have been used to deal with these issues in the context of pan-specific receptor-ligand predictions, and the MHC system the approach has proven highly effective for extrapolating information from a limited set of receptors with well characterized binding...

  18. To scavenge or not to scavenge: that is the question

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, Elzbieta; Brzuszkiewicz, Anna [Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Dauter, Miroslawa [SAIC-Frederick Inc., Basic Research Program, Argonne National Laboratory, Argonne, IL 60439 (United States); Dauter, Zbigniew, E-mail: dauter@anl.gov [Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States); Rosenbaum, Gerd, E-mail: dauter@anl.gov [Department of Biochemistry, University of Georgia, SER-CAT at the APS, Argonne, IL 60439 (United States); Synchrotron Radiation Research Section, MCL, National Cancer Institute, Argonne National Laboratory, Argonne, IL 60439 (United States)

    2009-09-01

    Analysis of a series of diffraction data sets measured from several native as well as nicotinic acid-soaked crystals of trypsin suggests that this potential scavenger does not have any statistically significant effect on the amount of radiation damage incurred in the crystals on X-ray irradiation at 100 K. Analysis of a series of diffraction data sets measured from four native as well as four nicotinic acid-soaked crystals of trypsin at 100 K shows a high variability in radiation-sensitivity among individual crystals for both nicotinic acid-soaked and native crystals. The level of radiation-sensitivity and the extent of its variability is statistically indistinguishable between the two conditions. This suggests that this potential scavenger does not have any statistically significant effect on the amount of radiation damage incurred in the crystals on X-ray irradiation. This is in contrast to previous results [Kauffmann et al. (2006 ▶), Structure, 14, 1099–1105] where only one crystal specimen was used for each condition (native and nicotinic acid-soaked)

  19. Differential actions of antiparkinson agents at multiple classes of monoaminergic receptor. III. Agonist and antagonist properties at serotonin, 5-HT(1) and 5-HT(2), receptor subtypes.

    Science.gov (United States)

    Newman-Tancredi, Adrian; Cussac, Didier; Quentric, Yann; Touzard, Manuelle; Verrièle, Laurence; Carpentier, Nathalie; Millan, Mark J

    2002-11-01

    Although certain antiparkinson agents interact with serotonin (5-HT) receptors, little information is available concerning functional actions. Herein, we characterized efficacies of apomorphine, bromocriptine, cabergoline, lisuride, piribedil, pergolide, roxindole, and terguride at human (h)5-HT(1A), h5-HT(1B), and h5-HT(1D) receptors [guanosine 5'-O-(3-[(35)S]thio)triphosphate ([(35)S]GTPgammaS) binding], and at h5-HT(2A), h5-HT(2B), and h5-HT(2C) receptors (depletion of membrane-bound [(3)H]phosphatydilinositol). All drugs stimulated h5-HT(1A) receptors with efficacies (compared with 5-HT, 100%) ranging from modest (apomorphine, 35%) to high (cabergoline, 93%). At h5-HT(1B) receptors, efficacies varied from mild (terguride, 37%) to marked (cabergoline, 102%) and potencies were modest (pEC(50) values of 5.8-7.6): h5-HT(1D) sites were activated with a similar range of efficacies and greater potency (7.1-8.5). Piribedil and apomorphine were inactive at h5-HT(1B) and h5-HT(1D) receptors. At h5-HT(2A) receptors, terguride, lisuride, bromocriptine, cabergoline, and pergolide displayed potent (7.6-8.8) agonist properties (49-103%), whereas apomorphine and roxindole were antagonists and piribedil was inactive. Only pergolide (113%/8.2) and cabergoline (123%/8.6) displayed pronounced agonist properties at h5-HT(2B) receptors. At 5-HT(2C) receptors, lisuride, bromocriptine, pergolide, and cabergoline were efficacious (75-96%) agonists, apomorphine and terguride were antagonists, and piribedil was inactive. MDL100,907 and SB242,084, selective antagonists at 5-HT(2A) and 5-HT(2C) receptors, respectively, abolished these actions of pergolide, cabergoline, and bromocriptine. In conclusion, antiparkinson agents display markedly different patterns of agonist and antagonist properties at multiple 5-HT receptor subtypes. Although all show modest (agonist) activity at 5-HT(1A) sites, their contrasting actions at 5-HT(2A) and 5-HT(2C) sites may be of particular significance to their

  20. MHC class II molecules deliver costimulatory signals in human T cells through a functional linkage with IL-2-receptors

    DEFF Research Database (Denmark)

    Odum, Niels; Kanner, S B; Ledbetter, J A

    1993-01-01

    MHC class II-positive T cells are found in tissues involved in autoimmune and infectious disorders. Because stimulation of class II molecules by mAb or bacterial superantigens induces protein tyrosine phosphorylation through activation of PTK3 in T cells, we hypothesized that class II signals play...... tyrosine phosphorylation of specific substrates including PLC-gamma 1. Combined stimulation of IL-2R and class II molecules had an additive effect on tyrosine phosphorylation. Pretreatment of T cells with a protein tyrosine kinase inhibitor, herbimycin A, inhibited IL-2 and class II-induced proliferation...... a regulatory function in T cell activation. Here, we show that cross-linking HLA-DR and -DP but not -DQ molecules by immobilized mAb enhanced proliferative T cell responses to IL-2. In contrast, class II stimulation had no effect on IL-4-induced proliferation. The costimulatory effect was most pronounced...

  1. Scavenging and recombination kinetics in radiation chemistry.

    Science.gov (United States)

    Al-Samra, Eyad H; Green, Nicholas J B

    2017-08-02

    This work describes stochastic models developed to study the competition between radical scavenging and recombination for simple model systems typical of radiation chemistry, where the reactive particles are tightly clustered and reactions are assumed fully diffusion limited. Three models are developed: a Monte Carlo random flights model with a periodic boundary condition for scavengers, Monte Carlo simulations in which the scavenging rate is calculated from the Smoluchowski theory for diffusion-limited reactions and a modification of the independent reaction times method where the scavengers close to the spur are explicitly included and the scavengers further away are treated as a continuum. The results indicate that the Smoluchowski theory makes a systematic overestimate of the scavenging rate when such competition is present. A correction for the Smoluchowski rate constant is suggested, an analytical justification is presented and it is tested against the simulations, and shown to be a substantial improvement.

  2. Energy scavenging from environmental vibration.

    Energy Technology Data Exchange (ETDEWEB)

    Galchev, Tzeno (University of Michigan); Apblett, Christopher Alan; Najafi, Khalil (University of Michigan)

    2009-10-01

    The goal of this project is to develop an efficient energy scavenger for converting ambient low-frequency vibrations into electrical power. In order to achieve this a novel inertial micro power generator architecture has been developed that utilizes the bi-stable motion of a mechanical mass to convert a broad range of low-frequency (< 30Hz), and large-deflection (>250 {micro}m) ambient vibrations into high-frequency electrical output energy. The generator incorporates a bi-stable mechanical structure to initiate high-frequency mechanical oscillations in an electromagnetic scavenger. This frequency up-conversion technique enhances the electromechanical coupling and increases the generated power. This architecture is called the Parametric Frequency Increased Generator (PFIG). Three generations of the device have been fabricated. It was first demonstrated using a larger bench-top prototype that had a functional volume of 3.7cm3. It generated a peak power of 558{micro}W and an average power of 39.5{micro}W at an input acceleration of 1g applied at 10 Hz. The performance of this device has still not been matched by any other reported work. It yielded the best power density and efficiency for any scavenger operating from low-frequency (<10Hz) vibrations. A second-generation device was then fabricated. It generated a peak power of 288{micro}W and an average power of 5.8{micro}W from an input acceleration of 9.8m/s{sup 2} at 10Hz. The device operates over a frequency range of 20Hz. The internal volume of the generator is 2.1cm{sup 3} (3.7cm{sup 3} including casing), half of a standard AA battery. Lastly, a piezoelectric version of the PFIG is currently being developed. This device clearly demonstrates one of the key features of the PFIG architecture, namely that it is suitable for MEMS integration, more so than resonant generators, by incorporating a brittle bulk piezoelectric ceramic. This is the first micro-scale piezoelectric generator capable of <10Hz operation. The

  3. Further assessment of scavenging feed resource base

    International Nuclear Information System (INIS)

    Sonaiya, E.B.; Dazogbo, J.S.; Olukosi, O.A.

    2002-01-01

    The scavenging feed resource base (SFRB) was estimated in four villages located in a rainforest ecozone in Nigeria. The average SFRB estimated for the villages was 110 kg dry weight/family flock/year. Productivity of the birds in the villages was low. A low survivability of chicks was detected indicating a lot of wastage of eggs that could have been used for human consumption. The SFRB was low in nutritive value with less than 2 g crude protein (CP) available to each bird daily. To more quantitatively describe the SFRB, the concept of using bird unit in determining what is available to each bird is suggested. This helped in evaluating at first glance the differential accessibility of each class of bird to the SFRB and assisted in strategic supplementation of the SFRB. The use of predictors of the SFRB could help in establishing prediction equation which would help in predicting the carrying capacity of the SFRB and in determining the optimum flock biomass more accurately. (author)

  4. CXCR7 functions as a scavenger for CXCL12 and CXCL11.

    Directory of Open Access Journals (Sweden)

    Ulrike Naumann

    2010-02-01

    Full Text Available CXCR7 (RDC1, the recently discovered second receptor for CXCL12, is phylogenetically closely related to chemokine receptors, but fails to couple to G-proteins and to induce typical chemokine receptor mediated cellular responses. The function of CXCR7 is controversial. Some studies suggest a signaling activity in mammalian cells and zebrafish embryos, while others indicate a decoy activity in fish. Here we investigated the two propositions in human tissues.We provide evidence and mechanistic insight that CXCR7 acts as specific scavenger for CXCL12 and CXCL11 mediating effective ligand internalization and targeting of the chemokine cargo for degradation. Consistently, CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand, both in mammalian cells and in zebrafish. In accordance with the proposed activity as a scavenger receptor CXCR7-dependent chemokine degradation does not become saturated with increasing ligand concentrations. Active CXCL12 sequestration by CXCR7 is demonstrated in adult mouse heart valves and human umbilical vein endothelium.The finding that CXCR7 specifically scavenges CXCL12 suggests a critical function of the receptor in modulating the activity of the ubiquitously expressed CXCR4 in development and tumor formation. Scavenger activity of CXCR7 might also be important for the fine tuning of the mobility of hematopoietic cells in the bone marrow and lymphoid organs.

  5. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures

    OpenAIRE

    Wootten, Denise; Reynolds, Christopher A.; Koole, Cassandra; Smith, Kevin J.; Mobarec, Juan C.; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G. B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.

    2016-01-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60190, N3.43240, Q7.49394, and H6.52363 as key residues involved in peptide-mediated biased agonism, with R2.60190, N3.43240, and Q7.49394 predicted to form a polar int...

  6. Americans with Disabilities Act Scavenger Hunt

    Science.gov (United States)

    Ramsey, Ursula

    2018-01-01

    This article describes a scavenger hunt for Business Law students. Specifically, students compete in this scavenger hunt to identify accessible design features on campus to undergird their study of Title III of the Americans with Disabilities Act (ADA). Title III of the ADA prohibits public accommodations from discriminating on the basis of…

  7. Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84

    DEFF Research Database (Denmark)

    Mahmud, Zobaer Al; Jenkins, Laura; Ulven, Trond

    2017-01-01

    Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diind...

  8. Development of a New Class of Drugs To Inhibit All Forms of Androgen Receptor in Castration Resistant Prostate Cancers

    Science.gov (United States)

    2016-10-01

    receptor, castration-resistant prostate cancer, DNA binding domain, androgen response element, AR inhibitor, chromatin, x-ray crystallography , pre-clinical...14228 (months 1-30) 3.2. Synthesis of derivatives of our lead compounds (months 6-30). 3.3.Experimental evaluation of the developed synthetic

  9. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. I. Recognition by two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Stryhn, A; Fugger, L

    2000-01-01

    dynamics. Next, three-dimensional models of two different T cell receptors (TCRs) both specific for the Ha255-262/Kk complex were generated based on previously published TCR X-ray structures. Finally, guided by the recently published X-ray structures of ternary TCR/peptide/MHC-I complexes, the TCR models...... the models. They were found to account well for the experimentally obtained data, lending considerable support to the proposed models and suggesting a universal docking mode for alpha beta TCRs to MHC-peptide complexes. Such models may also be useful in guiding future rational experimentation....

  10. Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

    KAUST Repository

    Tallerico, Rossana

    2013-01-23

    Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

  11. Human NK cells selective targeting of colon cancer-initiating cells: A role for natural cytotoxicity receptors and MHC class i molecules

    KAUST Repository

    Tallerico, Rossana; Todaro, Matilde; Di Franco, Simone; MacCalli, Cristina; Garofalo, Cinzia; Sottile, Rosa; Palmieri, Camillo; Tirinato, Luca; Pangigadde, Pradeepa N.; La Rocca, Rosanna; Mandelboim, Ofer; Stassi, Giorgio; Di Fabrizio, Enzo M.; Parmiani, Giorgio; Moretta, Alessandro; Dieli, Francesco; Kã rre, Klas; Carbone, Ennio

    2013-01-01

    Tumor cell populations have been recently proposed to be composed of two compartments: tumor-initiating cells characterized by a slow and asymmetrical growth, and the "differentiated" cancer cells with a fast and symmetrical growth. Cancer stem cells or cancer-initiating cells (CICs) play a crucial role in tumor recurrence. The resistance of CICs to drugs and irradiation often allows them to survive traditional therapy. NK cells are potent cytotoxic lymphocytes that can recognize tumor cells. In this study, we have analyzed the NK cell recognition of tumor target cells derived from the two cancer cell compartments of colon adenocarcinoma lesions. Our data demonstrate that freshly purified allogeneic NK cells can recognize and kill colorectal carcinoma- derived CICs whereas the non-CIC counterpart of the tumors (differentiated tumor cells), either autologous or allogeneic, is less susceptible to NK cells. This difference in the NK cell susceptibility correlates with higher expression on CICs of ligands for NKp30 and NKp44 in the natural cytotoxicity receptor (NCR) group of activating NK receptors. In contrast, CICs express lower levels of MHC class I, known to inhibit NK recognition, on their surface than do the "differentiated" tumor cells. These data have been validated by confocal microscopy where NCR ligands and MHC class I molecule membrane distribution have been analyzed. Moreover, NK cell receptor blockade in cytotoxicity assays demonstrates that NCRs play a major role in the recognition of CIC targets. This study strengthens the idea that biology-based therapy harnessing NK cells could be an attractive opportunity in solid tumors. Copyright © 2013 by The American Association of Immunologists, Inc. All rights reserved.

  12. Dielectric polymer: scavenging energy from human motion

    Science.gov (United States)

    Jean-Mistral, Claire; Basrour, Skandar; Chaillout, Jean-Jacques

    2008-03-01

    More and more sensors are embedded in human body for medical applications, for sport. The short lifetime of the batteries, available on the market, reveals a real problem of autonomy of these systems. A promising alternative is to scavenge the ambient energy such as the mechanical one. Up to now, few scavenging structures have operating frequencies compatible with ambient one. And, most of the developed structures are rigid and use vibration as mechanical source. For these reasons, we developed a scavenger that operates in a large frequency spectrum from quasi-static to dynamic range. This generator is fully flexible, light and does not hamper the human motion. Thus, we report in this paper an analytical model for dielectric generator with news electrical and mechanical characterization, and the development of an innovating application: scavenging energy from human motion. The generator is located on the knee and design to scavenge 0.1mJ per scavenging cycle at a frequency of 1Hz, enough to supply a low consumption system and with a poling voltage as low as possible to facilitate the power management. Our first prototype is a membrane with an area of 5*3cm and 31µm in thickness which scavenge 0.1mJ under 170V at constant charge Q.

  13. Peroxynitrite scavenging activity of herb extracts.

    Science.gov (United States)

    Choi, Hye Rhi; Choi, Jae Sue; Han, Yong Nam; Bae, Song Ja; Chung, Hae Young

    2002-06-01

    Peroxynitrite (ONOO(-)) is a cytotoxicant with strong oxidizing properties toward various cellular constituents, including sulphydryls, lipids, amino acids and nucleotides and can cause cell death, lipid peroxidation, carcinogenesis and aging. The aim of this study was to characterize ONOO(-) scavenging constituents from herbs. Twenty-eight herbs were screened for their ONOO(-) scavenging activities with the use of a fluorometric method. The potency of scavenging activity following the addition of authentic ONOO(-) was in the following order: witch hazel bark > rosemary > jasmine tea > sage > slippery elm > black walnut leaf > Queen Anne's lace > Linden flower. The extracts exhibited dose-dependent ONOO(-) scavenging activities. We found that witch hazel (Hamamelis virginiana L.) bark showed the strongest effect for scavenging ONOO(-) of the 28 herbs. Hamamelitannin, the major active component of witch hazel bark, was shown to have a strong ability to scavenge ONOO(-). It is suggested that hamamelitannin might be developed as an effective peroxynitrite scavenger for the prevention of ONOO(-) involved diseases. Copyright 2002 John Wiley & Sons, Ltd.

  14. Engineering chimeric human and mouse major histocompatibility complex (MHC) class I tetramers for the production of T-cell receptor (TCR) mimic antibodies

    Science.gov (United States)

    Bentley, Carol; Yates, Jenna; Salimi, Maryam; Greig, Jenny; Wiblin, Sarah; Hassanali, Tasneem; Banham, Alison H.

    2017-01-01

    Therapeutic monoclonal antibodies targeting cell surface or secreted antigens are among the most effective classes of novel immunotherapies. However, the majority of human proteins and established cancer biomarkers are intracellular. Peptides derived from these intracellular proteins are presented on the cell surface by major histocompatibility complex class I (MHC-I) and can be targeted by a novel class of T-cell receptor mimic (TCRm) antibodies that recognise similar epitopes to T-cell receptors. Humoural immune responses to MHC-I tetramers rarely generate TCRm antibodies and many antibodies recognise the α3 domain of MHC-I and β2 microglobulin (β2m) that are not directly involved in presenting the target peptide. Here we describe the production of functional chimeric human-murine HLA-A2-H2Dd tetramers and modifications that increase their bacterial expression and refolding efficiency. These chimeric tetramers were successfully used to generate TCRm antibodies against two epitopes derived from wild type tumour suppressor p53 (RMPEAAPPV and GLAPPQHLIRV) that have been used in vaccination studies. Immunisation with chimeric tetramers yielded no antibodies recognising the human α3 domain and β2m and generated TCRm antibodies capable of specifically recognising the target peptide/MHC-I complex in fully human tetramers and on the cell surface of peptide pulsed T2 cells. Chimeric tetramers represent novel immunogens for TCRm antibody production and may also improve the yield of tetramers for groups using these reagents to monitor CD8 T-cell immune responses in HLA-A2 transgenic mouse models of immunotherapy. PMID:28448627

  15. Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish

    Directory of Open Access Journals (Sweden)

    Mogensen Knud

    2003-07-01

    Full Text Available Abstract Background The high degree of sequence conservation between coding regions in fish and mammals can be exploited to identify genes in mammalian genomes by comparison with the sequence of similar genes in fish. Conversely, experimentally characterized mammalian genes may be used to annotate fish genomes. However, gene families that escape this principle include the rapidly diverging cytokines that regulate the immune system, and their receptors. A classic example is the class II helical cytokines (HCII including type I, type II and lambda interferons, IL10 related cytokines (IL10, IL19, IL20, IL22, IL24 and IL26 and their receptors (HCRII. Despite the report of a near complete pufferfish (Takifugu rubripes genome sequence, these genes remain undescribed in fish. Results We have used an original strategy based both on conserved amino acid sequence and gene structure to identify HCII and HCRII in the genome of another pufferfish, Tetraodon nigroviridis that is amenable to laboratory experiments. The 15 genes that were identified are highly divergent and include a single interferon molecule, three IL10 related cytokines and their potential receptors together with two Tissue Factor (TF. Some of these genes form tandem clusters on the Tetraodon genome. Their expression pattern was determined in different tissues. Most importantly, Tetraodon interferon was identified and we show that the recombinant protein can induce antiviral MX gene expression in Tetraodon primary kidney cells. Similar results were obtained in Zebrafish which has 7 MX genes. Conclusion We propose a scheme for the evolution of HCII and their receptors during the radiation of bony vertebrates and suggest that the diversification that played an important role in the fine-tuning of the ancestral mechanism for host defense against infections probably followed different pathways in amniotes and fish.

  16. Development and characterization of hepatitis C virus genotype 1-7 cell culture systems: role of CD81 and scavenger receptor class B type I and effect of antiviral drugs

    DEFF Research Database (Denmark)

    Gottwein, Judith M; Scheel, Troels K H; Jensen, Tanja B

    2009-01-01

    strains, as well as subtype 1b and 2b strains, we have completed a panel of culture systems for all major HCV genotypes. Efficient growth in Huh7.5 cells depended on adaptive mutations for HK6a/JFH1 (6a/2a, in E1 and E2) and J4/JFH1 (1b/2a, in NS2 and NS3); viability of J8/JFH1 (2b/2a) and QC69/JFH1 (7a/2......a) did not require adaptation. To facilitate comparative studies, we generated virus stocks of genotype 1-7 recombinants with infectivity titers of 10(3.7) to 10(5.2) 50% tissue culture infectious dose/mL and HCV RNA titers of 10(7.0) to 10(7.9) IU/mL. Huh7.5 cultures infected with genotype 1....... Recently, HCV research has been accelerated by cell culture systems based on the unique growth capacity of strain JFH1 (genotype 2a). By development of JFH1-based intergenotypic recombinants containing Core, envelope protein 1 and 2 (E1, E2), p7, and nonstructural protein 2 (NS2) of genotype 6a and 7a...

  17. receptores

    Directory of Open Access Journals (Sweden)

    Salete Regina Daronco Benetti

    2006-01-01

    Full Text Available Se trata de un estudio etnográfico, que tuvo lo objetivo de interpretar el sistema de conocimiento y del significado atribuidos a la sangre referente a la transfusión sanguínea por los donadores y receptores de un banco de sangre. Para la colecta de las informaciones se observaron los participantes y la entrevista etnográfica se realizó el análisis de dominio, taxonómicos y temáticos. Los dominios culturales fueron: la sangre es vida: fuente de vida y alimento valioso; creencias religiosas: fuentes simbólicas de apoyos; donación sanguínea: un gesto colaborador que exige cuidarse, gratifica y trae felicidad; donación sanguínea: fuente simbólica de inseguridad; estar enfermo es una condición para realizar transfusión sanguínea; transfusión sanguínea: esperanza de vida; Creencias populares: transfusión sanguínea como riesgo para la salud; donadores de sangre: personas benditas; donar y recibir sangre: como significado de felicidad. Temática: “líquido precioso que origina, sostiene, modifica la vida, provoca miedo e inseguridad”.

  18. Expression of NO scavenging hemoglobin is involved in the timing of bolting in Arabidopsis thaliana

    DEFF Research Database (Denmark)

    Hebelstrup, Kim Henrik; Jensen, Erik Østergaard

    2008-01-01

    -symbiotic hemoglobin gene, GLB2, in Arabidopsis thaliana. Lines with GLB1 silencing had a significant delay of bolting and after bolting, shoots reverted to the rosette vegetative phase by formation of aerial rosettes at lateral meristems. Lines with overexpression of GLB1 or GLB2 bolted earlier than wild type plants....... By germinating the lines in a medium containing the nitric oxide (NO) donor, sodium nitroprusside (SNP), it was demonstrated that both GLB1 and GLB2 promote bolting by antagonizing the effect of NO, suggesting that non-symbiotic plant hemoglobin controls bolting by scavenging the floral transition signal...... molecule, NO. So far, NO scavenging has only been demonstrated for class 1 non-symbiotic hemoglobins. A direct assay in Arabidopsis leaf cells shows that GLB1 as well as the class 2 non-symbiotic hemoglobin, GLB2, scavenge NO in vivo. NO has also been demonstrated to be a growth stimulating signal...

  19. Role of antioxidant scavenging enzymes and extracellular ...

    African Journals Online (AJOL)

    ChithrashreeGS

    2012-08-23

    Aug 23, 2012 ... peroxidase are two important antioxidant scavenging enzymes involved in ... Catalase was assayed using the method of Beers and Sizer. (1951) with .... yeast dextrose calcium carbonate agar (YDC) medium. Catalase and ...

  20. Flavonoids as scavengers of nitric oxide radical.

    NARCIS (Netherlands)

    van Acker, S.A.B.E.; Tromp, M.N.J.L.; Haenen, G.R.M.M.; van der Vijgh, W.J.F.; Bast, A.

    1995-01-01

    Flavonoids are a group of naturally occurring compounds used, e.g., in the treatment of vascular endothelial damage. They are known to be excellent scavengers of oxygen free radicals. Since the nitric oxide radical (

  1. Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84

    OpenAIRE

    Mahmud, Zobaer Al; Jenkins, Laura; Ulven, Trond; Labéguère, Frédéric; Gosmini, Romain; De Vos, Steve; Hudson, Brian D.; Tikhonova, Irina G.; Milligan, Graeme

    2017-01-01

    Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predic...

  2. FMRFamide-gated sodium channel and ASIC channels: a new class of ionotropic receptors for FMRFamide and related peptides.

    Science.gov (United States)

    Lingueglia, Eric; Deval, Emmanuel; Lazdunski, Michel

    2006-05-01

    FMRFamide and related peptides typically exert their action through G-protein coupled receptors. However, two ionotropic receptors for these peptides have recently been identified. They are both members of the epithelial amiloride-sensitive Na+ channel and degenerin (ENaC/DEG) family of ion channels. The invertebrate FMRFamide-gated Na+ channel (FaNaC) is a neuronal Na+-selective channel which is directly gated by micromolar concentrations of FMRFamide and related tetrapeptides. Its response is fast and partially desensitizing, and FaNaC has been proposed to participate in peptidergic neurotransmission. On the other hand, mammalian acid-sensing ion channels (ASICs) are not gated but are directly modulated by FMRFamide and related mammalian peptides like NPFF and NPSF. ASICs are activated by external protons and are therefore extracellular pH sensors. They are expressed both in the central and peripheral nervous system and appear to be involved in many physiological and pathophysiological processes such as hippocampal long-term potentiation and defects in learning and memory, acquired fear-related behavior, retinal function, brain ischemia, pain sensation in ischemia and inflammation, taste perception, hearing functions, and mechanoperception. The potentiation of ASIC activity by endogenous RFamide neuropeptides probably participates in the response to noxious acidosis in sensory and central neurons. Available data also raises the possibility of the existence of still unknown FMRFamide related endogenous peptides acting as direct agonists for ASICs.

  3. GPCR-SSFE 2.0-a fragment-based molecular modeling web tool for Class A G-protein coupled receptors.

    Science.gov (United States)

    Worth, Catherine L; Kreuchwig, Franziska; Tiemann, Johanna K S; Kreuchwig, Annika; Ritschel, Michele; Kleinau, Gunnar; Hildebrand, Peter W; Krause, Gerd

    2017-07-03

    G-protein coupled receptors (GPCRs) are key players in signal transduction and therefore a large proportion of pharmaceutical drugs target these receptors. Structural data of GPCRs are sparse yet important for elucidating the molecular basis of GPCR-related diseases and for performing structure-based drug design. To ameliorate this problem, GPCR-SSFE 2.0 (http://www.ssfa-7tmr.de/ssfe2/), an intuitive web server dedicated to providing three-dimensional Class A GPCR homology models has been developed. The updated web server includes 27 inactive template structures and incorporates various new functionalities. Uniquely, it uses a fingerprint correlation scoring strategy for identifying the optimal templates, which we demonstrate captures structural features that sequence similarity alone is unable to do. Template selection is carried out separately for each helix, allowing both single-template models and fragment-based models to be built. Additionally, GPCR-SSFE 2.0 stores a comprehensive set of pre-calculated and downloadable homology models and also incorporates interactive loop modeling using the tool SL2, allowing knowledge-based input by the user to guide the selection process. For visual analysis, the NGL viewer is embedded into the result pages. Finally, blind-testing using two recently published structures shows that GPCR-SSFE 2.0 performs comparably or better than other state-of-the art GPCR modeling web servers. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  4. The Sacubitril/Valsartan, a First-in-Class, Angiotensin Receptor Neprilysin Inhibitor (ARNI): Potential Uses in Hypertension, Heart Failure, and Beyond.

    Science.gov (United States)

    Kario, Kazuomi

    2018-01-27

    Sacubitril/valsartan (LCZ696) is a first-in-class, novel-acting, angiotensin receptor neprilysin inhibitor (ARNI) that provides inhibition of neprilysin and the angiotensin (AT 1 ) receptor. A recent clinical trial PRARDIGM-HF demonstrated that this drug is superior to angiotensin-converting enzyme (ACE) inhibitors for improving the prognosis in the patients with heart failure, and this has resulted in the drug being included in clinical practice guidelines for the management of heart failure with reduced ejection fraction (EF). In addition, sacubitril/valsartan has been developed for the management of hypertension, because it has unique anti-aging properties. However, the clinical evidence of mechanism has not been well validated. A recent mechanistic study PARAMETER demonstrated that sacubitril/valsartan (LCZ696) is superior to angiotensin receptor blocker (ARB) monotherapy for reducing central aortic systolic pressure (primary endpoint) as well as for central aortic pulse pressure (secondary endpoint) and nocturnal BP preferentially. Considering these results, sacubitril/valsartan may be an attractive therapeutic agent to treat the elderly with age-related hypertension phenotypes, such as drug-uncontrolled (resistant) hypertension characterized as systolic (central) hypertension (structural hypertension) and/or nocturnal hypertension (salt-sensitive hypertension). These are the high-risk hypertension phenotypes which are prone to develop heart failure with preserved EF and chronic kidney disease. Sacubitril/valsartan may be effective to suppress the age-related continuum from hypertension to heart failure, and it could be clinically useful not only for secondary prevention, but also as primary prevention of heart failure in uncontrolled elderly hypertensive patients.

  5. Boundary scavenging in the Pacific Ocean

    International Nuclear Information System (INIS)

    Anderson, R.F.; Lao, Y.; Broecker, W.S.; Trumbore, S.E.; Hofmann, H.J.; Wolfli, W.

    1990-01-01

    Concentrations of U, Th, 231 Pa and 10 Be were measured in Holocene sediments from two cores collected off the west coast of South America, two cores from the East Pacific Rise, two from the equatorial Pacific and one from the south Pacific central gyre. Our results, together with data from 5 cores reported in the literature, show that boundary scavenging plays a major role in the removal of 10 Be from the Pacific Ocean. Deposition rates of 10 Be at three margin sites are more than an order of magnitude greater than at sites of red clay accumulation in the deep central Pacific. Deposition of 231 Pa is 4 to 5-fold greater at the margin sites. The residence time of 10 Be with respect to chemical scavenging, defined as its inventory in the water column divided by its rate of removal to the sediments, varies regionally from >1000 years at the red-clay sites in the deep central Pacific to ∝100 years at the margin sites. Different factors control boundary scavenging of Pa and Be. For example, scavenging of 231 Pa is enhanced by metal-oxide coatings of particles, whereas this seems to have little influence on the scavenging of 10 Be. (orig.)

  6. Three classes of ligands each bind to distinct sites on the orphan G protein-coupled receptor GPR84.

    Science.gov (United States)

    Mahmud, Zobaer Al; Jenkins, Laura; Ulven, Trond; Labéguère, Frédéric; Gosmini, Romain; De Vos, Steve; Hudson, Brian D; Tikhonova, Irina G; Milligan, Graeme

    2017-12-20

    Medium chain fatty acids can activate the pro-inflammatory receptor GPR84 but so also can molecules related to 3,3'-diindolylmethane. 3,3'-Diindolylmethane and decanoic acid acted as strong positive allosteric modulators of the function of each other and analysis showed the affinity of 3,3'-diindolylmethane to be at least 100 fold higher. Methyl decanoate was not an agonist at GPR84. This implies a key role in binding for the carboxylic acid of the fatty acid. Via homology modelling we predicted and confirmed an integral role of arginine 172 , located in the 2nd extracellular loop, in the action of decanoic acid but not of 3,3'-diindolylmethane. Exemplars from a patented series of GPR84 antagonists were able to block agonist actions of both decanoic acid and 3,3'-diindolylmethane at GPR84. However, although a radiolabelled form of a related antagonist, [ 3 H]G9543, was able to bind with high affinity to GPR84, this was not competed for by increasing concentrations of either decanoic acid or 3,3'-diindolylmethane and was not affected adversely by mutation of arginine 172 . These studies identify three separable ligand binding sites within GPR84 and suggest that if medium chain fatty acids are true endogenous regulators then co-binding with a positive allosteric modulator would greatly enhance their function in physiological settings.

  7. The Prohibition of Employment as Manual Scavengers and their Rehabilitation Act, 2013: A Review

    Directory of Open Access Journals (Sweden)

    Aparajita Baruah

    2014-02-01

    Full Text Available Manual scavenging is a caste-based and hereditary occupation for Dalits (untouchables, which is predominantly linked with forced labour or slavery. In this article, an attempt has been made to trace out the brief history of the practice of manual scavenging in India. The author has also dwelt upon the constitutional commitment as well as measures taken up by the successive governments to improve the conditions of this class of people. The hallmark of the article lies in the detailed analysis along with some suitable suggestions on the Prohibition of Employment as Manual Scav- engers and their Rehabilitation Act, 2013 recently enacted by the Parliament of India.

  8. Ocular toxoplasmosis: susceptibility in respect to the genes encoding the KIR receptors and their HLA class I ligands

    Science.gov (United States)

    Ayo, Christiane Maria; Frederico, Fábio Batista; Siqueira, Rubens Camargo; Brandão de Mattos, Cinara de Cássia; Previato, Mariana; Barbosa, Amanda Pires; Murata, Fernando Henrique Antunes; Silveira-Carvalho, Aparecida Perpétuo; de Mattos, Luiz Carlos

    2016-01-01

    The objective of this study was to investigate the influence of the genes encoding the KIR receptors and their HLA ligands in the susceptibility of ocular toxoplasmosis. A total of 297 patients serologically-diagnosed with toxoplasmosis were selected and stratified according to the presence (n = 148) or absence (n = 149) of ocular scars/lesions due to toxoplasmosis. The group of patients with scars/lesions was further subdivided into two groups according to the type of ocular manifestation observed: primary (n = 120) or recurrent (n = 28). Genotyping was performed by PCR-SSOP. Statistical analyses were conducted using the Chi-square test, and odds ratio with a 95% confidence interval was also calculated to evaluate the risk association. The activating KIR3DS1 gene was associated with increased susceptibility for ocular toxoplasmosis. The activating KIR together with their HLA ligands (KIR3DS1-Bw4-80Ile and KIR2DS1+/C2++ KIR3DS1+/Bw4-80Ile+) were associated with increased susceptibility for ocular toxoplasmosis and its clinical manifestations. KIR-HLA inhibitory pairs -KIR2DL3/2DL3-C1/C1 and KIR2DL3/2DL3-C1- were associated with decreased susceptibility for ocular toxoplasmosis and its clinical forms, while the KIR3DS1−/KIR3DL1+/Bw4-80Ile+ combination was associated as a protective factor against the development of ocular toxoplasmosis and, in particular, against recurrent manifestations. Our data demonstrate that activating and inhibitory KIR genes may influence the development of ocular toxoplasmosis. PMID:27827450

  9. A gut-homing, oligoclonal CD4+ T cell population in severe-combined immunodeficient mice expressing a rearranged, transgenic class I-restricted alpha beta T cell receptor

    DEFF Research Database (Denmark)

    Reimann, J; Rudolphi, A; Spiess, S

    1995-01-01

    We studied the peripheral T cell compartment of H-2b severe combined immunodeficient (scid) mice that express a transgenic (tg) alpha beta T cell receptor (TcR) specific for the H-Y (male) epitope presented by the H-2 class I Db molecule. Large populations of CD3+ NK1.1-TCR beta T+ T cells were...

  10. Cellular receptors for human enterovirus species A

    Directory of Open Access Journals (Sweden)

    Yorihiro eNishimura

    2012-03-01

    Full Text Available Human enterovirus species A (HEV-A is one of the four species of HEV in the genus Enterovirus in the family Picornaviridae. Among HEV-A, coxsackievirus A16 (CVA16 and enterovirus 71 (EV71 are the major causative agents of hand, foot, and mouth disease (HFMD. Some other types of HEV-A are commonly associated with herpangina. Although HFMD and herpangina due to HEV-A are common febrile diseases among infants and children, EV71 can cause various neurological diseases, such as aseptic meningitis and fatal encephalitis.Recently, two human transmembrane proteins, P-selectin glycoprotein ligand-1 (PSGL-1 and scavenger receptor class B, member 2 (SCARB2, were identified as functional receptors for EV71 and CVA16. In in vitro infection experiments using the prototype HEV-A strains, PSGL-1 and SCARB2 could be responsible for the specific receptors for EV71 and CVA16. However, the involvement of both receptors in the in vitro and in vivo infections of clinical isolates of HEV-A has not been clarified yet. To elucidate a diverse array of the clinical outcome of HEV-A-associated diseases, the identification and characterization of HEV-A receptors may provide useful information in understanding the HEV-A pathogenesis at a molecular level.

  11. Free Radical Scavenging Properties of Annona squamosa

    Science.gov (United States)

    Vikas, Biba; Akhil B, S; P, Remani; Sujathan, K

    2017-10-26

    Annona squamosa has extensively been used in the traditional and folkloric medicine and found to possess many biological activities. Different solvents, petroleum ether, chloroform, ethyl acetate and methanol extracts of Annona squamosa seeds (ASPE, ASCH, ASEA, ASME) have been used to prepare plant extracts. The present investigations dealt with the free radical scavenging activity of four extracts using various techniques such as total reducing power estimation, total phenolic count, 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging effect, evaluation of ABTS cation decolorisation capacity, FRAP assay, hdroxyl radical scavenging assay, super oxide assay and Nitric oxide radical scavenging assay of the extracts. The results showed that the four extracts of Annona squamosa showed significant reducing power in four extracts. The total phenolic contents in petroleum ether, chloroform, ethyl acetate, methanol extracts and positive control were 0.64±0.17, 0.54±0.27, 0.49±0.24, 0.57±0.22 and 0.66±0.33. The antioxidant capacity by ABTS assay of ASPE, ASCH, ASEA, ASME and positive control, trolox showed 77.75±0.5,73.25±1.7,78.5± 1.2 , 80 ± 0.8 μg/ml and 94.2 ± 0.9 respectively. The (50 % scavenging activity) SA50 of ASPE and ASCH, ASEA and ASME was found to be 34.4 μg/ml, 43.8 μg/ml 34.7 μg/m and 28.8 μg/ml respectively by DPPH assay. The percentage of hydroxyl radical scavenging increased with the increasing concentration of the extracts. ASPE, ASCH, ASEA and ASME showed superoxide radical scavenging activity, as indicated by their values 66 ± 0.5, 68 ± 1 ,63 ± 1 and 70 ± 0.5 μg/ml respectively compared to gallic acid which was 97 ± 0.5 μg/ml. The values for scavenging of nitric oxide for ASPE, ASCH, ASEA and ASME were 91.0 ± 1.0, 66.75 ± 0.5, 71.75 ± 1.1 and 75.75 ± 1.15 μg/ml while value for standard ascorbic acid was 91.0 ± 1.0 μg/ml. The results revealed strong antioxidants in four extracts may lead to the development of potent

  12. Impairment of the class IIa bacteriocin receptor function and membrane structural changes are associated to enterocin CRL35 high resistance in Listeria monocytogenes.

    Science.gov (United States)

    Masias, Emilse; Dupuy, Fernando G; da Silva Sanches, Paulo Ricardo; Farizano, Juan Vicente; Cilli, Eduardo; Bellomio, Augusto; Saavedra, Lucila; Minahk, Carlos

    2017-07-01

    Enterocin CRL35 is a class IIa bacteriocin with anti-Listeria activity. Resistance to these peptides has been associated with either the downregulation of the receptor expression or changes in the membrane and cell walls. The scope of the present work was to characterize enterocin CRL35 resistant Listeria strains with MICs more than 10,000 times higher than the MIC of the WT sensitive strain. Listeria monocytogenes INS7 resistant isolates R2 and R3 were characterized by 16S RNA gene sequencing and rep-PCR. Bacterial growth kinetic was studied in different culture media. Plasma membranes of sensitive and resistant bacteria were characterized by FTIR and Langmuir monolayer techniques. The growth kinetic of the resistant isolates was slower as compared to the parental strain in TSB medium. Moreover, the resistant isolates barely grew in a glucose-based synthetic medium, suggesting that these cells had a major alteration in glucose transport. Resistant bacteria also had alterations in their cell wall and, most importantly, membrane lipids. In fact, even though enterocin CRL35 was able to bind to the membrane-water interface of both resistant and parental sensitive strains, this peptide was only able to get inserted into the latter membranes. These results indicate that bacteriocin receptor is altered in combination with membrane structural modifications in enterocin CRL35-resistant L. monocytogenes strains. Highly enterocin CRL35-resistant isolates derived from Listeria monocytogenes INS7 have not only an impaired glucose transport but also display structural changes in the hydrophobic core of their plasma membranes. Copyright © 2017. Published by Elsevier B.V.

  13. Nature or Nurture? Gender Roles Scavenger Hunt

    Science.gov (United States)

    Whalen, Shannon; Maurer-Starks, Suanne

    2008-01-01

    The examination of gender roles and stereotypes and their subsequent impact on sexual behavior is a concept for discussion in many sex education courses in college and sex education units in high school. This analysis often leads to a discussion of the impact of nature vs. nurture on gender roles. The gender roles scavenger hunt is an interactive…

  14. Role of antioxidant scavenging enzymes and extracellular ...

    African Journals Online (AJOL)

    In the present work, we studied the role of antioxidant scavenging enzymes of plant pathogenic bacteria: catalase, ascorbate peroxidase and a virulence factor; extracelluar polysaccharide production in determining the virulence of Xanthomonas oryzae pv. oryzae (Xoo) isolates and its differential reaction to rice cultivars.

  15. Antioxidant Capacity, Radical Scavenging Kinetics and Phenolic ...

    African Journals Online (AJOL)

    Antioxidant Capacity, Radical Scavenging Kinetics and Phenolic Profile of Methanol Extracts of Wild Plants of Southern Sonora, Mexico. EF Moran-Palacio, LA Zamora-Álvarez, NA Stephens-Camacho, GA Yáñez- Farías, A Virgen-Ortiz, O Martínez-Cruz, JA Rosas-Rodríguez ...

  16. Phytochemical screening, free radical scavenging and antibacterial ...

    African Journals Online (AJOL)

    Cassia sieberiana is a tropical plant, widely distributed throughout Sudan and Guinea savannah. It is used in traditional medicine for the treatment of malarial, cancer and stomach ache. The study was conducted to screen for phytochemicals, free radical scavenging and antibacterial potentials of the root bark.

  17. Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

    Science.gov (United States)

    Boardman, D A; Philippeos, C; Fruhwirth, G O; Ibrahim, M A A; Hannen, R F; Cooper, D; Marelli-Berg, F M; Watt, F M; Lechler, R I; Maher, J; Smyth, L A; Lombardi, G

    2017-04-01

    Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  18. Scavenging and recombination kinetics in a radiation spur: The successive ordered scavenging events

    Science.gov (United States)

    Al-Samra, Eyad H.; Green, Nicholas J. B.

    2018-03-01

    This study describes stochastic models to investigate the successive ordered scavenging events in a spur of four radicals, a model system based on a radiation spur. Three simulation models have been developed to obtain the probabilities of the ordered scavenging events: (i) a Monte Carlo random flight (RF) model, (ii) hybrid simulations in which the reaction rate coefficient is used to generate scavenging times for the radicals and (iii) the independent reaction times (IRT) method. The results of these simulations are found to be in agreement with one another. In addition, a detailed master equation treatment is also presented, and used to extract simulated rate coefficients of the ordered scavenging reactions from the RF simulations. These rate coefficients are transient, the rate coefficients obtained for subsequent reactions are effectively equal, and in reasonable agreement with the simple correction for competition effects that has recently been proposed.

  19. Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity.

    Science.gov (United States)

    Li, Qing; Sun, Xueqi; Gu, Guodong; Guo, Zhanyong

    2018-03-28

    Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating "click reaction" with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC 50 radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

  20. Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia.

    Science.gov (United States)

    Pai, Peiying; Lai, Ching Jung; Lin, Ching-Yuang; Liou, Yi-Fan; Huang, Chih-Yang; Lee, Shin-Da

    2016-04-15

    Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2 (-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo) at 5-6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances

  1. Investigation into Seasonal Scavenging Patterns of Raccoons on Human Decomposition.

    Science.gov (United States)

    Jeong, Yangseung; Jantz, Lee Meadows; Smith, Jake

    2016-03-01

    Although raccoons are known as one of the most common scavengers in the U.S., scavenging by these animals has seldom been studied in terms of forensic significance. In this research, the seasonal pattern of raccoon scavenging and its effect on human decomposition was investigated using 178 human cadavers placed at the Anthropological Research Facility (ARF) of the University of Tennessee, Knoxville (UTK) between February 2011 and December 2013. The results reveal that (i) the frequency of scavenging increases during summer, (ii) scavenging occurs relatively immediately and lasts shorter in summer months, and (iii) scavenging influences the decomposition process by hollowing limbs and by disturbing insect activities, both of which eventually increases the chance of mummification on the affected body. This information is expected to help forensic investigators identify raccoon scavenging as well as make a more precise interpretation of the effect of raccoon scavenging on bodies at crime scenes. © 2015 American Academy of Forensic Sciences.

  2. Modeling the interactions of a peptide-major histocompatibility class I ligand with its receptors. II. Cross-reaction between a monoclonal antibody and two alpha beta T cell receptors

    DEFF Research Database (Denmark)

    Rognan, D; Engberg, J; Stryhn, A

    2000-01-01

    -peptide pair into the Fab combining site. Interestingly, the most energetically favored binding mode shows numerous analogies to the recently determined recognition of class I MHC-peptide complexes by alpha beta T cell receptors (TCRs). The pSAN13.4.1 also binds diagonally across the MHC binding groove......The recombinant antibody, pSAN13.4.1, has a unique T cell like specificity; it binds an Influenza Hemagglutinin octapeptide (Ha255-262) in an MHC (H-2Kk)-restricted manner, and a detailed comparison of the fine specificity of pSAN13.4.1 with the fine specificity of two Ha255-262-specific, H-2Kk......-restricted T cell hybridomas has supported this contention. A three-dimensional model of pSAN13.4.1 has been derived by homology modeling techniques. Subsequently, the structure of the pSAN13.4.1 antibody in complex with the antigenic Ha-Kk ligand was derived after a flexible and automated docking of the MHC...

  3. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Smith, Kevin J; Mobarec, Juan C; Furness, Sebastian G B; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-10-15

    Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues located towards the TM helical boundaries of Class B GPCRs that are important for GLP-1 receptor stability and/or controlling signalling specificity and biased agonism. This includes (i) three positively charged residues (R3.30 227 , K4.64 288 , R5.40 310 ) located at the extracellular boundaries of TMs 3, 4 and 5 that are predicted in molecular models to stabilise extracellular loop 2, a crucial domain for ligand affinity and receptor activation; (ii) a predicted hydrogen bond network between residues located in TMs 2 (R2.46 176 ), 6 (R6.37 348 ) and 7 (N7.61 406 and E7.63 408 ) at the cytoplasmic face of the receptor that is important for stabilising the inactive receptor and directing signalling specificity, (iii) residues at the bottom of TM 5 (R5.56 326 ) and TM6 (K6.35 346 and K6.40 351 ) that are crucial for receptor activation and downstream signalling; (iv) residues predicted to be involved in stabilisation of TM4 (N2.52 182 and Y3.52 250 ) that also influence cell signalling. Collectively, this work expands our understanding of peptide-mediated signalling by the GLP-1 receptor. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Precipitation scavenging of tritiated water vapour (HTO)

    International Nuclear Information System (INIS)

    Ogram, G.L.

    1985-10-01

    Precipitation scavenging (or washout) is an important mechanism for the removal of HTO from the atmosphere. Methods of parameterizing the depletion of a plume of HTO released to the atmosphere are examined. Simple approaches, commonly used for atmospheric transport modelling purposes, such as the use of a constant washout coefficient or washout ratio, or the use of parameters based on equilibrium assumptions, are often not justified. It is shown that these parameters depend strongly on ambient temperature and plume dimensions, as well as rainfall rate. An approximate expression for washout ratio, as a function of these variables, is developed, and it is shown that near equilibrium washout conditions are only expected to hold at long plume travel distances. A possible method of treating scavenging by snow is also suggested

  5. Mobile vapor recovery and vapor scavenging unit

    International Nuclear Information System (INIS)

    Stokes, C.A.; Steppe, D.E.

    1991-01-01

    This patent describes a mobile anti- pollution apparatus, for the recovery of hydrocarbon emissions. It comprises a mobile platform upon which is mounted a vapor recovery unit for recovering vapors including light hydrocarbons, the vapor recovery unit having an inlet and an outlet end, the inlet end adapted for coupling to an external source of hydrocarbon vapor emissions to recover a portion of the vapors including light hydrocarbons emitted therefrom, and the outlet end adapted for connection to a means for conveying unrecovered vapors to a vapor scavenging unit, the vapor scavenging unit comprising an internal combustion engine adapted for utilizing light hydrocarbon in the unrecovered vapors exiting from the vapor recovery unit as supplemental fuel

  6. Energy scavenging sources for biomedical sensors

    International Nuclear Information System (INIS)

    Romero, E; Warrington, R O; Neuman, M R

    2009-01-01

    Energy scavenging has increasingly become an interesting option for powering electronic devices because of the almost infinite lifetime and the non-dependence on fuels for energy generation. Moreover, the rise of wireless technologies promises new applications in medical monitoring systems, but these still face limitations due to battery lifetime and size. A trade-off of these two factors has typically governed the size, useful life and capabilities of an autonomous system. Energy generation from sources such as motion, light and temperature gradients has been established as commercially viable alternatives to batteries for human-powered flashlights, solar calculators, radio receivers and thermal-powered wristwatches, among others. Research on energy harvesting from human activities has also addressed the feasibility of powering wearable or implantable systems. Biomedical sensors can take advantage of human-based activities as the energy source for energy scavengers. This review describes the state of the art of energy scavenging technologies for powering sensors and instrumentation of physiological variables. After a short description of the human power and the energy generation limits, the different transduction mechanisms, recent developments and challenges faced are reviewed and discussed. (topical review)

  7. Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2▿

    Science.gov (United States)

    Barrionuevo, Paula; Cassataro, Juliana; Delpino, M. Victoria; Zwerdling, Astrid; Pasquevich, Karina A.; Samartino, Clara García; Wallach, Jorge C.; Fossati, Carlos A.; Giambartolomei, Guillermo H.

    2008-01-01

    The strategies that allow Brucella abortus to survive inside macrophages for prolonged periods and to avoid the immunological surveillance of major histocompatibility complex class II (MHC-II)-restricted gamma interferon (IFN-γ)-producing CD4+ T lymphocytes are poorly understood. We report here that infection of THP-1 cells with B. abortus inhibited expression of MHC-II molecules and antigen (Ag) processing. Heat-killed B. abortus (HKBA) also induced both these phenomena, indicating the independence of bacterial viability and involvement of a structural component of the bacterium. Accordingly, outer membrane protein 19 (Omp19), a prototypical B. abortus lipoprotein, inhibited both MHC-II expression and Ag processing to the same extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics the structure of the protein lipid moiety also inhibited MHC-II expression, indicating that any Brucella lipoprotein could down-modulate MHC-II expression and Ag processing. Inhibition of MHC-II expression and Ag processing by either HKBA or lipidated Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and Ag processing of human monocytes. In addition, exposure to the synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation and IFN-γ production of peripheral blood mononuclear cells from Brucella-infected patients. Together, these results indicate that there is a mechanism by which B. abortus may prevent recognition by T cells to evade host immunity and establish a chronic infection. PMID:17984211

  8. Ranakinestatin-PPF from the skin secretion of the Fukien gold-striped pond frog, Pelophylax plancyi fukienensis: a prototype of a novel class of bradykinin B2 receptor antagonist peptide from ranid frogs.

    Science.gov (United States)

    Ma, Jie; Luo, Yu; Ge, Lilin; Wang, Lei; Zhou, Mei; Zhang, Yingqi; Duan, Jinao; Chen, Tianbao; Shaw, Chris

    2014-01-01

    The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin-a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV), named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10(-6)M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10(-11)M and 10(-5)M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140) and B2-receptor (HOE140) antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin-PPF-thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

  9. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor

    OpenAIRE

    Wootten, Denise; Reynolds, Christopher A.; Smith, Kevin J.; Mobarec, Juan C.; Furness, Sebastian G.B.; Miller, Laurence J.; Christopoulos, Arthur; Sexton, Patrick M.

    2016-01-01

    Class B GPCRs can activate multiple signalling effectors with the potential to exhibit biased agonism in response to ligand stimulation. Previously, we highlighted key TM domain polar amino acids that were crucial for the function of the GLP-1 receptor, a key therapeutic target for diabetes and obesity. Using a combination of mutagenesis, pharmacological characterisation, mathematical and computational molecular modelling, this study identifies additional highly conserved polar residues locat...

  10. Toll-like receptor 7 cooperates with IL-4 in activated B cells through antigen receptor or CD38 and induces class switch recombination and IgG1 production.

    Science.gov (United States)

    Tsukamoto, Yumiko; Nagai, Yoshinori; Kariyone, Ai; Shibata, Takuma; Kaisho, Tsuneyasu; Akira, Shizuo; Miyake, Kensuke; Takatsu, Kiyoshi

    2009-04-01

    IL-4 and 8-mercaptoguanosine (8-SGuo) stimulation of CD38-activated B cells induces mu to gamma1 class switch recombination (CSR) at the DNA level leading to a high level of IgG1 production. Although some of signaling events initiated by IL-4 in activated B cells have been characterized, the involvement of TLR/MyD88 and Btk pathway in IL-4-dependent mu to gamma1 CSR has not been thoroughly evaluated. In this study, we characterized receptors for 8-SGuo and differential roles of 8-SGuo and IL-4 in the induction and mu to gamma1 CSR and IgG1 production. The role of TLR7 and MyD88 in 8-SGuo-induced AID expression and mu to gamma1 CSR was documented, as 8-SGuo did not act on CD38-stimulated splenic B cells from Tlr7(-/-) and Myd88(-/-) mice. CD38-activated B cells from Btk-deficient mice failed to respond to TLR7 ligands for the AID expression and CSR, indicating that Btk is also indispensable for the system. Stimulation of CD38-activated B cells with 8-SGuo induced significant AID expression and DNA double strand breaks, but IL-4 stimulation by itself did not trigger mu to gamma1 CSR. Intriguingly, the mu to gamma1 CSR in the B cells stimulated with CD38 and 8-SGuo totally depends on IL-4 stimulation. Similar results were obtained in the activated B cells through BCR and loxoribine, a well-known TLR7 ligand, in place of 8-SGuo. In vivo administration of TLR7 ligand and anti-CD38 antibody induced the generation of CD138(+) IgG1(+) cells. These results indicate that TLR7 is a receptor for 8-SGuo and plays an essential role in the AID and Blimp-1 expression; however it is not enough to complete mu to gamma1 CSR in CD38-activated B cells. IL-4 may be required for the induction of DNA repair system together with AID for the completion of CSR.

  11. SMM-chemokines: a class of unnatural synthetic molecules as chemical probes of chemokine receptor biology and leads for therapeutic development.

    Science.gov (United States)

    Kumar, Santosh; Choi, Won-Tak; Dong, Chang-Zhi; Madani, Navid; Tian, Shaomin; Liu, Dongxiang; Wang, Youli; Pesavento, James; Wang, Jun; Fan, Xuejun; Yuan, Jian; Fritzsche, Wayne R; An, Jing; Sodroski, Joseph G; Richman, Douglas D; Huang, Ziwei

    2006-01-01

    Chemokines and their receptors play important roles in numerous physiological and pathological processes. To develop natural chemokines into receptor probes and inhibitors of pathological processes, the lack of chemokine-receptor selectivity must be overcome. Here, we apply chemical synthesis and the concept of modular modifications to generate unnatural synthetically and modularly modified (SMM)-chemokines that have high receptor selectivity and affinity, and reduced toxicity. A proof of the concept was shown by transforming the nonselective viral macrophage inflammatory protein-II into new analogs with enhanced selectivity and potency for CXCR4 or CCR5, two principal coreceptors for human immunodeficiency virus (HIV)-1 entry. These new analogs provided insights into receptor binding and signaling mechanisms and acted as potent HIV-1 inhibitors. These results support the concept of SMM-chemokines for studying and controlling the function of other chemokine receptors.

  12. Flavonoids: hemisynthesis, reactivity, characterization and free radical scavenging activity.

    Science.gov (United States)

    Es-Safi, Nour-Eddine; Ghidouche, Souhila; Ducrot, Paul Henri

    2007-09-26

    Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation products have been

  13. Flavonoids: Hemisynthesis, Reactivity, Characterization and Free Radical Scavenging Activity

    Directory of Open Access Journals (Sweden)

    Paul Henri Ducrot

    2007-09-01

    Full Text Available Phenolic compounds form one of the main classes of secondary metabolites. They display a large range of structures and they are responsible for the major organoleptic characteristics of plant-derived-foods and beverages, particularly color and taste properties and they also contribute to the nutritional qualities of fruits and vegetables. Phenolic compounds are also highly unstable compounds which undergo numerous enzymatic and chemical reactions during postharvest food storage and processing thus adding to the complexity of plant polyphenol composition. Among these compounds flavonoids constitute one of the most ubiquitous groups of all plant phenolics. Owing to their importance in food organoleptic properties and in human health, a better understanding of their structures, their reactivity and chemical properties in addition to the mechanisms generating them appears essential to predict and control food quality. The purpose of this work is an overview of our findings concerning the hemisynthesis, the reactivity and the enzymatic oxidation of some flavonoids and shed light on the mechanisms involved in some of these processes and the structures of the resulting products. The free radical scavenging activity of some of the synthesized compounds is also presented and a structure-activity relationship is discussed. The first part of this review concerns the synthesis and structural characterization of modified monomeric flavanols. The use of these compounds as precursor for the preparation of natural and modified dimeric procyanidin derivatives was then explored through different coupling reactions. The full characterization of the synthesized compounds was achieved by concerted use of NMR and ESI-MS techniques. The free radical scavenging activity of some of the synthesized compounds was investigated. The second part of this review concerns the enzymatic oxidation of several flavonols by Trametes versicolor laccase. Most of the major oxidation

  14. Differentiation of Forebrain and Hippocampal Dopamine 1-Class Receptors, D1R and D5R, in Spatial Learning and Memory

    Science.gov (United States)

    Sariñana, Joshua; Tonegawa, Susumu

    2017-01-01

    Activation of prefrontal cortical (PFC), striatal, and hippocampal dopamine 1-class receptors (D1R and D5R) is necessary for normal spatial information processing. Yet the precise role of the D1R versus the D5R in the aforementioned structures, and their specific contribution to the water-maze spatial learning task remains unknown. D1R- and D5R- specific in situ hybridization probes showed that forebrain restricted D1R and D5R KO mice (F-D1R/D5R KO) displayed D1R mRNA deletion in the medial (m)PFC, dorsal and ventral striatum, and the dentate gyrus (DG) of the hippocampus. D5R mRNA deletion was limited to the mPFC, the CA1 and DG hippocampal subregions. F-D1R/D5R KO mice were given water-maze training and displayed subtle spatial latency differences between genotypes and spatial memory deficits during both regular and reversal training. To differentiate forebrain D1R from D5R activation, forebrain restricted D1R KO (F-D1R KO) and D5R KO (F-D5R KO) mice were trained on the water-maze task. F-D1R KO animals exhibited escape latency deficits throughout regular and reversal training as well as spatial memory deficits during reversal training. F-D1R KO mice also showed perseverative behavior during the reversal spatial memory probe test. In contrast, F-D5R KO animals did not present observable deficits on the water-maze task. Because F-D1R KO mice showed water-maze deficits we tested the necessity of hippocampal D1R activation for spatial learning and memory. We trained DG restricted D1R KO (DG-D1R KO) mice on the water-maze task. DG-D1R KO mice did not present detectable spatial memory deficit, but did show subtle deficits during specific days of training. Our data provides evidence that forebrain D5R activation plays a unique role in spatial learning and memory in conjunction with D1R activation. Moreover, these data suggest that mPFC and striatal, but not DG D1R activation are essential for spatial learning and memory. PMID:26174222

  15. Genetic Variations in the Human G Protein-coupled Receptor Class C, Group 6, Member A (GPRC6A) Control Cell Surface Expression and Function

    DEFF Research Database (Denmark)

    Jorgensen, Stine; Have, Christian Theil; Underwood, Christina Rye

    2017-01-01

    -expressed murine and goldfish orthologs. The latter orthologs are Gq-coupled and lead to intracellular accumulation of inositol phosphates and calcium release. In the present study we cloned the bonobo chimpanzee GPRC6A receptor, which is 99% identical to the human receptor, and show that it is cell surface...

  16. Differential Scavenging Among Pig, Rabbit, and Human Subjects.

    Science.gov (United States)

    Steadman, Dawnie Wolfe; Dautartas, Angela; Kenyhercz, Michael W; Jantz, Lee M; Mundorff, Amy; Vidoli, Giovanna M

    2018-04-12

    Different animal species have been used as proxies for human remains in decomposition studies for decades, although few studies have sought to validate their use in research aimed at estimating the postmortem interval. This study examines 45 pig, rabbit, and human subjects placed in three seasonal trials at the Anthropology Research Facility. In an earlier paper, we found that overall decomposition trends did vary between species that could be due to differential insect and scavenger behavior. This study specifically examines if scavenger behavior differs by carrion species. Daily photographs, game camera photographs, written observations, and Total Body Score (TBS) documented scavenging and decomposition changes. Results show that raccoons were the most commonly observed vertebrate scavenger, that scavenging was most extensive in winter, and that certain human subjects were preferred over other humans and all non-human subjects. Finally, scavenging activity greatly reduces the accuracy of postmortem interval estimates based on TBS. © 2018 American Academy of Forensic Sciences.

  17. Co-evolution of human leukocyte antigen (HLA class I ligands with killer-cell immunoglobulin-like receptors (KIR in a genetically diverse population of sub-Saharan Africans.

    Directory of Open Access Journals (Sweden)

    Paul J Norman

    2013-10-01

    Full Text Available Interactions between HLA class I molecules and killer-cell immunoglobulin-like receptors (KIR control natural killer cell (NK functions in immunity and reproduction. Encoded by genes on different chromosomes, these polymorphic ligands and receptors correlate highly with disease resistance and susceptibility. Although studied at low-resolution in many populations, high-resolution analysis of combinatorial diversity of HLA class I and KIR is limited to Asian and Amerindian populations with low genetic diversity. At the other end of the spectrum is the West African population investigated here: we studied 235 individuals, including 104 mother-child pairs, from the Ga-Adangbe of Ghana. This population has a rich diversity of 175 KIR variants forming 208 KIR haplotypes, and 81 HLA-A, -B and -C variants forming 190 HLA class I haplotypes. Each individual we studied has a unique compound genotype of HLA class I and KIR, forming 1-14 functional ligand-receptor interactions. Maintaining this exceptionally high polymorphism is balancing selection. The centromeric region of the KIR locus, encoding HLA-C receptors, is highly diverse whereas the telomeric region encoding Bw4-specific KIR3DL1, lacks diversity in Africans. Present in the Ga-Adangbe are high frequencies of Bw4-bearing HLA-B*53:01 and Bw4-lacking HLA-B*35:01, which otherwise are identical. Balancing selection at key residues maintains numerous HLA-B allotypes having and lacking Bw4, and also those of stronger and weaker interaction with LILRB1, a KIR-related receptor. Correspondingly, there is a balance at key residues of KIR3DL1 that modulate its level of cell-surface expression. Thus, capacity to interact with NK cells synergizes with peptide binding diversity to drive HLA-B allele frequency distribution. These features of KIR and HLA are consistent with ongoing co-evolution and selection imposed by a pathogen endemic to West Africa. Because of the prevalence of malaria in the Ga-Adangbe and

  18. Radical scavenging activity of crude polysaccharides from Camellia sinensis

    Directory of Open Access Journals (Sweden)

    Yang Fan

    2011-01-01

    Full Text Available A preparation of crude polysaccharides (TPS was isolated from Camellia sinensis by precipitation and ultrafiltration. TPS1, TPS2, and TPS3 had molecular weights of 240, 21.4, and 2.46 kDa, respectively. The radical scavenging activities of TPS were evaluated by DPPH free radical, hydroxyl radical and superoxide radical scavenging. These results revealed that TPS exhibited strong radical scavenging activity in a concentration-dependent manner. TPS3 with lowest molecular weight showed a higher radical scavenging activity.

  19. Chimeric RXFP1 and RXFP2 receptors highlight the similar mechanism of activation utilizing their N-terminal low density lipoprotein class A modules

    Directory of Open Access Journals (Sweden)

    Shoni eBruell

    2013-11-01

    Full Text Available Relaxin family peptide (RXFP receptors 1 and 2 are unique G-protein coupled receptors in that they contain an N-terminal low density lipoprotein type A (LDLa module which is necessary for receptor activation. The current hypothesis suggests that upon ligand binding the LDLa module interacts with the transmembrane (TM domain of a homodimer partner receptor to induce the active receptor conformations. We recently demonstrated that three residues in the N-terminus of the RXFP1 LDLa module are potentially involved in hydrophobic interactions with the receptor to drive activation. RXFP2 shares two out of three of the residues implicated, suggesting that the two LDLa modules could be interchanged without adversely affecting activity. However, in 2007 it was shown that a chimera consisting of the RXFP1 receptor with its LDLa swapped for that of RXFP2 did not signal. We noticed this construct also contained the RXFP2 region linking the LDLa to the leucine-rich repeats. We therefore constructed chimeric RXFP1 and RXFP2 receptors with their LDLa modules swapped immediately C-terminally to the final cysteine residue of the module, retaining the native linker. In addition, we exchanged the TM domains of the chimeras to explore if matching the LDLa module with the TM domain of its native receptor altered activity. All of the chimeras were expressed at the surface of HEK293T cells with ligand binding profiles similar to the wild-type receptors. Importantly, as predicted, ligand binding was able to induce cAMP based signalling. Chimeras of RXFP1 with the LDLa of RXFP2 demonstrated reduced H2 relaxin potency with the pairing of the RXFP2 TM with the RXFP2 LDLa necessary for full ligand efficacy. In contrast the ligand mediated potencies and efficacies on the RXFP2 chimeras were similar suggesting the RXFP1 LDLa module has similar efficacy on the RXFP2 TM domain. Our studies demonstrate the LDLa modules of RXFP1 and RXFP2 modulate receptor activation via a

  20. Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

    Directory of Open Access Journals (Sweden)

    Jie Ma

    2014-01-01

    Full Text Available The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs. Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin gene-related peptide, kinestatin—a specific bradykinin B2-receptor antagonist from the skin of the giant fire-bellied toad, Bombina maxima. Here, we describe the identification, structural and functional characterization of a heptadecapeptide (DYTIRTRLHQGLSRKIV, named ranakinestatin-PPF, from the skin of the Chinese ranid frog, Pelophylax plancyi fukienensis, representing a prototype of a novel class of bradykinin B2-receptor specific antagonist. Using a preconstricted preparation of rat tail arterial smooth muscle, a single dose of 10−6 M of the peptide effectively inhibited the dose-dependent relaxation effect of bradykinin between 10−11 M and 10−5 M and subsequently, this effect was pharmacologically-characterized using specific bradykinin B1- (desArg-HOE140 and B2-receptor (HOE140 antagonists; the data from which demonstrated that the antagonism of the novel peptide was mediated through B2-receptors. Ranakinestatin—PPF—thus represents a prototype of an amphibian skin peptide family that functions as a bradykinin B2-receptor antagonist herein demonstrated using mammalian vascular smooth muscle.

  1. Rain scavenging studies. Progress report No. 11

    International Nuclear Information System (INIS)

    Dingle, A.N.

    1975-05-01

    The modeling of convective storm scavenging processes is going forward on two distinct fronts. The first of these relates to the microphysical processes, particularly to the study of their response to micro-dynamical components of the convective circulation. It is found that the droplet size spectra generated are responsive to variations of vertical velocity due to turbulence within the cloud and to humidity variations due to entrainment processes. Both sets of variations give responses that differ for different amplitudes and frequencies, i.e., rapid, small-amplitude eddies appear to enhance small-droplet development, whereas slow, large-amplitude oscillations tend to enhance large-droplet development. An allied study of the assumptions used in the microphysical equations is also being made. The second modeling effort is addressed to the problem of three-dimensional representation of convective dynamics. Equations are presented, and some of the problems under attack are discussed

  2. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

    Science.gov (United States)

    Hamada, K; Gleason, S L; Levi, B Z; Hirschfeld, S; Appella, E; Ozato, K

    1989-11-01

    Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, but not to other MHC cis-acting sequences or to mutant region II sequences, similar to the naturally occurring region II factor in mouse cells. The deduced amino acid sequence of H-2RIIBP revealed two putative zinc fingers homologous to the DNA-binding domain of steroid/thyroid hormone receptors. Although sequence similarity in other regions was minimal, H-2RIIBP has apparent modular domains characteristic of the nuclear hormone receptors. Further analyses showed that both H-2RIIBP and the natural region II factor bind to the estrogen response element (ERE) of the vitellogenin A2 gene. The ERE is composed of a palindrome, and half of this palindrome resembles the region II binding site of the MHC CRE. These results indicate that H-2RIIBP (i) is a member of the superfamily of nuclear hormone receptors and (ii) may regulate not only MHC class I genes but also genes containing the ERE and related sequences. Sequences homologous to the H-2RIIBP gene are widely conserved in the animal kingdom. H-2RIIBP mRNA is expressed in many mouse tissues, in agreement with the distribution of the natural region II factor.

  3. Carcass Type Affects Local Scavenger Guilds More than Habitat Connectivity.

    Directory of Open Access Journals (Sweden)

    Zachary H Olson

    Full Text Available Scavengers and decomposers provide an important ecosystem service by removing carrion from the environment. Scavenging and decomposition are known to be temperature-dependent, but less is known about other factors that might affect carrion removal. We conducted an experiment in which we manipulated combinations of patch connectivity and carcass type, and measured responses by local scavenger guilds along with aspects of carcass depletion. We conducted twelve, 1-month trials in which five raccoon (Procyon lotor, Virginia opossum (Didelphis virginiana, and domestic rabbit (Oryctolagus spp. carcasses (180 trials total were monitored using remote cameras in 21 forest patches in north-central Indiana, USA. Of 143 trials with complete data, we identified fifteen species of vertebrate scavengers divided evenly among mammalian (N = 8 and avian species (N = 7. Fourteen carcasses (9.8% were completely consumed by invertebrates, vertebrates exhibited scavenging behavior at 125 carcasses (87.4%, and four carcasses (2.8% remained unexploited. Among vertebrates, mammals scavenged 106 carcasses, birds scavenged 88 carcasses, and mammals and birds scavenged 69 carcasses. Contrary to our expectations, carcass type affected the assemblage of local scavenger guilds more than patch connectivity. However, neither carcass type nor connectivity explained variation in temporal measures of carcass removal. Interestingly, increasing richness of local vertebrate scavenger guilds contributed moderately to rates of carrion removal (≈6% per species increase in richness. We conclude that scavenger-specific differences in carrion utilization exist among carcass types and that reliable delivery of carrion removal as an ecosystem service may depend on robust vertebrate and invertebrate communities acting synergistically.

  4. Carcass Type Affects Local Scavenger Guilds More than Habitat Connectivity

    Science.gov (United States)

    Olson, Zachary H.; Beasley, James C.; Rhodes, Olin E.

    2016-01-01

    Scavengers and decomposers provide an important ecosystem service by removing carrion from the environment. Scavenging and decomposition are known to be temperature-dependent, but less is known about other factors that might affect carrion removal. We conducted an experiment in which we manipulated combinations of patch connectivity and carcass type, and measured responses by local scavenger guilds along with aspects of carcass depletion. We conducted twelve, 1-month trials in which five raccoon (Procyon lotor), Virginia opossum (Didelphis virginiana), and domestic rabbit (Oryctolagus spp.) carcasses (180 trials total) were monitored using remote cameras in 21 forest patches in north-central Indiana, USA. Of 143 trials with complete data, we identified fifteen species of vertebrate scavengers divided evenly among mammalian (N = 8) and avian species (N = 7). Fourteen carcasses (9.8%) were completely consumed by invertebrates, vertebrates exhibited scavenging behavior at 125 carcasses (87.4%), and four carcasses (2.8%) remained unexploited. Among vertebrates, mammals scavenged 106 carcasses, birds scavenged 88 carcasses, and mammals and birds scavenged 69 carcasses. Contrary to our expectations, carcass type affected the assemblage of local scavenger guilds more than patch connectivity. However, neither carcass type nor connectivity explained variation in temporal measures of carcass removal. Interestingly, increasing richness of local vertebrate scavenger guilds contributed moderately to rates of carrion removal (≈6% per species increase in richness). We conclude that scavenger-specific differences in carrion utilization exist among carcass types and that reliable delivery of carrion removal as an ecosystem service may depend on robust vertebrate and invertebrate communities acting synergistically. PMID:26886299

  5. Carcass Type Affects Local Scavenger Guilds More than Habitat Connectivity.

    Science.gov (United States)

    Olson, Zachary H; Beasley, James C; Rhodes, Olin E

    2016-01-01

    Scavengers and decomposers provide an important ecosystem service by removing carrion from the environment. Scavenging and decomposition are known to be temperature-dependent, but less is known about other factors that might affect carrion removal. We conducted an experiment in which we manipulated combinations of patch connectivity and carcass type, and measured responses by local scavenger guilds along with aspects of carcass depletion. We conducted twelve, 1-month trials in which five raccoon (Procyon lotor), Virginia opossum (Didelphis virginiana), and domestic rabbit (Oryctolagus spp.) carcasses (180 trials total) were monitored using remote cameras in 21 forest patches in north-central Indiana, USA. Of 143 trials with complete data, we identified fifteen species of vertebrate scavengers divided evenly among mammalian (N = 8) and avian species (N = 7). Fourteen carcasses (9.8%) were completely consumed by invertebrates, vertebrates exhibited scavenging behavior at 125 carcasses (87.4%), and four carcasses (2.8%) remained unexploited. Among vertebrates, mammals scavenged 106 carcasses, birds scavenged 88 carcasses, and mammals and birds scavenged 69 carcasses. Contrary to our expectations, carcass type affected the assemblage of local scavenger guilds more than patch connectivity. However, neither carcass type nor connectivity explained variation in temporal measures of carcass removal. Interestingly, increasing richness of local vertebrate scavenger guilds contributed moderately to rates of carrion removal (≈6% per species increase in richness). We conclude that scavenger-specific differences in carrion utilization exist among carcass types and that reliable delivery of carrion removal as an ecosystem service may depend on robust vertebrate and invertebrate communities acting synergistically.

  6. Nitric oxide radical scavenging potential of some Elburz medicinal ...

    African Journals Online (AJOL)

    Some plants scavenge nitric oxide (NO) with high affinity. For this purpose, forty extracts from 26 medicinal plants, growing extensively in Elburz mountains, were evaluated for their NO scavenging activity. Total phenolic and flavonoid contents of these extracts were also measured by Folin Ciocalteu and AlCl3 colorimetric ...

  7. Free Radical Scavenging Activities of Methanol Extract and ...

    African Journals Online (AJOL)

    Michael Horsfall

    fractions were subjected to in vitro antioxidant evaluation using the DPPH free radical scavenging ... The crude extract has IC-50 value for radical scavenging activity of 5μg/mL which was .... effective concentration of the sample that is required.

  8. Modeling of an Integrated Electromagnetic Generator for Energy Scavenging

    NARCIS (Netherlands)

    Lu, J.; Kovalgin, Alexeij Y.; Schmitz, Jurriaan

    2007-01-01

    The ubiquitous deploying of wireless electronic devices due to pervasive computing results in the idea of Energy Scavenging, i.e., harvesting ambient energy from surroundings of the electronic devices. As an approach to possible practical realization of such an energy scavenger, we aim at the

  9. Radical Scavenging Efficacy of Thiol Capped Silver Nanoparticles

    Indian Academy of Sciences (India)

    aSchool of Studies in Chemistry, Pt. Ravishankar Shukla University, Raipur 492 010, India. bDepartment of ... of nanosilver in foods, health care and consumer products as antimi- ... of the radical scavenging behavior of thiolated antiox- idants (alone) and ..... case of GSH@AgNPs; DPPH scavenging activity was found to be ...

  10. Identification of Radical Scavengers in Sweet Grass (Hierochloe odorata)

    NARCIS (Netherlands)

    Pukalskas, A.; Beek, van T.A.; Venskutonis, R.P.; Linssen, J.P.H.; Veldhuizen, van A.; Groot, de Æ.

    2002-01-01

    Extracts from aerial parts of sweet grass (Hierochloe odorata) were active DPPH free radical scavengers, The active compounds were detected in extract fractions using HPLC with on-line radical scavenging detection. After multistep fractionation of the extract, two new natural products possessing

  11. Characterization and DPPH Radical Scavenging Activity of Gallic ...

    African Journals Online (AJOL)

    Characterization and DPPH Radical Scavenging Activity of Gallic Acid-Lecithin Complex. C Liu, C Chen, H Ma, E Yuan, Q Li. Abstract. Purpose: To investigate the physicochemical properties and DPPH radical scavenging activity of gallic acid–lecithin complex. Methods: The complex of gallic acid with lecithin was prepared ...

  12. Selective scavenging of intra-mitochondrial superoxide corrects diclofenac-induced mitochondrial dysfunction and gastric injury: A novel gastroprotective mechanism independent of gastric acid suppression.

    Science.gov (United States)

    Mazumder, Somnath; De, Rudranil; Sarkar, Souvik; Siddiqui, Asim Azhar; Saha, Shubhra Jyoti; Banerjee, Chinmoy; Iqbal, Mohd Shameel; Nag, Shiladitya; Debsharma, Subhashis; Bandyopadhyay, Uday

    2016-12-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat multiple inflammatory diseases and pain but severe gastric mucosal damage is the worst outcome of NSAID-therapy. Here we report that mitoTEMPO, a mitochondrially targeted superoxide (O 2 - ) scavenger protected as well as healed gastric injury induced by diclofenac (DCF), the most commonly used NSAID. Common existing therapy against gastric injury involves suppression of gastric acid secretion by proton pump inhibitors and histamine H 2 receptor antagonists; however, dyspepsia, vitamin B12 deficiency and gastric microfloral dysbalance are the major drawbacks of acid suppression. Interestingly, mitoTEMPO did not inhibit gastric acid secretion but offered gastroprotection by preventing DCF-induced generation of O 2 - due to mitochondrial respiratory chain failure and by preventing mitochondrial oxidative stress (MOS)-mediated mitopathology. MitoTEMPO even restored DCF-stimulated reduced fatty acid oxidation, mitochondrial depolarization and bioenergetic crisis in gastric mucosa. MitoTEMPO also prevented the activation of mitochondrial pathway of apoptosis and MOS-mediated proinflammatory signaling through NF-κB by DCF. Furthermore, mitoTEMPO when administered in rats with preformed gastric lesions expedited the healing of gastric injury and the healed stomach exhibited its normal physiology as evident from gastric acid and pepsin secretions under basal or stimulated conditions. Thus, in contrast to the existing antiulcer drugs, mitochondrially targeted O 2 - scavengers like mitoTEMPO may represent a novel class of gastroprotective molecules that does not affect gastric acid secretion and may be used in combination with DCF, keeping its anti-inflammatory action intact, while reducing its gastrodamaging effects. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A Hydrogen-Bonded Polar Network in the Core of the Glucagon-Like Peptide-1 Receptor Is a Fulcrum for Biased Agonism: Lessons from Class B Crystal Structures.

    Science.gov (United States)

    Wootten, Denise; Reynolds, Christopher A; Koole, Cassandra; Smith, Kevin J; Mobarec, Juan C; Simms, John; Quon, Tezz; Coudrat, Thomas; Furness, Sebastian G B; Miller, Laurence J; Christopoulos, Arthur; Sexton, Patrick M

    2016-03-01

    The glucagon-like peptide 1 (GLP-1) receptor is a class B G protein-coupled receptor (GPCR) that is a key target for treatments for type II diabetes and obesity. This receptor, like other class B GPCRs, displays biased agonism, though the physiologic significance of this is yet to be elucidated. Previous work has implicated R2.60(190), N3.43(240), Q7.49(394), and H6.52(363) as key residues involved in peptide-mediated biased agonism, with R2.60(190), N3.43(240), and Q7.49(394) predicted to form a polar interaction network. In this study, we used novel insight gained from recent crystal structures of the transmembrane domains of the glucagon and corticotropin releasing factor 1 (CRF1) receptors to develop improved models of the GLP-1 receptor that predict additional key molecular interactions with these amino acids. We have introduced E6.53(364)A, N3.43(240)Q, Q7.49(394)N, and N3.43(240)Q/Q7.49(394)N mutations to probe the role of predicted H-bonding and charge-charge interactions in driving cAMP, calcium, or extracellular signal-regulated kinase (ERK) signaling. A polar interaction between E6.53(364) and R2.60(190) was predicted to be important for GLP-1- and exendin-4-, but not oxyntomodulin-mediated cAMP formation and also ERK1/2 phosphorylation. In contrast, Q7.49(394), but not R2.60(190)/E6.53(364) was critical for calcium mobilization for all three peptides. Mutation of N3.43(240) and Q7.49(394) had differential effects on individual peptides, providing evidence for molecular differences in activation transition. Collectively, this work expands our understanding of peptide-mediated signaling from the GLP-1 receptor and the key role that the central polar network plays in these events. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  14. A new class of pyrazolo[5,1-c][1,2,4]triazines as γ-aminobutyric type A (GABAA) receptor subtype ligand: synthesis and pharmacological evaluation.

    Science.gov (United States)

    Guerrini, Gabriella; Ciciani, Giovanna; Daniele, Simona; Martini, Claudia; Costagli, Camilla; Guarino, Chiara; Selleri, Silvia

    2018-05-15

    A comparison between compounds with pyrazolo[1,5-a]pyrimidine structure (series 4-6) and pyrazolo[5,1-c][1,2,4]triazine core (series 9) as ligands at GABA A -receptor subtype, was evaluated. Moreover, for pyrazolotriazine derivatives having binding recognition, the interaction on recombinant rat α(1-3,5) GABA A receptor subtypes, was performed. Among these latter, emerge compounds 9c, 9k, 9l, 9m and 9n as α1-selective and 9h as α2-selective ligands. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Effects of vulture exclusion on carrion consumption by facultative scavengers.

    Science.gov (United States)

    Hill, Jacob E; DeVault, Travis L; Beasley, James C; Rhodes, Olin E; Belant, Jerrold L

    2018-03-01

    Vultures provide an essential ecosystem service through removal of carrion, but globally, many populations are collapsing and several species are threatened with extinction. Widespread declines in vulture populations could increase the availability of carrion to other organisms, but the ways facultative scavengers might respond to this increase have not been thoroughly explored. We aimed to determine whether facultative scavengers increase carrion consumption in the absence of vulture competition and whether they are capable of functionally replacing vultures in the removal of carrion biomass from the landscape. We experimentally excluded 65 rabbit carcasses from vultures during daylight hours and placed an additional 65 carcasses that were accessible to vultures in forested habitat in South Carolina, USA during summer (June-August). We used motion-activated cameras to compare carrion use by facultative scavenging species between the experimental and control carcasses. Scavenging by facultative scavengers did not increase in the absence of competition with vultures. We found no difference in scavenger presence between control carcasses and those from which vultures were excluded. Eighty percent of carcasses from which vultures were excluded were not scavenged by vertebrates, compared to 5% of carcasses that were accessible to vultures. At the end of the 7-day trials, there was a 10.1-fold increase in the number of experimental carcasses that were not fully scavenged compared to controls. Facultative scavengers did not functionally replace vultures during summer in our study. This finding may have been influenced by the time of the year in which the study took place, the duration of the trials, and the spacing of carcass sites. Our results suggest that under the warm and humid conditions of our study, facultative scavengers would not compensate for loss of vultures. Carcasses would persist longer in the environment and consumption of carrion would likely shift from

  16. Dependent Classes

    DEFF Research Database (Denmark)

    Gasiunas, Vaidas; Mezini, Mira; Ostermann, Klaus

    2007-01-01

    of dependent classes and a machine-checked type soundness proof in Isabelle/HOL [29], the first of this kind for a language with virtual classes and path-dependent types. [29] T.Nipkow, L.C. Poulson, and M. Wenzel. Isabelle/HOL -- A Proof Assistant for Higher-Order Logic, volume 2283 of LNCS, Springer, 2002......Virtual classes allow nested classes to be refined in subclasses. In this way nested classes can be seen as dependent abstractions of the objects of the enclosing classes. Expressing dependency via nesting, however, has two limitations: Abstractions that depend on more than one object cannot...... be modeled and a class must know all classes that depend on its objects. This paper presents dependent classes, a generalization of virtual classes that expresses similar semantics by parameterization rather than by nesting. This increases expressivity of class variations as well as the flexibility...

  17. Effect of intrathecal non-NMDA EAA receptor antagonist LY293558 in rats: a new class of drugs for spinal anesthesia.

    Science.gov (United States)

    Von Bergen, Nicholas H; Subieta, Alberto; Brennan, Timothy J

    2002-07-01

    Excitatory amino acid receptors are important for both sensory and motor function in the spinal cord. We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia. Rats were tested before and 15-240 min after intrathecal injection of 5 nmol (in 10 microl) LY293558. Sensory function was tested at the hind paw using withdrawal response to pin prick and withdrawal to pinch with sharp forceps. Motor performance (ambulation, placing reflex, and Rotorod time), blood pressure, and heart rate were also evaluated. Some tests were repeated the next day. Responses after LY293558 were compared to injection of 40 microl bupivacaine, 0.75%. Pin-prick responses at the forepaw, chest, abdomen, hind leg, and hind paw were also examined after intrathecal LY293558. Intrathecal LY293558 blocked both sensory and motor responses through 180 min; complete recovery was present the following day. No change in blood pressure or heart rate occurred. The effects of LY293558 were more pronounced and sustained than those of bupivacaine. Segmental blockade of the response to pin prick was present after LY293558. Drugs like LY293558 that block alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors may be an alternative to local anesthetics for spinal anesthesia in humans.

  18. Rational design, efficient syntheses and biological evaluation of N,N '-symmetrically bis-substituted butylimidazole analogs as a new class of potent Angiotensin II receptor blockers

    Czech Academy of Sciences Publication Activity Database

    Agelis, G.; Resvani, A.; Koukoulitsa, C.; Tůmová, Tereza; Slaninová, Jiřina; Kalavrizioti, D.; Spyridaki, K.; Afantitis, A.; Melagraki, G.; Siafaka, A.; Gkini, E.; Megariotis, G.; Grdadolnik, S. G.; Papadopoulos, M. G.; Vlahakos, D.; Maragoudakis, M.; Liapakis, G.; Mavromoustakos, T.; Matsoukas, J.

    2013-01-01

    Roč. 62, Apr (2013), s. 352-370 ISSN 0223-5234 Institutional support: RVO:61388963 Keywords : AT1 receptor blockers * N,N '-Bis-alkylated butylimidazole analogs * synthesis * Wittig reaction * hydroxymethylation * structure elucidation Subject RIV: CC - Organic Chemistry Impact factor: 3.432, year: 2013

  19. Scavenger hunt in the CERN Computing Centre

    CERN Multimedia

    CERN Bulletin

    2013-01-01

    Hidden among the racks of servers and disks in the CERN Computing Centre, you’ll find Hawaiian dancers, space aliens, gorillas… all LEGO® figurines! These characters were placed about the Centre for the arrival of Google’s Street View team for the world to discover.   PLEASE NOTE THAT THE COMPETITION IS OVER. ONLY FOR REFERENCE, HERE IS THE ORIGINAL ARTICLE. We’re pleased to announce our first global scavenger hunt! Spot three LEGO® figurines using Google’s Street View and you’ll be entered to win a gift of your choice from our CERN Gift Guide. A LEGO® figurine in the CERN Computing Centre, as seen on Google Street View. Here are the details: Find at least three LEGO® figurines hidden around the CERN Computing Centre using Google Street View.   Take screencaps of the figurines and e-mail the pictures to TreasureHunt-ComputingCentre@cern.ch. This email is no longer active.   The...

  20. HUNT: Scavenger Hunt with Augmented Reality

    Directory of Open Access Journals (Sweden)

    Yan Lu

    2015-04-01

    Full Text Available This project shows a creative approach to the familiar scavenger hunt game. It involved the implementation of an iPhone application, HUNT, with Augmented Reality (AR capability for the users to play the game as well as an administrative website that game organizers can use to create and make available games for users to play. Using the HUNT mobile app, users will first make a selection from a list of games, and they will then be shown a list of objects that they must seek. Once the user finds a correct object and scans it with the built-in camera on the smartphone, the application will attempt to verify if it is the correct object and then display associated multi-media AR content that may include images and videos overlaid on top of real world views. HUNT not only provides entertaining activities within an environment that players can explore, but the AR contents can serve as an educational tool. The project is designed to increase user involvement by using a familiar and enjoyable game as a basis and adding an educational dimension by incorporating AR technology and engaging and interactive multimedia to provide users with facts about the objects that they have located

  1. A numerical model of aerosol scavenging

    International Nuclear Information System (INIS)

    Bradley, M.M.; Molenkamp, C.R.

    1991-10-01

    Using a three-dimensional numerical cloud/smoke-plume model, we have simulated the burning of a large, mid-latitude city following a nuclear exchange. The model includes 18 dynamic and microphysical equations that predict the fire-driven airflow, cloud processes, and smoke-cloud interactions. In the simulation, the intense heating from the burning city produces a firestorm with updraft velocities exceeding 60 m/s. Within 15 minutes of ignition, the smoke plume penetrates the tropopause. The updraft triggers a cumulonimbus cloud that produces significant quantities of ice, snow, and hail. These solid hydrometeors, as well as cloud droplets and rain, interact with the smoke particles from the fire. At the end of the one-hour simulation, over 20% of the smoke is in slowly falling snowflakes. If the snow reaches the ground before the flakes completely sublimate (or melt and then evaporate), then only approximately 50% of the smoke will survive the scavenging processes and remain in the atmosphere to affect the global climate

  2. Magnetic graphene based nanocomposite for uranium scavenging

    Energy Technology Data Exchange (ETDEWEB)

    El-Maghrabi, Heba H. [Egyptian Petroleum Research Institute, 11727, Cairo (Egypt); Abdelmaged, Shaimaa M. [Nuclear Materials Authority, 6530 P.O. Box Maadi, Cairo (Egypt); Nada, Amr A. [Egyptian Petroleum Research Institute, 11727, Cairo (Egypt); Zahran, Fouad, E-mail: f.zahran@quim.ucm.es [Faculty of Science, Helwan University, 11795, Cairo (Egypt); El-Wahab, Saad Abd; Yahea, Dena [Faculty of Science, Ain shams University, Cairo (Egypt); Hussein, G.M.; Atrees, M.S. [Nuclear Materials Authority, 6530 P.O. Box Maadi, Cairo (Egypt)

    2017-01-15

    Graphical abstract: Graphical representation of U{sup 6+} adsorption on Magnetic Ferberite-Graphene Nanocomposite. - Highlights: • Synthesis of new magnetic wolframite bimetallic nanostructure on graphene. • A promising adsorption capacity of 455 mg/g was recorded for FG-20 within 60 min at room temperature. • The uranium removal was followed pseudo-second order kinetics and Langmuir isotherm. - Abstract: Magnetic graphene based ferberite nanocomposite was tailored by simple, green, low cost and industrial effective method. The microstructure and morphology of the designed nanomaterials were examined via XRD, Raman, FTIR, TEM, EDX and VSM. The prepared nanocomposites were introduced as a novel adsorbent for uranium ions scavenging from aqueous solution. Different operating conditions of time, pH, initial uranium concentration, adsorbent amount and temperature were investigated. The experimental data shows a promising adsorption capacity. In particular, a maximum value of 455 mg/g was obtained within 60 min at room temperature with adsorption efficiency of 90.5%. The kinetics and isotherms adsorption data were fitted with the pseudo-second order model and Langmuir equation, respectively. Finally, the designed nanocomposites were found to have a great degree of sustainability (above 5 times of profiteering) with a complete maintenance of their parental morphology and adsorption capacity.

  3. Evaluation of Radical Scavenging Activity of Sempervivum tectorum and Corylus avellana Extracts with Different Phenolic Composition.

    Science.gov (United States)

    Alberti, Ágnes; Riethmüller, Eszter; Béni, Szabolcs; Kéry, Ágnes

    2016-04-01

    Semnpervivum tectorum L. and Corylus avellana L. are traditional herbal remedies exhibiting antioxidant activity and representing diverse phenolic composition. The aim of this study was to reveal the contribution of certain compounds to total radical scavenging activity by studying S. tectorum and C. avellana extracts prepared with solvents of different selectivity for diverse classes of phenolics. Antioxidant activity of S. tectorum and C. avellana samples was determined in the ABTS and DPPH radical scavenging assays, and phenolic composition was evaluated by high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). Correlations between antioxidant activity and phenolic content of houseleek extracts have been revealed. Significant differences regarding antioxidant activity have been shown between S. tectorum 80% (v/v) methanol extract and its fractions. Additionally, synergism among the constituents present together in the whole extract was assumed. Significantly higher radical scavenging activity of hazel extracts has been attributed to the differences in phenolic composition compared with houseleek extracts.

  4. Olfactory Receptor Database: a sensory chemoreceptor resource

    OpenAIRE

    Skoufos, Emmanouil; Marenco, Luis; Nadkarni, Prakash M.; Miller, Perry L.; Shepherd, Gordon M.

    2000-01-01

    The Olfactory Receptor Database (ORDB) is a WWW-accessible database that has been expanded from an olfactory receptor resource to a chemoreceptor resource. It stores data on six classes of G-protein-coupled sensory chemoreceptors: (i) olfactory receptor-like proteins, (ii) vomeronasal receptors, (iii) insect olfactory receptors, (iv) worm chemoreceptors, (v) taste papilla receptors and (vi) fungal pheromone receptors. A complementary database of the ligands of these receptors (OdorDB) has bee...

  5. Initial clinical experience with the first drug (sacubitril/valsartan) in a new class - angiotensin receptor neprilysin inhibitors in patients with heart failure with reduced left ventricular ejection fraction in Poland.

    Science.gov (United States)

    Kałużna-Oleksy, Marta; Kolasa, Jolanta; Migaj, Jacek; Pawlak, Agnieszka; Lelonek, Małgorzata; Nessler, Jadwiga; Straburzyńska-Migaj, Ewa

    2018-01-01

    Sacubitril/valsartan is the first drug from a new class of angiotensin receptor neprilysin inhibitors (ARNIs) recommended in the new European Society of Cardiology guidelines instead of angiotensin converting enzyme inhibitors (ACEI), or angiotensin receptor blockers (ARB) that are used if ACEI are not tolerated. Sacubitril/valsartan is recommended for further reduction in the risk of hospitalisation or death in outpatients with heart failure with reduced ejection fraction (HFrEF) if symptoms continue despite optimal treatment with ACEI/ARB, beta-blockers, and mineralocorticoid antagonists. The aim of this study is to present the initial experience with regard to the effectiveness, tolerance, and safety of sacubitril/valsartan in the outpatient cardiology practice in Poland. The study is a retrospective analysis of data obtained through a questionnaire filled in by the physicians who initiated the sacubitril/valsartan treatment in patients with HFrEF between 1 June 2016 and 30 September 2016. Patients were followed-up for three months. The analysis included data on 28 patients aged 61 ± 16 years, of whom 85.7% were males. The drug was used in patients in New York Heart Association (NYHA) class I-III. In 25 (89.2%) patients sacubitril/valsartan was started at the lowest dose (24/26 mg BID). During follow-up the sacubitril/valsartan-treated patients had a reduction in HF symptoms assessed using the NYHA functional class (p = 0.001), a significant drop in N-terminal-pro B-type natriuretic peptide levels (mean, from 2900 to 2270 pg/mL; p = 0.008), and improved exercise tolerance, which occurred shortly after treatment initiation - after a mean of 28 days. It was demonstrated that the use of sacubitril/valsartan in outpatients with HFrEF is safe and is associated with a significant clinical improvement.

  6. Synthesis and receptor binding studies of novel 4,4-disubstituted arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as a new class of σ1 ligands.

    Science.gov (United States)

    Sadeghzadeh, Masoud; Sheibani, Shahab; Ghandi, Mehdi; Daha, Fariba Johari; Amanlou, Massoud; Arjmand, Mohammad; Hasani Bozcheloie, Abolfazl

    2013-06-01

    This study presents the synthesis and biological evaluation of a new series of arylalkyl/arylalkylsulfonyl piperazine and piperidine-based derivatives as sigma receptor ligands. It was found that a number of halogen substituted sulfonamides display relatively high and low affinities to σ1 and σ2 receptors, respectively. The σ1 affinities and subtype selectivities of four piperidine derivatives were also found to be generally comparable to those of piperazine analogues. Compared to σ1-Rs compounds with n = 0 and 2, those with n = 1 proved to have optimal length of carbon chain by exhibiting higher affinities. Within this series, the 4-benzyl-1-(3-iodobenzylsulfonyl)piperidine sigma ligand was identified with 96-fold σ1/σ2 selectivity ratio (Kiσ1 = 0.96 ± 0.05 nM and Kiσ2 = 91.8 ± 8.1 nM). Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  7. Two classes of astrocytes in the adult human and pig retina in terms of their expression of high affinity NGF receptor (TrkA).

    Science.gov (United States)

    Ruiz-Ederra, Javier; Hitchcock, Peter F; Vecino, Elena

    2003-02-13

    Astrocytes have been implicated in axon guidance and synaptic regeneration in the retina and these processes involve activation of the high affinity nerve growth factor receptor, known as the tyrosine kinase A (TrkA) receptor. The purpose of the present study was to characterize the expression of TrkA in astrocytes of the adult pig and human retina. To this end, sections of human and pig retinas were immunolabeled with a combination of antibodies to glial fibrillary acidic protein (GFAP) and TrkA. Our study revealed that most of the GFAP-positive cells express TrkA, whereas a rare, novel subpopulation of astrocytes was found to be devoid of TrkA. Our results support the idea that astrocytes play an important neurotrophic role in the retina.

  8. A New Class of Potent N-Methyl-D-Aspartate Receptor Inhibitors: Sulfated Neuroactive Steroids with Lipophilic D-Ring Modifications

    Czech Academy of Sciences Publication Activity Database

    Kudová, Eva; Chodounská, Hana; Slavíková, Barbora; Buděšínský, Miloš; Nekardová, Michaela; Vyklický, Vojtěch; Krausová, Barbora; Švehla, Pavel; Vyklický ml., Ladislav

    2015-01-01

    Roč. 58, č. 15 (2015), s. 5950-5966 ISSN 0022-2623 R&D Projects: GA TA ČR(CZ) TE01020028; GA ČR(CZ) GAP303/12/1464; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388963 ; RVO:67985823 Keywords : NMDA receptor * noncovalent complexes * neurosteroids Subject RIV: CC - Organic Chemistry Impact factor: 5.589, year: 2015

  9. The research progress of several kinds of free radical scavengers

    International Nuclear Information System (INIS)

    Qian Liren; Huang Yuecheng; Cai Jianming

    2009-01-01

    Ionization radiation can generate free radicals in biological system, which could induce lipid peroxi-dation, biomacromolecule and biomembrane damage, lost of cell function, cell cycle disturbance, genetic mutation and so on. The scavenging free radicals can protect organism from radiation damage. Many radio-protective agents, such as amylase, hydroxyl-benzene derivatives, hormone, vitamin, have great abilities to protect organism from radiation via scavenging free radicals. In this paper, we mainly review the free radical scavenging effects of several kinds of radio-protective agents. (authors)

  10. Free Radical Scavenging and Cellular Antioxidant Properties of Astaxanthin.

    Science.gov (United States)

    Dose, Janina; Matsugo, Seiichi; Yokokawa, Haruka; Koshida, Yutaro; Okazaki, Shigetoshi; Seidel, Ulrike; Eggersdorfer, Manfred; Rimbach, Gerald; Esatbeyoglu, Tuba

    2016-01-14

    Astaxanthin is a coloring agent which is used as a feed additive in aquaculture nutrition. Recently, potential health benefits of astaxanthin have been discussed which may be partly related to its free radical scavenging and antioxidant properties. Our electron spin resonance (ESR) and spin trapping data suggest that synthetic astaxanthin is a potent free radical scavenger in terms of diphenylpicryl-hydrazyl (DPPH) and galvinoxyl free radicals. Furthermore, astaxanthin dose-dependently quenched singlet oxygen as determined by photon counting. In addition to free radical scavenging and singlet oxygen quenching properties, astaxanthin induced the antioxidant enzyme paroxoanase-1, enhanced glutathione concentrations and prevented lipid peroxidation in cultured hepatocytes. Present results suggest that, beyond its coloring properties, synthetic astaxanthin exhibits free radical scavenging, singlet oxygen quenching, and antioxidant activities which could probably positively affect animal and human health.

  11. Performance of Chickens under Semi-scavenging Conditions: A ...

    African Journals Online (AJOL)

    Performance of Chickens under Semi-scavenging Conditions: A Case Study of ... per household was lost per year due to diseases, predators, accidents, and theft. ... as well as chicken house construction so as to avoid the risks of predators.

  12. Nitric oxide radical scavenging potential of some Elburz medicinal ...

    African Journals Online (AJOL)

    ONOS

    2010-08-09

    Aug 9, 2010 ... NO is also implicated in inflammation and other pathological ... adhesion and prevention of smooth muscle cell prolife- ... reduce NO levels is making use of NO scavengers. For ..... human nutrition and health are considerable.

  13. Antimicrobial and free radical scavenging activities of five ...

    African Journals Online (AJOL)

    Extracts from five indigenous Palestinian medicinal plants including Rosmarinus officinalis, Pisidium guajava, Punica granatum peel, grape seeds and Teucrium polium were investigated for antimicrobial and free radical scavenging activities against eight microorganisms, using well diffusion method. The microorganisms ...

  14. Cutting Classes

    Science.gov (United States)

    Hacker, Andrew

    1976-01-01

    Provides critical reviews of three books, "The Political Economy of Social Class", "Ethnicity: Theory and Experience," and "Ethnicity in the United States," focusing on the political economy of social class and ethnicity. (Author/AM)

  15. Shark scavenging behavior in the presence of competition

    Directory of Open Access Journals (Sweden)

    Shannon P. GERRY, Andrea J. SCOTT

    2010-02-01

    Full Text Available The distribution of organisms within a community can often be determined by the degree of plasticity or degree of specialization of resource acquisition. Resource acquisition is often based on the morphology of an organism, behavior, or a combination of both. Performance tests of feeding can identify the possible interactions that allow one species to better exploit a prey item. Scavenging behaviors in the presence or absence of a competitor were investigated by quantifying prey selection in a trophic generalist, spiny dogfish Squalus acanthias, and a trophic specialist, smooth-hounds Mustelus canis, in order to determine if each shark scavenged according to its jaw morphology. The diet of dogfish consists of small fishes, squid, ctenophores, and bivalves; they are expected to be nonselective predators. Smooth-hounds primarily feed on crustaceans; therefore, they are predicted to select crabs over other prey types. Prey selection was quantified by ranking each prey item according to the order it was consumed. Dietary shifts were analyzed by comparing the percentage of each prey item selected during solitary versus competitive scavenging. When scavenging alone, dogfish prefer herring and squid, which are easily handled by the cutting dentition of dogfish. Dogfish shift their diet to include a greater number of prey types when scavenging with a competitor. Smooth-hounds scavenge on squid, herring, and shrimp when alone, but increase the number of crabs in the diet when scavenging competitively. Competition causes smooth-hounds to scavenge according to their jaw morphology and locomotor abilities, which enables them to feed on a specialized resource [Current Zoology 56 (1: 100–108 2010].

  16. Bergenin Content and Free Radical Scavenging Activity of Bergenia Extracts. .

    Science.gov (United States)

    Hendrychová, Helena; Martin, Jan; Tůmová, Lenka; Kočevar-Glavač, Nina

    2015-07-01

    Our research was focused on the evaluation of bergenin content and free radical scavenging activity of extracts prepared from three different species of Bergenia - B. crassifolia (L.) Fritsch., B. ciliata (Haw.) Sternb. and B. x ornata Stein. collected during different seasons. Using an HPLC method, the highest total amount of bergenin was revealed in the leaves of B. x ornata and B. crassifolia (4.9 - 5.1 mg x g(-1)). Free radical scavenging power was determined by two methods--FRAP and NADH. The best free radical scavengers were B. crassifolia (FRAP: 6.7 - 15.9 mg GAE. 100g(-1); NADH: 20.3 - 50.9%) and B. ornata (FRAP: 13.7 - 15.2 mg GAE. 100g(-1); NADH: 29.3 - 31.1%). The lowest content of bergenin and the weakest radical scavenger was B. ciliata (bergenin: 3.1 mg x g(-1); FRAP: 5.5 - 11.0 mg GAE.100g(-1); NADH: 23.2 - 25.6%). The presence of a large percentage of bergenin is responsible for the radical scavenging activity, as shown by the results from the FRAP and NADH assays. Significant, positive correlation was found between bergenin content and radical scavenging activity in both methods.

  17. Weight savings in aerospace vehicles through propellant scavenging

    Science.gov (United States)

    Schneider, Steven J.; Reed, Brian D.

    1988-01-01

    Vehicle payload benefits of scavenging hydrogen and oxygen propellants are addressed. The approach used is to select a vehicle and a mission and then select a scavenging system for detailed weight analysis. The Shuttle 2 vehicle on a Space Station rendezvous mission was chosen for study. The propellant scavenging system scavenges liquid hydrogen and liquid oxygen from the launch propulsion tankage during orbital maneuvers and stores them in well insulated liquid accumulators for use in a cryogenic auxiliary propulsion system. The fraction of auxiliary propulsion propellant which may be scavenged for propulsive purposes is estimated to be 45.1 percent. The auxiliary propulsion subsystem dry mass, including the proposed scavenging system, an additional 20 percent for secondary structure, an additional 5 percent for electrical service, a 10 percent weight growth margin, and 15.4 percent propellant reserves and residuals is estimated to be 6331 kg. This study shows that the fraction of the on-orbit vehicle mass required by the auxiliary propulsion system of this Shuttle 2 vehicle using this technology is estimated to be 12.0 percent compared to 19.9 percent for a vehicle with an earth-storable bipropellant system. This results in a vehicle with the capability of delivering an additional 7820 kg to the Space Station.

  18. An illicit economy: scavenging and recycling of medical waste.

    Science.gov (United States)

    Patwary, Masum A; O'Hare, William Thomas; Sarker, M H

    2011-11-01

    This paper discusses a significant illicit economy, including black and grey aspects, associated with medical waste scavenging and recycling in a megacity, considering hazards to the specific group involved in scavenging as well as hazards to the general population of city dwellers. Data were collected in Dhaka, Bangladesh, using a variety of techniques based on formal representative sampling for fixed populations (such as recycling operatives) and adaptive sampling for roaming populations (such as scavengers). Extremely hazardous items (including date expired medicines, used syringes, knives, blades and saline bags) were scavenged, repackaged and resold to the community. Some HCE employees were also observed to sell hazardous items directly to scavengers, and both employees and scavengers were observed to supply contaminated items to an informal plastics recycling industry. This trade was made possible by the absence of segregation, secure storage and proper disposal of medical waste. Corruption, a lack of accountability and individual responsibility were also found to be contributors. In most cases the individuals involved with these activities did not understand the risks. Although motivation was often for personal gain or in support of substance abuse, participants sometimes felt that they were providing a useful service to the community. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Weight savings in aerospace vehicles through propellant scavenging

    Science.gov (United States)

    Schneider, Steven J.; Reed, Brian D.

    1988-05-01

    Vehicle payload benefits of scavenging hydrogen and oxygen propellants are addressed. The approach used is to select a vehicle and a mission and then select a scavenging system for detailed weight analysis. The Shuttle 2 vehicle on a Space Station rendezvous mission was chosen for study. The propellant scavenging system scavenges liquid hydrogen and liquid oxygen from the launch propulsion tankage during orbital maneuvers and stores them in well insulated liquid accumulators for use in a cryogenic auxiliary propulsion system. The fraction of auxiliary propulsion propellant which may be scavenged for propulsive purposes is estimated to be 45.1 percent. The auxiliary propulsion subsystem dry mass, including the proposed scavenging system, an additional 20 percent for secondary structure, an additional 5 percent for electrical service, a 10 percent weight growth margin, and 15.4 percent propellant reserves and residuals is estimated to be 6331 kg. This study shows that the fraction of the on-orbit vehicle mass required by the auxiliary propulsion system of this Shuttle 2 vehicle using this technology is estimated to be 12.0 percent compared to 19.9 percent for a vehicle with an earth-storable bipropellant system. This results in a vehicle with the capability of delivering an additional 7820 kg to the Space Station.

  20. Rho-kinase signaling controls nucleocytoplasmic shuttling of class IIa Histone Deacetylase (HDAC7) and transcriptional activation of orphan nuclear receptor NR4A1

    Energy Technology Data Exchange (ETDEWEB)

    Compagnucci, Claudia; Barresi, Sabina [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Petrini, Stefania [Research Laboratories, Confocal Microscopy Core Facility, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy); Zanni, Ginevra, E-mail: ginevra.zanni@opbg.net [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Disorders, Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Rome (Italy)

    2015-04-03

    Rho-kinase (ROCK) has been well documented to play a key role in RhoA-induced actin remodeling. ROCK activation results in myosin light chain (MLC) phosphorylation either by direct action on MLC kinase (MLCK) or by inhibition of MLC phosphatase (MLCP), modulating actin–myosin contraction. We found that inhibition of the ROCK pathway in induced pluripotent stem cells, leads to nuclear export of HDAC7 and transcriptional activation of the orphan nuclear receptor NR4A1 while in cells with constitutive ROCK hyperactivity due to loss of function of the RhoGTPase activating protein Oligophrenin-1 (OPHN1), the orphan nuclear receptor NR4A1 is downregulated. Our study identify a new target of ROCK signaling via myosin phosphatase subunit (MYPT1) and Histone Deacetylase (HDAC7) at the nuclear level and provide new insights in the cellular functions of ROCK. - Highlights: • ROCK regulates nucleocytoplasmic shuttling of HDAC7 via phosphorylation of MYPT1. • Nuclear export of HDAC7 and upregulation of NR4A1 occurs with low ROCK activity. • High levels of ROCK activity due to OPHN1 loss of function downregulate NR4A1.

  1. NetMHCpan-3.0; improved prediction of binding to MHC class I molecules integrating information from multiple receptor and peptide length datasets

    DEFF Research Database (Denmark)

    Nielsen, Morten; Andreatta, Massimo

    2016-01-01

    Background: Binding of peptides to MHC class I molecules (MHC-I) is essential for antigen presentation to cytotoxic T-cells.Results: Here, we demonstrate how a simple alignment step allowing insertions and deletions in a pan-specific MHC-I binding machine-learning model enables combining informat...... specificities and ligand length scales, and demonstrated how this approach significantly improves the accuracy for prediction of peptide binding and identification of MHC ligands. The method is available at www.cbs.dtu.dk/services/NetMHCpan-3.0....

  2. Electron scavenging in ethylene glycol-water glass at 4 and 77 K: scavenging of trapped vs mobile electrons. [. gamma. -rays, x radiation

    Energy Technology Data Exchange (ETDEWEB)

    Lin, D P; Kevan, L [Wayne State Univ., Detroit, Mich. (USA). Dept. of Chemistry; Steen, H B

    1976-01-01

    Electron scavenging efficiencies have been measured at 77 and 4 K in ethylene glycol-water glass for the following scavengers which span a 250-fold range of scavenger efficiencies at 77 K: HCl, NaNO/sub 3/ and K/sub 2/Cr0/sub 4/. The range of scavenging efficiencies decreases to 62 at 4 K with the largest relative change occurring for the less efficient scavengers. These results are suggested to be most consistent with a model in which scavenging occurs by tunneling from shallowly and deeply trapped electrons at 4 and 77 K, respectively.

  3. Human leucocyte antigen class I-redirected anti-tumour CD4+ T cells require a higher T cell receptor binding affinity for optimal activity than CD8+ T cells.

    Science.gov (United States)

    Tan, M P; Dolton, G M; Gerry, A B; Brewer, J E; Bennett, A D; Pumphrey, N J; Jakobsen, B K; Sewell, A K

    2017-01-01

    CD4 + T helper cells are a valuable component of the immune response towards cancer. Unfortunately, natural tumour-specific CD4 + T cells occur in low frequency, express relatively low-affinity T cell receptors (TCRs) and show poor reactivity towards cognate antigen. In addition, the lack of human leucocyte antigen (HLA) class II expression on most cancers dictates that these cells are often unable to respond to tumour cells directly. These deficiencies can be overcome by transducing primary CD4 + T cells with tumour-specific HLA class I-restricted TCRs prior to adoptive transfer. The lack of help from the co-receptor CD8 glycoprotein in CD4 + cells might result in these cells requiring a different optimal TCR binding affinity. Here we compared primary CD4 + and CD8 + T cells expressing wild-type and a range of affinity-enhanced TCRs specific for the HLA A*0201-restricted NY-ESO-1- and gp100 tumour antigens. Our major findings are: (i) redirected primary CD4 + T cells expressing TCRs of sufficiently high affinity exhibit a wide range of effector functions, including cytotoxicity, in response to cognate peptide; and (ii) optimal TCR binding affinity is higher in CD4 + T cells than CD8 + T cells. These results indicate that the CD4 + T cell component of current adoptive therapies using TCRs optimized for CD8 + T cells is below par and that there is room for substantial improvement. © 2016 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.

  4. Novel Water Soluble Chitosan Derivatives with 1,2,3-Triazolium and Their Free Radical-Scavenging Activity

    Directory of Open Access Journals (Sweden)

    Qing Li

    2018-03-01

    Full Text Available Chitosan is an abundant and renewable polysaccharide, which exhibits attractive bioactivities and natural properties. Improvement such as chemical modification of chitosan is often performed for its potential of providing high bioactivity and good water solubility. A new class of chitosan derivatives possessing 1,2,3-triazolium charged units by associating “click reaction” with efficient 1,2,3-triazole quaternization were designed and synthesized. Their free radical-scavenging activity against three free radicals was tested. The inhibitory property and water solubility of the synthesized chitosan derivatives exhibited a remarkable improvement over chitosan. It is hypothesized that triazole or triazolium groups enable the synthesized chitosan to possess obviously better radical-scavenging activity. Moreover, the scavenging activity against superoxide radical of chitosan derivatives with triazolium (IC50 < 0.01 mg mL−1 was more efficient than that of derivatives with triazole and Vitamin C. In the 1,1-diphenyl-2-picrylhydrazyl (DPPH and hydroxyl radical-scavenging assay, the same pattern were observed, which should be related to the triazolium grafted at the periphery of molecular chains.

  5. Efficacy and safety of LCZ696, a first-in-class angiotensin receptor neprilysin inhibitor, in Asian patients with hypertension: a randomized, double-blind, placebo-controlled study.

    Science.gov (United States)

    Kario, Kazuomi; Sun, Ningling; Chiang, Fu-Tien; Supasyndh, Ouppatham; Baek, Sang Hong; Inubushi-Molessa, Akiko; Zhang, Ying; Gotou, Hiromi; Lefkowitz, Martin; Zhang, Jack

    2014-04-01

    LCZ696 (Japanese adopted name: sucabitril valsartan sodium hydrate), a first-in-class angiotensin receptor neprilysin inhibitor, concomitantly inhibits neprilysin and blocks angiotensin type 1 receptor. This randomized, double-blind, placebo-controlled study, the first in Asia for this drug, evaluated the dose-related efficacy and safety of LCZ696 in patients with hypertension using 24-hour ambulatory blood pressure (BP) monitoring. Asian patients aged ≥18 years (n=389) with hypertension were randomized to receive LCZ696 100 mg (n=100), 200 mg (n=101), 400 mg (n=96), or placebo (n=92) for 8 weeks. The primary end point was mean difference across the 3 single-dose pairwise comparisons of LCZ696 versus placebo in clinic diastolic BP after 8-week treatment. Key secondary efficacy variables included changes in clinic systolic BP and pulse pressure and changes in 24-hour, daytime, and nighttime ambulatory BPs and pulse pressure. Safety assessments included recording all adverse events and serious adverse events. A total of 362 patients completed the study. Reductions in clinic systolic BP, diastolic BP (Phypertension in Asian population and, in general, is safe and well tolerated. Clinical Trial Information- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01193101.

  6. The homeodomain-leucine zipper (HD-Zip) class I transcription factors ATHB7 and ATHB12 modulate abscisic acid signalling by regulating protein phosphatase 2C and abscisic acid receptor gene activities.

    Science.gov (United States)

    Valdés, Ana Elisa; Overnäs, Elin; Johansson, Henrik; Rada-Iglesias, Alvaro; Engström, Peter

    2012-11-01

    Plants perceiving drought activate multiple responses to improve survival, including large-scale alterations in gene expression. This article reports on the roles in the drought response of two Arabidopsis thaliana homeodomain-leucine zipper class I genes; ATHB7 and ATHB12, both strongly induced by water-deficit and abscisic acid (ABA). ABA-mediated transcriptional regulation of both genes is shown to depend on the activity of protein phosphatases type 2C (PP2C). ATHB7 and ATHB12 are, thus, targets of the ABA signalling mechanism defined by the PP2Cs and the PYR/PYL family of ABA receptors, with which the PP2C proteins interact. Our results from chromatin immunoprecipitation and gene expression analyses demonstrate that ATHB7 and ATHB12 act as positive transcriptional regulators of PP2C genes, and thereby as negative regulators of abscisic acid signalling. In support of this notion, our results also show that ATHB7 and ATHB12 act to repress the transcription of genes encoding the ABA receptors PYL5 and PYL8 in response to an ABA stimulus. In summary, we demonstrate that ATHB7 and ATHB12 have essential functions in the primary response to drought, as mediators of a negative feedback effect on ABA signalling in the plant response to water deficit.

  7. Robust immunohistochemical staining of several classes of proteins in tissues subjected to autolysis.

    Science.gov (United States)

    Maleszewski, Joseph; Lu, Jie; Fox-Talbot, Karen; Halushka, Marc K

    2007-06-01

    Despite the common use of immunohistochemistry in autopsy tissues, the stability of most proteins over extended time periods is unknown. The robustness of signal for 16 proteins (MMP1, MMP2, MMP3, MMP9, TIMP1, TIMP2, TIMP3, AGER, MSR, SCARB1, OLR1, CD36, LTF, LGALS3, LYZ, and DDOST) and two measures of advanced glycation end products (AGE, CML) was evaluated. Two formalin-fixed, paraffin-embedded human tissue arrays containing 16 tissues each were created to evaluate 48 hr of autolysis in a warm or cold environment. For these classes of proteins, matrix metalloproteinases and their inhibitors, scavenger receptors, and advanced glycation end product receptors, we saw no systematic diminution of signal intensity during a period of 24 hr. Analysis was performed by two independent observers and confirmed for a subset of proteins by digital analysis and Western blotting. We conclude that these classes of proteins degrade slowly and faithfully maintain their immunohistochemistry characteristics over at least a 24-hr time interval in devitalized tissues. This study supports the use of autopsy tissues with short postmortem intervals for immunohistochemical studies for diseases such as diabetic vascular disease, cancer, Alzheimer's disease, atherosclerosis, and other pathological states. This manuscript contains online supplemental material at http://www.jhc.org. Please visit this article online to view these materials.

  8. Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines

    Directory of Open Access Journals (Sweden)

    Frantisek Sersen

    2017-05-01

    Full Text Available Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene-N′-[2,6-dinitro-4-(trifluoromethyl]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH, galvinoxyl radical (GOR, and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid (ABTS radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.

  9. Synthesis and Free Radical Scavenging Activity of New Hydroxybenzylidene Hydrazines.

    Science.gov (United States)

    Sersen, Frantisek; Gregan, Fridrich; Kotora, Peter; Kmetova, Jarmila; Filo, Juraj; Loos, Dusan; Gregan, Juraj

    2017-05-29

    Hydroxybenzylidene hydrazines exhibit a wide spectrum of biological activities. Here, we report synthesis and free radical scavenging activity of nine new N-(hydroxybenzylidene)-N'-[2,6-dinitro-4-(trifluoromethyl)]phenylhydrazines. The chemical structures of these compounds were confirmed by 1H-NMR, 13C-NMR, 19F-NMR, IR spectroscopy, LC-MS, and elemental analysis. The prepared compounds were tested for their activity to scavenge 2,2-diphenyl-1-picrylhydrazyl (DPPH), galvinoxyl radical (GOR), and 2,2'-azino-bis(3-ethylbenzothiazoline)-6-sulphonic acid (ABTS) radicals. The free radical scavenging activity expressed as SC50 values of these compounds varied in a wide range, from a strong to no radical scavenging effect. The most effective radical scavengers were hydroxybenzylidene hydrazines containing three hydroxyl groups in the benzylidene part of their molecules. The prepared compounds were also tested for their activity to inhibit photosynthetic electron transport in spinach chloroplasts. IC50 values of these compounds varied in wide range, from an intermediate to no inhibitory effect.

  10. Multiple free-radical scavenging (MULTIS) capacity in cattle serum.

    Science.gov (United States)

    Sueishi, Yoshimi; Kamogawa, Erisa; Kimura, Anna; Kitahara, Go; Satoh, Hiroyuki; Asanuma, Taketoshi; Oowada, Shigeru

    2017-01-01

    Multiple free-radical scavenging (MULTIS) activity in cattle and human sera was evaluated with electron spin resonance spectroscopy. Scavenging rates against six active species, namely hydroxyl radical, superoxide anion, alkoxyl radical, alkylperoxyl radical, methyl radical, and singlet oxygen were quantified. The difference in the electron spin resonance signal intensity in the presence and absence of the serum was converted into the scavenging rates. Comparative MULTIS measurements were made in sera from eight beef cattle, three fetal calves and fifteen healthy human volunteers. Further, we determined the MULTIS value of albumin, the most abundant component in serum. MULTIS values in cattle sera indicated higher scavenging activity against most free radical species tested than human sera. In particular, cattle serum scavenging activities against superoxide and methyl radical were higher than human serum by 2.6 and 3.7 fold, respectively. In cattle serum, albumin appears to play a dominant role in MULTIS activity, but in human serum that is not the case. Previous data indicated that the abundance of uric acid in bovine blood is nearly 80% less than humans; however, this difference does not explain the deviation in MULTIS profile.

  11. CD34 Antigen and the MPL Receptor Expression Defines a Novel Class of Human Cord Blood-Derived Primitive Hematopoietic Stem Cells.

    Science.gov (United States)

    Matsuoka, Yoshikazu; Takahashi, Masaya; Sumide, Keisuke; Kawamura, Hiroshi; Nakatsuka, Ryusuke; Fujioka, Tatsuya; Sonoda, Yoshiaki

    2017-06-09

    In the murine hematopoietic stem cell (HSC) compartment, thrombopoietin (THPO)/MPL (THPO receptor) signaling plays an important role in the maintenance of adult quiescent HSCs. However, the role of THPO/MPL signaling in the human primitive HSC compartment has not yet been elucidated. We have identified very primitive human cord blood (CB)-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) using the intra-bone marrow injection method. In this study, we investigated the roles of the MPL expression in the human primitive HSC compartment. The SRC activities of the highly purified CB-derived 18Lin-CD34+/-MPL+/- cells were analyzed using NOG mice. In the primary recipient mice, nearly all mice that received CD34+/-MPL+/- cells were repopulated with human CD45+ cells. Nearly all of these mice that received CD34+MPL+/- and CD34-MPL- cells showed a secondary repopulation. Interestingly, the secondary recipient mice that received CD34+/-MPL- cells showed a distinct tertiary repopulation. These results clearly indicate that the CD34+/- SRCs not expressing MPL sustain a long-term (LT) (>1 year) human cell repopulation in NOG mice. Moreover, CD34- SRCs generate CD34+CD38-CD90+ SRCs in vitro and in vivo. These findings provide a new concept that CD34-MPL- SRCs reside at the apex of the human HSC hierarchy.

  12. In vitro free radical scavenging activity of Ixora coccinea L

    Directory of Open Access Journals (Sweden)

    Moni Rani Saha

    2008-06-01

    Full Text Available Antioxidant activity of the methanol extract of Ixora coccinea L. was determined by DPPH free radical scavenging assay, reducing power and total antioxidant capacity using phosphomolybdenum method. Preliminary phytochemical screening revealed that the extract of the flower of I. coccinea possesses flavonoids, steroids and tannin materials. The extract showed significant activities in all antioxidant assays compared to the standard antioxidant in a dose dependent manner and remarkable activities to scavenge reactive oxygen species (ROS may be attributed to the high amount of hydrophilic phenolics. In DPPH radical scavenging assay the IC50 value of the extract was found to be 100.53 μg/mL while ascorbic acid had the IC50 value 58.92 μg/mL. Moreover, I. coccinea extract showed strong reducing power and total antioxidant capacity.

  13. Scavenging energy from human motion with tubular dielectric polymer

    Science.gov (United States)

    Jean-Mistral, Claire; Basrour, Skandar

    2010-04-01

    Scavenging energy from human motion is a challenge to supply low consumption systems for sport or medical applications. A promising solution is to use electroactive polymers and especially dielectric polymers to scavenge mechanical energy during walk. In this paper, we present a tubular dielectric generator which is the first step toward an integration of these structures into textiles. For a 10cm length and under a strain of 100%, the structure is able to scavenge 1.5μJ for a poling voltage of 200V and up to 40μJ for a poling voltage of 1000V. A 30cm length structure is finally compared to our previous planar structure, and the power management module for those structures is discussed.

  14. Free radical scavenging properties of some wine probes

    International Nuclear Information System (INIS)

    Stasko, A.; Liptakova, M.; Malik, F.

    1999-01-01

    There are preliminary results of investigation of scavenging properties of 8 probes of Slovak wines (consisting of one reference, 3 probes of white wine and 4 probes of red wine). According to the literature so far, wine probes contain paramagnetic species (Mn 2+ , characterised with sextet spectrum, and a singlet line around g=2,00). In our probes we observed Mn 2+ signals, but no significant evidence for a single line of free radical was found. We can conclude that Mn 2+ content in the red wines is generally higher than in the white ones. Further, we investigated the scavenging activities of the probes adding solution of dinitropicryl hydrazyl (DPPH-stable radical) to them. Their ability to terminate free radicals resulted in the decrease of the final DPPH concentrations in the probes. The red wines have significantly higher capability to scavenge free radicals than the probes of white wines. (authors)

  15. Towards a thermodynamic definition of efficacy in partial agonism: The thermodynamics of efficacy and ligand proton transfer in a G protein-coupled receptor of the rhodopsin class.

    Science.gov (United States)

    Broadley, Kenneth J; Sykes, Shane C; Davies, Robin H

    2010-11-15

    The thermodynamic binding profiles of agonist and antagonist complexes of the 4-hydroxypropanolamine partial agonist, prenalterol, on the chronotropic adrenergic response in guinea-pig right atria were determined over a 15 °C temperature range. The tissue response was compared with data on the ethanolamine agonist, isoprenaline, given by binding studies in a number of rat tissues. Utilising the residue conservatism surrounding the known active conformers bound to either of two aspartate residues (α-helices II, III) in both receptors (β(1), β(2)) and species (guinea-pig, rat and human), no significant deformation in the extended side chain could be found in prenalterol's agonist binding compared to isoprenaline. Antagonist binding gave a highly favourable entropy contribution at 30.0 °C of -4.7±1.2 kcal/mol. The enthalpy change between bound agonist and antagonist complexes, a function of the efficacy alone, was -6.4±1.1 kcal/mol, coincident with the calculated intrinsic preference of a primary/secondary amine-aspartate interaction for a neutral hydrogen-bonded form over its ion pair state, giving values of 6.3-6.6 kcal/mol with calculations of good quality, a figure expected to be close to that shown within a hydrophobic environment. Delivery of a proton to a conserved aspartate anion (α-helix II) becomes the critical determinant for agonist action with resultant proton transfer stabilisation dominating the enthalpy change. A proposed monocation-driven ligand proton pumping mechanism within the ternary complex is consistent with the data, delivery between two acid groups being created by the movement of the cation and the counter-movement of the ligand protonated amine moving from Asp 138 (α-helix III) to Asp 104 (α-helix II). Copyright © 2010 Elsevier Inc. All rights reserved.

  16. High throughput assay for evaluation of reactive carbonyl scavenging capacity.

    Science.gov (United States)

    Vidal, N; Cavaille, J P; Graziani, F; Robin, M; Ouari, O; Pietri, S; Stocker, P

    2014-01-01

    Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

  17. High throughput assay for evaluation of reactive carbonyl scavenging capacity

    Directory of Open Access Journals (Sweden)

    N. Vidal

    2014-01-01

    Full Text Available Many carbonyl species from either lipid peroxidation or glycoxidation are extremely reactive and can disrupt the function of proteins and enzymes. 4-hydroxynonenal and methylglyoxal are the most abundant and toxic lipid-derived reactive carbonyl species. The presence of these toxics leads to carbonyl stress and cause a significant amount of macromolecular damages in several diseases. Much evidence indicates trapping of reactive carbonyl intermediates may be a useful strategy for inhibiting or decreasing carbonyl stress-associated pathologies. There is no rapid and convenient analytical method available for the assessment of direct carbonyl scavenging capacity, and a very limited number of carbonyl scavengers have been identified to date, their therapeutic potential being highlighted only recently. In this context, we have developed a new and rapid sensitive fluorimetric method for the assessment of reactive carbonyl scavengers without involvement glycoxidation systems. Efficacy of various thiol- and non-thiol-carbonyl scavenger pharmacophores was tested both using this screening assay adapted to 96-well microplates and in cultured cells. The scavenging effects on the formation of Advanced Glycation End-product of Bovine Serum Albumin formed with methylglyoxal, 4-hydroxynonenal and glucose-glycated as molecular models were also examined. Low molecular mass thiols with an α-amino-β-mercaptoethane structure showed the highest degree of inhibitory activity toward both α,β-unsaturated aldehydes and dicarbonyls. Cysteine and cysteamine have the best scavenging ability toward methylglyoxal. WR-1065 which is currently approved for clinical use as a protective agent against radiation and renal toxicity was identified as the best inhibitor of 4-hydroxynonenal.

  18. Multiple free-radical scavenging capacity in serum

    Science.gov (United States)

    Oowada, Shigeru; Endo, Nobuyuki; Kameya, Hiromi; Shimmei, Masashi; Kotake, Yashige

    2012-01-01

    We have developed a method to determine serum scavenging-capacity profile against multiple free radical species, namely hydroxyl radical, superoxide radical, alkoxyl radical, alkylperoxyl radical, alkyl radical, and singlet oxygen. This method was applied to a cohort of chronic kidney disease patients. Each free radical species was produced with a common experimental procedure; i.e., uv/visible-light photolysis of free-radical precursor/sensitizer. The decrease in free-radical concentration by the presence of serum was quantified with electron spin resonance spin trapping method, from which the scavenging capacity was calculated. There was a significant capacity change in the disease group (n = 45) as compared with the healthy control group (n = 30). The percent values of disease’s scavenging capacity with respect to control group indicated statistically significant differences in all free-radical species except alkylperoxyl radical, i.e., hydroxyl radical, 73 ± 12% (p = 0.001); superoxide radical, 158 ± 50% (p = 0.001); alkoxyl radical, 121 ± 30% (p = 0.005); alkylperoxyl radical, 123 ± 32% (p>0.1); alkyl radical, 26 ± 14% (p = 0.001); and singlet oxygen, 57 ± 18% (p = 0.001). The scavenging capacity profile was illustrated using a radar chart, clearly demonstrating the characteristic change in the disease group. Although the cause of the scavenging capacity change by the disease state is not completely understood, the profile of multiple radical scavenging capacities may become a useful diagnostic tool. PMID:22962529

  19. The Impact of Flight Hardware Scavenging on Space Logistics

    Science.gov (United States)

    Oeftering, Richard C.

    2011-01-01

    For a given fixed launch vehicle capacity the logistics payload delivered to the moon may be only roughly 20 percent of the payload delivered to the International Space Station (ISS). This is compounded by the much lower flight frequency to the moon and thus low availability of spares for maintenance. This implies that lunar hardware is much more scarce and more costly per kilogram than ISS and thus there is much more incentive to preserve hardware. The Constellation Lunar Surface System (LSS) program is considering ways of utilizing hardware scavenged from vehicles including the Altair lunar lander. In general, the hardware will have only had a matter of hours of operation yet there may be years of operational life remaining. By scavenging this hardware the program, in effect, is treating vehicle hardware as part of the payload. Flight hardware may provide logistics spares for system maintenance and reduce the overall logistics footprint. This hardware has a wide array of potential applications including expanding the power infrastructure, and exploiting in-situ resources. Scavenging can also be seen as a way of recovering the value of, literally, billions of dollars worth of hardware that would normally be discarded. Scavenging flight hardware adds operational complexity and steps must be taken to augment the crew s capability with robotics, capabilities embedded in flight hardware itself, and external processes. New embedded technologies are needed to make hardware more serviceable and scavengable. Process technologies are needed to extract hardware, evaluate hardware, reconfigure or repair hardware, and reintegrate it into new applications. This paper also illustrates how scavenging can be used to drive down the cost of the overall program by exploiting the intrinsic value of otherwise discarded flight hardware.

  20. Electron beam treatment with radical scavengers/enhancers

    International Nuclear Information System (INIS)

    Gehringer, P.

    1994-08-01

    E-beam treatment of low level contaminated groundwater is best apt to demonstrate the role of scavengers and enhancers, respectively because groundwater already contains some scavengers as natural solutes. The action of ionizing radiation to water is known to result in the formation of ions, molecular and free radical species. For low level contaminations of groundwater (pollutant concentration aqu - and H are of interest for pollutant decomposition. The pollutants have to compete for the free radical species with the natural solutes. 10 figures are discussed. (author)

  1. Free radical scavenging injectable hydrogels for regenerative therapy

    International Nuclear Information System (INIS)

    Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

    2017-01-01

    Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

  2. Free radical scavenging injectable hydrogels for regenerative therapy

    Energy Technology Data Exchange (ETDEWEB)

    Komeri, Remya [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India); Thankam, Finosh Gnanaprakasam [Dept. of Biomedical Sciences, Creighton University, 2500 California Plaza, Omaha NE68178 (United States); Muthu, Jayabalan, E-mail: mjayabalan52@gmail.com [Sree Chitra Tirunal Institute for Medical Sciences and Technology, Polymer Science Division, BMT Wing, Thiruvananthapuram 695 012, Kerala State (India)

    2017-02-01

    Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07 kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. - Graphical abstract: Injectable hydrogel with inherent free radical scavenging property for regenerative tissue engineering application. - Highlights: • Novel injectable hydrogel (PEAX-P) is prepared using D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer

  3. Free radical-scavenging delta-lactones from Boletus calopus.

    Science.gov (United States)

    Kim, Jin-Woo; Yoo, Ick-Dong; Kim, Won-Gon

    2006-12-01

    The methanol extracts from the fruiting body of the mushroom Boletus calopus showed free radical-scavenging activity. Bioactivity-guided fractionation of the methanol extracts led to a new hydroxylated calopin named calopin B, along with the known delta-lactones calopin and cyclocalopin A. The structure of the new calopin analogue was elucidated by spectroscopic methods. All compounds showed potent free radical-scavenging activity against superoxide, DPPH, and ABTS radicals with IC (50) values of 1.2 - 5.4 microg/mL.

  4. Process for scavenging hydrogen sulfide from hydrocarbon gases

    International Nuclear Information System (INIS)

    Fox, I.

    1981-01-01

    A process for scavenging hydrogen sulfide from hydrocarbon gases utilizes iron oxide particles of unique chemical and physical properties. These particles have large surface area, and are comprised substantially of amorphous Fe 2 O 3 containing a crystalline phase of Fe 2 O 3 , Fe 3 O 4 and combinations thereof. In scavenging hydrogen sulfide, the iron oxide particles are suspended in a liquid which enters into intimate mixing contact with hydrocarbon gases; the hydrogen sulfide is reacted at an exceptional rate and only acid-stable reaction products are formed. Thereafter, the sweetened hydrocarbon gases are collected

  5. Performance of zeolite scavenge column in Xe monitoring system

    International Nuclear Information System (INIS)

    Wang Qian; Wang Hongxia; Li Wei; Bian Zhishang

    2010-01-01

    In order to improve the performance of zeolite scavenge column, its ability of removal of humidity and carbon dioxide was studied by both static and dynamic approaches. The experimental results show that various factors, including the column length and diameter, the mass of zeolite, the content of water in air, the temperature rise during adsorption, and the activation effectiveness all effect the performance of zeolite column in scavenging humanity and carbon dioxide. Based on these results and previous experience, an optimized design of the zeolite column is made for use in xenon monitoring system. (authors)

  6. Free radical scavenging activity of Eagle tea and their flavonoids

    Directory of Open Access Journals (Sweden)

    Qiong Meng

    2012-06-01

    Full Text Available In this study, an online HPLC-DAD-MS coupled with 2,2′-azinobis (3-ethylbenzthiazoline-6-sulfonic acid diammonium salt (ABTS assay was employed for evaluating free radical scavenging activity of Eagle tea and their active components. Twenty-three chromatographic peaks were detected, and nineteen components had free radical scavenging activity. Among them, eight compounds were identified as flavonoids (hyperin, isoquercitrin, quercitrin, quercetin, kaempferol, catechins, chlorogenic acid and epicatechin based on MS data and standard chromatographic characters.

  7. Key Role of Toll-Like Receptor 2 in the Inflammatory Response and Major Histocompatibility Complex Class II Downregulation in Brucella abortus-Infected Alveolar Macrophages

    Science.gov (United States)

    Ferrero, Mariana C.; Hielpos, M. Soledad; Carvalho, Natalia B.; Barrionuevo, Paula; Corsetti, Patricia P.; Giambartolomei, Guillermo H.; Oliveira, Sergio C.

    2014-01-01

    Alveolar macrophages (AM) seem to constitute the main cellular target of inhaled brucellae. Here, we show that Brucella abortus invades and replicates in murine AM without inducing cytotoxicity. B. abortus infection induced a statistically significant increase of tumor necrosis factor alpha (TNF-α), CXCL1 or keratinocyte chemoattractant (KC), interleukin-1β (IL-1β), IL-6, and IL-12 in AM from C57BL/6 mice and BALB/c mice, but these responses were generally weaker and/or delayed compared to those elicited in peritoneal macrophages. Studies using knockout mice for TLR2, TLR4, and TLR9 revealed that TNF-α and KC responses were mediated by TLR2 recognition. Brucella infection reduced in a multiplicity of infection-dependent manner the expression of major histocompatibility complex class II (MHC-II) molecules induced by gamma interferon (IFN-γ) in AM. The same phenomenon was induced by incubation with heat-killed B. abortus (HKBA) or the lipidated form of the 19-kDa outer membrane protein of Brucella (L-Omp19), and it was shown to be mediated by TLR2 recognition. In contrast, no significant downregulation of MHC-II was induced by either unlipidated Omp19 or Brucella LPS. In a functional assay, treatment of AM with either L-Omp19 or HKBA reduced the MHC-II-restricted presentation of OVA peptides to specific T cells. One week after intratracheal infection, viable B. abortus was detected in AM from both wild-type and TLR2 KO mice, but CFU counts were higher in the latter. These results suggest that B. abortus survives in AM after inhalatory infection in spite of a certain degree of immune control exerted by the TLR2-mediated inflammatory response. Both the modest nature of the latter and the modulation of MHC-II expression by the bacterium may contribute to such survival. PMID:24478078

  8. Expression of the P2X2 receptor in different classes of ileum myenteric neurons in the female obese ob/ob mouse

    Science.gov (United States)

    Mizuno, Márcia Sanae; Crisma, Amanda Rabello; Borelli, Primavera; Castelucci, Patricia

    2012-01-01

    AIM: To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system abnormalities such as altered motility. METHODS: The study examined the distribution of the P2X2 receptor (P2X2R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X2R with neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice. In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm2) and area profile (μm²) of P2X2R-positive neurons. In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NADH) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and area. RESULTS: In the present study, we observed a 29.6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG). In addition, the average small intestine area was increased by approximately 29.6% in the OG compared to the CG. Immunoreactivity (IR) for the P2X2R, nNOS, ChAT and CalR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups. This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes. P2X2R-IR was observed to co-localize 100% with that for nNOS, ChAT and CalR in neurons of both groups. In the ob/ob group, however, we observed that the neuronal density (neuron/cm2) of P2X2R-IR cells was increased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice. The neuronal density of CalR-IR neurons was not different between the groups. Morphometric studies further demonstrated that the

  9. Clicked Cinnamic/Caffeic Esters and Amides as Radical Scavengers and 5-Lipoxygenase Inhibitors

    Directory of Open Access Journals (Sweden)

    Jérémie A. Doiron

    2014-01-01

    Full Text Available 5-Lipoxygenase (5-LO is the key enzyme responsible for the conversion of arachidonic acid to leukotrienes, a class of lipid mediators implicated in inflammatory disorders. In this paper, we describe the design, synthesis, and preliminary activity studies of novel clicked caffeic esters and amides as radical scavengers and 5-LO inhibitors. From known 5-LO inhibitor 3 as a lead, cinnamic esters 8a–h and amides 9a–h as well as caffeic esters 15a–h and amides 16a–h were synthesized by Cu(I-catalyzed [1,3]-dipolar cycloaddition with the appropriate azide precursors and terminal alkynes. All caffeic analogs are proved to be good radical scavengers (IC50: 10–20 μM. Esters 15g and 15f possessed excellent 5-LO inhibition activity in HEK293 cells and were equipotent with the known 5-LO inhibitor CAPE and more potent than Zileuton. Several synthesized esters possess activities rivaling Zileuton in stimulated human polymorphonuclear leukocytes.

  10. Word classes

    DEFF Research Database (Denmark)

    Rijkhoff, Jan

    2007-01-01

    in grammatical descriptions of some 50 languages, which together constitute a representative sample of the world’s languages (Hengeveld et al. 2004: 529). It appears that there are both quantitative and qualitative differences between word class systems of individual languages. Whereas some languages employ...... a parts-of-speech system that includes the categories Verb, Noun, Adjective and Adverb, other languages may use only a subset of these four lexical categories. Furthermore, quite a few languages have a major word class whose members cannot be classified in terms of the categories Verb – Noun – Adjective...... – Adverb, because they have properties that are strongly associated with at least two of these four traditional word classes (e.g. Adjective and Adverb). Finally, this article discusses some of the ways in which word class distinctions interact with other grammatical domains, such as syntax and morphology....

  11. Evaluation of Antioxidant and Free Radical Scavenging Abilities of ...

    African Journals Online (AJOL)

    Objective: This study was aimed at determining the antioxidants and free radical scavenging abilities of some packaged fruit juices (PFJ) widely used as source of fluids in Nigeria. Materials and methods: Packaged fruit juice samples produced by The Coca cola Company and Chi company namely: Apple(AP), blackcurrant, ...

  12. Scavenger and antioxidant properties of prenylflavones isolated from Artocarpus heterophyllus.

    Science.gov (United States)

    Ko, F N; Cheng, Z J; Lin, C N; Teng, C M

    1998-07-15

    The antioxidant properties of prenylflavones, isolated from Artocarpus heterophyllus Lam., was evaluated in this study. Among them, artocarpine, artocarpetin, artocarpetin A, and cycloheterophyllin diacetate and peracetate had no effect on iron-induced lipid peroxidation in rat brain homogenate. They also did not scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl. In contrast, cycloheterophyllin and artonins A and B inhibited iron-induced lipid peroxidation in rat brain homogenate and scavenged 1,1-diphenyl-2-picrylhydrazyl. They also scavenged peroxyl radicals and hydroxyl radicals that were generated by 2,2'-azobis(2-amidinopropane) dihydrochloride and the Fe3+-ascorbate-EDTA-H2O2 system, respectively. However, they did not inhibit xanthine oxidase activity or scavenge superoxide anion, hydrogen peroxide, carbon radical, or peroxyl radicals derived from 2,2'-azobis(2,4-dimethylvaleronitrile) in hexane. Moreover, cycloheterophyllin and artonins A and B inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity, thiobarbituric acid-reactive substance and conjugated-diene formations and electrophoretic mobility. It is concluded that cycloheterophyllin and artonins A and B serve as powerful antioxidants against lipid peroxidation when biomembranes are exposed to oxygen radicals.

  13. Energy scavenging strain absorber: application to kinetic dielectric elastomer generator

    Science.gov (United States)

    Jean-Mistral, C.; Beaune, M.; Vu-Cong, T.; Sylvestre, A.

    2014-03-01

    Dielectric elastomer generators (DEGs) are light, compliant, silent energy scavengers. They can easily be incorporated into clothing where they could scavenge energy from the human kinetic movements for biomedical applications. Nevertheless, scavengers based on dielectric elastomers are soft electrostatic generators requiring a high voltage source to polarize them and high external strain, which constitutes the two major disadvantages of these transducers. We propose here a complete structure made up of a strain absorber, a DEG and a simple electronic power circuit. This new structure looks like a patch, can be attached on human's wear and located on the chest, knee, elbow… Our original strain absorber, inspired from a sailing boat winch, is able to heighten the external available strain with a minimal factor of 2. The DEG is made of silicone Danfoss Polypower and it has a total area of 6cm per 2.5cm sustaining a maximal strain of 50% at 1Hz. A complete electromechanical analytical model was developed for the DEG associated to this strain absorber. With a poling voltage of 800V, a scavenged energy of 0.57mJ per cycle is achieved with our complete structure. The performance of the DEG can further be improved by enhancing the imposed strain, by designing a stack structure, by using a dielectric elastomer with high dielectric permittivity.

  14. Scavenging rate ecoassay: a potential indicator of estuary condition.

    Science.gov (United States)

    Porter, Augustine G; Scanes, Peter R

    2015-01-01

    Monitoring of estuary condition is essential due to the highly productive and often intensely impacted nature of these ecosystems. Assessment of the physico-chemical condition of estuaries is expensive and difficult due to naturally fluctuating water quality and biota. Assessing the vigour of ecosystem processes is an alternative method with potential to overcome much of the variability associated with physico-chemical measures. Indicators of estuary condition should have small spatial and temporal variability, have a predictable response to perturbation and be ecologically relevant. Here, we present tests of the first criterion, the spatio-temporal variability of a potential ecoassay measuring the rate of scavenging in estuaries. We hypothesised that the proposed scavenging ecoassay would not vary significantly among A) sites in an estuary, B) trips separated by weeks, or C) days in a trip. Because not all habitats are present in all estuaries, this test was undertaken in two habitats. When conducted over bare substrate there were occasional significant differences, but no discernible patterns, within levels of the experiment. When conducted over vegetated substrate, days within a trip did not vary significantly, but later trips experienced greater scavenging. This scavenging ecoassay shows potential as a tool for assessing the condition of estuarine ecosystems, and further exploration of this protocol is warranted by implementation in estuaries across a gradient of anthropogenic stress.

  15. Free radical scavenging activity and phenolic contents of ...

    African Journals Online (AJOL)

    Anthocleista djalonensis extract is widely used in Nigerian folk medicine to treat conditions whose pathogenesis implicate oxidative stress, such as diabetes and hepatitis. However, little is known of the mechanism underlying these activities. In this study, the free radical scavenging potential of a methanol extract of A.

  16. Contrasting Boundary Scavenging in two Eastern Boundary Current Regimes

    Science.gov (United States)

    Anderson, R. F.; Fleisher, M. Q.; Pavia, F. J.; Vivancos, S. M.; Lu, Y.; Zhang, P.; Cheng, H.; Edwards, R. L.

    2016-02-01

    We use data from two US GEOTRACES expeditions to compare boundary scavenging intensity in two eastern boundary current systems: the Canary Current off Mauritania and the Humboldt Current off Peru. Boundary scavenging refers to the enhanced removal of trace elements from the ocean by sorption to sinking particles in regions of greater than average particle abundance. Both regimes experience high rates of biological productivity and generation of biogenic particles, with rates of productivity potentially a little greater off Peru, whereas dust fluxes are an order of magnitude greater off NW Africa (see presentation by Vivancos et al., this meeting). Despite greater productivity off Peru, we find greater intensity of scavenging off NW Africa as measured by the residence time of dissolved 230Th integrated from the surface to a depth of 2500 m (10-11 years off NW Africa vs. 15-17 years off Peru). Dissolved 231Pa/230Th ratios off NW Africa (Hayes et al., Deep Sea Res.-II 116 (2015) 29-41) are nearly twice the values observed off Peru. We attribute this difference to the well-known tendency for lithogenic phases (dust) to strongly fractionate in favor of Th uptake during scavenging and removal, leaving the dissolved phase enriched in Pa. This behavior needs to be considered when interpreting sedimentary 231Pa/230Th ratios as a paleo proxy.

  17. Clustered DNA damage on subcellular level: effect of scavengers

    Czech Academy of Sciences Publication Activity Database

    Pachnerová Brabcová, Kateřina; Sihver, L.; Yasuda, N.; Matuo, Y.; Štěpán, Václav; Davídková, Marie

    2014-01-01

    Roč. 53, č. 4 (2014), s. 705-712 ISSN 0301-634X R&D Projects: GA MŠk LD12008 Institutional support: RVO:61389005 Keywords : clustered damage * indirect effects * haevy ion * plasmid in liquid water * scavenger Subject RIV: BO - Biophysics Impact factor: 1.528, year: 2014

  18. Hydroxyl radical scavenging activity of peptide from sea cucumber ...

    African Journals Online (AJOL)

    enzyme complex, sea cucumber protein hydrolysis was carried out to obtain hydrolysates that have hydroxyl-radical-scavenging activity (HRSA). The hydrolytic process was monitored by HRSA and conditions for this process were optimized as follows: pH 6.5, temperature 35°C, 12 mg enzyme complex in a reaction solution ...

  19. Free Radical Scavenging Activity of Scoparia dulcis Extract.

    Science.gov (United States)

    Babincová, M.; Sourivong, P.

    2001-01-01

    We studied the scavenging capabilities of an extract of Scoparia dulcis (a cosmopolitan weed widespread in Laos and Vietnam) for 1-diphenyl-2-picrylhydrazyl and measured hemoglobin-catalyzed linoleic acid peroxidation with an oxygen electrode. Our results demonstrated strong antioxidant activity corresponding to mitigation of the generation of hydroxyl radicals, a possible rationale for the observed therapeutic effects of this weed.

  20. Antioxidant and free radical scavenging activities of plant extracts ...

    African Journals Online (AJOL)

    Twenty-two species of medicinal plants collected in the Mexican state of Morelos were selected to evaluate their free radical scavenging and antioxidant activities. The extracts from the aerial parts of the plants were obtained using hexane, acetone and methanol (66 extracts). The initial qualitative screening of antioxidants ...

  1. Mitochondrial respiration scavenges extramitochondrial superoxide anion via a nonenzymatic mechanism.

    OpenAIRE

    Guidot, D M; Repine, J E; Kitlowski, A D; Flores, S C; Nelson, S K; Wright, R M; McCord, J M

    1995-01-01

    We determined that mitochondrial respiration reduced cytosolic oxidant stress in vivo and scavenged extramitochondrial superoxide anion (O2-.) in vitro. First, Saccharomyces cerevisiae deficient in both the cytosolic antioxidant cupro-zinc superoxide dismutase (Cu,Zn-SOD) and electron transport (Rho0 state) grew poorly (P 0.05) in all yeast. Seco...

  2. Free radical scavenging and cytotoxic activity of five commercial ...

    African Journals Online (AJOL)

    Polygonum cuspidatum), and pomegranate (Punica granatum). It shows radical scavenging activity in the following order, according to their median effective concentration (EC

  3. Using Scavenger Hunts to Familiarize Students with Scientific Journal Articles.

    Science.gov (United States)

    Lijek, Rebeccah S; Fankhauser, Sarah C

    2016-03-01

    Primary scientific literature can be difficult to navigate for anyone unfamiliar with its foreign, formal structure. We sought to create a fun, easy learning tool to help familiarize students of all ages with the structure of a scientific article. Our main learning objective was for the student to realize that science writing is formulaic-that specific information is found in predictable locations within an article-and that, with an understanding of the formula, anyone can comfortably navigate any journal article and accurately predict what to expect to find in each section. To this end, we designed a Journal Article Scavenger Hunt that requires the user to find and identify a series of commonplace features of a primary research article. The scavenger hunt activity is quick and easy to implement, and is adaptable to various ages and settings, including the classroom, lab, and at outreach events. The questions in the scavenger hunt can be scaled in difficulty and specificity to suit the instructor's needs. Over many years of using this activity, we have received positive feedback from students of all ages, from elementary school students to lay adult-learners as well as science teachers themselves. By making the unknown seem predictable and approachable, the scavenger hunt helps a variety of audiences feel more comfortable with science and more confident in their ability to engage directly with the scientific literature. Journal of Microbiology & Biology Education.

  4. Ambient RF energy scavenging: GSM and WLAN power density measurements

    NARCIS (Netherlands)

    Visser, H.J.; Reniers, A.C.F.; Theeuwes, J.A.C.

    2009-01-01

    To assess the feasibility of ambient RF energy scavenging, a survey of expected power density levels distant from GSM-900 and GSM-1800 base stations has been conducted and power density measurements have been performed in a WLAN environment. It appears that for distances ranging from 25 m to 100 m

  5. Forensically significant scavenging guilds in the southwest of Western Australia.

    Science.gov (United States)

    O'Brien, R Christopher; Forbes, Shari L; Meyer, Jan; Dadour, Ian

    2010-05-20

    Estimation of time since death is an important factor in forensic investigations and the state of decomposition of a body is a prime basis for such estimations. The rate of decomposition is, however, affected by many environmental factors such as temperature, rainfall, and solar radiation as well as by indoor or outdoor location, covering and the type of surface the body is resting upon. Scavenging has the potential for major impact upon the rate of decomposition of a body, but there is little direct research upon its effect. The information that is available relates almost exclusively to North American and European contexts. The Australian faunal assemblage is unique in that it includes no native large predators or large detrivorous avians. This research investigates the animals that scavenge carcasses in natural outdoor settings in southern Western Australia and the factors which can affect each scavenger's activity. The research was conducted at four locations around Perth, Western Australia with different environmental conditions. Pig carcasses, acting as models for the human body, were positioned in an outdoor environment with no protection from scavengers or other environmental conditions. Twenty-four hour continuous time-lapse video capture was used to observe the pattern of visits of all animals to the carcasses. The time of day, length of feeding, material fed upon, area of feeding, and any movement of the carcass were recorded for each feeding event. Some species were observed to scavenge almost continually throughout the day and night. Insectivores visited the carcasses mostly during bloat and putrefaction; omnivores fed during all stages of decomposition and scavenging by carnivores, rare at any time, was most likely to occur during the early stages of decomposition. Avian species, which were the most prolific visitors to the carcasses in all locations, like reptiles, fed only during daylight hours. Only mammals and amphibians, which were seldom seen

  6. Class size versus class composition

    DEFF Research Database (Denmark)

    Jones, Sam

    Raising schooling quality in low-income countries is a pressing challenge. Substantial research has considered the impact of cutting class sizes on skills acquisition. Considerably less attention has been given to the extent to which peer effects, which refer to class composition, also may affect...... bias from omitted variables, the preferred IV results indicate considerable negative effects due to larger class sizes and larger numbers of overage-for-grade peers. The latter, driven by the highly prevalent practices of grade repetition and academic redshirting, should be considered an important...

  7. Free radical scavenging injectable hydrogels for regenerative therapy.

    Science.gov (United States)

    Komeri, Remya; Thankam, Finosh Gnanaprakasam; Muthu, Jayabalan

    2017-02-01

    Pathological free radicals generated from inflamed and infarcted cardiac tissues interferes natural tissue repair mechanisms. Hypoxic microenvironment at the injured zone of non-regenerating cardiac tissues hinders the therapeutic attempts including cell therapy. Here we report an injectable, cytocompatible, free radical scavenging synthetic hydrogel formulation for regenerative therapy. New hydrogel (PEAX-P) is prepared with D-xylitol-co-fumarate-co-poly ethylene adipate-co-PEG comaromer (PEAX) and PEGDiacrylate. PEAX-P hydrogel swells 4.9 times the initial weight and retains 100.07kPa Young modulus at equilibrium swelling, which is suitable for cardiac applications. PEAX-P hydrogel retains elastic nature even at 60% compressive strain, which is favorable to fit with the dynamic and elastic natural tissue counterparts. PEAX-P hydrogel scavenges 51% DPPH radical, 40% hydroxyl radicals 41% nitrate radicals with 31% reducing power. The presence of hydrogel protects 62% cardiomyoblast cells treated with stress inducing media at LD 50 concentration. The free hydroxyl groups in sugar alcohols of the comacromer influence the free radical scavenging. Comparatively, PEAX-P hydrogel based on xylitol evinces slightly lower scavenging characteristics than with previously reported PEAM-P hydrogel containing mannitol having more hydroxyl groups. The possible free radical scavenging mechanism of the present hydrogel relies on the free π electrons associated with uncrosslinked fumarate bonds, hydrogen atoms associated with sugar alcohols/PEG and radical dilution by free water in the matrix. Briefly, the present PEAX-P hydrogel is a potential injectable system for combined antioxidant and regenerative therapy. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Scavenging Capacities of Some Wines and Wine Phenolic Extracts

    Directory of Open Access Journals (Sweden)

    Ioannis G. Roussis

    2005-01-01

    Full Text Available The aim of this study was to assess the ability of different wines – a sweet red, a dry red, a sweet white, and a dry white – to scavenge the stable 1,1’-diphenyl-2-picryl-hydrazyl radical (DPPH. and to determine their phenolic composition. Both red wines contained, apart from anthocyanins, also higher concentration of total phenolics, tartaric esters, and flavonols than the two white wines. All wines exhibited scavenging activity analogous to their total phenolic content. However, their phenolics differed in antiradical potency, which was visible in their EC50 values. The dry red wine, Xinomavro, had a lower EC50 value, indicating the higher antiradical potency of its phenolics. The scavenging capacities of phenolic extracts from Xinomavro red wine on hydroxyl radicals, superoxide radicals, and singlet oxygen were also assessed. Wine total extract was fractionated by extraction, and each of the three fractions was then subfractionated by column chromatography into two subfractions. Wine total extract, and its fractions and subfractions exhibited scavenging capacity on hydroxyl radicals, superoxide radicals, and singlet oxygen, indicating the activity of many wine phenolics. The most active wine extracts towards hydroxyl radicals were characterized by the high peaks of flavanols, anthocyanins and flavonols in their HPLC-DAD chromatograms. The most active extract towards superoxide radicals was rich in flavanols and anthocyanins. The characteristic phenolics of the most active wine extracts towards singlet oxygen were flavanols, flavonols and phenolic acids. The ability of all red wine phenolic extracts to scavenge singlet oxygen, along with hydroxyl and superoxide radicals, emphasizes its health functionality.

  9. Total peroxynitrite scavenging capacity of phenylethanoid and flavonoid glycosides from the flowers of Buddleja officinalis.

    Science.gov (United States)

    Tai, Bui Huu; Jung, Bong Yong; Cuong, Nguyen Manh; Linh, Pham Thuy; Tung, Nguyen Huu; Nhiem, Nguyen Xuan; Huong, Tran Thu; Anh, Ngo Thi; Kim, Jeong Ah; Kim, Sang Kyum; Kim, Young Ho

    2009-12-01

    Nine compounds, including six phenylethanoid glycosides: acteoside (1); bioside (2); echinacoside (3); poliumoside (4); phenylethyl glycoside (5); salidroside (6) and three flavonoids; linarin (7); apigenin (8); isorhoifolin (9), were isolated from the flowers of Buddleja officinalis MAXIM. (Buddlejaceae). Chemical structures were confirmed by (1)H-, and (13)C-NMR, and MS spectral methods and compared with those reported in the literature. Antioxidant activities of the methanol and water extracts, and all isolated compounds were evaluated using the total oxidant scavenging capacity (TOSC) assay against peroxynitrite. Results of the assay showed that the phenylethanoid glycosides, a major class of compounds of the flowers of B. officinalis, possess strong antioxidant activity. Of these, acteoside, echinacoside and poliumoside have 9.9-, 9.8- and 9.5-fold TOSC value, respectively, compared with the positive control, Trolox.

  10. Social Classes

    DEFF Research Database (Denmark)

    Aktor, Mikael

    2018-01-01

    . Although this social structure was ideal in nature and not equally confirmed in other genres of ancient and medieval literature, it has nevertheless had an immense impact on Indian society. The chapter presents an overview of the system with its three privileged classes, the Brahmins, the Kṣatriyas......The notions of class (varṇa) and caste (jāti) run through the dharmaśāstra literature (i.e. Hindu Law Books) on all levels. They regulate marriage, economic transactions, work, punishment, penance, entitlement to rituals, identity markers like the sacred thread, and social interaction in general...

  11. Free radical scavenging potential, reducing power, phenolic and biochemical constituents of Porphyra species from India

    Digital Repository Service at National Institute of Oceanography (India)

    Pise, N.M.; Jena, K.B.; Maharana, D.; Gaikwad, D.; Jagtap, T.G.

    . Antioxidant potentials of algae were assessed through phenolic content, 2, 2-diphenyl-1- picrylhydrazyl (DPPH) activity, hydrogen peroxide (H sub(2)O sub(2)), scavenging power and reducing potential. A dose-dependent free radical scavenging action against DPPH...

  12. Highly functionalized piperidines: Free radical scavenging, anticancer activity, DNA interaction and correlation with biological activity

    OpenAIRE

    Suvankar Das; Cristiane J. da Silva; Marina de M. Silva; Maria Dayanne de A. Dantas; Ângelo de Fátima; Ana Lúcia T. Góis Ruiz; Cleiton M. da Silva; João Ernesto de Carvalho; Josué C.C. Santos; Isis M. Figueiredo; Edeildo F. da Silva-Júnior; Thiago M. de Aquino; João X. de Araújo-Júnior; Goutam Brahmachari; Luzia Valentina Modolo

    2018-01-01

    Twenty-five piperidines were studied as potential radical scavengers and antitumor agents. Quantitative interaction of compounds with ctDNA using spectroscopic techniques was also evaluated. Our results demonstrate that the evaluated piperidines possesses different abilities to scavenge the radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the anion radical superoxide (·O2−). The piperidine 19 was the most potent radical DPPH scavenger, while the most effective to ·O2− scavenger was piperidine...

  13. Birthing Classes

    Science.gov (United States)

    ... management options. Breastfeeding basics. Caring for baby at home. Birthing classes are not just for new parents, though. ... midwife. Postpartum care. Caring for your baby at home, including baby first aid. Lamaze One of the most popular birthing techniques in the U.S., Lamaze has been around ...

  14. Water structure versus radical scavenger theories as explanations for the suppressive effects of DMSO and related compounds on radiation-induced transformation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Kennedy, A.R.; Symons, M.C.

    1987-05-01

    We report here that dimethylsulfoxide (DMSO): suppresses radiation-induced transformation in vitro, even when DMSO treatments begin as late as 10 days post-irradiation (when cells are in the confluent, stationary phase of growth); inhibits the 12-O-tetradecanoylphorbol-13-acetate (TPA) enhancement of radiation-induced transformation in vitro; does not affect the expression of transformed cells as foci (when surrounded by non-transformed cells); and may be affecting radiation-induced transformation through its solvent properties (i.e. the Water Structure theory), while its effects on the TPA enhancement of radiation transformation may be mediated by its free radical scavenging abilities. DMSO, dimethylformamide (DMF) and dimethylacetamide (DMA) are similar solvents which are all very effective in their ability to suppress radiation-induced transformation in vitro (at concentrations in the cellular media down to 0.01%). As DMSO is known to be an extremely effective OH. free-radical scavenging agent, while DMF and DMA are not as efficient at scavenging free radicals, our results suggest that properties other than free-radical scavenging ability may be important in the suppressive effects of these compounds on radiation-induced transformation in vitro. It is known that low concentrations of such basic aprotic solvents modify water structure so as to suppress the protic (H-bond donor) reactivity of water and enhance its basic (H-bond receptor) reactivity. These reactivity changes may well be responsible for the effects noted above. DMSO, DMF and DMA are also capable of suppressing the TPA enhancement of radiation transformation (at concentrations of the compounds of 0.1% or higher). For this effect, the ability of these compounds to scavenge OH. shows a general correlation with their ability to suppress the TPA enhancement of transformation, suggesting that the Radical Scavenger theory may explain the ability of DMSO to suppress promotion in vitro.

  15. Superoxide scavenging activity of pirfenidone-iron complex

    International Nuclear Information System (INIS)

    Mitani, Yoshihiro; Sato, Keizo; Muramoto, Yosuke; Karakawa, Tomohiro; Kitamado, Masataka; Iwanaga, Tatsuya; Nabeshima, Tetsuji; Maruyama, Kumiko; Nakagawa, Kazuko; Ishida, Kazuhiko; Sasamoto, Kazumi

    2008-01-01

    Pirfenidone (PFD) is focused on a new anti-fibrotic drug, which can minimize lung fibrosis etc. We evaluated the superoxide (O 2 ·- ) scavenging activities of PFD and the PFD-iron complex by electron spin resonance (ESR) spectroscopy, luminol-dependent chemiluminescence assay, and cytochrome c reduction assay. Firstly, we confirmed that the PFD-iron complex was formed by mixing iron chloride with threefold molar PFD, and the complex was stable in distillated water and ethanol. Secondary, the PFD-iron complex reduced the amount of O 2 ·- produced by xanthine oxidase/hypoxanthine without inhibiting the enzyme activity. Thirdly, it also reduced the amount of O 2 ·- released from phorbor ester-stimulated human neutrophils. PFD alone showed few such effects. These results suggest the possibility that the O 2 ·- scavenging effect of the PFD-iron complex contributes to the anti-fibrotic action of PFD used for treating idiopathic pulmonary fibrosis

  16. The significance of cooking for early hominin scavenging.

    Science.gov (United States)

    Smith, Alex R; Carmody, Rachel N; Dutton, Rachel J; Wrangham, Richard W

    2015-07-01

    Meat scavenged by early Homo could have contributed importantly to a higher-quality diet. However, it has been suggested that because carrion would normally have been contaminated by bacteria it would have been dangerous and therefore eaten rarely prior to the advent of cooking. In this study, we quantified bacterial loads on two tissues apparently eaten by hominins, meat and bone marrow. We tested the following three hypotheses: (1) the bacterial loads on exposed surfaces of raw meat increase within 24 h to potentially dangerous levels, (2) simple roasting of meat on hot coals kills most bacteria, and (3) fewer bacteria grow on marrow than on meat, making marrow a relatively safe food. Our results supported all three hypotheses. Our experimental data imply that early hominins would have found it difficult to scavenge safely without focusing on marrow, employing strategies of carrion selection to minimize pathogen load, or cooking. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Scavenging ratios, wet deposition, and in-cloud oxidation: An application to the oxides of sulphur and nitrogen

    International Nuclear Information System (INIS)

    Barrie, L.A.

    1985-01-01

    With special regard to the class of substances in precipitation that potentially originate from both gaseous and particulate precursors, the process of precipitation scavenging is discussed. A model relating daily average ground level scavenging ratios (W) to nucleation scavenging and in-cloud chemical transformation is introduced and is used as guidance in the regression analysis of 3 years of SO 4 = and NO 3 - scavenging-ratio observations made at six locations in eastern Canada. It was found that W of SO 4 = -, NO 3 = -, and SO 4 = -bearing particles is inversely proportional to the one-third power of the precipitation amount in the event. The best regression model explained 41% of the variance in log W for SO 4 = . It included the effects of location, precipitation amount, precipitation type, and in-cloud SO 2 oxidation. The last effect accounted for 50% of the variance explained. The analysis predicts that, on average, in-cloud SO 2 oxidation accounts for 42--79% of the SO 4 = observed in rain and with the exception of one site, less than 20% of the SO 4 = observed in snow. These results are consistent with a mechanism of SO 2 oxidation involving photochemically produced H 2 O 2 . A similar analysis for NO 3 - supports the hypothesis that throughout the year much of the NO 3 - in precipitation originates from in-cloud NO 2 oxidation. It suggests that, depending on location, oxidation of 0.5--1.2 ppbv of NO 2 is sufficient to explain observations. One possible mechanism of oxidation is the reaction with O 3 to form NO 3 and hence soluble N 2 O 5

  18. Radical scavenging compounds from the aerial parts of ...

    African Journals Online (AJOL)

    Results: The ethyl acetate and n-butanol fractions were the most active fractions and contained apigenin, apigenin glucuronide, luteolin, caffeic acid, methyl caffeate, rosmarinic acid and methyl rosmarinate as the radical scavenging compounds with EC50 values of 26.67 ± 0.31, 185.89 ± 1.02, 5.35 ± 0.31, 3.92 ± 0.06, ...

  19. In vitro free radical scavenging activity of platinum nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Aki; Kajita, Masashi; Kim, Juewon; Kanayama, Atsuhiro; Miyamoto, Yusei [Department of Integrated Biosciences, Graduate School of Frontier Sciences, University of Tokyo, Bioscience Building 402, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562 (Japan); Takahashi, Kyoko; Mashino, Tadahiko, E-mail: yusei74@k.u-tokyo.ac.j [Department of Pharmaceutical Sciences, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato, Tokyo 105-8512 (Japan)

    2009-11-11

    A polyacrylic acid (PAA)-protected platinum nanoparticle species (PAA-Pt) was prepared by alcohol reduction of hexachloroplatinate. The PAA-Pt nanoparticles were well dispersed and homogeneous in size with an average diameter of 2.0 {+-} 0.4 nm (n = 200). We used electron spin resonance to quantify the residual peroxyl radical AOO. generated from 2,2-azobis (2-aminopropane) dihydrochloride (AAPH) by thermal decomposition in the presence of O{sub 2} and a spectrophotometric method to quantify the residual 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. PAA-Pt scavenged these two radicals in a dose-dependent manner. Platinum was the functional component. PAA-Pt reduced the rate of oxygen consumption required for linoleic acid peroxidation initiated by AOO. generated from AAPH, indicating inhibition of the propagation of linolate peroxidation. A thiobarbituric acid test also revealed dose-dependent inhibition of the linolate peroxidation by PAA-Pt. Fifty micromolar platinum, as PAA-Pt, completely quenched 250 {mu}M DPPH radical for 5 min. Even when twice diluted in half, the PAA-Pt still quenched 100% of the 250 {mu}M DPPH radical. The scavenging activity of PAA-Pt is durable. These observations suggest that PAA-Pt is an efficient scavenger of free radicals.

  20. Scavenging of radionuclides in the marine environment, (1)

    International Nuclear Information System (INIS)

    Mahara, Yasunori

    1989-01-01

    It is very important to predict diffusion, scavenging and accumulation of the long lives radionuclides which may be discharged from the reprocessing plant in the marine environment, for the purpose of polishing up methods of the radiation does estimation to the high quality stage. This study reports that distribution and behavior of transuranic elements, which are extremely harmful for the human beings and are discharged probably from the reprocessing plant, are investigated in both the survey of bibliography and the in-situ observation. Results of the field observation on the distribution of transuranic elements in the marine show that plutonium and americium are easily scavenged from the sea water and are accumulated on the sea bottom. Transuranic elements, which are originated from fallout and are discharged from the reprocessing plant, have generally the similar distribution in the marine and the same chemical behavior. This facts suggest that the fallout data which are probably and easily collected in the world are available for fabrication of the scavenging model for transuranic elements discharged from the reprocessing plants. (author)

  1. Diet and scavenging habits of the smooth skate Dipturus innominatus.

    Science.gov (United States)

    Forman, J S; Dunn, M R

    2012-04-01

    The diet of smooth skate Dipturus innominatus was determined from examination of stomach contents of 321 specimens of 29·3-152·0 cm pelvic length, sampled from research and commercial trawlers at depths of 231-789 m on Chatham Rise, New Zealand. The diet was dominated by the benthic decapods Metanephrops challengeri and Munida gracilis, the natant decapod Campylonotus rathbunae and fishes from 17 families, of which hoki Macruronus novaezelandiae, sea perch Helicolenus barathri, various Macrouridae and a variety of discarded fishes were the most important. Multivariate analyses indicated the best predictors of diet variability were D. innominatus length and a spatial model. The diet of small D. innominatus was predominantly small crustaceans, with larger crustaceans, fishes and then scavenged discarded fishes increasing in importance as D. innominatus got larger. Scavenged discards were obvious as fish heads or tails only, or skeletal remains after filleting, often from pelagic species. Demersal fish prey were most frequent on the south and west Chatham Rise, in areas where commercial fishing was most active. Dipturus innominatus are highly vulnerable to overfishing, but discarding practices by commercial fishing vessels may provide a positive feedback to populations through improved scavenging opportunities. © 2012 NIWA. Journal of Fish Biology © 2012 The Fisheries Society of the British Isles.

  2. Body Size as a Driver of Scavenging in Theropod Dinosaurs.

    Science.gov (United States)

    Kane, Adam; Healy, Kevin; Ruxton, Graeme D; Jackson, Andrew L

    2016-06-01

    Theropod dinosaurs dominated Earth's terrestrial ecosystem as a diverse group of predators for more than 160 million years, yet little is known about their foraging ecology. Maintaining a balanced energy budget presented a major challenge for therapods, which ranged from the chicken-sized Microraptor up to the whale-sized Giganotosaurus, in the face of intense competition and the demands of ontogenetic growth. Facultative scavenging, a behavior present in almost all modern predators, may have been important in supplementing energetically expensive lifestyles. By using agent-based models based on the allometric relationship between size and foraging behaviors, we show that theropods between 27 and 1,044 kg would have gained a significant energetic advantage over individuals at both the small and large extremes of theropod body mass through their scavenging efficiency. These results were robust to rate of competition, primary productivity, and detection distance. Our models demonstrate the potential importance of facultative scavenging in theropods and the role of body size in defining its prevalence in Mesozoic terrestrial systems.

  3. Shape similarities and differences in the skulls of scavenging raptors.

    Science.gov (United States)

    Guangdi, S I; Dong, Yiyi; Ma, Yujun; Zhang, Zihui

    2015-04-01

    Feeding adaptations are a conspicuous feature of avian evolution. Bill and cranial shape as well as the jaw muscles are closely related to diet choice and feeding behaviors. Diurnal raptors of Falconiformes exhibit a wide range of foraging behaviors and prey preferences, and are assigned to seven dietary groups in this study. Skulls of 156 species are compared from the dorsal, lateral and ventral views, by using geometric morphometric techniques with those landmarks capturing as much information as possible on the overall shape of cranium, bill, orbits, nostrils and attachment area for different jaw muscles. The morphometric data showed that the skull shape of scavengers differ significantly from other raptors, primarily because of different feeding adaptations. As a result of convergent evolution, different scavengers share generalized common morphology, possessing relatively slender and lower skulls, longer bills, smaller and more sideward orbits, and more caudally positioned quadrates. Significant phylogenetic signals suggested that phylogeny also played important role in shape variation within scavengers. New World vultures can be distinguished by their large nostrils, narrow crania and small orbits; Caracaras typically show large palatines, crania and orbits, as well as short, deep and sharp bill.

  4. Separation of nanoparticles: Filtration and scavenging from waste incineration plants.

    Science.gov (United States)

    Förster, Henning; Thajudeen, Thaseem; Funk, Christine; Peukert, Wolfgang

    2016-06-01

    Increased amounts of nanoparticles are applied in products of everyday life and despite material recycling efforts, at the end of their life cycle they are fed into waste incineration plants. This raises the question on the fate of nanoparticles during incineration. In terms of environmental impact the key question is how well airborne nanoparticles are removed by separation processes on their way to the bag house filters and by the existing filtration process based on pulse-jet cleanable fibrous filter media. Therefore, we investigate the scavenging and the filtration of metal nanoparticles under typical conditions in waste incineration plants. The scavenging process is investigated by a population balance model while the nanoparticle filtration experiments are realized in a filter test rig. The results show that depending on the particle sizes, in some cases nearly 80% of the nanoparticles are scavenged by fly ash particles before they reach the bag house filter. For the filtration step dust cakes with a pressure drop of 500Pa or higher are found to be very effective in preventing nanoparticles from penetrating through the filter. Thus, regeneration of the filter must be undertaken with care in order to guarantee highly efficient collection of particles even in the lower nanometre size regime. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Impact of culture medium on maturation of bone marrow-derived murine dendritic cells via the aryl hydrocarbon receptor.

    Science.gov (United States)

    Ilchmann, Anne; Krause, Maren; Heilmann, Monika; Burgdorf, Sven; Vieths, Stefan; Toda, Masako

    2012-05-01

    The aryl hydrocarbon receptor (AhR) plays a role in modulating dendritic cell (DC) immunity. Iscove's modified Dulbecco's medium (IMDM) contains higher amounts of AhR ligands than RPMI1640 medium. Here, we examined the influence of AhR ligand-containing medium on the maturation and T-cell stimulatory capacity of bone marrow-derived murine dendritic cells (BMDCs). BMDCs generated in IMDM (BMDCs/IMDM) expressed higher levels of co-stimulatory and MHC class II molecules, and lower levels of pattern-recognition receptors, especially toll-like receptor (TLR) 2, TLR4, and scavenger receptor class A (SR-A), compared to BMDCs generated in RPMI1640 medium (BMDCs/RPMI). Cytokine responses against ligands of TLRs and antigen uptake mediated by SR-A were remarkably reduced in BMDCs/IMDM, whereas the T-cell stimulatory capacity of the cells was enhanced, compared to BMDCs/RPMI. The enhanced maturation of BMDCs/IMDM was attenuated in the presence of an AhR antagonist, indicating involvement of AhR in the maturation. Interestingly, BMDCs/IMDM induced Th2 and Th17 differentiation at low and high concentrations of antigen respectively, when co-cultured with CD4(+) T-cells from antigen-specific T-cell receptor transgenic mice. In contrast, BMDCs/RPMI induced Th1 differentiation predominantly in the co-culture. Taken together, optimal selection of medium seems necessary when studying BMDCs, depending on the target receptors on the cell surface of DCs and type of helper T-cells for the co-culture. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. The Capsicum annuum class IV chitinase ChitIV interacts with receptor-like cytoplasmic protein kinase PIK1 to accelerate PIK1-triggered cell death and defence responses

    Science.gov (United States)

    Kim, Dae Sung; Kim, Nak Hyun; Hwang, Byung Kook

    2015-01-01

    The pepper receptor-like cytoplasmic protein kinase, CaPIK1, which mediates signalling of plant cell death and defence responses was previously identified. Here, the identification of a class IV chitinase, CaChitIV, from pepper plants (Capsicum annuum), which interacts with CaPIK1 and promotes CaPIK1-triggered cell death and defence responses, is reported. CaChitIV contains a signal peptide, chitin-binding domain, and glycol hydrolase domain. CaChitIV expression was up-regulated by Xanthomonas campestris pv. vesicatoria (Xcv) infection. Notably, avirulent Xcv infection rapidly induced CaChitIV expression in pepper leaves. Bimolecular fluorescence complementation and co-immunoprecipitation revealed that CaPIK1 interacts with CaChitIV in planta, and that the CaPIK1–CaChitIV complex is localized mainly in the cytoplasm and plasma membrane. CaChitIV is also localized in the endoplasmic reticulum. Transient co-expression of CaChitIV with CaPIK1 enhanced CaPIK1-triggered cell death response and reactive oxygen species (ROS) and nitric oxide (NO) bursts. Co-silencing of both CaChitIV and CaPIK1 in pepper plants conferred enhanced susceptibility to Xcv infection, which was accompanied by a reduced induction of cell death response, ROS and NO bursts, and defence response genes. Ectopic expression of CaPIK1 in Arabidopsis enhanced basal resistance to Hyaloperonospora arabidopsidis infection. Together, the results suggest that CaChitIV positively regulates CaPIK1-triggered cell death and defence responses through its interaction with CaPIK1. PMID:25694549

  7. Coding Class

    DEFF Research Database (Denmark)

    Ejsing-Duun, Stine; Hansbøl, Mikala

    Denne rapport rummer evaluering og dokumentation af Coding Class projektet1. Coding Class projektet blev igangsat i skoleåret 2016/2017 af IT-Branchen i samarbejde med en række medlemsvirksomheder, Københavns kommune, Vejle Kommune, Styrelsen for IT- og Læring (STIL) og den frivillige forening...... Coding Pirates2. Rapporten er forfattet af Docent i digitale læringsressourcer og forskningskoordinator for forsknings- og udviklingsmiljøet Digitalisering i Skolen (DiS), Mikala Hansbøl, fra Institut for Skole og Læring ved Professionshøjskolen Metropol; og Lektor i læringsteknologi, interaktionsdesign......, design tænkning og design-pædagogik, Stine Ejsing-Duun fra Forskningslab: It og Læringsdesign (ILD-LAB) ved Institut for kommunikation og psykologi, Aalborg Universitet i København. Vi har fulgt og gennemført evaluering og dokumentation af Coding Class projektet i perioden november 2016 til maj 2017...

  8. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  9. Spatial complexity of carcass location influences vertebrate scavenger efficiency and species composition.

    Science.gov (United States)

    Smith, Joshua B; Laatsch, Lauren J; Beasley, James C

    2017-08-31

    Scavenging plays an important role in shaping communities through inter- and intra-specific interactions. Although vertebrate scavenger efficiency and species composition is likely influenced by the spatial complexity of environments, heterogeneity in carrion distribution has largely been disregarded in scavenging studies. We tested this hypothesis by experimentally placing juvenile bird carcasses on the ground and in nests in trees to simulate scenarios of nestling bird carrion availability. We used cameras to record scavengers removing carcasses and elapsed time to removal. Carrion placed on the ground was scavenged by a greater diversity of vertebrates and at > 2 times the rate of arboreal carcasses, suggesting arboreal carrion may represent an important resource to invertebrate scavengers, particularly in landscapes with efficient vertebrate scavenging communities. Nonetheless, six vertebrate species scavenged arboreal carcasses. Rat snakes (Elaphe obsolete), which exclusively scavenged from trees, and turkey vultures (Cathartes aura) were the primary scavengers of arboreal carrion, suggesting such resources are potentially an important pathway of nutrient acquisition for some volant and scansorial vertebrates. Our results highlight the intricacy of carrion-derived food web linkages, and how consideration of spatial complexity in carcass distribution (i.e., arboreal) may reveal important pathways of nutrient acquisition by invertebrate and vertebrate scavenging guilds.

  10. Integrated Analysis of the Scavenging Process in Marine Two-Stroke Diesel Engines

    DEFF Research Database (Denmark)

    Andersen, Fredrik Herland

    Large commercial ships such as container vessels and bulk carriers are propelledby low-speed, uniow scavenged two-stroke diesel engines. An integralin-cylinder process in this type of engine is the scavenging process, where the burned gases from the combustion process are evacuated through...... receiver fora two-stroke diesel engine. Time resolved boundary conditions corresponding to measurements obtained from an operating engine as well as realistic initial conditions are used in the simulations. The CFD model provides a detailed description of the in-cylinder ow from exhaust valve opening (EVO...... in the scavenge and exhaust receivers increase while the scavenge port exposure time, tscav, decrease. Further the scavenging pressure is varied while the engine speed is kept constant. From the perspective of the scavenging process this will resemble a load sweep following a generator curve. The scavenge port...

  11. Non-symbiotic haemoglobins-What's happening beyond nitric oxide scavenging?

    Science.gov (United States)

    Hill, Robert D

    2012-01-01

    Non-symbiotic haemoglobins have been an active research topic for over 30 years, during which time a considerable portfolio of knowledge has accumulated relative to their chemical and molecular properties, and their presence and mode of induction in plants. While progress has been made towards understanding their physiological role, there remain a number of unanswered questions with respect to their biological function. This review attempts to update recent progress in this area and to introduce a hypothesis as to how non-symbiotic haemoglobins might participate in regulating hormone signal transduction. Advances have been made towards understanding the structural nuances that explain some of the differences in ligand association characteristics of class 1 and class 2 non-symbiotic haemoglobins. Non-symbiotic haemoglobins have been found to function in seed development and germination, flowering, root development and differentiation, abiotic stress responses, pathogen invasion and symbiotic bacterial associations. Microarray analyses under various stress conditions yield uneven results relative to non-symbiotic haemoglobin expression. Increasing evidence of the role of nitric oxide (NO) in hormone responses and the known involvement of non-symbiotic haemoglobins in scavenging NO provide opportunities for fruitful research, particularly at the cellular level. Circumstantial evidence suggests that non-symbiotic haemoglobins may have a critical function in the signal transduction pathways of auxin, ethylene, jasmonic acid, salicylic acid, cytokinin and abscisic acid. There is a strong need for research on haemoglobin gene expression at the cellular level relative to hormone signal transduction.

  12. Non-symbiotic haemoglobins—What's happening beyond nitric oxide scavenging?

    Science.gov (United States)

    Hill, Robert D.

    2012-01-01

    Background and aims Non-symbiotic haemoglobins have been an active research topic for over 30 years, during which time a considerable portfolio of knowledge has accumulated relative to their chemical and molecular properties, and their presence and mode of induction in plants. While progress has been made towards understanding their physiological role, there remain a number of unanswered questions with respect to their biological function. This review attempts to update recent progress in this area and to introduce a hypothesis as to how non-symbiotic haemoglobins might participate in regulating hormone signal transduction. Principal results Advances have been made towards understanding the structural nuances that explain some of the differences in ligand association characteristics of class 1 and class 2 non-symbiotic haemoglobins. Non-symbiotic haemoglobins have been found to function in seed development and germination, flowering, root development and differentiation, abiotic stress responses, pathogen invasion and symbiotic bacterial associations. Microarray analyses under various stress conditions yield uneven results relative to non-symbiotic haemoglobin expression. Increasing evidence of the role of nitric oxide (NO) in hormone responses and the known involvement of non-symbiotic haemoglobins in scavenging NO provide opportunities for fruitful research, particularly at the cellular level. Conclusions Circumstantial evidence suggests that non-symbiotic haemoglobins may have a critical function in the signal transduction pathways of auxin, ethylene, jasmonic acid, salicylic acid, cytokinin and abscisic acid. There is a strong need for research on haemoglobin gene expression at the cellular level relative to hormone signal transduction. PMID:22479675

  13. Habitat of in vivo transformation influences the levels of free radical scavengers in Clinostomum complanatum: implications for free radical scavenger based vaccines against trematode infections.

    Science.gov (United States)

    Zafar, Atif; Rizvi, Asim; Ahmad, Irshad; Ahmad, Masood

    2014-01-01

    Since free radical scavengers of parasite origin like glutathione-S-transferase and superoxide dismutase are being explored as prospective vaccine targets, availability of these molecules within the parasite infecting different hosts as well as different sites of infection is of considerable importance. Using Clinostomum complanatum, as a model helminth parasite, we analysed the effects of habitat of in vivo transformation on free radical scavengers of this trematode parasite. Using three different animal models for in vivo transformation and markedly different sites of infection, progenetic metacercaria of C. complanatum were transformed to adult ovigerous worms. Whole worm homogenates were used to estimate the levels of lipid peroxidation, a marker of oxidative stress and free radical scavengers. Site of in vivo transformation was found to drastically affect the levels of free radical scavengers in this model trematode parasite. It was observed that oxygen availability at the site of infection probably influences levels of free radical scavengers in trematode parasites. This is the first report showing that habitat of in vivo transformation affects levels of free radical scavengers in trematode parasites. Since free radical scavengers are prospective vaccine targets and parasite infection at ectopic sites is common, we propose that infections at different sites, may respond differently to free radical scavenger based vaccines.

  14. SR-B1 Is a Silica Receptor that Mediates Canonical Inflammasome Activation

    Directory of Open Access Journals (Sweden)

    Misato Tsugita

    2017-01-01

    Full Text Available The inhalation of silica dust is associated with fibrosis and lung cancer, which are triggered by macrophage inflammatory responses; however, how macrophages recognize silica remains largely unknown. Here, we identify by functional expression cloning the class B scavenger receptor SR-B1 as a silica receptor. Through an extracellular α-helix, both mouse and human SR-B1 specifically recognized amorphous and crystalline silica, but not titanium dioxide nanoparticles, latex nanoparticles, or monosodium urate crystals, although all particles exhibited negative surface potentials. Genetic deletion of SR-B1 and masking of SR-B1 by monoclonal antibodies showed that SR-B1-mediated recognition of silica is associated with caspase-1-mediated inflammatory responses in mouse macrophages and human peripheral blood monocytes. Furthermore, SR-B1 was involved in silica-induced pulmonary inflammation in mice. These results indicate that SR-B1 is a silica receptor associated with canonical inflammasome activation.

  15. Flexible synthesis of poison-frog alkaloids of the 5,8-disubstituted indolizidine-class. II: Synthesis of (--209B, (--231C, (--233D, (--235B", (--221I, and an epimer of 193E and pharmacological effects at neuronal nicotinic acetylcholine receptors

    Directory of Open Access Journals (Sweden)

    Garraffo H Martin

    2007-09-01

    Full Text Available Abstract Background The 5,8-disubstituted indolizidines constitute the largest class of poison-frog alkaloids. Some alkaloids have been shown to act as noncompetitive blockers at nicotinic acetylcholine receptors but the proposed structures and the biological activities of most of the 5,8-disubstituted indolizidines have not been determined because of limited supplies of the natural products. We have therefore conducted experiments to confirm proposed structures and determine biological activities using synthetic compounds. Recently, we reported that one of this class of alkaloids, (--235B', acts as a noncompetitive antagonist for α4β2 nicotinic receptors, and its sensitivity is comparable to that of the classical competitive antagonist for this receptor, dihydro-β-erythroidine. Results The enantioselective syntheses of (--209B, (--231C, (--233D, (--235B", (--221I, and what proved to be an epimer of natural 193E, starting from common chiral lactams have been achieved. When we performed electrophysiological recordings to examine the effects of the synthetic alkaloids on two major subtypes of nicotinic receptors (α4β2 and α7 expressed in Xenopus laevis oocytes, (--231C effectively blocked α4β2 receptor responses (IC50 value, 1.5 μM with a 7.0-fold higher potency than for blockade of α7 receptor responses. In contrast, synthetic (--221I and (--epi-193E were more potent in blocking α7 receptor responses (IC50 value, 4.4 μM and 9.1 μM, respectively than α4β2 receptor responses (5.3-fold and 2.0-fold, respectively. Conclusion We achieved the total synthesis of (--209B, (--231C, (--233D, (--235B", (--221I, and an epimer of 193E starting from common chiral lactams, and the absolute stereochemistry of natural (--233D was determined. Furthermore, the relative stereochemistry of (--231C and (--221I was also determined. The present asymmetric synthesis of the proposed structure for 193E revealed that the C-8 configuration of natural 193E

  16. Surveillance for transmissible spongiform encephalopathy in scavengers of white-tailed deer carcasses in the chronic wasting disease area of wisconsin

    Science.gov (United States)

    Jennelle, C.S.; Samuel, M.D.; Nolden, C.A.; Keane, D.P.; Barr, D.J.; Johnson, Chad; Vanderloo, J.P.; Aiken, Judd M.; Hamir, A.N.; Hoover, E.A.

    2009-01-01

    Chronic wasting disease (CWD), a class of neurodegenerative transmissible spongiform encephalopathies (TSE) occurring in cervids, is found in a number of states and provinces across North America. Misfolded prions, the infectious agents of CWD, are deposited in the environment via carcass remains and excreta, and pose a threat of cross-species transmission. In this study tissues were tested from 812 representative mammalian scavengers, collected in the CWD-affected area of Wisconsin, for TSE infection using the IDEXX HerdChek enzyme-linked immunosorbent assay (ELISA). Only four of the collected mammals tested positive using the ELISA, but these were negative when tested by Western blot. While our sample sizes permitted high probabilities of detecting TSE assuming 1% population prevalence in several common scavengers (93%, 87%, and 87% for raccoons, opossums, and coyotes, respectively), insufficient sample sizes for other species precluded similar conclusions. One cannot rule out successful cross-species TSE transmission to scavengers, but the results suggest that such transmission is not frequent in the CWD-affected area of Wisconsin. The need for further surveillance of scavenger species, especially those known to be susceptible to TSE (e.g., cat, American mink, raccoon), is highlighted in both a field and laboratory setting.

  17. Scavenging of particulate elemental carbon into stratus cloud

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Naoki; Maeda, Takahisa [National Inst. for Resources and Environment, Tsukuba (Japan)

    1995-12-31

    The role of atmospheric aerosols on the alternation of cloud radiative properties has widely been recognized since 1977 when Tomey and his coworkers have numerically demonstrated the effect of increased cloud condensation nuclei (CCN). At the same time, cloud processes are one of the most important factor in controlling the residence time of atmospheric aerosols through the wet removal process. The redistribution of the size and the composition of pre-cloud aerosols is also the important role of cloud process on the nature of atmospheric aerosols. In order to study these cloud-aerosol interaction phenomena, the incorporation of aerosols into cloud droplets is the first mechanism to be investigated. Among the several mechanisms for the incorporation of aerosols into cloud droplets, nucleation scavenging, is the potentially important process in the view of cloud-aerosol interactions. This critical supersaturation for a given radius of a particle can be theoretically calculated only for pure species, e.g., NaCl. However, a significant portion of the atmospheric aerosols is in the form of internal mixture of multiple components, such as SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, NH{sub 4}{sup +} and particulate elemental carbon. The knowledge acquired by field measurements is therefore essential on this subject. The present study focuses on the scavenging of major components of urban atmospheric aerosols, in particular the incorporation of particulate elemental carbon into stratus cloud. Particulate elemental carbon is the strongest light absorbing species in visible region, and has potential to change the optical property of cloud. On the basis of the measurements conducted at a mountain located in the suburb of Tokyo Metropolitan area, Japan, some insights on the scavenging of particulate elemental carbon into cloud droplet will be presented

  18. Scavenging of particulate elemental carbon into stratus cloud

    Energy Technology Data Exchange (ETDEWEB)

    Kaneyasu, Naoki; Maeda, Takahisa [National Inst. for Resources and Environment, Tsukuba (Japan)

    1996-12-31

    The role of atmospheric aerosols on the alternation of cloud radiative properties has widely been recognized since 1977 when Tomey and his coworkers have numerically demonstrated the effect of increased cloud condensation nuclei (CCN). At the same time, cloud processes are one of the most important factor in controlling the residence time of atmospheric aerosols through the wet removal process. The redistribution of the size and the composition of pre-cloud aerosols is also the important role of cloud process on the nature of atmospheric aerosols. In order to study these cloud-aerosol interaction phenomena, the incorporation of aerosols into cloud droplets is the first mechanism to be investigated. Among the several mechanisms for the incorporation of aerosols into cloud droplets, nucleation scavenging, is the potentially important process in the view of cloud-aerosol interactions. This critical supersaturation for a given radius of a particle can be theoretically calculated only for pure species, e.g., NaCl. However, a significant portion of the atmospheric aerosols is in the form of internal mixture of multiple components, such as SO{sub 4}{sup 2-}, NO{sub 3}{sup -}, NH{sub 4}{sup +} and particulate elemental carbon. The knowledge acquired by field measurements is therefore essential on this subject. The present study focuses on the scavenging of major components of urban atmospheric aerosols, in particular the incorporation of particulate elemental carbon into stratus cloud. Particulate elemental carbon is the strongest light absorbing species in visible region, and has potential to change the optical property of cloud. On the basis of the measurements conducted at a mountain located in the suburb of Tokyo Metropolitan area, Japan, some insights on the scavenging of particulate elemental carbon into cloud droplet will be presented

  19. Trophic facilitation or limitation? Comparative effects of pumas and black bears on the scavenger community.

    Science.gov (United States)

    Allen, Maximilian L; Elbroch, L Mark; Wilmers, Christopher C; Wittmer, Heiko U

    2014-01-01

    Scavenging is a widespread behaviour and an important process influencing food webs and ecological communities. Large carnivores facilitate the movement of energy across trophic levels through the scavenging and decomposition of their killed prey, but competition with large carnivores is also likely to constrain acquisition of carrion by scavengers. We used an experimental approach based on motion-triggered video cameras at black-tailed deer (Odocoileus hemionus columbianus) carcasses to measure the comparative influences of two large carnivores in the facilitation and limitation of carrion acquisition by scavengers. We found that pumas (Puma concolor) and black bears (Ursus americanus) had different effects on their ecological communities. Pumas, as a top-level predator, facilitated the consumption of carrion by scavengers, despite significantly reducing their observed sum feeding times (165.7 min ± 21.2 SE at puma kills 264.3 min ± 30.1 SE at control carcasses). In contrast, black bears, as the dominant scavenger in the system, limited consumption of carrion by scavengers as evidenced by the observed reduction of scavenger species richness recorded at carcasses where they were present (mean = 2.33 ± 0.28 SE), compared to where they were absent (mean = 3.28 ± 0.23 SE). Black bears also had large negative effects on scavenger sum feeding times (88.5 min ± 19.8 SE at carcasses where bears were present, 372.3 min ± 50.0 SE at carcasses where bears were absent). In addition, we found that pumas and black bears both increased the nestedness (a higher level of order among species present) of the scavenger community. Our results suggest that scavengers have species-specific adaptions to exploit carrion despite large carnivores, and that large carnivores influence the structure and composition of scavenger communities. The interactions between large carnivores and scavengers should be considered in future studies of food webs and ecological communities.

  20. Trophic facilitation or limitation? Comparative effects of pumas and black bears on the scavenger community.

    Directory of Open Access Journals (Sweden)

    Maximilian L Allen

    Full Text Available Scavenging is a widespread behaviour and an important process influencing food webs and ecological communities. Large carnivores facilitate the movement of energy across trophic levels through the scavenging and decomposition of their killed prey, but competition with large carnivores is also likely to constrain acquisition of carrion by scavengers. We used an experimental approach based on motion-triggered video cameras at black-tailed deer (Odocoileus hemionus columbianus carcasses to measure the comparative influences of two large carnivores in the facilitation and limitation of carrion acquisition by scavengers. We found that pumas (Puma concolor and black bears (Ursus americanus had different effects on their ecological communities. Pumas, as a top-level predator, facilitated the consumption of carrion by scavengers, despite significantly reducing their observed sum feeding times (165.7 min ± 21.2 SE at puma kills 264.3 min ± 30.1 SE at control carcasses. In contrast, black bears, as the dominant scavenger in the system, limited consumption of carrion by scavengers as evidenced by the observed reduction of scavenger species richness recorded at carcasses where they were present (mean = 2.33 ± 0.28 SE, compared to where they were absent (mean = 3.28 ± 0.23 SE. Black bears also had large negative effects on scavenger sum feeding times (88.5 min ± 19.8 SE at carcasses where bears were present, 372.3 min ± 50.0 SE at carcasses where bears were absent. In addition, we found that pumas and black bears both increased the nestedness (a higher level of order among species present of the scavenger community. Our results suggest that scavengers have species-specific adaptions to exploit carrion despite large carnivores, and that large carnivores influence the structure and composition of scavenger communities. The interactions between large carnivores and scavengers should be considered in future studies of food webs and ecological communities.

  1. Discovery of a new class of potential multifunctional atypical antipsychotic agents targeting dopamine D3 and serotonin 5-HT1A and 5-HT2A receptors: design, synthesis, and effects on behavior

    DEFF Research Database (Denmark)

    Butini, Stefania; Gemma, Sandra; Campiani, Giuseppe

    2009-01-01

    with a low affinity for dopamine D(2) receptors (to minimize extrapyramidal side effects), serotonin 5-HT(2C) receptors (to reduce the risk of obesity under chronic treatment), and for hERG channels (to reduce incidence of torsade des pointes). Pharmacological and biochemical data, including specific c...

  2. Energy scavenging system by acoustic wave and integrated wireless communication

    Science.gov (United States)

    Kim, Albert

    The purpose of the project was developing an energy-scavenging device for other bio implantable devices. Researchers and scientist have studied energy scavenging method because of the limitation of traditional power source, especially for bio-implantable devices. In this research, piezoelectric power generator that activates by acoustic wave, or music was developed. Follow by power generator, a wireless communication also integrated with the device for monitoring the power generation. The Lead Zirconate Titanate (PZT) bimorph cantilever with a proof mass at the free end tip was studied to convert acoustic wave to power. The music or acoustic wave played through a speaker to vibrate piezoelectric power generator. The LC circuit integrated with the piezoelectric material for purpose of wireless monitoring power generation. However, wireless monitoring can be used as wireless power transmission, which means the signal received via wireless communication also can be used for power for other devices. Size of 74 by 7 by 7cm device could generate and transmit 100mVp from 70 mm distance away with electrical resonant frequency at 420.2 kHz..

  3. Phytoconstituents with Radical Scavenging and Cytotoxic Activities from Diospyros shimbaensis

    Directory of Open Access Journals (Sweden)

    Per Aronsson

    2016-01-01

    Full Text Available As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae, a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the new naphthoquinone 8,8′-oxo-biplumbagin (1 was isolated along with the known tetralones trans-isoshinanolone (2 and cis-isoshinanolone (3, and the naphthoquinones plumbagin (4 and 3,3′-biplumbagin (5. Compounds 2, 4, and 5 showed cytotoxicity (IC50 520–82.1 μM against MDA-MB-231 breast cancer cells. Moderate to low cytotoxicity was observed for the hexane, dichloromethane, and methanol extracts of the root bark (IC50 16.1, 29.7 and > 100 μg/mL, respectively, and for the methanol extract of the stem bark (IC50 59.6 μg/mL. The radical scavenging activity of the isolated constituents (1–5 was evaluated on the 2,2-diphenyl-1-picrylhydrazyl (DPPH radical scavenging assay. The applicability of the crude extracts and of the isolated constituents for controlling degenerative diseases is discussed.

  4. Phytoconstituents with Radical Scavenging and Cytotoxic Activities from Diospyros shimbaensis.

    Science.gov (United States)

    Aronsson, Per; Munissi, Joan J E; Gruhonjic, Amra; Fitzpatrick, Paul A; Landberg, Göran; Nyandoro, Stephen S; Erdelyi, Mate

    2016-01-15

    As part of our search for natural products having antioxidant and anticancer properties, the phytochemical investigation of Diospyros shimbaensis (Ebenaceae), a plant belonging to a genus widely used in East African traditional medicine, was carried out. From its stem and root barks the new naphthoquinone 8,8'-oxo-biplumbagin ( 1 ) was isolated along with the known tetralones trans -isoshinanolone ( 2 ) and cis -isoshinanolone ( 3 ), and the naphthoquinones plumbagin ( 4 ) and 3,3'-biplumbagin ( 5 ). Compounds 2 , 4 , and 5 showed cytotoxicity (IC 50 520-82.1 μM) against MDA-MB-231 breast cancer cells. Moderate to low cytotoxicity was observed for the hexane, dichloromethane, and methanol extracts of the root bark (IC 50 16.1, 29.7 and > 100 μg/mL, respectively), and for the methanol extract of the stem bark (IC 50 59.6 μg/mL). The radical scavenging activity of the isolated constituents ( 1 - 5 ) was evaluated on the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. The applicability of the crude extracts and of the isolated constituents for controlling degenerative diseases is discussed.

  5. Development of oxygen scavenger additives for jet fuels

    Energy Technology Data Exchange (ETDEWEB)

    Beaver, B.D.; Demunshi, R.; Sharief, V.; Tian, D.; Teng, Y. [Duquesne Univ., Pittsburgh, PA (United States)

    1995-05-01

    Our current research program is in response to the US Air Force`s FY93 New Initiative entitled {open_quotes}Advanced Fuel Composition and Use.{close_quotes} The critical goal of this initiative is to develop aircraft fuels which can operate at supercritical conditions. This is a vital objective since future aircraft designs will transfer much higher heat loads into the fuel as compared with current heat loads. In this paper it is argued that the thermal stability of most jet fuels would be dramatically improved by the efficient in flight-removal of a fuel`s dissolved oxygen. It is proposed herein to stabilize the bulk fuel by the addition of an additive which will be judiciously designed and programmed to react with oxygen and produce an innocuous product. It is envisioned that a thermally activated reaction will occur, between the oxygen scavenging additive and dissolved oxygen, in a controlled and directed manner. Consequently formation of insoluble thermal degradation products will be limited. It is believed that successful completion of this project will result in the development of a new type of jet fuel additive which will enable current conventional jet fuels to obtain sufficient thermal stability to function in significantly higher temperature regimes. In addition, it is postulated that the successful development of thermally activated oxygen scavengers will also provide the sub-critical thermal stability necessary for future development of endothermic fuels.

  6. The conserved scavenger receptor cysteine-rich superfamily in therapy and diagnosis

    DEFF Research Database (Denmark)

    Martínez, Vanesa Gabriela; Moestrup, Søren Kragh; Holmskov, Uffe

    2011-01-01

    members of the SRCR-SF, but also of the sequence versatility of the SRCR domains. Indeed, involvement of SRCR-SF members in quite different functions, such as pathogen recognition, modulation of the immune response, epithelial homeostasis, stem cell biology, and tumor development, have all been described...... expansion, now up to more than 30 members. The study of these members is attracting growing interest, which parallels that in innate immunity. No unifying function has been described to date for the SRCR domains, this being the result of the limited knowledge still available on the physiology of most...

  7. Pteromalus puparum venom impairs host cellular immune responses by decreasing expression of its scavenger receptor gene

    Science.gov (United States)

    Insect host/parasitoid interactions are co-evolved systems in which host defenses are balanced by parasitoid mechanisms to disable or hide from host immune effectors. Although there is a rich literature on these systems, parasitoid immune-disabling mechanisms have not been fully elucidated. Here we ...

  8. Reciprocal upregulation of scavenger receptors complicates interpretation of nanoparticle uptake in non-phagocytic cells

    NARCIS (Netherlands)

    Prapainop, Kanlaya; Miao, Rong; Åberg, Christoffer; Salvati, Anna; Dawson, Kenneth A

    2017-01-01

    Nanoparticles have great potential as drug delivery vehicles or as imaging agents for treatment and diagnosis of various diseases. It is therefore crucial to understand how nanoparticles are taken up by cells, both phagocytic and non-phagocytic. Small interference RNA has previously been used to

  9. Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3Leiden transgenic mice

    NARCIS (Netherlands)

    Winther, M.P.J. de; Gijbels, M.J.J.; Dijk, K.W. van; Gorp, P.J.J. van; Suzuki, H.; Kodama, T.; Frants, R.R.; Havekes, L.M.; Hofker, M.H.

    1999-01-01

    Apolipoprotein (apo) E3Leiden is a dysfunctional apo E variant associated with familial dysbetalipoproteinemia in humans. Transgenic mice carrying the APOE3Leiden gene develop hyperlipidemia and are highly susceptible to diet-induced atherosclerosis. An early step in atherosclerosis is foam cell

  10. Occurrence and distribution of nitrogen-scavenging bacteria in marine environment

    OpenAIRE

    Sugahara, Isao; Kimura, Toshio; Hayashi, Koichiro

    1987-01-01

    The occurrence and distribution nitrogen-scavenging bacteria in the water of coastal and oceanic of Japan were studied during the Seisui-Maru cruises from 1986 to 1987. Nitroben-scavenging bacteria in the water usually occurred at the level of 10-104 cfu/ml.This value was almost comparable to that of aerobic heterotrophic bacteria. It seems that nitrogen-scavenging bacteria play an important role in the efficient uptake of low levels of nitrogenous compounds in marine enviroment.

  11. Scavenging efficiency and red fox abundance in Mediterranean mountains with and without vultures

    Science.gov (United States)

    Morales-Reyes, Zebensui; Sánchez-Zapata, José A.; Sebastián-González, Esther; Botella, Francisco; Carrete, Martina; Moleón, Marcos

    2017-02-01

    Vertebrate scavenging assemblages include two major functional groups: obligate scavengers (i.e., vultures), which depend totally on carrion and are undergoing severe declines around the globe, and facultative scavengers, which exploit carrion opportunistically and are generally ubiquitous. Our goal was to investigate the hypothesis that vultures can indirectly regulate the abundance of mesopredators (i.e., facultative scavengers) through modulating their access to carrion resources. We studied scavenging efficiency and red fox (Vulpes vulpes) abundance in two neighbouring areas of South-eastern Spain where vultures (mainly griffon vultures Gyps fulvus) are present (Cazorla) and absent (Espuña). To do so, we monitored ungulate carcasses consumption during winter and summer, and counted red fox scats along walking transects as a proxy of fox density. Our results confirmed that scavenging efficiency was higher in Cazorla and in carcasses visited by vultures. This resulted in increasing scavenging opportunities for facultative scavengers where vultures were absent. Accordingly, mean red fox abundance was higher in Espuña. These results suggest the existence of a vulture-mediated mesopredator release (i.e., an increase of mesopredator numbers following vulture loss), which could trigger important indirect ecological effects. Also, our study demonstrates that facultative scavengers are hardly able to functionally replace vultures, mainly because the former exploit carrion on a slower time scale.

  12. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Hyun; Jang, Hae-Dong, E-mail: haedong@hnu.kr

    2015-02-15

    Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

  13. Energy scavenging sensors for ultra-low power sensor networks

    Science.gov (United States)

    O'Brien, Dominic C.; Liu, Jing Jing; Faulkner, Grahame E.; Vachiramon, Pithawat; Collins, Steve; Elston, Steven J.

    2010-08-01

    The 'internet of things' will require very low power wireless communications, preferably using sensors that scavenge power from their environment. Free space optics allows communications over long ranges, with simple transceivers at each end, offering the possibility of low energy consumption. In addition there can be sufficient energy in the communications beam to power simple terminals. In this paper we report experimental results from an architecture that achieves this. A base station that tracks sensors in its coverage area and communicates with them using low divergence optical beams is presented. Sensor nodes use modulated retro-reflectors to communicate with the base station, and the nodes are powered by the illuminating beam. The paper presents design and implementation details, as well as future directions for this work.

  14. The energy stabilization for the SLC scavenger beam

    International Nuclear Information System (INIS)

    Hsu, I.; Browne, M.; Himel, T.; Humphrey, R.; Jobe, K.; Ross, M.; Pellegrin, J.L.; Seeman, J.

    1991-01-01

    The energy of the SLC scavenger beam which is used to produce positrons must be carefully maintained so that the beam can be transported through the collimators in the dispersive region of the extraction line which leads from the Linac to the positron target. A feedforward control loop has been developed to compensate the energy fluctuations due to the beam intensity fluctuations. The loop detects the beam intensities in the damping rings and then calculates how much energy needs to be compensated due to beam loading effects. The energy is corrected by adjusting the acceleration phases of two sets of klystrons right before the extraction. Because there is feedback loop using the same controls, their interaction needs to be carefully treated. This paper presents an overview of the feedforward algorithms

  15. The energy stabilization for the SLC scavenger beam

    International Nuclear Information System (INIS)

    Hsu, Ian; Browne, M.; Himel, T.; Humphrey, R.; Jobe, K.; Ross, M.; Pellegrin, J.L.; Seeman, J.

    1990-08-01

    The energy of the SLC scavenger beam which is used to produce positrons must be carefully maintained so that the beam can be transported through the collimators in the dispersive region of the extraction line which leads from the Linac to the positron target. A feedforward control loop has been developed to compensate the energy fluctuations due to the beam intensity fluctuations. The loop detects the beam intensities in the damping rings and then calculates how much energy needs to be compensated due to beam loading effects. The energy is corrected by adjusting the acceleration phases of two sets of klystrons right before the extraction. Because there is feedback loop using the same controls, their interaction needs to be carefully treated. This paper presents an overview of the feedforward algorithms. 3 figs

  16. Molecular Mechanisms behind Free Radical Scavengers Function against Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Fereshteh Ahmadinejad

    2017-07-01

    Full Text Available Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer’s disease, Parkinson’s disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson’s disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively, collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase and nitric oxide synthase (NOS. Natural antioxidant systems are categorized into enzymatic and non-enzymatic antioxidant groups. The former includes a number of enzymes such as catalase and glutathione peroxidase, while the latter contains a number of antioxidants acquired from dietary sources including vitamin C, carotenoids, flavonoids and polyphenols. There are also scavengers used for therapeutic purposes, such as 3,4-dihydroxyphenylalanine (L-DOPA used routinely in the treatment of Parkinson’s disease (not as a free radical scavenger, and 3-methyl-1-phenyl-2-pyrazolin-5-one (Edaravone that acts as a free radical detoxifier frequently used in acute ischemic stroke. The cell surviving properties of L-DOPA and Edaravone against oxidative stress conditions rely on the alteration of a number of stress proteins such as Annexin A1, Peroxiredoxin-6 and PARK7/DJ-1 (Parkinson disease protein 7, also known as Protein deglycase DJ-1. Although they share the targets in reversing the cytotoxic effects of H2O2, they seem to have distinct mechanism of function. Exposure to L-DOPA may result in hypoxia condition and further induction of ORP150 (150-kDa oxygen-regulated protein with its concomitant cytoprotective effects but Edaravone seems to protect cells via direct induction of Peroxiredoxin-2 and inhibition of apoptosis.

  17. Study of atmospheric pollution scavenging. Seventeenth progress report

    Energy Technology Data Exchange (ETDEWEB)

    Semonin, R.G.; Bartlett, J.; Gatz, D.F.; Peden, M.E.; Skowron, L.M.; Stensland, G.J.

    1979-07-01

    The continued study of historical precipitation chemistry, air quality, and emissions data shows that the nitrate concentrations in precipitation have increased over the past 20 years with little change in sulfate concentrations. An analysis of aerosol concentrations at MAP3S precipitation collection sites shows consistently higher elemental concentrations at urban Champaign, Illinois, than sites at Whiteface Mountain, New York, and rural Champaign. Scavenging ratios at Whiteface exceeded those obtained previously at St. Louis, Missouri, possibly due to mid-tropospheric long-range transport and differing synoptic situations. Factor analysis of 6 storms during METROMEX shows that different deposition patterns were found for the soluble and insoluble concentrations of the same element. This suggests different scavenging processes may be active for these fractions. Using METROMEX data, no correlation was found between pollutant source strength and the urban-related precipitation anomaly. Four different Nuclepore air filter setups were used to compare air concentrations of sulfate, nitrate, and ammonium. The sulfate comparison was good, but the large variability for nitrate and ammonium raise serious questions on the credibility of measurements using Nuclepore as the collection medium. The details of a case study of wet deposition from SCORE-78 are presented and shows the pollutant concentrations are more variable than the rainfall. A brief description of the progress on the SCORE-79 project is presented. The progress on acid rainfall studies shows that the high pH values in the Midwest in the mid-1950's were due in part to elevated concentrations of calcium and magnesium. A variety of model calculations are presented to show the effects of adjusting past data to currently observed values. Recent results of continuing research on ionic stability of precipitation samples are given.

  18. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage.

    Science.gov (United States)

    Aswani, Andrew; Manson, Joanna; Itagaki, Kiyoshi; Chiazza, Fausto; Collino, Massimo; Wupeng, Winston Liao; Chan, Tze Khee; Wong, W S Fred; Hauser, Carl J; Thiemermann, Chris; Brohi, Karim

    2018-01-01

    Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS). Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs). Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA), could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr), at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. We have shown that the release of mt

  19. Scavenging Circulating Mitochondrial DNA as a Potential Therapeutic Option for Multiple Organ Dysfunction in Trauma Hemorrhage

    Directory of Open Access Journals (Sweden)

    Andrew Aswani

    2018-05-01

    Full Text Available Trauma is a leading cause of death worldwide with 5.8 million deaths occurring yearly. Almost 40% of trauma deaths are due to bleeding and occur in the first few hours after injury. Of the remaining severely injured patients up to 25% develop a dysregulated immune response leading to multiple organ dysfunction syndrome (MODS. Despite improvements in trauma care, the morbidity and mortality of this condition remains very high. Massive traumatic injury can overwhelm endogenous homeostatic mechanisms even with prompt treatment. The underlying mechanisms driving MODS are also not fully elucidated. As a result, successful therapies for trauma-related MODS are lacking. Trauma causes tissue damage that releases a large number of endogenous damage-associated molecular patterns (DAMPs. Mitochondrial DAMPs released in trauma, such as mitochondrial DNA (mtDNA, could help to explain part of the immune response in trauma given the structural similarities between mitochondria and bacteria. MtDNA, like bacterial DNA, contains an abundance of highly stimulatory unmethylated CpG DNA motifs that signal through toll-like receptor-9 to produce inflammation. MtDNA has been shown to be highly damaging when injected into healthy animals causing acute organ injury to develop. Elevated circulating levels of mtDNA have been reported in trauma patients but an association with clinically meaningful outcomes has not been established in a large cohort. We aimed to determine whether mtDNA released after clinical trauma hemorrhage is sufficient for the development of MODS. Secondly, we aimed to determine the extent of mtDNA release with varying degrees of tissue injury and hemorrhagic shock in a clinically relevant rodent model. Our final aim was to determine whether neutralizing mtDNA with the nucleic acid scavenging polymer, hexadimethrine bromide (HDMBr, at a clinically relevant time point in vivo would reduce the severity of organ injury in this model. Conclusions: We have

  20. Influence of various scavengers of •OH radicals on the radiation sensitivity of yeast and bacteria.

    Science.gov (United States)

    Múčka, Viliam; Bláha, Pavel; Čuba, Václav; Červenák, Jaroslav

    2013-12-01

    To quantitatively investigate the influence of various •OH (hydroxyl radical) scavengers on the radiation sensitivity of yeast and bacteria, particularly to define the relationship between the protective effect of a scavenger and its •OH scavenging efficiency. In order to study the protective effect of •OH scavengers we used various concentrations of four scavengers (methanol, potassium formate, ethanol and ascorbic acid) in isotonic salt solutions. These solutions containing live yeast (Saccharomyces cerevisiae) or bacteria (Escherichia coli) were irradiated with (60)Co isotope γ -radiation using two different doses and dose rates. The number of surviving cells was determined prior to and after irradiation both in suspension with and without scavengers. The surviving fractions after irradiation with and without the scavenger were evaluated. The main results of the paper were: The surviving fraction increased approximately linearly within the measured interval with increasing concentration of the scavenger. The same dependences were found for the protecting effect depending on the scavenging efficiency. The slopes of these dependences (k) were found to be characteristic for each scavenger. The k value determined the degree in which the scavenging of •OH radicals participated in the protection of living cells. The protective effects of scavengers at the same scavenging efficiency were different and unique for each scavenger. No simple relation was found between the efficiency of scavenger k and the rate constant kOH of the reactions between scavengers and •OH radicals. Our results suggest that the studied scavengers effectively protected yeast and bacteria against ionizing radiation. Although the scavenging of •OH radicals seems to be important for protection of living cells, it is clearly not the only process on which the protection is based.

  1. A Virtual Class Calculus

    DEFF Research Database (Denmark)

    Ernst, Erik; Ostermann, Klaus; Cook, William Randall

    2006-01-01

    Virtual classes are class-valued attributes of objects. Like virtual methods, virtual classes are defined in an object's class and may be redefined within subclasses. They resemble inner classes, which are also defined within a class, but virtual classes are accessed through object instances...... model for virtual classes has been a long-standing open question. This paper presents a virtual class calculus, vc, that captures the essence of virtual classes in these full-fledged programming languages. The key contributions of the paper are a formalization of the dynamic and static semantics of vc...

  2. Somatostatin receptors

    DEFF Research Database (Denmark)

    Møller, Lars Neisig; Stidsen, Carsten Enggaard; Hartmann, Bolette

    2003-01-01

    functional units, receptors co-operate. The total receptor apparatus of individual cell types is composed of different-ligand receptors (e.g. SRIF and non-SRIF receptors) and co-expressed receptor subtypes (e.g. sst(2) and sst(5) receptors) in characteristic proportions. In other words, levels of individual......-peptides, receptor agonists and antagonists. Relatively long half lives, as compared to those of the endogenous ligands, have been paramount from the outset. Motivated by theoretical puzzles or the shortcomings of present-day diagnostics and therapy, investigators have also aimed to produce subtype...

  3. Development and validation of a simple high performance thin layer chromatography method combined with direct 1,1-diphenyl-2-picrylhydrazyl assay to quantify free radical scavenging activity in wine.

    Science.gov (United States)

    Agatonovic-Kustrin, Snezana; Morton, David W; Yusof, Ahmad P

    2016-04-15

    The aim of this study was to: (a) develop a simple, high performance thin layer chromatographic (HPTLC) method combined with direct 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay to rapidly assess and compare free radical scavenging activity or anti-oxidant activity for major classes of polyphenolics present in wines; and (b) to investigate relationship between free radical scavenging activity to the total polyphenolic content (TPC) and total antioxidant capacity (TAC) in the wine samples. The most potent free radical scavengers that we tested for in the wine samples were found to be resveratrol (polyphenolic non-flavonoid) and rutin (flavonoid), while polyphenolic acids (caffeic acid and gallic acid) although present in all wine samples were found to be less potent free radical scavengers. Therefore, the total antioxidant capacity was mostly affected by the presence of resveratrol and rutin, while total polyphenolic content was mostly influenced by the presence of the less potent free radical scavengers gallic and caffeic acids. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. How Predictability of Feeding Patches Affects Home Range and Foraging Habitat Selection in Avian Social Scavengers?

    NARCIS (Netherlands)

    Monsarrat, S.; Benhamou, S.; Sarrazin, F.; Bessa-Gomes, C.; Bouten, W.; Duriez, O.

    2013-01-01

    Feeding stations are commonly used to sustain conservation programs of scavengers but their impact on behaviour is still debated. They increase the temporal and spatial predictability of food resources while scavengers have supposedly evolved to search for unpredictable resources. In the Grands

  5. The French Paradox: Determining the Superoxide-Scavenging Capacity of Red Wine and Other Beverages

    Science.gov (United States)

    Logan, Barry A.; Hammond, Matthew P.; Stormo, Benjamin M.

    2008-01-01

    Plant-derived phenolic compounds such as those found in red wine, tea, and certain fruit juices may protect against cardiovascular disease by detoxifying (scavenging) superoxide and other unstable reactive oxygen species. We present a laboratory exercise that can be used to assess the superoxide-scavenging capacity of beverages. Among the…

  6. Identification, characterisation and composition of scavengeable feed resources for rural poultry production in Central Tanzania

    NARCIS (Netherlands)

    Goromela, E.H.; Kwakkel, R.P.; Verstegen, M.W.A.; Katule, A.M.

    2007-01-01

    A participatory study was carried out in four villages of central Tanzania to appraise existing and potential scavengeable feed resources available for rural poultry. In addition, proximate analysis of selected scavengeable feed resources including chicken crop and gizzards contents was carried out

  7. Predatory blue crabs induce stronger nonconsumptive effects in eastern oysters Crassostrea virginica than scavenging blue crabs

    Directory of Open Access Journals (Sweden)

    Avery E. Scherer

    2017-02-01

    Full Text Available By influencing critical prey traits such as foraging or habitat selection, predators can affect entire ecosystems, but the nature of cues that trigger prey reactions to predators are not well understood. Predators may scavenge to supplement their energetic needs and scavenging frequency may vary among individuals within a species due to preferences and prey availability. Yet prey reactions to consumers that are primarily scavengers versus those that are active foragers have not been investigated, even though variation in prey reactions to scavengers or predators might influence cascading nonconsumptive effects in food webs. Oysters Crassostrea virginica react to crab predators by growing stronger shells. We exposed oysters to exudates from crabs fed live oysters or fed aged oyster tissue to simulate scavenging, and to controls without crab cues. Oysters grew stronger shells when exposed to either crab exudate, but their shells were significantly stronger when crabs were fed live oysters. The stronger response to predators than scavengers could be due to inherent differences in diet cues representative of reduced risk in the presence of scavengers or to degradation of conspecific alarm cues in aged treatments, which may mask risk from potential predators subsisting by scavenging.

  8. New actualistic data on the ecology and energetics of hominin scavenging opportunities.

    Science.gov (United States)

    Pobiner, Briana L

    2015-03-01

    For decades, the 'hunting-scavenging debate' has been an important research focus in Plio-Pleistocene hominin behavioral ecology. Here I present new data on potential scavenging opportunities from fresh carnivore kills on a conservancy in central Kenya. This ecosystem is dominated by felids (mainly lions) and has a different carnivore guild than in many earlier studies of scavenging opportunities that took place in areas such as Ngorongoro and Serengeti in Tanzania and Maasai Mara in Kenya, where lions face high levels of inter-specific competition from bone-crunching hyenas. I found that while scavenging opportunities vary among carcasses, most carcasses retained some scavengeable resources. Excluding within-bone resources, even the scavengeable meat on 'defleshed' larger sized prey carcasses is usually substantial enough to meet the total daily caloric requirements of at least one adult male Homo erectus individual. I argue, as others have before me, that scavenging opportunities in a particular ecosystem will vary in part due to carnivore taxon, density and guild composition; prey size, biomass and community structure; and habitat (e.g., vegetation, physiography). We should expect variability in scavenging opportunities in different locales and should focus our research efforts on identifying which variables condition these differences in order to make our findings applicable to the diversity of ecological settings characterizing the past. Published by Elsevier Ltd.

  9. Optimum injection dose rate of hydrogen sulfide scavenger for treatment of petroleum crude oil

    Directory of Open Access Journals (Sweden)

    T.M. Elshiekh

    2016-03-01

    Full Text Available Hydrogen sulfide H2S scavengers are chemicals that favorably react with hydrogen sulfide gas to eliminate it and produce environmental friendly products. These products depend on the type and composition of the scavenger and the conditions at which the reaction takes place. The scavenger should be widely available and economical for industry acceptance by having a low unit cost. The optimum values of H2S scavenger injection dose rate of scavenging hydrogen sulfide from the multiphase fluid produced at different wells conditions in one of the Petroleum Companies in Egypt were studied. The optimum values of H2S scavenger injection dose rate depend on pipe diameter, pipe length, gas molar mass velocity, inlet H2S concentration and pressure. The optimization results are obtained for different values of these parameters using the software program Lingo. In general, the optimum values of H2S scavenger injection dose rate of the scavenging of hydrogen sulfide are increased by increasing of the pipe diameter and increasing the inlet H2S concentration, and decreased by increasing the pipe length, gas molar mass velocity and pressure.

  10. Identification of Radical Scavenging Compounds in Rhaponticum carthamoides by Means of LC-DAD-SPE-NMR

    NARCIS (Netherlands)

    Miliauskas, G.; Beek, van T.A.; Waard, de P.; Venskutonis, R.P.; Sudhölter, E.J.R.

    2005-01-01

    A hyphenated LC-DAD-SPE-NMR setup in combination with on-line radical scavenging detection has been applied for the identification of radical scavenging compounds in extracts of Rhaponticum carthamoides. After NMR measurements, the pure compounds were infused into a mass spectrometer. The technique

  11. Isolation and Structure Elucidation of Radical Scavengers from Thymus vulgaris Leaves

    NARCIS (Netherlands)

    Dapkevicius, A.; Beek, van T.A.; Lelyveld, G.P.; Veldhuizen, van A.; Groot, de Æ.; Linssen, J.P.H.; Venskutonis, R.

    2002-01-01

    2,2-Diphenyl-1-picrylhydrazyl radical (DPPH*) scavenging activity-guided fractionation of a leaf extract of Thymus vulgaris led to the isolation of the radical scavengers rosmarinic acid 1, eriodictyol, taxifolin, luteolin 7-glucuronide, p-cymene 2,3-diol, p-cymene 2,3-diol 6-6'-dimer, carvacrol,

  12. Apoptotic and free radical scavenging properties of the methanolic extract of Gentianella alborosea.

    Science.gov (United States)

    Acero, Nuria; Llinares, Francisco; Galán de Mera, Antonio; Oltra, Beatriz; Muñoz-Mingarro, Dolores

    2006-09-01

    Gentianella alborosea ("Hercampure") is a Peruvian species used in folk medicine for the treatment of a variety of health disorders. We tested the free radical scavenging (DPPH) and induction of apoptosis on a human uterus tumor cell line (HeLa) by its methanolic extract. The results showed a noticeable radical scavenging activity and a dose-dependent apoptotic effect.

  13. A method for nitric oxide radical scavenging properties of sulfur containing compounds.

    NARCIS (Netherlands)

    Vriesman, M.F.; Haenen, G.R.M.M.; Westerveld, G.J.; Paquay, J.B.G.; Voss, H.P.; Bast, A.

    1997-01-01

    A new method for the quantification of the nitric oxide (NO) scavenging activity of compounds in aqueous solutions is described using an amperometric NO sensor. After correction for the spontaneous degradation of NO, second-order rate kinetics of the scavenging reaction are observed.

  14. pH-dependent radical scavenging capacity of green tea catechins

    NARCIS (Netherlands)

    Muzolf, M.; Szymusiak, H.; Gliszczynska-Swiglo, A.; Rietjens, I.M.C.M.; Tyrakowska, B.

    2008-01-01

    The effect of pH on the radical scavenging capacity of green tea catechins was investigated using experimental as well as theoretical methods. It was shown that the radical scavenging capacity of the catechins, quantified by the TEAC value, increases with increasing pH of the medium. Comparison of

  15. Comparative investigation of the free radical scavenging potential and anticancer property of Diospyros blancoi (Ebenaceae

    Directory of Open Access Journals (Sweden)

    Muhammad Ali Khan

    2016-05-01

    Conclusions: Our results indicate that Diospyros blancoi stem bark had the significant highest antioxidant and free radical scavenging properties as well as moderate anticancer activity. Hence, we assume that the anticancer activity of this plant can be, at least in part, attributed to its content in phenolic compounds as well as its significant free radical scavenging properties.

  16. Radical Scavenging Capacity of Wine Anthocyanins Is Strongly pH-Dependent

    NARCIS (Netherlands)

    Borowski, T.; Tyrakowska, B.; Oszmianski, J.; Rietjens, I.M.C.M.

    2005-01-01

    The radical scavenging capacity of red wine anthocyanins was quantified by the so-called TEAC assay with special emphasis on the influence of pH and conjugation on this activity. The pH appears to be a dominant factor in the radical scavenging capacity of wine anthocyanins, with higher pH values

  17. Interaction of epidermal growth factor receptors with the cytoskeleton is related to receptor clustering

    NARCIS (Netherlands)

    van Belzen, N.; Spaargaren, M.; Verkleij, A. J.; Boonstra, J.

    1990-01-01

    Recently it has been established that cytoskeleton-associated epidermal growth factor (EGF) receptors are predominantly of the high-affinity class and that EGF induces a recruitment of low-affinity receptors to the cytoskeleton. The nature of this EGF-induced receptor-cytoskeleton interaction,

  18. Fatal embryo chondral damage associated with fluoroquinolones in eggs of threatened avian scavengers

    International Nuclear Information System (INIS)

    Lemus, J.A.; Blanco, G.; Arroyo, B.; Martinez, F.; Grande, J.

    2009-01-01

    Stabled livestock reared in housed conditions are often subjected to intensive treatments with veterinary drug, which residues may be present in livestock meat ingested by scavengers, but nothing is known about their presence in eggs of wild birds and their potential detrimental effects on breeding success. We searched for residues of veterinary drugs and other toxicants in infertile and embryonated unhatched eggs of griffon vultures (Gyps fulvus) and red kites (Milvus milvus), two threatened avian scavengers. Quinolones (ciprofloxacin and enrofloxacin) were found in most unhatched eggs of both scavenger species clearly associated with severe alterations in the development of embryo cartilage and bones that could preclude embryo movements and subsequently normal development, pre-hatch position and successful hatching. The detrimental effects on developing eggs of veterinary drugs from livestock operations may help to explain reduced breeding success of avian scavengers. - Fluoroquinolones used in livestock farming and found in eggs of avian scavenger caused severe alterations in embryo cartilage and bone development.

  19. Fatal embryo chondral damage associated with fluoroquinolones in eggs of threatened avian scavengers

    Energy Technology Data Exchange (ETDEWEB)

    Lemus, J.A. [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain); Blanco, G., E-mail: gublanco2@yahoo.e [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain); Arroyo, B.; Martinez, F.; Grande, J. [Departamento de Ecologia Evolutiva, Museo Nacional de Ciencias Naturales (CSIC), J. Gutierrez Abascal 2, 28006 Madrid (Spain)

    2009-08-15

    Stabled livestock reared in housed conditions are often subjected to intensive treatments with veterinary drug, which residues may be present in livestock meat ingested by scavengers, but nothing is known about their presence in eggs of wild birds and their potential detrimental effects on breeding success. We searched for residues of veterinary drugs and other toxicants in infertile and embryonated unhatched eggs of griffon vultures (Gyps fulvus) and red kites (Milvus milvus), two threatened avian scavengers. Quinolones (ciprofloxacin and enrofloxacin) were found in most unhatched eggs of both scavenger species clearly associated with severe alterations in the development of embryo cartilage and bones that could preclude embryo movements and subsequently normal development, pre-hatch position and successful hatching. The detrimental effects on developing eggs of veterinary drugs from livestock operations may help to explain reduced breeding success of avian scavengers. - Fluoroquinolones used in livestock farming and found in eggs of avian scavenger caused severe alterations in embryo cartilage and bone development.

  20. Characterization of fatty acids, bioactive lipids, and radical scavenging activity of Canterbury bells seed oil

    Directory of Open Access Journals (Sweden)

    Hassanien, M. F.R.

    2014-06-01

    Full Text Available The aim of this study was to characterize the chemical composition and radical scavenging activity of Canterbury bells (Campanula medium seed oil. C. medium seeds contained 9.2% extractable oil. The lipid classes, fatty acids, phytosterol and tocopherol composition of C. medium seed oil were determined. The amount of neutral lipids in the oil was the highest, followed by glycolipids and phospholipids. Linoleic and oleic were the main fatty acids. C. medium oil is characterized by high levels of phytosterols and β-sitosterol was the main compound. β-Tocopherol constituted 42.5% of the total tocopherol content followed by γ-tocopherol. The radical scavenging activity (RSA toward 1,1-diphenyl-2-picrylhydrazyl (DPPH radicals and galvinoxyl radicals of C. medium oil were higher than those of extra virgin olive oil. The diverse potential uses of C. medium oil may make this plant industrially important.El objetivo de este estudio fue caracterizar la composición química y la actividad de captación de radicales de aceites de semillas de campanillas de Canterbury (Campanula medium. Las semillas de C. medium contenían 9,2 % de aceite extraíble. Se determinó la composición de las diferentes clases de lípidos, ácidos grasos, fitoesteroles y tocoferoles. La cantidad de lípidos neutros en el aceite fue mayoritario, seguido de glicolípidos y fosfolípidos. Linoleico y oleico fueron los ácidos grasos principales. El aceite de C. medium se caracteriza por altos niveles de fitoesteroles y β-sitosterol fue el compuesto principal. β-tocoferol constituía 42,5 % del contenido total de tocoferol seguido de γ-tocoferol. La actividad de captación de radicales (RSA a 1,1-difenil-2- picrilhidrazil (DPPH y radicales galvinoxil de C. medium fueron superiores a las de aceite de oliva virgen extra. Los diversos usos potenciales de los aceites de C. medium pueden hacer que esta planta pueda ser importante industrialmente.

  1. Molecular Basis of Natural Killer Cell Tumor Target Recognition: The NKr/MHC Class I Complex

    National Research Council Canada - National Science Library

    Hasemann, Charles

    1999-01-01

    .... We have pursued this via the heterologous expression of wild type and mutant NK receptors for the purpose of the determination of the atomic structure of an NK receptor/ class I MHC complex via X-ray crystallography...

  2. Participation of L3T4 in T cell activation in the absence of class II major histocompatibility complex antigens. Inhibition by anti-L3T4 antibodies is a function both of epitope density and mode of presentation of anti-receptor antibody

    DEFF Research Database (Denmark)

    Owens, T; Fazekas de St Groth, B

    1987-01-01

    two monoclonal antibodies, KJ16-133.18 and F23.1, that recognize a determinant encoded by the T cell receptor V beta 8 gene family. These antibodies were used to select two clones of T cells with surface phenotype Thy-1.2+, L3T4+, Lyt-2-, KJ16-133.18+, F23.1+, IA-, IE-. One of these clones (E9.D4......The recognition of many class II major histocompatibility complex (MHC)-associated antigens by T cells requires the participation of the L3T4 molecule. It has been proposed that this molecule acts to stabilize low affinity binding to antigen in association with MHC and thereby increases the avidity...... of T cell/antigen interactions. By using antibodies against the T cell antigen receptor (TCR) to activate T cells, thereby circumventing the requirement for antigen presenting cells and MHC-associated antigen, we have been able to study the function of L3T4 in the absence of class II MHC. We have used...

  3. Study of air pollution scavenging. Fourteenth progress report

    Energy Technology Data Exchange (ETDEWEB)

    Semonin, R.G.

    1976-04-01

    The field experiments were continued to estimate convective storm particulate scavenging efficiency in proximity to the St. Louis, Missouri urban-industrial complex. Complementary studies of the urban aerosol characterization, source strength, and removal processes were also studied. The 1975 field effort shifted emphasis from the immediate St. Louis area to the Alton-Wood River industrial complex. Along with the change in size and configuration of the network, there were increases in the numbers of most types of samplers. The new network yielded the following types of samples for analysis and interpretation: 1065 total rain samples from 85 sites; 68 sequential rainwater samples from 2 locations; 272 wet/dry samples from 7 locations; 216 air filter samples from 7 locations; 36 air filter samples from aircraft; and raindrop spectrometer data from 11 sites for the period 17 June-18 August. The analysis procedures require that all water samples undergo filtering for separate analyses of soluble and insoluble fractions of the elemental concentrations. This data collection effort provided a record number of samples for chemical analysis. Approximately 4000 pibals and over 370 radiosondes were released in the operational period, providing wind and thermodynamic data on 33 days. Aircraft missions were flown on 24 days, with one air tracer release of cesium on 19 July 1975. The status of the analysis of all types of data is described.

  4. Microbial fuel cell as a free-radical scavenging tool

    International Nuclear Information System (INIS)

    Koleva, Ralitza; Yemendzhiev, Hyusein; Nenov, Valentin

    2017-01-01

    Microbial fuel cells (MFCs) are known for their capability to directly convert organic substrates into electricity by the biochemical activity of specific microorganisms. Availability of a proper terminal electron acceptor is crucial for this process. Free radicals, with their one or more unpaired electrons, are extremely reducible and could be considered as electron acceptors in terms of cathodic processes in MFC. During this reduction, free radicals could be transformed in the same manner as they are transformed by antioxidants. The present study investigated this opportunity by utilization of 2,2-diphenyl-1-picrylhydrazyl (150 mmol/dm"3 methanol solution) as a free-radical molecule. During the studied process, over 90% radical neutralization was observed in less than 16 hours. The results obtained demonstrate for the first time the potential of MFC type bioelectrochemical systems to serve as a free-radical scavenging tool and to provide antioxidant and anti-radical activity. In this way, this study opens a completely new field of research and application of bio-electrochemical systems

  5. Rainwater capacities for BTEX scavenging from ambient air

    Science.gov (United States)

    Šoštarić, A.; Stanišić Stojić, S.; Vuković, G.; Mijić, Z.; Stojić, A.; Gržetić, I.

    2017-11-01

    The contribution of atmospheric precipitation to volatile organic compound (VOC) removal from the atmosphere remains a matter of scientific debate. The aim of this study was to examine the potential of rainwater for benzene, toluene, ethylbenzene and xylene (BTEX) scavenging from ambient air. To that end, air and rainwater samples were collected simultaneously during several rain events that occurred over two distinct time periods in the summer and autumn of 2015. BTEX concentrations in the gaseous and aqueous phases were determined using proton transfer reaction mass spectrometry. The results reveal that the registered amounts of BTEX in rainwater samples were higher than those predicted by Henry's law. Additional analysis, including physico-chemical characterization and source apportionment, was performed and a possible mechanism underlying the BTEX adsorption to the aqueous phase was considered and discussed herein. Finally, regression multivariate methods (MVA) were successfully applied (with relative errors from 20%) to examine the functional dependency of BTEX enrichment factor on gaseous concentrations, physico-chemical properties of rainwater and meteorological parameters.

  6. Microfibre-nanowire hybrid structure for energy scavenging.

    Science.gov (United States)

    Qin, Yong; Wang, Xudong; Wang, Zhong Lin

    2008-02-14

    A self-powering nanosystem that harvests its operating energy from the environment is an attractive proposition for sensing, personal electronics and defence technologies. This is in principle feasible for nanodevices owing to their extremely low power consumption. Solar, thermal and mechanical (wind, friction, body movement) energies are common and may be scavenged from the environment, but the type of energy source to be chosen has to be decided on the basis of specific applications. Military sensing/surveillance node placement, for example, may involve difficult-to-reach locations, may need to be hidden, and may be in environments that are dusty, rainy, dark and/or in deep forest. In a moving vehicle or aeroplane, harvesting energy from a rotating tyre or wind blowing on the body is a possible choice to power wireless devices implanted in the surface of the vehicle. Nanowire nanogenerators built on hard substrates were demonstrated for harvesting local mechanical energy produced by high-frequency ultrasonic waves. To harvest the energy from vibration or disturbance originating from footsteps, heartbeats, ambient noise and air flow, it is important to explore innovative technologies that work at low frequencies (such as wind energy and body-movement energy using fabrics.

  7. Postmortem Scavenging of Human Remains by Domestic Cats

    Directory of Open Access Journals (Sweden)

    Ananya Suntirukpong, M.D.

    2017-11-01

    Full Text Available Objective: Crime scene investigators, forensic medicine doctors and pathologists, and forensic anthropologists frequently encounter postmortem scavenging of human remains by household pets. Case presentation: The authors present a case report of a partially skeletonized adult male found dead after more than three months in his apartment in Thailand. The body was in an advanced stage of decomposition with nearly complete skeletonization of the head, neck, hands, and feet. The presence of maggots and necrophagous (flesh eating beetles on the body confirmed that insects had consumed much of the soft tissues. Examination of the hand and foot bones revealed canine tooth puncture marks. Evidence of chewing indicated that one or more of the decedent’s three house cats had fed on the body after death. Recognizing and identifying carnivore and rodent activity on the soft flesh and bones of human remains is important in interpreting and reconstructing postmortem damage. Thorough analysis may help explain why skeletal elements are missing, damaged, or out of anatomical position. Conclusion: This report presents a multi-disciplinary approach combining forensic anthropology and forensic medicine in examining and interpreting human remains.

  8. H-2RIIBP, a member of the nuclear hormone receptor superfamily that binds to both the regulatory element of major histocompatibility class I genes and the estrogen response element.

    OpenAIRE

    Hamada, K; Gleason, S L; Levi, B Z; Hirschfeld, S; Appella, E; Ozato, K

    1989-01-01

    Transcription of major histocompatibility complex (MHC) class I genes is regulated by the conserved MHC class I regulatory element (CRE). The CRE has two factor-binding sites, region I and region II, both of which elicit enhancer function. By screening a mouse lambda gt 11 library with the CRE as a probe, we isolated a cDNA clone that encodes a protein capable of binding to region II of the CRE. This protein, H-2RIIBP (H-2 region II binding protein), bound to the native region II sequence, bu...

  9. RxClass

    Data.gov (United States)

    U.S. Department of Health & Human Services — The RxClass Browser is a web application for exploring and navigating through the class hierarchies to find the RxNorm drug members associated with each class....

  10. Recovery of Li from alloys of Al- Li and Li- Al using engineered scavenger compounds

    Science.gov (United States)

    Riley, W. D.; Jong, B. W.; Collins, W. K.; Gerdemann, S. J.

    1994-01-01

    A method of producing lithium of high purity from lithium aluminum alloys using an engineered scavenger compound, comprising: I) preparing an engineered scavenger compound by: a) mixing and heating compounds of TiO2 and Li2CO3 at a temperature sufficient to dry the compounds and convert Li.sub.2 CO.sub.3 to Li.sub.2 O; and b) mixing and heating the compounds at a temperature sufficient to produce a scavenger Li.sub.2 O.3TiO.sub.2 compound; II) loading the scavenger into one of two electrode baskets in a three electrode cell reactor and placing an Al-Li alloy in a second electrode basket of the three electrode cell reactor; III) heating the cell to a temperature sufficient to enable a mixture of KCl-LiCl contained in a crucible in the cell to reach its melting point and become a molten bath; IV) immersing the baskets in the bath until an electrical connection is made between the baskets to charge the scavenger compound with Li until there is an initial current and voltage followed by a fall off ending current and voltage; and V) making a connection between the basket electrode containing engineered scavenger compound and a steel rod electrode disposed between the basket electrodes and applying a current to cause Li to leave the scavenger compound and become electrodeposited on the steel rod electrode.

  11. Scavenging by spiders (Araneae) and its relationship to pest management of the brown recluse spider.

    Science.gov (United States)

    Vetter, Richard S

    2011-06-01

    Experiments reported in Sandidge (2003; Nature 426: 30) indicated that the brown recluse spider, Loxosceles reclusa Gertsch & Mulaik, preferred to scavenge dead prey over live prey and that the spiders were not detrimentally affected when fed insecticide-killed crickets. Extrapolations made in subsequent media coverage disseminating the results of this research made counter-intuitive statements that pesticide treatment in houses would increase brown recluse populations in homes. This information was presented as if the scavenging behavior was specialized in the brown recluse; however, it was more likely that this behavior has not been well studied in other species. To provide a comparison, the current laboratory study examined the likelihood of non-Loxosceles spiders to scavenge dead prey. Of 100 non-Loxosceles spiders that were tested (from 11 families, 24 genera, and at least 29 species from a variety of spider hunting guilds), 99 scavenged dead crickets when offered in petri dishes. Some of the spiders were webspinners in which real-world scavenging of dead prey is virtually impossible, yet they scavenge when given the opportunity. Therefore, scavenging is a flexible opportunistic predatory behavior that is spread across a variety of taxa and is not a unique behavior in brown recluses. These findings are discussed in relation to pest management practices.

  12. Reactive oxygen species and lipid peroxidation product-scavenging ability of yogurt organisms.

    Science.gov (United States)

    Lin, M Y; Yen, C L

    1999-08-01

    The antioxidative activity of the intracellular extracts of yogurt organisms was investigated. All 11 strains tested, including five strains of Streptococcus thermophilus and six strains of Lactobacillus delbrueckii ssp. bulgaricus, demonstrated an antioxidative effect on the inhibition of linoleic acid peroxidation. The antioxidative effect of intracellular extracts of 10(8) cells of yogurt organisms was equivalent to 25 to 96 ppm butylated hydroxytoluene, which indicated that all strains demonstrated excellent antioxidative activity. The scavenging of reactive oxygen species, hydroxyl radical, and hydrogen peroxide was studied for intracellular extracts of yogurt organisms. All strains showed reactive oxygen species-scavenging ability. Lactobacillus delbrueckii ssp. bulgaricus Lb demonstrated the highest hydroxyl radical-scavenging ability at 234 microM. Streptococcus thermophilus MC and 821 and L. delbrueckii ssp. bulgaricus 448 and 449 scavenged the most hydrogen peroxide at approximately 50 microM. The scavenging ability of lipid peroxidation products, t-butylhydroperoxide and malondialdehyde, was also evaluated. Results showed that the extracts were not able to scavenge the t-butylhydroperoxide. Nevertheless, malondialdehyde was scavenged well by most strains.

  13. Modelling the effect of boundary scavenging on Thorium and Protactinium profiles in the ocean

    International Nuclear Information System (INIS)

    Roy-Barman, M.

    2009-01-01

    The 'boundary scavenging' box model is a cornerstone of our understanding of the particle-reactive radionuclide fluxes between the open ocean and the ocean margins. However, it does not describe the radionuclide profiles in the water column. Here, I present the transport-reaction equations for radionuclides transported vertically by reversible scavenging on settling particles and laterally by horizontal currents between the margin and the open ocean. Analytical solutions of these equations are compared with existing data. In the Pacific Ocean, the model produces 'almost' linear 230 Th profiles (as observed in the data) despite lateral transport. However, omitting lateral transport biases the 230 Th based particle flux estimates by as much as 50%. 231 Pa profiles are well reproduced in the whole water column of the Pacific Margin and from the surface down to 3000 m in the Pacific subtropical gyre. Enhanced bottom scavenging or inflow of 231 Pa-poor equatorial water may account for the model-data discrepancy below 3000 m. The lithogenic 232 Th is modelled using the same transport parameters as 230 Th but a different source function. The main source of the 232 Th scavenged in the open Pacific is advection from the ocean margin, whereas a net flux of 230 Th produced in the open Pacific is advected and scavenged at the margin, illustrating boundary exchange. In the Arctic Ocean, the model reproduces 230 Th measured profiles that the uni-dimensional scavenging model or the scavenging-ventilation model failed to explain. Moreover, if lateral transport is ignored, the 230 Th based particle settling speed may by underestimated by a factor 4 at the Arctic Ocean margin. The very low scavenging rate in the open Arctic Ocean combined with the enhanced scavenging at the margin accounts for the lack of high 231 Pa/ 230 Th ratio in arctic sediments. (authors)

  14. The scavenger activities of tea polyphenol and quercetin against oxygen radicals

    International Nuclear Information System (INIS)

    Fang Ruoying; Cheng Jiwu; Hu Tianxi; Tu Tiecheng; Dong Jirong; Wang Wenfeng; Lin nianyun

    1992-01-01

    Studies of free radical biology and medicine have shown that carcinogenesis, vascular diseases of heart and brain, radiation injuries, ageing etc are strictly correlated with free radical injury of tissues. Thus, pharmacologists and biologists are focusing attention on searching for scavengers, especially naturally occurring antioxidant of oxidizing free radicals. Previous studies have indicated that phenolic antioxidants have efficient scavenger activities. Utilizing following methods including chemical luminescence, ESR spectroscopy and pulse radiolysis techniques the scavenger activities of tea polyphenols and quercetin against active species of oxygen have been studied

  15. Numerical Investigation of the Scavenging Process in Marine Two-Stroke Diesel Engines

    DEFF Research Database (Denmark)

    Andersen, Fredrik Herland; Hult, Johan; Nogenmyr, Karl-Johan

    2013-01-01

    The scavenging process is an integral part of any two-stroke internal combustion engine cycle whether it is spark ignited or compression ignited. The scavenging process is responsible for transporting the burned gases from the previous working stroke out of the combustion chamber to allow...... for the fresh charge or fresh air to enter for the next combustion/working stroke. This implies that the scavenging process is responsible for setting the initial condition for the combustion process, consequently affecting fuel economy, power output and emission of hazardous gases. Two-stroke diesel engines...

  16. Ranakinestatin-PPF from the Skin Secretion of the Fukien Gold-Striped Pond Frog, Pelophylax plancyi fukienensis: A Prototype of a Novel Class of Bradykinin B2 Receptor Antagonist Peptide from Ranid Frogs

    OpenAIRE

    Ma, Jie; Luo, Yu; Ge, Lilin; Wang, Lei; Zhou, Mei; Zhang, Yingqi; Duan, Jinao; Chen, Tianbao; Shaw, Chris

    2014-01-01

    The defensive skin secretions of many amphibians are a rich source of bradykinins and bradykinin-related peptides (BRPs). Members of this peptide group are also common components of reptile and arthropod venoms due to their multiple biological functions that include induction of pain, effects on many smooth muscle types, and lowering systemic blood pressure. While most BRPs are bradykinin receptor agonists, some have curiously been found to be exquisite antagonists, such as the maximakinin ge...

  17. Radical scavenging propensity of Cu2 +, Fe3 + complexes of flavonoids and in-vivo radical scavenging by Fe3 +-primuletin

    Science.gov (United States)

    Jabeen, Erum; Janjua, Naveed Kausar; Ahmed, Safeer; Murtaza, Iram; Ali, Tahir; Hameed, Shahid

    2017-01-01

    Cu2 + and Fe3 + complexes of three flavonoids (morin or mo, quercetin or quer and primuletin or prim) were synthesized with the objective of improving antioxidant capacities of flavonoids. The radical scavenging activities of pure flavonoids and their metal complexes were assayed to monitor their tendencies towards sequestering of radicals at physiological conditions. The scavenger potencies of metal-flavonoid complexes were significantly higher than those of the parent flavonoids. Further, influence of the solvent polarity on the radical capturing by flavonoids and their metal complexes was in favor for the polar solvent. Fe3 +-prim displayed its radical scavenging ability via up gradation of CAT and SOD activities in in-vivo antioxidant assays.

  18. Attendance of scavenging seabirds at trawler discards off Galicia, Spain

    Directory of Open Access Journals (Sweden)

    Julio Valeiras

    2003-07-01

    Full Text Available The occurrence of scavenger seabirds at fishing trawlers was studied off Galicia, Spain. A total of 9,368 seabirds of 23 species were recorded during 92 fishing operations in 1998 and 1999. The most common species were the yellow-legged and lesser black-backed gull (Larus cachinnans and L. fuscus, Sabine´s gull (L. sabini, the northern gannet (Morus bassanus, the great shearwater (Puffinus gravis, sooty shearwater (P. griseus, the Manx and Balearic shearwater (P. puffinus and P. mauretanicus, the great skua (Catharacta skua and terns (mainly Sterna hirundo and S. paradisaea. Other species occurred in small numbers: Leach´s petrel (Oceanodroma leucorhoa, the storm petrel (Hydrobates pelagicus, the little shearwater (Puffinus assimilis, Cory´s shearwater (Calonectris diomedea, the parasitic skua (Stercorarius parasiticus, the pomarine skua (S. pomarinus, the black-headed gull (Larus ridibundus, the glaucous gull (L. hyperboreus, the kittiwake (Rissa tridactyla, the sandwich tern (Sterna sandvicensis, the black tern (Chlidonias niger, the guillemot (Uria aalge and the little auk (Alle alle. The maximum number of seabirds recorded at a haul was 320. The maximum number of a particular species ranged from 120 great shearwaters to 250 yellow-legged/lesser black-backed gulls during a single haul. The differences in ship-follower species abundance are related to migratory movements but fisheries could also have a strong influence at a smaller scale on the distribution of seabirds off Galicia. The degree to which seabirds rely on fishery discards as food was not quantified, but may be important for several species.

  19. Effects of edaravone, a radical scavenger, on hepatocyte transplantation.

    Science.gov (United States)

    Hayashi, Chihiro; Ito, Masahiro; Ito, Ryoutaro; Murakumo, Akiko; Yamamoto, Naoki; Hiramatsu, Noriko; Fox, Ira J; Horiguchi, Akihiko

    2014-12-01

    Hepatocyte transplantation (HTx) has yielded significant improvements in liver function and survival in experimentally induced acute liver failure and liver-based metabolic disease. However, transplantation is inefficient, and it is thought that transplanted hepatocytes have a shortened lifespan because of inflammation involving excess nitric oxide (NO). The present study aimed to clarify whether edaravone, a free radical scavenger used to treat ischemic stroke, could reduce ischemic changes in hepatocyte-transplanted livers. Edaravone (3 mg/kg) was administered intravenously 24 h before HTx to Nagase analbuminemic rats (NARs). Hepatocytes were isolated, and 30 × 10(6) cells were injected in a 1.0-ml volume directly into the spleens of NARs. All experimental groups studied received FK506 to control rejection. Animals in Group A received medium-only; Group B received HTx only; and Group C received HTx and edaravone. Forty-eight hours after transplantation, the hepatocytes from animals were isolated and analyzed for staining with propidium iodide- and annexin-V using flow cytometry. Liver sections were also studied by immunostaining for albumin, and TUNEL. Peripheral blood serum albumin levels were measured on post-transplant days 0, 3, 5, 7, 10 and 14 using ELISA. The edaravone-treated animals demonstrated an increased number of engrafted donor hepatocytes in the liver. The edaravone-treated liver sections also contained fewer TUNEL-positive cells and animals that received edaravone had higher serum albumin levels post-transplantation. Hepatocytes were also found to have increased in numbers 2 weeks following treatment with edaravone. Edaravone administration during HTx can suppress apoptosis near the transplanted cells, increasing engraftment. These studies indicate its potential usefulness for future clinical application. © 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  20. Study of atmospheric pollution scavenging. Eighteenth progress report

    Energy Technology Data Exchange (ETDEWEB)

    Semonin, R.G.; Bartlett, J.D.; Bowersox, V.C.; Gatz, D.F.; Naiman, D.Q.; Peden, M.E.; Stahlhut, R.K.; Stensland, G.J.

    1980-07-01

    The analysis of aerosol samples obtained in rural east-central Illinois reveals a seasonal maximum in SO/sub 4/ during May to July and a similar pattern for NH/sub 4/. The annual median SO/sub 4/ is about 1 to 1.5 ..mu..g/m/sup 3/. In contrast to these ions, NO/sub 3/ displays highest values in the cold season. Soil-related species (Ca, K) seem to maximize in relation to farm tillage and harvesting practices. The NO/sub 3/ in recent precipitation samples over the northeast US increased between 1 and 2 times the values observed in the mid-1950's. A case study from SCORE-78 suggests that all ion concentrations analyzed from sequentially collected samples decreased from the onset of rain to a minimum corresponding to the heaviest rain rates. Four groups of elements in 10 event rain samples were identified using factor analysis. The groups include soluble and insoluble crustal elements, soluble pollutant metals and sulfate, and insoluble pollutant metals. Utilizing the factor analysis approach, the St. Louis METROMEX precipitation chemistry data showed that the SO/sub 4/ deposition patterns group consistently with those of other soluble pollutants. Additional factor analysis efforts on the St. Louis rainwater data set revealed that soluble and insoluble concentrations of a given element have different deposition patterns suggesting that scavenging and/or precipitation formation processes dictate the patterns. An approach to managing the vast data base of rain chemistry used in the above studies is described. The software also examines the data for certain aspects of quality assurance. The procedures used to analyze ambient air filter samples are discussed.

  1. Polymorphic ROS scavenging revealed by CCCP in a lizard

    Science.gov (United States)

    Olsson, Mats; Wilson, Mark; Isaksson, Caroline; Uller, Tobias

    2009-07-01

    Ingestion of antioxidants has been argued to scavenge circulating reactive molecules (e.g., free radicals), play a part in mate choice (by mediating access to this important resource), and perhaps increase life span. However, recent work has come to question these relationships. We have shown elsewhere in the polychromatic lizard, Ctenophorus pictus, that diet supplementation of carotenoids as antioxidants does not depress circulating natural reactive oxygen species (ROS) levels and leads to no corresponding improvement of color traits. However, a much stronger test would be to experimentally manipulate the ROS levels themselves and assess carotenoid-induced ROS depression. Here, we achieve this by using carbonyl cyanide 3-chlorophenylhydrazone, which elevates superoxide (SO) formation approximately threefold at 10 μM in this model system. We then look for depressing effects on ROS of the carotenoids in order to assess whether ‘super-production’ of SO makes carotenoid effects on elevated ROS levels detectable. The rationale for this treatment was that if not even such elevated levels of SO are reduced by carotenoid supplementation, the putative link carotenoids, ROS depression, and mate quality (in terms of antioxidant capacity) is highly questionable. We conclude that there is no significant effect of carotenoids on mean SO levels even at the induced ROS levels. However, our results showed a significant interaction effect between carotenoid treatment and male color, with red males having higher ROS levels than yellow males. We suggest that this may be because different pigments are differently involved in the generation of the integumental colors in the two morphs with concomitant effects on ROS depletion depending on carotenoid uptake or allocation to coloration and antioxidation.

  2. A combined computational and structural model of the full-length human prolactin receptor

    DEFF Research Database (Denmark)

    Bugge, Katrine Østergaard; Papaleo, Elena; Haxholm, Gitte Wolfsberg

    2016-01-01

    The prolactin receptor is an archetype member of the class I cytokine receptor family, comprising receptors with fundamental functions in biology as well as key drug targets. Structurally, each of these receptors represent an intriguing diversity, providing an exceptionally challenging target for...... 40 different receptor chains, and reveals that the extracellular domain is merely the tip of a molecular iceberg....

  3. Age-Related Relationships between Innate Immunity and Plasma Carotenoids in an Obligate Avian Scavenger.

    Science.gov (United States)

    López-Rull, Isabel; Hornero-Méndez, Dámaso; Frías, Óscar; Blanco, Guillermo

    2015-01-01

    Variation in immunity is influenced by allocation trade-offs that are expected to change between age-classes as a result of the different environmental and physiological conditions that individuals encounter over their lifetime. One such trade-off occurs with carotenoids, which must be acquired with food and are involved in a variety of physiological functions. Nonetheless, relationships between immunity and carotenoids in species where these micronutrients are scarce due to diet are poorly studied. Among birds, vultures show the lowest concentrations of plasma carotenoids due to a diet based on carrion. Here, we investigated variations in the relationships between innate immunity (hemagglutination by natural antibodies and hemolysis by complement proteins), pathogen infection and plasma carotenoids in nestling and adult griffon vultures (Gyps fulvus) in the wild. Nestlings showed lower hemolysis, higher total carotenoid concentration and higher pathogen infection than adults. Hemolysis was negatively related to carotenoid concentration only in nestlings. A differential carotenoid allocation to immunity due to the incomplete development of the immune system of nestlings compared with adults is suggested linked to, or regardless of, potential differences in parasite infection, which requires experimental testing. We also found that individuals with more severe pathogen infections showed lower hemagglutination than those with a lower intensity infection irrespective of their age and carotenoid level. These results are consistent with the idea that intraspecific relationships between innate immunity and carotenoids may change across ontogeny, even in species lacking carotenoid-based coloration. Thus, even low concentrations of plasma carotenoids due to a scavenger diet can be essential to the development and activation of the immune system in growing birds.

  4. Computational study of the structure-free radical scavenging relationship of procyanidins.

    Science.gov (United States)

    Mendoza-Wilson, Ana María; Castro-Arredondo, Sergio Ivan; Balandrán-Quintana, René Renato

    2014-10-15

    Procyanidins (PCs) are effective free radical scavengers, however, their antioxidant ability is variable because they have different degrees of polymerisation, are composed by distinct types of subunits and are very susceptible to changes in conformation. In this work the structure-free radical scavenging relationship of monomers, dimers and trimers of PCs was studied through the hydrogen atom transfer (HAT), sequential proton-loss electron-transfer (SPLET) and single electron transfer followed by proton transfer (SET-PT) mechanisms in aqueous phase, employing the Density Functional Theory (DFT) computational method. The structure-free radical scavenging relationship of PCs showed a very similar behaviour in HAT and SET-PT mechanisms, but very different in the SPLET mechanism. The structural factor that showed more effects on the ability of PCs to scavenge free radicals in aqueous phase was the conformation. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Comparative in vitro study on free radical scavenging potential of selected bivalve species

    Digital Repository Service at National Institute of Oceanography (India)

    Shenai-Tirodkar, P.S.; Pawar, R.T.; Jagtap, T.G.

    Bivalves such as, Crassostrea spp., Meretrix casta, Placuna placenta and Polymesoda erosa are largely consumed as edible seafood. It forms natural source of nutrition in coastal and worldwide population. Free radical scavenging activities...

  6. Pigment and amylase production in Penicillium sp NIOM-02 and its radical scavenging activity

    Digital Repository Service at National Institute of Oceanography (India)

    Dhale, M.A.; VijayRaj, A.S.

    Penicillium sp NIOM-02 was isolated from the marine sediment, produced red pigment. The pigment extracted from this fungus scavenged 2, 2-diphenyl-1-pycrylhydrazyl (DPPH) radical. Penicillium sp NIOM-02 grown in media containing corn steep liquor...

  7. Antioxidant properties of a radical-scavenging peptide purified from enzymatically prepared fish skin gelatin hydrolysate.

    Science.gov (United States)

    Mendis, Eresha; Rajapakse, Niranjan; Kim, Se-Kwon

    2005-02-09

    Hoki (Johnius belengerii) skin gelatin was hydrolyzed with three commercial enzymes to identify radical-scavenging potencies of derived peptides. Peptides derived from tryptic hydrolysate exhibited the highest scavenging activities on superoxide, carbon-centered 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals assessed by ESR spectroscopy. Following consecutive chromatographic separations of tryptic hydroolysate, the peptide sequence His-Gly-Pro-Leu-Gly-Pro-Leu (797 Da) acted as a strong radical scavenger under studied conditions. Further, this peptide could act as an antioxidant against linoleic acid peroxidation and the activity was closer to the highly active synthetic antioxidant butylated hydroxytoluene (BHT). In addition, antioxidative enzyme levels in cultured human hepatoma cells were increased in the presence of this peptide and it was presumed to be the peptide involved in maintaining the redox balance in the cell environment. Present data indicate that free-radical-scavenging activities of hoki skin gelatin peptides substantially contribute to their antioxidant properties measured in different oxidative systems.

  8. Screening of radical scavenging activity of some medicinal and aromatic plant extracts

    NARCIS (Netherlands)

    Miliauskas, G.; Venskutonis, R.P.; Beek, van T.A.

    2004-01-01

    Extracts of 12 medicinal and aromatic plants were investigated for their radical scavenging activity using DPPH and ABTS assays: Salvia sclarea, Salvia glutinosa, Salvia pratensis, Lavandula angustifolia, Calendula officinalis, Matricaria recutita, Echinacea purpurea, Rhaponticum carthamoides,

  9. In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins

    International Nuclear Information System (INIS)

    Mack, John; Vermeiren, Christie; Heinrichs, David E.; Stillman, Martin J.

    2004-01-01

    We report the first characterization of the in vivo porphyrin scavenging abilities of two components of a newly discovered heme scavenging system involving iron-regulated surface determinant (Isd) proteins. These proteins are present within the cell envelope of the Gram-positive human pathogen Staphylococcus aureus. IsdC and IsdE, when expressed heterologously in Escherichia coli, efficiently scavenged intracellular heme and resulted in de novo heme synthesis in excess of 100-fold above background. Magnetic circular dichroism analyses showed that the heme-binding properties of the two proteins differ significantly from one another. IsdC bound almost exclusively free-base protoporphyrin IX, whereas the IsdE protein was associated with low spin Fe(III) and Fe(II) heme. These properties provide important insight into the possible mechanisms of iron scavenging from bound heme by Isd proteins

  10. Deer carcass decomposition and potential scavenger exposure to chronic wasting disease

    Science.gov (United States)

    Jennelle, C.S.; Samuel, M.D.; Nolden, C.A.; Berkley, E.A.

    2009-01-01

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy afflicting the Cervidae family in North America, causing neurodegeneration and ultimately death. Although there are no reports of natural cross-species transmission of CWD to noncervids, infected deer carcasses pose a potential risk of CWD exposure for other animals. We placed 40 disease-free white-tailed deer (Odocoileus virginianus) carcasses and 10 gut piles in the CWD-affected area of Wisconsin (USA) from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger visitation and relative activity. To evaluate factors driving the rate of carcass removal (decomposition), we used KaplanMeier survival analysis and a generalized linear mixed model. We recorded 14 species of scavenging mammals (6 visiting species) and 14 species of scavenging birds (8 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and Virginia opossums (Didelphis virginiana). We found no evidence that deer consumed conspecific remains, although they visited gut piles more often than carcasses relative to temporal availability in the environment. Domestic dogs, cats, and cows either scavenged or visited carcass sites, which could lead to human exposure to CWD. Deer carcasses persisted for 18 days to 101 days depending on the season and year, whereas gut piles lasted for 3 days. Habitat did not influence carcass decomposition, but mammalian and avian scavenger activity and higher temperatures were positively associated with faster removal. Infected deer carcasses or gut piles can serve as potential sources of CWD prions to a variety of scavengers. In areas where surveillance for CWD exposure is practical, management agencies should consider strategies for testing primary scavengers of deer carcass material.

  11. Scavenging capacity of medicinal plants against free radical-induced cellular damage by radiation and photoactivation

    Energy Technology Data Exchange (ETDEWEB)

    Gadkar, Shalaka [Ruia College, Mumbai (India); Mohan, H [Chemistry Group, Bhabha Atomic Research Centre, Mumbai (India); Kamat, J P [Radiation Biology and Health Science Division, Bhabha Atomic Research Centre, Mumbai (India)

    2004-01-01

    The scavenging capacity of medicinal plants. Andrographis paniculata (Ap) and Swertia chirata (Sc) was examined against cellular damage, induced by radiation and photo-activation in sub-cellular membranes. The results demonstrated significant radical scavenging capacity of the extracts. The rate constants as evaluated by deoxyribose degradation studies and the pulse radiolysis studies carried in presence of ABTS radical well supported the antioxidant properties of the extracts. (author)

  12. Uses and flock management practices of scavenging chickens in Wolaita Zone of southern Ethiopia.

    Science.gov (United States)

    Desta, Takele Taye; Wakeyo, Oli

    2012-03-01

    Rearing of scavenging chickens is among the most commonly practiced farm activities in Ethiopia. This system is dominated by indigenous chickens. Output from indigenous chickens is low due to poor management and absence of intense selection that is intended to improve economically important traits. This showed that village chickens are rather evolved for adaptation traits. However, the level of risk is low, and this has made rearing of scavenging chickens a choice of farm activity for smallholder farmers. The objective of this study was to characterize the scavenging chickens' production system in Wolaita Zone. Single-visit survey involving individual interview of 119 farmers and 6 focus group discussions was used to collect the data. Our results showed that rearing of scavenging chickens was constrained especially by disease and predation problems. However, farmers proposed a set of solutions to minimize the effect of these problems. Rearing of scavenging chickens fulfils the multi-functional need of the society. This system has special features because it can sustain in its own without the need for modern commercial chicken farming facilities. However, farmers also reported the drawbacks of rearing of scavenging chickens and these mainly include uproot of garden crops and tiresomeness of the night watching. Selection of chickens was mainly depending on physically observed traits like body size and plumage colour. The initial foundation flock was mainly obtained from the local market. The ideal place for scavenging chickens production is the one that has intermediate weather condition and has some trees that can be used as shade; however, it was substantiated that it has to be free from bush and shrubs, weeds and wet lands. Therefore, these pieces of knowledge embedded among smallholder farmers need to be well documented and synthesized to design an appropriate type of technology packages that can be communicated back to farmers to improve productivity of the

  13. Study of anti-oxidation and scavenging effects on free radicals of quercetin

    International Nuclear Information System (INIS)

    Wang Chongdao; Qiang Yizhong; Lao Qinhua; Shao Yuan

    1999-01-01

    The effects of Quercetin on the contents of lipid peroxides (LPO) in the mice caused by γ-whole-body irradiation by method of the modified spectrophotometry of TBA, and the scavenging effects of Quercetin on the free radicals of DNA induced by radiation exposure by means of ESR technique were investigated. The results demonstrates that Quercetin has a good anti-oxidation effect and is very effective in scavenging of free radicals

  14. Studies on free radical scavenging activity in Chinese seaweeds part I. Screening results

    Science.gov (United States)

    Yan, Xiao-Jun; Fang, Guo-Ming; Lou, Qing-Xiang

    1999-09-01

    Antioxidants have attracted the attention of researchers due to their beneficial effects as free radical scavengers. Application of a stable free radical named 1, 1-diphenyl-2-picrylhydrazyl(DPPH) to screen the free radical scavenging activity in 27 species of Chinese seaweed showed that 15 of them had significant activity in at least one of the organic solvent extracts. The most interesting seaweed species were Gelidium amansii, Gloiosiphonia capillaris, Polysiphonia urceolata, Sargassum kjellmanianum, Desmarestia viridis, and Rhodomela teres.

  15. Anti-oxidation and scavenging effects of some extracts from Chinese medicines on free radicals

    International Nuclear Information System (INIS)

    Wang Chongdao; Qiang Yizhong; Lao Qinhua; Cui Fengmei; Shao Yuan; Sun Cunpu

    1999-11-01

    The inhibiting effects of Chinonin, Quercetin and Tannic Acid on the lipid oxidation induced by radiation exposure were investigated by means of a modified TBA spectrophotometry. The scavenging effects on free radicals caused by γ-irradiation exposure of the three active principles were observed by technique of ESR. The results showed that anti-oxidation effects of Chinonin and Quercetin were better than that of Tannic Acid, while the scavenging effects of the three active principles on free radicals were similar

  16. Numerical modeling of aerosol particles scavenging by drops as a process of air depollution

    OpenAIRE

    Cherrier , Gaël

    2017-01-01

    This PhD-Thesis is dedicated to the numerical modeling of aerosol particles scavenging by drops. Investigated situations are about aerosol particles of aerodynamic diameter ranging from 1 nm to 100 µm captured in the air by water drops of diameter varying between 80 µm and 600 µm, with corresponding droplet Reynolds number ranging between 1 and 100. This air depollution modeling is achieved in two steps. The first step consists in obtaining a scavenging kernel predicting the flow rate of aero...

  17. Precipitation Scavenging of Aerosol Particles at a Rural Site in the Czech Republic.

    Czech Academy of Sciences Publication Activity Database

    Zíková, Naděžda; Ždímal, Vladimír

    2016-01-01

    Roč. 67, č. 2016 (2016), s. 27343 ISSN 0280-6509 R&D Projects: GA ČR GAP209/11/1342 EU Projects: European Commission(XE) 654109 - ACTRIS-2; European Commission(XE) 262254 - ACTRIS Institutional support: RVO:67985858 Keywords : below- cloud scavenging * in- cloud scavenging * hydrometeors Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.402, year: 2015

  18. Gallic acid as an oxygen scavenger in bio-based multilayer packaging films

    OpenAIRE

    Pant, Astrid; Sängerlaub, Sven; Müller, Kajetan

    2017-01-01

    Oxygen scavengers are used in food packaging to protect oxygen-sensitive food products. A mixture of gallic acid (GA) and sodium carbonate was used as an oxygen scavenger (OSc) in bio-based multilayer packaging films produced in a three-step process: compounding, flat film extrusion, and lamination. We investigated the film surface color as well as oxygen absorption at different relative humidities (RHs) and temperatures, and compared the oxygen absorption of OSc powder, monolayer films, and ...

  19. Increasing land-use intensity reverses the relative occupancy of two quadrupedal scavengers

    OpenAIRE

    Twining, Joshua P.; Bernard, Henry; Ewers, Robert M.

    2017-01-01

    Human land use is continuously altering the natural environment, yet the greater ecological implications of this change for many groups that are key to healthy ecosystem functioning remains uncharacterised in the tropics. Terrestrial scavenging vertebrates are one such group, providing integral ecosystem services through the removal of carrion which is a crucial component of both nutrient cycling and disease dynamics. To explore how anthropogenic processes may affect forest scavengers, we inv...

  20. The scavenging effects of tea polyphenol and quercetin on active oxygen species

    International Nuclear Information System (INIS)

    Fang Ruoying; Cheng Jiwu; Hu Tianxi; Tu Tiechen; Dong Jirong; Wang Wenfeng; Lin Nianyun

    1993-01-01

    The abilities of scavenging active oxygen species, O 2 free radical and OH., by tea polyphenols and quercetin have been studied by chemiluminescence, ESR and pulse radiolysis. Tea polyphenols and quercetin are all phenolic antioxidants. The synergetic studies show that both tea polyphenols and quercetin are strong free radical scavengers. Tea polyphenols are better than quercetin. the results from CL studies are in good accord with those from ESR and PR studies

  1. Discovery of α-Substituted Imidazole-4-acetic Acid Analogues as a Novel Class of ρ1 γ-Aminobutyric Acid Type A Receptor Antagonists with Effect on Retinal Vascular Tone

    DEFF Research Database (Denmark)

    Krall, Jacob; Brygger, Benjamin M.; Sigurðardóttir, Sara B.

    2016-01-01

    The ρ-containing γ-aminobutyric acid type A receptors (GABAA Rs) play an important role in controlling visual signaling. Therefore, ligands that selectively target these GABAA Rs are of interest. In this study, we demonstrate that the partial GABAA R agonist imidazole-4-acetic acid (IAA) is able...... to penetrate the blood-brain barrier in vivo; we prepared a series of α- and N-alkylated, as well as bicyclic analogues of IAA to explore the structure-activity relationship of this scaffold focusing on the acetic acid side chain of IAA. The compounds were prepared via IAA from l-histidine by an efficient...

  2. Effect of ultraviolet irradiation on free radical scavenging activity of immunosuppressants used in lung transplantation and comparative electron paramagnetic resonance study of kinetics of their interactions with model free radicals.

    Science.gov (United States)

    Stanjek-Cichoracka, A; Żegleń, S; Ramos, P; Pilawa, B; Wojarski, J

    2018-06-01

    The immunosuppressive drugs used in solid organ transplantation or autoimmunological processes were studied by electron paramagnetic resonance (EPR) spectroscopy to estimate their free radical scavenging activity. The interactions of immunosuppressants with free radicals were examined by an X-band (9.3 GHz) EPR spectroscopy and a model of DPPH free radicals. The EPR spectra of DPPH and DPPH interacting with individual drugs were compared. Kinetic studies were performed, and the effect of ultraviolet (UV) irradiation on the free radical scavenging activity of the tested drugs was determined. The free radical scavenging activity of non-irradiated drugs decreased in the order: rapamycin > mycophenolate mofetil > ciclosporin > tacrolimus. UV irradiation increased the free radical scavenging activity of all the tested immunosuppressive drugs, and the effect was highest for tacrolimus. For the non-irradiated samples, the speed of free radical interactions decreased in the order: ciclosporin > tacrolimus > mycophenolate mofetil > rapamycin. UV irradiation only slightly affected the speed of interactions of the immunosuppressive drugs with the model DPPH free radicals. Electron paramagnetic resonance spectroscopy is useful for obtaining information on interactions of immunosuppressive drugs with free radicals. We hypothesized that the long-term immunosuppressive effects of these drugs after transplantation or during autoimmune disorders may be mediated by anti-inflammatory action in addition to the known receptor/cell cycle inhibition. © 2018 John Wiley & Sons Ltd.

  3. Postmortem scavenging by the Virginia opossum (Didelphis virginiana): Impact on taphonomic assemblages and progression.

    Science.gov (United States)

    King, Kama A; Lord, Wayne D; Ketchum, Heather R; O'Brien, R Christopher

    2016-09-01

    The Virginia opossum (Didelphis virginiana) is a highly active scavenger whose behavior has significant impacts on rates of decomposition and skeletonization, which have previously not been addressed. In this study, scavenging by the opossum led to the skeletonization of carcasses in half of the accumulated degree days (ADD) of a comparable non-scavenged control carcass. Opossums used body orifices, as well as natural tears caused by the decomposition process, to access internal tissues and consume them. This activity resulted in little movement of the carcass and the retained appearance of natural undisturbed decomposition. This concealed activity has the potential to cause drastically incorrect estimates of time since deposition and post-mortem interval. Scavenging by opossums was also found to leave distinct tooth mark and other defects on bone, which have not been previously distinguished in the literature. This research suggests, beyond effects on PMI, that scavenging by opossums has been historically overlooked and misattributed to canid scavengers. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Silica-scavenging effects in ceria-based solid electrolytes

    Directory of Open Access Journals (Sweden)

    Ivanova, D.

    2008-08-01

    Full Text Available Composite materials based on gadolinium doped ceria (CGO with additions of silica, with both silica and lanthanum oxide, and with lanthanum silicate, were prepared by the conventional ceramic route, to assess the silica scavenging role of lanthanum oxide additions. Structural, microstructural and electrical characterization of these samples confirmed the formation of one apatite type lanthanum silicate-based phase from reaction of silica with lanthanum oxide. The formation of this phase occurred in parallel with a significant enhancement of the grain boundary conductivity of these composite materials. Further interaction between constituents, involving diffusion of La to CGO, and Ce and Gd to the apatite phase, had no significant consequences on the electrical performance of these materials. Overall, lanthanum oxide was shown to remove the siliceous phases from the grain boundaries of CGO.

    Se prepararon materiales compuestos basados en óxido de cerio dopado con gadolinio (TGO con adicciones de sílice, con sílice y óxido de lantano y silicato del lantano, mediante procesamiento cerámico convencional con objeto de confirmar el papel secuestrante de sílice de las adicciones. La caracterización estructural, microestructural y eléctrica de las muestras confirmó la formación de una fase tipo apatito basada en silicato de lantano a partir de la reacción de la sílice con el óxido de lantano. La formación de esta fase ocurre en paralelo con un incremento significativo de la conductividad a través del borde de grano de estos materiales. La interacción entre los constituyentes, incluyendo la difusión del La al CGO, y el Ce y el Gd a la fase apatito, no tiene consecuencias significativas sobre el comportamiento eléctrico de estos materiales. Resumiendo, el óxido de lantano es capaz de eliminar las fases silicias del borde de grano del CGO.

  5. The Green Route from Carbon Monoxide Fixation to Functional Polyamines : A Class of High-Performing Metal Ion Scavengers

    NARCIS (Netherlands)

    Toncelli, C.; Haijer, A.; Alberts, F.; Broekhuis, A. A.; Picchioni, F.

    2015-01-01

    The exploitation of the Paal-Knorr reaction as a postmodification tool of ethene/propene/CO polyketone terpolymers to produce thermoset beads for metal ion uptake is hereby presented. Its prominent green character (i.e., no catalyst or a solvent employed, biocompatible polymer precursor) renders

  6. The Scavenger Protein Apoptosis Inhibitor of Macrophages (AIM) Potentiates the Antimicrobial Response against Mycobacterium tuberculosis by Enhancing Autophagy

    Science.gov (United States)

    Sanjurjo, Lucía; Amézaga, Núria; Vilaplana, Cristina; Cáceres, Neus; Marzo, Elena; Valeri, Marta; Cardona, Pere-Joan; Sarrias, Maria-Rosa

    2013-01-01

    Apoptosis inhibitor of macrophages (AIM), a scavenger protein secreted by tissue macrophages, is transcriptionally regulated by the nuclear receptor Liver X Receptor (LXR) and Retinoid X Receptor (RXR) heterodimer. Given that LXR exerts a protective immune response against M. tuberculosis, here we analyzed whether AIM is involved in this response. In an experimental murine model of tuberculosis, AIM serum levels peaked dramatically early after infection with M. tuberculosis, providing an in vivo biological link to the disease. We therefore studied the participation of AIM in macrophage response to M. tuberculosis in vitro. For this purpose, we used the H37Rv strain to infect THP-1 macrophages transfected to stably express AIM, thereby increasing infected macrophage survival. Furthermore, the expression of this protein enlarged foam cell formation by enhancing intracellular lipid content. Phagocytosis assays with FITC-labeled M. tuberculosis bacilli indicated that this protein was not involved in bacterial uptake; however, AIM expression decreased the number of intracellular cfus by up to 70% in bacterial killing assays, suggesting that AIM enhances macrophage mycobactericidal activity. Accordingly, M. tuberculosis-infected AIM-expressing cells upregulated the production of reactive oxygen species. Moreover, real-time PCR analysis showed increased mRNA levels of the antimicrobial peptides cathelicidin and defensin 4B. These increases were concomitant with greater cellular concentrations of the autophagy-related molecules Beclin 1 and LC3II, as well as enhanced acidification of mycobacterial phagosomes and LC3 co-localization. In summary, our data support the notion that AIM contributes to key macrophage responses to M. tuberculosis. PMID:24223991

  7. Enhanced protection of PDMS-embedded palladium catalysts by co-embedding of sulphide-scavengers.

    Science.gov (United States)

    Comandella, Daniele; Ahn, Min Hyung; Kim, Hojeong; Mackenzie, Katrin

    2017-12-01

    For Pd-containing hydrodechlorination catalysts, coating with poly(dimethyl siloxane) (PDMS) was proposed earlier as promising protection scheme against poisoning. The PDMS coating can effectively repel non-permeating poisons (such as SO 3 2- ) retaining the hydrodechlorination Pd activity. In the present study, the previously achieved protection efficiency was enhanced by incorporation of sulphide scavengers into the polymer. The embedded scavengers were able to bind permeating non-ionic poisons (such as H 2 S) during their passage through PDMS prior to Pd contact which ensured an extended catalyst lifetime. Three scavenger types forming non-permeable sulphur species from H 2 S - alkaline, oxidative or iron-based compounds - were either incorporated into single-layer coats around individual Pd/Al 2 O 3 particles or into a second layer above Pd-containing PDMS films (Pd-PDMS). Hydrodechlorination and hydrogenation were chosen as model reactions, carried out in batch and continuous-flow reactors. Batch tests with all scavenger-containing catalysts showed extended Pd protection compared to scavenger-free catalysts. Solid alkaline compounds (Ca(OH) 2 , NaOH, CaO) and MnO 2 showed the highest instantaneous scavenger efficiencies (retained Pd activity=30-60%), while iron-based catalysts, such as nano zero-valent iron (nZVI) or ferrocene (FeCp 2 ), proved less efficient (1-10%). When stepwise poisoning was applied, the protection efficiency of iron-based and oxidizing compounds was higher in the long term than that of alkaline solids. Long-term experiments in mixed-flow reactors were performed with selected scavengers, revealing the following trend of protection efficiency: CaO 2 >Ca(OH) 2 >FeCp 2 . Under field-simulating conditions using a fixed-bed reactor, the combination of sulphide pre-oxidation in the water phase by H 2 O 2 and local scavenger-enhanced Pd protection was successful. The oxidizing agent H 2 O 2 does not disturb the Pd-catalysed reduction, while the

  8. Receptor assay

    Energy Technology Data Exchange (ETDEWEB)

    Kato, K; Ibayashi, H [Kyushu Univ., Fukuoka (Japan). Faculty of Medicine

    1975-05-01

    This paper summarized present status and problems of analysis of hormone receptor and a few considerations on clinical significance of receptor abnormalities. It was pointed that in future clinical field quantitative and qualitative analysis of receptor did not remain only in the etiological discussion, but that it was an epoch-making field of investigation which contained the possiblity of artificial change of sensitivity of living body on drugs and the development connected directly with treatment of various diseases.

  9. Opioid receptor desensitization: mechanisms and its link to tolerance

    Directory of Open Access Journals (Sweden)

    Stéphane eAllouche

    2014-12-01

    Full Text Available Opioid receptors are part of the class A of G-protein coupled receptors and the target of the opiates, the most powerful analgesic molecules used in clinic. During a protracted use, a tolerance to analgesic effect develops resulting in a reduction of the effectiveness. So understanding mechanisms of tolerance is a great challenge and may help to find new strategies to tackle this side effect. This review will summarize receptor-related mechanisms that could underlie tolerance especially receptor desensitization. We will focus on the latest data obtained on molecular mechanisms involved in opioid receptor desensitization: phosphorylation, receptor uncoupling, internalization and post-endocytic fate of the receptor.

  10. Receptor targeting of hemoglobin mediated by the haptoglobins

    DEFF Research Database (Denmark)

    Nielsen, Marianne Jensby; Moestrup, Søren Kragh

    2009-01-01

    Haptoglobin, the haptoglobin-hemoglobin receptor CD163, and the heme oxygenase-1 are proteins with a well-established function in the clearance and metabolism of "free" hemoglobin released during intravascular hemolysis. This scavenging system counteracts the potentially harmful oxidative and NO......-scavenging effects associated with "free" hemoglobin, and, furthermore, elicits an anti-inflammatory response. In the late primate evolution, haptoglobin variants with distinct functions have arisen, including haptoglobin polymers and the haptoglobin-related protein. The latter associates with a subspecies of high......-density lipoprotein (HDL) particles playing a crucial role in the innate immunity against certain trypanosome parasites. Recent studies have elucidated this fairly sophisticated immune defense mechanism that takes advantage of a trypanosomal haptoglobin-hemoglobin receptor evolved to supply the parasite with heme...

  11. Turbulent swirling flow in a dynamic model of a uniflow-scavenged two-stroke engine

    Science.gov (United States)

    Ingvorsen, K. M.; Meyer, K. E.; Walther, J. H.; Mayer, S.

    2014-06-01

    It is desirable to use computational fluid dynamics for optimization of the in-cylinder processes in low-speed two-stroke uniflow-scavenged marine diesel engines. However, the complex nature of the turbulent swirling in-cylinder flow necessitates experimental data for validation of the used turbulence models. In the present work, the flow in a dynamic scale model of a uniflow-scavenged cylinder is investigated experimentally. The model has a transparent cylinder and a moving piston driven by a linear motor. The flow is investigated using phase-locked stereoscopic particle image velocimetry (PIV) and time-resolved laser Doppler anemometry (LDA). Radial profiles of the phase-locked mean and rms velocities are computed from the velocity fields recorded with PIV, and the accuracy of the obtained profiles is demonstrated by comparison with reference LDA measurements. Measurements are carried out at five axial positions for 15 different times during the engine cycle and show the temporal and spatial development of the swirling in-cylinder flow. The tangential velocity profiles in the bottom of the cylinder near the end of the scavenge process are characterized by a concentrated swirl resulting in wake-like axial velocity profiles and the occurrence of a vortex breakdown. After scavenge port closing, the axial velocity profiles indicate that large transient swirl-induced structures exist in the cylinder. Comparison with profiles obtained under steady-flow conditions shows that the scavenge flow cannot be assumed to be quasi-steady. The temporal development of the swirl strength is investigated by computing the angular momentum. The swirl strength shows an exponential decay from scavenge port closing to scavenge port opening corresponding to a reduction of 34 %, which is in good agreement with theoretical predictions.

  12. Polyphenolic Compounds and Free Radical Scavenging Activity in Eight Lamiaceae Herbs of Manipur

    Directory of Open Access Journals (Sweden)

    Sandhyarani Devi KHOMDRAM

    2011-05-01

    Full Text Available Eight plants of Lamiaceae under subfamily Nepetoideae found in Manipur, India were selected for estimation of their polyphenolic compounds and free radical scavenging activity which is expressed on dry weight basis. In this present study, the total phenol and flavonoid contents as well as the free radical scavenging activity were studied using spectrophotometric method. The total phenol content was determined based on Folin-Ciocalteau reagent, flavonoid was determined by aluminium chloride spectrophotometric method and tannin by Folin Dennis Method. The free radical scavenging activity was determined by using DPPH radical which is expressed as IC50 (μg/ml. The total phenolic content varied from 21.39±0.927 to 46.28±0.543 mg/g, flavonoids content in the selected samples varied from 13.30±0.684 to 26.03±0.217 mg/g and tannin content varied from 8.72±0.160 to 17.04±0.206 mg/g. The free radical scavenging activity among the selected samples varied from 11.67±0.221 to 38.29±0.532 μg/ml. The correlation between the free radical scavenging activity with total phenol content (R2=0.511, with flavonoids (R2=0.241 and with tannin (R2=0.690 was calculated and maximum correlation value was found between tannin content and the free radical scavenging activity of the plant samples. The result supports that tannins were more responsible for free radical scavenging activity in the presently selected plants.

  13. Class 1 Areas

    Data.gov (United States)

    U.S. Environmental Protection Agency — A "Class 1" area is a geographic area recognized by the EPA as being of the highest environmental quality and requiring maximum protection. Class I areas are areas...

  14. PRCR Classes and Activities

    Data.gov (United States)

    Town of Cary, North Carolina — This data is specific to Parks and Recreation classes, workshops, and activities within the course catalog. It contains an entry for upcoming classes.*This data set...

  15. Suvorexant: The first orexin receptor antagonist to treat insomnia

    OpenAIRE

    Dubey, Ashok K.; Handu, Shailendra S.; Mediratta, Pramod K.

    2015-01-01

    Primary insomnia is mainly treated with drugs acting on benzodiazepine receptors and a few other classes of drugs used for different co-morbidities. A novel approach to treat insomnia has been introduced recently, with the approval of suvorexant, the first in a new class of orexin receptor antagonists. Orexin receptors in the brain have been found to play an important role in the regulation of various aspects of arousal and motivation. The drugs commonly used for insomnia therapy to date, hav...

  16. A multistep continuous-flow system for rapid on-demand synthesis of receptor ligands

    DEFF Research Database (Denmark)

    Petersen, Trine P; Ritzén, Andreas; Ulven, Trond

    2009-01-01

    A multistep continuous-flow system for synthesis of receptor ligands by assembly of three variable building blocks in a single unbroken flow is described. The sequence consists of three reactions and two scavenger steps, where a Cbz-protected diamine is reacted with an isocyanate, deprotected, an......, and reacted further with an alkylating agent....

  17. Class Notes for "Class-Y-News."

    Science.gov (United States)

    Stuart, Judy L.

    1991-01-01

    A self-contained class of students with mild to moderate disabilities published a monthly newsletter which was distributed to students' families. Students became involved in writing, typing, drawing, folding, basic editing, and disseminating. (JDD)

  18. Classed identities in adolescence

    OpenAIRE

    Jay, Sarah

    2015-01-01

    peer-reviewed The central argument of this thesis is that social class remains a persistent system of inequality in education, health, life chances and opportunities. Therefore class matters. But why is it that so little attention has been paid to class in the psychological literature? Three papers are presented here which draw together theoretical advances in psychological understandings of group processes and sociological understandings of the complexity of class. As western labour marke...

  19. Receptor complementation and mutagenesis reveal SR-BI as an essential HCV entry factor and functionally imply its intra- and extra-cellular domains.

    Directory of Open Access Journals (Sweden)

    Marlène Dreux

    2009-02-01

    Full Text Available HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI, a major receptor of high-density lipoprotein (HDL, the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection.

  20. A Broad G Protein-Coupled Receptor Internalization Assay that Combines SNAP-Tag Labeling, Diffusion-Enhanced Resonance Energy Transfer, and a Highly Emissive Terbium Cryptate.

    Science.gov (United States)

    Levoye, Angélique; Zwier, Jurriaan M; Jaracz-Ros, Agnieszka; Klipfel, Laurence; Cottet, Martin; Maurel, Damien; Bdioui, Sara; Balabanian, Karl; Prézeau, Laurent; Trinquet, Eric; Durroux, Thierry; Bachelerie, Françoise

    2015-01-01

    Although G protein-coupled receptor (GPCR) internalization has long been considered as a major aspect of the desensitization process that tunes ligand responsiveness, internalization is also involved in receptor resensitization and signaling, as well as the ligand scavenging function of some atypical receptors. Internalization thus contributes to the diversity of GPCR-dependent signaling, and its dynamics and quantification in living cells has generated considerable interest. We developed a robust and sensitive assay to follow and quantify ligand-induced and constitutive-induced GPCR internalization but also receptor recycling in living cells. This assay is based on diffusion-enhanced resonance energy transfer (DERET) between cell surface GPCRs labeled with a luminescent terbium cryptate donor and a fluorescein acceptor present in the culture medium. GPCR internalization results in a quantifiable reduction of energy transfer. This method yields a high signal-to-noise ratio due to time-resolved measurements. For various GPCRs belonging to different classes, we demonstrated that constitutive and ligand-induced internalization could be monitored as a function of time and ligand concentration, thus allowing accurate quantitative determination of kinetics of receptor internalization but also half-maximal effective or inhibitory concentrations of compounds. In addition to its selectivity and sensitivity, we provided evidence that DERET-based internalization assay is particularly suitable for characterizing biased ligands. Furthermore, the determination of a Z'-factor value of 0.45 indicates the quality and suitability of DERET-based internalization assay for high-throughput screening (HTS) of compounds that may modulate GPCRs internalization.

  1. A broad G protein-coupled receptor internalization assay that combines SNAP-tag labeling, diffusion-enhanced resonance energy transfer, and a highly emissive terbium cryptate acceptor

    Directory of Open Access Journals (Sweden)

    Angélique eLEVOYE

    2015-11-01

    Full Text Available Although G protein-coupled receptor (GPCR internalization has long been considered a major aspect of the desensitization process that tunes ligand responsiveness, internalization is also involved in receptor resensitization and signaling, as well as the ligand scavenging function of some atypical receptors. Internalization thus contributes to the diversity of GPCR-dependent signaling, and its dynamics and quantification in living cells has generated considerable interest. We developed a robust and sensitive assay to follow and quantify ligand-induced and constitutive GPCR internalization but also receptor recycling in living cells. This assay is based on diffusion-enhanced resonance energy transfer (DERET between cell surface GPCRs labeled with a luminescent terbium cryptate donor and a fluorescein acceptor present in the culture medium. GPCR internalization results in a quantifiable reduction of energy transfer. This method yields a high signal-to-noise ratio due to time-resolved measurements. For various GPCRs belonging to different classes, we demonstrated that constitutive and ligand-induced internalization could be monitored as a function of time and ligand concentration, thus allowing accurate quantitative determination of kinetics of receptor internalization but also half-maximal effective or inhibitory concentrations of compounds. In addition to its selectivity and sensitivity, we provided evidence that DERET-based internalization assay is particularly suitable for characterizing biased ligands. Furthermore, the determination of a Z’-factor value of 0.45 indicates the quality and suitability of DERET-based internalization assay for high-throughput screening (HTS of compounds that may modulate GPCRs internalization.

  2. Modelling the effect of boundary scavenging on Thorium and Protactinium profiles in the ocean

    Directory of Open Access Journals (Sweden)

    M. Roy-Barman

    2009-12-01

    Full Text Available The "boundary scavenging" box model is a cornerstone of our understanding of the particle-reactive radionuclide fluxes between the open ocean and the ocean margins. However, it does not describe the radionuclide profiles in the water column. Here, I present the transport-reaction equations for radionuclides transported vertically by reversible scavenging on settling particles and laterally by horizontal currents between the margin and the open ocean. Analytical solutions of these equations are compared with existing data. In the Pacific Ocean, the model produces "almost" linear 230Th profiles (as observed in the data despite lateral transport. However, omitting lateral transport biaises the 230Th based particle flux estimates by as much as 50%. 231Pa profiles are well reproduced in the whole water column of the Pacific Margin and from the surface down to 3000 m in the Pacific subtropical gyre. Enhanced bottom scavenging or inflow of 231Pa-poor equatorial water may account for the model-data discrepancy below 3000 m. The lithogenic 232Th is modelled using the same transport parameters as 230Th but a different source function. The main source of the 232Th scavenged in the open Pacific is advection from the ocean margin, whereas a net flux of 230Th produced in the open Pacific is advected and scavenged at the margin, illustrating boundary exchange. In the Arctic Ocean, the model reproduces 230Th measured profiles that the uni-dimensional scavenging model or the scavenging-ventilation model failed to explain. Moreover, if lateral transport is ignored, the 230Th based particle settling speed may by underestimated by a factor 4 at the Arctic Ocean margin. The very low scavenging rate in the open Arctic Ocean combined with the enhanced scavenging at the margin accounts for the lack of high 231Pa/230Th ratio in arctic

  3. Development of nitroxide radicals–containing polymer for scavenging reactive oxygen species from cigarette smoke

    International Nuclear Information System (INIS)

    Yoshitomi, Toru; Kuramochi, Kazuhiro; Binh Vong, Long; Nagasaki, Yukio

    2014-01-01

    We developed a nitroxide radicals–containing polymer (NRP), which is composed of poly(4-methylstyrene) possessing nitroxide radicals as a side chain via amine linkage, to scavenge reactive oxygen species (ROS) from cigarette smoke. In this study, the NRP was coated onto cigarette filters and its ROS-scavenging activity from streaming cigarette smoke was evaluated. The intensity of electron spin resonance signals of the NRP in the filter decreased after exposure to cigarette smoke, indicating consumption of nitroxide radicals. To evaluate the ROS-scavenging activity of the NRP-coated filter, the amount of peroxy radicals in an extract of cigarette smoke was measured using UV–visible spectrophotometry and 1,1-diphenyl-2-picrylhydrazyl (DPPH). The absorbance of DPPH at 517 nm decreased with exposure to cigarette smoke. When NRP-coated filters were used, the decrease in the absorbance of DPPH was prevented. In contrast, both poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters, which have no nitroxide radical, did not show any effect, indicating that the nitroxide radicals in the NRP scavenge the ROS in cigarette smoke. As a result, the extract of cigarette smoke passed through the NRP-coated filter has a lower cellular toxicity than smoke passed through poly[4-(cyclohexylamino)methylstyrene]- and poly(acrylic acid)-coated filters. Accordingly, NRP is a promising material for ROS scavenging from cigarette smoke. (papers)

  4. Scavenging capacity of strawberry tree (Arbutus unedo L.) leaves on free radicals.

    Science.gov (United States)

    Oliveira, Ivo; Coelho, Valentim; Baltasar, Raquel; Pereira, José Alberto; Baptista, Paula

    2009-07-01

    Despite strawberry tree (Arbutus unedo L.) leaves had a long use in traditional medicine due to its antiseptic, diuretic, astringent and depurative properties, the potential of their antioxidant activity are still lacking. Our study goals to assess the antioxidant and free radical scavenging potential of water, ethanol, methanol and diethyl ether extracts of A. unedo leaves. Total phenols content was achieved spectrophotometrically using Folin-Ciocalteau reagent with gallic acid as standard. Antioxidant activity was evaluated using three different methods: reducing power of iron (III)/ferricyanide complex assay, scavenging effect on DPPH (2,2-diphenyl-1-picrylhydrazyl) radicals and scavenging effect on superoxide radicals by using the PMS-NADH-nitroblue tetrazolium system. Ethanol extracts of A. unedo leaves were the highest in reducing power (IC(50) 232.7 microg/mL) and DPPH scavenging effect (IC(50) 63.2 microg/mL) followed by water extracts (with IC(50) of 287.7 and 73.7 microg/mL, respectively); whereas diethyl ether extracts were the lowest. In the scavenging on superoxide radical assay, methanol extracts obtained the best results (IC(50) 6.9 microg/mL). For all the methods tested the antioxidant activity was concentration dependent. In accordance with antioxidant activity, highest total phenols content were found in ethanol, followed by water, methanol and diethyl ether extract. The results indicated that A. unedo leaves are a potential source of natural antioxidants.

  5. Invertebrates outcompete vertebrate facultative scavengers in simulated lynx kills in the Bavarian Forest National Park, Germany

    Directory of Open Access Journals (Sweden)

    Ray, R.–R.

    2014-06-01

    Full Text Available Understanding the role of scavengers in ecosystems is important for species conservation and wildlife management. We used road–killed animals, 15 in summer 2003 (June–August and nine in winter 2003/2004 (from November to January, to test the following hypotheses: (1 vertebrate scavengers such as raven (Corvus corax, red fox (Vulpes vulpes and wild boar (Sus scrofa consume a higher proportion of the carcasses than invertebrates; (2 the consumption rate is higher in winter than in summer due to the scarcity of other food resources; and (3 vertebrate scavengers are effective competitors of Eurasian lynx. We monitored 65 animals belonging to eight different mammal and bird species with camera traps. Surprisingly, Eurasian lynx (Lynx lynx was the most important vertebrate scavenger. However, in both seasons, the consumption of vertebrate scavengers was of minor impact. In summer, the carcasses were completely consumed within 10 days, mostly by invertebrates. In winter, only 5% of the carcasses were consumed within 10 days and 16% within 15 days. We conclude that vertebrates in the Bavarian Forest National Park are not strong competitors for lynx.

  6. Low frequency energy scavenging using sub-wave length scale acousto-elastic metamaterial

    Directory of Open Access Journals (Sweden)

    Riaz U. Ahmed

    2014-11-01

    Full Text Available This letter presents the possibility of energy scavenging (ES utilizing the physics of acousto-elastic metamaterial (AEMM at low frequencies (<∼3KHz. It is proposed to use the AEMM in a dual mode (Acoustic Filter and Energy Harvester, simultaneously. AEMM’s are typically reported for filtering acoustic waves by trapping or guiding the acoustic energy, whereas this letter shows that the dynamic energy trapped inside the soft constituent (matrix of metamaterials can be significantly harvested by strategically embedding piezoelectric wafers in the matrix. With unit cell AEMM model, we experimentally asserted that at lower acoustic frequencies (< ∼3 KHz, maximum power in the micro Watts (∼35µW range can be generated, whereas, recently reported phononic crystal based metamaterials harvested only nano Watt (∼30nW power against 10KΩ resistive load. Efficient energy scavengers at low acoustic frequencies are almost absent due to large required size relevant to the acoustic wavelength. Here we report sub wave length scale energy scavengers utilizing the coupled physics of local, structural and matrix resonances. Upon validation of the argument through analytical, numerical and experimental studies, a multi-frequency energy scavenger (ES with multi-cell model is designed with varying geometrical properties capable of scavenging energy (power output from ∼10µW – ∼90µW between 0.2 KHz and 1.5 KHz acoustic frequencies.

  7. Free radical scavenging and COX-2 inhibition by simple colon metabolites of polyphenols: A theoretical approach.

    Science.gov (United States)

    Amić, Ana; Marković, Zoran; Marković, Jasmina M Dimitrić; Jeremić, Svetlana; Lučić, Bono; Amić, Dragan

    2016-12-01

    Free radical scavenging and inhibitory potency against cyclooxygenase-2 (COX-2) by two abundant colon metabolites of polyphenols, i.e., 3-hydroxyphenylacetic acid (3-HPAA) and 4-hydroxyphenylpropionic acid (4-HPPA) were theoretically studied. Different free radical scavenging mechanisms are investigated in water and pentyl ethanoate as a solvent. By considering electronic properties of scavenged free radicals, hydrogen atom transfer (HAT) and sequential proton loss electron transfer (SPLET) mechanisms are found to be thermodynamically probable and competitive processes in both media. The Gibbs free energy change for reaction of inactivation of free radicals indicates 3-HPAA and 4-HPPA as potent scavengers. Their reactivity toward free radicals was predicted to decrease as follows: hydroxyl>alkoxyls>phenoxyl≈peroxyls>superoxide. Shown free radical scavenging potency of 3-HPAA and 4-HPPA along with their high μM concentration produced by microbial colon degradation of polyphenols could enable at least in situ inactivation of free radicals. Docking analysis with structural forms of 3-HPAA and 4-HPPA indicates dianionic ligands as potent inhibitors of COX-2, an inducible enzyme involved in colon carcinogenesis. Obtained results suggest that suppressing levels of free radicals and COX-2 could be achieved by 3-HPAA and 4-HPPA indicating that these compounds may contribute to reduced risk of colon cancer development. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. [In vitro anti-inflammatory and free radical scavenging activities of flavans from Ilex centrochinensis].

    Science.gov (United States)

    Li, Lu-jun; Yu, Li-juan; Li, Yan-ci; Liu, Meng-yuan; Wu, Zheng-zhi

    2015-04-01

    This study was carried out to evaluate the anti-inflammatory and free radical scavenging activities of flavans from flex centrochinensis S. Y. Hu in vitro and their structure-activity relationship. LPS-stimulated RAW 264.7 macrophage was used as inflammatory model. MTT assay for cell availability, Griess reaction for nitric oxide (NO) production, the content of TNF-alpha, IL-1beta, IL-6 and PGE, were detected with ELISA kits; DPPH, superoxide anion and hydroxyl free radicals scavenging activities were also investigated. According to the result, all flavans tested exhibited anti-inflammatory effect in different levels. Among them, compounds 1, 3, 4 and 6 showed potent anti-inflammatory effect through the inhibition of NO, TNF-alpha, IL-lp and IL-6, of which 1 was the most effective inhibitor, however, 2 and 5 were relatively weak or inactive. The order of free radical scavenging activities was similar to that of anti-inflammatory activities. Therefore, these results suggest that 3, 4 and 6, especially of 1, were,in part responsible for the anti-inflammatory and free radical scavenging activity of Ilex centrochinensis. Hydroxyl group at 4'-position of B-ring plays an important role in the anti-inflammatory and free radical scavenging capacities.

  9. Free radical scavenging window of infertile patients with polycystic ovary syndrome: correlation with embryo quality.

    Science.gov (United States)

    Huang, Bo; Li, Zhou; Ren, Xinling; Ai, Jihui; Zhu, Lixia; Jin, Lei

    2017-06-01

    The activity of free radicals in follicular fluid was related to ovarian responsiveness, in vitro fertilization (IVF), and embryo transfer success rate. However, studies analyzing the relationship between the free radical scavenging capacity and embryo quality of infertile women with polycystic ovarian syndrome (PCOS) were lacking. The aim of this study was to evaluate the relationship between the free radical scavenging window of women with PCOS and their embryo quality. The free radical scavenging capacity of follicular fluid from women with PCOS was determined by a,a-diphenyl-b-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay, superoxide radical, and reactive oxygen species (ROS) assay. In the DPPH and ROS assays, the follicular fluid from grades I and II embryos was significantly higher than the follicular fluid from grades III and IVembryos. The lower control limit of DPPH radical scavenging capacity and upper control limit of ROS level were 13.2% and 109.0 cps, respectively. The calculated lower control limit and upper control limit were further confirmed in the follicular fluid of embryos of all grades. These cut-off values of free radical scavenging activity of follicular fluid could assist embryologists in choosing the development of embryos in PCOS patients undergoing IVF.

  10. Environment, urban poverty and scavenging: review of relationship and its effectiveness

    International Nuclear Information System (INIS)

    Chamhuri Siwar; Amzad Hossain; Norshamleeda Chamhuri

    2001-01-01

    Urban poverty and environment is interrelated to each other. Environmental degradation is a crucial factor for urban poverty and vice-versa. The generation of solid waste all over the world has reached an alarming proportion and constitutes one of the world's greatest sources of environmental degradation (fagan, 1974). Solid waste is one of the three major environmental problems faced by municipalities in Malaysia (World Bank, 1993) which is one of the major cause or contributor to urban poverty. However, urban solid waste consists of two strata such as source of environmental degradation and income generating agents for urban poor scavengers. In Malaysia, full-time and part-time scavengers are recycling 6% of total generated residential solid waste in some selected areas other wise its emitted or disposed to the environment. On the other hand, by doing this work full-time scavengers are earning wages of RM750 per month which is equal to that of the majority of Third world urbanities; part-time scavengers are earning 33% of their daily income. This paper discusses a theoretical framework of the relationship of environment and urban poverty. Policies, issues and some case studies of scavenging as a means of urban poverty reduction and environmental improvements of sustainable urban development are also explored. (Author)

  11. Free radical scavenging potential and HPTLC analysis of Indigofera tinctoria linn (Fabaceae

    Directory of Open Access Journals (Sweden)

    Sakthivel Srinivasan

    2016-04-01

    Full Text Available The objective of this study was to evaluate the free radical scavenging potential and high performance thin layer chromatography (HPTLC fingerprinting of Indigofera tinctoria (I. tinctoria. Phytochemical analysis was carried out using standard methods, and free radical scavenging activity of the plant was determined using 2,2-diphenyl-1-picrylhydrazy (DPPH, nitric oxide (NO and superoxide anion (O2− radical scavenging capacities. HPTLC plate was kept in CAMAG TLC Scanner 3 and the Rf values at fingerprint data were recorded by WINCATS software. Aqueous extract of I. tinctoria reliably showed the total phenolics (267.2±2.42 mg/g, flavonoids (75.43±3.36 mg/g and antioxidants (349.11±8.04 mg/g. The extract was found to have DPPH (52.08%, NO (23.12% and O2− (26.79% scavenging activities at the concentration of 250 μg/mL and the results were statistically significant compared with ascorbic acid standard (p<0.05. HPTLC results confirmed that the extract contained several potential active components such as phenols, flavonoids, saponins and terpenoids as the slides revealed multi-colored bands of varying intensities. This study confirmed that the plant had multipotential antioxidant and free radicals scavenging activities.

  12. Multi-dimensional scavenging analysis of a free-piston linear alternator based on numerical simulation

    Energy Technology Data Exchange (ETDEWEB)

    Mao, Jinlong; Zuo, Zhengxing; Li, Wen; Feng, Huihua [School of Mechanical Engineering, Beijing Institute of Technology, Beijing 100081 (China)

    2011-04-15

    A free-piston linear alternator (FPLA) is being developed by the Beijing Institute of Technology to improve the thermal efficiency relative to conventional crank-driven engines. A two-stroke scavenging process recharges the engine and is crucial to realizing the continuous operation of a free-piston engine. In order to study the FPLA scavenging process, the scavenging system was configured using computational fluid dynamics. As the piston dynamics of the FPLA are different to conventional crank-driven two-stroke engines, a time-based numerical simulation program was built using Matlab to define the piston's motion profiles. A wide range of design and operating options were investigated including effective stroke length, valve overlapping distance, operating frequency and charging pressure to find out their effects on the scavenging performance. The results indicate that a combination of high effective stroke length to bore ratio and long valve overlapping distance with a low supercharging pressure has the potential to achieve high scavenging and trapping efficiencies with low short-circuiting losses. (author)

  13. Investigation of the chemistry of liquid H{sub 2}S scavengers

    Energy Technology Data Exchange (ETDEWEB)

    Buhaug, Janne Bjoerntvedt

    2002-07-01

    The production of natural gas in the North Sea is facing a growing problem: contamination of the natural gas with dihydrogen sulfide, H{sub 2}S. As a gas reservoir is emptied, seawater containing sulfates is pumped into it, and the sulfates are reduced to dihydrogen sulfide by sulfate-reducing bacteria. Dihydrogen sulfide is then pumped up along with the oil, gas and water from the reservoir, causing severe corrosion of pipelines and contamination of the final natural gas product. Dihydrogen sulfide is extremely toxic, and in fields with especially large concentrations of H{sub 2}S this is a severe health risk for the platform workers. Hence, it is desirable to remove the dihydrogen sulfide at the earliest stage possible. There are four main methods for removing H{sub 2}S from natural gas: (1) Liquid scavengers, (2) Solid scavengers, (3) Liquid redox processes, (4) Amine / Claus catalyst. Liquid scavengers are widely used in the natural gas industry, especially at sites with relatively low concentrations of H{sub 2}S. As a rule of thumb, liquid scavengers are economically favourable at sites with a removal of less than 50 kg/day of H{sub 2}S. This thesis is concerned with the cyclic amine 1,3,5 -tris(2-hydroxyethyl)-1,3,5-triazinane, often referred to as Triazine. This is used in fields with relatively low concentration of H{sub 2}S and dominates the liquid scavenger market.

  14. Demonstration of physical phenomenas and scavenging activity from d-psicose and methionine maillard reaction products

    Directory of Open Access Journals (Sweden)

    Arum Tiyas Suminar

    2017-01-01

    Full Text Available Maillard reaction has been well understood as a non-enzymatic reaction between reducing sugars and amino acids to generate the Maillard reaction products (MRPs. This study is aimed to demonstrate the browning intensity, color development, spectra measurements, scavenging activity, and the correlation between browning intensity and scavenging activity of the MRPs generated from D-Psicose and Methionine (Psi-Met at 50℃. The browning intensity of MRPs was investigated based on the absorbance using spectrophotometer at 420 nm, the color development was observed using digital colorimeter to gained L*a*b* value then calculated as browning index, the spectra development was analyzed using spectrophotometer at 190 - 750 nm, and the scavenging activity was determined with ABTS method using spectrophotometer at 734 nm. The browning intensity, color development, and scavenging activity were improved along with the increase in heating process. Based on spectra analysis, MRPs from Psi-Met was initially detected at 21 h and Psi at 24 h of heating treatment, which indicating that Psi-Met have faster and better reaction than Psi during heating process. Positive non-linear and significant correlation between browning intensity and scavenging activity were assigned. This finding may provide beneficial information of D-psicose and MRPs to the next scientific research and to the food industries which applies MRPs in their products.

  15. Increasing land-use intensity reverses the relative occupancy of two quadrupedal scavengers.

    Directory of Open Access Journals (Sweden)

    Joshua P Twining

    Full Text Available Human land use is continuously altering the natural environment, yet the greater ecological implications of this change for many groups that are key to healthy ecosystem functioning remains uncharacterised in the tropics. Terrestrial scavenging vertebrates are one such group, providing integral ecosystem services through the removal of carrion which is a crucial component of both nutrient cycling and disease dynamics. To explore how anthropogenic processes may affect forest scavengers, we investigated the changes in the relative occupancy of two important terrestrial scavengers along a gradient of land use intensity, ranging from protected forest to oil palm plantation in Borneo. We found the Malay civet (Viverra tangalunga had highest, albeit variable, occupancy in areas of low land use intensity and the Southeast Asian water monitor (Varanus salvator macromaculatus had highest occupancy in areas of high land use intensity. Land use had no effect on the combined occupancy of the two species. In high land use intensity sites, individual water monitors were larger and had better body condition, but at population level had a highly biased sex ratio with more males than females and increased signs of intraspecific conflict. We did not assess scavenging rate or efficiency as a process, but the high occupancy rates and apparent health of the scavengers in high land use intensity landscapes suggests this ecological process is robust to land use change.

  16. Changes in free-radical scavenging ability of kombucha tea during fermentation.

    Science.gov (United States)

    Jayabalan, R; Subathradevi, P; Marimuthu, S; Sathishkumar, M; Swaminathan, K

    2008-07-01

    Kombucha tea is a fermented tea beverage produced by fermenting sugared black tea with tea fungus (kombucha). Free-radical scavenging abilities of kombucha tea prepared from green tea (GTK), black tea (BTK) and tea waste material (TWK) along with pH, phenolic compounds and reducing power were investigated during fermentation period. Phenolic compounds, scavenging activity on DPPH radical, superoxide radical (xanthine-xanthine oxidase system) and inhibitory activity against hydroxyl radical mediated linoleic acid oxidation (ammonium thiocyanate assay) were increased during fermentation period, whereas pH, reducing power, hydroxyl radical scavenging ability (ascorbic acid-iron EDTA) and anti-lipid peroxidation ability (thiobarbituric assay) were decreased. From the present study, it is obvious that there might be some chances of structural modification of components in tea due to enzymes liberated by bacteria and yeast during kombucha fermentation which results in better scavenging performance on nitrogen and superoxide radicals, and poor scavenging performance on hydroxyl radicals. Copyright © 2007 Elsevier Ltd. All rights reserved.

  17. TLX: An elusive receptor.

    Science.gov (United States)

    Benod, Cindy; Villagomez, Rosa; Webb, Paul

    2016-03-01

    TLX (tailless receptor) is a member of the nuclear receptor superfamily and belongs to a class of nuclear receptors for which no endogenous or synthetic ligands have yet been identified. TLX is a promising therapeutic target in neurological disorders and brain tumors. Thus, regulatory ligands for TLX need to be identified to complete the validation of TLX as a useful target and would serve as chemical probes to pursue the study of this receptor in disease models. It has recently been proved that TLX is druggable. However, to identify potent and specific TLX ligands with desirable biological activity, a deeper understanding of where ligands bind, how they alter TLX conformation and of the mechanism by which TLX mediates the transcription of its target genes is needed. While TLX is in the process of escaping from orphanhood, future ligand design needs to progress in parallel with improved understanding of (i) the binding cavity or surfaces to target with small molecules on the TLX ligand binding domain and (ii) the nature of the TLX coregulators in particular cell and disease contexts. Both of these topics are discussed in this review. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Loosely coupled class families

    DEFF Research Database (Denmark)

    Ernst, Erik

    2001-01-01

    are expressed using virtual classes seem to be very tightly coupled internally. While clients have achieved the freedom to dynamically use one or the other family, it seems that any given family contains a xed set of classes and we will need to create an entire family of its own just in order to replace one...... of the members with another class. This paper shows how to express class families in such a manner that the classes in these families can be used in many dierent combinations, still enabling family polymorphism and ensuring type safety....

  19. In vitro free radical scavenging activity of ethanolic extract of the whole plant of Evolvulus alsinoides (L.) L.

    Science.gov (United States)

    Gomathi, Duraisamy; Ravikumar, Ganesan; Kalaiselvi, Manokaran; Vidya, Balasubramaniam; Uma, Chandrasekar

    2015-06-01

    To identify the free radical scavenging activity of ethanolic extract of Evolvulus alsinoides. The free radical scavenging activity was evaluated by in vitro methods like reducing power assay, total antioxidant activity, 2,2-diphenyl-1-picrylhydrazyl (DPPH) reduction, superoxide radical scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+)) scavenging activity, hydroxyl radical scavenging assay, and nitric oxide radical scavenging assay, which were studied by using ascorbic acid as standard. The extract showed significant activities in all antioxidant assays compared with the reference antioxidant ascorbic acid. The total antioxidant activity as well as the reducing power was also found to increase in a dose-dependent manner. Evolvulus alsinoides may act as a chemopreventive agent, providing antioxidant properties and offering effective protection from free radicals.

  20. The WSXWS motif in cytokine receptors is a molecular switch involved in receptor activation

    DEFF Research Database (Denmark)

    Dagil, Robert; Knudsen, Maiken J.; Olsen, Johan Gotthardt

    2012-01-01

    The prolactin receptor (PRLR) is activated by binding of prolactin in a 2:1 complex, but the activation mechanism is poorly understood. PRLR has a conserved WSXWS motif generic to cytokine class I receptors. We have determined the nuclear magnetic resonance solution structure of the membrane...

  1. Scavenging of peroxynitrite by phycocyanin and phycocyanobilin from Spirulina platensis: protection against oxidative damage to DNA.

    Science.gov (United States)

    Bhat, V B; Madyastha, K M

    2001-07-13

    Peroxynitrite (ONOO(-)) is known to inactivate important cellular targets and also mediate oxidative damage in DNA. The present study has demonstrated that phycocyanin, a biliprotein from spirulina platensis and its chromophore, phycocyanobilin (PCB), efficiently scavenge ONOO(-), a potent physiological inorganic toxin. Scavenging of ONOO(-) by phycocyanin and PCB was established by studying their interaction with ONOO(-) and quantified by using competition kinetics of pyrogallol red bleaching assay. The relative antioxidant ratio and IC(50) value clearly indicate that phycocyanin is a more efficient ONOO(-) scavenger than PCB. The present study has also shown that PCB significantly inhibits the ONOO(-)-mediated single-strand breaks in supercoiled plasmid DNA in a dose-dependent manner with an IC(50) value of 2.9 +/- 0.6 microM. These results suggest that phycocyanin, has the ability to inhibit the ONOO(-)-mediated deleterious biological effects and hence has the potential to be used as a therapeutic agent. Copyright 2001 Academic Press.

  2. Trypsin Binding with Copper Ions Scavenges Superoxide: Molecular Dynamics-Based Mechanism Investigation

    Directory of Open Access Journals (Sweden)

    Xin Li

    2018-01-01

    Full Text Available Trypsin is a serine protease, which has been proved to be a novel superoxide scavenger. The burst of superoxide induced by polychlorinated biphenyls can be impeded by trypsin in both wild type and sod knockout mutants of Escherichia coli. The experimental results demonstrated that the activities of superoxide scavenging of trypsin were significantly accelerated by Cu ions. Also, with the addition of Cu ions, a new β-sheet (β7 transited from a random coil in the Cu(II-trypsin (TP system, which was favorable for the formation of more contacts with other sheets of trypsin. Residue–residue network analysis and the porcupine plots proved that the Cu ion in trypsin strengthened some native interactions among residues, which ultimately resulted in much greater stability of the Cu(II-TP system. Moreover, compact and stable trypsin structures with Cu ions might be responsible for significantly provoking the activity of superoxide scavenging.

  3. The salivary scavenger and agglutinin (SALSA binds MBL and regulates the lectin pathway of complement in solution and on surfaces

    Directory of Open Access Journals (Sweden)

    Martin eParnov Reichhardt

    2012-07-01

    Full Text Available The scavenger receptor cysteine-rich (SRCR protein SALSA, also known as gp340, salivary agglutinin (SAG and deleted in malignant brain tumor 1 (DMBT1, is a 340 kDa glycoprotein expressed on mucosal surfaces and secreted into several body fluids. SALSA binds to a broad variety of microbes and endogenous ligands, such as complement factor C1q, surfactant proteins D and A (SP-D and SP-A and IgA. Our search for novel ligands of SALSA by direct protein-interaction studies led to the identification of mannan binding lectin (MBL as a new binding partner. We observed that surface-associated SALSA activates complement via binding of MBL. On the other hand, soluble SALSA was found to inhibit C. albicans-induced complement activation. Thus, SALSA has a dual complement regulatory function. It activates the lectin pathway when bound to a surface and inhibits it when free in the fluid-phase. These activities are mediated via a direct interaction with MBL.

  4. Expression of scavenger receptor‐AI promotes alternative activation of murine macrophages to limit hepatic inflammation and fibrosis

    Science.gov (United States)

    Labonte, Adam C.; Sung, Sun‐Sang J.; Jennelle, Lucas T.; Dandekar, Aditya P.

    2016-01-01

    The liver maintains an immunologically tolerant environment as a result of continuous exposure to food and bacterial constituents from the digestive tract. Hepatotropic pathogens can take advantage of this niche and establish lifelong chronic infections causing hepatic fibrosis and hepatocellular carcinoma. Macrophages (Mϕ) play a critical role in regulation of immune responses to hepatic infection and regeneration of tissue. However, the factors crucial for Mϕ in limiting hepatic inflammation or resolving liver damage have not been fully understood. In this report, we demonstrate that expression of C‐type lectin receptor scavenger receptor‐AI (SR‐AI) is crucial for promoting M2‐like Mϕ activation and polarization during hepatic inflammation. Liver Mϕ uniquely up‐regulated SR‐AI during hepatotropic viral infection and displayed increased expression of alternative Mϕ activation markers, such as YM‐1, arginase‐1, and interleukin‐10 by activation of mer receptor tyrosine kinase associated with inhibition of mammalian target of rapamycin. Expression of these molecules was reduced on Mϕ obtained from livers of infected mice deficient for the gene encoding SR‐AI (msr1). Furthermore, in vitro studies using an SR‐AI‐deficient Mϕ cell line revealed impeded M2 polarization and decreased phagocytic capacity. Direct stimulation with virus was sufficient to activate M2 gene expression in the wild‐type (WT) cell line, but not in the knockdown cell line. Importantly, tissue damage and fibrosis were exacerbated in SR‐AI–/– mice following hepatic infection and adoptive transfer of WT bone‐marrow–derived Mϕ conferred protection against fibrosis in these mice. Conclusion: SR‐AI expression on liver Mϕ promotes recovery from infection‐induced tissue damage by mediating a switch to a proresolving Mϕ polarization state. (Hepatology 2017;65:32‐43). PMID:27770558

  5. Tourism in protected areas: Disentangling road and traffic effects on intra-guild scavenging processes.

    Science.gov (United States)

    Donázar, José Antonio; Ceballos, Olga; Cortés-Avizanda, Ainara

    2018-07-15

    The expansion of road networks and the increase in traffic have emerged in recent years as key threats to the conservation of biodiversity. This is particularly concerning in many protected areas because the increase of recreational activities requiring the use of vehicles. Effects of roads and traffic within guild scenarios and ecological processes remain however poorly known. Here we examined how road proximity and traffic intensity influence patterns of resource use in an Old-World avian scavenger guild living in a protected natural park in northern Spain. We experimentally placed 130 carcasses at different distances from a scenic road in the centre of the park. Vehicles were recorded by means of traffic counters which revealed that maximum numbers were reached during weekends and holidays and during the middle hours of the day. Avian scavenger attendance at carcasses was recorded by means of camera-traps. Obligated scavengers, Eurasian griffon (Gyps fulvus) and Egyptian vultures (Neophron percnopterus) were frequently observed (59.4% and 37.7% of the consumed carcasses) together with five other facultative scavenger species. We found that the richness (number of species) and the probability of consumption of the resource were reduced the smaller the distance to the road and in days with higher traffic intensity. The same factors affected the probability of presence of all the scavenger species. Moreover, some of them, notably griffon vultures, showed hourly patterns of carcass attendance suggesting avoidance of maximum traffic levels. Our results highlight that roads and traffic would trigger consequences on the structure and functioning of scavenger food webs, which may be particularly concerning in protected areas with remarkable levels of biodiversity. Future regulations at protected areas should couple both traffic and tourist affluence with wildlife conservation. In this way important ecological processes would be preserved while maintaining a good

  6. The scavenging of volatile anesthetic agents in the cardiovascular intensive care unit environment: a technical report.

    Science.gov (United States)

    Pickworth, Thomas; Jerath, Angela; DeVine, Rita; Kherani, Nazmin; Wąsowicz, Marcin

    2013-01-01

    The use of volatile-based sedation within critical care environments has been limited by difficulties of drug administration and safety concerns over environment pollution and staff exposure in an intensive care unit (ICU) with no scavenging. The aim of this study was to develop a simple scavenging system to be used with the Anesthesia Conserving Device (AnaConDa(®)) and to determine whether or not ambient concentrations of residual anesthetic are within current acceptable limits. The scavenging system consists of two Deltasorb(®) canisters attached to the ICU ventilator in series. AnaConDa is a miniature vaporizer designed to provide volatile-based sedation within an ICU. The first ten patients recruited into a larger randomized trial assessing outcomes after elective coronary graft bypass surgery were sedated within the cardiac ICU using either isoflurane or sevoflurane. Sedation was guided by the Sedation Agitation Scale, resulting in an end-tidal minimum anesthetic concentration of volatile agent ranging from 0.1-0.3. At one hour post ICU admission, infrared photometric analysis was used to assess environmental contamination at four points along the ventilator circuit and scavenging system and around the patient's head. All measurements taken within the patient's room were below 1 part per million, which satisfies criteria for occupational exposure. This study shows that volatile agents can be administered safely within critical care settings using a simple scavenging system. Our scavenging system used in conjunction with the AnaConDa device reduced the concentration of environmental contamination to a level that is acceptable to Canadian standards and standards in most Western countries and thus conforms to international safety standards. The related clinical trial was registered at www.clinicaltrials.gov (NCT01151254).

  7. Analysis of the Scavenging Process of a Two-Stroke Free-Piston Engine Based on the Selection of Scavenging Ports or Valves

    Directory of Open Access Journals (Sweden)

    Boru Jia

    2018-02-01

    Full Text Available The free-piston engine generator (FPEG is a linear energy conversion device with the objective of utilisation within a hybrid-electric automotive vehicle power system. In this research, the piston dynamic characteristics of an FPEG is compared with that of a conventional engine (CE of the same size, and the difference in the valve timing is compared for both port scavenging type and valve scavenging type, with the exhaust valve closing timing is selected as the parameter. A zero-dimensional simulation model is developed in Ricardo WAVE software (2016.1, with the piston dynamics obtained from the simulation model in Matlab/SIMULINK (R2017a. For the CE and FEPG using scavenging ports, in order to improve its power output to the same level as that of a CE, the inlet gas pressure is suggested to be improved to above 1.2 bar, approximately 0.2 bar higher than that used for a CE. If a CE cylinder with exhaust valves is adopted or referred to during the development of an FPEG prototype, the exhaust valve is suggested to be closed earlier to improve its power output, and a higher intake pressure is also suggested if its output power is expected to be the same or higher than that of a CE.

  8. Cloning the interleukin 1 receptor from human T cells

    International Nuclear Information System (INIS)

    Sims, J.E.; Acres, R.B.; Grubin, C.E.; McMahan, C.J.; Wignall, J.M.; March, C.J.; Dower, S.K.

    1989-01-01

    cDNA clones of the interleukin 1 (IL-1) receptor expressed in a human T-cell clone have been isolated by using a murine IL-1 receptor cDNA as a probe. The human and mouse receptors show a high degree of sequence conservation. Both are integral membrane proteins possessing a single membrane-spanning segment. Similar to the mouse receptor, the human IL-1 receptor contains a large cytoplasmic region and an extracellular, IL-1 binding portion composed of three immunoglobulin-like domains. When transfected into COS cells, the human IL-1 receptor cDNA clone leads to expression of two different affinity classes of receptors, with K a values indistinguishable from those determined for IL-1 receptors in the original T-cell clone. An IL-1 receptor expressed in human dermal fibroblasts has also been cloned and sequenced and found to be identical to the IL-1 receptor expressed in T cells

  9. Turbulent swirling flow in a dynamic model of a uniflow-scavenged two-stroke engine

    DEFF Research Database (Denmark)

    Ingvorsen, Kristian Mark; Meyer, Knud Erik; Walther, Jens Honore

    2014-01-01

    turbulence models. In the present work, the flow in a dynamic scale model of a uniflowscavenged cylinder is investigated experimentally. The model has a transparent cylinder and a moving piston driven by a linear motor. The flow is investigated using phase-locked stereoscopic particle image velocimetry (PIV...... cannot be assumed to be quasi-steady. The temporal development of the swirl strength is investigated by computing the angular momentum. The swirl strength shows an exponential decay from scavenge port closing to scavenge port opening corresponding to a reduction of 34 %, which is in good agreement...

  10. Class, Culture and Politics

    DEFF Research Database (Denmark)

    Harrits, Gitte Sommer

    2013-01-01

    Even though contemporary discussions of class have moved forward towards recognizing a multidimensional concept of class, empirical analyses tend to focus on cultural practices in a rather narrow sense, that is, as practices of cultural consumption or practices of education. As a result......, discussions within political sociology have not yet utilized the merits of a multidimensional conception of class. In light of this, the article suggests a comprehensive Bourdieusian framework for class analysis, integrating culture as both a structural phenomenon co-constitutive of class and as symbolic...... practice. Further, the article explores this theoretical framework in a multiple correspondence analysis of a Danish survey, demonstrating how class and political practices are indeed homologous. However, the analysis also points at several elements of field autonomy, and the concluding discussion...

  11. Class network routing

    Science.gov (United States)

    Bhanot, Gyan [Princeton, NJ; Blumrich, Matthias A [Ridgefield, CT; Chen, Dong [Croton On Hudson, NY; Coteus, Paul W [Yorktown Heights, NY; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Heidelberger, Philip [Cortlandt Manor, NY; Steinmacher-Burow, Burkhard D [Mount Kisco, NY; Takken, Todd E [Mount Kisco, NY; Vranas, Pavlos M [Bedford Hills, NY

    2009-09-08

    Class network routing is implemented in a network such as a computer network comprising a plurality of parallel compute processors at nodes thereof. Class network routing allows a compute processor to broadcast a message to a range (one or more) of other compute processors in the computer network, such as processors in a column or a row. Normally this type of operation requires a separate message to be sent to each processor. With class network routing pursuant to the invention, a single message is sufficient, which generally reduces the total number of messages in the network as well as the latency to do a broadcast. Class network routing is also applied to dense matrix inversion algorithms on distributed memory parallel supercomputers with hardware class function (multicast) capability. This is achieved by exploiting the fact that the communication patterns of dense matrix inversion can be served by hardware class functions, which results in faster execution times.

  12. Culture and social class.

    Science.gov (United States)

    Miyamoto, Yuri

    2017-12-01

    A large body of research in Western cultures has demonstrated the psychological and health effects of social class. This review outlines a cultural psychological approach to social stratification by comparing psychological and health manifestations of social class across Western and East Asian cultures. These comparisons suggest that cultural meaning systems shape how people make meaning and respond to material/structural conditions associated with social class, thereby leading to culturally divergent manifestations of social class. Specifically, unlike their counterparts in Western cultures, individuals of high social class in East Asian cultures tend to show high conformity and other-orientated psychological attributes. In addition, cultures differ in how social class impacts health (i.e. on which bases, through which pathways, and to what extent). Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Semantic Analysis of Virtual Classes and Nested Classes

    DEFF Research Database (Denmark)

    Madsen, Ole Lehrmann

    1999-01-01

    Virtual classes and nested classes are distinguishing features of BETA. Nested classes originated from Simula, but until recently they have not been part of main stream object- oriented languages. C++ has a restricted form of nested classes and they were included in Java 1.1. Virtual classes...... classes and parameterized classes have been made. Although virtual classes and nested classes have been used in BETA for more than a decade, their implementation has not been published. The purpose of this paper is to contribute to the understanding of virtual classes and nested classes by presenting...

  14. Class in disguise

    DEFF Research Database (Denmark)

    Faber, Stine Thidemann; Prieur, Annick

    This paper asks how class can have importance in one of the worlds’ most equal societies: Denmark. The answer is that class here appears in disguised forms. The field under study is a city, Aalborg, in the midst of transition from a stronghold of industrialism to a post industrial economy. The pa....... The paper also raises questions about how sociological discourses may contribute to the veiling of class....

  15. Influences of in-cloud aerosol scavenging parameterizations on aerosol concentrations and wet deposition in ECHAM5-HAM

    Directory of Open Access Journals (Sweden)

    B. Croft

    2010-02-01

    Full Text Available A diagnostic cloud nucleation scavenging scheme, which determines stratiform cloud scavenging ratios for both aerosol mass and number distributions, based on cloud droplet, and ice crystal number concentrations, is introduced into the ECHAM5-HAM global climate model. This scheme is coupled with a size-dependent in-cloud impaction scavenging parameterization for both cloud droplet-aerosol, and ice crystal-aerosol collisions. The aerosol mass scavenged in stratiform clouds is found to be primarily (>90% scavenged by cloud nucleation processes for all aerosol species, except for dust (50%. The aerosol number scavenged is primarily (>90% attributed to impaction. 99% of this impaction scavenging occurs in clouds with temperatures less than 273 K. Sensitivity studies are presented, which compare aerosol concentrations, burdens, and deposition for a variety of in-cloud scavenging approaches: prescribed fractions, a more computationally expensive prognostic aerosol cloud processing treatment, and the new diagnostic scheme, also with modified assumptions about in-cloud impaction and nucleation scavenging. Our results show that while uncertainties in the representation of in-cloud scavenging processes can lead to differences in the range of 20–30% for the predicted annual, global mean aerosol mass burdens, and near to 50% for accumulation mode aerosol number burden, the differences in predicted aerosol mass concentrations can be up to one order of magnitude, particularly for regions of the middle troposphere with temperatures below 273 K where mixed and ice phase clouds exist. Different parameterizations for impaction scavenging changed the predicted global, annual mean number removal attributed to ice clouds by seven-fold, and the global, annual dust mass removal attributed to impaction by two orders of magnitude. Closer agreement with observations of black carbon profiles from aircraft (increases near to one order of magnitude for mixed phase clouds

  16. Consumption of Big Game Remains by Scavengers: A Potential Risk as Regards Disease Transmission in Central Spain

    Directory of Open Access Journals (Sweden)

    Ricardo Carrasco-Garcia

    2018-03-01

    Full Text Available Understanding the role that facultative scavenger species may play in spreading infectious pathogens, and even becoming reservoirs for humans, domestic and wild ungulates or, on the contrary, preventing the spread of disease, requires a prior understanding of the pattern of carrion scavenging in specific scenarios. The objectives of this paper are (i to describe the guild of vertebrate scavengers and (ii to study the species-specific, habitat, and management-related factors involved in the usage of gut piles in South Central Spain (SCS, a tuberculosis (TB endemic area. We used camera trapping at 18 hunting piles on seven hunting estates. A total of eight bird and five mammal taxa were detected at the remains of hunting piles. The most frequently detected species in terms of number of gut piles visited (78% and scavenged (61% was the red fox Vulpes vulpes, followed by the griffon vulture Gyps fulvus (56% as regards both presence and scavenging and the raven Corvus corax (61 and 39% as regards presence and scavenging, respectively. We evidenced that griffon vultures accounted for most of the scavenging activity in open habitats, while facultative mammal scavengers, red fox, and wild boar Sus scrofa made the highest contribution to scavenging in vegetation-covered habitats. In the case of wild boar, the gut piles deposited during the evening and night favored higher rates of scavenging, while the opposite pattern was observed for griffons. Overall, our findings suggest that when disposing of hunting remains in areas of risk as regards disease transmission it is particularly important to consider the access that facultative mammals, and especially wild boar, have to material, while the presence of the resource needs to be safeguarded to protect specialist scavengers of conservation value. These results are of particular relevance in the case of wild boar in the current context of re-emerging TB and emerging African swine fever (ASF in Europe.

  17. Oligoclonal band phenotypes in MS differ in their HLA class II association, while specific KIR ligands at HLA class I show association to MS in general

    DEFF Research Database (Denmark)

    Gustavsen, Marte W; Viken, Marte K; Celius, Elisabeth G

    2014-01-01

    Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated the associ......Multiple sclerosis (MS) patients have been reported to have different HLA class II allele profiles depending on oligoclonal bands (OCBs) in the cerebrospinal fluid, but HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) ligands have not been studied. We investigated...

  18. Lipid organics in background aerosols, cloudwater, and snow and implication for organic scavenging

    International Nuclear Information System (INIS)

    Groellert, C.

    1998-01-01

    During three years free tropospheric snow, aerosol, and cloudwater samples were collected at Mount Sonnblick, Austria, at an elevation of 3106 m a.s.l. The samples were analyzed for their lipid organic trace components using extraction with n-hexane as sample pretreatment and gas chromatography-mass spectrometry-flame ionization detection for identification and quantification of the substances. The main components identified in all the samples were the phthalic acid esters which are of anthropogenic origin. Of further interest were aliphatic alcohols (not detected in aerosols) and phenols. They are of biogenic origin. The concentrations were found to be higher in spring than in the fall season. To compare the concentrations of aerosol, cloudwater and snow samples scavenging ratios (aerosol to snow), scavenging efficiencies (aerosol to cloud) and cloud to snow ratios were calculated for the first time for organic compounds. Scavenging ratios were 10 to 100 times lower, scavenging efficiencies 2 to 10 times lower than sulfate. This can result from the poor watersolubility of the compounds or from gas phase sorptions on the filter surface (overestimation of aerosol concentrations). The cloud to snow ratios were generally higher than for sulfate. However, a few components exhibited very low cloud to snow ratios which might be due to additional sources in snow for these substances (alcohols). (author)

  19. Evaluation of antioxidant, free radical scavenging and antimicrobial, activity of Quercus incana Roxb.

    Directory of Open Access Journals (Sweden)

    Rizwana eSarwar

    2015-11-01

    Full Text Available Considering the indigenous utilization of Quercus incana Roxb., the present study deals with the investigation of antioxidant, free radical scavenging activity, total phenolic content and antimicrobial activity of Quercus incana Roxb. In vitro antioxidant activity of the plant fractions were determined by DPPH and NO scavenging method. Total phenolic contents were determined by gallic acid equivalent (GAE and antimicrobial activities were determined by agar well diffusion method. It was observed that Quercus incana Roxb. showed significant antibacterial activity against Gram-positive and Gram-negative bacteria. n-Butanol fraction showed maximum activity against Micrococcus leuteus with 19 mm zone of inhibition. n-Butanol fraction of Quercus incana Roxb. showed immense antifungal activity against Aspergillus niger (32 mm ± 0.55 and Aspergillus flavus (28 mm ± 0.45. Similarly n-butanol fraction showed relatively good antioxidant activity with IC50 value of 55.4 ± 0.21μg/mL. The NO scavenging activity of ethyl acetate fraction (IC50 = 23.21 ± 0.31 μg/mL was fairly good compared to other fractions. The current study of Quercus incana Roxb. suggests the presences of synergetic action of some biological active compounds that may be present in the leaves of medicinal plant. Further studies are needed to better characterize the important active constituents responsible for the antimicrobial, antioxidant and free radical scavenging activity.

  20. Variation in bird-window collision mortality and scavenging rates within an urban landscape

    Science.gov (United States)

    Annual avian mortality from collisions with windows and buildings is estimated to range from a million to a billion birds in the United States alone. However, estimates of mortality based on carcass counts suffer from bias due to imperfect detection and carcass scavenging. We stu...