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Sample records for tlr2 mediates recognition

  1. Bovine TLR2 and TLR4 mediate Cryptosporidium parvum recognition in bovine intestinal epithelial cells.

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    Yang, Zhengtao; Fu, Yunhe; Gong, Pengtao; Zheng, Jingtong; Liu, Li; Yu, Yuqiang; Li, Jianhua; Li, He; Yang, Ju; Zhang, Xichen

    2015-08-01

    Cryptosporidium parvum (C. parvum) is an intestinal parasite that causes diarrhea in neonatal calves. It results in significant morbidity of neonatal calves and economic losses for producers worldwide. Innate resistance against C. parvum is thought to depend on engagement of pattern recognition receptors. However, the role of innate responses to C. parvum has not been elucidated in bovine. The aim of this study was to evaluate the role of TLRs in host-cell responses during C. parvum infection of cultured bovine intestinal epithelial cells. The expressions of TLRs in bovine intestinal epithelial cells were detected by qRT-PCR. To determine which, if any, TLRs may play a role in the response of bovine intestinal epithelial cells to C. parvum, the cells were stimulated with C. parvum and the expression of TLRs were tested by qRT-PCR. The expression of NF-κB was detected by western blotting. Further analyses were carried out in bovine TLRs transfected HEK293 cells and by TLRs-DN transfected bovine intestinal epithelial cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs. The expression of TLR2 and TLR4 were up-regulated when bovine intestinal epithelial cells were treated with C. parvum. Meanwhile, C. parvum induced IL-8 production in TLR2 or TLR4/MD-2 transfected HEK293 cells. Moreover, C. parvum induced NF-κB activation and cytokine expression in bovine intestinal epithelial cells. The induction of NF-κB activation and cytokine expression by C. parvum were reduced in TLR2-DN and TLR4-DN transfected cells. The results showed that bovine intestinal epithelial cells expressed all known TLRs, and bovine intestinal epithelial cells recognized and responded to C. parvum via TLR2 and TLR4. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Evolution of Recognition of Ligands from Gram-Positive Bacteria: Similarities and Differences in the TLR2-Mediated Response between Mammalian Vertebrates and Teleost Fish

    NARCIS (Netherlands)

    Ribeiro, Carla M. S.; Hermsen, Trudi; Taverne-Thiele, Anja J.; Savelkoul, Huub F. J.; Wiegertjes, Geert F.

    2010-01-01

    We investigated the role of the TLR2 receptor in the recognition of ligands from Gram-positive bacteria in fish. Comparative sequence analysis showed a highly conserved Toll/IL-1 receptor domain. Although the leucine-rich repeat domain was less conserved, the position of the critical peptidoglycan

  3. Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation

    OpenAIRE

    Kirschning, Carsten J; Dreher, Stefan; Maa?, Bj?rn; Fichte, Sylvia; Schade, Jutta; K?ster, Mario; Noack, Andreas; Lindenmaier, Werner; Wagner, Hermann; B?ldicke, Thomas

    2010-01-01

    Abstract Background Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to blo...

  4. Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation

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    Lindenmaier Werner

    2010-04-01

    Full Text Available Abstract Background Toll-like receptor (TLR 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (αT2ib which was generated from an antagonistic monoclonal antibody (mAb towards human and murine TLR2 (T2.5 to inhibit the function of TLR2. αT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser3 amino acid sequence. Results Coexpression of αT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with αT2ib indicated interaction of αT2ib with its cognate antigen within cells. αT2ib inhibited NF-κB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding αT2ib into HEK293 cells demonstrated high efficiency of the TLR2-αT2ib interaction. The αT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV-αT2ib. Transduction with AdVαT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM. Furthermore, TLR2 activation dependent TNFα mRNA accumulation, as well

  5. Generation of anti-TLR2 intrabody mediating inhibition of macrophage surface TLR2 expression and TLR2-driven cell activation.

    Science.gov (United States)

    Kirschning, Carsten J; Dreher, Stefan; Maass, Björn; Fichte, Sylvia; Schade, Jutta; Köster, Mario; Noack, Andreas; Lindenmaier, Werner; Wagner, Hermann; Böldicke, Thomas

    2010-04-13

    Toll-like receptor (TLR) 2 is a component of the innate immune system and senses specific pathogen associated molecular patterns (PAMPs) of both microbial and viral origin. Cell activation via TLR2 and other pattern recognition receptors (PRRs) contributes to sepsis pathology and chronic inflammation both relying on overamplification of an immune response. Intracellular antibodies expressed and retained inside the endoplasmatic reticulum (ER-intrabodies) are applied to block translocation of secreted and cell surface molecules from the ER to the cell surface resulting in functional inhibition of the target protein. Here we describe generation and application of a functional anti-TLR2 ER intrabody (alphaT2ib) which was generated from an antagonistic monoclonal antibody (mAb) towards human and murine TLR2 (T2.5) to inhibit the function of TLR2. alphaT2ib is a scFv fragment comprising the variable domain of the heavy chain and the variable domain of the light chain of mAb T2.5 linked together by a synthetic (Gly4Ser)3 amino acid sequence. Coexpression of alphaT2ib and mouse TLR2 in HEK293 cells led to efficient retention and accumulation of TLR2 inside the ER compartment. Co-immunoprecipitation of human TLR2 with alphaT2ib indicated interaction of alphaT2ib with its cognate antigen within cells. alphaT2ib inhibited NF-kappaB driven reporter gene activation via TLR2 but not through TLR3, TLR4, or TLR9 if coexpressed in HEK293 cells. Co-transfection of human TLR2 with increasing amounts of the expression plasmid encoding alphaT2ib into HEK293 cells demonstrated high efficiency of the TLR2-alphaT2ib interaction. The alphaT2ib open reading frame was integrated into an adenoviral cosmid vector for production of recombinant adenovirus (AdV)-alphaT2ib. Transduction with AdValphaT2ib specifically inhibited TLR2 surface expression of murine RAW264.7 and primary macrophages derived from bone marrow (BMM). Furthermore, TLR2 activation dependent TNFalpha mRNA accumulation, as

  6. The HIV-1 envelope transmembrane domain binds TLR2 through a distinct dimerization motif and inhibits TLR2-mediated responses.

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    Eliran Moshe Reuven

    2014-08-01

    Full Text Available HIV-1 uses a number of means to manipulate the immune system, to avoid recognition and to highjack signaling pathways. HIV-1 infected cells show limited Toll-Like Receptor (TLR responsiveness via as yet unknown mechanisms. Using biochemical and biophysical approaches, we demonstrate that the trans-membrane domain (TMD of the HIV-1 envelope (ENV directly interacts with TLR2 TMD within the membrane milieu. This interaction attenuates TNFα, IL-6 and MCP-1 secretion in macrophages, induced by natural ligands of TLR2 both in in vitro and in vivo models. This was associated with decreased levels of ERK phosphorylation. Furthermore, mutagenesis demonstrated the importance of a conserved GxxxG motif in driving this interaction within the membrane milieu. The administration of the ENV TMD in vivo to lipotechoic acid (LTA/Galactosamine-mediated septic mice resulted in a significant decrease in mortality and in tissue damage, due to the weakening of systemic macrophage activation. Our findings suggest that the TMD of ENV is involved in modulation of the innate immune response during HIV infection. Furthermore, due to the high functional homology of viral ENV proteins this function may be a general character of viral-induced immune modulation.

  7. Recognition of TLR2 N-Glycans: Critical Role in ArtinM Immunomodulatory Activity

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    da Silva, Thiago Aparecido; Ruas, Luciana Pereira; Nohara, Lilian L.; de Almeida, Igor Correia; Roque-Barreira, Maria Cristina

    2014-01-01

    TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL)-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties. PMID:24892697

  8. Recognition of TLR2 N-glycans: critical role in ArtinM immunomodulatory activity.

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    Vania Sammartino Mariano

    Full Text Available TLR2 plays a critical role in the protection against Paracoccidioides brasiliensis conferred by ArtinM administration. ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus, induces IL-12 production in macrophages and dendritic cells, which accounts for the T helper1 immunity that results from ArtinM administration. We examined the direct interaction of ArtinM with TLR2using HEK293A cells transfected with TLR2, alone or in combination with TLR1 or TLR6, together with accessory proteins. Stimulation with ArtinM induced NF-κB activation and interleukin (IL-8 production in cells transfected with TLR2, TLR2/1, or TLR2/6. Murine macrophages that were stimulated with ArtinM had augmented TLR2 mRNA expression. Furthermore, pre-incubation of unstimulated macrophages with an anti-TLR2 antibody reduced the cell labeling with ArtinM. In addition, a microplate assay revealed that ArtinM bound to TLR2 molecules that had been captured by specific antibodies from a macrophages lysate. Notably,ArtinM binding to TLR2 was selectively inhibited when the lectin was pre-incubated with mannotriose. The biological relevance of the direct interaction of ArtinM with TLR2 glycans was assessed using macrophages from TLR2-KOmice, which produced significantly lower levels of IL-12 and IL-10 in response to ArtinM than macrophages from wild-type mice. Pre-treatment of murine macrophages with pharmacological inhibitors of signaling molecules demonstrated the involvement of p38 MAPK and JNK in the IL-12 production induced by ArtinM and the involvement ofPI3K in IL-10 production. Thus, ArtinM interacts directly with TLR2 or TLR2 heterodimers in a carbohydrate recognition-dependent manner and functions as a TLR2 agonist with immunomodulatory properties.

  9. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages.

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    Yun Jeong Kim

    Full Text Available Botulinum neurotoxin type A (BoNT/A is the most potent protein toxin and causes fatal flaccid muscle paralysis by blocking neurotransmission. Application of BoNT/A has been extended to the fields of therapeutics and biodefense. Nevertheless, the global response of host immune cells to authentic BoNT/A has not been reported. Employing microarray analysis, we performed global transcriptional profiling of RAW264.7 cells, a murine alveolar macrophage cell line. We identified 70 genes that were modulated following 1 nM BoNT/A treatment. The altered genes were mainly involved in signal transduction, immunity and defense, protein metabolism and modification, neuronal activities, intracellular protein trafficking, and muscle contraction. Microarray data were validated with real-time RT-PCR for seven selected genes including tlr2, tnf, inos, ccl4, slpi, stx11, and irg1. Proinflammatory mediators such as nitric oxide (NO and tumor necrosis factor alpha (TNFα were induced in a dose-dependent manner in BoNT/A-stimulated RAW264.7 cells. Increased expression of these factors was inhibited by monoclonal anti-Toll-like receptor 2 (TLR2 and inhibitors specific to intracellular proteins such as c-Jun N-terminal kinase (JNK, extracellular signal-regulated kinase (ERK, and p38 mitogen-activated protein kinase (MAPK. BoNT/A also suppressed lipopolysaccharide-induced NO and TNFα production from RAW264.7 macrophages at the transcription level by blocking activation of JNK, ERK, and p38 MAPK. As confirmed by TLR2-/- knock out experiments, these results suggest that BoNT/A induces global gene expression changes in host immune cells and that host responses to BoNT/A proceed through a TLR2-dependent pathway, which is modulated by JNK, ERK, and p38 MAPK.

  10. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

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    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  11. Multifaceted effects of synthetic TLR2 ligand and Legionella pneumophilia on Treg-mediated suppression of T cell activation

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    Sutmuller Roger PM

    2011-03-01

    Full Text Available Abstract Background Regulatory T cells (Treg play a crucial role in maintaining immune homeostasis and self-tolerance. The immune suppressive effects of Tregs should however be limited in case effective immunity is required against pathogens or cancer cells. We previously found that the Toll-like receptor 2 (TLR2 agonist, Pam3CysSK4, directly stimulated Tregs to expand and temporarily abrogate their suppressive capabilities. In this study, we evaluate the effect of Pam3CysSK4 and Legionella pneumophila, a natural TLR2 containing infectious agent, on effector T (Teff cells and dendritic cells (DCs individually and in co-cultures with Tregs. Results TLR2 agonists can directly provide a co-stimulatory signal inducing enhanced proliferation and cytokine production of naive CD4+ Teff cells. With respect to cytokine production, DCs appear to be most sensitive to low amounts of TLR agonists. Using wild type and TLR2-deficient cells in Treg suppression assays, we accordingly show that all cells (e.g. Treg, Teff cells and DCs contributed to overcome Treg-mediated suppression of Teff cell proliferation. Furthermore, while TLR2-stimulated Tregs readily lost their ability to suppress Teff cell proliferation, cytokine production by Teff cells was still suppressed. Similar results were obtained upon stimulation with TLR2 ligand containing bacteria, Legionella pneumophila. Conclusions These findings indicate that both synthetic and natural TLR2 agonists affect DCs, Teff cells and Treg directly, resulting in multi-modal modulation of Treg-mediated suppression of Teff cells. Moreover, Treg-mediated suppression of Teff cell proliferation is functionally distinct from suppression of cytokine secretion.

  12. HMGB1 mediates endogenous TLR2 activation and brain tumor regression.

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    James F Curtin

    2009-01-01

    Full Text Available Glioblastoma multiforme (GBM is the most aggressive primary brain tumor that carries a 5-y survival rate of 5%. Attempts at eliciting a clinically relevant anti-GBM immune response in brain tumor patients have met with limited success, which is due to brain immune privilege, tumor immune evasion, and a paucity of dendritic cells (DCs within the central nervous system. Herein we uncovered a novel pathway for the activation of an effective anti-GBM immune response mediated by high-mobility-group box 1 (HMGB1, an alarmin protein released from dying tumor cells, which acts as an endogenous ligand for Toll-like receptor 2 (TLR2 signaling on bone marrow-derived GBM-infiltrating DCs.Using a combined immunotherapy/conditional cytotoxic approach that utilizes adenoviral vectors (Ad expressing Fms-like tyrosine kinase 3 ligand (Flt3L and thymidine kinase (TK delivered into the tumor mass, we demonstrated that CD4(+ and CD8(+ T cells were required for tumor regression and immunological memory. Increased numbers of bone marrow-derived, tumor-infiltrating myeloid DCs (mDCs were observed in response to the therapy. Infiltration of mDCs into the GBM, clonal expansion of antitumor T cells, and induction of an effective anti-GBM immune response were TLR2 dependent. We then proceeded to identify the endogenous ligand responsible for TLR2 signaling on tumor-infiltrating mDCs. We demonstrated that HMGB1 was released from dying tumor cells, in response to Ad-TK (+ gancyclovir [GCV] treatment. Increased levels of HMGB1 were also detected in the serum of tumor-bearing Ad-Flt3L/Ad-TK (+GCV-treated mice. Specific activation of TLR2 signaling was induced by supernatants from Ad-TK (+GCV-treated GBM cells; this activation was blocked by glycyrrhizin (a specific HMGB1 inhibitor or with antibodies to HMGB1. HMGB1 was also released from melanoma, small cell lung carcinoma, and glioma cells treated with radiation or temozolomide. Administration of either glycyrrhizin or anti

  13. Reprogramming of murine macrophages through TLR2 confers viral resistance via TRAF3-mediated, enhanced interferon production.

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    Darren J Perkins

    Full Text Available The cell surface/endosomal Toll-like Receptors (TLRs are instrumental in initiating immune responses to both bacteria and viruses. With the exception of TLR2, all TLRs and cytosolic RIG-I-like receptors (RLRs with known virus-derived ligands induce type I interferons (IFNs in macrophages or dendritic cells. Herein, we report that prior ligation of TLR2, an event previously shown to induce "homo" or "hetero" tolerance, strongly "primes" macrophages for increased Type I IFN production in response to subsequent TLR/RLR signaling. This occurs by increasing activation of the transcription factor, IFN Regulatory Factor-3 (IRF-3 that, in turn, leads to enhanced induction of IFN-β, while expression of other pro-inflammatory genes are suppressed (tolerized. In vitro or in vivo "priming" of murine macrophages with TLR2 ligands increase virus-mediated IFN induction and resistance to infection. This priming effect of TLR2 is mediated by the selective upregulation of the K63 ubiquitin ligase, TRAF3. Thus, we provide a mechanistic explanation for the observed antiviral actions of MyD88-dependent TLR2 and further define the role of TRAF3 in viral innate immunity.

  14. TLR2-dependent inhibition of macrophage responses to IFN-gamma is mediated by distinct, gene-specific mechanisms.

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    Sarah A Benson

    2009-07-01

    Full Text Available Mycobacterium tuberculosis uses multiple mechanisms to avoid elimination by the immune system. We have previously shown that M. tuberculosis can inhibit selected macrophage responses to IFN-gamma through TLR2-dependent and -independent mechanisms. To specifically address the role of TLR2 signaling in mediating this inhibition, we stimulated macrophages with the specific TLR2/1 ligand Pam(3CSK(4 and assayed responses to IFN-gamma. Pam(3CSK(4 stimulation prior to IFN-gamma inhibited transcription of the unrelated IFN-gamma-inducible genes, CIITA and CXCL11. Surface expression of MHC class II and secretion of CXCL11 were greatly reduced as well, indicating that the reduction in transcripts had downstream effects. Inhibition of both genes required new protein synthesis. Using chromatin immunoprecipitation, we found that TLR2 stimulation inhibited IFN-gamma-induced RNA polymerase II binding to the CIITA and CXCL11 promoters. Furthermore, TATA binding protein was unable to bind the TATA box of the CXCL11 promoter, suggesting that assembly of transcriptional machinery was disrupted. However, TLR2 stimulation affected chromatin modifications differently at each of the inhibited promoters. Histone H3 and H4 acetylation was reduced at the CIITA promoter but unaffected at the CXCL11 promoter. In addition, NF-kappaB signaling was required for inhibition of CXCL11 transcription, but not for inhibition of CIITA. Taken together, these results indicate that TLR2-dependent inhibition of IFN-gamma-induced gene expression is mediated by distinct, gene-specific mechanisms that disrupt binding of the transcriptional machinery to the promoters.

  15. Trichomonas vaginalis Induces Production of Proinflammatory Cytokines in Mouse Macrophages Through Activation of MAPK and NF-κB Pathways Partially Mediated by TLR2

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    Li, Ling; Li, Xin; Gong, Pengtao; Zhang, Xichen; Yang, Zhengtao; Yang, Ju; Li, Jianhua

    2018-01-01

    Trichomoniasis, caused by Trichomonas vaginalis infection, is the most prevalent sexually transmitted disease in female and male globally. However, the mechanisms by innate immunity against T. vaginalis infection have not been fully elucidated. Toll-like receptor2 (TLR2) has been shown to be involved in pathogen recognition, innate immunity activation, and inflammatory response to the pathogens. Nonetheless, the function of TLR2 against T. vaginalis remains unclear. In the present study, we investigated the role of TLR2 in mouse macrophages against T. vaginalis. RT-qPCR analysis revealed that T. vaginalis stimulation increased the gene expression of TLR2 in wild-type (WT) mouse macrophages. T. vaginalis also induced the secretion of IL-6, TNF-α, and IFN-γ in WT mouse macrophages, and the expression of these cytokines significantly decreased in TLR2-/- mouse macrophages and in WT mouse macrophages pretreated with MAPK inhibitors SB203580 (p38) and PD98059 (ERK). Western blot analysis demonstrated that T. vaginalis stimulation induced the activation of p38, ERK, and p65 NF-κB signal pathways in WT mouse macrophages, and the phosphorylation of p38, ERK, and p65 NF-κB significantly decreased in TLR2-/- mouse macrophages. Taken together, our data suggested that T. vaginalis may regulates proinflammatory cytokines production by activation of p38, ERK, and NF-κB p65 signal pathways via TLR2 in mouse macrophages. TLR2 might be involved in the defense and elimination of T. vaginalis infection. PMID:29692771

  16. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2

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    Holden, James A.; O'Brien-Simpson, Neil M.; Lenzo, Jason C.; Orth, Rebecca K. H.; Mansell, Ashley

    2017-01-01

    ABSTRACT Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2−/−, and TLR4−/− macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae-induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. PMID:28630066

  17. Porphyromonas gulae Activates Unprimed and Gamma Interferon-Primed Macrophages via the Pattern Recognition Receptors Toll-Like Receptor 2 (TLR2), TLR4, and NOD2.

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    Holden, James A; O'Brien-Simpson, Neil M; Lenzo, Jason C; Orth, Rebecca K H; Mansell, Ashley; Reynolds, Eric C

    2017-09-01

    Porphyromonas gulae is an anaerobic, Gram-negative coccobacillus that has been associated with periodontal disease in companion animals. The aims of this study were to analyze the ligation of pattern recognition receptors by P. gulae and the subsequent activation of macrophages. Exposure of HEK cells transfected with Toll-like receptors (TLRs) or NOD-like receptors to P. gulae resulted in the ligation of TLR2, TLR4, and NOD2. The effects of this engagement of receptors were investigated by measuring the synthesis of nitric oxide (NO), CD86 expression, and inflammatory cytokine production by wild-type, TLR2 -/- , and TLR4 -/- macrophages. The addition of P. gulae to unprimed and gamma interferon (IFN-γ)-primed (M1 phenotype) macrophages significantly increased the surface expression of CD86, but only M1 macrophages produced nitric oxide. P. gulae- induced expression of CD86 on unprimed macrophages was dependent on both TLR2 and TLR4, but CD86 expression and NO production in M1 macrophages were only TLR2 dependent. P. gulae induced an increase in secretion of interleukin-1α (IL-1α), IL-1β, IL-6, IL-12p70, IL-13, tumor necrosis factor alpha (TNF-α), granulocyte colony-stimulating factor (G-CSF), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1α (MIP-1α) by M1 macrophages compared to that by unprimed controls. Among these cytokines, secretion of IL-6 and TNF-α by M1 macrophages was dependent on either TLR2 or TLR4. Our data indicate that TLR2 and TLR4 are important for P. gulae activation of unprimed macrophages and that activation and effector functions induced in M1 macrophages by P. gulae are mainly dependent on TLR2. In conclusion, P. gulae induces a strong TLR2-dependent inflammatory M1 macrophage response which may be important in establishing the chronic inflammation associated with periodontal disease in companion animals. Copyright © 2017 American Society for Microbiology.

  18. Src-family-tyrosine kinase Lyn is critical for TLR2-mediated NF-κB activation through the PI 3-kinase signaling pathway.

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    Toubiana, Julie; Rossi, Anne-Lise; Belaidouni, Nadia; Grimaldi, David; Pene, Frederic; Chafey, Philippe; Comba, Béatrice; Camoin, Luc; Bismuth, Georges; Claessens, Yann-Erick; Mira, Jean-Paul; Chiche, Jean-Daniel

    2015-10-01

    TLR2 has a prominent role in host defense against a wide variety of pathogens. Stimulation of TLR2 triggers MyD88-dependent signaling to induce NF-κB translocation, and activates a Rac1-PI 3-kinase dependent pathway that leads to transactivation of NF-κB through phosphorylation of the P65 NF-κB subunit. This transactivation pathway involves tyrosine phosphorylations. The role of the tyrosine kinases in TLR signaling is controversial, with discrepancies between studies using only chemical inhibitors and knockout mice. Here, we show the involvement of the tyrosine-kinase Lyn in TLR2-dependent activation of NF-κB in human cellular models, by using complementary inhibition strategies. Stimulation of TLR2 induces the formation of an activation cluster involving TLR2, CD14, PI 3-kinase and Lyn, and leads to the activation of AKT. Lyn-dependent phosphorylation of the p110 catalytic subunit of PI 3-kinase is essential to the control of PI 3-kinase biological activity upstream of AKT and thereby to the transactivation of NF-κB. Thus, Lyn kinase activity is crucial in TLR2-mediated activation of the innate immune response in human mononuclear cells. © The Author(s) 2015.

  19. The combination of maltose-binding protein and BCG-induced Th1 activation is involved in TLR2/9-mediated upregulation of MyD88-TRAF6 and TLR4-mediated downregulation of TRIF-TRAF3.

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    Liu, Guomu; Zhai, Xiaoyu; Zhou, Hongyue; Yang, Xiaoyu; Zhang, Nannan; Tai, Guixiang; Ni, Weihua

    2018-03-01

    Our previous study demonstrated that maltose-binding protein (MBP) activated Th1 through the TLR2-mediated MyD88-dependent pathway and the TLR4-mediated TRIF-dependent pathway. The combination of MBP and BCG synergistically induced Th1 activation, and the TLR2/9-mediated MyD88-dependent pathway is involved in this process. To further explore this mechanism, we stimulated purified mouse CD4 + T cells with MBP and BCG in vitro. The results demonstrated that MBP combined with BCG synergistically increased IFN-γ production and TLR2/4/9 expression, suggesting the involvement of TLR2/4/9 in the combination-induced Th1 activation. Next, TLRs 2/4/9 were blocked to analyze the effects of TLRs on Th1 activation. The results demonstrated that MBP induced a low level of Th1 activation by upregulating TLR2-mediated MyD88-TRAF6 and TLR4-mediated TRIF-TRAF3 expression, whereas MBP combined with BCG induced synergistic Th1 activation, which was not only triggered by strong upregulation of TLR2/9-mediated MyD88-TRAF6 expression but also by shifting TLR4-mediated TRIF-TRAF3 into the TRIF-TRAF6 pathway. Moreover, we observed that a TLR4 antibody upregulated MyD88 expression and a TLR9 inhibitor downregulated TRIF expression, indicating that there was cross-talk between TLRs 2/4/9 in MBP combined with BCG-induced Th1 activation. Our findings may expand the knowledge regarding TLR cross-talk involved in regulating the Th1 response. Copyright © 2018 Elsevier Inc. All rights reserved.

  20. Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice – Implications for Superficial Erosion

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    Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K.; Swirski, Filip K.; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J.; Libby, Peter

    2017-01-01

    Rationale Superficial erosion currently causes up to a third of acute coronary syndromes (ACS), yet we lack understanding of its mechanisms. Thrombi due to superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. Objective This study tested in vivo the involvement of disturbed flow, and of neutrophils, hyaluronan, and TLR2 ligation in superficial intimal injury, a process implicated in superficial erosion. Methods and Results : In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell (EC) activation, neutrophil accumulation, EC death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. TLR2 agonism activated luminal ECs, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing EC injury and local thrombosis (p<0.05). Conclusions These results implicate flow disturbance, neutrophils, and TLR2 signaling as mechanisms that contribute to superficial erosion, a cause of ACS of likely growing importance in the statin era. PMID:28428204

  1. The anti-lung cancer activity of SEP is mediated by the activation and cytotoxicity of NK cells via TLR2/4 in vivo.

    Science.gov (United States)

    Ke, Mengyun; Wang, Hui; Zhang, Min; Tian, Yuwei; Wang, Yizhou; Li, Bing; Yu, Jie; Dou, Jie; Xi, Tao; Zhou, Changlin

    2014-05-01

    Strongylocentrotus nudus egg polysaccharide (SEP) has been reported to display antitumor activity. However, the effects of SEP and its underlying mechanism in the treatment of lung cancer remain unclear, particularly with an immunodeficient mouse model of human non-small cell lung cancer (NSCLC). In the present study, we investigated the anti-lung cancer effects of SEP and its underlying mechanism of action in both Lewis lung cancer (LLC)-bearing C57/BL6J mice and human NSCLC H460-bearing nude mice. Although SEP showed no inhibitory effects on tumor cells in vitro, it markedly stimulated the percentage of CD3-NK1.1(+) cells and natural killer (NK) cell cytotoxicity in the spleens of nude mice and C57/BL6J mice. In LLC-bearing mice, SEP not only inhibited tumor growth but also promoted NK-mediated cytotoxicity, the NK1.1(+) cell population, and IL-2 and IFN-γ secretion. SEP significantly suppressed H460 growth in nude mice, which was abrogated by the selective depletion of NK cells via the intraperitoneal injection of anti-asialo GM-1 antibodies. Furthermore, anti-TLR2/4 antibodies blocked both SEP and NK cell binding and SEP-induced perforin secretion. SEP-induced proliferation and IFN-γ secretion by NK cells in wild type mice were partially impaired in TLR2 or TLR4 knockout mice. These results suggest that SEP-promoted NK cytotoxicity, which was partially mediated via TLR2 and TLR4, was the main contributing factor to lung cancer inhibition in vivo and that SEP may be a potential immunotherapy candidate for the treatment of lung cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Inhibition of TLR2 signaling by small molecule inhibitors targeting a pocket within the TLR2 TIR domain

    Science.gov (United States)

    Mistry, Pragnesh; Laird, Michelle H. W.; Schwarz, Ryan S.; Greene, Shannon; Dyson, Tristan; Snyder, Greg A.; Xiao, Tsan Sam; Chauhan, Jay; Fletcher, Steven; Toshchakov, Vladimir Y.; MacKerell, Alexander D.; Vogel, Stefanie N.

    2015-01-01

    Toll-like receptor (TLR) signaling is initiated by dimerization of intracellular Toll/IL-1 receptor resistance (TIR) domains. For all TLRs except TLR3, recruitment of the adapter, myeloid differentiation primary response gene 88 (MyD88), to TLR TIR domains results in downstream signaling culminating in proinflammatory cytokine production. Therefore, blocking TLR TIR dimerization may ameliorate TLR2-mediated hyperinflammatory states. The BB loop within the TLR TIR domain is critical for mediating certain protein–protein interactions. Examination of the human TLR2 TIR domain crystal structure revealed a pocket adjacent to the highly conserved P681 and G682 BB loop residues. Using computer-aided drug design (CADD), we sought to identify a small molecule inhibitor(s) that would fit within this pocket and potentially disrupt TLR2 signaling. In silico screening identified 149 compounds and 20 US Food and Drug Administration-approved drugs based on their predicted ability to bind in the BB loop pocket. These compounds were screened in HEK293T-TLR2 transfectants for the ability to inhibit TLR2-mediated IL-8 mRNA. C16H15NO4 (C29) was identified as a potential TLR2 inhibitor. C29, and its derivative, ortho-vanillin (o-vanillin), inhibited TLR2/1 and TLR2/6 signaling induced by synthetic and bacterial TLR2 agonists in human HEK-TLR2 and THP-1 cells, but only TLR2/1 signaling in murine macrophages. C29 failed to inhibit signaling induced by other TLR agonists and TNF-α. Mutagenesis of BB loop pocket residues revealed an indispensable role for TLR2/1, but not TLR2/6, signaling, suggesting divergent roles. Mice treated with o-vanillin exhibited reduced TLR2-induced inflammation. Our data provide proof of principle that targeting the BB loop pocket is an effective approach for identification of TLR2 signaling inhibitors. PMID:25870276

  3. A Staphylococcus aureus TIR domain protein virulence factor blocks TLR2-mediated NF-κB signaling.

    Science.gov (United States)

    Askarian, Fatemeh; van Sorge, Nina M; Sangvik, Maria; Beasley, Federico C; Henriksen, Jørn R; Sollid, Johanna U E; van Strijp, Jos A G; Nizet, Victor; Johannessen, Mona

    2014-01-01

    Signaling through Toll-like receptors (TLRs), crucial molecules in the induction of host defense responses, requires adaptor proteins that contain a Toll/interleukin-1 receptor (TIR) domain. The pathogen Staphylococcus aureus produces several innate immune-evasion molecules that interfere with the host's innate immune response. A database search analysis suggested the presence of a gene encoding a homologue of the human TIR domain in S. aureus MSSA476 which was named staphylococcal TIR domain protein (TirS). Ectopic expression of TirS in human embryonic kidney, macrophage and keratinocyte cell lines interfered with signaling through TLR2, including MyD88 and TIRAP, NF-κB and/or mitogen-activated protein kinase pathways. Moreover, the presence of TirS reduced the levels of cytokines MCP-1 and G-CSF secreted in response to S. aureus. The effects on NF-κB pathway were confirmed using S. aureus MSSA476 wild type, an isogenic mutant MSSA476ΔtirS, and complemented MSSA476ΔtirS +pTirS in a Transwell system where bacteria and host cells were physically separated. Finally, in a systematic mouse infection model, TirS promoted bacterial accumulation in several organs 4 days postinfection. The results of this study reveal a new S. aureus virulence factor that can interfere with PAMP-induced innate immune signaling in vitro and bacterial survival in vivo. © 2014 S. Karger AG, Basel.

  4. Mycobacterium tuberculosis complex enhances susceptibility of CD4 T cells to HIV through a TLR2-mediated pathway.

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    Seema M Thayil

    Full Text Available Among HIV-infected individuals, co-infection with Mycobacterium tuberculosis is associated with faster progression to AIDS. We investigated the hypothesis that M. bovis BCG and M. tuberculosis (Mtb complex could enhance susceptibility of CD4+ cells to HIV infection. Peripheral blood mononuclear cells (PBMCs collected from healthy donors were stimulated with M. bovis BCG, M. tuberculosis CDC1551 and M. smegmatis MC(2155, and stimulated CD4+ cells were infected with R5-and X4-tropic single replication-competent pseudovirus. CD4+ cells stimulated with Mtb complex showed enhanced infection with R5- and X4-tropic HIV, compared to unstimulated cells or cells stimulated with M. smegmatis (p<0.01. Treatment with TLR2 siRNA reversed the increased susceptibility of CD4+ cells with R5- and X4-tropic virus induced by Mtb complex. These findings suggest that TB infection and/or BCG vaccination may be a risk factor for HIV acquisition.

  5. Postnatal TLR2 activation impairs learning and memory in adulthood.

    Science.gov (United States)

    Madar, Ravit; Rotter, Aviva; Waldman Ben-Asher, Hiba; Mughal, Mohamed R; Arumugam, Thiruma V; Wood, W H; Becker, K G; Mattson, Mark P; Okun, Eitan

    2015-08-01

    Neuroinflammation in the central nervous system is detrimental for learning and memory, as evident form epidemiological studies linking developmental defects and maternal exposure to harmful pathogens. Postnatal infections can also induce neuroinflammatory responses with long-term consequences. These inflammatory responses can lead to motor deficits and/or behavioral disabilities. Toll like receptors (TLRs) are a family of innate immune receptors best known as sensors of microbial-associated molecular patterns, and are the first responders to infection. TLR2 forms heterodimers with either TLR1 or TLR6, is activated in response to gram-positive bacterial infections, and is expressed in the brain during embryonic development. We hypothesized that early postnatal TLR2-mediated neuroinflammation would adversely affect cognitive behavior in the adult. Our data indicate that postnatal TLR2 activation affects learning and memory in adult mice in a heterodimer-dependent manner. TLR2/6 activation improved motor function and fear learning, while TLR2/1 activation impaired spatial learning and enhanced fear learning. Moreover, developmental TLR2 deficiency significantly impairs spatial learning and enhances fear learning, stressing the involvement of the TLR2 pathway in learning and memory. Analysis of the transcriptional effects of TLR2 activation reveals both common and unique transcriptional programs following heterodimer-specific TLR2 activation. These results imply that adult cognitive behavior could be influenced in part, by activation or alterations in the TLR2 pathway at birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Outer membrane protein A (OmpA of Shigella flexneri 2a induces TLR2-mediated activation of B cells: involvement of protein tyrosine kinase, ERK and NF-κB.

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    Rajsekhar Bhowmick

    Full Text Available B cells are critically important in combating bacterial infections and their differentiation into plasma cells and memory cells aids bacterial clearance and long-lasting immunity conferred by essentially all vaccines. Outer membrane protein A (OmpA of Shigella flexneri 2a has been demonstrated to induce the production of IgG and IgA in vivo following immunization of mice through intranasal route, but the direct involvement of B cells in OmpA-mediated immune regulation was not determined. Consequently, we investigated whether OmpA can modulate B cell functions and identified the molecular events involved in OmpA-induced B cell immune response in vitro. We show that OmpA of S. flexneri 2a activates B cells to produce protective cytokines, IL-6 and IL-10 as well as facilitates their differentiation into antibody secreting cells (ASCs. The immunostimulatory properties of OmpA are attributed to the increased surface expression of MHCII and CD86 on B cells. We also report here that B cell activation by OmpA is mediated strictly through recognition by TLR2, resulting in initiation of cascades of signal transduction events, involving increased phosphorylation of protein tyrosine kinases (PTKs, ERK and IκBα, leading to nuclear translocation of NF-κB. Importantly, a TLR2 antibody diminishes OmpA-induced upregulation of MHCII and CD86 on B cell surface as well as significantly inhibits B cell differentiation and cytokine secretion. Furthermore, we illustrate that B cell differentiation into ASCs and induction of cytokine secretion by OmpA are dependent on PTKs activity. Moreover, we identify that OmpA-induced B cell differentiation is entirely dependent on ERK pathway, whereas both NF-κB and ERK are essential for cytokine secretion by B cells. Overall, our data demonstrate that OmpA of S. flexneri 2a amplifies TLR signaling in B cells and triggers B cell immune response, which is critical for the development of an effective adaptive immunity to an

  7. Innate immune response of alveolar macrophage to house dust mite allergen is mediated through TLR2/-4 co-activation.

    Directory of Open Access Journals (Sweden)

    Chia-Fang Liu

    Full Text Available House dust mite, Dermatophagoides pteronyssinus (Der p, is one of the major allergens responsible for allergic asthma. However, the putative receptors involved in the signalization of Der p to the innate immune cells are still poorly defined as well as the impact of their activation on the outcome of the allergen-induced cell response. We previously reported that the HDM activation of mouse alveolar macrophages (AM involves the TLR4/CD14 cell surface receptor complex. Here using a TLR ligand screening essay, we demonstrate that HDM protein extract engages the TLR2, in addition to the TLR4, in engineered TLR-transfected HEK cells but also in the MH-S mouse alveolar macrophage cell line model. Moreover we found that the concomitant recruitment of the MH-S cell's TLR2 and TLR4 receptors by the HDM extract activates the MyD88-dependent signaling pathway and leads to the secretion of the NF-κB regulated pro-inflammatory factors NO and TNF-α. However unlike with the canonical TLR4 ligand (i.e. the bacterial LPS mobilization of TLR4 by the HDM extract induces a reduced production of the IL-12 pro-inflammatory cytokine and fails to trigger the expression of the T-bet transcription factor. Finally we demonstrated that HDM extract down-regulates LPS induced IL-12 and T-bet expression through a TLR2 dependent mechanism. Therefore, we propose that the simultaneous engagement of the TLR2 and TLR4 receptors by the HDM extract results in a cross regulated original activation pattern of the AM which may contribute to the Th2 polarization of the allergen-induced immune response. The deciphering of these cross-regulation networks is of prime importance to open the way for original therapeutic strategies taking advantage of these receptors and their associated signaling pathways to treat allergic asthma.

  8. Role of innate immune receptors TLR2 and TLR4 as mediators of the inflammatory reaction in human visceral adipose tissue.

    Science.gov (United States)

    Fusaru, Ana Marina; Stănciulescu, Camelia Elena; Surlin, V; Taisescu, C; Bold, Adriana; Pop, O T; Baniţă, Ileana Monica; Crăiţoiu, Stefania; Pisoschi, Cătălina Gabriela

    2012-01-01

    White adipose tissue from different locations is characterized by significant differences in the structure of adipocyte "secretoma". Fat accumulation in the central-visceral depots is usually associated with a chronic inflammatory state, which is complicated by the metabolic syndrome. Recently, the adipose tissue was emerged to have an essential role in the innate immunity, adipocytes being considered effector cells due to the presence of the Toll-like receptors (TLRs). In this study, we compared the expression of TNF-α, TLR2 and TLR4 in peripheral-subcutaneous and central-peritoneal adipose depots in three different conditions - lean, obese and obese diabetic - using immunohistochemistry. Our results suggest a correlation between the incidence of the stromal vascular cells and adipocytes TNF-α and TLR4 in the visceral depots in strong correlation with adipose tissue expansion. TLR2 positive cells were seen in the peripheral depots from all groups without any association with fat accumulation. These results focus on the existence of a new pathogenic pathway, the activation of TLR4, for the involvement of visceral adipose tissue in the activation and maintenance of the inflammatory cascade in obesity.

  9. Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice

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    Sandro M. Krieg

    2017-08-01

    Full Text Available Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs. Since the role of TLR2 and 4 after traumatic brain injury (TBI is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4−/− and wild-type (WT mice. Tlr2/4−/− and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI. Contusion volume was significantly attenuated in Tlr2/4−/− mice (29.7 ± 0.7 mm3 as compared to 33.5 ± 0.8 mm3 in WT; p < 0.05 after CCI while brain edema was not affected. Only interleukin (IL-1β gene expression was increased after CCI in the Tlr2/4−/− relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4−/− mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI.

  10. Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1.

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    Patrycja Konieczna

    Full Text Available The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1. Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

  11. Human Dendritic Cell DC-SIGN and TLR-2 Mediate Complementary Immune Regulatory Activities in Response to Lactobacillus rhamnosus JB-1

    Science.gov (United States)

    Konieczna, Patrycja; Schiavi, Elisa; Ziegler, Mario; Groeger, David; Healy, Selena; Grant, Ray; O’Mahony, Liam

    2015-01-01

    The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses. PMID:25816321

  12. Human dendritic cell DC-SIGN and TLR-2 mediate complementary immune regulatory activities in response to Lactobacillus rhamnosus JB-1.

    Science.gov (United States)

    Konieczna, Patrycja; Schiavi, Elisa; Ziegler, Mario; Groeger, David; Healy, Selena; Grant, Ray; O'Mahony, Liam

    2015-01-01

    The microbiota is required for optimal host development and ongoing immune homeostasis. Lactobacilli are common inhabitants of the mammalian large intestine and immunoregulatory effects have been described for certain, but not all, strains. The mechanisms underpinning these protective effects are beginning to be elucidated. One such protective organism is Lactobacillus rhamnosus JB-1 (Lb. rhamnosus JB-1). Lb. murinus has no such anti-inflammatory protective effects and was used as a comparator organism. Human monocyte-derived dendritic cells (MDDCs) were co-incubated with bacteria and analysed over time for bacterial adhesion and intracellular processing, costimulatory molecule expression, cytokine secretion and induction of lymphocyte polarization. Neutralising antibodies were utilized to identify the responsible MDDC receptors. Lb. rhamnosus JB-1 adhered to MDDCs, but internalization and intracellular processing was significantly delayed, compared to Lb. murinus which was rapidly internalized and processed. Lb. murinus induced CD80 and CD86 expression, accompanied by high levels of cytokine secretion, while Lb. rhamnosus JB-1 was a poor inducer of costimulatory molecule expression and cytokine secretion. Lb. rhamnosus JB-1 primed MDDCs induced Foxp3 expression in autologous lymphocytes, while Lb. murinus primed MDDCs induced Foxp3, T-bet and Ror-γt expression. DC-SIGN was required for Lb. rhamnosus JB-1 adhesion and influenced IL-12 secretion, while TLR-2 influenced IL-10 and IL-12 secretion. Here we demonstrate that the delayed kinetics of bacterial processing by MDDCs correlates with MDDC activation and stimulation of lymphocytes. Thus, inhibition or delay of intracellular processing may be a novel strategy by which certain commensals may avoid the induction of proinflammatory responses.

  13. Hepatitis C Virus NS3 Mediated Microglial Inflammation via TLR2/TLR6 MyD88/NF-κB Pathway and Toll Like Receptor Ligand Treatment Furnished Immune Tolerance.

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    Ayilam Ramachandran Rajalakshmy

    Full Text Available Recent evidence suggests the neurotrophic potential of hepatitis C virus (HCV. HCV NS3 protein is one of the potent antigens of this virus mediating inflammatory response in different cell types. Microglia being the immune surveillance cells in the central nervous system (CNS, the inflammatory potential of NS3 on microglia was studied. Role of toll like receptor (TLR ligands Pam2CSK3 and Pam3CSK4 in controlling the NS3 mediated microglial inflammation was studied using microglial cell line CHME3.IL (Interleukin-8, IL-6, TNF-α (Tumor nicrosis factor alpha and IL-1β gene expressions were measured by semi quantitative RT-PCR (reverse transcription-PCR. ELISA was performed to detect IL-8, IL-6, TNF-α, IL-1β and IL-10 secretion. FACS (Flourescent activated cell sorting was performed to quantify TLR1, TLR2, TLR6, MyD88 (Myeloid differntiation factor 88, IkB-α (I kappaB alpha and pNF-κB (phosphorylated nuclear factor kappaB expression. Immunofluorescence staining was performed for MyD88, TLR6 and NF-κB (Nuclear factor kappaB. Student's t-test or One way analysis of variance with Bonferoni post hoc test was performed and p < 0.05 was considered significant.Microglia responded to NS3 by secreting IL-8, IL-6, TNF-α and IL-1β via TLR2 or TLR6 mediated MyD88/NF-κB pathway. Transcription factor NF-κB was involved in activating the cytokine gene expression and the resultant inflammatory response was controlled by NF-κB inhibitor, Ro106-9920, which is known to down regulate pro-inflammatory cytokine secretion. Activation of the microglia by TLR agonists Pam3CSK4 and Pam2CSK4 induced immune tolerance against NS3. TLR ligand treatment significantly down regulated pro-inflammatory cytokine secretion in the microglia. IL-10 secretion was suggested as the possible mechanism by which TLR agonists induced immune tolerance. NS3 as such was not capable of self-inducing immune tolerance in microglia.In conclusion, NS3 protein was capable of activating

  14. Genomic evidence of gene duplication and adaptive evolution of Toll like receptors (TLR2 and TLR4) in reptiles.

    Science.gov (United States)

    Shang, Shuai; Zhong, Huaming; Wu, Xiaoyang; Wei, Qinguo; Zhang, Huanxin; Chen, Jun; Chen, Yao; Tang, Xuexi; Zhang, Honghai

    2018-04-01

    Toll-like receptors (TLRs) encoded by the TLR multigene family play an important role in initial pathogen recognition in vertebrates. Among the TLRs, TLR2 and TLR4 may be of particular importance to reptiles. In order to study the evolutionary patterns and structural characteristics of TLRs, we explored the available genomes of several representative members of reptiles. 25 TLR2 genes and 19 TLR4 genes from reptiles were obtained in this study. Phylogenetic results showed that the TLR2 gene duplication occurred in several species. Evolutionary analysis by at least two methods identified 30 and 13 common positively selected codons in TLR2 and TLR4, respectively. Most positively selected sites of TLR2 and TLR4 were located in the Leucine-rich repeat (LRRs). Branch model analysis showed that TLR2 genes were under different evolutionary forces in reptiles, while the TLR4 genes showed no significant selection pressure. The different evolutionary adaptation of TLR2 and TLR4 among the reptiles might be due to their different function in recognizing bacteria. Overall, we explored the structure and evolution of TLR2 and TLR4 genes in reptiles for the first time. Our study revealed valuable information regarding TLR2 and TLR4 in reptiles, and provided novel insights into the conservation concern of natural populations. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study.

    Science.gov (United States)

    Kopp, Tine Iskov; Vogel, Ulla; Tjonneland, Anne; Andersen, Vibeke

    2018-03-01

    Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important modulators of diet-induced CRC together with other inflammatory mediators. Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors. Additionally, interactions with previously studied polymorphisms in IL10, IL1B, PTGS2, and NFKB1 were assessed in order to examine possible biological pathways in meat-induced CRC. A nested case-cohort study of 897 CRC cases and 1689 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using Cox proportional hazard models and the likelihood ratio test. We found associations between polymorphisms in TLR2 (P = 0.018) and TLR4 (P = 0.044) and risk of CRC per se, interactions between intake of red and processed meat (10 g/d) and polymorphisms in TLR1 (P-interaction = 0.032) and TLR10 (P-interaction = 0.026 and 0.036), and intake of cereals (50 g/d) and TLR4 (P-interaction = 0.044) in relation to risk of CRC. Intake of red and processed meat also interacted with combinations of polymorphisms in TLR1 and TLR10 and polymorphisms in NFKB1, IL10, IL1B, and PTGS2 (P-interaction; TLR1/rs4833095 × PTGS2/rs20417 = 0.021, TLR10/rs11096955 × IL10/rs3024505 = 0.047, TLR10/rs11096955 × PTGS2/rs20417 = 0.017, TLR10/rs4129009 × NFKB1/rs28362491 = 0.027, TLR10/rs4129009 × IL1B/rs4848306 = 0.020, TLR10/rs4129009 × IL1B/rs1143623 = 0.021, TLR10/rs4129009 × PTGS2/rs20417 = 0.027), whereas intake of dietary fiber (10 g/d) interacted with combinations of polymorphisms in TLR4, IL10, and PTGS2 (P-interaction; TLR4/rs1554973 × IL10/rs3024505 = 0.0012, TLR4/rs1554973 × PTGS2/rs20417 = 0.0041, TLR4/rs1554973 × PTGS

  16. NOD2 and TLR2 ligands trigger the activation of basophils and eosinophils by interacting with dermal fibroblasts in atopic dermatitis-like skin inflammation

    Science.gov (United States)

    Jiao, Delong; Wong, Chun-Kwok; Qiu, Huai-Na; Dong, Jie; Cai, Zhe; Chu, Man; Hon, Kam-Lun; Tsang, Miranda Sin-Man; Lam, Christopher Wai-Kei

    2016-01-01

    The skin of patients with atopic dermatitis (AD) has a unique predisposition for colonization by Staphylococcus aureus (S. aureus), which contributes to the inflammation and grim prognosis of AD. Although the mechanism underlying the S. aureus-induced exacerbation of AD remains unclear, recent studies have found a pivotal role for pattern recognition receptors in regulating the inflammatory responses in S. aureus infection. In the present study, we used a typical mouse model of AD-like skin inflammation and found that S. aureus-associated nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and toll-like receptor 2 (TLR2) ligands exacerbated AD-like symptoms, which were further deteriorated by the in vivo expansion of basophils and eosinophils. Subsequent histological analyses revealed that dermal fibroblasts were pervasive in the AD-like skin lesions. Co-culture of human dermal fibroblasts with basophils and eosinophils resulted in a vigorous cytokine/chemokine response to the NOD2/TLR2 ligands and the enhanced expression of intercellular adhesion molecule-1 on the dermal fibroblasts. Basophils and eosinophils were primarily responsible for the AD-related cytokine/chemokine expression in the co-cultures. Direct intercellular contact was necessary for the crosstalk between basophils and dermal fibroblasts, while soluble mediators were sufficient to mediate the eosinophil–fibroblast interactions. Moreover, the intracellular p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and nuclear factor-kappa B signaling pathways were essential for NOD2/TLR2 ligand-mediated activation of basophils, eosinophils, and dermal fibroblasts in AD-related inflammation. This study provides the evidence of NOD2/TLR2-mediated exacerbation of AD through activation of innate immune cells and therefore sheds light on a novel mechanistic pathway by which S. aureus contributes to the pathophysiology of AD. PMID:26388234

  17. TLR2 and TLR9 Synergistically Control Herpes Simplex Virus Infection in the Brain

    DEFF Research Database (Denmark)

    Sørensen, Louise Nørgaard; Reinert, Line; Malmgaard, Lene

    2008-01-01

    Viruses are recognized by the innate immune system through pattern recognition receptors (PRRs). For instance, HSV virions and genomic DNA are recognized by TLR2 and TLR9, respectively. Although several viruses and viral components have been shown to stimulate cells through TLRs, only very few st...

  18. Pam2 lipopeptides systemically increase myeloid-derived suppressor cells through TLR2 signaling

    Energy Technology Data Exchange (ETDEWEB)

    Maruyama, Akira; Shime, Hiroaki, E-mail: shime@med.hokudai.ac.jp; Takeda, Yohei; Azuma, Masahiro; Matsumoto, Misako; Seya, Tsukasa, E-mail: seya-tu@pop.med.hokudai.ac.jp

    2015-02-13

    Myeloid-derived suppressor cells (MDSCs) are immature myeloid cells that exhibit potent immunosuppressive activity. They are increased in tumor-bearing hosts and contribute to tumor development. Toll-like receptors (TLRs) on MDSCs may modulate the tumor-supporting properties of MDSCs through pattern-recognition. Pam2 lipopeptides represented by Pam2CSK4 serve as a TLR2 agonist to exert anti-tumor function by dendritic cell (DC)-priming that leads to NK cell activation and cytotoxic T cell proliferation. On the other hand, TLR2 enhances tumor cell progression/invasion by activating tumor-infiltrating macrophages. How MDSCs respond to TLR2 agonists has not yet been determined. In this study, we found intravenous administration of Pam2CSK4 systemically up-regulated the frequency of MDSCs in EG7 tumor-bearing mice. The frequency of tumor-infiltrating MDSCs was accordingly increased in response to Pam2CSK4. MDSCs were not increased by Pam2CSK4 stimuli in TLR2 knockout (KO) mice. Adoptive transfer experiments using CFSE-labeled MDSCs revealed that the TLR2-positive MDSCs survived long in tumor-bearing mice in response to Pam2CSK4 treatment. Since the increased MDSC population sustained immune-suppressive properties, our study suggests that Pam2CSK4-triggered TLR2 activation enhances the MDSC potential and suppress antitumor immune response in tumor microenvironment. - Highlights: • Pam2CSK4 administration induces systemic accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • TLR2 is essential for Pam2CSK4-induced accumulation of CD11b{sup +}Gr1{sup +} MDSCs. • Pam2CSK4 supports survival of CD11b{sup +}Gr1{sup +} MDSCs in vivo.

  19. Molecular and functional characterization of Toll-like receptor (Tlr)1 and Tlr2 in common carp (Cyprinus carpio).

    Science.gov (United States)

    Fink, Inge R; Pietretti, Danilo; Voogdt, Carlos G P; Westphal, Adrie H; Savelkoul, Huub F J; Forlenza, Maria; Wiegertjes, Geert F

    2016-09-01

    Toll-like receptors (TLRs) are fundamental components of innate immunity that play significant roles in the defence against pathogen invasion. In this study, we present the molecular characterization of the full-length coding sequence of tlr1, tlr2a and tlr2b from common carp (Cyprinus carpio). Each is encoded within a single exon and contains a conserved number of leucine-rich repeats, a transmembrane region and an intracellular TIR domain for signalling. Indeed, sequence, phylogenetic and synteny analysis of carp tlr1, tlr2a and tlr2b support that these genes are orthologues of mammalian TLR1 and TLR2. The tlr genes are expressed in various immune organs and cell types. Furthermore, the carp sequences exhibited a good three-dimensional fit with the heterodimer structure of human TLR1-TLR2, including the potential to bind to the ligand Pam3CSK4. This supports the possible formation of carp Tlr1-Tlr2 heterodimers. However, we were unable to demonstrate Tlr1/Tlr2-mediated ligand binding in transfected cell lines through NF-κB activation, despite showing the expression and co-localization of Tlr1 and Tlr2. We discuss possible limitations when studying ligand-specific activation of NF-κB after expression of Tlr1 and/or Tlr2 in human but also fish cell lines and we propose alternative future strategies for studying ligand-binding properties of fish Tlrs. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Altered Expression of TLR2 and TLR4 on Peripheral CD14+ Blood Monocytes in Children with Urinary Tract Infection.

    Science.gov (United States)

    Karananou, Panagiota; Fleva, Alexandra; Tramma, Despoina; Alataki, Anastasia; Pavlitou-Tsiontsi, Aikaterini; Emporiadou-Peticopoulou, Maria; Papadopoulou-Alataki, Efimia

    2016-01-01

    Urinary tract infection (UTI) is the second most common bacterial infection, after otitis media, in infants and children. The mechanisms of disease susceptibility and the role of immunity in the pathogenesis of UTI in children have been evaluated. In recent years, Toll-Like Receptors (TLRs) have been recognized as specific components of the innate immune system constituting important mediators in host immune recognition. The aim of the present study was to determine ΤLR2 and TLR4 expression during the acute phase of UTI in infants and children by measuring the CD14/TLR2 and CD14/TLR4 expression on monocytes. We also attempted to compare the TLRs expression with the immunological status of the patients to healthy children. The study group consisted of 60 children (36 females and 24 males) and the control group included 60 age-matched pediatric subjects (27 females and 33 males). In our study, no antibody deficiency was found either in the children with UTI or in healthy subjects. There might be a connection between low IgA, IgG, and IgG subclasses serum levels and UTI as there was a statistically significant difference between patients and healthy children. A higher expression of CD14/TLR2 was revealed in patients (90,07%) compared to controls (85,48%) as well as CD14/TLR4 in patients (90,53%) compared to controls (87,25%) (statistically significant difference, p UTIs' pathogenesis in children.

  1. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo.

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    Yin-Ping Jia

    Full Text Available Toll-like receptors (TLRs 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.

  2. Otitis media induced by peptidoglycan-polysaccharide (PGPS) in TLR2-deficient (Tlr2(-/-)) mice for developing drug therapy.

    Science.gov (United States)

    Zhang, Xiaolin; Zheng, Tihua; Sang, Lu; Apisa, Luke; Zhao, Hongchun; Fu, Fenghua; Wang, Qingzhu; Wang, Yanfei; Zheng, Qingyin

    2015-10-01

    Toll like receptor 2 (TLR2) signaling can regulate the pathogenesis of otitis media (OM). However, the precise role of TLR2 signaling in OM has not been clarified due to the lack of an optimal animal model. Peptidoglycan-polysaccharide (PGPS) of the bacterial cell wall can induce inflammation by activating the TLR2 signaling. This study aimed at examining the pathogenic characteristics of OM induced by PGPS in Tlr2(-/-) mice, and the potential therapeutic effect of sodium aescinate (SA) in this model. Wild-type (WT) and Tlr2(-/-) mice were inoculated with streptococcal PGPS into their middle ears (MEs) and treated intravenously with vehicle or SA daily beginning at 3days prior to PGPS for 6 consecutive days. The pathologic changes of individual mice were evaluated longitudinally. In comparison with WT mice, Tlr2(-/-) mice were susceptible to PGPS-induced OM. Tlr2(-/-) mice displayed greater hearing loss, tympanic membrane damage, ME mucosal thickening, longer inflammation state, cilia and goblet cell loss. SA-treatment decreased neutrophil infiltration, modulated TLR2-related gene expression and improved ciliary organization. PGPS induced a relatively stable OM in Tlr2(-/-) mice, providing a new model for OM research. Treatment with SA mitigated the pathogenic damage in the ME and may be valuable for intervention of OM. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Polymorphisms at the innate immune receptor TLR2 are associated with Borrelia infection in a wild rodent population.

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    Tschirren, Barbara; Andersson, Martin; Scherman, Kristin; Westerdahl, Helena; Mittl, Peer R E; Råberg, Lars

    2013-05-22

    The discovery of the key role of Toll-like receptors (TLRs) in initiating innate immune responses and modulating adaptive immunity has revolutionized our understanding of vertebrate defence against pathogens. Yet, despite their central role in pathogen recognition and defence initiation, there is little information on how variation in TLRs influences disease susceptibility in natural populations. Here, we assessed the extent of naturally occurring polymorphisms at TLR2 in wild bank voles (Myodes glareolus) and tested for associations between TLR2 variants and infection with Borrelia afzelii, a common tick-transmitted pathogen in rodents and one of the causative agents of human Lyme disease. Bank voles in our population had 15 different TLR2 haplotypes (10 different haplotypes at the amino acid level), which grouped in three well-separated clusters. In a large-scale capture-mark-recapture study, we show that voles carrying TLR2 haplotypes of one particular cluster (TLR2c2) were almost three times less likely to be Borrelia infected than animals carrying other haplotypes. Moreover, neutrality tests suggested that TLR2 has been under positive selection. This is, to our knowledge, the first demonstration of an association between TLR polymorphism and parasitism in wildlife, and a striking example that genetic variation at innate immune receptors can have a large impact on host resistance.

  4. TLR2 deficiency aggravates lung injury caused by mechanical ventilation

    NARCIS (Netherlands)

    Kuipers, Maria Theresa; Jongsma, Geartsje; Hegeman, Maria A; Tuip-de Boer, Anita M; Wolthuis, Esther K; Choi, Goda; Bresser, Paul; van der Poll, Tom; Schultz, Marcus J; Wieland, Catharina W

    Innate immunity pathways are found to play an important role in ventilator-induced lung injury. We analyzed pulmonary expression of Toll-like receptor 2 (TLR2) in humans and mice and determined the role of TLR2 in the pathogenesis of ventilator-induced lung injury in mice. Toll-like receptor 2 gene

  5. Cholesterol Oxidase Binds TLR2 and Modulates Functional Responses of Human Macrophages

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    Katarzyna Bednarska

    2014-01-01

    Full Text Available Cholesterol oxidase (ChoD is considered to be an important virulence factor for Mycobacterium tuberculosis (Mtb, but its influence on macrophage activity is unknown. Here we used Nocardia erythropolis ChoD, which is very similar to the Mtb enzyme (70% identity at the amino-acid level, to evaluate the impact of bacterial ChoD on the activity of THP-1-derived macrophages in vitro. We found that ChoD decreased the surface expression of Toll-like receptor type 2 (TLR2 and complement receptor 3 (CR3 on these macrophages. Flow cytometry and confocal microscopy showed that ChoD competed with lipoteichoic acid for ligand binding sites on TLR2 but not on CR3, suggesting that ChoD signaling is mediated via TLR2. Binding of ChoD to the membrane of macrophages had diverse effects on the activity of macrophages, activating p38 mitogen activated kinase and stimulating production of a large amount of interleukin-10. Moreover, ChoD primed macrophages to enhance the production of reactive oxygen species in response to the phorbol myristate acetate, which was reduced by “switching off” TLR-derived signaling through interleukin-1 receptor-associated kinases 1 and 4 inhibition. Our study revealed that ChoD interacts directly with macrophages via TLR2 and influences the biological activity of macrophages during the development of the initial response to infection.

  6. Meat and fiber intake and interaction with pattern recognition receptors (TLR1, TLR2, TLR4, and TLR10) in relation to colorectal cancer in a Danish prospective, case-cohort study

    DEFF Research Database (Denmark)

    Kopp, Tine Iskov; Vogel, Ulla; Tjonneland, Anne

    2018-01-01

    Background: Meat and dietary fiber are associated with increased and decreased risk of colorectal cancer (CRC), respectively. Toll-like receptors (TLRs) regulate the intestinal immune response in a complex interplay between the mucosal epithelium and the microbiota and may therefore be important...... modulators of diet-induced CRC together with other inflammatory mediators. Objective: Our aim was to investigate the association between functional TLR polymorphisms and risk of CRC and the interaction with dietary factors. Additionally, interactions with previously studied polymorphisms in IL10, IL1B, PTGS2......, and NFKB1 were assessed in order to examine possible biological pathways in meat-induced CRC. Design: A nested case-cohort study of 897 CRC cases and 1689 randomly selected participants from the Danish prospective "Diet, Cancer and Health" study encompassing 57,053 persons was performed using Cox...

  7. The effects of Ostertagia occidentalis somatic antigens on ovine TLR2 and TLR4 expression

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    Hassan BORJI

    2015-10-01

    Full Text Available Background: Recognition of helminth-derived pathogen associated molecular patterns (PAMPs by pattern recognition receptors (PRRs, including toll like recep­tors (TLRs is the first step towards initiating anti–helminth immune re­sponses.Methods: Using somatic antigens of Ostertagia occidentalis, an important abomasal parasite of ruminants, the expression of ovine TLR2 and TLR4 in peripheral blood mononuclear cells (PBMCs was analyzed by real-time quatitative reverse-transcrip­tion polymerase chain reaction (qRT-PCR. Somatic antigens of O. occidentalis were prepared to stimulate ovine PBMCs in a time and dose dependent manner.Results: A high expression of TLR2 and TLR4 was observed in PBMCs cultured with somatic antigens of the parasites specially when PBMCs were cultured with 100 µg/ml of somatic antigens and incubated for 2h. Up-regulation of TLR2 expres­sion was more pronounced and evident in our study.Conclsusion: Somatic antigens of O. occidentalis have immunostimulatory and domi­nant role on peripheral immune cells. This study provide for the first time evidence of induction of TLRs in ovine PBMCs by somatic antigen of O. occidentalis

  8. In Vivo Role of TLR2 and MyD88 Signaling in Eliciting Innate Immune Responses in Staphylococcal Endophthalmitis

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    Talreja, Deepa; Singh, Pawan Kumar; Kumar, Ashok

    2015-01-01

    Purpose. The purpose of this study was to investigate the protective mechanisms evoked by TLR2 and MyD88 signaling in bacterial endophthalmitis in vivo. Methods. Endophthalmitis was induced in wild-type (WT), TLR2−/−, MyD88−/−, and Cnlp−/− mice by intravitreal injections of a laboratory strain (RN6390) and two endophthalmitis isolates of Staphylococcus aureus. Disease progression was monitored by assessing corneal and vitreous haze, bacterial burden, and retinal tissue damage. Levels of inflammatory cytokines/chemokines were determined using quantitative RT-PCR (qRT-PCR) and ELISA. Flow cytometry was used to assess neutrophil infiltration. Cathelicidin-related antimicrobial peptide (CRAMP) expression was determined by immunostaining and dot blot. Results. Eyes infected with either laboratory or clinical isolates exhibited higher levels of inflammatory mediators at the early stages of infection (≤24 hours) in WT mice than in TLR2−/− or MyD88−/− mice. However, their levels surpassed that of WT mice at the later stages of infection (>48 hours), coinciding with increased bacterial burden and retinal damage. Both TLR2−/− and MyD88−/− retinas produced reduced levels of CRAMP, and its deficiency (Cnlp−/−) rendered the mice susceptible to increased bacterial burden and retinal tissue damage as early as 1 day post infection. Analyses of inflammatory mediators and neutrophil levels in WT versus Cnlp−/− mice showed a trend similar to that observed in TLR2 and MyD88 KO mice. Furthermore, we observed that even a 10-fold lower infective dose of S. aureus was sufficient to cause endophthalmitis in TLR2−/− and MyD88−/− mice. Conclusions. TLR2 and MyD88 signaling plays an important role in protecting the retina from staphylococcal endophthalmitis by production of the antimicrobial peptide CRAMP. PMID:25678692

  9. TLR2−/− Mice Display Decreased Severity of Giardiasis via Enhanced Proinflammatory Cytokines Production Dependent on AKT Signal Pathway

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    Xin Li

    2017-09-01

    Full Text Available Giardia infection is one of the most common causes of waterborne diarrheal disease in a wide array of mammalian hosts, including humans globally. Although numerous studies have indicated that adaptive immune responses are important for Giardia defense, however, whether the host innate immune system such as TLRs recognizes Giardia remains poorly understood. TLR2 plays a crucial role in pathogen recognition, innate immunity activation, and the eventual pathogen elimination. In this study, we investigated the role of TLR2 as a non-protective inflammatory response on controlling the severity of giardiasis. RT-PCR analysis suggested that TLR2 expression was increased in vitro. We demonstrated that Giardia lamblia-induced cytokines expression by the activation of p38 and ERK pathways via TLR2. Interestingly, the expression of IL-12 p40, TNF-α, and IL-6, but not IFN-γ, was enhanced in TLR2-blocked and TLR2−/− mouse macrophages exposed to G. lamblia trophozoites compared with wild-type (WT mouse macrophages. Further analysis demonstrated that G. lamblia trophozoites reduced cytokines secretion by activating AKT pathway in WT mouse macrophages. Immunohistochemical staining in G. lamblia cysts infected TLR2−/− and WT mice showed that TLR2 was highly expressed in duodenum in infected WT mice. Also, infected TLR2−/− and AKT-blocked mice showed an increased production of IL-12 p40 and IFN-γ compared with infected WT mice at the early stage during infection. Interestingly, infected TLR2−/− and AKT-blocked mice displayed a decreased parasite burden, an increased weight gain rate, and short parasite persistence. Histological morphometry showed shortened villus length, hyperplastic crypt and decreased ratio of villus height/crypt depth in infected WT mice compared with in infected TLR2−/− and AKT-blocked mice. Together, our results suggested that TLR2 deficiency leads to alleviation of giardiasis and reduction of parasite burden through

  10. TLR9 played a more important role than TLR2 in the combination of maltose-binding protein and BCG-induced Th1 activation.

    Science.gov (United States)

    Ni, Weihua; Wang, Fang; Liu, Guomu; Zhang, Nannan; Yuan, Hongyan; Jie, Jing; Tai, Guixiang

    2016-11-01

    Our previous study demonstrated that maltose-binding protein (MBP) combined with BCG induced synergistic mouse Th1 activation in vivo. Here, to explore the mechanism of MBP combined with BCG on Th1 activation, mouse purified CD4 + T cells were stimulated with MBP and BCG in vitro. The results showed that MBP combined with BCG synergistically increased IFN-γ production, accompanied with the upregulation of TLR2/9 expressions, suggesting that TLR2/9 were involved in the combination-induced Th1 activation. Next, TLR2 antibodies and TLR9 inhibitor were used to further analyze the effects of TLRs in Th1 activation. Results showed TLR2 antibody partly decreased MBP combined with BCG-induced IFN-γ production, MyD88 expression and IκB phosphorylation, indicating that TLR2-mediated MyD88-dependent pathway was involved in the MBP combined with BCG-induced Th1 activation. Moreover, MBP combined with BCG-induced Th1 activation was completely abrogated by TLR9 inhibitor, suggesting that TLR9-mediated MyD88-dependent pathway played a more important role than TLR2 in the combination-induced Th1 activation. Further study showed that TLR9 inhibitor downregulated TLR2 expression, suggesting that TLR9 signaling regulated TLR2 activation to favor Th1 resonse induced by MBP combined with BCG. Collectively, we demonstrated for the first time that the cross-talk of TLR2 and TLR9 triggered Th1 activation collaboratively and our findings provided valuable information about designing more effective adjuvant for cancer therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. In situ TLR2 and TLR4 expression in a murine model of mycetoma caused by Nocardia brasiliensis.

    Science.gov (United States)

    Millán-Chiu, Blanca Edith; Hernández-Hernández, Francisca; Pérez-Torres, Armando; Méndez-Tovar, Luis Javier; López-Martínez, Rubén

    2011-04-01

    Actinomycetoma caused by Nocardia brasiliensis is a common disease in tropical regions. This ailment is characterized by a localized chronic inflammation that mainly affects the lower limbs. Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, inducing the production of proinflammatory mediators. The role of TLRs in the immune response against N. brasiliensis is unknown. The aim of this work was to locate and quantify in a murine model the expression of TLR2 and TLR4 in the infection site using reverse transcription-PCR and immunohistochemistry. The results showed that TLR2 expression increased in the infected tissue, whereas TLR4 expression decreased. The presence of TLR2 and TLR4 was demonstrated in different cell populations throughout the chronic infectious process. In the early stages of this process, TLR2 was expressed in neutrophils and macrophages in direct contact with the inoculum, whereas TLR4 was observed in mast cells. In the advanced stages of the infection, TLR2 was expressed in foam cells and fibroblasts and was likely associated with bacterial containment, while TLR4 was downregulated, probably resulting in an imbalance between the host immune response and the bacterial load that favoured chronic disease. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  12. Effect of experimental ileitis on expression of tlr-2 in lymphfocytes of small intestine

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    A. S. Zherebiatiev

    2013-08-01

    Full Text Available Introduction Crohn’s disease and ulcerative colitis are the main clinical phenotypes of inflammatory bowel disease (IBD. Both forms of IBD can increase the incidence of gastrointestinal and colon cancers, and both ones are associated with significant morbidity and mortality worldwide. In addition, they can begin early in life and persist for long periods. The pathogenesis of IBD is complex and multifactorial. Differential alteration of Toll-like receptor (TLR expression in inflammatory bowel disease was first described 15 years ago. Studies have led to the current concept that TLRs represent key mediators of innate host defense in the intestine, and they are involved in mucosa maintaining as well as commensal homeostasis. Recent findings in diverse murine models of ileitis have helped to reveal the importance of TLR dysfunction mechanisms in IBD pathogenesis. The aim of research The aim of this study was to investigate the effect of acute ileitis on expression intensity of TLR-2 in lymphocytes of small intestine. Materials and methods Male Wistar rats with weight 200–250 g were housed in standard wire-mesh bottom cages at constant temperature of 25°C and 12/12 h light/dark cycles. The rats were given water and standard laboratory diet with no restriction prior to indomethacin injection. A total number of 20 rats were examined, including control group (n = 10. For induction of acute ileitis, rats received one subcutaneous dose of indomethacin (Sigma, 15 mg/kg. Tissue was examined on the fifth day. For histological examination sections were colored with haematoxylin and eosin. The TLR-2+cells were determined using a direct immunofluorescence technique with using monoclonal rat anti-TLR-2 antibodies. Images were taken by using a fluorescence microscope PrimoStar (ZEISS, Germany with a computer-assisted video system AxioCam 5c (ZEISS, Germany including the NIH-Image software (NIH Image version 1·46. All statistical analyses were performed

  13. Lipid raft localization of TLR2 and its co-receptors is independent of membrane lipid composition

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    Christine Hellwing

    2018-01-01

    Full Text Available Background Toll like receptors (TLRs are an important and evolutionary conserved class of pattern recognition receptors associated with innate immunity. The recognition of Gram-positive cell wall constituents strongly depends on TLR2. In order to be functional, TLR2 predominantly forms a heterodimer with TLR1 or TLR6 within specialized membrane microdomains, the lipid rafts. The membrane lipid composition and the physicochemical properties of lipid rafts are subject to modification by exogenous fatty acids. Previous investigations of our group provide evidence that macrophage enrichment with polyunsaturated fatty acids (PUFA induces a reordering of lipid rafts and non-rafts based on the incorporation of supplemented PUFA as well as their elongation and desaturation products. Methods In the present study we investigated potential constraining effects of membrane microdomain reorganization on the clustering of TLR2 with its co-receptors TLR1 and TLR6 within lipid rafts. To this end, RAW264.7 macrophages were supplemented with either docosahexaenoic acid (DHA or arachidonic acid (AA and analyzed for receptor expression and microdomain localization in context of TLR stimulation. Results and Conclusions Our analyses showed that receptor levels and microdomain localization were unchanged by PUFA supplementation. The TLR2 pathway, in contrast to the TLR4 signaling cascade, is not affected by exogenous PUFA at the membrane level.

  14. Modulation of neonatal microbial recognition: TLR-mediated innate immune responses are specifically and differentially modulated by human milk.

    Science.gov (United States)

    LeBouder, Emmanuel; Rey-Nores, Julia E; Raby, Anne-Catherine; Affolter, Michael; Vidal, Karine; Thornton, Catherine A; Labéta, Mario O

    2006-03-15

    The mechanisms controlling innate microbial recognition in the neonatal gut are still to be fully understood. We have sought specific regulatory mechanisms operating in human breast milk relating to TLR-mediated microbial recognition. In this study, we report a specific and differential modulatory effect of early samples (days 1-5) of breast milk on ligand-induced cell stimulation via TLRs. Although a negative modulation was exerted on TLR2 and TLR3-mediated responses, those via TLR4 and TLR5 were enhanced. This effect was observed in human adult and fetal intestinal epithelial cell lines, monocytes, dendritic cells, and PBMC as well as neonatal blood. In the latter case, milk compensated for the low capacity of neonatal plasma to support responses to LPS. Cell stimulation via the IL-1R or TNFR was not modulated by milk. This, together with the differential effect on TLR activation, suggested that the primary effect of milk is exerted upstream of signaling proximal to TLR ligand recognition. The analysis of TLR4-mediated gene expression, used as a model system, showed that milk modulated TLR-related genes differently, including those coding for signal intermediates and regulators. A proteinaceous milk component of > or =80 kDa was found to be responsible for the effect on TLR4. Notably, infant milk formulations did not reproduce the modulatory activity of breast milk. Together, these findings reveal an unrecognized function of human milk, namely, its capacity to influence neonatal microbial recognition by modulating TLR-mediated responses specifically and differentially. This in turn suggests the existence of novel mechanisms regulating TLR activation.

  15. Combined effect of TLR2 gene polymorphism and early life stress on the age at onset of bipolar disorders.

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    José Oliveira

    Full Text Available Gene-environment interactions may play an important role in modulating the impact of early-life stressful events on the clinical course of bipolar disorder (BD, particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2 and 4 (TLR4, major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified, genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02. Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

  16. Gram-positive bacterial lipoglycans based on a glycosylated diacylglycerol lipid anchor are microbe-associated molecular patterns recognized by TLR2.

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    Landry Blanc

    Full Text Available Innate immune recognition is the first line of host defense against invading microorganisms. It is a based on the detection, by pattern recognition receptors (PRRs, of invariant molecular signatures that are unique to microorganisms. TLR2 is a PRR that plays a major role in the detection of Gram-positive bacteria by recognizing cell envelope lipid-linked polymers, also called macroamphiphiles, such as lipoproteins, lipoteichoic acids and mycobacterial lipoglycans. These microbe-associated molecular patterns (MAMPs display a structure based on a lipid anchor, being either an acylated cysteine, a glycosylated diacylglycerol or a mannosyl-phosphatidylinositol respectively, and having in common a diacylglyceryl moiety. A fourth class of macroamphiphile, namely lipoglycans, whose lipid anchor is made, as for lipoteichoic acids, of a glycosylated diacylglycerol unit rather than a mannosyl-phosphatidylinositol, is found in Gram-positive bacteria and produced by certain Actinobacteria, including Micrococcus luteus, Stomatococcus mucilaginosus and Corynebacterium glutamicum. We report here that these alternative lipoglycans are also recognized by TLR2 and that they stimulate TLR2-dependant cytokine production, including IL-8, TNF-α and IL-6, and cell surface co-stimulatory molecule CD40 expression by a human macrophage cell line. However, they differ by their co-receptor requirement and the magnitude of the innate immune response they elicit. M. luteus and S. mucilaginosus lipoglycans require TLR1 for recognition by TLR2 and induce stronger responses than C. glutamicum lipoglycan, sensing of which by TLR2 is dependent on TLR6. These results expand the repertoire of MAMPs recognized by TLR2 to lipoglycans based on a glycosylated diacylglycerol lipid anchor and reinforce the paradigm that macroamphiphiles based on such an anchor, including lipoteichoic acids and alternative lipoglycans, induce TLR2-dependant innate immune responses.

  17. Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection.

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    Jincheng Chen

    2015-07-01

    Full Text Available Dengue virus (DV infection is the most prevalent mosquito-borne viral disease and its manifestation has been shown to be contributed in part by the host immune responses. In this study, pathogen recognition receptors, Toll-like receptor (TLR 2 and TLR6 were found to be up-regulated in DV-infected human PBMC using immunofluorescence staining, flow cytometry and Western blot analyses. Using ELISA, IL-6 and TNF-α, cytokines downstream of TLR2 and TLR6 signaling pathways were also found to be up-regulated in DV-infected PBMC. IL-6 and TNF-α production by PBMC were reduced when TLR2 and TLR6 were blocked using TLR2 and TLR6 neutralizing antibodies during DV infection. These results suggested that signaling pathways of TLR2 and TLR6 were activated during DV infection and its activation contributed to IL-6 and TNF-α production. DV NS1 protein was found to significantly increase the production of IL-6 and TNF-α when added to PBMC. The amount of IL-6 and TNF-α stimulated by DV NS1 protein was reduced when TLR2 and TLR6 were blocked, suggesting that DV NS1 protein is the viral protein responsible for the activation of TLR2 and TLR6 during DV infection. Secreted alkaline phosphatase (SEAP reporter assay was used to further confirm activation of TLR2 and TLR6 by DV NS1 protein. In addition, DV-infected and DV NS1 protein-treated TLR6-/- mice have higher survivability compared to DV-infected and DV NS1 protein-treated wild-type mice. Hence, activation of TLR6 via DV NS1 protein could potentially play an important role in the immunopathogenesis of DV infection.

  18. Coxiella burnetii lipopolysaccharide blocks p38α-MAPK activation through the disruption of TLR-2 and TLR-4 association

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    Filippo eConti

    2015-01-01

    Full Text Available To survive in macrophages, Coxiella burnetii hijacks the activation pathway of macrophages. Recently, we have demonstrated that C. burnetii, via its lipopolysaccharide (LPS, avoids the activation of p38α-MAPK through an antagonistic engagement of Toll-like receptor (TLR-4. We investigated the fine-tuned mechanism leading to the absence of activation of the p38α-MAPK despite TLR-4 engagement. In macrophages challenged with Escherichia coli LPS or with the LPS from the avirulent variants of C. burnetii, TLR-4 and TLR-2 co-immunoprecipitated. This association was absent in cells challenged by the LPS of pathogenic C. burnetii. The disruption makes TLRs unable to signal during the recognition of the LPS of pathogenic C. burnetii. The disruption of TLR-2 and TLR-4 was induced by the re-organization of the macrophage cytoskeleton by C. burnetii LPS. Interestingly, blocking the actin cytoskeleton re-organization relieved the disruption of the association TLR-2/TLR-4 by pathogenic C. burnetii and rescued the p38α-MAPK activation by C. burnetii. We elucidated an unexpected mechanism allowing pathogenic C. burnetii to avoid activating macrophages by the disruption of the TLR-2 and TLR-4 association.

  19. The inflammatory cytokine effect of Pam3CSK4 TLR2 agonist alone or in combination with Leishmania infantum antigen on ex-vivo whole blood from sick and resistant dogs.

    Science.gov (United States)

    Martínez-Orellana, Pamela; Quirola-Amores, Paulina; Montserrat-Sangrà, Sara; Ordeix, Laura; Llull, Joan; Álvarez-Fernández, Alejandra; Solano-Gallego, Laia

    2017-03-13

    A wide spectrum of clinical manifestations and immune responses exist in canine L. infantum infection. Ibizan hounds are more "resistant" to disease than other dog breeds. Recognition of pathogen-associated molecule patterns by toll like receptors (TLRs) rapidly triggers a variety of anti-microbial immune responses through the induction of pro-inflammatory cytokines such as TNF-α and IL-6 which may play an important role in controlling Leishmania infection. The main objective of this study was to investigate and compare the effect of a TLR2 agonist (TLR2a) alone or in combination with L. infantum antigen (LSA) on ex vivo whole blood cytokine production from healthy seronegative IFN-γ non-producer dogs from an area of low in canine leishmaniosis endemicity (n = 11); sick seropositive dogs with low production of IFN-γ (n = 17) and healthy seronegative or low positive Ibizan hounds with a predominant IFN-γ production (n = 21) from a highly endemic area. Whole blood was stimulated with medium alone (Ø), LSA, concanavalin A, TLR2 (Pam3CSK4) receptor agonist (Ø + TLR2a) and TLR2a and LSA (LSA + TLR2a) for 48 h. Supernatants were harvested for measurement of canine TNF-α and IL-6 cytokines by ELISA. A significant increase of TNF-α was found in the supernatants of stimulated blood from all groups (Ø + TLR2a and LSA + TLR2a) when compared with medium alone. A similar pattern was observed for IL-6. Interestingly, a significant increase of TNF-α production was only observed when stimulation with LSA + TLR2a was compared with TLR2a alone in Ibizan hounds. A significant increase of TNF-α production was observed with stimulation of LSA + TLR2a when compared with LSA in all groups. Significantly higher concentrations of TNF-α and IL-6 were detected in Ibizan hounds, especially for the Ø + TLR2a and LSA + TLR2a treatments compared with other groups. This study demonstrated that TLR2a alone enhances the production of the

  20. TLR2-Modulating Lipoproteins of the Mycobacterium tuberculosis Complex Enhance the HIV Infectivity of CD4+ T Cells.

    Science.gov (United States)

    Skerry, Ciaran; Klinkenberg, Lee G; Page, Kathleen R; Karakousis, Petros C

    2016-01-01

    Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA). In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (ΔlspA). Exposure of human peripheral blood mononuclear cells (PBMC) to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01), LprH (p<0.05), LprI (p<0.05), LprP (p<0.001), LprQ (p<0.005), MPT83 (p<0.005), or PhoS1 (p<0.05), resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with ΔlspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05). These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission.

  1. T cells exacerbate Lyme borreliosis in TLR2-deficient mice

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    Carrie E. Lasky

    2016-11-01

    Full Text Available Infection of humans with the spirochete, Borrelia burgdorferi, causes Lyme borreliosis and can lead to clinical manifestations such as, arthritis, carditis and neurological conditions. Experimental infection of mice recapitulates many of these symptoms and serves as a model system for the investigation of disease pathogenesis and immunity. Innate immunity is known to drive the development of Lyme arthritis and carditis, but the mechanisms driving this response remain unclear. Innate immune cells recognize B. burgdorferi surface lipoproteins primarily via Toll-like receptor (TLR2; however, previous work has demonstrated TLR2-/- mice had exacerbated disease and increased bacterial burden. We demonstrate increased CD4 and CD8 T cell infiltrates in B. burgdorferi-infected joints and hearts of C3H TLR2-/- mice. In vivo depletion of either CD4 or CD8 T cells reduced Borrelia-induced joint swelling and lowered tissue spirochete burden, while depletion of CD8 T cells alone reduced disease severity scores. Exacerbation of Lyme arthritis correlated with increased production of CXCL9 by synoviocytes and this was reduced with CD8 T cell depletion. These results demonstrate T cells can exacerbate Lyme disease pathogenesis and prolong disease resolution possibly through dysregulation of inflammatory responses and inhibition of bacterial clearance.

  2. Contrasting patterns of diversity and population differentiation at the innate immunity gene toll-like receptor 2 (TLR2) in two sympatric rodent species.

    Science.gov (United States)

    Tschirren, Barbara; Andersson, Martin; Scherman, Kristin; Westerdahl, Helena; Råberg, Lars

    2012-03-01

    Comparing patterns of diversity and divergence between populations at immune genes and neutral markers can give insights into the nature and geographic scale of parasite-mediated selection. To date, studies investigating such patterns of selection in vertebrates have primarily focused on the acquired branch of the immune system, whereas it remains largely unknown how parasite-mediated selection shapes innate immune genes both within and across vertebrate populations. Here, we present a study on the diversity and population differentiation at the innate immune gene Toll-like receptor 2 (TLR2) across nine populations of yellow-necked mice (Apodemus flavicollis) and bank voles (Myodes glareolus) in southern Sweden. In yellow-necked mice, TLR2 diversity was very low, as was TLR2 population differentiation compared to neutral loci. In contrast, several TLR2 haplotypes co-occurred at intermediate frequencies within and across bank vole populations, and pronounced isolation by distance between populations was observed. The diversity and differentiation at neutral loci was similar in the two species. These results indicate that parasite-mediated selection has been acting in dramatically different ways on a given immune gene in ecologically similar and sympatric species. Furthermore, the finding of TLR2 population differentiation at a small geographical scale in bank voles highlights that vertebrate innate immune defense may be evolutionarily more dynamic than has previously been appreciated. © 2011 The Author(s). Evolution© 2011 The Society for the Study of Evolution.

  3. Both TLR2 and TRIF contribute to interferon-β production during Listeria infection.

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    Camille Aubry

    Full Text Available Synthesis of interferon-β (IFN-β is an innate response to cytoplasmic infection with bacterial pathogens. Our recent studies showed that Listeria monocytogenes limits immune detection and IFN-β synthesis via deacetylation of its peptidoglycan, which renders the bacterium resistant to lysozyme degradation. Here, we examined signaling requirements for the massive IFN-β production resulting from the infection of murine macrophages with a mutant strain of L. monocytogenes, ΔpgdA, which is unable to modify its peptidoglycan. We report the identification of unconventional signaling pathways to the IFN-β gene, requiring TLR2 and bacterial internalization. Induction of IFN-β was independent of the Mal/TIRAP adaptor protein but required TRIF and the transcription factors IRF3 and IRF7. These pathways were stimulated to a lesser degree by wild-type L. monocytogenes. They operated in both resident and inflammatory macrophages derived from the peritoneal cavity, but not in bone marrow-derived macrophages. The novelty of our findings thus lies in the first description of TLR2 and TRIF as two critical components leading to the induction of the IFN-β gene and in uncovering that individual macrophage populations adopt different strategies to link pathogen recognition signals to IFN-β gene expression.

  4. Pimecrolimus enhances TLR2/6-induced expression of antimicrobial peptides in keratinocytes.

    Science.gov (United States)

    Büchau, Amanda S; Schauber, Jürgen; Hultsch, Thomas; Stuetz, Anton; Gallo, Richard L

    2008-11-01

    Calcineurin inhibitors are potent inhibitors of T-cell-receptor mediated activation of the adaptive immune system. The effects of this class of drug on the innate immune response system are not known. Keratinocytes are essential to innate immunity in skin and rely on toll-like receptors (TLRs) and antimicrobial peptides to appropriately recognize and respond to injury or microbes. In this study we examined the response of cultured human keratinocytes to pimecrolimus. We observed that pimecrolimus enhances distinct expression of cathelicidin, CD14, and human beta-defensin-2 and beta-defensin-3 in response to TLR2/6 ligands. Some of these responses were further enhanced by 1,25 vitamin D3. Pimecrolimus also increased the functional capacity of keratinocytes to inhibit growth of Staphylococcus aureus and decreased TLR2/6-induced expression of IL-10 and IL-1beta. Furthermore, pimecrolimus inhibited nuclear translocation of NFAT and NF-kappaB in keratinocytes. These observations uncover a previously unreported function for pimecrolimus in cutaneous innate host defense.

  5. Early decreased TLR2 expression on monocytes is associated with their reduced phagocytic activity and impaired maturation in a porcine polytrauma model

    Science.gov (United States)

    Schimunek, Lukas; Serve, Rafael; Teuben, Michel P. J.; Störmann, Philipp; Auner, Birgit; Woschek, Mathias; Pfeifer, Roman; Horst, Klemens; Simon, Tim-P.; Kalbitz, Miriam; Sturm, Ramona; Pape, Hans-C.; Hildebrand, Frank; Marzi, Ingo

    2017-01-01

    In their post-traumatic course, trauma patients suffering from multiple injuries have a high risk for immune dysregulation, which may contribute to post-injury complications and late mortality. Monocytes as specific effector cells of the innate immunity play a crucial role in inflammation. Using their Pattern Recognition Receptors (PRRs), notably Toll-Like Receptors (TLR), the monocytes recognize pathogens and/or pathogen-associated molecular patterns (PAMPs) and organize their clearance. TLR2 is the major receptor for particles of gram-positive bacteria, and initiates their phagocytosis. Here, we investigated the phagocytizing capability of monocytes in a long-term porcine severe trauma model (polytrauma, PT) with regard to their TLR2 expression. Polytrauma consisted of femur fracture, unilateral lung contusion, liver laceration, hemorrhagic shock with subsequent resuscitation and surgical fracture fixation. After induction of PT, peripheral blood was withdrawn before (-1 h) and directly after trauma (0 h), as well as 3.5 h, 5.5 h, 24 h and 72 h later. CD14+ monocytes were identified and the expression levels of H(S)LA-DR and TLR2 were investigated by flow cytometry. Additionally, the phagocytizing activity of monocytes by applying S. aureus particles labelled with pHrodo fluorescent reagent was also assessed by flow cytometry. Furthermore, blood samples from 10 healthy pigs were exposed to a TLR2-neutralizing antibody and subsequently to S. aureus particles. Using flow cytometry, phagocytizing activity was determined. P below 0.05 was considered significant. The number of CD14+ monocytes of all circulating leukocytes remained constant during the observational time period, while the percentage of CD14+H(S)LA-DR+ monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of TLR2+ expressing cells out of all monocytes significantly decreased directly, 3.5 h and 5.5 h after trauma. The percentage of phagocytizing monocytes decreased

  6. TLR2-Modulating Lipoproteins of the Mycobacterium tuberculosis Complex Enhance the HIV Infectivity of CD4+ T Cells.

    Directory of Open Access Journals (Sweden)

    Ciaran Skerry

    Full Text Available Co-infection with Mycobacterium tuberculosis accelerates progression from HIV to AIDS. Our previous studies showed that M. tuberculosis complex, unlike M. smegmatis, enhances TLR2-dependent susceptibility of CD4+ T cells to HIV. The M. tuberculosis complex produces multiple TLR2-stimulating lipoproteins, which are absent in M. smegmatis. M. tuberculosis production of mature lipoproteins and TLR2 stimulation is dependent on cleavage by lipoprotein signal peptidase A (LspA. In order to determine the role of potential TLR2-stimulating lipoproteins on mycobacterial-mediated HIV infectivity of CD4+ T cells, we generated M. smegmatis recombinant strains overexpressing genes encoding various M. bovis BCG lipoproteins, as well as a Mycobacterium bovis BCG strain deficient in LspA (ΔlspA. Exposure of human peripheral blood mononuclear cells (PBMC to M. smegmatis strains overexpressing the BCG lipoproteins, LprF (p<0.01, LprH (p<0.05, LprI (p<0.05, LprP (p<0.001, LprQ (p<0.005, MPT83 (p<0.005, or PhoS1 (p<0.05, resulted in increased HIV infectivity of CD4+ T cells isolated from these PBMC. Conversely, infection of PBMC with ΔlspA reduced HIV infectivity of CD4+ T cells by 40% relative to BCG-infected cells (p<0.05. These results may have important implications for TB vaccination programs in areas with high mother-to-child HIV transmission.

  7. Stimulus effects and the mediation of recognition memory.

    Science.gov (United States)

    McAdoo, Ryan M; Key, Kylie N; Gronlund, Scott D

    2018-04-19

    Two broad approaches characterize the type of evidence that mediates recognition memory: discrete state and continuous. Discrete-state models posit a thresholded memory process that provides accurate information about an item (it is detected) or, failing that, no mnemonic information about the item. Continuous models, in contrast, posit the existence of graded mnemonic information about an item. Evidence favoring 1 approach over the other has been mixed, suggesting the possibility that the mediation of recognition memory may be adaptable and influenced by other factors. We tested this possibility with 2 experiments that varied the semantic similarity of word targets and fillers. Experiment 1, which used semantically similar fillers, displayed evidence of continuous mediation (contrary to Kellen & Klauer, 2015), whereas Experiment 2, which used semantically dissimilar fillers, displayed evidence of discrete mediation. The results have implications for basic theories of recognition memory, as well as for theories of applied domains like eyewitness identification. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  8. IMPDHII Protein Inhibits Toll-like Receptor 2-mediated Activation of NF-κB*

    Science.gov (United States)

    Toubiana, Julie; Rossi, Anne-Lise; Grimaldi, David; Belaidouni, Nadia; Chafey, Philippe; Clary, Guilhem; Courtine, Emilie; Pene, Frederic; Mira, Jean-Paul; Claessens, Yann-Erick; Chiche, Jean-Daniel

    2011-01-01

    Toll-like receptor 2 (TLR2) plays an essential role in innate immunity by the recognition of a large variety of pathogen-associated molecular patterns. It induces its recruitment to lipid rafts induces the formation of a membranous activation cluster necessary to enhance, amplify, and control downstream signaling. However, the exact composition of the TLR2-mediated molecular complex is unknown. We performed a proteomic analysis in lipopeptide-stimulated THP1 and found IMPDHII protein rapidly recruited to lipid raft. Whereas IMPDHII is essential for lymphocyte proliferation, its biologic function within innate immune signal pathways has not been established yet. We report here that IMPDHII plays an important role in the negative regulation of TLR2 signaling by modulating PI3K activity. Indeed, IMPDHII increases the phosphatase activity of SHP1, which participates to the inactivation of PI3K. PMID:21460227

  9. Porphyromonas gingivalis evasion of autophagy and intracellular killing by human myeloid dendritic cells involves DC-SIGN-TLR2 crosstalk.

    Science.gov (United States)

    El-Awady, Ahmed R; Miles, Brodie; Scisci, Elizabeth; Kurago, Zoya B; Palani, Chithra D; Arce, Roger M; Waller, Jennifer L; Genco, Caroline A; Slocum, Connie; Manning, Matthew; Schoenlein, Patricia V; Cutler, Christopher W

    2015-02-01

    Signaling via pattern recognition receptors (PRRs) expressed on professional antigen presenting cells, such as dendritic cells (DCs), is crucial to the fate of engulfed microbes. Among the many PRRs expressed by DCs are Toll-like receptors (TLRs) and C-type lectins such as DC-SIGN. DC-SIGN is targeted by several major human pathogens for immune-evasion, although its role in intracellular routing of pathogens to autophagosomes is poorly understood. Here we examined the role of DC-SIGN and TLRs in evasion of autophagy and survival of Porphyromonas gingivalis in human monocyte-derived DCs (MoDCs). We employed a panel of P. gingivalis isogenic fimbriae deficient strains with defined defects in Mfa-1 fimbriae, a DC-SIGN ligand, and FimA fimbriae, a TLR2 agonist. Our results show that DC-SIGN dependent uptake of Mfa1+P. gingivalis strains by MoDCs resulted in lower intracellular killing and higher intracellular content of P. gingivalis. Moreover, Mfa1+P. gingivalis was mostly contained within single membrane vesicles, where it survived intracellularly. Survival was decreased by activation of TLR2 and/or autophagy. Mfa1+P. gingivalis strain did not induce significant levels of Rab5, LC3-II, and LAMP1. In contrast, P. gingivalis uptake through a DC-SIGN independent manner was associated with early endosomal routing through Rab5, increased LC3-II and LAMP-1, as well as the formation of double membrane intracellular phagophores, a characteristic feature of autophagy. These results suggest that selective engagement of DC-SIGN by Mfa-1+P. gingivalis promotes evasion of antibacterial autophagy and lysosome fusion, resulting in intracellular persistence in myeloid DCs; however TLR2 activation can overcome autophagy evasion and pathogen persistence in DCs.

  10. Microglia are required for astroglial toll-like receptor 4 response and for optimal TLR2 and TLR3 response

    DEFF Research Database (Denmark)

    Holm, Thomas H; Draeby, Dina; Owens, Trevor

    2012-01-01

    Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond as stron......Within the central nervous system, astrocytes and microglia are the primary responders to endogenous ligands released upon injury and stress, as well as to infectious pathogens. Toll-like receptors (TLRs) are implicated in recognition of both types of stimulus. Whether astrocytes respond...... astrocytes from mixed glial cultures and measured their response to TLR agonists. Our results show that the response of astrocytes to TLR2 and TLR3 agonists is greatly enhanced by, and response to TLR4 agonists is completely dependent on, the presence of functional microglia. In the case of the TLR4 response...

  11. Polymorphisms within the Toll-Like Receptor (TLR-2, -4, and -6 Genes in Cattle

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    Marco Mariotti

    2009-07-01

    Full Text Available In mammals, members of the TLR gene family play a primary role in the recognition of pathogen-associated molecular patterns from bacteria, viruses, protozoa and fungi. Recently, cattle TLR genes have been mapped to chromosomes using a radiation hybrid panel. Nucleotide sequences of bovine TLR2, TLR4 and TLR6 genes were screened to identify novel SNPs that can be used in studies of cattle resistance to diseases. In total, 8 SNPs were identified and were submitted to the NCBI dbSNP database. The frequencies of the SNPs were assessed in 16 different bovine European cattle breeds and a phylogenetic analysis carried out to describe the relationships between the breeds. Even if from our analysis the SNPs do not appear located in loci under selection, a deviation of three SNPs from Hardy Weinberg equilibrium was observed, and we hypothesize that some of the polymorphisms may be fixated since many generations. The described variations in immune function related genes will contribute to research on disease response in cattle. In fact, the SNPs can be used in association studies between polymorphisms and cattle resistance to diseases.

  12. Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

    Directory of Open Access Journals (Sweden)

    I-Chun Lin

    modulating TLR2-mediated immune activation on CD14+ monocytes.

  13. Augmented TLR2 expression on monocytes in both human Kawasaki disease and a mouse model of coronary arteritis.

    Science.gov (United States)

    Lin, I-Chun; Kuo, Ho-Chang; Lin, Ying-Jui; Wang, Feng-Shen; Wang, Lin; Huang, Shun-Chen; Chien, Shao-Ju; Huang, Chien-Fu; Wang, Chih-Lu; Yu, Hong-Ren; Chen, Rong-Fu; Yang, Kuender D

    2012-01-01

    Kawasaki disease (KD) of unknown immunopathogenesis is an acute febrile systemic vasculitis and the leading cause of acquired heart diseases in childhood. To search for a better strategy for the prevention and treatment of KD, this study compared and validated human KD immunopathogenesis in a mouse model of Lactobacillus casei cell wall extract (LCWE)-induced coronary arteritis. Recruited subjects fulfilled the criteria of KD and were admitted for intravenous gamma globulin (IVIG) treatment at the Kaohsiung Chang Gung Memorial Hospital from 2001 to 2009. Blood samples from KD patients were collected before and after IVIG treatment, and cardiovascular abnormalities were examined by transthoracic echocardiography. Wild-type male BALB/c mice (4-week-old) were intraperitoneally injected with LCWE (1 mg/mL) to induce coronary arteritis. The induced immune response in mice was examined on days 1, 3, 7, and 14 post injections, and histopathology studies were performed on days 7 and 14. Both human KD patients and LCWE-treated mice developed coronary arteritis, myocarditis, valvulitis, and pericarditis, as well as elevated plasma levels of interleukin (IL)-2, IL-6, IL-10, monocyte chemoattractant protein (MCP)-1, and tumor necrosis factor (TNF)-α in acute phase. Most of these proinflammatory cytokines declined to normal levels in mice, whereas normal levels were achieved in patients only after IVIG treatment, with a few exceptions. Toll-like receptor (TLR)-2, but not TLR4 surface enhancement on circulating CD14+ monocytes, was augmented in KD patients before IVIG treatment and in LCWE-treated mice, which declined in patients after IVIG treatment. This result suggests that that not only TLR2 augmentation on CD14+ monocytes might be an inflammatory marker for both human KD patients and LCWE-induced CAL mouse model but also this model is feasible for studying therapeutic strategies of coronary arteritis in human KD by modulating TLR2-mediated immune activation on CD14

  14. The role of TLR2 and bacterial lipoprotein in enhancing airway inflammation and immunity

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    Amit A Lugade

    2011-04-01

    Full Text Available Non-typeable Haemophilus influenzae (NTHI colonizes the lower respiratory tract of patients with chronic obstructive pulmonary disease (COPD and also causes exacerbations of the disease. The 16-kDa lipoprotein P6 has been widely studied as a potential vaccine antigen due to its highly conserved expression amongst NTHI strains. Although P6 is known to induce potent inflammatory responses, its role in the pathogenesis of NTHI infection in vivo has not been examined. Additionally, the presence of an amino-terminal lipid motif on P6 serves to activate host TLR2 signaling. The role of host Toll-like receptor 2 (TLR2 and NTHI expression of the lipoprotein P6 on the induction of airway inflammation and generation of adaptive immune responses following chronic NTHI stimulation was evaluated with TLR2-deficient mice and a P6-deficient NTHI strain. Absence of either host TLR2 or bacterial P6 resulted in diminished levels of immune cell infiltration within lungs of mice exposed to NTHI. Pro-inflammatory cytokine secretion was also reduced in lungs that did not express TLR2 or were exposed to NTHI devoid of P6. Induction of specific antibodies to P6 was severely limited in TLR2-deficient mice. Although mice exposed to the P6-deficient NTHI strain were capable of generating antibodies to other surface antigens of NTHI, these levels were lower compared to those observed in mice exposed to P6-expressing NTHI. Therefore, cognate interaction between host TLR2 and bacterial P6 serves to enhance lung inflammation and elicit robust adaptive immune responses during NTHI exposure. Strategies to limit NTHI inflammation while simultaneously promoting robust immune responses may benefit from targeting the TLR2:P6 signaling axis.

  15. The Probiotic Lactobacillus Prevents Citrobacter rodentium-Induced Murine Colitis in a TLR2-Dependent Manner.

    Science.gov (United States)

    Ryu, Seung-Hyun; Park, Jong-Hyung; Choi, Soo-Young; Jeon, Hee-Yeon; Park, Jin-Il; Kim, Jun-Young; Ham, Seung-Hoon; Choi, Yang-Kyu

    2016-07-28

    The main objective of this study was to investigate whether Lactobacillus rhamnosus GG (LGG) ameliorated the effects of Citrobactor rodentium infection in Toll-like receptor 2 (TLR2) knockout (KO) and TLR4 KO mice, as well as in wild-type C57BL/6 (B6) mice. TLR2 KO, TLR4 KO, and B6 mice were divided into three groups per each strain. Each group had an uninfected control group (n = 5), C. rodentium-infected group (n = 8), and LGG-pretreated C. rodentium-infected group (n = 8). The survival rate of B6 mice infected with C. rodentium was higher when pretreated with LGG. Pretreatment with LGG ameliorated C. rodentium-induced mucosal hyperplasia in B6 and TLR4 KO mice. However, in C-rodentium-infected TLR2 KO mice, mucosal hyperplasia persisted, regardless of pretreatment with LGG. In addition, LGG-pretreated B6 and TLR4 KO mice showed a decrease in spleen weight and downregulation of tumor necrosis factor alpha, interferon gamma, and monocyte chemotactic protein 1 mRNA expression compared with the non-pretreated group. In contrast, such changes were not observed in TLR2 KO mice, regardless of pretreatment with LGG. From the above results, we conclude that pretreatment with LGG ameliorates C. rodentium-induced colitis in B6 and TLR4 KO mice, but not in TLR2 KO mice. Therefore, LGG protects mice from C. rodentium-induced colitis in a TLR2-dependent manner.

  16. TLR2 ligands induce NF-κB activation from endosomal compartments of human monocytes.

    Directory of Open Access Journals (Sweden)

    Karim J Brandt

    Full Text Available Localization of Toll-like receptors (TLR in subcellular organelles is a major strategy to regulate innate immune responses. While TLR4, a cell-surface receptor, signals from both the plasma membrane and endosomal compartments, less is known about the functional role of endosomal trafficking upon TLR2 signaling. Here we show that the bacterial TLR2 ligands Pam3CSK4 and LTA activate NF-κB-dependent signaling from endosomal compartments in human monocytes and in a NF-κB sensitive reporter cell line, despite the expression of TLR2 at the cell surface. Further analyses indicate that TLR2-induced NF-κB activation is controlled by a clathrin/dynamin-dependent endocytosis mechanism, in which CD14 serves as an important upstream regulator. These findings establish that internalization of cell-surface TLR2 into endosomal compartments is required for NF-κB activation. These observations further demonstrate the need of endocytosis in the activation and regulation of TLR2-dependent signaling pathways.

  17. Extracellular histones promote thrombin generation through platelet-dependent mechanisms: involvement of platelet TLR2 and TLR4

    Science.gov (United States)

    Semeraro, Fabrizio; Ammollo, Concetta T.; Morrissey, James H.; Dale, George L.; Friese, Paul; Esmon, Naomi L.

    2011-01-01

    The release of histones from dying cells is associated with microvascular thrombosis and, because histones activate platelets, this could represent a possible pathogenic mechanism. In the present study, we assessed the influence of histones on the procoagulant potential of human platelets in platelet-rich plasma (PRP) and in purified systems. Histones dose-dependently enhanced thrombin generation in PRP in the absence of any trigger, as evaluated by calibrated automated thrombinography regardless of whether the contact phase was inhibited. Activation of coagulation required the presence of fully activatable platelets and was not ascribable to platelet tissue factor, whereas targeting polyphosphate with phosphatase reduced thrombin generation even when factor XII (FXII) was blocked or absent. In the presence of histones, purified polyphosphate was able to induce thrombin generation in plasma independently of FXII. In purified systems, histones induced platelet aggregation; P-selectin, phosphatidylserine, and FV/Va expression; and prothrombinase activity. Blocking platelet TLR2 and TLR4 with mAbs reduced the percentage of activated platelets and lowered the amount of thrombin generated in PRP. These data show that histone-activated platelets possess a procoagulant phenotype that drives plasma thrombin generation and suggest that TLR2 and TLR4 mediate the activation process. PMID:21673343

  18. Synergic activation of toll-like receptor (TLR) 2/6 and 9 in response to Ureaplasma parvum & urealyticum in human amniotic epithelial cells.

    Science.gov (United States)

    Triantafilou, Martha; De Glanville, Benjamin; Aboklaish, Ali F; Spiller, O Brad; Kotecha, Sailesh; Triantafilou, Kathy

    2013-01-01

    Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM), preterm labour (PL) pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs) in order to "sense" pathogens. One such family of PRRs are the Toll like receptor family (TLR). In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK) transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA), trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.

  19. Synergic activation of toll-like receptor (TLR 2/6 and 9 in response to Ureaplasma parvum & urealyticum in human amniotic epithelial cells.

    Directory of Open Access Journals (Sweden)

    Martha Triantafilou

    Full Text Available Ureaplasma species are the most frequently isolated microorganisms inside the amniotic cavity and have been associated with spontaneous abortion, chorioamnionitis, premature rupture of the membranes (PROM, preterm labour (PL pneumonia in neonates and bronchopulmonary dysplasia in neonates. The mechanisms by which Ureaplasmas cause such diseases remain unclear, but it is believed that inappropriate induction of inflammatory responses is involved, triggered by the innate immune system. As part of its mechanism of activation, the innate immune system employs germ-lined encoded receptors, called pattern recognition receptors (PRRs in order to "sense" pathogens. One such family of PRRs are the Toll like receptor family (TLR. In the current study we aimed to elucidate the role of TLRs in Ureaplasma-induced inflammation in human amniotic epithelial cells. Using silencing, as well as human embryonic kidney (HEK transfected cell lines, we demonstrate that TLR2, TLR6 and TLR9 are involved in the inflammatory responses against Ureaplasma parvum and urealyticum serovars. Ureaplasma lipoproteins, such as Multiple Banded antigen (MBA, trigger responses via TLR2/TLR6, whereas the whole bacterium is required for TLR9 activation. No major differences were observed between the different serovars. Cell activation by Ureaplasma parvum and urealyticum seem to require lipid raft function and formation of heterotypic receptor complexes comprising of TLR2 and TLR6 on the cell surface and TLR9 intracellularly.

  20. Interveillance: A New Culture of Recognition and Mediatization

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    André Jansson

    2015-10-01

    Full Text Available The everyday uses of networked media technologies, especially social media, have revolutionized the classical model of top-down surveillance. This article sketches the contours of an emerging culture of interveillance where non-hierarchical and non-systematic monitoring practices are part of everyday life. It also introduces a critical perspective on how the industrial logics of dominant social media, through which interveillance practices are normalized, resonate with social forces already at play in individualized societies. The argument is developed in three steps. Firstly, it is argued that the concept of interveillance is needed, and must be distinguished from surveillance, in order to critically assess the everyday mutual sharing and disclosure of private information (of many different kinds. Secondly, it is argued that the culture of interveillance responds to the social deficit of recognition that characterizes highly individualized societies. Finally, it is argued that the culture of interveillance constitutes a defining instance and even represents a new stage of the meta-process of mediatization. The dialectical nature of interveillance integrates and reinforces the overarching ambiguities of mediatization, whereby the opportunities for individuals and groups to achieve growing freedom and autonomy are paralleled by limitations and dependences vis-à-vis media.

  1. Identification of the key differential transcriptional responses of human whole blood following TLR2 or TLR4 ligation in-vitro.

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    Simon Blankley

    Full Text Available The use of human whole blood for transcriptomic analysis has potential advantages over the use of isolated immune cells for studying the transcriptional response to pathogens and their products. Whole blood stimulation can be carried out in a laboratory without the expertise or equipment to isolate immune cells from blood, with the added advantage of being able to undertake experiments using very small volumes of blood. Toll like receptors (TLRs are a family of pattern recognition receptors which recognise highly conserved microbial products. Using the TLR2 ligand (Pam3CSK4 and the TLR4 ligand (LPS, human whole blood was stimulated for 0, 1, 3, 6, 12 or 24 hours at which times mRNA was isolated and a comparative microarray was undertaken. A common NFκB transcriptional programme was identified following both TLR2 and TLR4 ligation which peaked at between 3 to 6 hours including upregulation of many of the NFκB family members. In contrast an interferon transcriptional response was observed following TLR4 but not TLR2 ligation as early as 1 hour post stimulation and peaking at 6 hours. These results recapitulate the findings observed in previously published studies using isolated murine and human myeloid cells indicating that in vitro stimulated human whole blood can be used to interrogate the early transcriptional kinetic response of innate cells to TLR ligands. Our study demonstrates that a transcriptomic analysis of mRNA isolated from human whole blood can delineate both the temporal response and the key transcriptional differences following TLR2 and TLR4 ligation.

  2. Gut microbial colonization orchestrates TLR2 expression, signaling and epithelial proliferation in the small intestinal mucosa.

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    Nives Hörmann

    Full Text Available The gut microbiota is an environmental factor that determines renewal of the intestinal epithelium and remodeling of the intestinal mucosa. At present, it is not resolved if components of the gut microbiota can augment innate immune sensing in the intestinal epithelium via the up-regulation of Toll-like receptors (TLRs. Here, we report that colonization of germ-free (GF Swiss Webster mice with a complex gut microbiota augments expression of TLR2. The microbiota-dependent up-regulation of components of the TLR2 signaling complex could be reversed by a 7 day broad-spectrum antibiotic treatment. TLR2 downstream signaling via the mitogen-activated protein kinase (ERK1/2 and protein-kinase B (AKT induced by bacterial TLR2 agonists resulted in increased proliferation of the small intestinal epithelial cell line MODE-K. Mice that were colonized from birth with a normal gut microbiota (conventionally-raised; CONV-R showed signs of increased small intestinal renewal and apoptosis compared with GF controls as indicated by elevated mRNA levels of the proliferation markers Ki67 and Cyclin D1, elevated transcripts of the apoptosis marker Caspase-3 and increased numbers of TUNEL-positive cells per intestinal villus structure. In accordance, TLR2-deficient mice showed reduced proliferation and reduced apoptosis. Our findings suggest that a tuned proliferation response of epithelial cells following microbial colonization could aid to protect the host from its microbial colonizers and increase intestinal surface area.

  3. Gut microbiota is a key modulator of insulin resistance in TLR 2 knockout mice.

    Directory of Open Access Journals (Sweden)

    Andréa M Caricilli

    2011-12-01

    Full Text Available Environmental factors and host genetics interact to control the gut microbiota, which may have a role in the development of obesity and insulin resistance. TLR2-deficient mice, under germ-free conditions, are protected from diet-induced insulin resistance. It is possible that the presence of gut microbiota could reverse the phenotype of an animal, inducing insulin resistance in an animal genetically determined to have increased insulin sensitivity, such as the TLR2 KO mice. In the present study, we investigated the influence of gut microbiota on metabolic parameters, glucose tolerance, insulin sensitivity, and signaling of TLR2-deficient mice. We investigated the gut microbiota (by metagenomics, the metabolic characteristics, and insulin signaling in TLR2 knockout (KO mice in a non-germ free facility. Results showed that the loss of TLR2 in conventionalized mice results in a phenotype reminiscent of metabolic syndrome, characterized by differences in the gut microbiota, with a 3-fold increase in Firmicutes and a slight increase in Bacteroidetes compared with controls. These changes in gut microbiota were accompanied by an increase in LPS absorption, subclinical inflammation, insulin resistance, glucose intolerance, and later, obesity. In addition, this sequence of events was reproduced in WT mice by microbiota transplantation and was also reversed by antibiotics. At the molecular level the mechanism was unique, with activation of TLR4 associated with ER stress and JNK activation, but no activation of the IKKβ-IκB-NFκB pathway. Our data also showed that in TLR2 KO mice there was a reduction in regulatory T cell in visceral fat, suggesting that this modulation may also contribute to the insulin resistance of these animals. Our results emphasize the role of microbiota in the complex network of molecular and cellular interactions that link genotype to phenotype and have potential implications for common human disorders involving obesity, diabetes

  4. Signatures of selection acting on the innate immunity gene Toll-like receptor 2 (TLR2) during the evolutionary history of rodents.

    Science.gov (United States)

    Tschirren, B; Råberg, L; Westerdahl, H

    2011-06-01

    Patterns of selection acting on immune defence genes have recently been the focus of considerable interest. Yet, when it comes to vertebrates, studies have mainly focused on the acquired branch of the immune system. Consequently, the direction and strength of selection acting on genes of the vertebrate innate immune defence remain poorly understood. Here, we present a molecular analysis of selection on an important receptor of the innate immune system of vertebrates, the Toll-like receptor 2 (TLR2), across 17 rodent species. Although purifying selection was the prevalent evolutionary force acting on most parts of the rodent TLR2, we found that codons in close proximity to pathogen-binding and TLR2-TLR1 heterodimerization sites have been subject to positive selection. This indicates that parasite-mediated selection is not restricted to acquired immune system genes like the major histocompatibility complex, but also affects innate defence genes. To obtain a comprehensive understanding of evolutionary processes in host-parasite systems, both innate and acquired immunity thus need to be considered. © 2011 The Authors. Journal of Evolutionary Biology © 2011 European Society For Evolutionary Biology.

  5. Siderocalin-mediated recognition, sensitization, and cellular uptake of actinides.

    Science.gov (United States)

    Allred, Benjamin E; Rupert, Peter B; Gauny, Stacey S; An, Dahlia D; Ralston, Corie Y; Sturzbecher-Hoehne, Manuel; Strong, Roland K; Abergel, Rebecca J

    2015-08-18

    Synthetic radionuclides, such as the transuranic actinides plutonium, americium, and curium, present severe health threats as contaminants, and understanding the scope of the biochemical interactions involved in actinide transport is instrumental in managing human contamination. Here we show that siderocalin, a mammalian siderophore-binding protein from the lipocalin family, specifically binds lanthanide and actinide complexes through molecular recognition of the ligands chelating the metal ions. Using crystallography, we structurally characterized the resulting siderocalin-transuranic actinide complexes, providing unprecedented insights into the biological coordination of heavy radioelements. In controlled in vitro assays, we found that intracellular plutonium uptake can occur through siderocalin-mediated endocytosis. We also demonstrated that siderocalin can act as a synergistic antenna to sensitize the luminescence of trivalent lanthanide and actinide ions in ternary protein-ligand complexes, dramatically increasing the brightness and efficiency of intramolecular energy transfer processes that give rise to metal luminescence. Our results identify siderocalin as a potential player in the biological trafficking of f elements, but through a secondary ligand-based metal sequestration mechanism. Beyond elucidating contamination pathways, this work is a starting point for the design of two-stage biomimetic platforms for photoluminescence, separation, and transport applications.

  6. Expression of TLR-2, TLR-4, NOD2 and pNF-kappaB in a neonatal rat model of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Aurelie Le Mandat Schultz

    Full Text Available BACKGROUND: The etiology of necrotizing enterocolitis (NEC results from a combination of several risk factors that act synergistically and occurs in the same circumstances as those which lead to innate immunity activation. Pattern recognition molecules could be an important player in the initiation of an exaggerated inflammatory response leading to intestinal injury in NEC. METHODOLOGY/PRINCIPAL FINDINGS: We specifically evaluated intestinal epithelial cell (IEC expression of Toll-like receptor 2 (TLR-2, TLR-4, NOD2 and phosphorylated NF-kappaB (pNF-kappaB after mucosal injury in a rat model of NEC induced by prematurity, systemic hypoxia, and a rich protein formula. In the control group (group 1, neonatal rats were full-term and breast-fed; in the experimental groups, rat pups were preterm at day 21 of gestation and rat-milk fed (group 2 or hand-gavaged with a protein rich formula after a hypoxia-reoxygenation procedure (group 3. Morphological mucosal changes in the small bowel were scored on hematoxylin- and eosin-stained sections. Immunohistochemistry was performed on frozen tissue sections using anti TLR-2 and active pNF-kappaB p65 antibodies. Real-time RT-PCR was performed to assess mRNA expression of NOD2, TLR-2 and TLR-4. Proliferation and apoptosis were studied in paraffin sections using anti Ki-67 and caspase-3 antibodies, respectively. The combination of immaturity, protein rich formula and a hypoxia-reoxygenation procedure induces pathological mucosal damage consistent with NEC. There was an overexpression of TLR-2, and pNF-kappaB in IECs that was correlated with the severity of mucosal damage, together with an increase of apoptotic IECs and markedly impaired proliferation. In addition, these immunological alterations appeared before severe mucosal damage. TLR-2 mRNA were also increased in NEC together with TLR-4 mRNA using real-time RT-PCR whereas NOD2 expression was unchanged. CONCLUSIONS/SIGNIFICANCE: These results show that this

  7. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain

    DEFF Research Database (Denmark)

    Sørensen, Louise N; Reinert, Line S; Malmgaard, Lene

    2008-01-01

    toward HSV-2 infection. After a systemic infection, the cytokine serum response was markedly reduced in the double knockout mice, but only partly affected in either strain of the single knockout mice. This was supported by in vitro data showing that HSV-induced cytokine expression relayed on TLR2 and TLR...... stimulate innate antiviral activities, thereby protecting against HSV infection in the brain....

  8. TLR2 Controls Intestinal Carcinogen Detoxication by CYP1A1

    DEFF Research Database (Denmark)

    Do, Khoa; Fink, Lisbeth Nielsen; Jensen, Thomas Elbenhardt

    2012-01-01

    of ligands for TLR2 of bacterial origin seems to be crucial for detoxication of luminal carcinogens by CYP1A1 in the intestine. This unprecedented finding indicates a complex interplay between the immune system of the host and intestinal bacteria with detoxication mechanisms. This highlights the relevance...

  9. Retinal astrocytes pretreated with NOD2 and TLR2 ligands activate uveitogenic T cells.

    Directory of Open Access Journals (Sweden)

    Guomin Jiang

    Full Text Available On entering the tissues, infiltrating autoreactive T cells must be reactivated locally to gain pathogenic activity. We have previously reported that, when activated by Toll-like receptor 3 (TLR3 and TLR4 ligands, retinal astrocytes (RACs are able to function as antigen-presenting cells to re-activate uveitogenic T cells and allow responder T cells to induce uveitis in mice. In the present study, we found that, although the triggering of TLR2 or nucleotide-binding oligomerization domain receptor 2 (NOD2 alone did not activate RACs, their combined triggering induced RACs with the phenotypes required to efficiently re-activate interphotoreceptor retinoid-binding protein (IRBP-specific T cells. The synergistic effect of TLR2 and NOD2 ligands on RAC activation might be explained by the observations that bacterial lipoprotein (BLP, a TLR2 ligand was able to upregulate NOD2 expression and the combination of BLP and muramyldipeptide (MDP, a NOD2 ligand enhanced the expression of RICK (Rip2, the signaling molecule of NOD2. Moreover, the synergistic effect of MDP and BLP on RACs was lost when the RACs were derived from NOD2 knockout mice or were pre-treated with Rip2 antagonist. Thus, our data suggest that exogenous or endogenous molecules acting on both TLR2 and NOD2 on RACs might have an enhancing effect on susceptibility to autoimmune uveitis.

  10. Histones from Dying Renal Cells Aggravate Kidney Injury via TLR2 and TLR4

    Science.gov (United States)

    Allam, Ramanjaneyulu; Scherbaum, Christina Rebecca; Darisipudi, Murthy Narayana; Mulay, Shrikant R.; Hägele, Holger; Lichtnekert, Julia; Hagemann, Jan Henrik; Rupanagudi, Khader Valli; Ryu, Mi; Schwarzenberger, Claudia; Hohenstein, Bernd; Hugo, Christian; Uhl, Bernd; Reichel, Christoph A.; Krombach, Fritz; Monestier, Marc; Liapis, Helen; Moreth, Kristin; Schaefer, Liliana

    2012-01-01

    In AKI, dying renal cells release intracellular molecules that stimulate immune cells to secrete proinflammatory cytokines, which trigger leukocyte recruitment and renal inflammation. Whether the release of histones, specifically, from dying cells contributes to the inflammation of AKI is unknown. In this study, we found that dying tubular epithelial cells released histones into the extracellular space, which directly interacted with Toll-like receptor (TLR)-2 (TLR2) and TLR4 to induce MyD88, NF-κB, and mitogen activated protein kinase signaling. Extracellular histones also had directly toxic effects on renal endothelial cells and tubular epithelial cells in vitro. In addition, direct injection of histones into the renal arteries of mice demonstrated that histones induce leukocyte recruitment, microvascular vascular leakage, renal inflammation, and structural features of AKI in a TLR2/TLR4-dependent manner. Antihistone IgG, which neutralizes the immunostimulatory effects of histones, suppressed intrarenal inflammation, neutrophil infiltration, and tubular cell necrosis and improved excretory renal function. In summary, the release of histones from dying cells aggravates AKI via both its direct toxicity to renal cells and its proinflammatory effects. Because the induction of proinflammatory cytokines in dendritic cells requires TLR2 and TLR4, these results support the concept that renal damage triggers an innate immune response, which contributes to the pathogenesis of AKI. PMID:22677551

  11. Evaluation of an intranasal virosomal vaccine against respiratory syncytial virus in mice: effect of TLR2 and NOD2 ligands on induction of systemic and mucosal immune responses.

    Directory of Open Access Journals (Sweden)

    Muhammad Shafique

    Full Text Available INTRODUCTION: RSV infection remains a serious threat to newborns and the elderly. Currently, there is no vaccine available to prevent RSV infection. A mucosal RSV vaccine would be attractive as it could induce mucosal as well as systemic antibodies, capable of protecting both the upper and lower respiratory tract. Previously, we reported on a virosomal RSV vaccine for intramuscular injection with intrinsic adjuvant properties mediated by an incorporated lipophilic Toll-like receptor 2 (TLR2 ligand. However, it has not been investigated whether this virosomal RSV vaccine candidate would be suitable for use in mucosal immunization strategies and if additional incorporation of other innate receptor ligands, like NOD2-ligand, could further enhance the immunogenicity and protective efficacy of the vaccine. OBJECTIVE: To explore if intranasal (IN immunization with a virosomal RSV vaccine, supplemented with TLR2 and/or NOD2-ligands, is an effective strategy to induce RSV-specific immunity. METHODS: We produced RSV-virosomes carrying TLR2 (Pam3CSK4 and/or NOD2 (L18-MDP ligands. We tested the immunopotentiating properties of these virosomes in vitro, using TLR2- and/or NOD2-ligand-responsive murine and human cell lines, and in vivo by assessing induction of protective antibody and cellular responses upon IN immunization of BALB/c mice. RESULTS: Incorporation of Pam3CSK4 and/or L18-MDP potentiates the capacity of virosomes to activate (antigen-presenting cells in vitro, as demonstrated by NF-κB induction. In vivo, incorporation of Pam3CSK4 in virosomes boosted serum IgG antibody responses and mucosal antibody responses after IN immunization. While L18-MDP alone was ineffective, incorporation of L18-MDP in Pam3CSK4-carrying virosomes further boosted mucosal antibody responses. Finally, IN immunization with adjuvanted virosomes, particularly Pam3CSK4/L18-MDP-adjuvanted-virosomes, protected mice against infection with RSV, without priming for enhanced

  12. Live Faecalibacterium prausnitzii induces greater TLR2 and TLR2/6 activation than the dead bacterium in an apical anaerobic co-culture system.

    Science.gov (United States)

    Maier, Eva; Anderson, Rachel C; Altermann, Eric; Roy, Nicole C

    2018-02-01

    Inappropriate activation of intestinal innate immune receptors, such as toll-like receptors (TLRs), by pathogenic bacteria is linked to chronic inflammation. In contrast, a "tonic" level of TLR activation by commensal bacteria is required for intestinal homeostasis. A technical challenge when studying this activation in vitro is the co-culturing of oxygen-requiring mammalian cells with obligate anaerobic commensal bacteria. To overcome this, we used a novel apical anaerobic co-culture system to successfully adapt a TLR activation assay to be conducted in conditions optimised for both cell types. Live Faecalibacterium prausnitzii, an abundant obligate anaerobe of the colonic microbiota, induced higher TLR2 and TLR2/6 activation than the dead bacterium. This enhanced TLR induction by live F. prausnitzii, which until now has not previously been described, may contribute to maintenance of gastrointestinal homeostasis. This highlights the importance of using physiologically relevant co-culture systems to decipher the mechanisms of action of live obligate anaerobes. © 2017 John Wiley & Sons Ltd.

  13. What Types of Visual Recognition Tasks Are Mediated by the Neural Subsystem that Subserves Face Recognition?

    Science.gov (United States)

    Brooks, Brian E.; Cooper, Eric E.

    2006-01-01

    Three divided visual field experiments tested current hypotheses about the types of visual shape representation tasks that recruit the cognitive and neural mechanisms underlying face recognition. Experiment 1 found a right hemisphere advantage for subordinate but not basic-level face recognition. Experiment 2 found a right hemisphere advantage for…

  14. [TLR2 modulates Staphylococcus aureus-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway].

    Science.gov (United States)

    Li, Shuai; Fang, Lei; Wang, Jiong; Liu, Rongyu

    2017-09-01

    Objective To investigate the molecular mechanisms of Toll-like receptor 2 (TLR2) taking part in inflammatory response in Staphylococcus aureus (SA)-induced asthma. Methods We established the cell inflammatory response model through stimulating mouse RAW264.7 macrophages with SA. The TLR2, myeloid differentiation factor 88 (MyD88), phosphoinositide-3 kinase (PI3K), nuclear factor κBp65 (NF-κBp65), phospho-NF-κBp65, beclin-1 and microtubule-associated protein 1 light chain 3B (LC3B) were detected by Western blot analysis after treatment with TLR2 small interfering RNA (siRNA) and 3-methyladenine (3-MA), and the tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were determined by ELISA. In addition, the number of autolysosomes was observed by the laser scanning confocal microscope. Results SA-stimulated macrophages activated various signaling pathways including TLR2. TLR2 siRNA markedly repressed the expressions of PI3K, phospho-NF-κBp65, the autophagy protein beclin-1 and LC3B as well as the number of autolysosomes and the production of TNF- and IL-6. We also demonstrated that 3-MA had the same effect on autophagy and inflammation as TLR2 siRNA did. Conclusion TLR2 modulates SA-induced inflammatory response and autophagy in macrophages through PI3K signaling pathway.

  15. Association of TLR1, TLR2, TLR4, TLR6, and TIRAP polymorphisms with disease susceptibility.

    Science.gov (United States)

    Noreen, Mamoona; Arshad, Muhammad

    2015-06-01

    Toll like receptors (TLRs) play a crucial role in regulation of innate as well as adaptive immunity. TLRs recognize a distinct but limited repertoire of conserved microbial products. Ligand binding to TLRs activates the signaling cascade and results in activation of multiple inflammatory genes. Variation in this immune response is under genetic control. Polymorphisms in genes associated with inflammatory pathway especially influence the outcome of diseases. TLR2 makes heterodimer with TLR1 or TLR6 and recognizes a wide variety of microbial ligands. In this review, we summarize studies of polymorphisms in genes encoding TLR1, TLR2, TLR4, TLR6, and most polymorphic adaptor protein, Mal/TIRAP, revealing their effect on susceptibility to diseases.

  16. Carbohydrate self-recognition mediates marine sponge cellular adhesion

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Haseley, S.R.; Vermeer, H.J.; Kamerling, J.P.

    2001-01-01

    Sponges (Porifera), the simplest and earliest multicellular organisms, are thought to have evolved from their unicellular ancestors about 1 billion years ago by developing cell-recognition and adhesion mechanisms to discriminate against 'non-self.' Consequently, they are used as models for

  17. Wax combs mediate nestmate recognition by guard honeybees

    DEFF Research Database (Denmark)

    D'Ettorre, Patrizia; Wenseleers, Tom; Dawson, Jenny

    2006-01-01

    Research has shown that the wax combs are important in the acquisition of colony odour in the honeybee, Apis mellifera. However, many of these studies were conducted in the laboratory or under artificial conditions. We investigated the role of the wax combs in nestmate recognition in the natural...

  18. Microglia Induce Neurotoxic IL-17+ γδ T Cells Dependent on TLR2, TLR4, and TLR9 Activation.

    Directory of Open Access Journals (Sweden)

    Katja Derkow

    Full Text Available Interleukin-17 (IL-17 acts as a key regulator in central nervous system (CNS inflammation. γδ T cells are an important innate source of IL-17. Both IL-17+ γδ T cells and microglia, the major resident immune cells of the brain, are involved in various CNS disorders such as multiple sclerosis and stroke. Also, activation of Toll-like receptor (TLR signaling pathways contributes to CNS damage. However, the mechanisms underlying the regulation and interaction of these cellular and molecular components remain unclear.In this study, we investigated the crosstalk between γδ T cells and microglia activated by TLRs in the context of neuronal damage. To this end, co-cultures of IL-17+ γδ T cells, neurons, and microglia were analyzed by immunocytochemistry, flow cytometry, ELISA and multiplex immunoassays.We report here that IL-17+ γδ T cells but not naïve γδ T cells induce a dose- and time-dependent decrease of neuronal viability in vitro. While direct stimulation of γδ T cells with various TLR ligands did not result in up-regulation of CD69, CD25, or in IL-17 secretion, supernatants of microglia stimulated by ligands specific for TLR2, TLR4, TLR7, or TLR9 induced activation of γδ T cells through IL-1β and IL-23, as indicated by up-regulation of CD69 and CD25 and by secretion of vast amounts of IL-17. This effect was dependent on the TLR adaptor myeloid differentiation primary response gene 88 (MyD88 expressed by both γδ T cells and microglia, but did not require the expression of TLRs by γδ T cells. Similarly to cytokine-primed IL-17+ γδ T cells, IL-17+ γδ T cells induced by supernatants derived from TLR-activated microglia also caused neurotoxicity in vitro. While these neurotoxic effects required stimulation of TLR2, TLR4, or TLR9 in microglia, neuronal injury mediated by bone marrow-derived macrophages did not require TLR signaling. Neurotoxicity mediated by IL-17+ γδ T cells required a direct cell-cell contact between T

  19. Valsartan independent of AT1 receptor inhibits tissue factor, TLR-2 and-4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions

    Science.gov (United States)

    Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

    2014-01-01

    Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and-4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and-4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2,-4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. PMID:25109475

  20. Valsartan independent of AT₁ receptor inhibits tissue factor, TLR-2 and -4 expression by regulation of Egr-1 through activation of AMPK in diabetic conditions.

    Science.gov (United States)

    Ha, Yu Mi; Park, Eun Jung; Kang, Young Jin; Park, Sang Won; Kim, Hye Jung; Chang, Ki Churl

    2014-10-01

    Patients suffering from diabetes mellitus (DM) are at a severe risk of atherothrombosis. Early growth response (Egr)-1 is well characterized as a central mediator in vascular pathophysiology. We tested whether valsartan independent of Ang II type 1 receptor (AT1R) can reduce tissue factor (TF) and toll-like receptor (TLR)-2 and -4 by regulating Egr-1 in THP-1 cells and aorta in streptozotocin-induced diabetic mice. High glucose (HG, 15 mM) increased expressions of Egr-1, TF, TLR-2 and -4 which were significantly reduced by valsartan. HG increased Egr-1 expression by activation of PKC and ERK1/2 in THP-1 cells. Valsartan increased AMPK phosphorylation in a concentration and time-dependent manner via activation of LKB1. Valsartan inhibited Egr-1 without activation of PKC or ERK1/2. The reduced expression of Egr-1 by valsartan was reversed by either silencing Egr-1, or compound C, or DN-AMPK-transfected cells. Valsartan inhibited binding of NF-κB and Egr-1 to TF promoter in HG condition. Furthermore, valsartan reduced inflammatory cytokine (TNF-α, IL-6 and IL-1β) production and NF-κB activity in HG-activated THP-1 cells. Interestingly, these effects of valsartan were not affected by either silencing AT1R in THP-1 cells or CHO cells, which were devoid of AT1R. Importantly, administration of valsartan (20 mg/kg, i.p) for 8 weeks significantly reduced plasma TF activity, expression of Egr-1, TLR-2, -4 and TF in thoracic aorta and improved glucose tolerance of streptozotocin-induced diabetic mice. Taken together, we concluded that valsartan may reduce atherothrombosis in diabetic conditions through AMPK/Egr-1 regulation. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  1. Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of caspase-3 activity: regulatory roles for CD14 and TLR-2.

    LENUS (Irish Health Repository)

    Power, Colm P

    2012-02-03

    The human sepsis syndrome resulting from bacterial infection continues to account for a significant proportion of hospital mortality. Neutralizing strategies aimed at individual bacterial wall products (such as LPS) have enjoyed limited success in this arena. Bacterial lipoprotein (BLP) is a major constituent of the wall of diverse bacterial forms and profoundly influences cellular function in vivo and in vitro, and has been implicated in the etiology of human sepsis. Delayed polymorphonuclear cell (PMN) apoptosis is a characteristic feature of human sepsis arising from Gram-negative or Gram-positive bacterial infection. Bacterial wall product ligation and subsequent receptor-mediated events upstream of caspase inhibition in neutrophils remain incompletely understood. BLP has been shown to exert its cellular effects primarily through TLR-2, and it is now widely accepted that lateral associations with the TLRs represent the means by which CD14 communicates intracellular messages. In this study, we demonstrate that BLP inhibits neutrophil mitochondrial membrane depolarization with a subsequent reduction in caspase-3 processing, ultimately leading to a significant delay in PMN apoptosis. Pretreatment of PMNs with an anti-TLR-2 mAb or anti-CD14 mAb prevented BLP from delaying PMN apoptosis to such a marked degree. Combination blockade using both mAbs completely prevented the effects of BLP (in 1 and 10 ng\\/ml concentrations) on PMN apoptosis. At higher concentrations of BLP, the antiapoptotic effects were observed, but were not as pronounced. Our findings therefore provide the first evidence of a crucial role for both CD14 and TLR-2 in delayed PMN apoptosis arising from bacterial infection.

  2. Right parietal cortex mediates recognition memory for melodies.

    Science.gov (United States)

    Schaal, Nora K; Javadi, Amir-Homayoun; Halpern, Andrea R; Pollok, Bettina; Banissy, Michael J

    2015-07-01

    Functional brain imaging studies have highlighted the significance of right-lateralized temporal, frontal and parietal brain areas for memory for melodies. The present study investigated the involvement of bilateral posterior parietal cortices (PPCs) for the recognition memory of melodies using transcranial direct current stimulation (tDCS). Participants performed a recognition task before and after tDCS. The task included an encoding phase (12 melodies), a retention period, as well as a recognition phase (24 melodies). Experiment 1 revealed that anodal tDCS over the right PPC led to a deterioration of overall memory performance compared with sham. Experiment 2 confirmed the results of Experiment 1 and further showed that anodal tDCS over the left PPC did not show a modulatory effect on memory task performance, indicating a right lateralization for musical memory. Furthermore, both experiments revealed that the decline in memory for melodies can be traced back to an interference of anodal stimulation on the recollection process (remember judgements) rather than to familiarity judgements. Taken together, this study revealed a causal involvement of the right PPC for memory for melodies and demonstrated a key role for this brain region in the recollection process of the memory task. © 2015 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  3. CD200R1 supports HSV-1 viral replication and licenses pro-inflammatory signaling functions of TLR2.

    Directory of Open Access Journals (Sweden)

    Roy J Soberman

    Full Text Available The CD200R1:CD200 axis is traditionally considered to limit tissue inflammation by down-regulating pro-inflammatory signaling in myeloid cells bearing the receptor. We generated CD200R1(-/- mice and employed them to explore both the role of CD200R1 in regulating macrophage signaling via TLR2 as well as the host response to an in vivo, TLR2-dependent model, herpes simplex virus 1 (HSV-1 infection. CD200R1(-/- peritoneal macrophages demonstrated a 70-75% decrease in the generation of IL-6 and CCL5 (Rantes in response to the TLR2 agonist Pam(2CSK(4 and to HSV-1. CD200R1(-/- macrophages could neither up-regulate the expression of TLR2, nor assemble a functional inflammasome in response to HSV-1. CD200R1(-/- mice were protected from HSV-1 infection and exhibited dysfunctional TLR2 signaling. Finally, both CD200R1(-/- mice and CD200R1(-/- fibroblasts and macrophages showed a markedly reduced ability to support HSV-1 replication. In summary, our data demonstrate an unanticipated and novel requirement for CD200R1 in "licensing" pro-inflammatory functions of TLR2 and in limiting viral replication that are supported by ex vivo and in vivo evidence.

  4. Chemical cues mediate species recognition in field crickets

    Directory of Open Access Journals (Sweden)

    Frances eTyler

    2015-05-01

    Full Text Available Cuticular hydrocarbons (CHCs are important in mate choice in many insects, and may be used for species recognition if CHC profiles differ between potentially hybridizing species. In the sibling field cricket species Gryllus campestris and G. bimaculatus, females of G. bimaculatus are tolerant towards G. campestris males and can mate with them. However, G. campestris females are highly aggressive towards heterospecific G. bimaculatus males, and matings between them never happen. We examined whether cricket females might use CHCs to determine the species identity of their potential mates. We firstly analyzed the cuticular chemical profile by gas chromatography and mass spectrometry to assess the potential of CHCs to be used for species recognition in these crickets. We then manipulated females’ ability to detect chemical cues by carrying out chemical ablation of the antennae, and measured changes in aggressive responses to heterospecific males. We show that there are significant interspecies differences in CHC expression for both sexes, and that females with chemically ablated antennae reduce aggressive behavior towards heterospecific males. Our findings support the prediction that cuticular semiochemicals can play a key role in reproductive isolation between closely related insect species.

  5. Extracellular vesicles modulate host-microbe responses by altering TLR2 activity and phagocytosis.

    Directory of Open Access Journals (Sweden)

    Jeroen van Bergenhenegouwen

    Full Text Available Oral delivery of Gram positive bacteria, often derived from the genera Lactobacillus or Bifidobacterium, can modulate immune function. Although the exact mechanisms remain unclear, immunomodulatory effects may be elicited through the direct interaction of these bacteria with the intestinal epithelium or resident dendritic cell (DC populations. We analyzed the immune activation properties of Lactobacilli and Bifidobacterium species and made the surprising observation that cellular responses in vitro were differentially influenced by the presence of serum, specifically the extracellular vesicle (EV fraction. In contrast to the tested Lactobacilli species, tested Bifidobacterium species induce TLR2/6 activity which is inhibited by the presence of EVs. Using specific TLR ligands, EVs were found to enhance cellular TLR2/1 and TLR4 responses while TLR2/6 responses were suppressed. No effect could be observed on cellular TLR5 responses. We determined that EVs play a role in bacterial aggregation, suggesting that EVs interact with bacterial surfaces. EVs were found to slightly enhance DC phagocytosis of Bifidobacterium breve whereas phagocytosis of Lactobacillus rhamnosus was virtually absent upon serum EV depletion. DC uptake of a non-microbial substance (dextran was not affected by the different serum fractions suggesting that EVs do not interfere with DC phagocytic capacity but rather modify the DC-microbe interaction. Depending on the microbe, combined effects of EVs on TLR activity and phagocytosis result in a differential proinflammatory DC cytokine release. Overall, these data suggest that EVs play a yet unrecognized role in host-microbe responses, not by interfering in recipient cellular responses but via attachment to, or scavenging of, microbe-associated molecular patterns. EVs can be found in any tissue or bodily fluid, therefore insights into EV-microbe interactions are important in understanding the mechanism of action of potential

  6. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Directory of Open Access Journals (Sweden)

    Shweta Jain

    Full Text Available Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID, signifying class switch recombination (CSR. Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  7. CD40 signaling synergizes with TLR-2 in the BCR independent activation of resting B cells.

    Science.gov (United States)

    Jain, Shweta; Chodisetti, Sathi Babu; Agrewala, Javed N

    2011-01-01

    Conventionally, signaling through BCR initiates sequence of events necessary for activation and differentiation of B cells. We report an alternative approach, independent of BCR, for stimulating resting B (RB) cells, by involving TLR-2 and CD40--molecules crucial for innate and adaptive immunity. CD40 triggering of TLR-2 stimulated RB cells significantly augments their activation, proliferation and differentiation. It also substantially ameliorates the calcium flux, antigen uptake capacity and ability of B cells to activate T cells. The survival of RB cells was improved and it increases the number of cells expressing activation induced deaminase (AID), signifying class switch recombination (CSR). Further, we also observed increased activation rate and decreased threshold period required for optimum stimulation of RB cells. These results corroborate well with microarray gene expression data. This study provides novel insights into coordination between the molecules of innate and adaptive immunity in activating B cells, in a BCR independent manner. This strategy can be exploited to design vaccines to bolster B cell activation and antigen presenting efficiency, leading to faster and better immune response.

  8. Ventromedial prefrontal cortex mediates visual attention during facial emotion recognition.

    Science.gov (United States)

    Wolf, Richard C; Philippi, Carissa L; Motzkin, Julian C; Baskaya, Mustafa K; Koenigs, Michael

    2014-06-01

    The ventromedial prefrontal cortex is known to play a crucial role in regulating human social and emotional behaviour, yet the precise mechanisms by which it subserves this broad function remain unclear. Whereas previous neuropsychological studies have largely focused on the role of the ventromedial prefrontal cortex in higher-order deliberative processes related to valuation and decision-making, here we test whether ventromedial prefrontal cortex may also be critical for more basic aspects of orienting attention to socially and emotionally meaningful stimuli. Using eye tracking during a test of facial emotion recognition in a sample of lesion patients, we show that bilateral ventromedial prefrontal cortex damage impairs visual attention to the eye regions of faces, particularly for fearful faces. This finding demonstrates a heretofore unrecognized function of the ventromedial prefrontal cortex-the basic attentional process of controlling eye movements to faces expressing emotion. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. DNA sensor cGAS-mediated immune recognition

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    Pengyan Xia

    2016-09-01

    Full Text Available Abstract The host takes use of pattern recognition receptors (PRRs to defend against pathogen invasion or cellular damage. Among microorganism-associated molecular patterns detected by host PRRs, nucleic acids derived from bacteria or viruses are tightly supervised, providing a fundamental mechanism of host defense. Pathogenic DNAs are supposed to be detected by DNA sensors that induce the activation of NFκB or TBK1-IRF3 pathway. DNA sensor cGAS is widely expressed in innate immune cells and is a key sensor of invading DNAs in several cell types. cGAS binds to DNA, followed by a conformational change that allows the synthesis of cyclic guanosine monophosphate–adenosine monophosphate (cGAMP from adenosine triphosphate and guanosine triphosphate. cGAMP is a strong activator of STING that can activate IRF3 and subsequent type I interferon production. Here we describe recent progresses in DNA sensors especially cGAS in the innate immune responses against pathogenic DNAs.

  10. Stimulants of Toll-like receptor (TLR)-2 and TLR-4 are abundant in certain minimally-processed vegetables.

    Science.gov (United States)

    Erridge, Clett

    2011-06-01

    Stimulants of the innate immune receptors Toll-like receptor (TLR)-2 and TLR4 have been shown to promote insulin resistance and atherosclerosis in animal models of these diseases. As minimally processed vegetables (MPV) can contain a relatively large bacterial load compared to other foodstuffs, we aimed to quantify the abundance of stimulants of TLR2 and TLR4 in MPV using a transfection-based bioassay calibrated with Escherichia coli LPS and the synthetic lipopeptide Pam(3)CSK(4). Of 5 classes of MPV and 3 classes of related vegetable products considered to be likely to contain a high microbial load, diced onion and bean sprouts contained the highest levels of stimulants of TLR2 (up to 18.5 μg Pam(3)CSK(4)-equivalents per g) and TLR4 (up to 11.4 μg LPS-equivalents per g). By contrast, the majority of fresh whole vegetables examined reproducibly contained minimal or undetectable levels of TLR2- or TLR4-stimulants. The accumulation of TLR-stimulants in MPVs correlated well with growth of enterobacterial spoilage organisms. In conclusion, the modern trend towards eating minimally processed vegetables rather than whole foods is likely to be associated with increased oral exposure to stimulants of TLR2 and TLR4. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Dysregulation of toll-like receptor (TLR) 2 expression on monocytes and upregulation of the frequency of T cells expressing TLR2 in patients with chronic hepatitis C virus infection

    DEFF Research Database (Denmark)

    Ronit, Andreas; Salem, Mohammad; Hartling, Hans J

    2013-01-01

    Toll-like receptors (TLRs) initiate inflammatory responses that may play a role in disease progression in patients infected with hepatitis C virus (HCV). TLR2 and TLR4 surface expression were assessed on CD14(+) monocytes, CD4(+) and CD8(+) T cells in treatment naïve patients with chronic HCV...... infection with fibrosis, without fibrosis, co-infected with human immunodeficiency virus (HIV), and in healthy controls. Increased expression of TLR2 was found on monocytes in HCV-infected patients with fibrosis (p...

  12. Bifidobacterium breve C50 secretes lipoprotein with CHAP domain recognized in aggregated form by TLR2.

    Science.gov (United States)

    Scuotto, Angelo; Djorie, Serge; Colavizza, Michel; Romond, Pierre-Charles; Romond, Marie-Bénédicte

    2014-12-01

    Extracellular components secreted by Bifidobacterium breve C50 can induce maturation, high IL-10 production and prolonged survival of dendritic cells via a TLR2 pathway. In this study, the components were isolated from the supernatant by gel filtration chromatography. Antibodies raised against the major compounds with molecular weight above 600 kDa (Bb C50BC) also recognized compounds of lower molecular weight (200–600 kDa). TLR2 and TLR6 bound to the components already recognized by the antibodies. Trypsin digestion of Bb C50BC released three major peptides whose sequences displayed close similarities to a putative secreted protein with a CHAP amidase domain from B. breve. The 1300-bp genomic region corresponding to the hypothetical protein was amplified by PCR. The deduced polypeptide started with an N-terminal signal sequence of 45 amino acids, containing the lipobox motif (LAAC) with the cysteine in position 25, and 2 positively charged residues within the first 14 residues of the signal sequence. Lipid detection in Bb C50BC by GC/MS further supported the implication of a lipoprotein. Sugars were also detected in Bb C50BC. Close similarity with the glucan-binding protein B from Bifidobacterium animalis of two released peptides from Bb C50BC protein suggested that glucose moieties, possibly in glucan form, could be bound to the lipoprotein. Finally, heating at 100 °C for 5 min led to the breakdown of Bb C50BC in compounds of molecular weight below 67 kDa, which suggested that Bb C50BC was an aggregate. One might assume that a basic unit was formed by the lipoprotein bound putatively to glucan. Besides the other sugars and hexosamines recognized by galectin 1 were localized at the surface of the Bb C50BC aggregate. In conclusion, the extracellular components secreted by B. breve C50 were constituted of a lipoprotein putatively associated with glucose moieties and acting in an aggregating form as an agonist of TLR2/TLR6.

  13. DMPD: The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17449723 The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. Sh...Show The Troll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. PubmedID 17449723 Title The Tro...ll in Toll: Mal and Tram as bridges for TLR2 and TLR4 signaling. Authors Sheedy F

  14. ST2 negatively regulates TLR2 signaling, but is not required for bacterial lipoprotein-induced tolerance.

    LENUS (Irish Health Repository)

    Liu, Jinghua

    2010-05-15

    Activation of TLR signaling is critical for host innate immunity against bacterial infection. Previous studies reported that the ST2 receptor, a member of the Toll\\/IL-1 receptor superfamily, functions as a negative regulator of TLR4 signaling and maintains LPS tolerance. However, it is undetermined whether ST2 negatively regulates TLR2 signaling and furthermore, whether a TLR2 agonist, bacterial lipoprotein (BLP)-induced tolerance is dependent on ST2. In this study, we show that BLP stimulation-induced production of proinflammatory cytokines and immunocomplex formation of TLR2-MyD88 and MyD88-IL-1R-associated kinase (IRAK) were significantly enhanced in ST2-deficient macrophages compared with those in wild-type controls. Furthermore, overexpression of ST2 dose-dependently attenuated BLP-induced NF-kappaB activation, suggesting a negative regulatory role of ST2 in TLR2 signaling. A moderate but significantly attenuated production of TNF-alpha and IL-6 on a second BLP stimulation was observed in BLP-pretreated, ST2-deficient macrophages, which is associated with substantially reduced IRAK-1 protein expression and downregulated TLR2-MyD88 and MyD88-IRAK immunocomplex formation. ST2-deficient mice, when pretreated with a nonlethal dose of BLP, benefitted from an improved survival against a subsequent lethal BLP challenge, indicating BLP tolerance develops in the absence of the ST2 receptor. Taken together, our results demonstrate that ST2 acts as a negative regulator of TLR2 signaling, but is not required for BLP-induced tolerance.

  15. Structure-based discovery of an immunomodulatory inhibitor of TLR1-TLR2 heterodimerization from a natural product-like database.

    Science.gov (United States)

    Zhong, Zhangfeng; Liu, Li-Juan; Dong, Zhi-Qiang; Lu, Lihua; Wang, Modi; Leung, Chung-Hang; Ma, Dik-Lung; Wang, Yitao

    2015-06-30

    We report herein the identification of an immunomodulatory natural product-like compound as a direct inhibitor of TLR1-TLR2 heterodimerization. Compound suppressed TNF-α and IL-6 secretion in Pam3CSK4-induced macrophages. Moreover, compound inhibited the phagocytic activity of macrophages, presumably through modulation of TLR1-TLR2 signaling and inactivation of NF-κB. Molecular docking revealed that compound bound to the interface region of TLR1-TLR2 by forming two hydrogen bonds with residues lining the binding site. To our knowledge, compound has been only the second inhibitor overall of TLR1-TLR2 heterodimerization reported to date.

  16. TLR-2 and TLR-4 expression in monocytes of newborns with late-onset sepsis,

    Directory of Open Access Journals (Sweden)

    Ana C.C. Redondo

    2014-09-01

    Full Text Available Objetivos: Analisar a expressão dos TLR-2 e TLR-4 em monócitos de recém-nascidos com sepse tardia. Métodos: Trata-se de um estudo prospectivo com 27 recém-nascidos a termo entre 8 e 29 dias de vida com diagnóstico clínico e laboratorial de sepse tardia dos quais dez (37% apresentaram cultura positiva. As citocinas foram determinadas por teste de CBA em sangue periférico enquanto que a expressão e MFI (mediana de intensidade de fluorescência dos TLR-2 e TLR-4 foi determinado por imunofenotipagem em monócitos de sangue periférico total através de análise pelo citômetro de fluxo BD FACSDiva. O grupo usado para comparação foi de adultos saudáveis. Resultados: Microrganismos foram identificados em 37% dos pacientes e estes juntamente com os pacientes com sepse clínica tiveram níveis elevados de citocinas pró-inflamatórias (IL-8, IL-6, IL-1β e de citocina anti-inflamatória (IL-10 corroborando o processo inflamatório/infeccioso. No monócito, a frequência de expressão do TLR-4 foi mais elevada (p = 0,01. Conclusões: Este estudo analisou a resposta imune inata no recém-nascido com sepse. Recémnascidos sépticos que dependem quase exclusivamente do sistema imune inato apresentaram pouca resposta in vivo na ativação de monócitos o que sugere uma resposta imune deficiente e maior susceptibilidade à infecção.

  17. Mycobacterium abscessus glycopeptidolipid prevents respiratory epithelial TLR2 signaling as measured by HβD2 gene expression and IL-8 release.

    Directory of Open Access Journals (Sweden)

    Lisa B Davidson

    Full Text Available Mycobacterium abscessus has emerged as an important cause of lung infection, particularly in patients with bronchiectasis. Innate immune responses must be highly effective at preventing infection with M. abscessus because it is a ubiquitous environmental saprophyte and normal hosts are not commonly infected. M. abscessus exists as either a glycopeptidolipid (GPL expressing variant (smooth phenotype in which GPL masks underlying bioactive cell wall lipids, or as a variant lacking GPL which is immunostimulatory and invasive in macrophage infection models. Respiratory epithelium has been increasingly recognized as playing an important role in the innate immune response to pulmonary pathogens. Respiratory epithelial cells express toll-like receptors (TLRs which mediate the innate immune response to pulmonary pathogens. Both interleukin-8 (IL-8 and human β-defensin 2 (HβD2 are expressed by respiratory epithelial cells in response to toll-like receptor 2 (TLR2 receptor stimulation. In this study, we demonstrate that respiratory epithelial cells respond to M. abscessus variants lacking GPL with expression of IL-8 and HβD2. Furthermore, we demonstrate that this interaction is mediated through TLR2. Conversely, M. abscessus expressing GPL does not stimulate expression of IL-8 or HβD2 by respiratory epithelial cells which is consistent with "masking" of underlying bioactive cell wall lipids by GPL. Because GPL-expressing smooth variants are the predominant phenotype existing in the environment, this provides an explanation whereby initial M. abscessus colonization of abnormal lung airways escapes detection by the innate immune system.

  18. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    Directory of Open Access Journals (Sweden)

    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  19. TLR9 is required for MAPK/NF-κB activation but does not cooperate with TLR2 or TLR6 to induce host resistance to Brucella abortus.

    Science.gov (United States)

    Gomes, Marco Túlio; Campos, Priscila Carneiro; Pereira, Guilherme de Sousa; Bartholomeu, Daniella Castanheira; Splitter, Gary; Oliveira, Sergio Costa

    2016-05-01

    Brucella abortus is a Gram-negative intracellular bacterial pathogen that causes a zoonosis of worldwide occurrence, leading to undulant fever in humans and abortion in domestic animals. B. abortus is recognized by several pattern-recognition receptors triggering pathways during the host innate immune response. Therefore, here, we determined the cooperative role of TLR9 with TLR2 or TLR6 receptors in sensing Brucella Furthermore, we deciphered the host innate immune response against B. abortus or its DNA, emphasizing the role of TLR9-MAPK/NF-κB signaling pathways in the production of proinflammatory cytokines. TLR9 is required for the initial host control of B. abortus, but this TLR was dispensable after 6 wk of infection. The susceptibility of TLR9(-/-)-infected animals to Brucella paralleled with lower levels of IFN-γ produced by mouse splenocytes stimulated with this pathogen compared with wild-type cells. However, no apparent cooperative interplay was observed between TLR2-TLR9 or TLR6-TLR9 receptors to control infection. Moreover, B. abortus or its DNA induced activation of MAPK/NF-κB pathways and production of IL-12 and TNF-α by macrophages partially dependent on TLR9 but completely dependent on MyD88. In addition, B. abortus-derived CpG oligonucleotides required TLR9 to promote IL-12 and TNF-α production by macrophages. By confocal microscopy, we demonstrated that TLR9 redistributed and colocalized with lysosomal-associated membrane protein-1 upon Brucella infection. Thus, B. abortus induced TLR9 traffic, leading to cell signaling activation and IL-12 and TNF-α production. Although TLR9 recognized Brucella CpG motifs, our results suggest a new pathway of B. abortus DNA-activating macrophages independent of TLR9. © Society for Leukocyte Biology.

  20. Up-regulation of TLR2 and TLR4 in high mobility group Box1-stimulated macrophages in pulpitis patients

    Science.gov (United States)

    Mahmoudi, Javad; Sabermarouf, Babak; Baradaran, Behzad; Sadat-Hatamnezhad, Leila; Shotorbani, Siamak Sandoghchian

    2017-01-01

    Objective(s): High Mobility Group Box1 (HMGB1) is a nonhistone, DNA-binding protein that serves a crucial role in regulating gene transcription and is involved in a variety of proinflammatory, extracellular activities. The aim of this study was to explore whether HMGB1 stimulation can up-regulate the expression of Toll-like Receptor 2 (TLR2) and Toll-like Receptor 4 (TLR4) on macrophages from pulpitis and to clarify the subsequent events involving Th17 cells and Th17 cell-associated cytokine changes. Materials and Methods: Having prepared dental pulp tissues of pulpitis and healthy controls, macrophage were isolated and cultured. Macrophages were thereafter stimulated by HMGB1 time course. RT-QPCR, flowcytometer, immunofluorescence, Western blotting, and ELISA techniques were used in the present research. Results: Our results showed that the expression of TLR2 and TLR4 on macrophages stimulated with HMGB1 increased in pulpitis compared with controls (macrophages without HMGB1 stimulation) with a statistical significance (Ppulpitis increased, and NF-kB, the downstream target of TLR2 and TLR4, also showed a marked elevation after macrophages’ stimulation by HMGB1. Conclusion: The evidence from the present study suggests that the enhanced TLR2 and TLR4 pathways and Th17 cell polarization may be due to HMGB1 stimulation in pulpitis. PMID:28293399

  1. Staphylococcus epidermidis polysaccharide intercellular adhesin induces IL-8 expression in human astrocytes via a mechanism involving TLR2.

    LENUS (Irish Health Repository)

    Stevens, Niall T

    2009-03-01

    Staphylococcus epidermidis is an opportunistic biofilm-forming pathogen associated with neurosurgical device-related meningitis. Expression of the polysaccharide intercellular adhesin (PIA) on its surface promotes S. epidermidis biofilm formation. Here we investigated the pro-inflammatory properties of PIA against primary and transformed human astrocytes. PIA induced IL-8 expression in a dose- and\\/or time-dependent manner from U373 MG cells and primary normal human astrocytes. This effect was inhibited by depletion of N-acetyl-beta-d-glucosamine polymer from the PIA preparation with Lycopersicon esculentum lectin or sodium meta-periodate. Expression of dominant-negative versions of the TLR2 and TLR4 adaptor proteins MyD88 and Mal in U373 MG cells inhibited PIA-induced IL-8 production. Blocking IL-1 had no effect. PIA failed to induce IL-8 production from HEK293 cells stably expressing TLR4. However, in U373 MG cells which express TLR2, neutralization of TLR2 impaired PIA-induced IL-8 production. In addition to IL-8, PIA also induced expression of other cytokines from U373 MG cells including IL-6 and MCP-1. These data implicate PIA as an important immunogenic component of the S. epidermidis biofilm that can regulate pro-inflammatory cytokine production from human astrocytes, in part, via TLR2.

  2. Attitude and Entrepreneurial Intention Among Rural Community: the Mediating Role of Entrepreneurial Opportunity Recognition

    Directory of Open Access Journals (Sweden)

    Dahalan Norziani

    2015-01-01

    Full Text Available Entrepreneurship has been well documented to have an economic and social implication for the nation to increase income. Most of developing countries give further consideration to include entrepreneurship as an agenda to help the poor to increase the living standard. In fact, entrepreneurship offers various business opportunities for rural communities to achieve better quality of life. However, the crucial part of doing business is to recognize business opportunity. Entrepreneurship and opportunity are two terms that complement each other. Opportunity recognition enables the entrepreneur to identify a good idea and transform it into a business concept. The purpose of this study is to examine the relationship between attitude (attitude toward money, attitude toward start-up and entrepreneurial intention. This paper also intends to understand the role of entrepreneurial opportunity recognition as a mediator between attitude and entrepreneurial intention. The aim of this research is to support training providers, to identify input for entrepreneurial training, specifically developing business concepts among rural community. From the practical perspective, it might help the government to understand the necessity to encourage entrepreneurial movement among rural community as to ensure business ideas flow. This research employed the quantitative method of data collection. The questionnaires were distributed to 500 local populations according to districts and villages. The findings of this study showed that both attitude (attitude toward money, attitude toward start-up influence entrepreneurial intention. The relationship between attitude toward start-up and entrepreneurial intention was mediated by opportunity recognition.

  3. Recognition

    DEFF Research Database (Denmark)

    Gimmler, Antje

    2017-01-01

    In this article, I shall examine the cognitive, heuristic and theoretical functions of the concept of recognition. To evaluate both the explanatory power and the limitations of a sociological concept, the theory construction must be analysed and its actual productivity for sociological theory mus...

  4. Sibling Rivalry in Myxococcus xanthus Is Mediated by Kin Recognition and a Polyploid Prophage.

    Science.gov (United States)

    Dey, Arup; Vassallo, Christopher N; Conklin, Austin C; Pathak, Darshankumar T; Troselj, Vera; Wall, Daniel

    2016-01-19

    Myxobacteria form complex social communities that elicit multicellular behaviors. One such behavior is kin recognition, in which cells identify siblings via their polymorphic TraA cell surface receptor, to transiently fuse outer membranes and exchange their contents. In addition, outer membrane exchange (OME) regulates behaviors, such as inhibition of wild-type Myxococcus xanthus (DK1622) from swarming. Here we monitored the fate of motile cells and surprisingly found they were killed by nonmotile siblings. The kill phenotype required OME (i.e., was TraA dependent). The genetic basis of killing was traced to ancestral strains used to construct DK1622. Specifically, the kill phenotype mapped to a large "polyploid prophage," Mx alpha. Sensitive strains contained a 200-kb deletion that removed two of three Mx alpha units. To explain these results, we suggest that Mx alpha expresses a toxin-antitoxin cassette that uses the OME machinery of M. xanthus to transfer a toxin that makes the population "addicted" to Mx alpha. Thus, siblings that lost Mx alpha units (no immunity) are killed by cells that harbor the element. To test this, an Mx alpha-harboring laboratory strain was engineered (by traA allele swap) to recognize a closely related species, Myxococcus fulvus. As a result, M. fulvus, which lacks Mx alpha, was killed. These TraA-mediated antagonisms provide an explanation for how kin recognition specificity might have evolved in myxobacteria. That is, recognition specificity is determined by polymorphisms in traA, which we hypothesize were selected for because OME with non-kin leads to lethal outcomes. The transition from single cell to multicellular life is considered a major evolutionary event. Myxobacteria have successfully made this transition. For example, in response to starvation, individual cells aggregate into multicellular fruiting bodies wherein cells differentiate into spores. To build fruits, cells need to recognize their siblings, and in part, this is

  5. Virus-mediated suppression of host non-self recognition facilitates horizontal transmission of heterologous viruses.

    Directory of Open Access Journals (Sweden)

    Songsong Wu

    2017-03-01

    Full Text Available Non-self recognition is a common phenomenon among organisms; it often leads to innate immunity to prevent the invasion of parasites and maintain the genetic polymorphism of organisms. Fungal vegetative incompatibility is a type of non-self recognition which often induces programmed cell death (PCD and restricts the spread of molecular parasites. It is not clearly known whether virus infection could attenuate non-self recognition among host individuals to facilitate its spread. Here, we report that a hypovirulence-associated mycoreovirus, named Sclerotinia sclerotiorum mycoreovirus 4 (SsMYRV4, could suppress host non-self recognition and facilitate horizontal transmission of heterologous viruses. We found that cell death in intermingled colony regions between SsMYRV4-infected Sclerotinia sclerotiorum strain and other tested vegetatively incompatible strains was markedly reduced and inhibition barrage lines were not clearly observed. Vegetative incompatibility, which involves Heterotrimeric guanine nucleotide-binding proteins (G proteins signaling pathway, is controlled by specific loci termed het (heterokaryon incompatibility loci. Reactive oxygen species (ROS plays a key role in vegetative incompatibility-mediated PCD. The expression of G protein subunit genes, het genes, and ROS-related genes were significantly down-regulated, and cellular production of ROS was suppressed in the presence of SsMYRV4. Furthermore, SsMYRV4-infected strain could easily accept other viruses through hyphal contact and these viruses could be efficiently transmitted from SsMYRV4-infected strain to other vegetatively incompatible individuals. Thus, we concluded that SsMYRV4 is capable of suppressing host non-self recognition and facilitating heterologous viruses transmission among host individuals. These findings may enhance our understanding of virus ecology, and provide a potential strategy to utilize hypovirulence-associated mycoviruses to control fungal diseases.

  6. Vitamin K2 can suppress the expression of Toll-like receptor 2 (TLR2) and TLR4, and inhibit calcification of aortic intima in ApoE-/- mice as well as smooth muscle cells.

    Science.gov (United States)

    Wang, Zhaojun; Wang, Zhongqun; Zhu, Jie; Long, Xinguang; Yan, Jinchuan

    2018-02-01

    Background and objectives Vascular calcification is a common complication in atherosclerosis. Accumulating evidence showed that Toll-like receptors (TLRs) mediate pro-inflammatory and atherosclerosis. Recent studies demonstrated that vascular calcification is one of the detrimental effects of vitamin K (Vit K) antagonists. However, the effects of Vit K on the expression of TLR2 and 4 and intimal calcification in artery remained unidentified. Methods and results Eighteen ApoE -/- mice were randomly divided into model group, Vit K-treated group, and control group. The mice of model and Vit K-treated group were fed with high-fat diet, while control group mice were fed with normal diet. Mice of Vit K-treated group were administered orally with vitamin K2 (40 mg.kg -1 .day -1 ) for 12 weeks. Twelve weeks later the aortic sections of mice were acquired and stained with hematoxylin and eosin and von Kossa, respectively. Calcium content and activity of alkaline phosphatase (ALP) at aortic tissues were measured. The expression levels of TLR2 and TLR4 in aorta sections were detected by immunohistochemisty and RT-PCR, respectively. The effects of Vit K on cellular calcification were further studied in A7r5 SMCs. Results demonstrated that high-fat diet induced typical atherosclerosis with intimal calcification in ApoE -/- mice, while in Vit K-treated group atherosclerosis and calcium deposits were not serious; Vit K2 also inhibited cellular calcification in A7r5 SMCs. Quantitative analysis showed that calcium and ALP activity at aortic tissues in the Vit K-treated mice were significantly lower than that of the model group ( P < 0.01); Compared to the control group, the expression levels of TLR2 and TLR4 in the model group were significantly higher ( P < 0.05), while in Vit K-treated group the levels of TLR2 and 4 were significantly lower than that in the model group. Furthermore, the content of calcium was positively related to the expression levels of TLR2 and TLR4

  7. MiR-23a-5p modulates mycobacterial survival and autophagy during mycobacterium tuberculosis infection through TLR2/MyD88/NF-κB pathway by targeting TLR2.

    Science.gov (United States)

    Gu, Xing; Gao, Yan; Mu, De-Guang; Fu, En-Qing

    2017-05-15

    Autophagy plays a pivotal role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M.tb.). The emerging roles of microRNAs (miRNAs) in regulating immune responses have attracted increasing attention in recent years. Appreciating the potential of host-directed therapies designed to control autophagy during mycobacterial infection, we focused on the influence of miR-23a-5p on the activation of macrophage autophagy during M.tb. infection in bone marrow-derived macrophages (BMDMs) and murine RAW264.7 cells. Here, we demonstrated that M.tb.-infection of macrophages lead to markedly enhanced expression of miR-23a-5p in a time- and dose-dependent manner. Furthermore, forced expression of miR-23a-5p accelerated the survival rate of intracellular mycobacteria, while transfection with miR-23a-5p inhibitors attenuated mycobacterial survival. More importantly, overexpression of miR-23a-5p dramatically prevented M.tb.-induced activation of autophagy in macrophages, whereas inhibitors of miR-23a-5p remarkably accelerated M.tb.-induced autophagy. Mechanistically, miR-23a-5p is able to modulate TLR2/MyD88/NF-κB signaling activity by targeting TLR2 in RAW264.7 cells in response to M.tb.-infection. Collectively, these findings demonstrated that miR-23a-5p modulated the innate host defense by promoting mycobacteria survival and inhibiting the activation of autophagy against M.tb. through TLR2/MyD88/NF-κB pathway by targeting TLR2, which may provide a promising therapeutic target for tuberculosis. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Relative judgment theory and the mediation of facial recognition: Implications for theories of eyewitness identification.

    Science.gov (United States)

    McAdoo, Ryan M; Gronlund, Scott D

    2016-01-01

    Many in the eyewitness identification community believe that sequential lineups are superior to simultaneous lineups because simultaneous lineups encourage inappropriate choosing due to promoting comparisons among choices (a relative judgment strategy), but sequential lineups reduce this propensity by inducing comparisons of lineup members directly to memory rather than to each other (an absolute judgment strategy). Different versions of the relative judgment theory have implicated both discrete-state and continuous mediation of eyewitness decisions. The theory has never been formally specified, but (Yonelinas, J Exp Psychol Learn Mem Cogn 20:1341-1354, 1994) dual-process models provide one possible specification, thereby allowing us to evaluate how eyewitness decisions are mediated. We utilized a ranking task (Kellen and Klauer, J Exp Psychol Learn Mem Cogn 40:1795-1804, 2014) and found evidence for continuous mediation when facial stimuli match from study to test (Experiment 1) and when they mismatch (Experiment 2). This evidence, which is contrary to a version of relative judgment theory that has gained a lot of traction in the legal community, compels reassessment of the role that guessing plays in eyewitness identification. Future research should continue to test formal explanations in order to advance theory, expedite the development of new procedures that can enhance the reliability of eyewitness evidence, and to facilitate the exploration of task factors and emergent strategies that might influence when recognition is continuously or discretely mediated.

  9. TOLL-LIKE RECEPTORS (TLR 2 AND 4 EXPRESSION OF KERATINOCYTES FROM PATIENTS WITH LOCALIZED AND DISSEMINATED DERMATOPHYTOSIS

    Directory of Open Access Journals (Sweden)

    Cristiane Beatriz de Oliveira

    2015-02-01

    Full Text Available There are few studies on the role of innate immune response in dermatophytosis. An investigation was conducted to define the involvement of Toll-Like Receptors (TLRs 2 and 4 in localized (LD and disseminated (DD dermatophytosis due to T. rubrum. Fifteen newly diagnosed patients, eight patients with LD and seven with DD, defined by involvement of at least three body segments were used in this study. Controls comprised twenty skin samples from healthy individuals undergoing plastic surgery. TLR2 and TLR4 were quantified in skin lesions by immunohistochemistry. A reduced expression of TLR4 in the lower and upper epidermis of both LD and DD patients was found compared to controls; TLR2 expression was preserved in the upper and lower epidermis of all three groups. As TLR4 signaling induces the production of inflammatory cytokines and neutrophils recruitment, its reduced expression likely contributed to the lack of resolution of the infection and the consequent chronic nature of the dermatophytosis. As TLR2 expression acts to limit the inflammatory process and preserves the epidermal structure, its preserved expression may also contribute to the persistent infection and limited inflammation that are characteristic of dermatophytic infections.

  10. Distinct parietal sites mediate the influences of mood, arousal, and their interaction on human recognition memory.

    Science.gov (United States)

    Greene, Ciara M; Flannery, Oliver; Soto, David

    2014-12-01

    The two dimensions of emotion, mood valence and arousal, have independent effects on recognition memory. At present, however, it is not clear how those effects are reflected in the human brain. Previous research in this area has generally dealt with memory for emotionally valenced or arousing stimuli, but the manner in which interacting mood and arousal states modulate responses in memory substrates remains poorly understood. We investigated memory for emotionally neutral items while independently manipulating mood valence and arousal state by means of music exposure. Four emotional conditions were created: positive mood/high arousal, positive mood/low arousal, negative mood/high arousal, and negative mood/low arousal. We observed distinct effects of mood valence and arousal in parietal substrates of recognition memory. Positive mood increased activity in ventral posterior parietal cortex (PPC) and orbitofrontal cortex, whereas arousal condition modulated activity in dorsal PPC and the posterior cingulate. An interaction between valence and arousal was observed in left ventral PPC, notably in a parietal area distinct from the those identified for the main effects, with a stronger effect of mood on recognition memory responses here under conditions of relative high versus low arousal. We interpreted the PPC activations in terms of the attention-to-memory hypothesis: Increased arousal may lead to increased top-down control of memory, and hence dorsal PPC activation, whereas positive mood valence may result in increased activity in ventral PPC regions associated with bottom-up attention to memory. These findings indicate that distinct parietal sites mediate the influences of mood, arousal, and their interplay during recognition memory.

  11. Slp-76 is a critical determinant of NK cell-mediated recognition of missing-self targets

    OpenAIRE

    Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

    2015-01-01

    Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying “missing-self” recognition, including the involvement of activating receptors, remain poorly understood. Using ENU mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell-mediated recognition and elimination of “missing-self” targets. The causative mutation was linked to chromosome 11 and identified as a mi...

  12. Theory of mind as a mediator of reasoning and facial emotion recognition: findings from 200 healthy people.

    Science.gov (United States)

    Lee, Seul Bee; Koo, Se Jun; Song, Yun Young; Lee, Mi Kyung; Jeong, Yu-Jin; Kwon, Catherine; Park, Kyoung Ri; Park, Jin Young; Kang, Jee In; Lee, Eun; An, Suk Kyoon

    2014-04-01

    It was proposed that the ability to recognize facial emotions is closely related to complex neurocognitive processes and/or skills related to theory of mind (ToM). This study examines whether ToM skills mediate the relationship between higher neurocognitive functions, such as reasoning ability, and facial emotion recognition. A total of 200 healthy subjects (101 males, 99 females) were recruited. Facial emotion recognition was measured through the use of 64 facial emotional stimuli that were selected from photographs from the Korean Facial Expressions of Emotion (KOFEE). Participants were requested to complete the Theory of Mind Picture Stories task and Standard Progressive Matrices (SPM). Multiple regression analysis showed that the SPM score (t=3.19, p=0.002, β=0.22) and the overall ToM score (t=2.56, p=0.011, β=0.18) were primarily associated with a total hit rate (%) of the emotion recognition task. Hierarchical regression analysis through a three-step mediation model showed that ToM may partially mediate the relationship between SPM and performance on facial emotion recognition. These findings imply that higher neurocognitive functioning, inclusive of reasoning, may not only directly contribute towards facial emotion recognition but also influence ToM, which in turn, influences facial emotion recognition. These findings are particularly true for healthy young people.

  13. Theory of Mind as a Mediator of Reasoning and Facial Emotion Recognition: Findings from 200 Healthy People

    Science.gov (United States)

    Lee, Seul Bee; Koo, Se Jun; Song, Yun Young; Lee, Mi Kyung; Jeong, Yu-Jin; Kwon, Catherine; Park, Kyoung Ri; Kang, Jee In; Lee, Eun

    2014-01-01

    Objective It was proposed that the ability to recognize facial emotions is closely related to complex neurocognitive processes and/or skills related to theory of mind (ToM). This study examines whether ToM skills mediate the relationship between higher neurocognitive functions, such as reasoning ability, and facial emotion recognition. Methods A total of 200 healthy subjects (101 males, 99 females) were recruited. Facial emotion recognition was measured through the use of 64 facial emotional stimuli that were selected from photographs from the Korean Facial Expressions of Emotion (KOFEE). Participants were requested to complete the Theory of Mind Picture Stories task and Standard Progressive Matrices (SPM). Results Multiple regression analysis showed that the SPM score (t=3.19, p=0.002, β=0.22) and the overall ToM score (t=2.56, p=0.011, β=0.18) were primarily associated with a total hit rate (%) of the emotion recognition task. Hierarchical regression analysis through a three-step mediation model showed that ToM may partially mediate the relationship between SPM and performance on facial emotion recognition. Conclusion These findings imply that higher neurocognitive functioning, inclusive of reasoning, may not only directly contribute towards facial emotion recognition but also influence ToM, which in turn, influences facial emotion recognition. These findings are particularly true for healthy young people. PMID:24843363

  14. Helping, mediating, and gaining recognition: The everyday identity work of Romanian health social workers.

    Science.gov (United States)

    Ciocănel, Alexandra; Lazăr, Florin; Munch, Shari; Harmon, Cara; Rentea, Georgiana-Cristina; Gaba, Daniela; Mihai, Anca

    2018-03-01

    Health social work is a field with challenges, opportunities, and ways of professing social work that may vary between different national contexts. In this article, we look at how Romanian health social workers construct their professional identity through their everyday identity work. Drawing on a qualitative study based on interviews with 21 health social workers working in various organizational contexts, we analyze what health social workers say they do and how this shapes their self-conception as professionals. Four main themes emerged from participants' descriptions: being a helping professional, being a mediator, gaining recognition, and contending with limits. Through these themes, participants articulated the everyday struggles and satisfactions specific to working as recently recognized professionals in Romanian health and welfare systems not always supportive of their work.

  15. Novel glycolipid TLR2 ligands of the type Pam2Cys-α-Gal: synthesis and biological properties.

    Science.gov (United States)

    Thomann, Jean-Sébastien; Monneaux, Fanny; Creusat, Gaëlle; Spanedda, Maria Vittoria; Heurtault, Béatrice; Habermacher, Chloé; Schuber, Francis; Bourel-Bonnet, Line; Frisch, Benoît

    2012-05-01

    A more complete understanding of the mechanism of action of TLR agonists has fueled the investigation of new synthetic immunoadjuvants. In this context, we designed and synthesized glycolipids of the type Pam(2)Cys-α-Galactose as novel immunoadjuvants. Their synthesis required modifying a hydrophobic tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety, i.e. the minimal structure required for TLR2 agonist activity, by addition of a hydrophilic head, either an α-Galactosylpyranose or an α-Galactosylfuranose to gain respectively Pam(2)CGalp and Pam(2)CGalf. While preparing a carbohydrate building block, an unexpected stereoselectivity was observed during a halide ion-catalytic process on a protected galactofuranose: the alpha anomer was obtained with surprisingly high selectivity (α/β ratio>9) and with good isolated yield (51%). The TLR2 binding properties of Pam(2)CGalp and Pam(2)CGalf were then fully evaluated. Their efficiency in triggering the proliferation of BALB/c mouse splenocytes was also compared to that of Pam(2)CAG and Pam(3)CAG, two well-established ligands of TLRs. Moreover, the maturation state of murine dendritic cells previously incubated with either Pam(2)CGalp or Pam(2)CGalf was monitored by flow cytometry and compared to that induced by lipopolysaccharide. Pam(2)CGalp and Pam(2)CGalf were found to be equivalent TLR2 agonists, and induced splenocyte proliferation and DC maturation. With very similar activity, Pam(2)CGalp and Pam(2)CGalf were also 10-fold to 100-fold better than Pam(2)CAG and Pam(3)CAG at inducing B cell proliferation. This represents the first time a glucidic head has been added to the tBoc-[2,3-bispalmitoyloxy-(2R)-propyl]-R-cysteinyl moiety whilst maintaining the immunomodulating activity. This should greatly enrich the data available on Pam(2)C structure/activity relationships. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  16. Computer-Mediated Input, Output and Feedback in the Development of L2 Word Recognition from Speech

    Science.gov (United States)

    Matthews, Joshua; Cheng, Junyu; O'Toole, John Mitchell

    2015-01-01

    This paper reports on the impact of computer-mediated input, output and feedback on the development of second language (L2) word recognition from speech (WRS). A quasi-experimental pre-test/treatment/post-test research design was used involving three intact tertiary level English as a Second Language (ESL) classes. Classes were either assigned to…

  17. An Agent-mediated Ontology-based Approach for Composite Activity Recognition in Smart Homes

    OpenAIRE

    Okeyo, George; Chen, Liming; Wang, H.

    2013-01-01

    Activity recognition enables ambient assisted living applications to provide activity-aware services to users in smart homes. Despite significant progress being made in activity recognition research, the focus has been on simple activity recognition leaving composite activity recognition an open problem. For instance, knowledge-driven activity recognition has recently attracted increasing attention but mainly focused on simple activities. This paper extends previous work by introducing a know...

  18. A novel CCR-2/TLR-2 triggered signaling in murine peritoneal macrophages intensifies bacterial (Staphylococcus aureus) killing by reactive oxygen species through TNF-R1.

    Science.gov (United States)

    Nandi, Ajeya; Bishayi, Biswadev

    2017-10-01

    Macrophages are remarkably versatile in their ability to recognize and respond to a wide range of stimuli by expressing a variety of surface and intracellular receptors and triggering multiple signal transduction pathways. The onset of microbial infection is primarily determined by the initial contacts made by the microbes with the host macrophages. Although there prevail a relationship between the chemokine receptor and Toll like receptors during disease, particularly TLR-2 and CCR-2 signaling interdependence on each other has not been yet investigated during acute staphylococcal infection. Thus, the present study was aimed to trace possible interaction between CCR-2 and TLR-2 in peritoneal macrophages during acute Staphylococcus aureus infection. We found that neutralization of CCR-2 attenuates TLR-2 expression and restricts S. aureus burden but TLR-2 neutralization augments CCR-2 expression in macrophages, along with compromised host-derived reactive oxygen species production. S. aureus infection to CCR-2 intact but TLR-2 neutralized macrophages triggered production of IL-1β, TNF-α, IL-6, IFN-γ, MCP-1 and expression of iNOS, TNFR-1 and GPx with concomitant decrease in IL-10 production. Further, study with NG-monomethyl-l-arginine (L-NMMA) [iNOS blocker] and buthionine sulfoximine (BSO) [GPx blocker] revealed that S. aureus infection enhanced TLR-2 expression in CCR-2 intact and TLR-2 neutralized macrophages possibly via iNOS and TNFR-1 up regulation and GPx down regulation. Overall, our data indicate that targeting CCR-2 with neutralizing antibody in the early phase of S. aureus infection could restrict excessive inflammation with less compromised bacterial killing. It certainly would be a therapeutic strategy in S. aureus induced inflammatory and infective diseases. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  19. Differences in the Expression of TLR-2, NOD2, and NF-κB in Placenta Between Twins.

    Science.gov (United States)

    Szylberg, Łukasz; Bodnar, Magdalena; Lebioda, Anna; Krepska, Patrycja; Kowalewski, Adam; Bręborowicz, Grzegorz; Marszałek, Andrzej

    2018-05-23

    Dizygotic twins share the same type of genetic relationship as non-twin siblings. Whereas monozygotic (MZ) twins are considered to have identical genetic material, they still differ. There is a number of reasons for early MZ twin discordance, including differences in the in utero environment, stochasticity, genetic mosaicism, and epigenetic factors. During gestation, the efficient innate immune system is of utmost importance. Our study was based on immunohistochemical evaluation of the differences in innate immune protein expression (TLR-2, NOD2, and NF-κB) in the 95 placentas between twins. Our study revealed statistical significant differences between diamniotic-dichorionic and monoamniotic-dichorionic twins. Monoamniotic-monochorionic twins exhibited no significant differences in protein expressions. To identify epigenetic factors causing the differences between twins, we made a series of comparisons with clinical data. The study revealed more cases with infections, miscarriages, in vitro fertilization, and premature rupture of membranes within the group with higher differences level of NF-κB, NOD2 and TLR-2 between twins. In case of twin-to-twin transfusion syndrome, there were no significant differences in innate immune protein expressions between twins. These results show that dissimilar genetic material and separate in utero environment promote discordance in innate immune protein expressions between twins. Moreover, additional blood flow between twins may be favorable in life-threatening conditions ensuring similar microenvironment.

  20. Activated human neonatal CD8+ T cells are subject to immunomodulation by direct TLR2 or TLR5 stimulation.

    LENUS (Irish Health Repository)

    McCarron, Mark

    2012-02-01

    In conditions of optimal priming, the neonate possesses competency to mount quantitatively adult-like responses. Vaccine formulations containing sufficiently potent adjuvants may overcome the neonate\\'s natural tendency for immunosuppression and provoke a similarly robust immune response. TLR expression on T cells represents the possibility of directly enhancing T cell immunity. We examined the ex vivo responsiveness of highly purified human cord blood-derived CD8(+) T cells to direct TLR ligation by a repertoire of TLR agonists. In concert with TCR stimulation, only Pam(3)Cys (palmitoyl-3-Cys-Ser-(Lys)(4)) and flagellin monomers significantly enhanced proliferation, CD25(+) expression, IL-2, IFN-gamma, TNF-alpha, and intracellular granzyme B expression. TLR2 and TLR5 mRNA was detected in the CD8(+) T cells. Blocking studies confirmed that the increase in IFN-gamma production was by the direct triggering of surface TLR2 or TLR5. The simultaneous exposure of CD8(+) T cells to both TLR agonists had an additive effect on IFN-gamma production. These data suggest that a combination of the two TLR ligands would be a potent T cell adjuvant. This may represent a new approach to TLR agonist-based adjuvant design for future human neonatal vaccination strategies requiring a CD8(+) component.

  1. Induction of TLR-2 and TLR-5 expression by Helicobacter pylori switches cagPAI-dependent signalling leading to the secretion of IL-8 and TNF-α.

    Directory of Open Access Journals (Sweden)

    Suneesh Kumar Pachathundikandi

    2011-05-01

    Full Text Available Helicobacter pylori is the causative agent for developing gastritis, gastric ulcer, and even gastric cancer. Virulent strains carry the cag pathogenicity island (cagPAI encoding a type-IV secretion system (T4SS for injecting the CagA protein. However, mechanisms of sensing this pathogen through Toll-like receptors (TLRs and downstream signalling pathways in the development of different pathologies are widely unclear. Here, we explored the involvement of TLR-2 and TLR-5 in THP-1 cells and HEK293 cell lines (stably transfected with TLR-2 or TLR-5 during infection with wild-type H. pylori and isogenic cagPAI mutants. H. pylori triggered enhanced TLR-2 and TLR-5 expression in THP-1, HEK293-TLR2 and HEK293-TLR5 cells, but not in the HEK293 control. In addition, IL-8 and TNF-α cytokine secretion in THP-1 cells was induced in a cagPAI-dependent manner. Furthermore, we show that HEK293 cells are not competent for the uptake of T4SS-delivered CagA, and are therefore ideally suited for studying TLR signalling in the absence of T4SS functions. HEK293 control cells, which do not induce TLR-2 and TLR-5 expression during infection, only secreted cytokines in small amounts, in agreement with T4SS functions being absent. In contrast, HEK293-TLR2 and HEK293-TLR5 cells were highly competent for inducing the secretion of IL-8 and TNF-α cytokines in a cagPAI-independent manner, suggesting that the expression of TLR-2 or TLR-5 has profoundly changed the capability to trigger pro-inflammatory signalling upon infection. Using phospho-specific antibodies and luciferase reporter assays, we further demonstrate that H. pylori induces IRAK-1 and IκB phosphorylation in a TLR-dependent manner, and this was required for activation of transcription factor NF-κB. Finally, NF-κB activation in HEK293-TLR2 and HEK293-TLR5 cells was confirmed by expressing p65-GFP which was translocated from the cytoplasm into the nucleus. These data indicate that H. pylori-induced expression

  2. Emotion recognition and emergent leadership : Unraveling mediating mechanisms and boundary conditions

    NARCIS (Netherlands)

    Walter, F.; Cole, M.S.; van der Vegt, G.S.; Rubin, R.S.; Bommer, W.H.

    2012-01-01

    This study examines the complex connection between individuals' emotion recognition capability and their emergence as leaders. It is hypothesized that emotion recognition and extraversion interactively relate with an individual's task coordination behavior which, in turn, influences the likelihood

  3. Self-recognition of high-mannose type glycans mediating adhesion of embryonal fibroblasts.

    Science.gov (United States)

    Yoon, Seon-Joo; Utkina, Natalia; Sadilek, Martin; Yagi, Hirokazu; Kato, Koichi; Hakomori, Sen-itiroh

    2013-07-01

    High-mannose type N-linked glycan with 6 mannosyl residues, termed "M6Gn2", displayed clear binding to the same M6Gn2, conjugated with ceramide mimetic (cer-m) and incorporated in liposome, or coated on polystyrene plates. However, the conjugate of M6Gn2-cer-m did not interact with complex-type N-linked glycan with various structures having multiple GlcNAc termini, conjugated with cer-m. The following observations indicate that hamster embryonic fibroblast NIL-2 K cells display homotypic autoadhesion, mediated through the self-recognition capability of high-mannose type glycans expressed on these cells: (i) NIL-2 K cells display clear binding to lectins capable of binding to high-mannose type glycans (e.g., ConA), but not to other lectins capable of binding to other carbohydrates (e.g. GS-II). (ii) NIL-2 K cells adhere strongly to plates coated with M6Gn2-cer-m, but not to plates coated with complex-type N-linked glycans having multiple GlcNAc termini, conjugated with cer-m; (iii) degree of NIL-2 K cell adhesion to plates coated with M6Gn2-cer-m showed a clear dose-dependence on the amount of M6Gn2-cer-m; and (iv) the degree of NIL-2 K adhesion to plates coated with M6Gn2-cer-m was inhibited in a dose-dependent manner by α1,4-L-mannonolactone, the specific inhibitor in high-mannose type glycans addition. These data indicate that adhesion of NIL-2 K is mediated by self-aggregation of high mannose type glycan. Further studies are to be addressed on auto-adhesion of other types of cells based on self interaction of high mannose type glycans.

  4. The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo.

    Science.gov (United States)

    Koymans, Kirsten J; Goldmann, Oliver; Karlsson, Christofer A Q; Sital, Wiedjai; Thänert, Robert; Bisschop, Adinda; Vrieling, Manouk; Malmström, Johan; van Kessel, Kok P M; de Haas, Carla J C; van Strijp, Jos A G; Medina, Eva

    2017-01-01

    Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus. Many studies have demonstrated the importance of TLR2 in murine S. aureus infection. S. aureus evades TLR2 activation by secreting two proteins, staphylococcal superantigen-like protein 3 (SSL3) and 4 (SSL4). In this study, we demonstrate that antibodies against SSL3 and SSL4 are found in healthy individuals, indicating that humans are exposed to these proteins during S. aureus colonization or infection. To investigate the TLR2-antagonistic properties of SSL3 and SSL4, we compared the infection with wild-type and SSL3/4 knockout S. aureus strains in an intravenous murine infection model. Direct evaluation of the contribution of SSL3/4 to infection pathogenesis was hindered by the fact that the SSLs were not expressed in the murine system. To circumvent this limitation, an SSL3-overproducing strain (pLukM-SSL3) was generated, resulting in constitutive expression of SSL3. pLukM-SSL3 exhibited increased virulence compared to the parental strain in a murine model that was found to be TLR2 dependent. Altogether, these data indicate that SSL3 contributes to S. aureus virulence in vivo. © 2017 S. Karger AG, Basel.

  5. Recognition Decisions from Visual Working Memory Are Mediated by Continuous Latent Strengths

    Science.gov (United States)

    Ricker, Timothy J.; Thiele, Jonathan E.; Swagman, April R.; Rouder, Jeffrey N.

    2017-01-01

    Making recognition decisions often requires us to reference the contents of working memory, the information available for ongoing cognitive processing. As such, understanding how recognition decisions are made when based on the contents of working memory is of critical importance. In this work we examine whether recognition decisions based on the…

  6. Pattern recognition receptor-mediated cytokine response in infants across 4 continents.

    Science.gov (United States)

    Smolen, Kinga K; Ruck, Candice E; Fortuno, Edgardo S; Ho, Kevin; Dimitriu, Pedro; Mohn, William W; Speert, David P; Cooper, Philip J; Esser, Monika; Goetghebuer, Tessa; Marchant, Arnaud; Kollmann, Tobias R

    2014-03-01

    Susceptibility to infection as well as response to vaccination varies among populations. To date, the underlying mechanisms responsible for these clinical observations have not been fully delineated. Because innate immunity instructs adaptive immunity, we hypothesized that differences between populations in innate immune responses may represent a mechanistic link to variation in susceptibility to infection or response to vaccination. Determine whether differences in innate immune responses exist among infants from different continents of the world. We determined the innate cytokine response following pattern recognition receptor (PRR) stimulation of whole blood from 2-year-old infants across 4 continents (Africa, North America, South America, and Europe). We found that despite the many possible genetic and environmental exposure differences in infants across 4 continents, innate cytokine responses were similar for infants from North America, South America, and Europe. However, cells from South African infants secreted significantly lower levels of cytokines than did cells from infants from the 3 other sites, and did so following stimulation of extracellular and endosomal but not cytosolic PRRs. Substantial differences in innate cytokine responses to PRR stimulation exist among different populations of infants that could not have been predicted. Delineating the underlying mechanism(s) for these differences will not only aid in improving vaccine-mediated protection but possibly also provide clues for the susceptibility to infection in different regions of the world. Copyright © 2013 The Authors. Published by Mosby, Inc. All rights reserved.

  7. Neonatal immune responses to TLR2 stimulation: Influence of maternal atopy on Foxp3 and IL-10 expression

    Directory of Open Access Journals (Sweden)

    Gold Diane R

    2006-03-01

    Full Text Available Abstract Background Maternal atopic background and stimulation of the adaptive immune system with allergen interact in the development of allergic disease. Stimulation of the innate immune system through microbial exposure, such as activation of the innate Toll-like-receptor 2 (TLR2, may reduce the development of allergy in childhood. However, little is known about the immunological effects of microbial stimulation on early immune responses and in association with maternal atopy. Methods We analyzed immune responses of cord blood mononuclear cells (CBMC from 50 healthy neonates (31 non-atopic and 19 atopic mothers. Cells were stimulated with the TLR2 agonist peptidoglycan (Ppg or the allergen house dust mite Dermatophagoides farinae (Derf1, and results compared to unstimulated cells. We analyzed lymphocyte proliferation and cytokine secretion of CBMC. In addition, we assessed gene expression associated with T regulatory cells including the transcription factor Foxp3, the glucocorticoid-induced TNF receptor (GITR, and the cytotoxic lymphocyte antigen 4 (CTLA4. Lymphocyte proliferation was measured by 3H-Thymidine uptake, cytokine concentrations determined by ELISA, mRNA expression of T cell markers by real-time RT-PCR. Results Ppg stimulation induced primarily IL-10 cytokine production, in addition to IFN-γ, IL-13 and TNF-α secretion. GITR was increased following Ppg stimulation (p = 0.07. Ppg-induced IL-10 production and induction of Foxp3 were higher in CBMC without, than with maternal atopy (p = 0.04, p = 0.049. IL-10 production was highly correlated with increased expression of Foxp3 (r = 0.53, p = 0.001, GITR (r = 0.47, p = 0.004 and CTLA4 (r = 0.49, p = 0.003, independent of maternal atopy. Conclusion TLR2 stimulation with Ppg induces IL-10 and genes associated with T regulatory cells, influenced by maternal atopy. Increased IL-10 and Foxp3 induction in CBMC of non-atopic compared to atopic mothers, may indicate an increased capacity to

  8. TLR2 signal influences the iNOS/NO responses and worm development in C57BL/6J mice infected with Clonorchis sinensis.

    Science.gov (United States)

    Yang, Qing-Li; Shen, Ji-Qing; Jiang, Zhi-Hua; Shi, Yun-Liang; Wan, Xiao-Ling; Yang, Yi-Chao

    2017-08-07

    Although the responses of inducible nitric oxide synthase (iNOS) and associated cytokine after Clonorchis sinensis infection have been studied recently, their mechanisms remain incompletely understood. In this study, we investigated the effects of toll-like receptor 2 (TLR2) signals on iNOS/nitric oxide (NO) responses after C. sinensis infection. We also evaluated the correlations between iNOS responses and worm development, which are possibly regulated by TLR2 signal. TLR2 wild-type and mutant C57BL/6 J mice were infected with 60 C. sinensis metacercariae, and the samples were collected at 30, 60, 90 and 120 days post-infection (dpi). The total serum NO levels were detected using Griess reagent after nitrate was reduced to nitrite. Hepatic tissue samples from the infected mice were sliced and stained with hematoxylin and eosin (HE) to observe worm development in the intrahepatic bile ducts. The iNOS mRNA transcripts in the splenocytes were examined by real time reverse transcriptase polymerase chain reaction (qRT-PCR), and iNOS expression was detected by immunohistochemistry. Developing C. sinensis juvenile worms were more abundant in the intrahepatic bile ducts of TLR2 mutant mice than those of TLR2 wild-type mice. However, no eggs were found in the faeces of both mice samples. The serum levels of total NO significantly increased in TLR2 mutant mice infected with C. sinensis at 30 (t (5)  = 2.595, P = 0.049), 60 (t (5)  = 7.838, P = 0.001) and 90 dpi (t (5)  = 3.032, P = 0.029). Meanwhile, no changes occurred in TLR2 wild-type mice compared with uninfected controls during the experiment. The iNOS expression in splenocytes showed unexpected higher background levels in TLR2 mutant mice than those in TLR2 wild-type mice. Furthermore, the iNOS mRNA transcripts in splenocytes were significantly increased in the TLR2 wild-type mice infected with C. sinensis at 30 (t (5)  = 5.139, P = 0.004), 60 (t (5)  = 6.138, P = 0.002) and 90 dpi (t (5)  = 6

  9. Comparative Study of the Effect of Baicalin and Its Natural Analogs on Neurons with Oxygen and Glucose Deprivation Involving Innate Immune Reaction of TLR2/TNFα

    Directory of Open Access Journals (Sweden)

    Hui-Ying Li

    2012-01-01

    Full Text Available This work is to study the baicalin and its three analogs, baicalin, wogonoside, and wogonin, on the protective effect of neuron from oxygen-glucose deprivation (OGD and toll-like receptor 2 (TLR2 expression in OGD damage. The results showed that baicalin and its three analogs did protect neurons from OGD damage and downregulated protein level of TLR2. D-Glucopyranosiduronic acid on site 7 in the structure played a core of cytotoxicity of these flavonoid analogs. The methoxyl group on carbon 8 of the structure had the relation with TLR2 protein expression, as well as the anti-inflammation. In addition, we detected caspase3 and antioxidation capability, to investigate the effect of four analogs on cell apoptosis and total antioxidation competence in OGD model.

  10. [Changes of FoxP3, CD4(+)CD25(+) regulatory T cells, TLR2 and TLR9 in children with infectious mononucleosis].

    Science.gov (United States)

    Wang, Qiang; Wang, Zuo-Feng; Cao, Mei; Wang, Zhi-Ying

    2013-04-01

    The aim of this study was to investigate the effects of TLR2, TLR9, CD4(+)CD25(+) regulatory T cells (Treg) and transcription factor FoxP3 in the pathogenesis of children with infectious mononucleosis (IM). Thirty-five acute IM patients admitted in our hospital from April 2010 to January 2011 were enrolled in this study. Thirty-five healthy subjects were taken as control. The thirty-five patients before treatment were considered as patients in acute stage, after treatment and without clinical symptom they were thought as patients in recovery stage. The expression levels of TLR2, TLR9 and FoxP3 mRNA were detected by real time PCR using SYBR Green I. The expression of T lymphocyte subset CD4(+)CD25(+) in peripheral blood mononuclear cells was detected by flow cytometry. The results showed that the relative levels of TLR2 mRNA (4.03 ± 0.56), TLR9 mRNA (8.88 ± 1.56) in peripheral blood mononuclear cells of IM patients in acute stage were significantly higher than those of the controls [TLR2 mRNA (2.22 ± 0.57), TLR9 mRNA (3.63 ± 1.30)] and IM patients in recovery stage [TLR2 mRNA (2.76 ± 0.83), TLR9 mRNA (5.34 ± 1.60)] (P 0.05). It is concluded that the expression of CD4(+)CD25(+)regulatory T cells is reduced, and its special transcription factor FoxP3 mRNA is down-regulated, but expression levels of TLR2 mRNA, TLR9 mRNA are up-regulated in IM patients of acute stage.

  11. Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice: Implications for Superficial Erosion.

    Science.gov (United States)

    Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K; Swirski, Filip K; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J; Libby, Peter

    2017-06-23

    Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion. In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis ( P <0.05). These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era. © 2017 American Heart Association, Inc.

  12. The TLR2 Antagonist Staphylococcal Superantigen-Like Protein 3 Acts as a Virulence Factor to Promote Bacterial Pathogenicity in vivo

    NARCIS (Netherlands)

    Koymans, Kirsten J.; Goldmann, Oliver; Karlsson, Christofer A.Q.; Sital, Wiedjai; Thänert, Robert; Bisschop, Adinda; Vrieling, Manouk; Malmström, Johan; van Kessel, Kok P M; De Haas, Carla J.C.; Van Strijp, Jos A.G.; Medina, Eva

    2017-01-01

    Toll-like receptor (TLR) signaling is important in the initiation of immune responses and subsequent instigation of adaptive immunity. TLR2 recognizes bacterial lipoproteins and plays a central role in the host defense against bacterial infections, including those caused by Staphylococcus aureus.

  13. Customized laboratory TLR4 and TLR2 detection method from peripheral human blood for early detection of doxorubicin-induced cardiotoxicity.

    Science.gov (United States)

    Pop-Moldovan, A L; Trofenciuc, N-M; Dărăbanţiu, D A; Precup, C; Branea, H; Christodorescu, R; Puşchiţă, M

    2017-05-01

    Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%. Exclusion criteria consisted of the following: previous anthracycline therapy, previous radiotherapy, history of heart failure or chronic renal failure, atrial fibrillation, and pregnancy. In all patients, in fasting state, a blood sample was drawn for the assessment of TLR2 and TLR4 gene expression. Gene expression was assessed by quantitative reverse transcription PCR (qRT-PCR) using blood collection, RNA isolation, cDNA reverse transcription, qRT-PCR and quantification of the relative expression. At enrollment, all patients were evaluated clinically; an ECG and an echocardiography were performed. The average amount of gene expression units was 0.113 for TLR4 (range 0.059-0.753) and 0.218 for TLR2 (range 0.046-0.269). The mean mRNA extracted quantity was 113 571 ng/μl. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean values for TLR4 were 0.1198625 and for TLR2 were 0.16454 gene expression units. As for the diastolic function parameters, criteria for diastolic dysfunction were present after 6 months in 16 patients (64%). In these patients, the mean value for TLR2 was 0.30±0.19 and for TLR4 was 0.15±0.04. The corresponding values for the patients who did not

  14. Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity.

    Science.gov (United States)

    Ojeda-Ojeda, Miriam; Martínez-García, M Ángeles; Alpañés, Macarena; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

    2016-02-01

    Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. Slp-76 is a critical determinant of NK cell-mediated recognition of missing-self targets

    Science.gov (United States)

    Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

    2015-01-01

    Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying “missing-self” recognition, including the involvement of activating receptors, remain poorly understood. Using ENU mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell-mediated recognition and elimination of “missing-self” targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation [Thr428Ile] in the SH2 domain of Slp-76—a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele—while no major defects were observed in conventional T cell development/function, a marked defect in NK cell-mediated elimination of β2-Microglobulin (β2M)-deficient target cells was observed. Further studies revealed Slp-76 to control NK cell receptor expression and maturation, however, activation of Slp-76ace/ace NK cells through ITAM-containing NK cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M−/− target cell synapse, revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76ace/ace NK cells. Overall these studies establish Slp-76 as a critical determinant of NK cell development and NK cell-mediated elimination of missing-self target cells. PMID:25929249

  16. Genetic Diversity of IFγ, IL1β, TLR2, and TLR8 Loci in Pulmonary Tuberculosis in Kazakhstan

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    Dauren Yerezhepov

    2014-12-01

    Full Text Available Introduction. Tuberculosis (TB is caused by bacterium Mycobacterium tuberculosis (MTB, and according to the WHO, up to 30% of world population is infected with latent TB. Pathogenesis of TB is multifactorial, and its development depends on environmental, social, microbial, and genetic factors of both the bacterium and the host. The number of TB cases in Kazakhstan has decreased in the past decade, but multidrug-resistant (MDR TB cases are dramatically increasing. Polymorphisms in genes responsible for immune response have been associated with TB susceptibility. The objective of this study was to investigate the risk of developing pulmonary TB (PTB associated with polymorphisms in several inflammatory pathway genes among Kazakhstani population.Methods. 703 participants from 3 regions of Kazakhstan were recruited for a case-control study. 251 participants had pulmonary TB (PTB, and 452 were healthy controls (HC. Males and females represented 42.39% and 57.61%, respectively. Of all participants, 67.4% were Kazakhs, 22.8% Russians, 3.4% Ukrainians, and 6.4% were of other origins. Clinical and epidemiological data were collected from medical records, interviews, and questionnaires. DNA samples were genotyped using TaqMan assay on 4 polymorphisms: IFNγ (rs2430561 and IL1β (rs16944, TLR2 (rs5743708 and TLR8 (rs3764880. Statistical data was analyzed using SPSS 19.Results. Genotyping by IFγ, IL1β, TLR2 showed no significant association with PTB susceptibility (p > 0.05. TLR8 genotype A/G was significantly higher in females (F/M – 41.5%/1.3% and G/G in males (M/F – 49%/20.7% (χ2=161.43, p < 0.001. A significantly increased risk of PTB development was observed for TLR A/G with an adjusted OR of 1.48 (95%, CI: 0.96 - 2.28, and a protective feature was revealed for TLR8 G/G genotype (OR: 0.81, 95%, CI: 0.56 - 1.16, p = 0.024. Additional grouping by gender revealed that TLR8 G/G contributes as protective genotype (OR: 1.83, 95%, CI: 1.18 - 2.83, p

  17. Trichoderma asperelloides Spores Downregulate dectin1/2 and TLR2 Receptors of Mice Macrophages and Decrease Candida parapsilosis Phagocytosis Independent of the M1/M2 Polarization

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    Andréa G. dos Santos

    2017-09-01

    had reduced expression of pattern recognition receptors, such as TLR2, dectin-1 and dectin-2, all involved in the first line of defense against clinically important yeasts. Our data could infer that T. asperelloides spores may confer susceptibility to infection by C. parapsilosis.

  18. The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex.

    Science.gov (United States)

    Gribble, Kristin E; Mark Welch, David B

    2012-08-01

    Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP), a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Isolates of the B. plicatilis species complex have 1-4 copies of mmr-b, each composed of 2-9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving rapidly, and novel alleles may be maintained and increase in

  19. The mate recognition protein gene mediates reproductive isolation and speciation in the Brachionus plicatilis cryptic species complex

    Directory of Open Access Journals (Sweden)

    Gribble Kristin E

    2012-08-01

    Full Text Available Abstract Background Chemically mediated prezygotic barriers to reproduction likely play an important role in speciation. In facultatively sexual monogonont rotifers from the Brachionus plicatilis cryptic species complex, mate recognition of females by males is mediated by the Mate Recognition Protein (MRP, a globular glycoprotein on the surface of females, encoded by the mmr-b gene family. In this study, we sequenced mmr-b copies from 27 isolates representing 11 phylotypes of the B. plicatilis species complex, examined the mode of evolution and selection of mmr-b, and determined the relationship between mmr-b genetic distance and mate recognition among isolates. Results Isolates of the B. plicatilis species complex have 1–4 copies of mmr-b, each composed of 2–9 nearly identical tandem repeats. The repeats within a gene copy are generally more similar than are gene copies among phylotypes, suggesting concerted evolution. Compared to housekeeping genes from the same isolates, mmr-b has accumulated only half as many synonymous differences but twice as many non-synonymous differences. Most of the amino acid differences between repeats appear to occur on the outer face of the protein, and these often result in changes in predicted patterns of phosphorylation. However, we found no evidence of positive selection driving these differences. Isolates with the most divergent copies were unable to mate with other isolates and rarely self-crossed. Overall the degree of mate recognition was significantly correlated with the genetic distance of mmr-b. Conclusions Discrimination of compatible mates in the B. plicatilis species complex is determined by proteins encoded by closely related copies of a single gene, mmr-b. While concerted evolution of the tandem repeats in mmr-b may function to maintain identity, it can also lead to the rapid spread of a mutation through all copies in the genome and thus to reproductive isolation. The mmr-b gene is evolving

  20. Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR) and Neural System Function during Facial Recognition: A Pilot Study

    Science.gov (United States)

    Nishikawa, Saori

    2015-01-01

    This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy) during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18) aged between 22 to 37 years old (mean age = 24.05 years old) provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing]), and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task), and a gene × environment (G×E) interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links. PMID:26418317

  1. Perceived Parenting Mediates Serotonin Transporter Gene (5-HTTLPR and Neural System Function during Facial Recognition: A Pilot Study.

    Directory of Open Access Journals (Sweden)

    Saori Nishikawa

    Full Text Available This study examined changes in prefrontal oxy-Hb levels measured by NIRS (Near-Infrared Spectroscopy during a facial-emotion recognition task in healthy adults, testing a mediational/moderational model of these variables. Fifty-three healthy adults (male = 35, female = 18 aged between 22 to 37 years old (mean age = 24.05 years old provided saliva samples, completed a EMBU questionnaire (Swedish acronym for Egna Minnen Beträffande Uppfostran [My memories of upbringing], and participated in a facial-emotion recognition task during NIRS recording. There was a main effect of maternal rejection on RoxH (right frontal activation during an ambiguous task, and a gene × environment (G × E interaction on RoxH, suggesting that individuals who carry the SL or LL genotype and who endorse greater perceived maternal rejection show less right frontal activation than SL/LL carriers with lower perceived maternal rejection. Finally, perceived parenting style played a mediating role in right frontal activation via the 5-HTTLPR genotype. Early-perceived parenting might influence neural activity in an uncertain situation i.e. rating ambiguous faces among individuals with certain genotypes. This preliminary study makes a small contribution to the mapping of an influence of gene and behaviour on the neural system. More such attempts should be made in order to clarify the links.

  2. Oviposition site-selection by Bactrocera dorsalis is mediated through an innate recognition template tuned to γ-octalactone.

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    Kamala Jayanthi Pagadala Damodaram

    Full Text Available Innate recognition templates (IRTs in insects are developed through many years of evolution. Here we investigated olfactory cues mediating oviposition behavior in the oriental fruit fly, Bactrocera dorsalis, and their role in triggering an IRT for oviposition site recognition. Behavioral assays with electrophysiologically active compounds from a preferred host, mango, revealed that one of the volatiles tested, γ-octalactone, had a powerful effect in eliciting oviposition by gravid B. dorsalis females. Electrophysiological responses were obtained and flies clearly differentiated between treated and untreated substrates over a wide range of concentrations of γ-octalactone. It triggered an innate response in flies, overriding inputs from other modalities required for oviposition site evaluation. A complex blend of mango volatiles not containing γ-octalactone elicited low levels of oviposition, whereas γ-octalactone alone elicited more oviposition response. Naïve flies with different rearing histories showed similar responses to γ-octalactone. Taken together, these results indicate that oviposition site selection in B. dorsalis is mediated through an IRT tuned to γ-octalactone. Our study provides empirical data on a cue underpinning innate behavior and may also find use in control operations against this invasive horticultural pest.

  3. Cooperative DNA Recognition Modulated by an Interplay between Protein-Protein Interactions and DNA-Mediated Allostery.

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    Felipe Merino

    2015-06-01

    Full Text Available Highly specific transcriptional regulation depends on the cooperative association of transcription factors into enhanceosomes. Usually, their DNA-binding cooperativity originates from either direct interactions or DNA-mediated allostery. Here, we performed unbiased molecular simulations followed by simulations of protein-DNA unbinding and free energy profiling to study the cooperative DNA recognition by OCT4 and SOX2, key components of enhanceosomes in pluripotent cells. We found that SOX2 influences the orientation and dynamics of the DNA-bound configuration of OCT4. In addition SOX2 modifies the unbinding free energy profiles of both DNA-binding domains of OCT4, the POU specific and POU homeodomain, despite interacting directly only with the first. Thus, we demonstrate that the OCT4-SOX2 cooperativity is modulated by an interplay between protein-protein interactions and DNA-mediated allostery. Further, we estimated the change in OCT4-DNA binding free energy due to the cooperativity with SOX2, observed a good agreement with experimental measurements, and found that SOX2 affects the relative DNA-binding strength of the two OCT4 domains. Based on these findings, we propose that available interaction partners in different biological contexts modulate the DNA exploration routes of multi-domain transcription factors such as OCT4. We consider the OCT4-SOX2 cooperativity as a paradigm of how specificity of transcriptional regulation is achieved through concerted modulation of protein-DNA recognition by different types of interactions.

  4. Tunable Complex Stability in Surface Molecular Recognition Mediated by Self-Complementary Quadruple Hydrogen Bonds

    NARCIS (Netherlands)

    Zou, S(han); Zhang, Zhihong; Forch, Renate; Knoll, Wolfgang; Schönherr, Holger; Vancso, Gyula J.

    2003-01-01

    We show that surfaces modified with asymmetric 2-ureido-4[1H]-pyrimidinone-hydroxyalkane disulfide adsorbates exhibit efficient and controllable self-complementary molecular recognition of the pyrimidinone moieties. Two novel asymmetric 2-ureido-4[1H]-pyrimidinone-hydroxyalkane disulfide adsorbates,

  5. Slp-76 is a critical determinant of NK-cell mediated recognition of missing-self targets.

    Science.gov (United States)

    Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

    2015-07-01

    Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying "missing-self" recognition, including the involvement of activating receptors, remain poorly understood. Using ethyl-N-nitrosourea mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell mediated recognition and elimination of "missing-self" targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation (Thr428Ile) in the SH2 domain of Slp-76-a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele-while no major defects were observed in conventional T-cell development/function, a marked defect in NK cell mediated elimination of β2-microglobulin (β2M) deficient target cells was observed. Further studies revealed Slp-76 to control NK-cell receptor expression and maturation; however, activation of Slp-76(ace/ace) NK cells through ITAM-containing NK-cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M(-/-) target cell synapse revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76(ace/ace) NK cells. Overall these studies establish Slp-76 as a critical determinant of NK-cell development and NK cell mediated elimination of missing-self target cells in mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. TLR2, TLR4 and the MYD88 signaling pathway are crucial for neutrophil migration in acute kidney injury induced by sepsis.

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    Angela Castoldi

    Full Text Available The aim of this study was to investigate the role of TLR2, TLR4 and MyD88 in sepsis-induced AKI. C57BL/6 TLR2(-/-, TLR4(-/- and MyD88(-/- male mice were subjected to sepsis by cecal ligation and puncture (CLP. Twenty four hours later, kidney tissue and blood samples were collected for analysis. The TLR2(-/-, TLR4(-/- and MyD88(-/- mice that were subjected to CLP had preserved renal morphology, and fewer areas of hypoxia and apoptosis compared with the wild-type C57BL/6 mice (WT. MyD88(-/- mice were completely protected compared with the WT mice. We also observed reduced expression of proinflammatory cytokines in the kidneys of the knockout mice compared with those of the WT mice and subsequent inhibition of increased vascular permeability in the kidneys of the knockout mice. The WT mice had increased GR1(+low cells migration compared with the knockout mice and decreased in GR1(+high cells migration into the peritoneal cavity. The TLR2(-/-, TLR4(-/-, and MyD88(-/- mice had lower neutrophil infiltration in the kidneys. Depletion of neutrophils in the WT mice led to protection of renal function and less inflammation in the kidneys of these mice. Innate immunity participates in polymicrobial sepsis-induced AKI, mainly through the MyD88 pathway, by leading to an increased migration of neutrophils to the kidney, increased production of proinflammatory cytokines, vascular permeability, hypoxia and apoptosis of tubular cells.

  7. Within-individual variation in bullfrog vocalizations: implications for a vocally mediated social recognition system.

    Science.gov (United States)

    Bee, Mark A

    2004-12-01

    Acoustic signals provide a basis for social recognition in a wide range of animals. Few studies, however, have attempted to relate the patterns of individual variation in signals to behavioral discrimination thresholds used by receivers to discriminate among individuals. North American bullfrogs (Rana catesbeiana) discriminate among familiar and unfamiliar individuals based on individual variation in advertisement calls. The sources, patterns, and magnitudes of variation in eight acoustic properties of multiple-note advertisement calls were examined to understand how patterns of within-individual variation might either constrain, or provide additional cues for, vocal recognition. Six of eight acoustic properties exhibited significant note-to-note variation within multiple-note calls. Despite this source of within-individual variation, all call properties varied significantly among individuals, and multivariate analyses indicated that call notes were individually distinct. Fine-temporal and spectral call properties exhibited less within-individual variation compared to gross-temporal properties and contributed most toward statistically distinguishing among individuals. Among-individual differences in the patterns of within-individual variation in some properties suggest that within-individual variation could also function as a recognition cue. The distributions of among-individual and within-individual differences were used to generate hypotheses about the expected behavioral discrimination thresholds of receivers.

  8. Chloroplastic protein NRIP1 mediates innate immune receptor recognition of a viral effector

    Science.gov (United States)

    Caplan, Jeffrey L.; Mamillapalli, Padmavathi; Burch-Smith, Tessa M.; Czymmek, Kirk; Dinesh-Kumar, S.P.

    2008-01-01

    Summary Plant innate immunity relies on the recognition of pathogen effector molecules by nucleotide-binding-leucine-rich repeat (NB-LRR) immune receptor families. Previously we have shown the N immune receptor, a member of TIR-NB-LRR family, indirectly recognizes the 50-kDa helicase (p50) domain of Tobacco mosaic virus (TMV) through its TIR domain. We have identified an N receptor-interacting protein, NRIP1, that directly interacts with both N's TIR domain and p50. NRIP1 is a functional rhodanese sulfurtransferase and is required for N to provide complete resistance to TMV. Interestingly, NRIP1 that normally localizes to the chloroplasts is recruited to the cytoplasm and nucleus by the p50 effector. As a consequence, NRIP1 interacts with N only in the presence of the p50 effector. Our findings show that a chloroplastic protein is intimately involved in pathogen recognition. We propose that N's activation requires a pre-recognition complex containing the p50 effector and NRIP1. PMID:18267075

  9. Effects of total glucosides of paeony on immune regulatory toll-like receptors TLR2 and 4 in the kidney from diabetic rats.

    Science.gov (United States)

    Xu, Xing-xin; Qi, Xiang-Ming; Zhang, Wei; Zhang, Chao-Qun; Wu, Xiao-Xu; Wu, Yong-Gui; Wang, Kun; Shen, Ji-Jia

    2014-05-15

    TLRs are a family of receptors that play a critical role in the pathogenesis of diabetic nephropathy. TGP have been shown to have anti-inflammatory and immuno-regulatory activities. However, the relation between TGP and TLRs on diabetic nephropathy remains unknown. In this study, we examined effects of TGP on immune regulatory TLR2 and 4 in the kidney from streptozotocin-induced diabetic rats. TGP decreased the levels of 24h urinary albumin excretion rate significantly in diabetic rats. Western blot analysis showed that TGP significantly inhibited the expression of TLR2 and 4, MyD88, p-IRAK1, NF-κB p65, p-IRF3, TNF-α and IL-1β. Quantitative real-time PCR analysis showed that the significantly increased levels of TLR2 and 4, and MyD88mRNA in the kidneys of diabetic rats were significantly suppressed by TGP treatment. Macrophages infiltration were also markedly increased in the kidneys of the diabetic rats, but were significantly inhibited by TGP in a dose-dependent manner. These results suggest that TGP has protective effects on several pharmacological targets in the progress of diabetic nephropathy by selectively blocking TLRs activation in vivo. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. 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

  11. Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala.

    Science.gov (United States)

    Gur, Rotem; Tendler, Alex; Wagner, Shlomo

    2014-09-01

    Recognition of specific individuals is fundamental to mammalian social behavior and is mediated in most mammals by the main and accessory olfactory systems. Both these systems innervate the medial amygdala (MeA), where activity of the neuropeptide oxytocin is thought to mediate social recognition memory (SRM). The specific contribution of the MeA to SRM formation and the specific actions of oxytocin in the MeA are unknown. We used the social discrimination test to evaluate short-term and long-term SRM in adult Sprague-Dawley male rats (n = 38). The role of protein synthesis in the MeA was investigated by local application of the protein synthesis blocker anisomycin (n = 11). Synaptic plasticity was assessed in vivo by recording the MeA evoked field potential responses to stimulation of the main (n = 21) and accessory (n = 56) olfactory bulbs before and after theta burst stimulation. Intracerebroventricular administration of saline, oxytocin, or oxytocin receptor antagonist was used to measure the effect of oxytocin on synaptic plasticity. Anisomycin application to the MeA prevented the formation of long-term SRM. In addition, the responses of MeA neurons underwent long-term depression (LTD) after theta burst stimulation of the accessory olfactory bulb, but not the main accessory bulb, in an oxytocin-dependent manner. No LTD was found in socially isolated rats, which are known to lack long-term SRM. Finally, accessory olfactory bulb stimulation before SRM acquisition blocked long-term SRM, supporting the involvement of LTD in the MeA in formation of long-term SRM. Our results indicate that long-term SRM in rats involves protein synthesis and oxytocin-dependent LTD in the MeA. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

    Directory of Open Access Journals (Sweden)

    Voils Stacy A

    2009-05-01

    Full Text Available Abstract Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC. A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes. Postoperative bleeding may result from issues such as loosened ties or clips or the occurrence of a coagulopathy due to hemodilution, vitamin K deficiency, disseminated intravascular coagulation (DIC or post-transfusion, post-shock coagulopathic states. Other causes, such as liver disease, may be ruled out by a careful patient history and common pre-operative liver function tests. Less common are coagulopathies secondary to pathologic immune responses. Such coagulopathies include those that may result from inherent patient problems such as patients with an immune dysfunction related to systemic lupus erythrematosus (SLE or lymphoma that can invoke antibodies against native coagulation factors. Medical interventions may also provoke antibody formation in the form of self-directed anti-coagulation factor antibodies, that result in problematic bleeding; it is these iatrogenic post-operative coagulopathies, including those associated with bovine thrombin

  13. Toll‐Like Receptor‐2 Mediates Adaptive Cardiac Hypertrophy in Response to Pressure Overload Through Interleukin‐1β Upregulation via Nuclear Factor κB Activation

    Science.gov (United States)

    Higashikuni, Yasutomi; Tanaka, Kimie; Kato, Megumi; Nureki, Osamu; Hirata, Yasunobu; Nagai, Ryozo; Komuro, Issei; Sata, Masataka

    2013-01-01

    Background Inflammation is induced in the heart during the development of cardiac hypertrophy. The initiating mechanisms and the role of inflammation in cardiac hypertrophy, however, remain unclear. Toll‐like receptor‐2 (TLR2) recognizes endogenous molecules that induce noninfectious inflammation. Here, we examined the role of TLR2mediated inflammation in cardiac hypertrophy. Methods and Results At 2 weeks after transverse aortic constriction, Tlr2−/− mice showed reduced cardiac hypertrophy and fibrosis with greater left ventricular dilatation and impaired systolic function compared with wild‐type mice, which indicated impaired cardiac adaptation in Tlr2−/− mice. Bone marrow transplantation experiment revealed that TLR2 expressed in the heart, but not in bone marrow–derived cells, is important for cardiac adaptive response to pressure overload. In vitro experiments demonstrated that TLR2 signaling can induce cardiomyocyte hypertrophy and fibroblast and vascular endothelial cell proliferation through nuclear factor–κB activation and interleukin‐1β upregulation. Systemic administration of a nuclear factor–κB inhibitor or anti–interleukin‐1β antibodies to wild‐type mice resulted in impaired adaptive cardiac hypertrophy after transverse aortic constriction. We also found that heat shock protein 70, which was increased in murine plasma after transverse aortic constriction, can activate TLR2 signaling in vitro and in vivo. Systemic administration of anti–heat shock protein 70 antibodies to wild‐type mice impaired adaptive cardiac hypertrophy after transverse aortic constriction. Conclusions Our results demonstrate that TLR2mediated inflammation induced by extracellularly released heat shock protein 70 is essential for adaptive cardiac hypertrophy in response to pressure overload. Thus, modulation of TLR2 signaling in the heart may provide a novel strategy for treating heart failure due to inadequate adaptation to hemodynamic

  14. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

    2015-03-01

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

  15. Rim Pathway-Mediated Alterations in the Fungal Cell Wall Influence Immune Recognition and Inflammation.

    Science.gov (United States)

    Ost, Kyla S; Esher, Shannon K; Leopold Wager, Chrissy M; Walker, Louise; Wagener, Jeanette; Munro, Carol; Wormley, Floyd L; Alspaugh, J Andrew

    2017-01-31

    Compared to other fungal pathogens, Cryptococcus neoformans is particularly adept at avoiding detection by innate immune cells. To explore fungal cellular features involved in immune avoidance, we characterized cell surface changes of the C. neoformans rim101Δ mutant, a strain that fails to organize and shield immunogenic epitopes from host detection. These cell surface changes are associated with an exaggerated, detrimental inflammatory response in mouse models of infection. We determined that the disorganized strain rim101Δ cell wall increases macrophage detection in a contact-dependent manner. Using biochemical and microscopy methods, we demonstrated that the rim101Δ strain shows a modest increase in the levels of both cell wall chitin and chitosan but that it shows a more dramatic increase in chito-oligomer exposure, as measured by wheat germ agglutinin staining. We also created a series of mutants with various levels of cell wall wheat germ agglutinin staining, and we demonstrated that the staining intensity correlates with the degree of macrophage activation in response to each strain. To explore the host receptors responsible for recognizing the rim101Δ mutant, we determined that both the MyD88 and CARD9 innate immune signaling proteins are involved. Finally, we characterized the immune response to the rim101Δ mutant in vivo, documenting a dramatic and sustained increase in Th1 and Th17 cytokine responses. These results suggest that the Rim101 transcription factor actively regulates the C. neoformans cell wall to prevent the exposure of immune stimulatory molecules within the host. These studies further explored the ways in which immune cells detect C. neoformans and other fungal pathogens by mechanisms that include sensing N-acetylglucosamine-containing structures, such as chitin and chitosan. Infectious microorganisms have developed many ways to avoid recognition by the host immune system. For example, pathogenic fungi alter their cell surfaces to

  16. TLR4, NOD1 and NOD2 mediate immune recognition of putative newly identified periodontal pathogens.

    Science.gov (United States)

    Marchesan, Julie; Jiao, Yizu; Schaff, Riley A; Hao, Jie; Morelli, Thiago; Kinney, Janet S; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J; Inohara, Naohiro; Giannobile, William V

    2016-06-01

    Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. Although the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, six being classical pathogens and four putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone-marrow-derived macrophages (BMDM) from wild-type (WT) and Toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. Campylobacter concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2 stimulatory activity. These studies allowed us to provide important evidence on newly identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Structural Change in Microbiota by a Probiotic Cocktail Enhances the Gut Barrier and Reduces Cancer via TLR2 Signaling in a Rat Model of Colon Cancer.

    Science.gov (United States)

    Kuugbee, Eugene Dogkotenge; Shang, Xueqi; Gamallat, Yaser; Bamba, Djibril; Awadasseid, Annoor; Suliman, Mohammed Ahmed; Zang, Shizhu; Ma, Yufang; Chiwala, Gift; Xin, Yi; Shang, Dong

    2016-10-01

    Structural change in the gut microbiota is implicated in cancer. The beneficial modulation of the microbiota composition with probiotics and prebiotics prevents diseases. We investigated the effect of oligofructose-maltodextrin-enriched Lactobacillus acidophilus, Bifidobacteria bifidum, and Bifidobacteria infantum (LBB), on the gut microbiota composition and progression of colorectal cancer. Sprague Dawley rats were acclimatized, given ampicillin (75 mg/kg), and treated as follows; GCO: normal control; GPR: LBB only; GPC: LBB+ 1,2-dimethylhydrazine dihydrochloride (DMH); and GCA: DMH only (cancer control). 16S V4 Pyrosequencing for gut microbiota analysis, tumor studies, and the expression of MUC2, ZO-1, occludin, TLR2, TLR4, caspase 3, COX-2, and β-catenin were conducted at the end of experiment. Probiotic LBB treatment altered the gut microbiota. The relative abundance of genera Pseudomonas, Congregibacter, Clostridium, Candidactus spp., Phaeobacter, Escherichia, Helicobacter, and HTCC was decreased (P cancer control. The altered gut microbiota was associated with decreased tumor incidence (80 % in GPC vs. 100 % in GCA, P = 0.0001), tumor volume (GPC 84.23 (42.75-188.4) mm(3) vs. GCA 243 (175.5-344.5) mm(3), P cancer control GCA (P colon cancer development by decreasing tumor incidence, multiplicity/count, and volume via enhanced TLR2-improved gut mucosa epithelial barrier integrity and suppression of apoptosis and inflammation.

  18. Single-nucleotide polymorphisms in Toll-like receptor (TLR)-2, TLR4 and heat shock protein 70 genes and susceptibility to scrub typhus.

    Science.gov (United States)

    Janardhanan, Jeshina; Joseph Martin, Sherry; Astrup, Elisabeth; Veeramanikandan, R; Aukrust, Pål; Abraham, Ooriapadickal C; Varghese, George M

    2013-11-01

    Scrub typhus is a highly prevalent bacterial infection in India and South Asia that is caused by Orientia tsutsugamushi. The innate immune response to infections is modulated by Toll-like receptors (TLRs) and heat shock proteins (HSPs). This study was done to assess the prevalence and possible association of TLR and HSP polymorphisms in scrub typhus. TLR4 Asp299Gly, TLR4 Thr399Ile, TLR2 Arg753Gln and HSP70-2 A1267G are single-nucleotide polymorphisms (SNPs) that may modulate their activities, and these SNPs were assessed in 137 scrub typhus patients and 134 controls by PCR restriction fragment length polymorphism. We found that the two TLR4 mutations, TLR4 D299G and TLR4T399I, were present in 19.5% and 22% of the study population, respectively, and was in significant linkage disequilibrium with a D' of 0.8. The TLR2 mutation was found to be rare, whereas the HSP A>G mutation was very common (77.5%). Compared with the controls, the prevalence of heterozygous genotype of the TLR4D299G SNP, but not any of the other SNPs, was significantly higher among scrub typhus patients. Further studies using a larger sample size and more candidate genes may better enable in determining the role of these associations in susceptibility and severity of scrub typhus.

  19. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Science.gov (United States)

    Frazer, Lauren C; Darville, Toni; Chandra-Kuntal, Kumar; Andrews, Charles W; Zurenski, Matthew; Mintus, Margaret; AbdelRahman, Yasser M; Belland, Robert J; Ingalls, Robin R; O'Connell, Catherine M

    2012-01-01

    Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL) in C. caviae. However, 2-deoxyglucose (2DG) treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  20. Plasmid-cured Chlamydia caviae activates TLR2-dependent signaling and retains virulence in the guinea pig model of genital tract infection.

    Directory of Open Access Journals (Sweden)

    Lauren C Frazer

    Full Text Available Loss of the conserved "cryptic" plasmid from C. trachomatis and C. muridarum is pleiotropic, resulting in reduced innate inflammatory activation via TLR2, glycogen accumulation and infectivity. The more genetically distant C. caviae GPIC is a natural pathogen of guinea pigs and induces upper genital tract pathology when inoculated intravaginally, modeling human disease. To examine the contribution of pCpGP1 to C. caviae pathogenesis, a cured derivative of GPIC, strain CC13, was derived and evaluated in vitro and in vivo. Transcriptional profiling of CC13 revealed only partial conservation of previously identified plasmid-responsive chromosomal loci (PRCL in C. caviae. However, 2-deoxyglucose (2DG treatment of GPIC and CC13 resulted in reduced transcription of all identified PRCL, including glgA, indicating the presence of a plasmid-independent glucose response in this species. In contrast to plasmid-cured C. muridarum and C. trachomatis, plasmid-cured C. caviae strain CC13 signaled via TLR2 in vitro and elicited cytokine production in vivo similar to wild-type C. caviae. Furthermore, inflammatory pathology induced by infection of guinea pigs with CC13 was similar to that induced by GPIC, although we observed more rapid resolution of CC13 infection in estrogen-treated guinea pigs. These data indicate that either the plasmid is not involved in expression or regulation of virulence in C. caviae or that redundant effectors prevent these phenotypic changes from being observed in C. caviae plasmid-cured strains.

  1. The CRF1 and the CRF2 receptor mediate recognition memory deficits and vulnerability induced by opiate withdrawal.

    Science.gov (United States)

    Morisot, Nadège; Contarino, Angelo

    2016-06-01

    Opiate use disorders are associated with impaired cognitive function and altered stress-responsive systems. The corticotropin-releasing factor (CRF) system mediates stress responses via CRF1 and CRF2 receptors and may be implicated in substance use disorders. However, the specific role for each of the two known CRF receptor subtypes in cognitive impairment induced by opiate administration and withdrawal remains to be elucidated. In the present study, CRF1-/-, CRF2-/- and their respective wild-type mice are injected with escalating doses of morphine and cognitive function assessed by the novel object recognition (NOR) memory task throughout relatively long periods of opiate withdrawal. Early (2 days) phases of opiate withdrawal impair NOR memory in wild-type, CRF1-/- and CRF2-/- mice. However, the duration of opiate withdrawal-induced NOR memory deficits is prolonged in CRF1-/- but shortened in CRF2-/- mice, as compared to their respective wild-type mice, indicating opposite roles for the two CRF receptor subtypes. Nevertheless, following apparent recovery, exposure to an environmental stressor induces the reemergence of NOR memory deficits in long-term opiate-withdrawn wild-type but not CRF1-/- or CRF2-/- mice, indicating an essential role for both CRF receptor subtypes in stress vulnerability. These findings bring initial evidence of a complex physiopathological role for the CRF system in cognitive deficits and the long-lasting vulnerability induced by opiate drugs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Divergent short- and long-term effects of acute stress in object recognition memory are mediated by endogenous opioid system activation.

    Science.gov (United States)

    Nava-Mesa, Mauricio O; Lamprea, Marisol R; Múnera, Alejandro

    2013-11-01

    Acute stress induces short-term object recognition memory impairment and elicits endogenous opioid system activation. The aim of this study was thus to evaluate whether opiate system activation mediates the acute stress-induced object recognition memory changes. Adult male Wistar rats were trained in an object recognition task designed to test both short- and long-term memory. Subjects were randomly assigned to receive an intraperitoneal injection of saline, 1 mg/kg naltrexone or 3 mg/kg naltrexone, four and a half hours before the sample trial. Five minutes after the injection, half the subjects were submitted to movement restraint during four hours while the other half remained in their home cages. Non-stressed subjects receiving saline (control) performed adequately during the short-term memory test, while stressed subjects receiving saline displayed impaired performance. Naltrexone prevented such deleterious effect, in spite of the fact that it had no intrinsic effect on short-term object recognition memory. Stressed subjects receiving saline and non-stressed subjects receiving naltrexone performed adequately during the long-term memory test; however, control subjects as well as stressed subjects receiving a high dose of naltrexone performed poorly. Control subjects' dissociated performance during both memory tests suggests that the short-term memory test induced a retroactive interference effect mediated through light opioid system activation; such effect was prevented either by low dose naltrexone administration or by strongly activating the opioid system through acute stress. Both short-term memory retrieval impairment and long-term memory improvement observed in stressed subjects may have been mediated through strong opioid system activation, since they were prevented by high dose naltrexone administration. Therefore, the activation of the opioid system plays a dual modulating role in object recognition memory. Copyright © 2013 Elsevier Inc. All rights

  3. Immune receptors involved in Streptococcus suis recognition by dendritic cells.

    Directory of Open Access Journals (Sweden)

    Marie-Pier Lecours

    Full Text Available Streptococcus suis is an important swine pathogen and an emerging zoonotic agent of septicemia and meningitis. Knowledge on host immune responses towards S. suis, and strategies used by this pathogen for subversion of these responses is scarce. The objective of this study was to identify the immune receptors involved in S. suis recognition by dendritic cells (DCs. Production of cytokines and expression of co-stimulatory molecules by DCs were shown to strongly rely on MyD88-dependent signaling pathways, suggesting that DCs recognize S. suis and become activated mostly through Toll-like receptor (TLR signaling. Supporting this fact, TLR2(-/- DCs were severely impaired in the release of several cytokines and the surface expression of CD86 and MHC-II. The release of IL-12p70 and CXC10, and the expression of CD40 were found to depend on signaling by both TLR2 and TLR9. The release of IL-23 and CXCL1 were partially dependent on NOD2. Finally, despite the fact that MyD88 signaling was crucial for DC activation and maturation, MyD88-dependent pathways were not implicated in S. suis internalization by DCs. This first study on receptors involved in DC activation by S. suis suggests a major involvement of MyD88 signaling pathways, mainly (but not exclusively through TLR2. A multimodal recognition involving a combination of different receptors seems essential for DC effective response to S. suis.

  4. Pattern-recognition receptors: signaling pathways and dysregulation in canine chronic enteropathies-brief review.

    Science.gov (United States)

    Heilmann, Romy M; Allenspach, Karin

    2017-11-01

    Pattern-recognition receptors (PRRs) are expressed by innate immune cells and recognize pathogen-associated molecular patterns (PAMPs) as well as endogenous damage-associated molecular pattern (DAMP) molecules. With a large potential for synergism or convergence between their signaling pathways, PRRs orchestrate a complex interplay of cellular mediators and transcription factors, and thus play a central role in homeostasis and host defense. Aberrant activation of PRR signaling, mutations of the receptors and/or their downstream signaling molecules, and/or DAMP/PAMP complex-mediated receptor signaling can potentially lead to chronic auto-inflammatory diseases or development of cancer. PRR signaling pathways appear to also present an interesting new avenue for the modulation of inflammatory responses and to serve as potential novel therapeutic targets. Evidence for a dysregulation of the PRR toll-like receptor (TLR)2, TLR4, TLR5, and TLR9, nucleotide-binding oligomerization domain-containing protein (NOD)2, and the receptor of advanced glycation end products (RAGE) exists in dogs with chronic enteropathies. We describe the TLR, NOD2, and RAGE signaling pathways and evaluate the current veterinary literature-in comparison to human medicine-to determine the role of TLRs, NOD2, and RAGE in canine chronic enteropathies.

  5. Chirality of TLR-2 ligand Pam3CysSK4 in fully synthetic peptide conjugates critically influences the induction of specific CD8+ T-cells.

    Science.gov (United States)

    Khan, Selina; Weterings, Jimmy J; Britten, Cedrik M; de Jong, Ana R; Graafland, Dirk; Melief, Cornelis J M; van der Burg, Sjoerd H; van der Marel, Gijs; Overkleeft, Hermen S; Filippov, Dmitri V; Ossendorp, Ferry

    2009-03-01

    Covalent conjugation of synthetic Toll-like receptor ligands (TLR-L) to synthetic antigenic peptides provides well-defined constructs that have significantly improved capacity to induce efficient priming of CD8(+) T lymphocytes in vivo. We have recently explored the cellular mechanisms underlying the efficient induction of a CD8(+) cytotoxic T lymphocyte response by such synthetic model vaccines [Khan, S., Bijker, M.S., Weterings, J.J., Tanke, H.J., Adema, G.J., van, H.T., Drijfhout, J.W., Melief, C.J., Overkleeft, H.S., van der Marel, G.A., Filippov, D.V., van der Burg, S.H., Ossendorp, F., 2007. Distinct uptake mechanisms but similar intracellular processing of two different toll-like receptor ligand-peptide conjugates in dendritic cells. J. Biol. Chem. 282, 21145-21159.]. In the current study we have investigated the behaviour of two diastereomers of the TLR-2 ligand Pam(3)CSK(4) (Pam) derivatives, namely the R- and S-epimers at C-2 of the glycerol moiety. Other studies have shown that the Pam(3)Cys based lipopeptides of R-configuration (Pam(R)) in the glycerol moiety enhanced macrophage and B-cell activation compared to those with S-configuration (Pam(S)). Here we report that Pam(R)-conjugates lead to better activation of dendritic cells than the Pam(S)-conjugates as judged by higher IL-12 secretion, upregulation of relevant markers for dendritic cell maturation. In contrast both epimers were internalized equally efficient in a clathrin-dependent manner indicating no qualitative difference in the uptake of the two stereoisomeric Pam-conjugates. We conclude that the enhanced DC activation is due to enhanced TLR-2 triggering by the Pam(R)-conjugate in contrast to the Pam(S)-conjugate. Importantly, induction of specific CD8(+) T-cells was significantly higher in mice injected with the Pam(R)-conjugates compared to mice injected with the Pam(S)-conjugate. In summary we show that the favourable effects of the Pam(R)-configuration of TLR-2 ligand can be attributed to

  6. Mycobacterium tuberculosis Upregulates TNF-α Expression via TLR2/ERK Signaling and Induces MMP-1 and MMP-9 Production in Human Pleural Mesothelial Cells.

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    Wei-Lin Chen

    Full Text Available Tumor necrosis factor (TNF-α and matrix metalloproteinases (MMPs are elevated in pleural fluids of tuberculous pleuritis (TBP where pleural mesothelial cells (PMCs conduct the first-line defense against Mycobacterium tuberculosis (MTB. However, the clinical implication of TNF-α and MMPs in TBP and the response of PMCs to MTB infection remain unclear.We measured pleural fluid levels of TNF-α and MMPs in patients with TBP (n = 18 or heart failure (n = 18 as controls. Radiological scores for initial effusion amount and residual pleural fibrosis at 6-month follow-up were assessed. In vitro human PMC experiments were performed to assess the effect of heat-killed M. tuberculosis H37Ra (MTBRa on the expression of TNF-α and MMPs.As compared with controls, the effusion levels of TNF-α, MMP-1 and MMP-9 were significantly higher and correlated positively with initial effusion amount in patients with TBP, while TNF-α and MMP-1, but not MMP-9, were positively associated with residual pleural fibrosis of TBP. Moreover, effusion levels of TNF-α had positive correlation with those of MMP-1 and MMP-9 in TBP. In cultured PMCs, MTBRa enhanced TLR2 and TLR4 expression, activated ERK signaling, and upregulated TNF-α mRNA and protein expression. Furthermore, knockdown of TLR2, but not TLR4, significantly inhibited ERK phosphorylation and TNF-α expression. Additionally, both MTBRa and TNF-α markedly induced MMP-1 and MMP-9 synthesis in human PMCs, and TNF-α neutralization substantially reduced the production of MMP-1, but not MMP-9, in response to MTBRa stimulation.MTBRa activates TLR2/ERK signalings to induce TNF-α and elicit MMP-1 and MMP-9 in human PMCs, which are associated with effusion volume and pleural fibrosis and may contribute to pathogenesis of TBP. Further investigation of manipulation of TNF-α and MMP expression in pleural mesothelium may provide new insights into the mechanisms and rational treatment strategies for TBP.

  7. Toll-Like Receptor 2 mediates in vivo pro- and anti-inflammatory effects of Mycobacterium tuberculosis and modulates autoimmune encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Alessia ePiermattei

    2016-05-01

    Full Text Available Mycobacteria display pro- and anti-inflammatory effects in human and experimental pathology. We show here that both effects are mediated by Toll like receptor 2 (Tlr2, by exploiting a previously characterized Tlr2 variant (Met82Ile. Tlr2 82ile promoted self-specific pro-inflammatory polarization as well as expansion of ag-specific FoxP3+ Tregs, while Tlr2 82met impairs the expansion of Tregs and reduces the production of IFN-γ and IL-17 pro-inflammatory cytokines. Preferential dimerization with Tlr1 or Tlr6 could not explain these differences. In silico, we showed that Tlr2 variant Met82Ile modified the binding pocket for peptidoglycans and participate directly to a putative binding pocket for sugars and Cadherins. The distinct pro- and anti-inflammatory actions impacted on severity, extent of remission and distribution of the lesions within the Central Nervous System of Experimental Autoimmune Encephalomyelitis. Thus, Tlr2 has a janus function in vivo as mediator of the role of bacterial products in balancing pro- and anti-inflammatory immune responses.

  8. Atopy and new-onset asthma in young Danish farmers and CD14, TLR2, and TLR4 genetic polymorphisms: a nested case-control study

    DEFF Research Database (Denmark)

    Smit, L A M; Bongers, S I M; Ruven, H J T

    2007-01-01

    BACKGROUND: Evidence exists that exposure to high levels of microbial agents such as endotoxin in the farm environment decreases the risk of atopic sensitization. Genetic variation in innate immunity genes may modulate the response to microbial agents and thus influence susceptibility to asthma...... and atopy. OBJECTIVE: To study potential associations between single nucleotide polymorphisms (SNPs) in CD14, Toll-like receptor 2 (TLR2), and TLR4 genes, and atopy and new-onset asthma in young farmers. METHODS: A nested case-control study was conducted within a cohort of 1901 young Danish farmers. We....../-651 promoter polymorphisms are associated with atopy prevalence among young adults exposed to farm environments. Udgivelsesdato: 2007-Nov...

  9. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants.

    Science.gov (United States)

    Rossi, Omar; Pesce, Isabella; Giannelli, Carlo; Aprea, Susanna; Caboni, Mariaelena; Citiulo, Francesco; Valentini, Sara; Ferlenghi, Ilaria; MacLennan, Calman Alexander; D'Oro, Ugo; Saul, Allan; Gerke, Christiane

    2014-09-05

    Outer membrane particles from Gram-negative bacteria are attractive vaccine candidates as they present surface antigens in their natural context. We previously developed a high yield production process for genetically derived particles, called generalized modules for membrane antigens (GMMA), from Shigella. As GMMA are derived from the outer membrane, they contain immunostimulatory components, especially lipopolysaccharide (LPS). We examined ways of reducing their reactogenicity by modifying lipid A, the endotoxic part of LPS, through deletion of late acyltransferase genes, msbB or htrB, in GMMA-producing Shigella sonnei and Shigella flexneri strains. GMMA with resulting penta-acylated lipid A from the msbB mutants showed a 600-fold reduced ability, and GMMA from the S. sonnei ΔhtrB mutant showed a 60,000-fold reduced ability compared with GMMA with wild-type lipid A to stimulate human Toll-like receptor 4 (TLR4) in a reporter cell line. In human peripheral blood mononuclear cells, GMMA with penta-acylated lipid A showed a marked reduction in induction of inflammatory cytokines (S. sonnei ΔhtrB, 800-fold; ΔmsbB mutants, 300-fold). We found that the residual activity of these GMMA is largely due to non-lipid A-related TLR2 activation. In contrast, in the S. flexneri ΔhtrB mutant, a compensatory lipid A palmitoleoylation resulted in GMMA with hexa-acylated lipid A with ∼10-fold higher activity to stimulate peripheral blood mononuclear cells than GMMA with penta-acylated lipid A, mostly due to retained TLR4 activity. Thus, for use as vaccines, GMMA will likely require lipid A penta-acylation. The results identify the relative contributions of TLR4 and TLR2 activation by GMMA, which need to be taken into consideration for GMMA vaccine development. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  10. Innate recognition of bacteria in human milk is mediated by a milk-derived highly expressed pattern recognition receptor, soluble CD14.

    OpenAIRE

    Lab?ta, MO; Vidal, K; Nores, JE; Arias, M; Vita, N; Morgan, BP; Guillemot, JC; Loyaux, D; Ferrara, P; Schmid, D; Affolter, M; Borysiewicz, LK; Donnet-Hughes, A; Schiffrin, EJ

    2000-01-01

    Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum ...

  11. Innate Recognition of Bacteria in Human Milk Is Mediated by a Milk-Derived Highly Expressed Pattern Recognition Receptor, Soluble Cd14

    OpenAIRE

    Labéta, Mario O.; Vidal, Karine; Nores, Julia E. Rey; Arias, Mauricio; Vita, Natalio; Morgan, B. Paul; Guillemot, Jean Claude; Loyaux, Denis; Ferrara, Pascual; Schmid, Daniel; Affolter, Michael; Borysiewicz, Leszek K.; Donnet-Hughes, Anne; Schiffrin, Eduardo J.

    2000-01-01

    Little is known about innate immunity to bacteria after birth in the hitherto sterile fetal intestine. Breast-feeding has long been associated with a lower incidence of gastrointestinal infections and inflammatory and allergic diseases. We found in human breast milk a 48-kD polypeptide, which we confirmed by mass spectrometry and sequencing to be a soluble form of the bacterial pattern recognition receptor CD14 (sCD14). Milk sCD14 (m-sCD14) concentrations were up to 20-fold higher than serum ...

  12. TLR-mediated inflammatory responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial lipoproteins.

    Science.gov (United States)

    Tomlinson, Gillian; Chimalapati, Suneeta; Pollard, Tracey; Lapp, Thabo; Cohen, Jonathan; Camberlein, Emilie; Stafford, Sian; Periselneris, Jimstan; Aldridge, Christine; Vollmer, Waldemar; Picard, Capucine; Casanova, Jean-Laurent; Noursadeghi, Mahdad; Brown, Jeremy

    2014-10-01

    Streptococcus pneumoniae infections induce inflammatory responses that contribute toward both disease pathogenesis and immunity, but the host-pathogen interactions that mediate these effects are poorly defined. We used the surface lipoprotein-deficient ∆lgt pneumococcal mutant strain to test the hypothesis that lipoproteins are key determinants of TLR-mediated immune responses to S. pneumoniae. We show using reporter assays that TLR2 signaling is dependent on pneumococcal lipoproteins, and that macrophage NF-κB activation and TNF-α release were reduced in response to the ∆lgt strain. Differences in TNF-α responses between Δlgt and wild-type bacteria were abrogated for macrophages from TLR2- but not TLR4-deficient mice. Transcriptional profiling of human macrophages revealed attenuated TLR2-associated responses to ∆lgt S. pneumoniae, comprising many NF-κB-regulated proinflammatory cytokine and chemokine genes. Importantly, non-TLR2-associated responses were preserved. Experiments using leukocytes from IL-1R-associated kinase-4-deficient patients and a mouse pneumonia model confirmed that proinflammatory responses were lipoprotein dependent. Our data suggest that leukocyte responses to bacterial lipoproteins are required for TLR2- and IL-1R-associated kinase-4-mediated inflammatory responses to S. pneumoniae. Copyright © 2014 The Authors.

  13. TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro.

    Science.gov (United States)

    Li, Jia-Yun; Liu, Yuan; Gao, Xiao-Xue; Gao, Xiang; Cai, Hong

    2014-09-01

    Brucella abortus is a zoonotic Gram-negative pathogen that causes brucelosis in ruminants and humans. Toll-like receptors (TLRs) recognize Brucella abortus and initiate antigen-presenting cell activities that affect both innate and adaptive immunity. In this study, we focused on recombinant Brucella cell-surface protein 31 (rBCSP31) to determine its effects on mouse macrophages. Our results demonstrated that rBCSP31 induced TNF-α, IL-6 and IL-12p40 production, which depended on the activation of mitogen-activated protein kinases (MAPKs) by stimulating the rapid phosphorylation of p38 and JNK and the activation of transcription factor NF-κB in macrophages. In addition, continuous exposure (>24 h) of RAW264.7 cells to rBCSP31 significantly enhanced IFN-γ-induced expression of MHC-II and the ability to present rBCSP31 peptide to CD4(+) T cells. Furthermore, we found that rBCSP31 could interact with both TLR2 and TLR4. The rBCSP31-induced cytokine production by macrophages from TLR2(-/-) and TLR4(-/-) mice was lower than that from C57BL/6 macrophages, and the activation of NF-κB and MAPKs was attenuated in macrophages from TLR2(-/-) and TLR4(-/-) mice. In addition, CD4(+) T cells from C57BL/6 mice immunized with rBCSP31 produced higher levels of IFN-γ and IL-2 compared with CD4(+) T cells from TLR2(-/-) and TLR4(-/-) mice. Macrophages from immunized C57BL/6 mice produced higher levels of IL-12p40 than those from TLR2(-/-) and TLR4(-/-) mice. Furthermore, immunization with rBCSP31 provided better protection in C57BL/6 mice than in TLR2(-/-) and TLR4(-/-) mice after B. abortus 2308 challenge. These results indicate that rBCSP31 is a TLR2 and TLR4 agonist that induces cytokine production, upregulates macrophage function and induces the Th1 immune response.

  14. Role of pattern recognition receptors of the neurovascular unit in inflamm-aging.

    Science.gov (United States)

    Wilhelm, Imola; Nyúl-Tóth, Ádám; Kozma, Mihály; Farkas, Attila E; Krizbai, István A

    2017-11-01

    Aging is associated with chronic inflammation partly mediated by increased levels of damage-associated molecular patterns, which activate pattern recognition receptors (PRRs) of the innate immune system. Furthermore, many aging-related disorders are associated with inflammation. PRRs, such as Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs), are expressed not only in cells of the innate immune system but also in other cells, including cells of the neurovascular unit and cerebral vasculature forming the blood-brain barrier. In this review, we summarize our present knowledge about the relationship between activation of PRRs expressed by cells of the neurovascular unit-blood-brain barrier, chronic inflammation, and aging-related pathologies of the brain. The most important damage-associated molecular pattern-sensing PRRs in the brain are TLR2, TLR4, and NLR family pyrin domain-containing protein-1 and pyrin domain-containing protein-3, which are activated during physiological and pathological aging in microglia, neurons, astrocytes, and possibly endothelial cells and pericytes. Copyright © 2017 the American Physiological Society.

  15. Reading the viral signature by Toll-like receptors and other pattern recognition receptors.

    Science.gov (United States)

    Mogensen, Trine H; Paludan, Søren R

    2005-03-01

    Successful host defense against viral infections relies on early production of type I interferon (IFN) and subsequent activation of a cellular cytotoxic response. The acute IFN and inflammatory response against virus infections is mediated by cellular pattern-recognition receptors (PRRs) that recognize specific molecular structures on viral particles or products of viral replication. Toll-like receptors (TLRs) constitute a class of membrane-bound PRRs capable of detecting microbial infections. While TLR2 and TLR4, which were first identified to recognize Gram-positive and Gram-negative bacteria, respectively, sense specific viral proteins on the cell surface, TLRs 3, 7, 8, and 9 serve as receptors for viral nucleic acids in endosomic compartments. In addition to TLRs, cells express cytoplasmic PRRs such as the RNA helicase retinoic acid inducible gene I and the kinase double-stranded RNA-activated protein kinase R, both of which sense dsRNA, a characteristic signature of viral replication, and initiate a protective cellular response. Here we review the recent progress in our understanding of PRRs and viral infections and discuss the molecular and cellular responses evoked by virus-activated PRRs. Finally, we look into what is currently known about the role of PRRs in viral infections in vivo.

  16. CD8 cells of patients with diffuse cutaneous leishmaniasis display functional exhaustion: the latter is reversed, in vitro, by TLR2 agonists.

    Directory of Open Access Journals (Sweden)

    Joselín Hernández-Ruiz

    Full Text Available Leishmania mexicana (Lm causes localized (LCL and diffuse (DCL cutaneous leishmaniasis. DCL patients have a poor cellular immune response leading to chronicity. It has been proposed that CD8 T lymphocytes (CD8 play a crucial role in infection clearance, although the role of CD8 cytotoxicity in disease control has not been elucidated. Lesions of DCL patients have been shown to harbor low numbers of CD8, as compared to patients with LCL, and leishmanicidal treatment restores CD8 numbers. The marked response of CD8 towards Leishmania parasites led us to analyze possible functional differences between CD8 from patients with LCL and DCL. We compared IFNγ production, antigen-specific proliferation, and cytotoxicity of CD8 purified from PBMC against autologous macrophages (MO infected with Leishmania mexicana (MOi. Additionally, we analyzed tissue biopsies from both groups of patients for evidence of cytotoxicity associated with apoptotic cells in the lesions. We found that CD8 cell of DCL patients exhibited low cytotoxicity, low antigen-specific proliferation and low IFNγ production when stimulated with MOi, as compared to LCL patients. Additionally, DCL patients had significantly less TUNEL+ cells in their lesions. These characteristics are similar to cellular "exhaustion" described in chronic infections. We intended to restore the functional capacity of CD8 cells of DCL patients by preincubating them with TLR2 agonists: Lm lipophosphoglycan (LPG or Pam3Cys. Cytotoxicity against MOi, antigen-specific proliferation and IFNγ production were restored with both stimuli, whereas PD-1 (a molecule associated with cellular exhaustion expression, was reduced. Our work suggests that CD8 response is associated with control of Lm infection in LCL patients and that chronic infection in DCL patients leads to a state of CD8 functional exhaustion, which could facilitate disease spread. This is the first report that shows the presence of functionally exhausted CD8

  17. Investigating the relationship between employees’ empowerment and organizational commitment with organizational health mediation in Tehran Municipality, Revenue Recognition and Collection department

    Directory of Open Access Journals (Sweden)

    B. Movahedi

    2016-07-01

    Full Text Available In today’s leading organizations, employees’ empowerment is considered as a significant issue in human resource management cycle and it has become a central theme of management functions and practices. The present study aimed to investigate the relationship between empowerment of staffs and organizational commitment with organizational health mediation. The results showed that there is a relationship between staffs empowerment and organizational commitment, and the aspects of empowerment (competence, effectiveness, autonomy, trust, choice right are also associated with organizational commitment and that the variable of organizational health plays a mediation role in the relationship between staffs’ empowerment and organizational commitment in the office of revenue recognition and collection in Tehran Municipality. This research is of descriptive type. To analyze the data, initially the normality of data was examined by using Kolmogorov-Smirnov test, and then assumptions were evaluated by using the model of structural equations and LISREL software.

  18. Cholesterol crystals enhance TLR2-and TLR4-mediated pro-inflammatory cytokine responses of monocytes to the proatherogenic oral bacterium Porphyromonas gingivalis

    DEFF Research Database (Denmark)

    Køllgaard, Tania Maria Simonsen; Enevold, Christian; Bendtzen, Klaus

    2017-01-01

    , including Porphyromonas gingivalis, have been found in atherosclerotic plaques in humans and mice. We aimed to determine whether cholesterol crystals (CHCs) and oral bacteria synergize in the stimulation of human monocytes. Incubation of human monocytes with CHCs induced secretion of interleukin (IL)-1β......β secretion induced by P. gingivalis LPS and IL-1β secretion induced by whole P. gingivalis bacteria. This enhancement was abrogated by the NLRP3 inflammasome inhibitors Z-YVAD-FMK and glibenclamide. CHCs had no effect on cytokine production induced by P. gingivalis gingipains. Taken together, our...... findings support that CHCs, via stimulation of NLRP3 inflammasomes, act in synergy with the periodontal pathogen P. gingivalis to promote monocyte secretion of pro-atherogenic cytokines....

  19. Cd1b-Mediated T Cell Recognition of a Glycolipid Antigen Generated from Mycobacterial Lipid and Host Carbohydrate during Infection

    Science.gov (United States)

    Moody, D. Branch; Guy, Mark R.; Grant, Ethan; Cheng, Tan-Yun; Brenner, Michael B.; Besra, Gurdyal S.; Porcelli, Steven A.

    2000-01-01

    T cells recognize microbial glycolipids presented by CD1 proteins, but there is no information regarding the generation of natural glycolipid antigens within infected tissues. Therefore, we determined the molecular basis of CD1b-restricted T cell recognition of mycobacterial glycosylated mycolates, including those produced during tissue infection in vivo. Transfection of the T cell receptor (TCR) α and β chains from a glucose monomycolate (GMM)-specific T cell line reconstituted GMM recognition in TCR-deficient T lymphoblastoma cells. This TCR-mediated response was highly specific for natural mycobacterial glucose-6-O-(2R, 3R) monomycolate, including the precise structure of the glucose moiety, the stereochemistry of the mycolate lipid, and the linkage between the carbohydrate and the lipid. Mycobacterial production of antigenic GMM absolutely required a nonmycobacterial source of glucose that could be supplied by adding glucose to media at concentrations found in mammalian tissues or by infecting tissue in vivo. These results indicate that mycobacteria synthesized antigenic GMM by coupling mycobacterial mycolates to host-derived glucose. Specific T cell recognition of an epitope formed by interaction of host and pathogen biosynthetic pathways provides a mechanism for immune response to those pathogenic mycobacteria that have productively infected tissues, as distinguished from ubiquitous, but innocuous, environmental mycobacteria. PMID:11015438

  20. Molecular recognition of naphthalene diimide ligands by telomeric quadruplex-DNA: the importance of the protonation state and mediated hydrogen bonds.

    Science.gov (United States)

    Spinello, A; Barone, G; Grunenberg, J

    2016-01-28

    In depth Monte Carlo conformational scans in combination with molecular dynamics (MD) simulations and electronic structure calculations were applied in order to study the molecular recognition process between tetrasubstituted naphthalene diimide (ND) guests and G-quadruplex (G4) DNA receptors. ND guests are a promising class of telomere stabilizers due to which they are used in novel anticancer therapeutics. Though several ND guests have been studied experimentally in the past, the protonation state under physiological conditions is still unclear. Based on chemical intuition, in the case of N-methyl-piperazine substitution, different protonation states are possible and might play a crucial role in the molecular recognition process by G4-DNA. Depending on the proton concentration, different nitrogen atoms of the N-methyl-piperazine might (or might not) be protonated. This fact was considered in our simulation in terms of a case by case analysis, since the process of molecular recognition is determined by possible donor or acceptor positions. The results of our simulations show that the electrostatic interactions between the ND ligands and the G4 receptor are maximized in the case of the protonation of the terminal nitrogen atoms, forming compact ND G4 complexes inside the grooves. The influence of different protonation states in terms of the ability to form hydrogen bonds with the sugar-phosphate backbone, as well as the importance of mediated vs. direct hydrogen bonding, was analyzed in detail by MD and relaxed force constant (compliance constant) simulations.

  1. Does Set for Variability Mediate the Influence of Vocabulary Knowledge on the Development of Word Recognition Skills?

    Science.gov (United States)

    Tunmer, William E.; Chapman, James W.

    2012-01-01

    This study investigated the hypothesis that vocabulary influences word recognition skills indirectly through "set for variability", the ability to determine the correct pronunciation of approximations to spoken English words. One hundred forty children participating in a 3-year longitudinal study were administered reading and…

  2. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory

    Science.gov (United States)

    Heisler, Jillian M.; O’Connor, Jason C.

    2015-01-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. PMID:26130057

  3. Indoleamine 2,3-dioxygenase-dependent neurotoxic kynurenine metabolism mediates inflammation-induced deficit in recognition memory.

    Science.gov (United States)

    Heisler, Jillian M; O'Connor, Jason C

    2015-11-01

    Cognitive dysfunction in depression is a prevalent and debilitating symptom that is poorly treated by the currently available pharmacotherapies. Research over the past decade has provided evidence for proinflammatory involvement in the neurobiology of depressive disorders and symptoms associated with these disorders, including aspects of memory dysfunction. Recent clinical studies implicate inflammation-related changes in kynurenine metabolism as a potential pathogenic factor in the development of a range of depressive symptoms, including deficits in cognition and memory. Additionally, preclinical work has demonstrated a number of mood-related depressive-like behaviors to be dependent on indoleamine 2,3-dioxygenase-1 (IDO1), the inflammation-induced rate-limiting enzyme of the kynurenine pathway. Here, we demonstrate in a mouse model, that peripheral administration of endotoxin induced a deficit in recognition memory. Mice deficient in IDO were protected from cognitive impairment. Furthermore, endotoxin-induced inflammation increased kynurenine metabolism within the perirhinal/entorhinal cortices, brain regions which have been implicated in recognition memory. A single peripheral injection of kynurenine, the metabolic product of IDO1, was sufficient to induce a deficit in recognition memory in both control and IDO null mice. Finally, kynurenine monooxygenase (KMO) deficient mice were also protected from inflammation-induced deficits on novel object recognition. These data implicate IDO-dependent neurotoxic kynurenine metabolism as a pathogenic factor for cognitive dysfunction in inflammation-induced depressive disorders and a potential novel target for the treatment of these disorders. Published by Elsevier Inc.

  4. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity.

    Science.gov (United States)

    Querec, Troy; Bennouna, Soumaya; Alkan, Sefik; Laouar, Yasmina; Gorden, Keith; Flavell, Richard; Akira, Shizuo; Ahmed, Rafi; Pulendran, Bali

    2006-02-20

    The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-alpha. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.

  5. Sodium Octanoate Modulates the Innate Immune Response of Bovine Mammary Epithelial Cells through the TLR2/P38/JNK/ERK1/2 Pathway: Implications during Staphylococcus aureus Internalization.

    Science.gov (United States)

    Alva-Murillo, Nayeli; Ochoa-Zarzosa, Alejandra; López-Meza, Joel E

    2017-01-01

    Bovine mammary epithelial cells (bMECs) contribute to mammary gland defense against invading pathogens, such as Staphylococcus aureus (intracellular facultative), which is recognized by TLR2. In a previous report, we showed that sodium octanoate [NaO, a medium chain fatty acid (C8)] induces (0.25 mM) or inhibits (1 mM) S. aureus internalization into bMECs and differentially regulates the innate immune response (IIR). However, the molecular mechanisms have not been described, which was the aim of this study. The results showed that α5β1 integrin membrane abundance (MA) was increased in 0.25 mM NaO-treated cells, but TLR2 or CD36 MA was not modified. When these receptors were blocked individually, 0.25 mM NaO-increased S. aureus internalization was notably reduced. Interestingly, in this condition, the IIR of the bMECs was impaired because MAPK (p38, JNK, and ERK1/2) phosphorylation and the activation of transcription factors related to these pathways were decreased. In addition, the 1 mM NaO treatment induced TLR2 MA, but neither the integrin nor CD36 MA was modified. The reduction in S. aureus internalization induced by 1 mM NaO was increased further when TLR2 was blocked. In addition, the phosphorylation levels of the MAPKs increased, and 13 transcriptional factors related to the IIR were slightly activated (CBF, CDP, c-Myb, AP-1, Ets-1/Pea-3, FAST-1, GAS/ISRE, AP-2, NFAT-1, OCT-1, RAR/DR-5, RXR/DR-1, and Stat-3). Moreover, the 1 mM NaO treatment up-regulated gene expression of IL-8 and RANTES and secretion of IL-1β. Notably, when 1 mM NaO-treated bMECs were challenged with S. aureus , the gene expression of IL-8 and IL-10 increased, while IL-1β secretion was reduced. In conclusion, our results showed that α5β1 integrin, TLR2 and CD36 are involved in 0.25 mM NaO-increased S. aureus internalization in bMECs. In addition, 1 mM NaO activates bMECs via the TLR2 signaling pathways (p38, JNK, and ERK1/2), which improves IIR before S. aureus invasion. Additionally

  6. Mediatization

    DEFF Research Database (Denmark)

    Hjarvard, Stig

    2017-01-01

    Mediatization research shares media effects studies' ambition of answering the difficult questions with regard to whether and how media matter and influence contemporary culture and society. The two approaches nevertheless differ fundamentally in that mediatization research seeks answers...... to these general questions by distinguishing between two concepts: mediation and mediatization. The media effects tradition generally considers the effects of the media to be a result of individuals being exposed to media content, i.e. effects are seen as an outcome of mediated communication. Mediatization...... research is concerned with long-term structural changes involving media, culture, and society, i.e. the influences of the media are understood in relation to how media are implicated in social and cultural changes and how these processes come to create new conditions for human communication and interaction...

  7. Extensive protein hydrolyzation is indispensable to prevent IgE-mediated poultry allergen recognition in dogs and cats

    OpenAIRE

    Olivry, Thierry; Bexley, Jennifer; Mougeot, Isabelle

    2017-01-01

    Background The central premise for the commercialization of diets with hydrolyzed ingredients is that the small-sized digested peptides would be unable to crosslink allergen-specific IgE at the surface of tissue mast cells and induce their degranulation. Evidence for the validity of this concept to diagnose food allergies in dogs and cats is limited, however. Our objectives were to study the recognition of standard and variably hydrolyzed poultry extracts by sera from dogs and cats with eleva...

  8. Toll-like receptor 2 mediates ischemia-reperfusion injury of the small intestine in adult mice.

    Directory of Open Access Journals (Sweden)

    Toshio Watanabe

    Full Text Available Toll-like receptor 2 (TLR2 recognizes conserved molecular patterns associated with both gram-negative and gram-positive bacteria, and detects some endogenous ligands. Previous studies demonstrated that in ischemia-reperfusion (I/R injury of the small intestine, the TLR2-dependent signaling exerted preventive effects on the damage in young mice, but did not have a significant effect in neonatal mice. We investigated the role of TLR2 in adult ischemia-reperfusion injury in the small intestine. Wild-type and TLR2 knockout mice at 16 weeks of age were subjected to intestinal I/R injury. Some wild-type mice received anti-Ly-6G antibodies to deplete circulating neutrophils. In wild-type mice, I/R induced severe small intestinal injury characterized by infiltration by inflammatory cells, disruption of the mucosal epithelium, and mucosal bleeding. Compared to wild-type mice, TLR2 knockout mice exhibited less severe mucosal injury induced by I/R, with a 35%, 33%, and 43% reduction in histological grading score and luminal concentration of hemoglobin, and the numbers of apoptotic epithelial cells, respectively. The I/R increased the activity of myeloperoxidase (MPO, a marker of neutrophil infiltration, and the levels of mRNA expression of tumor necrosis factor-α (TNF-α, intercellular adhesion molecule-1 (ICAM-1, and cyclooxygenase-2 (COX-2 in the small intestine of the wild-type mice by 3.3-, 3.2-, and 13.0-fold, respectively. TLR2 deficiency significantly inhibited the I/R-induced increase in MPO activity and the expression of mRNAs for TNF-α and ICAM-1, but did not affect the expression of COX-2 mRNA. I/R also enhanced TLR2 mRNA expression by 2.9-fold. TLR2 proteins were found to be expressed in the epithelial cells, inflammatory cells, and endothelial cells. Neutrophil depletion prevented intestinal I/R injury in wild-type mice. These findings suggest that TLR2 may mediate I/R injury of the small intestine in adult mice via induction of inflammatory

  9. Cuticular Hydrocarbons of Tribolium confusum Larvae Mediate Trail Following and Host Recognition in the Ectoparasitoid Holepyris sylvanidis.

    Science.gov (United States)

    Fürstenau, Benjamin; Hilker, Monika

    2017-09-01

    Parasitic wasps which attack insects infesting processed stored food need to locate their hosts hidden inside these products. Their host search is well-known to be guided by host kairomones, perceived via olfaction or contact. Among contact kairomones, host cuticular hydrocarbons (CHCs) may provide reliable information for a parasitoid. However, the chemistry of CHC profiles of hosts living in processed stored food products is largely unknown. Here we showed that the ectoparasitoid Holepyris sylvanidis uses CHCs of its host Tribolium confusum, a worldwide stored product pest, as kairomones for host location and recognition at short range. Chemical analysis of T. confusum larval extracts by gas chromatography coupled with mass spectrometry revealed a rich blend of long-chain (C25-C30) hydrocarbons, including n-alkanes, mono-, and dimethylalkanes. We further studied whether host larvae leave sufficient CHCs on a substrate where they walk along, thus allowing parasitoids to perceive a CHC trail and follow it to their host larvae. We detected 18 CHCs on a substrate that had been exposed to host larvae. These compounds were also found in crude extracts of host larvae and made up about a fifth of the CHC amount extracted. Behavioral assays showed that trails of host CHCs were followed by the parasitoids and reduced their searching time until successful host recognition. Host CHC trails deposited on different substrates were persistent for about a day. Hence, the parasitoid H. sylvanidis exploits CHCs of T. confusum larvae for host finding by following host CHC trails and for host recognition by direct contact with host larvae.

  10. Leptospira santorosai Serovar Shermani detergent extract induces an increase in fibronectin production through a Toll-like receptor 2-mediated pathway.

    Science.gov (United States)

    Tian, Ya-Chung; Hung, Cheng-Chieh; Li, Yi-Jung; Chen, Yung-Chang; Chang, Ming-Yang; Yen, Tzung-Hai; Hsu, Hsiang-Hao; Wu, Mai-Szu; Phillips, Aled; Yang, Chih-Wei

    2011-03-01

    Leptospirosis can activate inflammatory responses through Toll-like receptors (TLRs) and may cause renal tubulointerstitial fibrosis characterized by the accumulation of extracellular matrix (ECM). We have previously demonstrated that Leptospira santorosai serovar Shermani detergent extract stimulates ECM accumulation in vitro. The aim of this study was to examine the mechanistic basis of these previous observations and, in particular, to examine the potential involvement of TLRs. The addition of serovar Shermani detergent extract led to an increase in fibronectin gene expression and production. Inhibition of TLR2 but not TLR4 expression abrogated serovar Shermani detergent extract-mediated increases in fibronectin production. This response was also blocked by the knockdown of the gene expression of the TLR2 downstream transducers myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6). Serovar Shermani detergent extract also activated nuclear factor-κB, and its inhibition by curcumin-attenuated serovar Shermani detergent extract induced increases in fibronectin production. These effects were also mimicked by the specific TLR2 agonist, Pam(3)CsK(4), a response that was also abrogated by the knockdown of MyD88 and TRAF6. Similarly, the administration of live leptospires to cells also induced fibronectin production that was blocked by inhibition of TLR2 and MyD88 expression. In conclusion, serovar Shermani detergent extract can induce fibronectin production through the TLR2-associated cascade, providing evidence of an association between TLRs and leptospirosis-mediated ECM deposition.

  11. The LasB Elastase of Pseudomonas aeruginosa Acts in Concert with Alkaline Protease AprA To Prevent Flagellin-Mediated Immune Recognition.

    Science.gov (United States)

    Casilag, Fiordiligie; Lorenz, Anne; Krueger, Jonas; Klawonn, Frank; Weiss, Siegfried; Häussler, Susanne

    2016-01-01

    The opportunistic pathogen Pseudomonas aeruginosa is capable of establishing severe and persistent infections in various eukaryotic hosts. It encodes a wide array of virulence factors and employs several strategies to evade immune detection. In the present study, we screened the Harvard Medical School transposon mutant library of P. aeruginosa PA14 for bacterial factors that modulate interleukin-8 responses in A549 human airway epithelial cells. We found that in addition to the previously identified alkaline protease AprA, the elastase LasB is capable of degrading exogenous flagellin under calcium-replete conditions and prevents flagellin-mediated immune recognition. Our results indicate that the production of two proteases with anti-flagellin activity provides a failsafe mechanism for P. aeruginosa to ensure the maintenance of protease-dependent immune-modulating functions. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  12. A unique dual recognition hairpin probe mediated fluorescence amplification method for sensitive detection of uracil-DNA glycosylase and endonuclease IV activities.

    Science.gov (United States)

    Wu, Yushu; Yan, Ping; Xu, Xiaowen; Jiang, Wei

    2016-03-07

    Uracil-DNA glycosylase (UDG) and endonuclease IV (Endo IV) play cooperative roles in uracil base-excision repair (UBER) and inactivity of either will interrupt the UBER to cause disease. Detection of UDG and Endo IV activities is crucial to evaluate the UBER process in fundamental research and diagnostic application. Here, a unique dual recognition hairpin probe mediated fluorescence amplification method was developed for sensitively and selectively detecting UDG and Endo IV activities. For detecting UDG activity, the uracil base in the probe was excised by the target enzyme to generate an apurinic/apyrimidinic (AP) site, achieving the UDG recognition. Then, the AP site was cleaved by a tool enzyme Endo IV, releasing a primer to trigger rolling circle amplification (RCA) reaction. Finally, the RCA reaction produced numerous repeated G-quadruplex sequences, which interacted with N-methyl-mesoporphyrin IX to generate an enhanced fluorescence signal. Alternatively, for detecting Endo IV activity, the uracil base in the probe was first converted into an AP site by a tool enzyme UDG. Next, the AP site was cleaved by the target enzyme, achieving the Endo IV recognition. The signal was then generated and amplified in the same way as those in the UDG activity assay. The detection limits were as low as 0.00017 U mL(-1) for UDG and 0.11 U mL(-1) for Endo IV, respectively. Moreover, UDG and Endo IV can be well distinguished from their analogs. This method is beneficial for properly evaluating the UBER process in function studies and disease prognoses.

  13. Comprehensive Cross-Clade Characterization of Antibody-Mediated Recognition, Complement-Mediated Lysis, and Cell-Mediated Cytotoxicity of HIV-1 Envelope-Specific Antibodies toward Eradication of the HIV-1 Reservoir.

    Science.gov (United States)

    Mujib, Shariq; Liu, Jun; Rahman, A K M Nur-Ur; Schwartz, Jordan A; Bonner, Phil; Yue, Feng Yun; Ostrowski, Mario A

    2017-08-15

    Immunotherapy with passive administration of broadly neutralizing HIV-1 envelope-specific antibodies (bnAbs) in the setting of established infection in vivo has yielded mixed results. The contribution of different antibodies toward the direct elimination of infected cells is poorly understood. In this study, we determined the ability of 12 well-characterized anti-HIV-1 neutralizing antibodies to recognize and eliminate primary CD4 T cells infected with HIV-1 belonging to clades A, B, C, and D, via antibody-dependent complement-mediated lysis (ADCML) and antibody-dependent cell-mediated cytotoxicity (ADCC), in vitro We further tested unique combinations of these antibodies to determine the optimal antibody cocktails to be tested in future clinical trials. We report that antibody binding to infected CD4 T cells is highly variable and correlates with ADCML and ADCC processes. Particularly, antibodies targeting the envelope glycan shield (2G12) and V1/V2 site (PG9, PG16, and PGT145) are best at recognizing HIV-1-infected CD4 T cells. However, only PG9 and PG16 and their combinations with other bnAbs sufficiently induced the elimination of HIV-1-infected CD4 T cells by ADCML, ADCC, or both. Notably, CD4 binding site antibodies VRC01, 3BNC117, and NIH45-46 G54W did not exhibit recognition of infected cells and were unable to induce their killing. Future trials geared toward the development of a cure for HIV/AIDS should incorporate V1/V2 antibodies for maximal clearance of infected cells. With the use of only primary immune cells, we conducted a comprehensive cross-clade physiological analysis to aid the direction of antibodies as therapeutics toward the development of a cure for HIV/AIDS. IMPORTANCE Several antibodies capable of neutralizing the majority of circulating HIV-1 strains have been identified to date and have been shown to prevent infection in animal models. However, the use of combinations of such broadly neutralizing antibodies (bnAbs) for the treatment and

  14. Extensive protein hydrolyzation is indispensable to prevent IgE-mediated poultry allergen recognition in dogs and cats.

    Science.gov (United States)

    Olivry, Thierry; Bexley, Jennifer; Mougeot, Isabelle

    2017-08-17

    The central premise for the commercialization of diets with hydrolyzed ingredients is that the small-sized digested peptides would be unable to crosslink allergen-specific IgE at the surface of tissue mast cells and induce their degranulation. Evidence for the validity of this concept to diagnose food allergies in dogs and cats is limited, however. Our objectives were to study the recognition of standard and variably hydrolyzed poultry extracts by sera from dogs and cats with elevated chicken-specific serum IgE. Forty sera from dogs and 40 from cats with undetectable, low, medium or high serum levels of chicken-specific IgE were tested by ELISA on plates coated with the positive controls chicken, duck and turkey meat extracts and the negative controls beef meat (dogs) or wheat (cats). Plates were also coated with a non-hydrolyzed chicken meal, and mildly- or extensively-hydrolyzed poultry feather extracts. The frequencies of dogs with positive IgE against the various extracts were: chicken meat: 100%, duck and turkey meats: 97%, beef meat: 3%, non-hydrolyzed chicken meal: 73%, mildly-hydrolyzed poultry feathers: 37% and extensively-hydrolyzed poultry feathers: 0%. For cats, these respective percentages were (with wheat replacing beef as a negative control): 100, 84, 97, 7, 7, 0 and 0%. To detect any allergenic cross-reactivity between poultry meat-based and feather hydrolysate-derived extracts, an IgE ELISA inhibition was also done. Ten canine sera with the highest level of anti-poultry IgE in the previous experiment were incubated overnight with a previously optimized 50 μg amount of each of the extracts used above. We performed ELISA on plates coated with chicken, duck or turkey meats with or without inhibitors. The median inhibition percentages after incubation with the non-hydrolyzed chicken meal were ~22%, with the mildly-hydrolyzed poultry feathers: 14-22%, and those with the extensively-hydrolyzed poultry feathers: 5 to 10%; the last inhibition level was

  15. Nanostructured hydroxyapatite surfaces-mediated adsorption alters recognition of BMP receptor IA and bioactivity of bone morphogenetic protein-2.

    Science.gov (United States)

    Huang, Baolin; Yuan, Yuan; Ding, Sai; Li, Jianbo; Ren, Jie; Feng, Bo; Li, Tong; Gu, Yuantong; Liu, Changsheng

    2015-11-01

    Highly efficient loading of bone morphogenetic protein-2 (BMP-2) onto carriers with desirable performance is still a major challenge in the field of bone regeneration. Till now, the nanoscaled surface-induced changes of the structure and bioactivity of BMP-2 remains poorly understood. Here, the effect of nanoscaled surface on the adsorption and bioactivity of BMP-2 was investigated with a series of hydroxyapatite surfaces (HAPs): HAP crystal-coated surface (HAP), HAP crystal-coated polished surface (HAP-Pol), and sintered HAP crystal-coated surface (HAP-Sin). The adsorption dynamics of recombinant human BMP-2 (rhBMP-2) and the accessibility of the binding epitopes of adsorbed rhBMP-2 for BMP receptors (BMPRs) were examined by a quartz crystal microbalance with dissipation. Moreover, the bioactivity of adsorbed rhBMP-2 and the BMP-induced Smad signaling were investigated with C2C12 model cells. A noticeably high mass-uptake of rhBMP-2 and enhanced recognition of BMPR-IA to adsorbed rhBMP-2 were found on the HAP-Pol surface. For the rhBMP-2-adsorbed HAPs, both ALP activity and Smad signaling increased in the order of HAP-Sinuses of rhBMP-2 in clinical applications and arouse broad interests among researchers in the fields of nano-biotechnology, biomaterials and bone tissue engineering. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  16. Tomato Cf resistance proteins mediate recognition of cognate homologous effectors from fungi pathogenic on dicots and monocots.

    Science.gov (United States)

    Stergiopoulos, Ioannis; van den Burg, Harrold A; Okmen, Bilal; Beenen, Henriek G; van Liere, Sabine; Kema, Gert H J; de Wit, Pierre J G M

    2010-04-20

    Most fungal effectors characterized so far are species-specific and facilitate virulence on a particular host plant. During infection of its host tomato, Cladosporium fulvum secretes effectors that function as virulence factors in the absence of cognate Cf resistance proteins and induce effector-triggered immunity in their presence. Here we show that homologs of the C. fulvum Avr4 and Ecp2 effectors are present in other pathogenic fungi of the Dothideomycete class, including Mycosphaerella fijiensis, the causal agent of black Sigatoka disease of banana. We demonstrate that the Avr4 homolog of M. fijiensis is a functional ortholog of C. fulvum Avr4 that protects fungal cell walls against hydrolysis by plant chitinases through binding to chitin and, despite the low overall sequence homology, triggers a Cf-4-mediated hypersensitive response (HR) in tomato. Furthermore, three homologs of C. fulvum Ecp2 are found in M. fijiensis, one of which induces different levels of necrosis or HR in tomato lines that lack or contain a putative cognate Cf-Ecp2 protein, respectively. In contrast to Avr4, which acts as a defensive virulence factor, M. fijiensis Ecp2 likely promotes virulence by interacting with a putative host target causing host cell necrosis, whereas Cf-Ecp2 could possibly guard the virulence target of Ecp2 and trigger a Cf-Ecp2-mediated HR. Overall our data suggest that Avr4 and Ecp2 represent core effectors that are collectively recognized by single cognate Cf-proteins. Transfer of these Cf genes to plant species that are attacked by fungi containing these cognate core effectors provides unique ways for breeding disease-resistant crops.

  17. Differential Effects of Peptidoglycan Recognition Proteins on Experimental Atopic and Contact Dermatitis Mediated by Treg and Th17 Cells

    Science.gov (United States)

    Park, Shin Yong; Gupta, Dipika; Kim, Chang H.; Dziarski, Roman

    2011-01-01

    Skin protects the body from the environment and is an important component of the innate and adaptive immune systems. Atopic dermatitis and contact dermatitis are among the most frequent inflammatory skin diseases and are both determined by multigenic predisposition, environmental factors, and aberrant immune response. Peptidoglycan Recognition Proteins (Pglyrps) are expressed in the skin and we report here that they modulate sensitivity to experimentally-induced atopic dermatitis and contact dermatitis. Pglyrp3 −/− and Pglyrp4 −/− mice (but not Pglyrp2 −/− mice) develop more severe oxazolone-induced atopic dermatitis than wild type (WT) mice. The common mechanism underlying this increased sensitivity of Pglyrp3 −/− and Pglyrp4 −/− mice to atopic dermatitis is reduced recruitment of Treg cells to the skin and enhanced production and activation Th17 cells in Pglyrp3 −/− and Pglyrp4 −/− mice, which results in more severe inflammation and keratinocyte proliferation. This mechanism is supported by decreased inflammation in Pglyrp3 −/− mice following in vivo induction of Treg cells by vitamin D or after neutralization of IL-17. By contrast, Pglyrp1 −/− mice develop less severe oxazolone-induced atopic dermatitis and also oxazolone-induced contact dermatitis than WT mice. Thus, Pglyrp3 and Pglyrp4 limit over-activation of Th17 cells by promoting accumulation of Treg cells at the site of chronic inflammation, which protects the skin from exaggerated inflammatory response to cell activators and allergens, whereas Pglyrp1 has an opposite pro-inflammatory effect in the skin. PMID:21949809

  18. Cyclic GMP-mediated memory enhancement in the object recognition test by inhibitors of phosphodiesterase-2 in mice.

    Science.gov (United States)

    Lueptow, Lindsay M; Zhan, Chang-Guo; O'Donnell, James M

    2016-02-01

    Cyclic nucleotide phosphodiesterase-2 (PDE2) is a potential therapeutic target for the treatment of cognitive dysfunction. Using the object recognition test (ORT), this study assessed the effects of two PDE2 inhibitors, Bay 60-7550 and ND7001, on learning and memory, and examined underlying mechanisms. To assess the role of PDE2 inhibition on phases of memory, Bay 60-7550 (3 mg/kg) was administered: 30 min prior to training; 0, 1, or 3 h after training; or 30 min prior to recall testing. To assess cyclic nucleotide involvement in PDE2 inhibitor-enhanced memory consolidation, either the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg; intraperitoneal (IP)), soluble guanylyl cyclase inhibitor 1H-[-1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 20 mg/kg; IP), protein kinase G inhibitor KT5823 (2.5 μg; intracerebroventricular (ICV)), or protein kinase A inhibitor H89 (1 μg; ICV) was administered 30 min prior to the PDE2 inhibitor Bay 60-7550 (3 mg/kg) or ND7001 (3 mg/kg). Changes in the phosphorylation of 3'5'-cyclic adenosine monophosphate (cAMP) response element binding protein (CREB) at Ser-133 and vasodilator-stimulated phosphoprotein (VASP) at Ser-239 were determined to confirm activation of cAMP and 3'5'-cyclic guanosine monophosphate (cGMP) signaling. Bay 60-7550 (3 mg/kg) enhanced memory of mice in the ORT when given 30 min prior to training, immediately after training, or 30 min prior to recall. Inhibitors of the cGMP pathway blocked the memory-enhancing effects of both Bay 60-7550 (3 mg/kg) and ND7001 (3 mg/kg) on early consolidation processes. Bay 60-7550 (3 mg/kg) enhanced phosphorylation of CREB and VASP, both targets of cGMP-dependent protein kinase (PKG). These results confirm a potential of PDE2, or components of its signaling pathway, as a therapeutic target for drug discovery focused on restoring memory function.

  19. Ursolic acid isolated from Uncaria rhynchophylla activates human dendritic cells via TLR2 and/or TLR4 and induces the production of IFN-gamma by CD4+ naïve T cells.

    Science.gov (United States)

    Jung, Tae-Young; Pham, Thanh Nhan Nguyen; Umeyama, Akemi; Shoji, Noboru; Hashimoto, Toshihiro; Lee, Je-Jung; Takei, Masao

    2010-09-25

    Ursolic acid is triterpene isolated from Uncaria rhynchophylla and is a pharmacologically active substance. The induction of dendritic cell maturation is critical for the induction of Ag-specific T-lymphocyte response and may be essential for the development of human vaccine relying on T cell immunity. In this study, we investigated that the effect of Ursolic acid on the phenotypic and functional maturation of human monocyte-derived dendritic cells in vitro. Dendritic cells harvested on day 8 were examined using functional assay. The expression levels of CD1a, CD80, CD83, CD86, HLA-DR and CCR7 on Ursolic acid-primed dendritic cells was slightly enhanced. Ursolic acid dose-dependently enhanced the T cell stimulatory capacity in an allogeneic mixed lymphocyte reaction, as measured by T cell proliferation. The production of IL-12p70 induced by Ursolic acid-primed dendritic cells was inhibited by the anti-Toll-like receptor-2 (TLR2) mAb and anti-TLR4 mAb. Moreover, Ursolic acid-primed dendritic cells expressed levels of mRNA coding for both TLR2 and TLR4. The majority of cells produced considerable interferon-gamma (IFN-gamma), but also small amounts of interleukin (IL-4)-4. Ursolic acid-primed dendritic cells have an intermediate migratory capacity towards CCL19 and CCL21. These results suggest that Ursolic acid modulates human dendritic cells function in a fashion that favors Th1 polarization via the activation of IL-12p70 dependent on TLR2 and/or TLR4, and may be used on dendritic cells-based vaccines for cancer immunotherapy. 2010 Elsevier B.V. All rights reserved.

  20. Human Mediator Enhances Activator-Facilitated Recruitment of RNA Polymerase II and Promoter Recognition by TATA-Binding Protein (TBP) Independently of TBP-Associated Factors

    OpenAIRE

    Wu, Shwu-Yuan; Zhou, Tianyuan; Chiang, Cheng-Ming

    2003-01-01

    Mediator is a general cofactor implicated in the functions of many transcriptional activators. Although Mediator with different protein compositions has been isolated, it remains unclear how Mediator facilitates activator-dependent transcription, independent of its general stimulation of basal transcription. To define the mechanisms of Mediator function, we isolated two forms of human Mediator complexes (Mediator-P.5 and Mediator-P.85) and demonstrated that Mediator-P.5 clearly functions by e...

  1. The murine cytomegalovirus M35 protein antagonizes type I IFN induction downstream of pattern recognition receptors by targeting NF-κB mediated transcription.

    Directory of Open Access Journals (Sweden)

    Baca Chan

    2017-05-01

    Full Text Available The type I interferon (IFN response is imperative for the establishment of the early antiviral immune response. Here we report the identification of the first type I IFN antagonist encoded by murine cytomegalovirus (MCMV that shuts down signaling following pattern recognition receptor (PRR sensing. Screening of an MCMV open reading frame (ORF library identified M35 as a novel and strong negative modulator of IFNβ promoter induction following activation of both RNA and DNA cytoplasmic PRR. Additionally, M35 inhibits the proinflammatory cytokine response downstream of Toll-like receptors (TLR. Using a series of luciferase-based reporters with specific transcription factor binding sites, we determined that M35 targets NF-κB-, but not IRF-mediated, transcription. Expression of M35 upon retroviral transduction of immortalized bone marrow-derived macrophages (iBMDM led to reduced IFNβ transcription and secretion upon activation of stimulator of IFN genes (STING-dependent signaling. On the other hand, M35 does not antagonize interferon-stimulated gene (ISG 56 promoter induction or ISG transcription upon exogenous stimulation of the type I IFN receptor (IFNAR. M35 is present in the viral particle and, upon MCMV infection of fibroblasts, is immediately shuttled to the nucleus where it exerts its immunomodulatory effects. Deletion of M35 from the MCMV genome and hence from the viral particle resulted in elevated type I IFN transcription and secretion in vitro and in vivo. In the absence of M35, lower viral titers are observed during acute infection of the host, and productive infection in the salivary glands was not detected. In conclusion, the M35 protein is released by MCMV immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-κB-mediated transcription. The identification of this novel viral protein reinforces the importance of timely countermeasures in the complex relationship between virus and host.

  2. TLR4, NOD1 and NOD2 Mediate Immune Recognition of Putative Newly-Identified Periodontal Pathogens

    Science.gov (United States)

    Schaff, Riley A.; Hao, Jie; Morelli, Thiago; Kinney, Janet S.; Gerow, Elizabeth; Sheridan, Rachel; Rodrigues, Vinicius; Paster, Bruce J.; Inohara, Naohiro; Giannobile, William V.

    2015-01-01

    SUMMARY Periodontitis is a polymicrobial inflammatory disease that results from the interaction between the oral microbiota and the host immunity. While the innate immune response is important for disease initiation and progression, the innate immune receptors that recognize both classical and putative periodontal pathogens that elicit an immune response have not been elucidated. By using the Human Oral Microbe Identification Microarray (HOMIM), we identified multiple predominant oral bacterial species in human plaque biofilm that strongly associate with severe periodontitis. Ten of the identified species were evaluated in greater depth, 6 being classical pathogens and 4 putative novel pathogens. Using human peripheral blood monocytes (HPBM) and murine bone marrow–derived macrophages (BMDM) from wild-type (WT) and toll-like receptor (TLR)-specific and MyD88 knockouts (KOs), we demonstrated that heat-killed Campylobacter concisus, Campylobacter rectus, Selenomonas infelix, Porphyromonas endodontalis, Porphyromonas gingivalis, and Tannerella forsythia mediate high immunostimulatory activity. C. concisus, C. rectus, and S. infelix exhibited robust TLR4 stimulatory activity. Studies using mesothelial cells from WT and NOD1-specific KOs and NOD2-expressing human embryonic kidney (HEK) cells demonstrated that Eubacterium saphenum, Eubacterium nodatum and Filifactor alocis exhibit robust NOD1 stimulatory activity, and that Porphyromonas endodontalis and Parvimonas micra have the highest NOD2-stimulatory activity. These studies allowed us to provide important evidence on newly-identified putative pathogens in periodontal disease pathogenesis showing that these bacteria exhibit different immunostimulatory activity via TLR4, NOD1, and NOD2 (Clinicaltrials.gov NCT01154855). PMID:26177212

  3. Damage-recognition proteins as a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to ultraviolet radiation

    International Nuclear Information System (INIS)

    Chao, C.C.-K.

    1992-01-01

    The authors compared damage-recognition proteins in cells expressing different sensitivities to DNA damage. An increase in damage-recognition proteins and an enhancement of plasmid re-activation were detected in HeLa cells resistant to cisplatin and u.v. However, repair-defective cells derived from xeroderma-pigmentosum (a rare skin disease) patients did not express less cisplatin damage-recognition proteins than repair-competent cells, suggesting that damage-recognition-protein expression may not be related to DNA repair. By contrast, cells resistant to DNA damage consistently expressed high levels of u.v.-modified-DNA damage-recognition proteins. The results support the notion that u.v. damage-recognition proteins are different from those that bind to cisplatin. Findings also suggest that the damage-recognition proteins identified could be used as potential indicators of the sensitivity or resistance of cells to u.v. (author)

  4. Hepatitis C Virus Frameshift/Alternate Reading Frame Protein Suppresses Interferon Responses Mediated by Pattern Recognition Receptor Retinoic-Acid-Inducible Gene-I.

    Directory of Open Access Journals (Sweden)

    Seung Bum Park

    Full Text Available Hepatitis C virus (HCV actively evades host interferon (IFN responses but the mechanisms of how it does so are not completely understood. In this study, we present evidence for an HCV factor that contributes to the suppression of retinoic-acid-inducible gene-I (RIG-I-mediated IFN induction. Expression of frameshift/alternate reading frame protein (F/ARFP from HCV -2/+1 frame in Huh7 hepatoma cells suppressed type I IFN responses stimulated by HCV RNA pathogen-associated molecular pattern (PAMP and poly(IC. The suppression occurred independently of other HCV factors; and activation of interferon stimulated genes, TNFα, IFN-λ1, and IFN-λ2/3 was likewise suppressed by HCV F/ARFP. Point mutations in the full-length HCV sequence (JFH1 genotype 2a strain were made to introduce premature termination codons in the -2/+1 reading frame coding for F/ARFP while preserving the original reading frame, which enhanced IFNα and IFNβ induction by HCV. The potentiation of IFN response by the F/ARFP mutations was diminished in Huh7.5 cells, which already have a defective RIG-I, and by decreasing RIG-I expression in Huh7 cells. Furthermore, adding F/ARFP back via trans-complementation suppressed IFN induction in the F/ARFP mutant. The F/ARFP mutants, on the other hand, were not resistant to exogenous IFNα. Finally, HCV-infected human liver samples showed significant F/ARFP antibody reactivity, compared to HCV-uninfected control livers. Therefore, HCV F/ARFP likely cooperates with other viral factors to suppress type I and III IFN induction occurring through the RIG-I signaling pathway. This study identifies a novel mechanism of pattern recognition receptor modulation by HCV and suggests a biological function of the HCV alternate reading frame in the modulation of host innate immunity.

  5. Pattern recognition

    CERN Document Server

    Theodoridis, Sergios

    2003-01-01

    Pattern recognition is a scientific discipline that is becoming increasingly important in the age of automation and information handling and retrieval. Patter Recognition, 2e covers the entire spectrum of pattern recognition applications, from image analysis to speech recognition and communications. This book presents cutting-edge material on neural networks, - a set of linked microprocessors that can form associations and uses pattern recognition to ""learn"" -and enhances student motivation by approaching pattern recognition from the designer's point of view. A direct result of more than 10

  6. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    Energy Technology Data Exchange (ETDEWEB)

    Moyer, Benjamin J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Rojas, Itzel Y. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Kerley-Hamilton, Joanna S. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Hazlett, Haley F. [Department of Pharmacology & Toxicology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Nemani, Krishnamurthy V. [Department of Radiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Trask, Heidi W.; West, Rachel J. [Norris Cotton Cancer Center, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Lupien, Leslie E. [Department of Medicine, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); Collins, Alan J. [Department of Immunology & Microbiology, Geisel School of Medicine at Dartmouth, Dartmouth Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756 (United States); and others

    2016-06-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  7. Inhibition of the aryl hydrocarbon receptor prevents Western diet-induced obesity. Model for AHR activation by kynurenine via oxidized-LDL, TLR2/4, TGFβ, and IDO1

    International Nuclear Information System (INIS)

    Moyer, Benjamin J.; Rojas, Itzel Y.; Kerley-Hamilton, Joanna S.; Hazlett, Haley F.; Nemani, Krishnamurthy V.; Trask, Heidi W.; West, Rachel J.; Lupien, Leslie E.; Collins, Alan J.

    2016-01-01

    Obesity is an increasingly urgent global problem, yet, little is known about its causes and less is known how obesity can be effectively treated. We showed previously that the aryl hydrocarbon receptor (AHR) plays a role in the regulation of body mass in mice fed Western diet. The AHR is a ligand-activated nuclear receptor that regulates genes involved in a number of biological pathways, including xenobiotic metabolism and T cell polarization. This study was an investigation into whether inhibition of the AHR prevents Western diet-based obesity. Male C57Bl/6J mice were fed control and Western diets with and without the AHR antagonist α-naphthoflavone or CH-223191, and a mouse hepatocyte cell line was used to delineate relevant cellular pathways. Studies are presented showing that the AHR antagonists α-naphthoflavone and CH-223191 significantly reduce obesity and adiposity and ameliorates liver steatosis in male C57Bl/6J mice fed a Western diet. Mice deficient in the tryptophan metabolizing enzyme indoleamine 2,3-dioxygenase 1 (IDO1) were also resistant to obesity. Using an AHR-directed, luciferase-expressing mouse hepatocyte cell line, we show that the transforming growth factor β1 (TGFβ1) signaling pathway via PI3K and NF-κB and the toll-like receptor 2/4 (TLR2/4) signaling pathway stimulated by oxidized low-density lipoproteins via NF-κB, each induce luciferase expression; however, TLR2/4 signaling was significantly reduced by inhibition of IDO1. At physiological levels, kynurenine but not kynurenic acid (both tryptophan metabolites and known AHR agonists) activated AHR-directed luciferase expression. We propose a hepatocyte-based model, in which kynurenine production is increased by enhanced IDO1 activity stimulated by TGFβ1 and TLR2/4 signaling, via PI3K and NF-κB, to perpetuate a cycle of AHR activation to cause obesity; and inhibition of the AHR, in turn, blocks the cycle's output to prevent obesity. The AHR with its broad ligand binding

  8. Consumption of Bifidobacterium animalis subsp. lactis BB-12 in yogurt reduced expression of TLR-2 on peripheral blood-derived monocytes and pro-inflammatory cytokine secretion in young adults.

    Science.gov (United States)

    Meng, Huicui; Ba, Zhaoyong; Lee, Yujin; Peng, Jiayu; Lin, Junli; Fleming, Jennifer A; Furumoto, Emily J; Roberts, Robert F; Kris-Etherton, Penny M; Rogers, Connie J

    2017-03-01

    Probiotic bacteria modulate immune parameters and inflammatory outcomes. Emerging evidence demonstrates that the matrix used to deliver probiotics may influence the efficacy of probiotic interventions in vivo. The aims of the current study were to evaluate (1) the effect of one species, Bifidobacterium animalis subsp. lactis BB-12 at a dose of log10 ± 0.5 CFUs/day on immune responses in a randomized, partially blinded, 4-period crossover, free-living study, and (2) whether the immune response to BB-12 differed depending on the delivery matrix. Healthy adults (n = 30) aged 18-40 years were recruited and received four treatments in a random order: (A) yogurt smoothie alone; smoothie with BB-12 added (B) before or (C) after yogurt fermentation, or (D) BB-12 given in capsule form. At baseline and after each 4-week treatment, peripheral blood mononuclear cells (PBMCs) were isolated, and functional and phenotypic marker expression was assessed. BB-12 interacted with peripheral myeloid cells via Toll-like receptor 2 (TLR-2). The percentage of CD14 + HLA-DR + cells in peripheral blood was increased in male participants by all yogurt-containing treatments compared to baseline (p = 0.0356). Participants who consumed yogurt smoothie with BB-12 added post-fermentation had significantly lower expression of TLR-2 on CD14 + HLA-DR + cells (p = 0.0186) and reduction in TNF-α secretion from BB-12- (p = 0.0490) or LPS-stimulated (p = 0.0387) PBMCs compared to baseline. These findings not only demonstrate a potential anti-inflammatory effect of BB-12 in healthy adults, but also indicate that the delivery matrix influences the immunomodulatory properties of BB-12.

  9. Evolution of Soybean mosaic virus-G7 molecularly cloned genome in Rsv1-genotype soybean results in emergence of a mutant capable of evading Rsv1-mediated recognition

    International Nuclear Information System (INIS)

    Hajimorad, M.R.; Eggenberger, A.L.; Hill, J.H.

    2003-01-01

    Plant resistance (R) genes direct recognition of pathogens harboring matching avirluent signals leading to activation of defense responses. It has long been hypothesized that under selection pressure the infidelity of RNA virus replication together with large population size and short generation times results in emergence of mutants capable of evading R-mediated recognition. In this study, the Rsv1/Soybean mosaic virus (SMV) pathosystem was used to investigate this hypothesis. In soybean line PI 96983 (Rsv1), the progeny of molecularly cloned SMV strain G7 (pSMV-G7) provokes a lethal systemic hypersensitive response (LSHR) with up regulation of a defense-associated gene transcript (PR-1). Serial passages of a large population of the progeny in PI 96983 resulted in emergence of a mutant population (vSMV-G7d), incapable of provoking either Rsv1-mediated LSHR or PR-1 protein gene transcript up regulation. An infectious clone of the mutant (pSMV-G7d) was synthesized whose sequences were very similar but not identical to the vSMV-G7d population; however, it displayed a similar phenotype. The genome of pSMV-G7d differs from parental pSMV-G7 by 17 substitutions, of which 10 are translationally silent. The seven amino acid substitutions in deduced sequences of pSMV-G7d differ from that of pSMV-G7 by one each in P1 proteinase, helper component-proteinase, and coat protein, respectively, and by four in P3. To the best of our knowledge, this is the first demonstration in which experimental evolution of a molecularly cloned plant RNA virus resulted in emergence of a mutant capable of evading an R-mediated recognition

  10. Mapping the pulmonary environment of animals protected from virulent H1N1 influenza infection using the TLR-2 agonist Pam₂Cys.

    Science.gov (United States)

    Mifsud, Edin J; Tan, Amabel C L; Reading, Patrick C; Jackson, David C

    2016-02-01

    We have previously shown that intranasal administration of the Toll-like receptor-2 agonist, S-(2,3-bis(palmitoyloxy)propyl) cysteine (Pam2Cys), provides immediate and antigen independent protection against challenge with influenza virus. Here we characterize the cellular pulmonary environments of mice which had either been treated with Pam2Cys or placebo and then challenged with influenza virus. We show that Pam2Cys treatment results in the influx of innate immune cells into the lungs and that depletion of phagocytic cells from this influx using clodronate-loaded liposomes caused a reduction in the number of interstitial macrophages and monocytes. This resulted in abolition of the protective effect indicating the importance of this cellular subset in Pam2Cys-mediated protection.

  11. Speech Recognition

    Directory of Open Access Journals (Sweden)

    Adrian Morariu

    2009-01-01

    Full Text Available This paper presents a method of speech recognition by pattern recognition techniques. Learning consists in determining the unique characteristics of a word (cepstral coefficients by eliminating those characteristics that are different from one word to another. For learning and recognition, the system will build a dictionary of words by determining the characteristics of each word to be used in the recognition. Determining the characteristics of an audio signal consists in the following steps: noise removal, sampling it, applying Hamming window, switching to frequency domain through Fourier transform, calculating the magnitude spectrum, filtering data, determining cepstral coefficients.

  12. Leptospira surface adhesin (Lsa21) induces Toll like receptor 2 and 4 mediated inflammatory responses in macrophages

    OpenAIRE

    Syed M. Faisal; Vivek P. Varma; M. Subathra; Sarwar Azam; Anil K. Sunkara; Mohd Akif; Mirza. S. Baig; Yung-Fu Chang

    2016-01-01

    Leptospirosis is zoonotic and emerging infectious disease of global importance. Little is understood about Leptospira pathogenesis and host immune response. In the present work we have investigated how Leptospira modulates the host innate immune response mediated by Toll-like receptors (TLRs) via surface exposed proteins. We screened Leptospira outer membrane/surface proteins for their ability to activate/inhibit TLR2/4 signaling in HEK293 cell lines. Of these the 21?kDa Leptospira surface ad...

  13. Generation of herpesvirus entry mediator (HVEM)-restricted herpes simplex virus type 1 mutant viruses: resistance of HVEM-expressing cells and identification of mutations that rescue nectin-1 recognition.

    Science.gov (United States)

    Uchida, Hiroaki; Shah, Waris A; Ozuer, Ali; Frampton, Arthur R; Goins, William F; Grandi, Paola; Cohen, Justus B; Glorioso, Joseph C

    2009-04-01

    Both initial infection and cell-to-cell spread by herpes simplex virus type 1 (HSV-1) require the interaction of the viral glycoprotein D (gD) with an entry receptor on the cell surface. The two major HSV entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, mediate infection independently but are coexpressed on a variety of cells. To determine if both receptors are active in these instances, we have established mutant viruses that are selectively impaired for recognition of one or the other receptor. In plaque assays, these viruses showed approximately 1,000-fold selectivity for the matched receptor over the mismatched receptor. Separate assays showed that each virus is impaired for both infection and spread through the mismatched receptor. We tested several human tumor cell lines for susceptibility to these viruses and observed that HT29 colon carcinoma cells are susceptible to infection by nectin-1-restricted virus but are highly resistant to HVEM-restricted virus infection, despite readily detectable HVEM expression on the cell surface. HVEM cDNA isolated from HT29 cells rendered HSV-resistant cells permissive for infection by the HVEM-restricted virus, suggesting that HT29 cells lack a cofactor for HVEM-mediated infection or express an HVEM-specific inhibitory factor. Passaging of HVEM-restricted virus on nectin-1-expressing cells yielded a set of gD missense mutations that each restored functional recognition of nectin-1. These mutations identify residues that likely play a role in shaping the nectin-1 binding site of gD. Our findings illustrate the utility of these receptor-restricted viruses in studying the early events in HSV infection.

  14. The Cek1‑mediated MAP kinase pathway regulates exposure of α‑1,2 and β‑1,2‑mannosides in the cell wall of Candida albicans modulating immune recognition.

    Science.gov (United States)

    Román, E; Correia, I; Salazin, A; Fradin, C; Jouault, T; Poulain, D; Liu, F-T; Pla, J

    2016-07-03

    The Cek1 MAP kinase (MAPK) mediates vegetative growth and cell wall biogenesis in the fungal pathogen Candida albicans. Alterations in the fungal cell wall caused by a defective Cek1‑mediated signaling pathway leads to increased β‑1,3‑glucan exposure influencing dectin‑1 fungal recognition by immune cells. We show here that cek1 cells also display an increased exposure of α‑1,2 and β‑1,2‑mannosides (α‑M and β‑M), a phenotype shared by strains defective in the activating MAPKK Hst7, suggesting a general defect in cell wall assembly. cek1 cells display walls with loosely bound material as revealed by transmission electron microscopy and are sensitive to tunicamycin, an inhibitor of N‑glycosylation. Transcriptomal analysis of tunicamycin treated cells revealed a differential pattern between cek1 and wild type cells which involved mainly cell wall and stress related genes. Mapping α‑M and β‑M epitopes in the mannoproteins of different cell wall fractions (CWMP) revealed an important shift in the molecular weight of the mannan derived from mutants defective in this MAPK pathway. We have also assessed the role of galectin‑3, a member of a β‑galactoside‑binding protein family shown to bind to and kill C. albicans through β‑M recognition, in the infection caused by cek1 mutants. Increased binding of cek1 to murine macrophages was shown to be partially blocked by lactose. Galectin-3(-/-) mice showed increased resistance to fungal infection, although galectin-3 did not account for the reduced virulence of cek1 mutants in a mouse model of systemic infection. All these data support a role for the Cek1‑mediated pathway in fungal cell wall maintenance, virulence and antifungal discovery.

  15. TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

    Directory of Open Access Journals (Sweden)

    Elham Hakimizadeh

    2017-08-01

    Full Text Available Objective(s: Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1 channels and toll-like receptors (TLRs are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist -treated and capsaicin (TRPV1 agonist -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke.

  16. TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats

    Science.gov (United States)

    Hakimizadeh, Elham; Shamsizadeh, Ali; Roohbakhsh, Ali; Arababadi, Mohammad Kazemi; Hajizadeh, Mohammad Reza; Shariati, Mehdi; Fatemi, Iman; Moghadam-ahmadi, Amir; Bazmandegan, Gholamreza; Rezazadeh, Hossein; Allahtavakoli, Mohammad

    2017-01-01

    Objective(s): Stroke is known as a main cause of mortality and prolonged disability in adults. Both transient receptor potential V1 (TRPV1) channels and toll-like receptors (TLRs) are involved in mediating the inflammatory responses. In the present study, the effects of TRPV1 receptor activation and blockade on stroke outcome and gene expression of TLR2 and TLR4 were assessed following permanent middle cerebral artery occlusion in rats Materials and Methods: Eighty male Wistar rats were divided into four groups as follows: sham, vehicle, AMG9810 (TRPV1 antagonist) -treated and capsaicin (TRPV1 agonist) -treated. For Stroke induction, the middle cerebral artery was permanently occluded and then behavioral functions were evaluated 1, 3 and 7 days after stroke. Results: TRPV1 antagonism significantly reduced the infarct volume compared to the stroke group. Also, neurological deficits were decreased by AMG9810 seven days after cerebral ischemia. In the ledged beam-walking test, the slip ratio was enhanced following ischemia. AMG9810 decreased this index in stroke animals. However, capsaicin improved the ratio 3 and 7 days after cerebral ischemia. Compared to the sham group, the mRNA expression of TLR2 and TLR4 was significantly increased in the stroke rats. AMG9810 Administration significantly reduced the mRNA expression of TLR2 and TLR4. However, capsaicin did not significantly affect the gene expression of TLR2 and TLR4. Conclusion: Our results demonstrated that TRPV1 antagonism by AMG9810 attenuates behavioral function and mRNA expression of TLR2 and TLR4. Thus, it might be useful to shed light on future therapeutic strategies for the treatment of ischemic stroke. PMID:29085577

  17. Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.

    Science.gov (United States)

    Loures, Flávio V; Röhm, Marc; Lee, Chrono K; Santos, Evelyn; Wang, Jennifer P; Specht, Charles A; Calich, Vera L G; Urban, Constantin F; Levitz, Stuart M

    2015-02-01

    Plasmacytoid dendritic cells (pDCs) were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs) containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs). The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.

  18. Recognition of Aspergillus fumigatus hyphae by human plasmacytoid dendritic cells is mediated by dectin-2 and results in formation of extracellular traps.

    Directory of Open Access Journals (Sweden)

    Flávio V Loures

    2015-02-01

    Full Text Available Plasmacytoid dendritic cells (pDCs were initially considered as critical for innate immunity to viruses. However, our group has shown that pDCs bind to and inhibit the growth of Aspergillus fumigatus hyphae and that depletion of pDCs renders mice hypersusceptible to experimental aspergillosis. In this study, we examined pDC receptors contributing to hyphal recognition and downstream events in pDCs stimulated by A. fumigatus hyphae. Our data show that Dectin-2, but not Dectin-1, participates in A. fumigatus hyphal recognition, TNF-α and IFN-α release, and antifungal activity. Moreover, Dectin-2 acts in cooperation with the FcRγ chain to trigger signaling responses. In addition, using confocal and electron microscopy we demonstrated that the interaction between pDCs and A. fumigatus induced the formation of pDC extracellular traps (pETs containing DNA and citrullinated histone H3. These structures closely resembled those of neutrophil extracellular traps (NETs. The microarray analysis of the pDC transcriptome upon A. fumigatus infection also demonstrated up-regulated expression of genes associated with apoptosis as well as type I interferon-induced genes. Thus, human pDCs directly recognize A. fumigatus hyphae via Dectin-2; this interaction results in cytokine release and antifungal activity. Moreover, hyphal stimulation of pDCs triggers a distinct pattern of pDC gene expression and leads to pET formation.

  19. The role of Ca(2+) mediated signaling pathways on the effect of taurine against Streptococcus uberis infection.

    Science.gov (United States)

    Dai, Bin; Zhang, Jinqiu; Liu, Ming; Lu, Jinye; Zhang, Yuanshu; Xu, Yuanyuan; Miao, Jinfeng; Yin, Yulong

    2016-08-30

    To provide insight into the mechanisms of taurine attenuation of pro-inflammatory response in mouse mammary epithelial cell line (EpH4-Ev, purchased by ATCC, USA) after Streptococcus uberis (S. uberis, 0140J) challenge, we infected MECs with S. uberis (2.5×10(7)cfumL(-1), MOI=10) for 3h and quantified changes in TLR-2 and calcium (Ca(2+)) mediated signaling pathways. The results indicate that S. uberis infection significantly increases the expression of TLR-2, intracellular Ca(2+) levels, PLC-γ1 and PKC-α, the activities of transcription factors NF-κB and NFAT, and related cytokines (TNF-α, IL-1β, IL-6, G-CSF, IL-2, KC, IL-15, FasL, MCP-1, and LIX) in culture supernatants. Taurine administration downregulated all these indices, the activities of NF-κB and NFAT. Cytokine secretions were similar using special PKC inhibitor Go 6983 and NFAT inhibitor VIVIT. Our data indicate that S. uberis infection induces pro-inflammatory response of MECs through a TLR-2 mediated signaling pathway. In addition, taurine can prevent MEC damage by affecting both PLC-γ1-Ca(2+)-PKC-α-NF-κB and PLC-γ1-Ca(2+)-NFATs signaling pathways. This is the first report to demonstrate the mechanisms of taurine attenuated pro-inflammatory response in MECs after S. uberis challenge. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Expression of Pattern Recognition Receptors in Epithelial Cells Around Clinically Healthy Implants and Healthy Teeth.

    Science.gov (United States)

    Calcaterra, Roberta; Di Girolamo, Michele; Mirisola, Concetta; Baggi, Luigi

    2016-06-01

    Gingival epithelial cells have a pivotal role in the recognition of microorganisms and damage-associated molecular pattern molecules and in the regulation of the immune response. The investigation of the behavior of Toll-like receptors (TLRs) and nucleotide oligomerization domain (NOD) like receptors (NLRs) around a healthy implant may help to address the first step of periimplantitis pathogenesis. To investigate by quantitative real-time polymerase chain reaction, the mRNA expressions of TLR2, TLR3, TLR4, TLR5, TLR6, TLR9, NOD1, NOD2, and NLRP3 from gingival epithelial cells of the sulcus around healthy implants and around healthy teeth. Two types of implant-abutment systems with tube-in-tube interface were tested. After 6 months of implant restoration, gingival epithelial cells were obtained from the gingival sulcus around the implants and around the adjacent teeth of 10 patients. Our results did not reach statistical significance among the mRNA expressions of TLR2, TLR3, TLR4, TLR5, TLR6, TLR9, NOD1, NOD2, and NLRP3 in epithelial cells around the implant versus around natural teeth. This study shows that the implant-abutment systems tested did not induce an immune response by the surrounding epithelial cells at 6 months since their positioning, as well as in the adjacent clincally healthy teeth.

  1. Curcuma DMSO extracts and curcumin exhibit an anti-inflammatory and anti-catabolic effect on human intervertebral disc cells, possibly by influencing TLR2 expression and JNK activity

    Science.gov (United States)

    2012-01-01

    Background As proinflammatory cytokines seem to play a role in discogenic back pain, substances exhibiting anti-inflammatory effects on intervertebral disc cells may be used as minimal-invasive therapeutics for intradiscal/epidural injection. The purpose of this study was to investigate the anti-inflammatory and anti-catabolic potential of curcuma, which has been used in the Indian Ayurvedic medicine to treat multiple ailments for a long time. Methods Human disc cells were treated with IL-1β to induce an inflammatory/catabolic cascade. Different extracts of curcuma as well as curcumin (= a component selected based on results with curcuma extracts and HPLC/MS analysis) were tested for their ability to reduce mRNA expression of proinflammatory cytokines and matrix degrading enzymes after 6 hours (real-time RT-PCR), followed by analysis of typical inflammatory signaling mechanisms such as NF-κB (Western Blot, Transcription Factor Assay), MAP kinases (Western Blot) and Toll-like receptors (real-time RT-PCR). Quantitative data was statistically analyzed using a Mann Whitney U test with a significance level of p curcuma DMSO extract significantly reduced levels of IL-6, MMP1, MMP3 and MMP13. The DMSO-soluble component curcumin, whose occurrence within the DMSO extract was verified by HPLC/MS, reduced levels of IL-1β, IL-6, IL-8, MMP1, MMP3 and MMP13 and both caused an up-regulation of TNF-α. Pathway analysis indicated that curcumin did not show involvement of NF-κB, but down-regulated TLR2 expression and inhibited the MAP kinase JNK while activating p38 and ERK. Conclusions Based on its anti-inflammatory and anti-catabolic effects, intradiscal injection of curcumin may be an attractive treatment alternative. However, whether the anti-inflammatory properties in vitro lead to analgesia in vivo will need to be confirmed in an appropriate animal model. PMID:22909087

  2. Ex-vivo expanded human NK cells express activating receptors that mediate cytotoxicity of allogeneic and autologous cancer cell lines by direct recognition and antibody directed cellular cytotoxicity

    Directory of Open Access Journals (Sweden)

    Campana Dario

    2010-10-01

    Full Text Available Abstract Background The possibility that autologous NK cells could serve as an effective treatment modality for solid tumors has long been considered. However, implementation is hampered by (i the small number of NK cells in peripheral blood, (ii the difficulties associated with large-scale production of GMP compliant cytolytic NK cells, (iii the need to activate the NK cells in order to induce NK cell mediated killing and (iv the constraints imposed by autologous inhibitory receptor-ligand interactions. To address these issues, we determined (i if large numbers of NK cells could be expanded from PBMC and GMP compliant cell fractions derived by elutriation, (ii their ability to kill allogeneic and autologous tumor targets by direct cytotoxitiy and by antibody-mediated cellular cytotoxicity and (iii defined NK cell specific receptor-ligand interactions that mediate tumor target cell killing. Methods Human NK cells were expanded during 14 days. Expansion efficiency, NK receptor repertoire before and after expansion, expression of NK specific ligands, cytolytic activity against allogeneic and autologous tumor targets, with and without the addition of chimeric EGFR monoclonal antibody, were investigated. Results Cell expansion shifted the NK cell receptor repertoire towards activation and resulted in cytotoxicity against various allogeneic tumor cell lines and autologous gastric cancer cells, while sparing normal PBMC. Blocking studies confirmed that autologous cytotoxicity is established through multiple activating receptor-ligand interactions. Importantly, expanded NK cells also mediated ADCC in an autologous and allogeneic setting by antibodies that are currently being used to treat patients with select solid tumors. Conclusion These data demonstrate that large numbers of cytolytic NK cells can be generated from PBMC and lymphocyte-enriched fractions obtained by GMP compliant counter current elutriation from PBMC, establishing the preclinical

  3. Intestinal Serotonin Transporter Inhibition by Toll-Like Receptor 2 Activation. A Feedback Modulation.

    Directory of Open Access Journals (Sweden)

    Eva Latorre

    Full Text Available TLR2 is a microbiota recognition receptor that has been described to contribute to intestinal homeostasis and to ameliorate inflammatory intestinal injury. In this context, serotonin (5-HT has shown to be an essential intestinal physiological neuromodulator that is also involved in intestinal inflammatory diseases. Since the interaction between TLR2 activation and the intestinal serotoninergic system remains non-investigated, our main aim was to analyze the effect of TLR2 on intestinal serotonin transporter (SERT activity and expression and the intracellular pathways involved. Caco-2/TC7 cells were used to analyze SERT and TLR2 molecular expression and SERT activity by measuring 5-HT uptake. The results showed that apical TLR2 activation inhibits SERT activity in Caco-2/TC7 cells mainly by reducing SERT protein level either in the plasma membrane, after short-term TLR2 activation or in both the plasma membrane and cell lysate, after long-term activation. cAMP/PKA pathway appears to mediate short-term inhibitory effect of TLR2 on SERT; however, p38 MAPK pathway has been shown to be involved in both short- and long-term TLR2 effect. Reciprocally, 5-HT long-term treatment yielded TLR2 down regulation in Caco-2/TC7 cells. Finally, results from in vivo showed an augmented intestinal SERT expression in mice Tlr2-/-, thus confirming our inhibitory effect of TLR2 on intestinal SERT in vitro. The present work infers that TLR2 may act in intestinal pathophysiology, not only by its inherent innate immune role, but also by regulating the intestinal serotoninergic system.

  4. Speaker Recognition

    DEFF Research Database (Denmark)

    Mølgaard, Lasse Lohilahti; Jørgensen, Kasper Winther

    2005-01-01

    Speaker recognition is basically divided into speaker identification and speaker verification. Verification is the task of automatically determining if a person really is the person he or she claims to be. This technology can be used as a biometric feature for verifying the identity of a person...

  5. Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of CD34{sup +} cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xingbing, E-mail: wangxingbing91@hotmail.com [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Cheng, Qiansong; Li, Lailing; Wang, Jian; Xia, Liang [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Xu, Xiucai [The Center Laboratory of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China); Sun, Zimin [Department of Hematology of Anhui Provincial Hospital, Anhui Medical University, Hefei, Anhui (China)

    2012-02-01

    Bone marrow derived-mesenchymal stromal cells (BM-MSCs) are multipotent, nonhematopoietic progenitors in a hematopoietic microenvironment and indispensable for regulating hematopoiesis. Several studies have reported that toll-like receptors (TLRs) are expressed in mesenchymal stromal cells (MSCs) to modulate their biological functions. In this study, we investigated the possible role(s) of TLRs in mediating the hematopoiesis-supporting role of human BM-MSCs. Human BM-MSCs were analyzed for mRNA expression of TLR1-10 by reverse transcription-polymerase chain reaction. TLR1-6, but not TLR7-10 were expressed by BM-MSCs. The protein expression of TLR2 and TLR4 was also confirmed by flow cytometry. We further explored the role of TLR2 and TLR4 in mediating the capacity of BM-MSCs to support the proliferation and differentiation of CD34{sup +} hematopoietic stem/progenitor cells obtained from cord blood. BM-MSCs increased proliferation of CD34{sup +} cells and promoted the differentiation towards the myeloid lineage 7 or 14 days after co-culture, as well as colony formation by those cells and the production of interleukin 1 (IL-1), IL-8, IL-11, stem cell factor (SCF), granulocyte colony-stimulating factor (CSF), macrophage CSF and granulocyte-macrophage CSF, if MSCs had been stimulated with TLR2 agonist (PAM{sub 3}CSK{sub 4}) or TLR4 agonist (LPS). Interestingly, although these effects were elevated in a different degree, a synergistic effect was not observed in BM-MSCs co-stimulated with PAM{sub 3}CSK{sub 4} and LPS. Together, our findings suggest that TLR2 and TLR4 signaling may indirectly regulate hematopoiesis by modulating BM-MSCs' functions. The increased hematopoietic proliferation and differentiation could be mediated, at least in part, by augmented hematopoiesis-related cytokine production of BM-MSCs.

  6. Toll-like receptors 2 and 4 mediate the capacity of mesenchymal stromal cells to support the proliferation and differentiation of CD34+ cells

    International Nuclear Information System (INIS)

    Wang, Xingbing; Cheng, Qiansong; Li, Lailing; Wang, Jian; Xia, Liang; Xu, Xiucai; Sun, Zimin

    2012-01-01

    Bone marrow derived-mesenchymal stromal cells (BM-MSCs) are multipotent, nonhematopoietic progenitors in a hematopoietic microenvironment and indispensable for regulating hematopoiesis. Several studies have reported that toll-like receptors (TLRs) are expressed in mesenchymal stromal cells (MSCs) to modulate their biological functions. In this study, we investigated the possible role(s) of TLRs in mediating the hematopoiesis-supporting role of human BM-MSCs. Human BM-MSCs were analyzed for mRNA expression of TLR1–10 by reverse transcription-polymerase chain reaction. TLR1–6, but not TLR7–10 were expressed by BM-MSCs. The protein expression of TLR2 and TLR4 was also confirmed by flow cytometry. We further explored the role of TLR2 and TLR4 in mediating the capacity of BM-MSCs to support the proliferation and differentiation of CD34 + hematopoietic stem/progenitor cells obtained from cord blood. BM-MSCs increased proliferation of CD34 + cells and promoted the differentiation towards the myeloid lineage 7 or 14 days after co-culture, as well as colony formation by those cells and the production of interleukin 1 (IL-1), IL-8, IL-11, stem cell factor (SCF), granulocyte colony-stimulating factor (CSF), macrophage CSF and granulocyte-macrophage CSF, if MSCs had been stimulated with TLR2 agonist (PAM 3 CSK 4 ) or TLR4 agonist (LPS). Interestingly, although these effects were elevated in a different degree, a synergistic effect was not observed in BM-MSCs co-stimulated with PAM 3 CSK 4 and LPS. Together, our findings suggest that TLR2 and TLR4 signaling may indirectly regulate hematopoiesis by modulating BM-MSCs' functions. The increased hematopoietic proliferation and differentiation could be mediated, at least in part, by augmented hematopoiesis-related cytokine production of BM-MSCs.

  7. Anti-PD-L1/TGFβR2 (M7824) fusion protein induces immunogenic modulation of human urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated recognition and lysis.

    Science.gov (United States)

    Grenga, Italia; Donahue, Renee N; Gargulak, Morgan L; Lepone, Lauren M; Roselli, Mario; Bilusic, Marijo; Schlom, Jeffrey

    2018-03-01

    Avelumab has recently been approved by the Food and Drug Administration for the therapy of Merkel cell carcinoma and urothelial carcinoma. M7824 is a novel first-in-class bifunctional fusion protein comprising a monoclonal antibody against programmed death-ligand 1 (PD-L1, avelumab), fused to the extracellular domain of human transforming growth factor beta (TGFβ) receptor 2, which functions as a TGFβ "trap." Advanced urothelial tumors have been shown to express TGFβ, which possesses immunosuppressive properties that promote cancer progression and metastasis. The rationale for a combined molecule is to block the PD-1/PD-L1 interaction between tumor cells and immune cell infiltrate and simultaneously reduce or eliminate TGFβ from the tumor microenvironment. In this study, we explored the effect of M7824 on invasive urothelial carcinoma cell lines. Human urothelial (transitional cell) carcinoma cell lines HTB-4, HTB-1, and HTB-5 were treated with M7824, M7824mut (M7824 that is mutated in the anti-PD-L1 portion of the molecule and thus does not bind PD-L1), anti-PD-L1 (avelumab), or IgG1 isotype control monoclonal antibody, and were assessed for gene expression, cell-surface phenotype, and sensitivity to lysis by TRAIL, antigen-specific cytotoxic T lymphocytes and natural killer cells. M7824 retains the ability to mediate antibody-dependent cellular cytotoxicity of tumor cells, although in some cases to a lesser extent than anti-PD-L1. However, compared to anti-PD-L1, M7824 increases (A) gene expression of molecules involved in T-cell trafficking in the tumor (e.g., CXCL11), (B) TRAIL-mediated tumor cell lysis, and (C) antigen-specific CD8 + T-cell-mediated lysis of tumor cells. These studies demonstrate the immunomodulatory properties of M7824 on both tumor cell phenotype and immune-mediated lysis. Compared to anti-PD-L1 or M7824mut, M7824 induces immunogenic modulation of urothelial carcinoma cell lines, rendering them more susceptible to immune-mediated

  8. Heat shock protein 90-mediated peptide-selective presentation of cytosolic tumor antigen for direct recognition of tumors by CD4(+) T cells.

    Science.gov (United States)

    Tsuji, Takemasa; Matsuzaki, Junko; Caballero, Otavia L; Jungbluth, Achim A; Ritter, Gerd; Odunsi, Kunle; Old, Lloyd J; Gnjatic, Sacha

    2012-04-15

    Tumor Ag-specific CD4(+) T cells play important functions in tumor immunosurveillance, and in certain cases they can directly recognize HLA class II-expressing tumor cells. However, the underlying mechanism of intracellular Ag presentation to CD4(+) T cells by tumor cells has not yet been well characterized. We analyzed two naturally occurring human CD4(+) T cell lines specific for different peptides from cytosolic tumor Ag NY-ESO-1. Whereas both lines had the same HLA restriction and a similar ability to recognize exogenous NY-ESO-1 protein, only one CD4(+) T cell line recognized NY-ESO-1(+) HLA class II-expressing melanoma cells. Modulation of Ag processing in melanoma cells using specific molecular inhibitors and small interfering RNA revealed a previously undescribed peptide-selective Ag-presentation pathway by HLA class II(+) melanoma cells. The presentation required both proteasome and endosomal protease-dependent processing mechanisms, as well as cytosolic heat shock protein 90-mediated chaperoning. Such tumor-specific pathway of endogenous HLA class II Ag presentation is expected to play an important role in immunosurveillance or immunosuppression mediated by various subsets of CD4(+) T cells at the tumor local site. Furthermore, targeted activation of tumor-recognizing CD4(+) T cells by vaccination or adoptive transfer could be a suitable strategy for enhancing the efficacy of tumor immunotherapy.

  9. Lexical mediation of phonotactic frequency effects on spoken word recognition: A Granger causality analysis of MRI-constrained MEG/EEG data.

    Science.gov (United States)

    Gow, David W; Olson, Bruna B

    2015-07-01

    Phonotactic frequency effects play a crucial role in a number of debates over language processing and representation. It is unclear however, whether these effects reflect prelexical sensitivity to phonotactic frequency, or lexical "gang effects" in speech perception. In this paper, we use Granger causality analysis of MR-constrained MEG/EEG data to understand how phonotactic frequency influences neural processing dynamics during auditory lexical decision. Effective connectivity analysis showed weaker feedforward influence from brain regions involved in acoustic-phonetic processing (superior temporal gyrus) to lexical areas (supramarginal gyrus) for high phonotactic frequency words, but stronger top-down lexical influence for the same items. Low entropy nonwords (nonwords judged to closely resemble real words) showed a similar pattern of interactions between brain regions involved in lexical and acoustic-phonetic processing. These results contradict the predictions of a feedforward model of phonotactic frequency facilitation, but support the predictions of a lexically mediated account.

  10. The Recognition of N-Glycans by the Lectin ArtinM Mediates Cell Death of a Human Myeloid Leukemia Cell Line

    Science.gov (United States)

    Carvalho, Fernanda Caroline; Soares, Sandro Gomes; Tamarozzi, Mirela Barros; Rego, Eduardo Magalhães; Roque-Barreira, Maria-Cristina

    2011-01-01

    ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus (jackfruit), interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6)Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC50 = 10 µg/mL), as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment. PMID:22132163

  11. The recognition of N-glycans by the lectin ArtinM mediates cell death of a human myeloid leukemia cell line.

    Directory of Open Access Journals (Sweden)

    Fernanda Caroline Carvalho

    Full Text Available ArtinM, a D-mannose-binding lectin from Artocarpus heterophyllus (jackfruit, interacts with N-glycosylated receptors on the surface of several cells of hematopoietic origin, triggering cell migration, degranulation, and cytokine release. Because malignant transformation is often associated with altered expression of cell surface glycans, we evaluated the interaction of ArtinM with human myelocytic leukemia cells and investigated cellular responses to lectin binding. The intensity of ArtinM binding varied across 3 leukemia cell lines: NB4>K562>U937. The binding, which was directly related to cell growth suppression, was inhibited in the presence of Manα1-3(Manα1-6Manβ1, and was reverted in underglycosylated NB4 cells. ArtinM interaction with NB4 cells induced cell death (IC(50 = 10 µg/mL, as indicated by cell surface exposure of phosphatidylserine and disruption of mitochondrial membrane potential unassociated with caspase activation or DNA fragmentation. Moreover, ArtinM treatment of NB4 cells strongly induced reactive oxygen species generation and autophagy, as indicated by the detection of acidic vesicular organelles in the treated cells. NB4 cell death was attributed to ArtinM recognition of the trimannosyl core of N-glycans containing a ß1,6-GlcNAc branch linked to α1,6-mannose. This modification correlated with higher levels of N-acetylglucosaminyltransferase V transcripts in NB4 cells than in K562 or U937 cells. Our results provide new insights into the potential of N-glycans containing a β1,6-GlcNAc branch linked to α1,6-mannose as a novel target for anti-leukemia treatment.

  12. Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Aleš Procházka

    2018-05-01

    Full Text Available Multimodal signal analysis based on sophisticated sensors, efficient communicationsystems and fast parallel processing methods has a rapidly increasing range of multidisciplinaryapplications. The present paper is devoted to pattern recognition, machine learning, and the analysisof sleep stages in the detection of sleep disorders using polysomnography (PSG data, includingelectroencephalography (EEG, breathing (Flow, and electro-oculogram (EOG signals. The proposedmethod is based on the classification of selected features by a neural network system with sigmoidaland softmax transfer functions using Bayesian methods for the evaluation of the probabilities of theseparate classes. The application is devoted to the analysis of the sleep stages of 184 individualswith different diagnoses, using EEG and further PSG signals. Data analysis points to an averageincrease of the length of the Wake stage by 2.7% per 10 years and a decrease of the length of theRapid Eye Movement (REM stages by 0.8% per 10 years. The mean classification accuracy for givensets of records and single EEG and multimodal features is 88.7% ( standard deviation, STD: 2.1 and89.6% (STD:1.9, respectively. The proposed methods enable the use of adaptive learning processesfor the detection and classification of health disorders based on prior specialist experience andman–machine interaction.

  13. The inflammatory cytokine effect of Pam3CSK4 TLR2 agonist alone or in combination with Leishmania infantum antigen on ex-vivo whole blood from sick and resistant dogs

    OpenAIRE

    Mart?nez-Orellana, Pamela; Quirola-Amores, Paulina; Montserrat-Sangr?, Sara; Ordeix, Laura; Llull, Joan; ?lvarez-Fern?ndez, Alejandra; Solano-Gallego, Laia

    2017-01-01

    Background A wide spectrum of clinical manifestations and immune responses exist in canine L. infantum infection. Ibizan hounds are more ?resistant? to disease than other dog breeds. Recognition of pathogen-associated molecule patterns by toll like receptors (TLRs) rapidly triggers a variety of anti-microbial immune responses through the induction of pro-inflammatory cytokines such as TNF-? and IL-6 which may play an important role in controlling Leishmania infection. The main objective of th...

  14. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

    Science.gov (United States)

    Madan, Monika; Amar, Salomon

    2008-09-12

    Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice. To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g) (10(7) CFU) or vehicle (normal saline). Animals were euthanized 24 weeks after the first inoculation. ApoE(+/-)-TLR2(+/+) mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/-)-TLR2(+/+) mice were significantly higher than from ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/-)-TLR2(+/+) mice compared to ApoE(+/-)-TLR2(+/-) and TLR2(-/-) mice, irrespective of diet or bacterial challenge. ApoE(+/-)-TLR2(+/+) mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist) also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/-)-TLR2(-/-) mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS) of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/-)-TLR2(+/+) mice

  15. Toll-like receptor-2 mediates diet and/or pathogen associated atherosclerosis: proteomic findings.

    Directory of Open Access Journals (Sweden)

    Monika Madan

    2008-09-01

    Full Text Available Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/- mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/--TLR2(+/+, ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice were fed either a high fat diet or a regular chow diet. All mice were inoculated intravenously, once per week for 24 consecutive weeks, with 50 microl live Porphyromonas gingivalis (P.g (10(7 CFU or vehicle (normal saline. Animals were euthanized 24 weeks after the first inoculation. ApoE(+/--TLR2(+/+ mice showed a significant increase in atheromatous lesions in proximal aorta and aortic tree compared to ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice for all diet conditions. They also displayed profound changes in plaque composition, as evidenced by increased macrophage infiltration and apoptosis, increased lipid content, and decreased smooth muscle cell mass, all reflecting an unstable plaque phenotype. SAA levels from ApoE(+/--TLR2(+/+ mice were significantly higher than from ApoE(+/--TLR2(+/- and ApoE(+/--TLR2(-/- mice. Serum cytokine analysis revealed increased levels of pro-inflammatory cytokines in ApoE(+/--TLR2(+/+ mice compared to ApoE(+/--TLR2(+/- and TLR2(-/- mice, irrespective of diet or bacterial challenge. ApoE(+/--TLR2(+/+ mice injected weekly for 24 weeks with FSL-1 (a TLR2 agonist also demonstrated significant increases in atherosclerotic lesions, SAA and serum cytokine levels compared to ApoE(+/--TLR2(-/- mice under same treatment condition. Finally, mass-spectrometry (MALDI-TOF-MS of aortic samples analyzed by 2-dimensional gel electrophoresis differential display, identified 6 proteins upregulated greater than 2-fold in ApoE(+/--TLR2(+/+ mice fed the high fat

  16. Toll-Like Receptor-2 Mediates Diet and/or Pathogen Associated Atherosclerosis: Proteomic Findings

    OpenAIRE

    Madan, Monika; Amar, Salomon

    2008-01-01

    Accumulating evidence implicates a fundamental link between the immune system and atherosclerosis. Toll-like receptors are principal sensors of the innate immune system. Here we report an assessment of the role of the TLR2 pathway in atherosclerosis associated with a high-fat diet and/or bacteria in ApoE(+/-) mice.To explore the role of TLR2 in inflammation- and infection-associated atherosclerosis, 10 week-old ApoE(+/-)-TLR2(+/+), ApoE(+/-)-TLR2(+/-) and ApoE(+/-)-TLR2(-/-) mice were fed eit...

  17. Toll-Like Receptor 2 Stimulation of Osteoblasts Mediates Staphylococcus Aureus Induced Bone Resorption and Osteoclastogenesis through Enhanced RANKL

    Science.gov (United States)

    Kassem, Ali; Lindholm, Catharina; Lerner, Ulf H

    2016-01-01

    Severe Staphylococcus aureus (S. aureus) infections pose an immense threat to population health and constitute a great burden for the health care worldwide. Inter alia, S. aureus septic arthritis is a disease with high mortality and morbidity caused by destruction of the infected joints and systemic bone loss, osteoporosis. Toll-Like receptors (TLRs) are innate immune cell receptors recognizing a variety of microbial molecules and structures. S. aureus recognition via TLR2 initiates a signaling cascade resulting in production of various cytokines, but the mechanisms by which S. aureus causes rapid and excessive bone loss are still unclear. We, therefore, investigated how S. aureus regulates periosteal/endosteal osteoclast formation and bone resorption. S. aureus stimulation of neonatal mouse parietal bone induced ex vivo bone resorption and osteoclastic gene expression. This effect was associated with increased mRNA and protein expression of receptor activator of NF-kB ligand (RANKL) without significant change in osteoprotegerin (OPG) expression. Bone resorption induced by S. aureus was abolished by OPG. S. aureus increased the expression of osteoclastogenic cytokines and prostaglandins in the parietal bones but the stimulatory effect of S. aureus on bone resorption and Tnfsf11 mRNA expression was independent of these cytokines and prostaglandins. Stimulation of isolated periosteal osteoblasts with S. aureus also resulted in increased expression of Tnfsf11 mRNA, an effect lost in osteoblasts from Tlr2 knockout mice. S. aureus stimulated osteoclastogenesis in isolated periosteal cells without affecting RANKL-stimulated resorption. In contrast, S. aureus inhibited RANKL-induced osteoclast formation in bone marrow macrophages. These data show that S. aureus enhances bone resorption and periosteal osteoclast formation by increasing osteoblast RANKL production through TLR2. Our study indicates the importance of using different in vitro approaches for studies of how S

  18. Recognition of social identity in ants

    DEFF Research Database (Denmark)

    Bos, Nick; d'Ettorre, Patrizia

    2012-01-01

    Recognizing the identity of others, from the individual to the group level, is a hallmark of society. Ants, and other social insects, have evolved advanced societies characterized by efficient social recognition systems. Colony identity is mediated by colony specific signature mixtures, a blend...

  19. Face Detection and Recognition

    National Research Council Canada - National Science Library

    Jain, Anil K

    2004-01-01

    This report describes research efforts towards developing algorithms for a robust face recognition system to overcome many of the limitations found in existing two-dimensional facial recognition systems...

  20. Graphical symbol recognition

    OpenAIRE

    K.C. , Santosh; Wendling , Laurent

    2015-01-01

    International audience; The chapter focuses on one of the key issues in document image processing i.e., graphical symbol recognition. Graphical symbol recognition is a sub-field of a larger research domain: pattern recognition. The chapter covers several approaches (i.e., statistical, structural and syntactic) and specially designed symbol recognition techniques inspired by real-world industrial problems. It, in general, contains research problems, state-of-the-art methods that convey basic s...

  1. Implicit recognition based on lateralized perceptual fluency.

    Science.gov (United States)

    Vargas, Iliana M; Voss, Joel L; Paller, Ken A

    2012-02-06

    In some circumstances, accurate recognition of repeated images in an explicit memory test is driven by implicit memory. We propose that this "implicit recognition" results from perceptual fluency that influences responding without awareness of memory retrieval. Here we examined whether recognition would vary if images appeared in the same or different visual hemifield during learning and testing. Kaleidoscope images were briefly presented left or right of fixation during divided-attention encoding. Presentation in the same visual hemifield at test produced higher recognition accuracy than presentation in the opposite visual hemifield, but only for guess responses. These correct guesses likely reflect a contribution from implicit recognition, given that when the stimulated visual hemifield was the same at study and test, recognition accuracy was higher for guess responses than for responses with any level of confidence. The dramatic difference in guessing accuracy as a function of lateralized perceptual overlap between study and test suggests that implicit recognition arises from memory storage in visual cortical networks that mediate repetition-induced fluency increments.

  2. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms...... or interpretations of recognition and toleration are considered, confusing and problematic uses of the terms are noted, and the compatibility of toleration and recognition is discussed. The article argues that there is a range of legitimate and importantly different conceptions of both toleration and recognition...

  3. Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

    Science.gov (United States)

    He, YingYing; Lawlor, Nathan T

    2016-01-01

    Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

  4. A motivational determinant of facial emotion recognition: regulatory focus affects recognition of emotions in faces.

    Science.gov (United States)

    Sassenrath, Claudia; Sassenberg, Kai; Ray, Devin G; Scheiter, Katharina; Jarodzka, Halszka

    2014-01-01

    Two studies examined an unexplored motivational determinant of facial emotion recognition: observer regulatory focus. It was predicted that a promotion focus would enhance facial emotion recognition relative to a prevention focus because the attentional strategies associated with promotion focus enhance performance on well-learned or innate tasks - such as facial emotion recognition. In Study 1, a promotion or a prevention focus was experimentally induced and better facial emotion recognition was observed in a promotion focus compared to a prevention focus. In Study 2, individual differences in chronic regulatory focus were assessed and attention allocation was measured using eye tracking during the facial emotion recognition task. Results indicated that the positive relation between a promotion focus and facial emotion recognition is mediated by shorter fixation duration on the face which reflects a pattern of attention allocation matched to the eager strategy in a promotion focus (i.e., striving to make hits). A prevention focus did not have an impact neither on perceptual processing nor on facial emotion recognition. Taken together, these findings demonstrate important mechanisms and consequences of observer motivational orientation for facial emotion recognition.

  5. 8 CFR 1292.2 - Organizations qualified for recognition; requests for recognition; withdrawal of recognition...

    Science.gov (United States)

    2010-01-01

    ...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. 1292.2...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. (a) Qualifications of organizations. A non-profit religious, charitable, social service, or similar organization...

  6. Recognition of Cladosporium fulvum Ecp2 elicitor by non-host Nicotiana spp. is mediated by a single dominant gene that is not homologous to known Cf-genes

    NARCIS (Netherlands)

    Kock, de M.J.D.; Iskandar, H.M.; Brandwagt, B.F.; Laugé, R.; Wit, de P.J.G.M.; Lindhout, W.H.

    2004-01-01

    Cladosporium fulvum is a fungal pathogen of tomato that grows exclusively in the intercellular spaces of leaves. Ecp2 is one of the elicitor proteins that is secreted by C. fulvum and is specifically recognized by tomato plants containing the resistance gene Cf-Ecp2. Recognition is followed by a

  7. Optical Pattern Recognition

    Science.gov (United States)

    Yu, Francis T. S.; Jutamulia, Suganda

    2008-10-01

    Contributors; Preface; 1. Pattern recognition with optics Francis T. S. Yu and Don A. Gregory; 2. Hybrid neural networks for nonlinear pattern recognition Taiwei Lu; 3. Wavelets, optics, and pattern recognition Yao Li and Yunglong Sheng; 4. Applications of the fractional Fourier transform to optical pattern recognition David Mendlovic, Zeev Zalesky and Haldum M. Oxaktas; 5. Optical implementation of mathematical morphology Tien-Hsin Chao; 6. Nonlinear optical correlators with improved discrimination capability for object location and recognition Leonid P. Yaroslavsky; 7. Distortion-invariant quadratic filters Gregory Gheen; 8. Composite filter synthesis as applied to pattern recognition Shizhou Yin and Guowen Lu; 9. Iterative procedures in electro-optical pattern recognition Joseph Shamir; 10. Optoelectronic hybrid system for three-dimensional object pattern recognition Guoguang Mu, Mingzhe Lu and Ying Sun; 11. Applications of photrefractive devices in optical pattern recognition Ziangyang Yang; 12. Optical pattern recognition with microlasers Eung-Gi Paek; 13. Optical properties and applications of bacteriorhodopsin Q. Wang Song and Yu-He Zhang; 14. Liquid-crystal spatial light modulators Aris Tanone and Suganda Jutamulia; 15. Representations of fully complex functions on real-time spatial light modulators Robert W. Cohn and Laurence G. Hassbrook; Index.

  8. Stimulation of toll-like receptor 2 with bleomycin results in cellular activation and secretion of pro-inflammatory cytokines and chemokines

    International Nuclear Information System (INIS)

    Razonable, Raymund R.; Henault, Martin; Paya, Carlos V.

    2006-01-01

    The clinical use of bleomycin results in systemic and pulmonary inflammatory syndromes that are mediated by the production of cytokines and chemokines. In this study, we demonstrate that cell activation is initiated upon the recognition of bleomycin as a pathogen-associated molecular pattern by toll-like receptor (TLR) 2. The THP1 human monocytic cell line, which constitutively expresses high levels of TLR2, secretes interleukin (IL)-1β, IL-8, and tumor necrosis factor (TNF)-α during bleomycin exposure. The TLR2-dependent nature of cell activation and cytokine secretion is supported by (1) the inability of TLR2-deficient human embryonic kidney (HEK) 293 cells to exhibit nuclear factor-kappa B (NF-κB) activation and secrete IL-8 in response to bleomycin; (2) the acquired ability of HEK293 to exhibit NF-κB activation and secrete IL-8 upon experimental expression of TLR2; and (3) the inhibition of cell activation in TLR2-expressing HEK293 and THP1 by anti-TLR2 monoclonal antibody. Collectively, these observations identify TLR2 activation as a critical event that triggers NF-κB activation and secretion of cytokines and chemokines during bleomycin exposure. Our in vitro findings could serve as a molecular mechanism underlying the pro-inflammatory toxicity associated with bleomycin. Whether bleomycin engages with other cellular receptors that results in activation of alternate signaling pathways and whether the TLR2-agonist activity of bleomycin contribute to its anti-neoplastic property deserve further study

  9. Implicit Recognition Based on Lateralized Perceptual Fluency

    Directory of Open Access Journals (Sweden)

    Iliana M. Vargas

    2012-02-01

    Full Text Available In some circumstances, accurate recognition of repeated images in an explicit memory test is driven by implicit memory. We propose that this “implicit recognition” results from perceptual fluency that influences responding without awareness of memory retrieval. Here we examined whether recognition would vary if images appeared in the same or different visual hemifield during learning and testing. Kaleidoscope images were briefly presented left or right of fixation during divided-attention encoding. Presentation in the same visual hemifield at test produced higher recognition accuracy than presentation in the opposite visual hemifield, but only for guess responses. These correct guesses likely reflect a contribution from implicit recognition, given that when the stimulated visual hemifield was the same at study and test, recognition accuracy was higher for guess responses than for responses with any level of confidence. The dramatic difference in guessing accuracy as a function of lateralized perceptual overlap between study and test suggests that implicit recognition arises from memory storage in visual cortical networks that mediate repetition-induced fluency increments.

  10. Probiotic Bacteria Alter Pattern-Recognition Receptor Expression and Cytokine Profile in a Human Macrophage Model Challenged with Candida albicans and Lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Victor H. Matsubara

    2017-11-01

    Full Text Available Probiotics are live microorganisms that confer benefits to the host health. The infection rate of potentially pathogenic organisms such as Candida albicans, the most common agent associated with mucosal candidiasis, can be reduced by probiotics. However, the mechanisms by which the probiotics interfere with the immune system are largely unknown. We evaluated the effect of probiotic bacteria on C. albicans challenged human macrophages. Macrophages were pretreated with lactobacilli alone (Lactobacillus rhamnosus LR32, Lactobacillus casei L324m, or Lactobacillus acidophilus NCFM or associated with Escherichia coli lipopolysaccharide (LPS, followed by the challenge with C. albicans or LPS in a co-culture assay. The expression of pattern-recognition receptors genes (CLE7A, TLR2, and TLR4 was determined by RT-qPCR, and dectin-1 reduced levels were confirmed by flow cytometry. The cytokine profile was determined by ELISA using the macrophage cell supernatant. Overall probiotic lactobacilli down-regulated the transcription of CLEC7A (p < 0.05, resulting in the decreased expression of dectin-1 on probiotic pretreated macrophages. The tested Lactobacillus species down-regulated TLR4, and increased TLR2 mRNA levels in macrophages challenged with C. albicans. The cytokines profile of macrophages challenged with C. albicans or LPS were altered by the probiotics, which generally led to increased levels of IL-10 and IL-1β, and reduction of IL-12 production by macrophages (p < 0.05. Our data suggest that probiotic lactobacilli impair the recognition of PAMPs by macrophages, and alter the production of pro/anti-inflammatory cytokines, thus modulating inflammation.

  11. Pattern recognition & machine learning

    CERN Document Server

    Anzai, Y

    1992-01-01

    This is the first text to provide a unified and self-contained introduction to visual pattern recognition and machine learning. It is useful as a general introduction to artifical intelligence and knowledge engineering, and no previous knowledge of pattern recognition or machine learning is necessary. Basic for various pattern recognition and machine learning methods. Translated from Japanese, the book also features chapter exercises, keywords, and summaries.

  12. Statistical Pattern Recognition

    CERN Document Server

    Webb, Andrew R

    2011-01-01

    Statistical pattern recognition relates to the use of statistical techniques for analysing data measurements in order to extract information and make justified decisions.  It is a very active area of study and research, which has seen many advances in recent years. Applications such as data mining, web searching, multimedia data retrieval, face recognition, and cursive handwriting recognition, all require robust and efficient pattern recognition techniques. This third edition provides an introduction to statistical pattern theory and techniques, with material drawn from a wide range of fields,

  13. Paradigms in object recognition

    International Nuclear Information System (INIS)

    Mutihac, R.; Mutihac, R.C.

    1999-09-01

    A broad range of approaches has been proposed and applied for the complex and rather difficult task of object recognition that involves the determination of object characteristics and object classification into one of many a priori object types. Our paper revises briefly the three main different paradigms in pattern recognition, namely Bayesian statistics, neural networks, and expert systems. (author)

  14. Infant Visual Recognition Memory

    Science.gov (United States)

    Rose, Susan A.; Feldman, Judith F.; Jankowski, Jeffery J.

    2004-01-01

    Visual recognition memory is a robust form of memory that is evident from early infancy, shows pronounced developmental change, and is influenced by many of the same factors that affect adult memory; it is surprisingly resistant to decay and interference. Infant visual recognition memory shows (a) modest reliability, (b) good discriminant…

  15. Recognition and Toleration

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2010-01-01

    Recognition and toleration are ways of relating to the diversity characteristic of multicultural societies. The article concerns the possible meanings of toleration and recognition, and the conflict that is often claimed to exist between these two approaches to diversity. Different forms or inter...

  16. Challenging ocular image recognition

    Science.gov (United States)

    Pauca, V. Paúl; Forkin, Michael; Xu, Xiao; Plemmons, Robert; Ross, Arun A.

    2011-06-01

    Ocular recognition is a new area of biometric investigation targeted at overcoming the limitations of iris recognition performance in the presence of non-ideal data. There are several advantages for increasing the area beyond the iris, yet there are also key issues that must be addressed such as size of the ocular region, factors affecting performance, and appropriate corpora to study these factors in isolation. In this paper, we explore and identify some of these issues with the goal of better defining parameters for ocular recognition. An empirical study is performed where iris recognition methods are contrasted with texture and point operators on existing iris and face datasets. The experimental results show a dramatic recognition performance gain when additional features are considered in the presence of poor quality iris data, offering strong evidence for extending interest beyond the iris. The experiments also highlight the need for the direct collection of additional ocular imagery.

  17. 8 CFR 292.2 - Organizations qualified for recognition; requests for recognition; withdrawal of recognition...

    Science.gov (United States)

    2010-01-01

    ...; requests for recognition; withdrawal of recognition; accreditation of representatives; roster. 292.2...; withdrawal of recognition; accreditation of representatives; roster. (a) Qualifications of organizations. A non-profit religious, charitable, social service, or similar organization established in the United...

  18. Object recognition memory: neurobiological mechanisms of encoding, consolidation and retrieval.

    Science.gov (United States)

    Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2008-07-01

    Tests of object recognition memory, or the judgment of the prior occurrence of an object, have made substantial contributions to our understanding of the nature and neurobiological underpinnings of mammalian memory. Only in recent years, however, have researchers begun to elucidate the specific brain areas and neural processes involved in object recognition memory. The present review considers some of this recent research, with an emphasis on studies addressing the neural bases of perirhinal cortex-dependent object recognition memory processes. We first briefly discuss operational definitions of object recognition and the common behavioural tests used to measure it in non-human primates and rodents. We then consider research from the non-human primate and rat literature examining the anatomical basis of object recognition memory in the delayed nonmatching-to-sample (DNMS) and spontaneous object recognition (SOR) tasks, respectively. The results of these studies overwhelmingly favor the view that perirhinal cortex (PRh) is a critical region for object recognition memory. We then discuss the involvement of PRh in the different stages--encoding, consolidation, and retrieval--of object recognition memory. Specifically, recent work in rats has indicated that neural activity in PRh contributes to object memory encoding, consolidation, and retrieval processes. Finally, we consider the pharmacological, cellular, and molecular factors that might play a part in PRh-mediated object recognition memory. Recent studies in rodents have begun to indicate the remarkable complexity of the neural substrates underlying this seemingly simple aspect of declarative memory.

  19. Harmonization versus Mutual Recognition

    DEFF Research Database (Denmark)

    Jørgensen, Jan Guldager; Schröder, Philipp

    The present paper examines trade liberalization driven by the coordination of product standards. For oligopolistic firms situated in separate markets that are initially sheltered by national standards, mutual recognition of standards implies entry and reduced profits at home paired with the oppor......The present paper examines trade liberalization driven by the coordination of product standards. For oligopolistic firms situated in separate markets that are initially sheltered by national standards, mutual recognition of standards implies entry and reduced profits at home paired...... countries and three firms, where firms first lobby for the policy coordination regime (harmonization versus mutual recognition), and subsequently, in case of harmonization, the global standard is auctioned among the firms. We discuss welfare effects and conclude with policy implications. In particular......, harmonized standards may fail to harvest the full pro-competitive effects from trade liberalization compared to mutual recognition; moreover, the issue is most pronounced in markets featuring price competition....

  20. CASE Recognition Awards.

    Science.gov (United States)

    Currents, 1985

    1985-01-01

    A total of 294 schools, colleges, and universities received prizes in this year's CASE Recognition program. Awards were given in: public relations programs, student recruitment, marketing, program pulications, news writing, fund raising, radio programming, school periodicals, etc. (MLW)

  1. Forensic speaker recognition

    NARCIS (Netherlands)

    Meuwly, Didier

    2013-01-01

    The aim of forensic speaker recognition is to establish links between individuals and criminal activities, through audio speech recordings. This field is multidisciplinary, combining predominantly phonetics, linguistics, speech signal processing, and forensic statistics. On these bases, expert-based

  2. The Recognition Of Fatigue

    DEFF Research Database (Denmark)

    Elsass, Peter; Jensen, Bodil; Mørup, Rikke

    2007-01-01

    Elsass P., Jensen B., Morup R., Thogersen M.H. (2007). The Recognition Of Fatigue: A qualitative study of life-stories from rehabilitation clients. International Journal of Psychosocial Rehabilitation. 11 (2), 75-87......Elsass P., Jensen B., Morup R., Thogersen M.H. (2007). The Recognition Of Fatigue: A qualitative study of life-stories from rehabilitation clients. International Journal of Psychosocial Rehabilitation. 11 (2), 75-87...

  3. Evaluating music emotion recognition

    DEFF Research Database (Denmark)

    Sturm, Bob L.

    2013-01-01

    A fundamental problem with nearly all work in music genre recognition (MGR)is that evaluation lacks validity with respect to the principal goals of MGR. This problem also occurs in the evaluation of music emotion recognition (MER). Standard approaches to evaluation, though easy to implement, do...... not reliably differentiate between recognizing genre or emotion from music, or by virtue of confounding factors in signals (e.g., equalization). We demonstrate such problems for evaluating an MER system, and conclude with recommendations....

  4. Why recognition is rational

    Directory of Open Access Journals (Sweden)

    Clintin P. Davis-Stober

    2010-07-01

    Full Text Available The Recognition Heuristic (Gigerenzer and Goldstein, 1996; Goldstein and Gigerenzer, 2002 makes the counter-intuitive prediction that a decision maker utilizing less information may do as well as, or outperform, an idealized decision maker utilizing more information. We lay a theoretical foundation for the use of single-variable heuristics such as the Recognition Heuristic as an optimal decision strategy within a linear modeling framework. We identify conditions under which over-weighting a single predictor is a mini-max strategy among a class of a priori chosen weights based on decision heuristics with respect to a measure of statistical lack of fit we call ``risk''. These strategies, in turn, outperform standard multiple regression as long as the amount of data available is limited. We also show that, under related conditions, weighting only one variable and ignoring all others produces the same risk as ignoring the single variable and weighting all others. This approach has the advantage of generalizing beyond the original environment of the Recognition Heuristic to situations with more than two choice options, binary or continuous representations of recognition, and to other single variable heuristics. We analyze the structure of data used in some prior recognition tasks and find that it matches the sufficient conditions for optimality in our results. Rather than being a poor or adequate substitute for a compensatory model, the Recognition Heuristic closely approximates an optimal strategy when a decision maker has finite data about the world.

  5. Intercultural Mediation

    OpenAIRE

    Dragos Marian Radulescu; Denisa Mitrut

    2012-01-01

    The Intercultural Mediator facilitates exchanges between people of different socio-cultural backgrounds and acts as a bridge between immigrants and national and local associations, health organizations, services and offices in order to foster integration of every single individual. As the use mediation increases, mediators are more likely to be involved in cross-cultural mediation, but only the best mediators have the opportunity to mediate cross border business disputes or international poli...

  6. Does Employee Recognition Affect Positive Psychological Functioning and Well-Being?

    Science.gov (United States)

    Merino, M Dolores; Privado, Jesús

    2015-09-14

    Employee recognition is one of the typical characteristics of healthy organizations. The majority of research on recognition has studied the consequences of this variable on workers. But few investigations have focused on understanding what mechanisms mediate between recognition and its consequences. This work aims to understand whether the relationship between employee recognition and well-being, psychological resources mediate. To answer this question a sample of 1831 workers was used. The variables measured were: employee recognition, subjective well-being and positive psychological functioning (PPF), which consists of 11 psychological resources. In the analysis of data, structural equation models were applied. The results confirmed our hypothesis and showed that PPF mediate the relationship between recognition and well-being. The effect of recognition over PPF is two times greater (.39) with peer-recognition than with supervisor-recognition (.20), and, the effect of PPF over well-being is .59. This study highlights the importance of promoting employee recognition policies in organizations for the impact it has, not only on well-being, but also on the positive psychological functioning of the workers.

  7. Page Recognition: Quantum Leap In Recognition Technology

    Science.gov (United States)

    Miller, Larry

    1989-07-01

    No milestone has proven as elusive as the always-approaching "year of the LAN," but the "year of the scanner" might claim the silver medal. Desktop scanners have been around almost as long as personal computers. And everyone thinks they are used for obvious desktop-publishing and business tasks like scanning business documents, magazine articles and other pages, and translating those words into files your computer understands. But, until now, the reality fell far short of the promise. Because it's true that scanners deliver an accurate image of the page to your computer, but the software to recognize this text has been woefully disappointing. Old optical-character recognition (OCR) software recognized such a limited range of pages as to be virtually useless to real users. (For example, one OCR vendor specified 12-point Courier font from an IBM Selectric typewriter: the same font in 10-point, or from a Diablo printer, was unrecognizable!) Computer dealers have told me the chasm between OCR expectations and reality is so broad and deep that nine out of ten prospects leave their stores in disgust when they learn the limitations. And this is a very important, very unfortunate gap. Because the promise of recognition -- what people want it to do -- carries with it tremendous improvements in our productivity and ability to get tons of written documents into our computers where we can do real work with it. The good news is that a revolutionary new development effort has led to the new technology of "page recognition," which actually does deliver the promise we've always wanted from OCR. I'm sure every reader appreciates the breakthrough represented by the laser printer and page-makeup software, a combination so powerful it created new reasons for buying a computer. A similar breakthrough is happening right now in page recognition: the Macintosh (and, I must admit, other personal computers) equipped with a moderately priced scanner and OmniPage software (from Caere

  8. Recognition of social identity in ants

    Directory of Open Access Journals (Sweden)

    Nick eBos

    2012-03-01

    Full Text Available Recognizing the identity of others, from the individual to the group level, is a hallmark of society. Ants, and other social insects, have evolved advanced societies characterized by efficient social recognition systems. Colony identity is mediated by colony specific signature mixtures, a blend of hydrocarbons present on the cuticle of every individual (the label. Recognition occurs when an ant encounters another individual, and compares the label it perceives to an internal representation of its own colony odor (the template. A mismatch between label and template leads to rejection of the encountered individual. Although advances have been made in our understanding of how the label is produced and acquired, contradictory evidence exists about information processing of recognition cues. Here, we review the literature on template acquisition in ants and address how and when the template is formed, where in the nervous system it is localized, and the possible role of learning. We combine seemingly contradictory evidence in to a novel, parsimonious theory for the information processing of nestmate recognition cues.

  9. Probabilistic Open Set Recognition

    Science.gov (United States)

    Jain, Lalit Prithviraj

    Real-world tasks in computer vision, pattern recognition and machine learning often touch upon the open set recognition problem: multi-class recognition with incomplete knowledge of the world and many unknown inputs. An obvious way to approach such problems is to develop a recognition system that thresholds probabilities to reject unknown classes. Traditional rejection techniques are not about the unknown; they are about the uncertain boundary and rejection around that boundary. Thus traditional techniques only represent the "known unknowns". However, a proper open set recognition algorithm is needed to reduce the risk from the "unknown unknowns". This dissertation examines this concept and finds existing probabilistic multi-class recognition approaches are ineffective for true open set recognition. We hypothesize the cause is due to weak adhoc assumptions combined with closed-world assumptions made by existing calibration techniques. Intuitively, if we could accurately model just the positive data for any known class without overfitting, we could reject the large set of unknown classes even under this assumption of incomplete class knowledge. For this, we formulate the problem as one of modeling positive training data by invoking statistical extreme value theory (EVT) near the decision boundary of positive data with respect to negative data. We provide a new algorithm called the PI-SVM for estimating the unnormalized posterior probability of class inclusion. This dissertation also introduces a new open set recognition model called Compact Abating Probability (CAP), where the probability of class membership decreases in value (abates) as points move from known data toward open space. We show that CAP models improve open set recognition for multiple algorithms. Leveraging the CAP formulation, we go on to describe the novel Weibull-calibrated SVM (W-SVM) algorithm, which combines the useful properties of statistical EVT for score calibration with one-class and binary

  10. HPV18 Persistence Impairs Basal and DNA Ligand-Mediated IFN-β and IFN-λ1 Production through Transcriptional Repression of Multiple Downstream Effectors of Pattern Recognition Receptor Signaling.

    Science.gov (United States)

    Albertini, Silvia; Lo Cigno, Irene; Calati, Federica; De Andrea, Marco; Borgogna, Cinzia; Dell'Oste, Valentina; Landolfo, Santo; Gariglio, Marisa

    2018-03-15

    Although it is clear that high-risk human papillomaviruses (HPVs) can selectively infect keratinocytes and persist in the host, it still remains to be unequivocally determined whether they can escape antiviral innate immunity by interfering with pattern recognition receptor (PRR) signaling. In this study, we have assessed the innate immune response in monolayer and organotypic raft cultures of NIKS cells harboring multiple copies of episomal HPV18 (NIKSmcHPV18), which fully recapitulates the persistent state of infection. We show for the first time, to our knowledge, that NIKSmcHPV18, as well as HeLa cells (a cervical carcinoma-derived cell line harboring integrated HPV18 DNA), display marked downregulation of several PRRs, as well as other PRR downstream effectors, such as the adaptor protein stimulator of IFN genes and the transcription factors IRF1 and 7. Importantly, we provide evidence that downregulation of stimulator of IFN genes, cyclic GMP-AMP synthase, and retinoic acid-inducible gene I mRNA levels occurs at the transcriptional level through a novel epigenetic silencing mechanism, as documented by the accumulation of repressive heterochromatin markers seen at the promoter region of these genes. Furthermore, stimulation of NIKSmcHPV18 cells with salmon sperm DNA or poly(deoxyadenylic-deoxythymidylic) acid, two potent inducers of PRR signaling, only partially restored PRR protein expression. Accordingly, the production of IFN-β and IFN-λ 1 was significantly reduced in comparison with the parental NIKS cells, indicating that HPV18 exerts its immunosuppressive activity through downregulation of PRR signaling. Altogether, our findings indicate that high-risk human papillomaviruses have evolved broad-spectrum mechanisms that allow simultaneous depletion of multiple effectors of the innate immunity network, thereby creating an unreactive cellular milieu suitable for viral persistence. Copyright © 2018 by The American Association of Immunologists, Inc.

  11. Touchless palmprint recognition systems

    CERN Document Server

    Genovese, Angelo; Scotti, Fabio

    2014-01-01

    This book examines the context, motivation and current status of biometric systems based on the palmprint, with a specific focus on touchless and less-constrained systems. It covers new technologies in this rapidly evolving field and is one of the first comprehensive books on palmprint recognition systems.It discusses the research literature and the most relevant industrial applications of palmprint biometrics, including the low-cost solutions based on webcams. The steps of biometric recognition are described in detail, including acquisition setups, algorithms, and evaluation procedures. Const

  12. [Prosopagnosia and facial expression recognition].

    Science.gov (United States)

    Koyama, Shinichi

    2014-04-01

    This paper reviews clinical neuropsychological studies that have indicated that the recognition of a person's identity and the recognition of facial expressions are processed by different cortical and subcortical areas of the brain. The fusiform gyrus, especially the right fusiform gyrus, plays an important role in the recognition of identity. The superior temporal sulcus, amygdala, and medial frontal cortex play important roles in facial-expression recognition. Both facial recognition and facial-expression recognition are highly intellectual processes that involve several regions of the brain.

  13. Electrophysiological distinctions between recognition memory with and without awareness

    Science.gov (United States)

    Ko, Philip C.; Duda, Bryant; Hussey, Erin P.; Ally, Brandon A.

    2013-01-01

    The influence of implicit memory representations on explicit recognition may help to explain cases of accurate recognition decisions made with high uncertainty. During a recognition task, implicit memory may enhance the fluency of a test item, biasing decision processes to endorse it as “old”. This model may help explain recognition-without-identification, a remarkable phenomenon in which participants make highly accurate recognition decisions despite the inability to identify the test item. The current study investigated whether recognition-without-identification for pictures elicits a similar pattern of neural activity as other types of accurate recognition decisions made with uncertainty. Further, this study also examined whether recognition-without-identification for pictures could be attained by the use of perceptual and conceptual information from memory. To accomplish this, participants studied pictures and then performed a recognition task under difficult viewing conditions while event-related potentials (ERPs) were recorded. Behavioral results showed that recognition was highly accurate even when test items could not be identified, demonstrating recognition-without identification. The behavioral performance also indicated that recognition-without-identification was mediated by both perceptual and conceptual information, independently of one another. The ERP results showed dramatically different memory related activity during the early 300 to 500 ms epoch for identified items that were studied compared to unidentified items that were studied. Similar to previous work highlighting accurate recognition without retrieval awareness, test items that were not identified, but correctly endorsed as “old,” elicited a negative posterior old/new effect (i.e., N300). In contrast, test items that were identified and correctly endorsed as “old,” elicited the classic positive frontal old/new effect (i.e., FN400). Importantly, both of these effects were

  14. Optical Character Recognition.

    Science.gov (United States)

    Converso, L.; Hocek, S.

    1990-01-01

    This paper describes computer-based optical character recognition (OCR) systems, focusing on their components (the computer, the scanner, the OCR, and the output device); how the systems work; and features to consider in selecting a system. A list of 26 questions to ask to evaluate systems for potential purchase is included. (JDD)

  15. Recognition of fractal graphs

    NARCIS (Netherlands)

    Perepelitsa, VA; Sergienko, [No Value; Kochkarov, AM

    1999-01-01

    Definitions of prefractal and fractal graphs are introduced, and they are used to formulate mathematical models in different fields of knowledge. The topicality of fractal-graph recognition from the point of view, of fundamental improvement in the efficiency of the solution of algorithmic problems

  16. Facial Expression Recognition

    NARCIS (Netherlands)

    Pantic, Maja; Li, S.; Jain, A.

    2009-01-01

    Facial expression recognition is a process performed by humans or computers, which consists of: 1. Locating faces in the scene (e.g., in an image; this step is also referred to as face detection), 2. Extracting facial features from the detected face region (e.g., detecting the shape of facial

  17. Assessing the Dissociability of Recollection and Familiarity in Recognition Memory

    Science.gov (United States)

    Pratte, Michael S.; Rouder, Jeffrey N.

    2012-01-01

    Recognition memory is often modeled as constituting 2 separate processes, recollection and familiarity, rather than as constituting a single process mediated by a generic latent strength. One way of stating evidence for the more complex 2-process model is to show dissociations with select manipulations, in which one manipulation affects…

  18. Galeotti on recognition as inclusion

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2008-01-01

    Anna Elisabetta Galeotti's theory of 'toleration as recognition' has been criticised by Peter Jones for being conceptually incoherent, since liberal toleration presupposes a negative attitude to differences, whereas multicultural recognition requires positive affirmation hereof. The paper spells ...

  19. School IPM Recognition and Certification

    Science.gov (United States)

    Schools and school districts can get support and recognition for implementation of school IPM. EPA is developing a program to provide recognition for school districts that are working towards or have achieved a level of success with school IPM programs.

  20. Stereotype Associations and Emotion Recognition

    NARCIS (Netherlands)

    Bijlstra, Gijsbert; Holland, Rob W.; Dotsch, Ron; Hugenberg, Kurt; Wigboldus, Daniel H. J.

    We investigated whether stereotype associations between specific emotional expressions and social categories underlie stereotypic emotion recognition biases. Across two studies, we replicated previously documented stereotype biases in emotion recognition using both dynamic (Study 1) and static

  1. Mediation Analysis with Multiple Mediators.

    Science.gov (United States)

    VanderWeele, T J; Vansteelandt, S

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects through other pathways. The approaches proposed here accommodate exposure-mediator interactions and, to a certain extent, mediator-mediator interactions as well. The methods handle binary or continuous mediators and binary, continuous or count outcomes. When the mediators affect one another, the strategy of trying to assess direct and indirect effects one mediator at a time will in general fail; the approach given in this paper can still be used. A characterization is moreover given as to when the sum of the mediated effects for multiple mediators considered separately will be equal to the mediated effect of all of the mediators considered jointly. The approach proposed in this paper is robust to unmeasured common causes of two or more mediators.

  2. A REVIEW: OPTICAL CHARACTER RECOGNITION

    OpenAIRE

    Swati Tomar*1 & Amit Kishore2

    2018-01-01

    This paper presents detailed review in the field of Optical Character Recognition. Various techniques are determine that have been proposed to realize the center of character recognition in an optical character recognition system. Even though, sufficient studies and papers are describes the techniques for converting textual content from a paper document into machine readable form. Optical character recognition is a process where the computer understands automatically the image of handwritten ...

  3. Superficial Priming in Episodic Recognition

    Science.gov (United States)

    Dopkins, Stephen; Sargent, Jesse; Ngo, Catherine T.

    2010-01-01

    We explored the effect of superficial priming in episodic recognition and found it to be different from the effect of semantic priming in episodic recognition. Participants made recognition judgments to pairs of items, with each pair consisting of a prime item and a test item. Correct positive responses to the test item were impeded if the prime…

  4. Word Recognition in Auditory Cortex

    Science.gov (United States)

    DeWitt, Iain D. J.

    2013-01-01

    Although spoken word recognition is more fundamental to human communication than text recognition, knowledge of word-processing in auditory cortex is comparatively impoverished. This dissertation synthesizes current models of auditory cortex, models of cortical pattern recognition, models of single-word reading, results in phonetics and results in…

  5. Visual Recognition Memory across Contexts

    Science.gov (United States)

    Jones, Emily J. H.; Pascalis, Olivier; Eacott, Madeline J.; Herbert, Jane S.

    2011-01-01

    In two experiments, we investigated the development of representational flexibility in visual recognition memory during infancy using the Visual Paired Comparison (VPC) task. In Experiment 1, 6- and 9-month-old infants exhibited recognition when familiarization and test occurred in the same room, but showed no evidence of recognition when…

  6. Forensic Face Recognition: A Survey

    NARCIS (Netherlands)

    Ali, Tauseef; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.; Quaglia, Adamo; Epifano, Calogera M.

    2012-01-01

    The improvements of automatic face recognition during the last 2 decades have disclosed new applications like border control and camera surveillance. A new application field is forensic face recognition. Traditionally, face recognition by human experts has been used in forensics, but now there is a

  7. Semantic Activity Recognition

    OpenAIRE

    Thonnat , Monique

    2008-01-01

    International audience; Extracting automatically the semantics from visual data is a real challenge. We describe in this paper how recent work in cognitive vision leads to significative results in activity recognition for visualsurveillance and video monitoring. In particular we present work performed in the domain of video understanding in our PULSAR team at INRIA in Sophia Antipolis. Our main objective is to analyse in real-time video streams captured by static video cameras and to recogniz...

  8. Pattern Recognition Control Design

    Science.gov (United States)

    Gambone, Elisabeth A.

    2018-01-01

    Spacecraft control algorithms must know the expected vehicle response to any command to the available control effectors, such as reaction thrusters or torque devices. Spacecraft control system design approaches have traditionally relied on the estimated vehicle mass properties to determine the desired force and moment, as well as knowledge of the effector performance to efficiently control the spacecraft. A pattern recognition approach was used to investigate the relationship between the control effector commands and spacecraft responses. Instead of supplying the approximated vehicle properties and the thruster performance characteristics, a database of information relating the thruster ring commands and the desired vehicle response was used for closed-loop control. A Monte Carlo simulation data set of the spacecraft dynamic response to effector commands was analyzed to establish the influence a command has on the behavior of the spacecraft. A tool developed at NASA Johnson Space Center to analyze flight dynamics Monte Carlo data sets through pattern recognition methods was used to perform this analysis. Once a comprehensive data set relating spacecraft responses with commands was established, it was used in place of traditional control methods and gains set. This pattern recognition approach was compared with traditional control algorithms to determine the potential benefits and uses.

  9. Threshold models of recognition and the recognition heuristic

    Directory of Open Access Journals (Sweden)

    Edgar Erdfelder

    2011-02-01

    Full Text Available According to the recognition heuristic (RH theory, decisions follow the recognition principle: Given a high validity of the recognition cue, people should prefer recognized choice options compared to unrecognized ones. Assuming that the memory strength of choice options is strongly correlated with both the choice criterion and recognition judgments, the RH is a reasonable strategy that approximates optimal decisions with a minimum of cognitive effort (Davis-Stober, Dana, and Budescu, 2010. However, theories of recognition memory are not generally compatible with this assumption. For example, some threshold models of recognition presume that recognition judgments can arise from two types of cognitive states: (1 certainty states in which judgments are almost perfectly correlated with memory strength and (2 uncertainty states in which recognition judgments reflect guessing rather than differences in memory strength. We report an experiment designed to test the prediction that the RH applies to certainty states only. Our results show that memory states rather than recognition judgments affect use of recognition information in binary decisions.

  10. Usage of semantic representations in recognition memory.

    Science.gov (United States)

    Nishiyama, Ryoji; Hirano, Tetsuji; Ukita, Jun

    2017-11-01

    Meanings of words facilitate false acceptance as well as correct rejection of lures in recognition memory tests, depending on the experimental context. This suggests that semantic representations are both directly and indirectly (i.e., mediated by perceptual representations) used in remembering. Studies using memory conjunction errors (MCEs) paradigms, in which the lures consist of component parts of studied words, have reported semantic facilitation of rejection of the lures. However, attending to components of the lures could potentially cause this. Therefore, we investigated whether semantic overlap of lures facilitates MCEs using Japanese Kanji words in which a whole-word image is more concerned in reading. Experiments demonstrated semantic facilitation of MCEs in a delayed recognition test (Experiment 1), and in immediate recognition tests in which participants were prevented from using phonological or orthographic representations (Experiment 2), and the salient effect on individuals with high semantic memory capacities (Experiment 3). Additionally, analysis of the receiver operating characteristic suggested that this effect is attributed to familiarity-based memory judgement and phantom recollection. These findings indicate that semantic representations can be directly used in remembering, even when perceptual representations of studied words are available.

  11. Mediation Analysis with Multiple Mediators

    OpenAIRE

    VanderWeele, T.J.; Vansteelandt, S.

    2014-01-01

    Recent advances in the causal inference literature on mediation have extended traditional approaches to direct and indirect effects to settings that allow for interactions and non-linearities. In this paper, these approaches from causal inference are further extended to settings in which multiple mediators may be of interest. Two analytic approaches, one based on regression and one based on weighting are proposed to estimate the effect mediated through multiple mediators and the effects throu...

  12. Re-thinking employee recognition: understanding employee experiences of recognition

    OpenAIRE

    Smith, Charlotte

    2013-01-01

    Despite widespread acceptance of the importance of employee recognition for both individuals and organisations and evidence of its increasing use in organisations, employee recognition has received relatively little focused attention from academic researchers. Particularly lacking is research exploring the lived experience of employee recognition and the interpretations and meanings which individuals give to these experiences. Drawing on qualitative interviews conducted as part of my PhD rese...

  13. Protective effects of methanolic extract of Adhatoda vasica Nees leaf in collagen-induced arthritis by modulation of synovial toll-like receptor-2 expression and release of pro-inflammatory mediators

    Directory of Open Access Journals (Sweden)

    Rana Adhikary

    2016-03-01

    Full Text Available RA associated with oxidative stress and chronic inflammation has been a major health problem among the population worldwide. In this study protective effect of methanolic extract of Adhatoda vasica leaf (AVE was evaluated on Collagen-induced arthritis in male Swiss albino mice. Post oral administration of AVE at 50, 100 and 200 mg/kg body weight doses decreased the arthritic index and footpad swelling. AVE administration diminished pro-inflammatory cytokines in serum and synovial tissues. Reduced chemokines and neutrophil infiltration in synovial tissues after AVE administration dictated its protective effect against RA. Decreased LPO content and SOD activity along with concomitant rise in GSH and CAT activities from liver, spleen and synovial tissues indicated regulation of oxidative stress by AVE. In addition decreased CRP in serum along with suppressed TLR-2 expression in CIA mice after AVE treatment was also observed. Protective effect of AVE in RA is further supported from histopathological studies which showed improvement during bone damage. In conclusion this study demonstrated A. vasica is capable of regulating oxidative stress during CIA and therefore down regulated local and systemic release of pro-inflammatory mediators, which might be linked to mechanism of decreasing synovial TLR-2 expression via downregulating release of its regular endogenous ligands like CRP.

  14. Human activity recognition and prediction

    CERN Document Server

    2016-01-01

    This book provides a unique view of human activity recognition, especially fine-grained human activity structure learning, human-interaction recognition, RGB-D data based action recognition, temporal decomposition, and causality learning in unconstrained human activity videos. The techniques discussed give readers tools that provide a significant improvement over existing methodologies of video content understanding by taking advantage of activity recognition. It links multiple popular research fields in computer vision, machine learning, human-centered computing, human-computer interaction, image classification, and pattern recognition. In addition, the book includes several key chapters covering multiple emerging topics in the field. Contributed by top experts and practitioners, the chapters present key topics from different angles and blend both methodology and application, composing a solid overview of the human activity recognition techniques. .

  15. [Comparative studies of face recognition].

    Science.gov (United States)

    Kawai, Nobuyuki

    2012-07-01

    Every human being is proficient in face recognition. However, the reason for and the manner in which humans have attained such an ability remain unknown. These questions can be best answered-through comparative studies of face recognition in non-human animals. Studies in both primates and non-primates show that not only primates, but also non-primates possess the ability to extract information from their conspecifics and from human experimenters. Neural specialization for face recognition is shared with mammals in distant taxa, suggesting that face recognition evolved earlier than the emergence of mammals. A recent study indicated that a social insect, the golden paper wasp, can distinguish their conspecific faces, whereas a closely related species, which has a less complex social lifestyle with just one queen ruling a nest of underlings, did not show strong face recognition for their conspecifics. Social complexity and the need to differentiate between one another likely led humans to evolve their face recognition abilities.

  16. Genetic specificity of face recognition.

    Science.gov (United States)

    Shakeshaft, Nicholas G; Plomin, Robert

    2015-10-13

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

  17. Radically enhanced molecular recognition

    KAUST Repository

    Trabolsi, Ali; Khashab, Niveen M.; Fahrenbach, Albert C.; Friedman, Douglas C.; Colvin, Michael T.; Coti, Karla K.; Bení tez, Diego S.; Tkatchouk, Ekaterina; Olsen, John Carl; Belowich, Matthew E.; Carmieli, Raanan; Khatib, Hussam A.; Goddard, William Andrew III; Wasielewski, Michael R.; Stoddart, Fraser Fraser Raser

    2009-01-01

    The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication. © 2010 Macmillan Publishers Limited. All rights reserved.

  18. Radically enhanced molecular recognition

    KAUST Repository

    Trabolsi, Ali

    2009-12-17

    The tendency for viologen radical cations to dimerize has been harnessed to establish a recognition motif based on their ability to form extremely strong inclusion complexes with cyclobis(paraquat-p-phenylene) in its diradical dicationic redox state. This previously unreported complex involving three bipyridinium cation radicals increases the versatility of host-guest chemistry, extending its practice beyond the traditional reliance on neutral and charged guests and hosts. In particular, transporting the concept of radical dimerization into the field of mechanically interlocked molecules introduces a higher level of control within molecular switches and machines. Herein, we report that bistable and tristable [2]rotaxanes can be switched by altering electrochemical potentials. In a tristable [2]rotaxane composed of a cyclobis(paraquat-p-phenylene) ring and a dumbbell with tetrathiafulvalene, dioxynaphthalene and bipyridinium recognition sites, the position of the ring can be switched. On oxidation, it moves from the tetrathiafulvalene to the dioxynaphthalene, and on reduction, to the bipyridinium radical cation, provided the ring is also reduced simultaneously to the diradical dication. © 2010 Macmillan Publishers Limited. All rights reserved.

  19. Type I interferon and pattern recognition receptor signaling following particulate matter inhalation

    Directory of Open Access Journals (Sweden)

    Erdely Aaron

    2012-07-01

    Full Text Available Abstract Background Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc – stainless steel (GMA-SS welding fume at 40 mg/m3 for 3 hr/d for 10 d and sacrificed 4 hr, 14 d and 28 d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. Results The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28 d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10. In addition, pulmonary expression of interferon α and β and Irf7 specific pattern recognition receptors (PRR and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3 were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88 to inhalation of GMA-SS. Conclusion This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure.

  20. Speech Recognition on Mobile Devices

    DEFF Research Database (Denmark)

    Tan, Zheng-Hua; Lindberg, Børge

    2010-01-01

    in the mobile context covering motivations, challenges, fundamental techniques and applications. Three ASR architectures are introduced: embedded speech recognition, distributed speech recognition and network speech recognition. Their pros and cons and implementation issues are discussed. Applications within......The enthusiasm of deploying automatic speech recognition (ASR) on mobile devices is driven both by remarkable advances in ASR technology and by the demand for efficient user interfaces on such devices as mobile phones and personal digital assistants (PDAs). This chapter presents an overview of ASR...

  1. Molecular Mechanisms of Odor Recognition

    National Research Council Canada - National Science Library

    Anholt, Robert

    2000-01-01

    .... We characterized the transduction pathway for the recognition of pheromones in the vomeronasal organ and also characterized subpopulations of olfactory neurons expressing different axonal G proteins...

  2. Markov Models for Handwriting Recognition

    CERN Document Server

    Plotz, Thomas

    2011-01-01

    Since their first inception, automatic reading systems have evolved substantially, yet the recognition of handwriting remains an open research problem due to its substantial variation in appearance. With the introduction of Markovian models to the field, a promising modeling and recognition paradigm was established for automatic handwriting recognition. However, no standard procedures for building Markov model-based recognizers have yet been established. This text provides a comprehensive overview of the application of Markov models in the field of handwriting recognition, covering both hidden

  3. Sudden Event Recognition: A Survey

    Directory of Open Access Journals (Sweden)

    Mohd Asyraf Zulkifley

    2013-08-01

    Full Text Available Event recognition is one of the most active research areas in video surveillance fields. Advancement in event recognition systems mainly aims to provide convenience, safety and an efficient lifestyle for humanity. A precise, accurate and robust approach is necessary to enable event recognition systems to respond to sudden changes in various uncontrolled environments, such as the case of an emergency, physical threat and a fire or bomb alert. The performance of sudden event recognition systems depends heavily on the accuracy of low level processing, like detection, recognition, tracking and machine learning algorithms. This survey aims to detect and characterize a sudden event, which is a subset of an abnormal event in several video surveillance applications. This paper discusses the following in detail: (1 the importance of a sudden event over a general anomalous event; (2 frameworks used in sudden event recognition; (3 the requirements and comparative studies of a sudden event recognition system and (4 various decision-making approaches for sudden event recognition. The advantages and drawbacks of using 3D images from multiple cameras for real-time application are also discussed. The paper concludes with suggestions for future research directions in sudden event recognition.

  4. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara; Rockwood, Alyn; Ghanem, Bernard

    2015-01-01

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR's ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  5. Iris Recognition Using Wavelet

    Directory of Open Access Journals (Sweden)

    Khaliq Masood

    2013-08-01

    Full Text Available Biometric systems are getting more attention in the present era. Iris recognition is one of the most secure and authentic among the other biometrics and this field demands more authentic, reliable and fast algorithms to implement these biometric systems in real time. In this paper, an efficient localization technique is presented to identify pupil and iris boundaries using histogram of the iris image. Two small portions of iris have been used for polar transformation to reduce computational time and to increase the efficiency of the system. Wavelet transform is used for feature vector generation. Rotation of iris is compensated without shifts in the iris code. System is tested on Multimedia University Iris Database and results show that proposed system has encouraging performance.

  6. SAR: Stroke Authorship Recognition

    KAUST Repository

    Shaheen, Sara

    2015-10-15

    Are simple strokes unique to the artist or designer who renders them? If so, can this idea be used to identify authorship or to classify artistic drawings? Also, could training methods be devised to develop particular styles? To answer these questions, we propose the Stroke Authorship Recognition (SAR) approach, a novel method that distinguishes the authorship of 2D digitized drawings. SAR converts a drawing into a histogram of stroke attributes that is discriminative of authorship. We provide extensive classification experiments on a large variety of data sets, which validate SAR\\'s ability to distinguish unique authorship of artists and designers. We also demonstrate the usefulness of SAR in several applications including the detection of fraudulent sketches, the training and monitoring of artists in learning a particular new style and the first quantitative way to measure the quality of automatic sketch synthesis tools. © 2015 The Eurographics Association and John Wiley & Sons Ltd.

  7. Complex Mediation

    DEFF Research Database (Denmark)

    Bødker, Susanne; Andersen, Peter Bøgh

    2005-01-01

    This article has its starting point in a large number of empirical findings regarding computer-mediated work. These empirical findings have challenged our understanding of the role of mediation in such work; on the one hand as an aspect of communication and cooperation at work and on the other hand...... as an aspect of human engagement with instruments of work. On the basis of previous work in activity-theoretical and semiotic human—computer interaction, we propose a model to encompass both of these aspects. In a dialogue with our empirical findings we move on to propose a number of types of mediation...... that have helped to enrich our understanding of mediated work and the design of computer mediation for such work....

  8. Aromatic-Mediated Carbohydrate Recognition in Processive Serratia marcescens Chitinases.

    Science.gov (United States)

    Jana, Suvamay; Hamre, Anne Grethe; Wildberger, Patricia; Holen, Matilde Mengkrog; Eijsink, Vincent G H; Beckham, Gregg T; Sørlie, Morten; Payne, Christina M

    2016-02-25

    Microorganisms use a host of enzymes, including processive glycoside hydrolases, to deconstruct recalcitrant polysaccharides to sugars. Processive glycoside hydrolases closely associate with polymer chains and repeatedly cleave glycosidic linkages without dissociating from the crystalline surface after each hydrolytic step; they are typically the most abundant enzymes in both natural secretomes and industrial cocktails by virtue of their significant hydrolytic potential. The ubiquity of aromatic residues lining the enzyme catalytic tunnels and clefts is a notable feature of processive glycoside hydrolases. We hypothesized that these aromatic residues have uniquely defined roles, such as substrate chain acquisition and binding in the catalytic tunnel, that are defined by their local environment and position relative to the substrate and the catalytic center. Here, we investigated this hypothesis with variants of Serratia marcescens family 18 processive chitinases ChiA and ChiB. We applied molecular simulation and free energy calculations to assess active site dynamics and ligand binding free energies. Isothermal titration calorimetry provided further insight into enthalpic and entropic contributions to ligand binding free energy. Thus, the roles of six aromatic residues, Trp-167, Trp-275, and Phe-396 in ChiA, and Trp-97, Trp-220, and Phe-190 in ChiB, have been examined. We observed that point mutation of the tryptophan residues to alanine results in unfavorable changes in the free energy of binding relative to wild-type. The most drastic effects were observed for residues positioned at the "entrances" of the deep substrate-binding clefts and known to be important for processivity. Interestingly, phenylalanine mutations in ChiA and ChiB had little to no effect on chito-oligomer binding, in accordance with the limited effects of their removal on chitinase functionality.

  9. Systematic discovery of new recognition peptides mediating protein interaction networks

    DEFF Research Database (Denmark)

    Neduva, Victor; Linding, Rune; Su-Angrand, Isabelle

    2005-01-01

    Many aspects of cell signalling, trafficking, and targeting are governed by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or "linear motif" (e.g., SH3 binding to PxxP). Many domains...... by interactions between globular protein domains and short peptide segments. These domains often bind multiple peptides that share a common sequence pattern, or "linear motif" (e.g., SH3 binding to PxxP). Many domains are known, though comparatively few linear motifs have been discovered. Their short length...

  10. Expression of functional toll-like receptor-2 and -4 on alveolar epithelial cells.

    Science.gov (United States)

    Armstrong, Lynne; Medford, Andrew R L; Uppington, Kay M; Robertson, John; Witherden, Ian R; Tetley, Teresa D; Millar, Ann B

    2004-08-01

    The recognition of potentially harmful microorganisms involves the specific recognition of pathogen-associated molecular patterns (PAMPs) and the family of Toll-like receptors (TLRs) is known to play a central role in this process. TLR-4 is the major recognition receptor for lipopolysaccharide (LPS), a component of gram-negative bacterial cell walls, whereas TLR-2 responds to bacterial products from gram-positive organisms. Although resident alveolar macrophages are the first line of defense against microbial attack, it is now understood that the alveolar epithelium also plays a pivotal role in the innate immunity of the lung. The purpose of the current study was to determine whether human primary type II alveolar epithelial cells (ATII) express functional TLR-2 and TLR-4 and how they may be regulated by inflammatory mediators. We have used reverse transcriptase-polymerase chain reaction and flow cytometry to determine basal and inducible expression on ATII. We have used highly purified preparations of the gram-positive bacterial product lipoteichoic acid (LTA) and LPS to look at the functional consequences of TLR-2 and TLR-4 ligation, respectively, in terms of interleukin-8 release. We have shown that human primary ATII cells express mRNA and protein for both TLR-2 and TLR-4, which can be modulated by incubation with LPS and tumor necrosis factor. Furthermore, we have demonstrated that these receptors are functional. This suggests that ATII have the potential to contribute significantly to the host defense of the human alveolus against bacteria.

  11. The Legal Recognition of Sign Languages

    Science.gov (United States)

    De Meulder, Maartje

    2015-01-01

    This article provides an analytical overview of the different types of explicit legal recognition of sign languages. Five categories are distinguished: constitutional recognition, recognition by means of general language legislation, recognition by means of a sign language law or act, recognition by means of a sign language law or act including…

  12. Mediators of mucosal inflammation : Implications for therapy

    NARCIS (Netherlands)

    VanDullemen, H; Meenan, J; Stronkhorst, A; Tytgat, GNJ; VanDenenter, SJH

    1997-01-01

    Treatment of inflammatory bowel disease remains a challenge. The major shortcoming in the development of new therapeutic approaches is the fact that the cause of inflammatory bowel disease is still unknown. Recognition of the importance of the arachidonic acid cascade of inflammatory mediators

  13. Eicosanoid-mediated immunity in insects

    Science.gov (United States)

    Eicosanoid is a collective term for oxygenated metabolites of C20 polyunsaturated fatty acids. As seen in mammals, eicosanoids play crucial roles in mediating various physiological processes, including immune responses, in insects. Upon microbial pathogen infection, non-self recognition signals are ...

  14. Unequal recognition, misrecognition and injustice

    DEFF Research Database (Denmark)

    Lægaard, Sune

    2012-01-01

    by the state of religious minorities. It argues that state–religion relations can be analysed as relations of recognition, which are not only unequal but also multi-dimensional, and that it is difficult to answer the question whether multi-dimensional recognitive inequalities are unjust or wrong if one...

  15. Side-View Face Recognition

    NARCIS (Netherlands)

    Santemiz, P.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.; van den Biggelaar, Olivier

    As a widely used biometrics, face recognition has many advantages such as being non-intrusive, natural and passive. On the other hand, in real-life scenarios with uncontrolled environment, pose variation up to side-view positions makes face recognition a challenging work. In this paper we discuss

  16. Infants' Recognition Memory for Hue

    Science.gov (United States)

    Bornstein, Marc H.

    1976-01-01

    Fifty 4-month-old infants were habituated to one wavelength of light and then tested for recognition with the original and two new spectral lights. After short- and long-term delays with different types of retroactive interference, the results indicated that the infants' recognition memory for hue was quite resilient to interference or delay. (JMB)

  17. Forensic Face Recognition: A Survey

    NARCIS (Netherlands)

    Ali, Tauseef; Veldhuis, Raymond N.J.; Spreeuwers, Lieuwe Jan

    2010-01-01

    Beside a few papers which focus on the forensic aspects of automatic face recognition, there is not much published about it in contrast to the literature on developing new techniques and methodologies for biometric face recognition. In this report, we review forensic facial identification which is

  18. Side-View Face Recognition

    NARCIS (Netherlands)

    Santemiz, P.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

    2010-01-01

    Side-view face recognition is a challenging problem with many applications. Especially in real-life scenarios where the environment is uncontrolled, coping with pose variations up to side-view positions is an important task for face recognition. In this paper we discuss the use of side view face

  19. FILTWAM and Voice Emotion Recognition

    NARCIS (Netherlands)

    Bahreini, Kiavash; Nadolski, Rob; Westera, Wim

    2014-01-01

    This paper introduces the voice emotion recognition part of our framework for improving learning through webcams and microphones (FILTWAM). This framework enables multimodal emotion recognition of learners during game-based learning. The main goal of this study is to validate the use of microphone

  20. Online handwritten mathematical expression recognition

    Science.gov (United States)

    Büyükbayrak, Hakan; Yanikoglu, Berrin; Erçil, Aytül

    2007-01-01

    We describe a system for recognizing online, handwritten mathematical expressions. The system is designed with a user-interface for writing scientific articles, supporting the recognition of basic mathematical expressions as well as integrals, summations, matrices etc. A feed-forward neural network recognizes symbols which are assumed to be single-stroke and a recursive algorithm parses the expression by combining neural network output and the structure of the expression. Preliminary results show that writer-dependent recognition rates are very high (99.8%) while writer-independent symbol recognition rates are lower (75%). The interface associated with the proposed system integrates the built-in recognition capabilities of the Microsoft's Tablet PC API for recognizing textual input and supports conversion of hand-drawn figures into PNG format. This enables the user to enter text, mathematics and draw figures in a single interface. After recognition, all output is combined into one LATEX code and compiled into a PDF file.

  1. Viewpoint Manifolds for Action Recognition

    Directory of Open Access Journals (Sweden)

    Souvenir Richard

    2009-01-01

    Full Text Available Abstract Action recognition from video is a problem that has many important applications to human motion analysis. In real-world settings, the viewpoint of the camera cannot always be fixed relative to the subject, so view-invariant action recognition methods are needed. Previous view-invariant methods use multiple cameras in both the training and testing phases of action recognition or require storing many examples of a single action from multiple viewpoints. In this paper, we present a framework for learning a compact representation of primitive actions (e.g., walk, punch, kick, sit that can be used for video obtained from a single camera for simultaneous action recognition and viewpoint estimation. Using our method, which models the low-dimensional structure of these actions relative to viewpoint, we show recognition rates on a publicly available dataset previously only achieved using multiple simultaneous views.

  2. Recognition Strategies of Group 3 Innate Lymphoid Cells

    OpenAIRE

    Killig, Monica; Glatzer, Timor; Romagnani, Chiara

    2014-01-01

    During the early phase of an inflammatory response, innate cells can use different strategies to sense environmental danger. These include the direct interaction of specific activating receptors (actR) with pathogen-encoded/danger molecules or the engagement of cytokine receptors by pro-inflammatory mediators produced by antigen presenting cells (APC) in the course of the infection. These general recognition strategies, which have been extensively described for innate myeloid cells, are share...

  3. Specification for projects of radiogeologic recognition

    International Nuclear Information System (INIS)

    1979-01-01

    This instruction is a guidance to achievement of radiogeologic recognition projects. The radiogeologic recognition is a prospecting method that join the classic geologic recognition with measures of rock radioactivity. (C.M.)

  4. T cell recognition of breast cancer antigens

    DEFF Research Database (Denmark)

    Petersen, Nadia Viborg; Andersen, Sofie Ramskov; Andersen, Rikke Sick

    Recent studies are encouraging research of breast cancer immunogenicity to evaluate the applicability ofimmunotherapy as a treatment strategy. The epitope landscape in breast cancer is minimally described, thus it is necessary to identify T cell targets to develop immune mediated therapies.......This project investigates four proteins commonly upregulated in breast cancer and thus probable tumor associated antigens (TAAs). Aromatase, prolactin, NEK3, and PIAS3 contribute to increase growth, survival, and motility of malignant cells. Aspiring to uncover novel epitopes for cytotoxic T cells, a reverse...... recognition utilizing DNA barcode labeled MHC multimers to screen peripheral blood lymphocytes from breast cancer patients and healthy donor samples. Signif-icantly more TAA specific T cell responses were detected in breast cancer patients than healthy donors for both HLA-A*0201 (P

  5. No strong evidence for lateralisation of word reading and face recognition deficits following posterior brain injury

    DEFF Research Database (Denmark)

    Gerlach, Christian; Marstrand, Lisbet; Starrfelt, Randi

    2014-01-01

    Face recognition and word reading are thought to be mediated by relatively independent cognitive systems lateralized to the right and left hemisphere respectively. In this case, we should expect a higher incidence of face recognition problems in patients with right hemisphere injury and a higher......-construction, motion perception), we found that both patient groups performed significantly worse than a matched control group. In particular we found a significant number of face recognition deficits in patients with left hemisphere injury and a significant number of patients with word reading deficits following...... right hemisphere injury. This suggests that face recognition and word reading may be mediated by more bilaterally distributed neural systems than is commonly assumed....

  6. Serotonergic modulation of face-emotion recognition

    Directory of Open Access Journals (Sweden)

    C.M. Del-Ben

    2008-04-01

    Full Text Available Facial expressions of basic emotions have been widely used to investigate the neural substrates of emotion processing, but little is known about the exact meaning of subjective changes provoked by perceiving facial expressions. Our assumption was that fearful faces would be related to the processing of potential threats, whereas angry faces would be related to the processing of proximal threats. Experimental studies have suggested that serotonin modulates the brain processes underlying defensive responses to environmental threats, facilitating risk assessment behavior elicited by potential threats and inhibiting fight or flight responses to proximal threats. In order to test these predictions about the relationship between fearful and angry faces and defensive behaviors, we carried out a review of the literature about the effects of pharmacological probes that affect 5-HT-mediated neurotransmission on the perception of emotional faces. The hypothesis that angry faces would be processed as a proximal threat and that, as a consequence, their recognition would be impaired by an increase in 5-HT function was not supported by the results reviewed. In contrast, most of the studies that evaluated the behavioral effects of serotonin challenges showed that increased 5-HT neurotransmission facilitates the recognition of fearful faces, whereas its decrease impairs the same performance. These results agree with the hypothesis that fearful faces are processed as potential threats and that 5-HT enhances this brain processing.

  7. Pattern Recognition of the Multiple Sclerosis Syndrome

    Science.gov (United States)

    Stewart, Renee; Healey, Kathleen M.

    2017-01-01

    During recent decades, the autoimmune disease neuromyelitis optica spectrum disorder (NMOSD), once broadly classified under the umbrella of multiple sclerosis (MS), has been extended to include autoimmune inflammatory conditions of the central nervous system (CNS), which are now diagnosable with serum serological tests. These antibody-mediated inflammatory diseases of the CNS share a clinical presentation to MS. A number of practical learning points emerge in this review, which is geared toward the pattern recognition of optic neuritis, transverse myelitis, brainstem/cerebellar and hemispheric tumefactive demyelinating lesion (TDL)-associated MS, aquaporin-4-antibody and myelin oligodendrocyte glycoprotein (MOG)-antibody NMOSD, overlap syndrome, and some yet-to-be-defined/classified demyelinating disease, all unspecifically labeled under MS syndrome. The goal of this review is to increase clinicians’ awareness of the clinical nuances of the autoimmune conditions for MS and NMSOD, and to highlight highly suggestive patterns of clinical, paraclinical or imaging presentations in order to improve differentiation. With overlay in clinical manifestations between MS and NMOSD, magnetic resonance imaging (MRI) of the brain, orbits and spinal cord, serology, and most importantly, high index of suspicion based on pattern recognition, will help lead to the final diagnosis. PMID:29064441

  8. Autonomy, recognition and education

    Directory of Open Access Journals (Sweden)

    Angelo Vitório Cenci

    2015-01-01

    Full Text Available This paper addresses Honneth’s concept of autonomy from two dimensions of his work, distinct, though inseparable. The first one is suggested through the subject’s positive practical self-relation linked to the patterns of reciprocal recognition of love, right and social esteem; the second is formulated as non-centered autonomy opposed to the present-day criticism of the modern autonomous subject encompassing three levels, namely: the capacity of linguistic articulation, the narrative coherence of life and the complementation of being guided by principles with some criteria of moral sensitivity to the context. We defend the position that, by metaphysically anchoring the concept of autonomy onto the intersubjective assumptions of his/her theory of the subject, and exploring it linked to the subject’s positive practical self-relation and to a non-centered meaning, Honneth has managed to renew it, which allows drawing important consequences of such effort to the field of education.

  9. Pattern recognition in spectra

    International Nuclear Information System (INIS)

    Gebran, M; Paletou, F

    2017-01-01

    We present a new automated procedure that simultaneously derives the effective temperature T eff , surface gravity log g , metallicity [ Fe/H ], and equatorial projected rotational velocity v e sin i for stars. The procedure is inspired by the well-known PCA-based inversion of spectropolarimetric full-Stokes solar data, which was used both for Zeeman and Hanle effects. The efficiency and accuracy of this procedure have been proven for FGK, A, and late type dwarf stars of K and M spectral types. Learning databases are generated from the Elodie stellar spectra library using observed spectra for which fundamental parameters were already evaluated or with synthetic data. The synthetic spectra are calculated using ATLAS9 model atmospheres. This technique helped us to detect many peculiar stars such as Am, Ap, HgMn, SiEuCr and binaries. This fast and efficient technique could be used every time a pattern recognition is needed. One important application is the understanding of the physical properties of planetary surfaces by comparing aboard instrument data to synthetic ones. (paper)

  10. Vision-Based Navigation and Recognition

    National Research Council Canada - National Science Library

    Rosenfeld, Azriel

    1998-01-01

    .... (4) Invariants: both geometric and other types. (5) Human faces: Analysis of images of human faces, including feature extraction, face recognition, compression, and recognition of facial expressions...

  11. Vision-Based Navigation and Recognition

    National Research Council Canada - National Science Library

    Rosenfeld, Azriel

    1996-01-01

    .... (4) Invariants -- both geometric and other types. (5) Human faces: Analysis of images of human faces, including feature extraction, face recognition, compression, and recognition of facial expressions...

  12. Recognition Using Classification and Segmentation Scoring

    National Research Council Canada - National Science Library

    Kimball, Owen; Ostendorf, Mari; Rohlicek, Robin

    1992-01-01

    .... We describe an approach to connected word recognition that allows the use of segmental information through an explicit decomposition of the recognition criterion into classification and segmentation scoring...

  13. Auditory Modeling for Noisy Speech Recognition

    National Research Council Canada - National Science Library

    2000-01-01

    ... digital filtering for noise cancellation which interfaces to speech recognition software. It uses auditory features in speech recognition training, and provides applications to multilingual spoken language translation...

  14. Kernel learning algorithms for face recognition

    CERN Document Server

    Li, Jun-Bao; Pan, Jeng-Shyang

    2013-01-01

    Kernel Learning Algorithms for Face Recognition covers the framework of kernel based face recognition. This book discusses the advanced kernel learning algorithms and its application on face recognition. This book also focuses on the theoretical deviation, the system framework and experiments involving kernel based face recognition. Included within are algorithms of kernel based face recognition, and also the feasibility of the kernel based face recognition method. This book provides researchers in pattern recognition and machine learning area with advanced face recognition methods and its new

  15. Facial recognition in education system

    Science.gov (United States)

    Krithika, L. B.; Venkatesh, K.; Rathore, S.; Kumar, M. Harish

    2017-11-01

    Human beings exploit emotions comprehensively for conveying messages and their resolution. Emotion detection and face recognition can provide an interface between the individuals and technologies. The most successful applications of recognition analysis are recognition of faces. Many different techniques have been used to recognize the facial expressions and emotion detection handle varying poses. In this paper, we approach an efficient method to recognize the facial expressions to track face points and distances. This can automatically identify observer face movements and face expression in image. This can capture different aspects of emotion and facial expressions.

  16. Iris recognition via plenoptic imaging

    Science.gov (United States)

    Santos-Villalobos, Hector J.; Boehnen, Chris Bensing; Bolme, David S.

    2017-11-07

    Iris recognition can be accomplished for a wide variety of eye images by using plenoptic imaging. Using plenoptic technology, it is possible to correct focus after image acquisition. One example technology reconstructs images having different focus depths and stitches them together, resulting in a fully focused image, even in an off-angle gaze scenario. Another example technology determines three-dimensional data for an eye and incorporates it into an eye model used for iris recognition processing. Another example technology detects contact lenses. Application of the technologies can result in improved iris recognition under a wide variety of scenarios.

  17. Face Recognition using Approximate Arithmetic

    DEFF Research Database (Denmark)

    Marso, Karol

    Face recognition is image processing technique which aims to identify human faces and found its use in various different fields for example in security. Throughout the years this field evolved and there are many approaches and many different algorithms which aim to make the face recognition as effective...... processing applications the results do not need to be completely precise and use of the approximate arithmetic can lead to reduction in terms of delay, space and power consumption. In this paper we examine possible use of approximate arithmetic in face recognition using Eigenfaces algorithm....

  18. Evaluating music emotion recognition:Lessons from music genre recognition?

    OpenAIRE

    Sturm, Bob L.

    2013-01-01

    A fundamental problem with nearly all work in music genre recognition (MGR)is that evaluation lacks validity with respect to the principal goals of MGR. This problem also occurs in the evaluation of music emotion recognition (MER). Standard approaches to evaluation, though easy to implement, do not reliably differentiate between recognizing genre or emotion from music, or by virtue of confounding factors in signals (e.g., equalization). We demonstrate such problems for evaluating an MER syste...

  19. The Impact of Mutual Recognition: Inbuilt Limits and Domestic Responses to the Single Market

    OpenAIRE

    Schmidt, S.

    2002-01-01

    What have been the consequences of integrating the single market via mutual recognition? Did competitive deregulation result? Or were its implications less significant than expected? In this paper I analyse two previously highly regulated service sectors, insurance and road haulage, and study the impact of European policies in Germany and France. I find that the Council instituted mutual recognition in a restrictive way. This limits its impact on member states, which is moreover mediated by n...

  20. Success with voice recognition.

    Science.gov (United States)

    Sferrella, Sheila M

    2003-01-01

    You need a compelling reason to implement voice recognition technology. At my institution, the compelling reason was a turnaround time for Radiology results of more than two days. Only 41 percent of our reports were transcribed and signed within 24 hours. In November 1998, a team from Lehigh Valley Hospital went to RSNA and reviewed every voice system on the market. The evaluation was done with the radiologist workflow in mind, and we came back from the meeting with the vendor selection completed. The next steps included developing a business plan, approval of funds, reference calls to more than 15 sites and contract negotiation, all of which took about six months. The department of Radiology at Lehigh Valley Hospital and Health Network (LVHHN) is a multi-site center that performs over 360,000 procedures annually. The department handles all modalities of radiology: general diagnosis, neuroradiology, ultrasound, CT Scan, MRI, interventional radiology, arthography, myelography, bone densitometry, nuclear medicine, PET imaging, vascular lab and other advanced procedures. The department consists of 200 FTEs and a medical staff of more than 40 radiologists. The budget is in the $10.3 million range. There are three hospital sites and four outpatient imaging center sites where services are provided. At Lehigh Valley Hospital, radiologists are not dedicated to one subspecialty, so implementing a voice system by modality was not an option. Because transcription was so far behind, we needed to eliminate that part of the process. As a result, we decided to deploy the system all at once and with the radiologists as editors. The planning and testing phase took about four months, and the implementation took two weeks. We deployed over 40 workstations and trained close to 50 physicians. The radiologists brought in an extra radiologist from our group for the two weeks of training. That allowed us to train without taking a radiologist out of the department. We trained three to six

  1. The Role of Binocular Disparity in Rapid Scene and Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Matteo Valsecchi

    2013-04-01

    Full Text Available We investigated the contribution of binocular disparity to the rapid recognition of scenes and simpler spatial patterns using a paradigm combining backward masked stimulus presentation and short-term match-to-sample recognition. First, we showed that binocular disparity did not contribute significantly to the recognition of briefly presented natural and artificial scenes, even when the availability of monocular cues was reduced. Subsequently, using dense random dot stereograms as stimuli, we showed that observers were in principle able to extract spatial patterns defined only by disparity under brief, masked presentations. Comparing our results with the predictions from a cue-summation model, we showed that combining disparity with luminance did not per se disrupt the processing of disparity. Our results suggest that the rapid recognition of scenes is mediated mostly by a monocular comparison of the images, although we can rely on stereo in fast pattern recognition.

  2. Indoor navigation by image recognition

    Science.gov (United States)

    Choi, Io Teng; Leong, Chi Chong; Hong, Ka Wo; Pun, Chi-Man

    2017-07-01

    With the progress of smartphones hardware, it is simple on smartphone using image recognition technique such as face detection. In addition, indoor navigation system development is much slower than outdoor navigation system. Hence, this research proves a usage of image recognition technique for navigation in indoor environment. In this paper, we introduced an indoor navigation application that uses the indoor environment features to locate user's location and a route calculating algorithm to generate an appropriate path for user. The application is implemented on Android smartphone rather than iPhone. Yet, the application design can also be applied on iOS because the design is implemented without using special features only for Android. We found that digital navigation system provides better and clearer location information than paper map. Also, the indoor environment is ideal for Image recognition processing. Hence, the results motivate us to design an indoor navigation system using image recognition.

  3. Pattern recognition and string matching

    CERN Document Server

    Cheng, Xiuzhen

    2002-01-01

    The research and development of pattern recognition have proven to be of importance in science, technology, and human activity. Many useful concepts and tools from different disciplines have been employed in pattern recognition. Among them is string matching, which receives much theoretical and practical attention. String matching is also an important topic in combinatorial optimization. This book is devoted to recent advances in pattern recognition and string matching. It consists of twenty eight chapters written by different authors, addressing a broad range of topics such as those from classifica­ tion, matching, mining, feature selection, and applications. Each chapter is self-contained, and presents either novel methodological approaches or applications of existing theories and techniques. The aim, intent, and motivation for publishing this book is to pro­ vide a reference tool for the increasing number of readers who depend upon pattern recognition or string matching in some way. This includes student...

  4. License plate recognition (phase B).

    Science.gov (United States)

    2010-06-01

    License Plate Recognition (LPR) technology has been used for off-line automobile enforcement purposes. The technology has seen mixed success with correct reading rate as high as 60 to 80% depending on the specific application and environment. This li...

  5. Similarity measures for face recognition

    CERN Document Server

    Vezzetti, Enrico

    2015-01-01

    Face recognition has several applications, including security, such as (authentication and identification of device users and criminal suspects), and in medicine (corrective surgery and diagnosis). Facial recognition programs rely on algorithms that can compare and compute the similarity between two sets of images. This eBook explains some of the similarity measures used in facial recognition systems in a single volume. Readers will learn about various measures including Minkowski distances, Mahalanobis distances, Hansdorff distances, cosine-based distances, among other methods. The book also summarizes errors that may occur in face recognition methods. Computer scientists "facing face" and looking to select and test different methods of computing similarities will benefit from this book. The book is also useful tool for students undertaking computer vision courses.

  6. [Neurological disease and facial recognition].

    Science.gov (United States)

    Kawamura, Mitsuru; Sugimoto, Azusa; Kobayakawa, Mutsutaka; Tsuruya, Natsuko

    2012-07-01

    To discuss the neurological basis of facial recognition, we present our case reports of impaired recognition and a review of previous literature. First, we present a case of infarction and discuss prosopagnosia, which has had a large impact on face recognition research. From a study of patient symptoms, we assume that prosopagnosia may be caused by unilateral right occipitotemporal lesion and right cerebral dominance of facial recognition. Further, circumscribed lesion and degenerative disease may also cause progressive prosopagnosia. Apperceptive prosopagnosia is observed in patients with posterior cortical atrophy (PCA), pathologically considered as Alzheimer's disease, and associative prosopagnosia in frontotemporal lobar degeneration (FTLD). Second, we discuss face recognition as part of communication. Patients with Parkinson disease show social cognitive impairments, such as difficulty in facial expression recognition and deficits in theory of mind as detected by the reading the mind in the eyes test. Pathological and functional imaging studies indicate that social cognitive impairment in Parkinson disease is possibly related to damages in the amygdalae and surrounding limbic system. The social cognitive deficits can be observed in the early stages of Parkinson disease, and even in the prodromal stage, for example, patients with rapid eye movement (REM) sleep behavior disorder (RBD) show impairment in facial expression recognition. Further, patients with myotonic dystrophy type 1 (DM 1), which is a multisystem disease that mainly affects the muscles, show social cognitive impairment similar to that of Parkinson disease. Our previous study showed that facial expression recognition impairment of DM 1 patients is associated with lesion in the amygdalae and insulae. Our study results indicate that behaviors and personality traits in DM 1 patients, which are revealed by social cognitive impairment, are attributable to dysfunction of the limbic system.

  7. Voice congruency facilitates word recognition.

    Directory of Open Access Journals (Sweden)

    Sandra Campeanu

    Full Text Available Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  8. Voice congruency facilitates word recognition.

    Science.gov (United States)

    Campeanu, Sandra; Craik, Fergus I M; Alain, Claude

    2013-01-01

    Behavioral studies of spoken word memory have shown that context congruency facilitates both word and source recognition, though the level at which context exerts its influence remains equivocal. We measured event-related potentials (ERPs) while participants performed both types of recognition task with words spoken in four voices. Two voice parameters (i.e., gender and accent) varied between speakers, with the possibility that none, one or two of these parameters was congruent between study and test. Results indicated that reinstating the study voice at test facilitated both word and source recognition, compared to similar or no context congruency at test. Behavioral effects were paralleled by two ERP modulations. First, in the word recognition test, the left parietal old/new effect showed a positive deflection reflective of context congruency between study and test words. Namely, the same speaker condition provided the most positive deflection of all correctly identified old words. In the source recognition test, a right frontal positivity was found for the same speaker condition compared to the different speaker conditions, regardless of response success. Taken together, the results of this study suggest that the benefit of context congruency is reflected behaviorally and in ERP modulations traditionally associated with recognition memory.

  9. 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

  10. Oxytocin Reduces Face Processing Time but Leaves Recognition Accuracy and Eye-Gaze Unaffected.

    Science.gov (United States)

    Hubble, Kelly; Daughters, Katie; Manstead, Antony S R; Rees, Aled; Thapar, Anita; van Goozen, Stephanie H M

    2017-01-01

    Previous studies have found that oxytocin (OXT) can improve the recognition of emotional facial expressions; it has been proposed that this effect is mediated by an increase in attention to the eye-region of faces. Nevertheless, evidence in support of this claim is inconsistent, and few studies have directly tested the effect of oxytocin on emotion recognition via altered eye-gaze Methods: In a double-blind, within-subjects, randomized control experiment, 40 healthy male participants received 24 IU intranasal OXT and placebo in two identical experimental sessions separated by a 2-week interval. Visual attention to the eye-region was assessed on both occasions while participants completed a static facial emotion recognition task using medium intensity facial expressions. Although OXT had no effect on emotion recognition accuracy, recognition performance was improved because face processing was faster across emotions under the influence of OXT. This effect was marginally significant (pfaces and this was not related to recognition accuracy or face processing time. These findings suggest that OXT-induced enhanced facial emotion recognition is not necessarily mediated by an increase in attention to the eye-region of faces, as previously assumed. We discuss several methodological issues which may explain discrepant findings and suggest the effect of OXT on visual attention may differ depending on task requirements. (JINS, 2017, 23, 23-33).

  11. Molecular Recognition in the Colloidal World.

    Science.gov (United States)

    Elacqua, Elizabeth; Zheng, Xiaolong; Shillingford, Cicely; Liu, Mingzhu; Weck, Marcus

    2017-11-21

    Colloidal self-assembly is a bottom-up technique to fabricate functional nanomaterials, with paramount interest stemming from programmable assembly of smaller building blocks into dynamic crystalline domains and photonic materials. Multiple established colloidal platforms feature diverse shapes and bonding interactions, while achieving specific orientations along with short- and long-range order. A major impediment to their universal use as building blocks for predesigned architectures is the inability to precisely dictate and control particle functionalization and concomitant reversible self-assembly. Progress in colloidal self-assembly necessitates the development of strategies that endow bonding specificity and directionality within assemblies. Methodologies that emulate molecular and polymeric three-dimensional (3D) architectures feature elements of covalent bonding, while high-fidelity molecular recognition events have been installed to realize responsive reconfigurable assemblies. The emergence of anisotropic 'colloidal molecules', coupled with the ability to site-specifically decorate particle surfaces with supramolecular recognition motifs, has facilitated the formation of superstructures via directional interactions and shape recognition. In this Account, we describe supramolecular assembly routes to drive colloidal particles into precisely assembled architectures or crystalline lattices via directional noncovalent molecular interactions. The design principles are based upon the fabrication of colloidal particles bearing surface-exposed functional groups that can undergo programmable conjugation to install recognition motifs with high fidelity. Modular and versatile by design, our strategy allows for the introduction and integration of molecular recognition principles into the colloidal world. We define noncovalent molecular interactions as site-specific forces that are predictable (i.e., feature selective and controllable complementary bonding partners

  12. Mediatized play

    DEFF Research Database (Denmark)

    Johansen, Stine Liv

    Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....

  13. Mediating Business

    DEFF Research Database (Denmark)

    "Mediating Business" is a study of the expansion of business journalism. Building on evidence from Denmark, Finland, Norway and Sweden, "Mediating Business" is a comparative and multidisciplinary study of one of the major transformations of the mass media and the realm of business - nationally...... and globally. The book explores the history of key innovations and innovators in the business press. It analyzes changes in the discourse of business journalism associated with the growth in business news and the development of new ways of framing business issues and events. Finally, it examines...... the organizational implications of the increased media visibility of business and, in particular, the development of corporate governance and media relations....

  14. Comparing Face Detection and Recognition Techniques

    OpenAIRE

    Korra, Jyothi

    2016-01-01

    This paper implements and compares different techniques for face detection and recognition. One is find where the face is located in the images that is face detection and second is face recognition that is identifying the person. We study three techniques in this paper: Face detection using self organizing map (SOM), Face recognition by projection and nearest neighbor and Face recognition using SVM.

  15. The Neuropsychology of Familiar Person Recognition from Face and Voice

    Directory of Open Access Journals (Sweden)

    Guido Gainotti

    2014-05-01

    Full Text Available Prosopagnosia has been considered for a long period of time as the most important and almost exclusive disorder in the recognition of familiar people. In recent years, however, this conviction has been undermined by the description of patients showing a concomitant defect in the recognition of familiar faces and voices as a consequence of lesions encroaching upon the right anterior temporal lobe (ATL. These new data have obliged researchers to reconsider on one hand the construct of ‘associative prosopagnosia’ and on the other hand current models of people recognition. A systematic review of the patterns of familiar people recognition disorders observed in patients with right and left ATL lesions has shown that in patients with right ATL lesions face familiarity feelings and the retrieval of person-specific semantic information from faces are selectively affected, whereas in patients with left ATL lesions the defect selectively concerns famous people naming. Furthermore, some patients with right ATL lesions and intact face familiarity feelings show a defect in the retrieval of person-specific semantic knowledge greater from face than from name. These data are at variance with current models assuming: (a that familiarity feelings are generated at the level of person identity nodes (PINs where information processed by various sensory modalities converge, and (b that PINs provide a modality-free gateway to a single semantic system, where information about people is stored in an amodal format. They suggest, on the contrary: (a that familiarity feelings are generated at the level of modality-specific recognition units; (b that face and voice recognition units are represented more in the right than in the left ATLs; (c that in the right ATL are mainly stored person-specific information based on a convergence of perceptual information, whereas in the left ATLs are represented verbally-mediated person-specific information.

  16. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    Science.gov (United States)

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory. SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  17. Bidirectional Modulation of Recognition Memory.

    Science.gov (United States)

    Ho, Jonathan W; Poeta, Devon L; Jacobson, Tara K; Zolnik, Timothy A; Neske, Garrett T; Connors, Barry W; Burwell, Rebecca D

    2015-09-30

    Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects. For example, animals and humans with perirhinal damage are unable to distinguish familiar from novel objects in recognition memory tasks. In the normal brain, perirhinal neurons respond to novelty and familiarity by increasing or decreasing firing rates. Recent work also implicates oscillatory activity in the low-beta and low-gamma frequency bands in sensory detection, perception, and recognition. Using optogenetic methods in a spontaneous object exploration (SOR) task, we altered recognition memory performance in rats. In the SOR task, normal rats preferentially explore novel images over familiar ones. We modulated exploratory behavior in this task by optically stimulating channelrhodopsin-expressing perirhinal neurons at various frequencies while rats looked at novel or familiar 2D images. Stimulation at 30-40 Hz during looking caused rats to treat a familiar image as if it were novel by increasing time looking at the image. Stimulation at 30-40 Hz was not effective in increasing exploration of novel images. Stimulation at 10-15 Hz caused animals to treat a novel image as familiar by decreasing time looking at the image, but did not affect looking times for images that were already familiar. We conclude that optical stimulation of PER at different frequencies can alter visual recognition memory bidirectionally. Significance statement: Recognition of novelty and familiarity are important for learning, memory, and decision making. Perirhinal cortex (PER) has a well established role in the familiarity-based recognition of individual items and objects, but how novelty and familiarity are encoded and transmitted in the brain is not known. Perirhinal neurons respond to novelty and familiarity by changing firing rates, but recent work suggests that brain oscillations may also be important for recognition. In this study, we showed that stimulation of

  18. [Asymmetric confusability effect in recognition memory of cats pictures].

    Science.gov (United States)

    Ando, M; Hakoda, Y

    1999-06-01

    Performance superiority of the addition of features in the stimuli over the deletion on recognition (asymmetric confusability effect) has been shown in previous studies (Pezdek, Maki, Valencia-Laver, Whetstone, Stoeckert, & Dougherty, 1988; Ando & Hakoda, 1998). We investigated the same effect by using a familiar living thing (cat) as a stimulus. Ten subjects were given a recognition task using pictures of cats with feature changes (additions, deletions, or no change). Results showed that the picture with deletions were easier to recognize than those with additions, which was opposite to the previous studies. Then, we examined the possibility that performance superiority of the deletions over the additions was mediated by the factor of impression. Another group of 18 subjects was asked to rate the impression scales consisting of a "typicality-reality factor", a "stability-balance factor", and a "grotesque-disgust factor". Results showed that there was a significant difference in impression ratings for each factor between the additions and the deletions, and that impression ratings predicted recognition performance well. It was concluded that performance superiority of the deletions over the additions was mediated by the factor of impression.

  19. Cognitive object recognition system (CORS)

    Science.gov (United States)

    Raju, Chaitanya; Varadarajan, Karthik Mahesh; Krishnamurthi, Niyant; Xu, Shuli; Biederman, Irving; Kelley, Troy

    2010-04-01

    We have developed a framework, Cognitive Object Recognition System (CORS), inspired by current neurocomputational models and psychophysical research in which multiple recognition algorithms (shape based geometric primitives, 'geons,' and non-geometric feature-based algorithms) are integrated to provide a comprehensive solution to object recognition and landmarking. Objects are defined as a combination of geons, corresponding to their simple parts, and the relations among the parts. However, those objects that are not easily decomposable into geons, such as bushes and trees, are recognized by CORS using "feature-based" algorithms. The unique interaction between these algorithms is a novel approach that combines the effectiveness of both algorithms and takes us closer to a generalized approach to object recognition. CORS allows recognition of objects through a larger range of poses using geometric primitives and performs well under heavy occlusion - about 35% of object surface is sufficient. Furthermore, geon composition of an object allows image understanding and reasoning even with novel objects. With reliable landmarking capability, the system improves vision-based robot navigation in GPS-denied environments. Feasibility of the CORS system was demonstrated with real stereo images captured from a Pioneer robot. The system can currently identify doors, door handles, staircases, trashcans and other relevant landmarks in the indoor environment.

  20. An audiovisual emotion recognition system

    Science.gov (United States)

    Han, Yi; Wang, Guoyin; Yang, Yong; He, Kun

    2007-12-01

    Human emotions could be expressed by many bio-symbols. Speech and facial expression are two of them. They are both regarded as emotional information which is playing an important role in human-computer interaction. Based on our previous studies on emotion recognition, an audiovisual emotion recognition system is developed and represented in this paper. The system is designed for real-time practice, and is guaranteed by some integrated modules. These modules include speech enhancement for eliminating noises, rapid face detection for locating face from background image, example based shape learning for facial feature alignment, and optical flow based tracking algorithm for facial feature tracking. It is known that irrelevant features and high dimensionality of the data can hurt the performance of classifier. Rough set-based feature selection is a good method for dimension reduction. So 13 speech features out of 37 ones and 10 facial features out of 33 ones are selected to represent emotional information, and 52 audiovisual features are selected due to the synchronization when speech and video fused together. The experiment results have demonstrated that this system performs well in real-time practice and has high recognition rate. Our results also show that the work in multimodules fused recognition will become the trend of emotion recognition in the future.

  1. Kazakh Traditional Dance Gesture Recognition

    Science.gov (United States)

    Nussipbekov, A. K.; Amirgaliyev, E. N.; Hahn, Minsoo

    2014-04-01

    Full body gesture recognition is an important and interdisciplinary research field which is widely used in many application spheres including dance gesture recognition. The rapid growth of technology in recent years brought a lot of contribution in this domain. However it is still challenging task. In this paper we implement Kazakh traditional dance gesture recognition. We use Microsoft Kinect camera to obtain human skeleton and depth information. Then we apply tree-structured Bayesian network and Expectation Maximization algorithm with K-means clustering to calculate conditional linear Gaussians for classifying poses. And finally we use Hidden Markov Model to detect dance gestures. Our main contribution is that we extend Kinect skeleton by adding headwear as a new skeleton joint which is calculated from depth image. This novelty allows us to significantly improve the accuracy of head gesture recognition of a dancer which in turn plays considerable role in whole body gesture recognition. Experimental results show the efficiency of the proposed method and that its performance is comparable to the state-of-the-art system performances.

  2. Interplay of oxytocin, vasopressin, and sex hormones in the regulation of social recognition.

    Science.gov (United States)

    Gabor, Christopher S; Phan, Anna; Clipperton-Allen, Amy E; Kavaliers, Martin; Choleris, Elena

    2012-02-01

    Social Recognition is a fundamental skill that forms the basis of behaviors essential to the proper functioning of pair or group living in most social species. We review here various neurobiological and genetic studies that point to an interplay of oxytocin (OT), arginine-vasopressin (AVP), and the gonadal hormones, estrogens and testosterone, in the mediation of social recognition. Results of a number of studies have shown that OT and its actions at the medial amygdala seem to be essential for social recognition in both sexes. Estrogens facilitate social recognition, possibly by regulating OT production in the hypothalamus and the OT receptors at the medial amygdala. Estrogens also affect social recognition on a rapid time scale, likely through nongenomic actions. The mechanisms of these rapid effects are currently unknown but available evidence points at the hippocampus as the possible site of action. Male rodents seem to be more dependent on AVP acting at the level of the lateral septum for social recognition than female rodents. Results of various studies suggest that testosterone and its metabolites (including estradiol) influence social recognition in males primarily through the AVP V1a receptor. Overall, it appears that gonadal hormone modulation of OT and AVP regulates and fine tunes social recognition and those behaviors that depend upon it (e.g., social bonds, social hierarchies) in a sex specific manner. This points at an important role for these neuroendocrine systems in the regulation of the sex differences that are evident in social behavior and of sociality as a whole.

  3. Infliximab ameliorates AD-associated object recognition memory impairment.

    Science.gov (United States)

    Kim, Dong Hyun; Choi, Seong-Min; Jho, Jihoon; Park, Man-Seok; Kang, Jisu; Park, Se Jin; Ryu, Jong Hoon; Jo, Jihoon; Kim, Hyun Hee; Kim, Byeong C

    2016-09-15

    Dysfunctions in the perirhinal cortex (PRh) are associated with visual recognition memory deficit, which is frequently detected in the early stage of Alzheimer's disease. Muscarinic acetylcholine receptor-dependent long-term depression (mAChR-LTD) of synaptic transmission is known as a key pathway in eliciting this type of memory, and Tg2576 mice expressing enhanced levels of Aβ oligomers are found to have impaired mAChR-LTD in this brain area at as early as 3 months of age. We found that the administration of Aβ oligomers in young normal mice also induced visual recognition memory impairment and perturbed mAChR-LTD in mouse PRh slices. In addition, when mice were treated with infliximab, a monoclonal antibody against TNF-α, visual recognition memory impaired by pre-administered Aβ oligomers dramatically improved and the detrimental Aβ effect on mAChR-LTD was annulled. Taken together, these findings suggest that Aβ-induced inflammation is mediated through TNF-α signaling cascades, disturbing synaptic transmission in the PRh, and leading to visual recognition memory deficits. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Role of salivary epithelial toll-like receptors 2 and 4 in modulating innate immune responses in chronic periodontitis.

    Science.gov (United States)

    Swaminathan, V; Prakasam, S; Puri, V; Srinivasan, M

    2013-12-01

    Chronic periodontitis is initiated by sequential colonization with a broad array of bacteria and is perpetuated by an immune-inflammatory response to the changing biofilm. Host recognition of microbes is largely mediated by toll-like receptors (TLRs), which interact with conserved pathogen-associated molecular patterns. Based on ligand recognition, TLR-2 and TLR-4 interact with most periodontal pathogens. Extracrevicular bacterial reservoirs, such as the oral epithelial cells, contribute to the persistence of periodontitis. Human saliva is a rich source of oral epithelial cells that express functional TLRs. In this study we investigated the role of salivary epithelial cell (SEC) TLR-2 and TLR-4 in patients with generalized chronic periodontitis. Unstimulated whole saliva (UWS) was collected from patients with generalized chronic periodontitis and from healthy individuals after obtaining informed consent. Epithelial cells isolated from each UWS sample were assessed for TLR-2, TLR-4, peptidoglycan recognition protein (PGRP)-3 and PGRP-4 by quantitative real-time PCR. In addition, the SECs were stimulated in vitro with microbial products for up to 24 h. The culture supernatant was assessed for cytokines by ELISA. Stimulation with TLR-2- or TLR-4-specific ligands induced cytokine secretion with differential kinetics and up-regulated TLR2 and TLR4 mRNAs, respectively, in cultures of SECs from patients with periodontitis. In addition, the SECs from patients with periodontitis exhibited reduced PGRP3 and PGRP4 mRNAs, the TLR-responsive genes with antibacterial properties. SECs derived from the UWS of patients with chronic periodontitis are phenotypically distinct and could represent potential resources for assessing the epithelial responses to periodontal pathogens in the course of disease progression and persistence. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. On speech recognition during anaesthesia

    DEFF Research Database (Denmark)

    Alapetite, Alexandre

    2007-01-01

    This PhD thesis in human-computer interfaces (informatics) studies the case of the anaesthesia record used during medical operations and the possibility to supplement it with speech recognition facilities. Problems and limitations have been identified with the traditional paper-based anaesthesia...... and inaccuracies in the anaesthesia record. Supplementing the electronic anaesthesia record interface with speech input facilities is proposed as one possible solution to a part of the problem. The testing of the various hypotheses has involved the development of a prototype of an electronic anaesthesia record...... interface with speech input facilities in Danish. The evaluation of the new interface was carried out in a full-scale anaesthesia simulator. This has been complemented by laboratory experiments on several aspects of speech recognition for this type of use, e.g. the effects of noise on speech recognition...

  6. Discriminative learning for speech recognition

    CERN Document Server

    He, Xiadong

    2008-01-01

    In this book, we introduce the background and mainstream methods of probabilistic modeling and discriminative parameter optimization for speech recognition. The specific models treated in depth include the widely used exponential-family distributions and the hidden Markov model. A detailed study is presented on unifying the common objective functions for discriminative learning in speech recognition, namely maximum mutual information (MMI), minimum classification error, and minimum phone/word error. The unification is presented, with rigorous mathematical analysis, in a common rational-functio

  7. Acoustic modeling for emotion recognition

    CERN Document Server

    Anne, Koteswara Rao; Vankayalapati, Hima Deepthi

    2015-01-01

     This book presents state of art research in speech emotion recognition. Readers are first presented with basic research and applications – gradually more advance information is provided, giving readers comprehensive guidance for classify emotions through speech. Simulated databases are used and results extensively compared, with the features and the algorithms implemented using MATLAB. Various emotion recognition models like Linear Discriminant Analysis (LDA), Regularized Discriminant Analysis (RDA), Support Vector Machines (SVM) and K-Nearest neighbor (KNN) and are explored in detail using prosody and spectral features, and feature fusion techniques.

  8. Simultaneous tracking and activity recognition

    DEFF Research Database (Denmark)

    Manfredotti, Cristina Elena; Fleet, David J.; Hamilton, Howard J.

    2011-01-01

    be used to improve the prediction step of the tracking, while, at the same time, tracking information can be used for online activity recognition. Experimental results in two different settings show that our approach 1) decreases the error rate and improves the identity maintenance of the positional......Many tracking problems involve several distinct objects interacting with each other. We develop a framework that takes into account interactions between objects allowing the recognition of complex activities. In contrast to classic approaches that consider distinct phases of tracking and activity...... tracking and 2) identifies the correct activity with higher accuracy than standard approaches....

  9. Human ear recognition by computer

    CERN Document Server

    Bhanu, Bir; Chen, Hui

    2010-01-01

    Biometrics deals with recognition of individuals based on their physiological or behavioral characteristics. The human ear is a new feature in biometrics that has several merits over the more common face, fingerprint and iris biometrics. Unlike the fingerprint and iris, it can be easily captured from a distance without a fully cooperative subject, although sometimes it may be hidden with hair, scarf and jewellery. Also, unlike a face, the ear is a relatively stable structure that does not change much with the age and facial expressions. ""Human Ear Recognition by Computer"" is the first book o

  10. Familiar Person Recognition: Is Autonoetic Consciousness More Likely to Accompany Face Recognition Than Voice Recognition?

    Science.gov (United States)

    Barsics, Catherine; Brédart, Serge

    2010-11-01

    Autonoetic consciousness is a fundamental property of human memory, enabling us to experience mental time travel, to recollect past events with a feeling of self-involvement, and to project ourselves in the future. Autonoetic consciousness is a characteristic of episodic memory. By contrast, awareness of the past associated with a mere feeling of familiarity or knowing relies on noetic consciousness, depending on semantic memory integrity. Present research was aimed at evaluating whether conscious recollection of episodic memories is more likely to occur following the recognition of a familiar face than following the recognition of a familiar voice. Recall of semantic information (biographical information) was also assessed. Previous studies that investigated the recall of biographical information following person recognition used faces and voices of famous people as stimuli. In this study, the participants were presented with personally familiar people's voices and faces, thus avoiding the presence of identity cues in the spoken extracts and allowing a stricter control of frequency exposure with both types of stimuli (voices and faces). In the present study, the rate of retrieved episodic memories, associated with autonoetic awareness, was significantly higher from familiar faces than familiar voices even though the level of overall recognition was similar for both these stimuli domains. The same pattern was observed regarding semantic information retrieval. These results and their implications for current Interactive Activation and Competition person recognition models are discussed.

  11. Micro-Recognition - Erving Goffman as Recognition Thinker

    DEFF Research Database (Denmark)

    Jacobsen, Michael Hviid; Kristiansen, Søren

    2009-01-01

    and civil inattention guide the conduct of people in many of their face-to-face encounters with each other. This article therefore shows how Goffman may in fact supplement many of the most fashionable and celebrated contemporary recognition theories as advanced by e.g. Nancy Fraser, Charles Taylor or Axel...

  12. Face recognition : implementation of face recognition on AMIGO

    NARCIS (Netherlands)

    Geelen, M.J.A.J.; Molengraft, van de M.J.G.; Elfring, J.

    2011-01-01

    In this (traineeship)report two possible methods of face recognition were presented. The first method describes how to detect and recognize faces by using the SURF algorithm. This algorithm finally was not used for recognizing faces, with the reason that the Eigenface algorithm was an already tested

  13. Innate recognition of water bodies in echolocating bats.

    Science.gov (United States)

    Greif, Stefan; Siemers, Björn M

    2010-11-02

    In the course of their lives, most animals must find different specific habitat and microhabitat types for survival and reproduction. Yet, in vertebrates, little is known about the sensory cues that mediate habitat recognition. In free flying bats the echolocation of insect-sized point targets is well understood, whereas how they recognize and classify spatially extended echo targets is currently unknown. In this study, we show how echolocating bats recognize ponds or other water bodies that are crucial for foraging, drinking and orientation. With wild bats of 15 different species (seven genera from three phylogenetically distant, large bat families), we found that bats perceived any extended, echo-acoustically smooth surface to be water, even in the presence of conflicting information from other sensory modalities. In addition, naive juvenile bats that had never before encountered a water body showed spontaneous drinking responses from smooth plates. This provides the first evidence for innate recognition of a habitat cue in a mammal.

  14. Under what conditions is recognition spared relative to recall after selective hippocampal damage in humans?

    Science.gov (United States)

    Holdstock, J S; Mayes, A R; Roberts, N; Cezayirli, E; Isaac, C L; O'Reilly, R C; Norman, K A

    2002-01-01

    The claim that recognition memory is spared relative to recall after focal hippocampal damage has been disputed in the literature. We examined this claim by investigating object and object-location recall and recognition memory in a patient, YR, who has adult-onset selective hippocampal damage. Our aim was to identify the conditions under which recognition was spared relative to recall in this patient. She showed unimpaired forced-choice object recognition but clearly impaired recall, even when her control subjects found the object recognition task to be numerically harder than the object recall task. However, on two other recognition tests, YR's performance was not relatively spared. First, she was clearly impaired at an equivalently difficult yes/no object recognition task, but only when targets and foils were very similar. Second, YR was clearly impaired at forced-choice recognition of object-location associations. This impairment was also unrelated to difficulty because this task was no more difficult than the forced-choice object recognition task for control subjects. The clear impairment of yes/no, but not of forced-choice, object recognition after focal hippocampal damage, when targets and foils are very similar, is predicted by the neural network-based Complementary Learning Systems model of recognition. This model postulates that recognition is mediated by hippocampally dependent recollection and cortically dependent familiarity; thus hippocampal damage should not impair item familiarity. The model postulates that familiarity is ineffective when very similar targets and foils are shown one at a time and subjects have to identify which items are old (yes/no recognition). In contrast, familiarity is effective in discriminating which of similar targets and foils, seen together, is old (forced-choice recognition). Independent evidence from the remember/know procedure also indicates that YR's familiarity is normal. The Complementary Learning Systems model can

  15. Target recognition by wavelet transform

    International Nuclear Information System (INIS)

    Li Zhengdong; He Wuliang; Zheng Xiaodong; Cheng Jiayuan; Peng Wen; Pei Chunlan; Song Chen

    2002-01-01

    Wavelet transform has an important character of multi-resolution power, which presents pyramid structure, and this character coincides the way by which people distinguish object from coarse to fineness and from large to tiny. In addition to it, wavelet transform benefits to reducing image noise, simplifying calculation, and embodying target image characteristic point. A method of target recognition by wavelet transform is provided

  16. Face recognition, a landmarks tale

    NARCIS (Netherlands)

    Beumer, G.M.

    2009-01-01

    Face recognition is a technology that appeals to the imagination of many people. This is particularly reflected in the popularity of science-fiction films and forensic detective series such as CSI, CSI New York, CSI Miami, Bones and NCIS. Although these series tend to be set in the present, their

  17. Mobile Visual Recognition on Smartphones

    Directory of Open Access Journals (Sweden)

    Zhenwen Gui

    2013-01-01

    Full Text Available This paper addresses the recognition of large-scale outdoor scenes on smartphones by fusing outputs of inertial sensors and computer vision techniques. The main contributions can be summarized as follows. Firstly, we propose an ORD (overlap region divide method to plot image position area, which is fast enough to find the nearest visiting area and can also reduce the search range compared with the traditional approaches. Secondly, the vocabulary tree-based approach is improved by introducing GAGCC (gravity-aligned geometric consistency constraint. Our method involves no operation in the high-dimensional feature space and does not assume a global transform between a pair of images. Thus, it substantially reduces the computational complexity and memory usage, which makes the city scale image recognition feasible on the smartphone. Experiments on a collected database including 0.16 million images show that the proposed method demonstrates excellent recognition performance, while maintaining the average recognition time about 1 s.

  18. Data complexity in pattern recognition

    CERN Document Server

    Kam Ho Tin

    2006-01-01

    Machines capable of automatic pattern recognition have many fascinating uses. Algorithms for supervised classification, where one infers a decision boundary from a set of training examples, are at the core of this capability. This book looks at data complexity and its role in shaping the theories and techniques in different disciplines

  19. The Army word recognition system

    Science.gov (United States)

    Hadden, David R.; Haratz, David

    1977-01-01

    The application of speech recognition technology in the Army command and control area is presented. The problems associated with this program are described as well as as its relevance in terms of the man/machine interactions, voice inflexions, and the amount of training needed to interact with and utilize the automated system.

  20. Speech recognition from spectral dynamics

    Indian Academy of Sciences (India)

    Some of the history of gradual infusion of the modulation spectrum concept into Automatic recognition of speech (ASR) comes next, pointing to the relationship of modulation spectrum processing to wellaccepted ASR techniques such as dynamic speech features or RelAtive SpecTrAl (RASTA) filtering. Next, the frequency ...

  1. Speech recognition implementation in radiology

    International Nuclear Information System (INIS)

    White, Keith S.

    2005-01-01

    Continuous speech recognition (SR) is an emerging technology that allows direct digital transcription of dictated radiology reports. The SR systems are being widely deployed in the radiology community. This is a review of technical and practical issues that should be considered when implementing an SR system. (orig.)

  2. Color Textons for Texture Recognition

    NARCIS (Netherlands)

    Burghouts, G.J.; Geusebroek, J.M.

    2006-01-01

    Texton models have proven to be very discriminative for the recognition of grayvalue images taken from rough textures. To further improve the discriminative power of the distinctive texton models of Varma and Zisserman (VZ model) (IJCV, vol. 62(1), pp. 61-81, 2005), we propose two schemes to exploit

  3. Output Interference in Recognition Memory

    Science.gov (United States)

    Criss, Amy H.; Malmberg, Kenneth J.; Shiffrin, Richard M.

    2011-01-01

    Dennis and Humphreys (2001) proposed that interference in recognition memory arises solely from the prior contexts of the test word: Interference does not arise from memory traces of other words (from events prior to the study list or on the study list, and regardless of similarity to the test item). We evaluate this model using output…

  4. License plate recognition using DTCNNs

    NARCIS (Netherlands)

    ter Brugge, M.H; Stevens, J.H; Nijhuis, J.A G; Spaanenburg, L; Tavsanonoglu, V

    1998-01-01

    Automatic license plate recognition requires a series of complex image processing steps. For practical use, the amount of data to he processed must be minimized early on. This paper shows that the computationally most intensive steps can be realized by DTCNNs. Moreover; high-level operations like

  5. Matching score based face recognition

    NARCIS (Netherlands)

    Boom, B.J.; Beumer, G.M.; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

    2006-01-01

    Accurate face registration is of vital importance to the performance of a face recognition algorithm. We propose a new method: matching score based face registration, which searches for optimal alignment by maximizing the matching score output of a classifier as a function of the different

  6. Towards automatic forensic face recognition

    NARCIS (Netherlands)

    Ali, Tauseef; Spreeuwers, Lieuwe Jan; Veldhuis, Raymond N.J.

    2011-01-01

    In this paper we present a methodology and experimental results for evidence evaluation in the context of forensic face recognition. In forensic applications, the matching score (hereafter referred to as similarity score) from a biometric system must be represented as a Likelihood Ratio (LR). In our

  7. Investigating an Innovative Computer Application to Improve L2 Word Recognition from Speech

    Science.gov (United States)

    Matthews, Joshua; O'Toole, John Mitchell

    2015-01-01

    The ability to recognise words from the aural modality is a critical aspect of successful second language (L2) listening comprehension. However, little research has been reported on computer-mediated development of L2 word recognition from speech in L2 learning contexts. This report describes the development of an innovative computer application…

  8. Synergy between ficolin-2 and pentraxin 3 boosts innate immune recognition and complement deposition

    DEFF Research Database (Denmark)

    Ma, Ying Jie; Doni, Andrea; Hummelshøj, Tina

    2009-01-01

    The long pentraxin 3 (PTX3) is a multifunctional soluble pattern recognition molecule that is crucial in innate immune protection against opportunistic fungal pathogens such as Aspergillus fumigatus. The mechanisms that mediate downstream effects of PTX3 are largely unknown. However, PTX3 interac...

  9. How Learning Goal Orientation Fosters Leadership Recognition in Self-managed Teams

    DEFF Research Database (Denmark)

    Lee, Yih-Teen; Paunova, Minna

    2017-01-01

    understudied. Drawing on social exchange theory, we propose and test an individual-level two-stage process model of generalised exchange linking LGO and leadership recognition in self-managed teams. Specifically, we posit that learning-oriented individuals will tend to feel safer in self-managed teams, which......Defined as a mental framework for how individuals interpret and respond to achievement situations, learning goal orientation (LGO) has received increasing attention in organisational research. However, its effect on leadership, especially in contexts absent of formal leadership, remains......, but that contextual role behavior alone does not mediate the effect of LGO on leadership recognition. LGO has an indirect effect on leadership recognition through the joint mediation of felt safety and contextual role behavior. Our results offer insight on the link between LGO and leadership, with practical...

  10. Effects of Power on Mental Rotation and Emotion Recognition in Women.

    Science.gov (United States)

    Nissan, Tali; Shapira, Oren; Liberman, Nira

    2015-10-01

    Based on construal-level theory (CLT) and its view of power as an instance of social distance, we predicted that high, relative to low power would enhance women's mental-rotation performance and impede their emotion-recognition performance. The predicted effects of power emerged both when it was manipulated via a recall priming task (Study 1) and environmental cues (Studies 2 and 3). Studies 3 and 4 found evidence for mediation by construal level of the effect of power on emotion recognition but not on mental rotation. We discuss potential mediating mechanisms for these effects based on both the social distance/construal level and the approach/inhibition views of power. We also discuss implications for optimizing performance on mental rotation and emotion recognition in everyday life. © 2015 by the Society for Personality and Social Psychology, Inc.

  11. Object recognition memory in zebrafish.

    Science.gov (United States)

    May, Zacnicte; Morrill, Adam; Holcombe, Adam; Johnston, Travis; Gallup, Joshua; Fouad, Karim; Schalomon, Melike; Hamilton, Trevor James

    2016-01-01

    The novel object recognition, or novel-object preference (NOP) test is employed to assess recognition memory in a variety of organisms. The subject is exposed to two identical objects, then after a delay, it is placed back in the original environment containing one of the original objects and a novel object. If the subject spends more time exploring one object, this can be interpreted as memory retention. To date, this test has not been fully explored in zebrafish (Danio rerio). Zebrafish possess recognition memory for simple 2- and 3-dimensional geometrical shapes, yet it is unknown if this translates to complex 3-dimensional objects. In this study we evaluated recognition memory in zebrafish using complex objects of different sizes. Contrary to rodents, zebrafish preferentially explored familiar over novel objects. Familiarity preference disappeared after delays of 5 mins. Leopard danios, another strain of D. rerio, also preferred the familiar object after a 1 min delay. Object preference could be re-established in zebra danios by administration of nicotine tartrate salt (50mg/L) prior to stimuli presentation, suggesting a memory-enhancing effect of nicotine. Additionally, exploration biases were present only when the objects were of intermediate size (2 × 5 cm). Our results demonstrate zebra and leopard danios have recognition memory, and that low nicotine doses can improve this memory type in zebra danios. However, exploration biases, from which memory is inferred, depend on object size. These findings suggest zebrafish ecology might influence object preference, as zebrafish neophobia could reflect natural anti-predatory behaviour. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Atypical evening cortisol profile induces visual recognition memory deficit in healthy human subjects

    Directory of Open Access Journals (Sweden)

    Gilpin Heather

    2008-08-01

    Full Text Available Abstract Background Diurnal rhythm-mediated endogenous cortisol levels in humans are characterised by a peak in secretion after awakening that declines throughout the day to an evening trough. However, a significant proportion of the population exhibits an atypical cycle of diurnal cortisol due to shift work, jet-lag, aging, and mental illness. Results The present study has demonstrated a correlation between elevation of cortisol in the evening and deterioration of visual object recognition memory. However, high evening cortisol levels have no effect on spatial memory. Conclusion This study suggests that atypical evening salivary cortisol levels have an important role in the early deterioration of recognition memory. The loss of recognition memory, which is vital for everyday life, is a major symptom of the amnesic syndrome and early stages of Alzheimer's disease. Therefore, this study will promote a potential physiologic marker of early deterioration of recognition memory and a possible diagnostic strategy for Alzheimer's disease.

  13. Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation.

    Science.gov (United States)

    Han, Ren-Wen; Xu, Hong-Jiao; Zhang, Rui-San; Wang, Pei; Chang, Min; Peng, Ya-Li; Deng, Ke-Yu; Wang, Rui

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Efficient CEPSTRAL Normalization for Robust Speech Recognition

    National Research Council Canada - National Science Library

    Liu, Fu-Hua; Stern, Richard M; Huang, Xuedong; Acero, Alejandro

    1993-01-01

    In this paper we describe and compare the performance of a series of cepstrum-based procedures that enable the CMU SPHINX-II speech recognition system to maintain a high level of recognition accuracy...

  15. The contribution of the body and motion to whole person recognition.

    Science.gov (United States)

    Simhi, Noa; Yovel, Galit

    2016-05-01

    While the importance of faces in person recognition has been the subject of many studies, there are relatively few studies examining recognition of the whole person in motion even though this most closely resembles daily experience. Most studies examining the whole body in motion use point light displays, which have many advantages but are impoverished and unnatural compared to real life. To determine which factors are used when recognizing the whole person in motion we conducted two experiments using naturalistic videos. In Experiment 1 we used a matching task in which the first stimulus in each pair could either be a video or multiple still images from a video of the full body. The second stimulus, on which person recognition was performed, could be an image of either the full body or face alone. We found that the body contributed to person recognition beyond the face, but only after exposure to motion. Since person recognition was performed on still images, the contribution of motion to person recognition was mediated by form-from-motion processes. To assess whether dynamic identity signatures may also contribute to person recognition, in Experiment 2 we presented people in motion and examined person recognition from videos compared to still images. Results show that dynamic identity signatures did not contribute to person recognition beyond form-from-motion processes. We conclude that the face, body and form-from-motion processes all appear to play a role in unfamiliar person recognition, suggesting the importance of considering the whole body and motion when examining person perception. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Data structures, computer graphics, and pattern recognition

    CERN Document Server

    Klinger, A; Kunii, T L

    1977-01-01

    Data Structures, Computer Graphics, and Pattern Recognition focuses on the computer graphics and pattern recognition applications of data structures methodology.This book presents design related principles and research aspects of the computer graphics, system design, data management, and pattern recognition tasks. The topics include the data structure design, concise structuring of geometric data for computer aided design, and data structures for pattern recognition algorithms. The survey of data structures for computer graphics systems, application of relational data structures in computer gr

  17. Recognition of an Independent Self-Consciousness

    DEFF Research Database (Denmark)

    Bjerre, Henrik Jøker

    2009-01-01

    Hegel's concept in the Phenomenology of the Spirit of the "recognition of an independent self-consciousness" is investigated as a point of separation for contemporary philosophy of recognition. I claim that multiculturalism and the theories of recognition (such as Axel Honneth's) based on empiric...... psychology neglect or deny crucial metaphysical aspects of the Hegelian legacy. Instead, I seek to point at an additional, "spiritual", level of recognition, based on the concept of the subject in Lacanian psychoanalysis....

  18. Case-Based Policy and Goal Recognition

    Science.gov (United States)

    2015-09-30

    Policy and Goal Recognizer (PaGR), a case- based system for multiagent keyhole recognition. PaGR is a knowledge recognition component within a decision...However, unlike our agent in the BVR domain, these recognition agents have access to perfect information. Single-agent keyhole plan recognition can be...listed below: 1. Facing Target 2. Closing on Target 3. Target Range 4. Within a Target’s Weapon Range 5. Has Target within Weapon Range 6. Is in Danger

  19. Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

    Directory of Open Access Journals (Sweden)

    Muhammad Hameed Siddiqi

    2013-12-01

    Full Text Available Over the last decade, human facial expressions recognition (FER has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER.

  20. Hierarchical Recognition Scheme for Human Facial Expression Recognition Systems

    Science.gov (United States)

    Siddiqi, Muhammad Hameed; Lee, Sungyoung; Lee, Young-Koo; Khan, Adil Mehmood; Truc, Phan Tran Ho

    2013-01-01

    Over the last decade, human facial expressions recognition (FER) has emerged as an important research area. Several factors make FER a challenging research problem. These include varying light conditions in training and test images; need for automatic and accurate face detection before feature extraction; and high similarity among different expressions that makes it difficult to distinguish these expressions with a high accuracy. This work implements a hierarchical linear discriminant analysis-based facial expressions recognition (HL-FER) system to tackle these problems. Unlike the previous systems, the HL-FER uses a pre-processing step to eliminate light effects, incorporates a new automatic face detection scheme, employs methods to extract both global and local features, and utilizes a HL-FER to overcome the problem of high similarity among different expressions. Unlike most of the previous works that were evaluated using a single dataset, the performance of the HL-FER is assessed using three publicly available datasets under three different experimental settings: n-fold cross validation based on subjects for each dataset separately; n-fold cross validation rule based on datasets; and, finally, a last set of experiments to assess the effectiveness of each module of the HL-FER separately. Weighted average recognition accuracy of 98.7% across three different datasets, using three classifiers, indicates the success of employing the HL-FER for human FER. PMID:24316568

  1. [Effect of opioid receptors on acute stress-induced changes in recognition memory].

    Science.gov (United States)

    Liu, Ying; Wu, Yu-Wei; Qian, Zhao-Qiang; Yan, Cai-Fang; Fan, Ka-Min; Xu, Jin-Hui; Li, Xiao; Liu, Zhi-Qiang

    2016-12-25

    Although ample evidence has shown that acute stress impairs memory, the influences of acute stress on different phases of memory, such as acquisition, consolidation and retrieval, are different. Experimental data from both human and animals support that endogenous opioid system plays a role in stress, as endogenous opioid release is increased and opioid receptors are activated during stress experience. On the other hand, endogenous opioid system mediates learning and memory. The aim of the present study was to investigate the effect of acute forced swimming stress on recognition memory of C57 mice and the role of opioid receptors in this process by using a three-day pattern of new object recognition task. The results showed that 15-min acute forced swimming damaged the retrieval of recognition memory, but had no effect on acquisition and consolidation of recognition memory. No significant change of object recognition memory was found in mice that were given naloxone, an opioid receptor antagonist, by intraperitoneal injection. But intraperitoneal injection of naloxone before forced swimming stress could inhibit the impairment of recognition memory retrieval caused by forced swimming stress. The results of real-time PCR showed that acute forced swimming decreased the μ opioid receptor mRNA levels in whole brain and hippocampus, while the injection of naloxone before stress could reverse this change. These results suggest that acute stress may impair recognition memory retrieval via opioid receptors.

  2. Embedded Face Detection and Recognition

    Directory of Open Access Journals (Sweden)

    Göksel Günlü

    2012-10-01

    Full Text Available The need to increase security in open or public spaces has in turn given rise to the requirement to monitor these spaces and analyse those images on-site and on-time. At this point, the use of smart cameras – of which the popularity has been increasing – is one step ahead. With sensors and Digital Signal Processors (DSPs, smart cameras generate ad hoc results by analysing the numeric images transmitted from the sensor by means of a variety of image-processing algorithms. Since the images are not transmitted to a distance processing unit but rather are processed inside the camera, it does not necessitate high-bandwidth networks or high processor powered systems; it can instantaneously decide on the required access. Nonetheless, on account of restricted memory, processing power and overall power, image processing algorithms need to be developed and optimized for embedded processors. Among these algorithms, one of the most important is for face detection and recognition. A number of face detection and recognition methods have been proposed recently and many of these methods have been tested on general-purpose processors. In smart cameras – which are real-life applications of such methods – the widest use is on DSPs. In the present study, the Viola-Jones face detection method – which was reported to run faster on PCs – was optimized for DSPs; the face recognition method was combined with the developed sub-region and mask-based DCT (Discrete Cosine Transform. As the employed DSP is a fixed-point processor, the processes were performed with integers insofar as it was possible. To enable face recognition, the image was divided into sub-regions and from each sub-region the robust coefficients against disruptive elements – like face expression, illumination, etc. – were selected as the features. The discrimination of the selected features was enhanced via LDA (Linear Discriminant Analysis and then employed for recognition. Thanks to its

  3. Hidden neural networks: application to speech recognition

    DEFF Research Database (Denmark)

    Riis, Søren Kamaric

    1998-01-01

    We evaluate the hidden neural network HMM/NN hybrid on two speech recognition benchmark tasks; (1) task independent isolated word recognition on the Phonebook database, and (2) recognition of broad phoneme classes in continuous speech from the TIMIT database. It is shown how hidden neural networks...

  4. Complement Receptor 3-Mediated Inhibition of Inflammasome Priming by Ras GTPase-Activating Protein During Francisella tularensis Phagocytosis by Human Mononuclear Phagocytes

    Directory of Open Access Journals (Sweden)

    Ky V. Hoang

    2018-03-01

    Full Text Available Francisella tularensis is a remarkably infectious facultative intracellular bacterium of macrophages that causes tularemia. Early evasion of host immune responses contributes to the success of F. tularensis as a pathogen. F. tularensis entry into human monocytes and macrophages is mediated by the major phagocytic receptor, complement receptor 3 (CR3, CD11b/CD18. We recently determined that despite a significant increase in macrophage uptake following C3 opsonization of the virulent Type A F. tularensis spp. tularensis Schu S4, this phagocytic pathway results in limited pro-inflammatory cytokine production. Notably, MAP kinase/ERK activation is suppressed immediately during C3-opsonized Schu S4-CR3 phagocytosis. A mathematical model of CR3-TLR2 crosstalk predicted early involvement of Ras GTPase-activating protein (RasGAP in immune suppression by CR3. Here, we link CR3-mediated uptake of opsonized Schu S4 by human monocytes and macrophages with inhibition of early signal 1 inflammasome activation, evidenced by limited caspase-1 cleavage and IL-18 release. This inhibition is due to increased RasGAP activity, leading to a reduction in the Ras-ERK signaling cascade upstream of the early inflammasome activation event. Thus, our data uncover a novel signaling pathway mediated by CR3 following engagement of opsonized virulent F. tularensis to limit inflammasome activation in human phagocytic cells, thereby contributing to evasion of the host innate immune system.

  5. The automaticity of emotion recognition.

    Science.gov (United States)

    Tracy, Jessica L; Robins, Richard W

    2008-02-01

    Evolutionary accounts of emotion typically assume that humans evolved to quickly and efficiently recognize emotion expressions because these expressions convey fitness-enhancing messages. The present research tested this assumption in 2 studies. Specifically, the authors examined (a) how quickly perceivers could recognize expressions of anger, contempt, disgust, embarrassment, fear, happiness, pride, sadness, shame, and surprise; (b) whether accuracy is improved when perceivers deliberate about each expression's meaning (vs. respond as quickly as possible); and (c) whether accurate recognition can occur under cognitive load. Across both studies, perceivers quickly and efficiently (i.e., under cognitive load) recognized most emotion expressions, including the self-conscious emotions of pride, embarrassment, and shame. Deliberation improved accuracy in some cases, but these improvements were relatively small. Discussion focuses on the implications of these findings for the cognitive processes underlying emotion recognition.

  6. Individual Recognition in Ant Queens

    DEFF Research Database (Denmark)

    D'Ettorre, Patrizia; Heinze, Jürgen

    2005-01-01

    Personal relationships are the cornerstone of vertebrate societies, but insect societies are either too large for individual recognition, or their members were assumed to lack the necessary cognitive abilities 1 and 2 . This paradigm has been challenged by the recent discovery that paper wasps...... recognize each other's unique facial color patterns [3] . Individual recognition is advantageous when dominance hierarchies control the partitioning of work and reproduction 2 and 4 . Here, we show that unrelated founding queens of the ant Pachycondyla villosa use chemical cues to recognize each other...... individually. Aggression was significantly lower in pairs of queens that had previously interacted than in pairs with similar social history but no experience with one another. Moreover, subordinates discriminated familiar and unfamiliar dominants in choice experiments in which physical contact, but not odor...

  7. Motion Primitives for Action Recognition

    DEFF Research Database (Denmark)

    Fihl, Preben; Holte, Michael Boelstoft; Moeslund, Thomas B.

    2007-01-01

    the actions as a sequence of temporal isolated instances, denoted primitives. These primitives are each defined by four features extracted from motion images. The primitives are recognized in each frame based on a trained classifier resulting in a sequence of primitives. From this sequence we recognize......The number of potential applications has made automatic recognition of human actions a very active research area. Different approaches have been followed based on trajectories through some state space. In this paper we also model an action as a trajectory through a state space, but we represent...... different temporal actions using a probabilistic Edit Distance method. The method is tested on different actions with and without noise and the results show recognition rates of 88.7% and 85.5%, respectively....

  8. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  9. Symbol Recognition using Spatial Relations

    OpenAIRE

    K.C., Santosh; Lamiroy, Bart; Wendling, Laurent

    2012-01-01

    International audience; In this paper, we present a method for symbol recognition based on the spatio-structural description of a 'vocabulary' of extracted visual elementary parts. It is applied to symbols in electrical wiring diagrams. The method consists of first identifying vocabulary elements into different groups based on their types (e.g., circle, corner ). We then compute spatial relations between the possible pairs of labelled vocabulary types which are further used as a basis for bui...

  10. Automated road marking recognition system

    Science.gov (United States)

    Ziyatdinov, R. R.; Shigabiev, R. R.; Talipov, D. N.

    2017-09-01

    Development of the automated road marking recognition systems in existing and future vehicles control systems is an urgent task. One way to implement such systems is the use of neural networks. To test the possibility of using neural network software has been developed with the use of a single-layer perceptron. The resulting system based on neural network has successfully coped with the task both when driving in the daytime and at night.

  11. Visual recognition of permuted words

    Science.gov (United States)

    Rashid, Sheikh Faisal; Shafait, Faisal; Breuel, Thomas M.

    2010-02-01

    In current study we examine how letter permutation affects in visual recognition of words for two orthographically dissimilar languages, Urdu and German. We present the hypothesis that recognition or reading of permuted and non-permuted words are two distinct mental level processes, and that people use different strategies in handling permuted words as compared to normal words. A comparison between reading behavior of people in these languages is also presented. We present our study in context of dual route theories of reading and it is observed that the dual-route theory is consistent with explanation of our hypothesis of distinction in underlying cognitive behavior for reading permuted and non-permuted words. We conducted three experiments in lexical decision tasks to analyze how reading is degraded or affected by letter permutation. We performed analysis of variance (ANOVA), distribution free rank test, and t-test to determine the significance differences in response time latencies for two classes of data. Results showed that the recognition accuracy for permuted words is decreased 31% in case of Urdu and 11% in case of German language. We also found a considerable difference in reading behavior for cursive and alphabetic languages and it is observed that reading of Urdu is comparatively slower than reading of German due to characteristics of cursive script.

  12. DNA recognition by synthetic constructs.

    Science.gov (United States)

    Pazos, Elena; Mosquera, Jesús; Vázquez, M Eugenio; Mascareñas, José L

    2011-09-05

    The interaction of transcription factors with specific DNA sites is key for the regulation of gene expression. Despite the availability of a large body of structural data on protein-DNA complexes, we are still far from fully understanding the molecular and biophysical bases underlying such interactions. Therefore, the development of non-natural agents that can reproduce the DNA-recognition properties of natural transcription factors remains a major and challenging goal in chemical biology. In this review we summarize the basics of double-stranded DNA recognition by transcription factors, and describe recent developments in the design and preparation of synthetic DNA binders. We mainly focus on synthetic peptides that have been designed by following the DNA interaction of natural proteins, and we discuss how the tools of organic synthesis can be used to make artificial constructs equipped with functionalities that introduce additional properties to the recognition process, such as sensing and controllability. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Gender recognition from vocal source

    Science.gov (United States)

    Sorokin, V. N.; Makarov, I. S.

    2008-07-01

    Efficiency of automatic recognition of male and female voices based on solving the inverse problem for glottis area dynamics and for waveform of the glottal airflow volume velocity pulse is studied. The inverse problem is regularized through the use of analytical models of the voice excitation pulse and of the dynamics of the glottis area, as well as the model of one-dimensional glottal airflow. Parameters of these models and spectral parameters of the volume velocity pulse are considered. The following parameters are found to be most promising: the instant of maximum glottis area, the maximum derivative of the area, the slope of the spectrum of the glottal airflow volume velocity pulse, the amplitude ratios of harmonics of this spectrum, and the pitch. On the plane of the first two main components in the space of these parameters, an almost twofold decrease in the classification error relative to that for the pitch alone is attained. The male voice recognition probability is found to be 94.7%, and the female voice recognition probability is 95.9%.

  14. Quadcopter Control Using Speech Recognition

    Science.gov (United States)

    Malik, H.; Darma, S.; Soekirno, S.

    2018-04-01

    This research reported a comparison from a success rate of speech recognition systems that used two types of databases they were existing databases and new databases, that were implemented into quadcopter as motion control. Speech recognition system was using Mel frequency cepstral coefficient method (MFCC) as feature extraction that was trained using recursive neural network method (RNN). MFCC method was one of the feature extraction methods that most used for speech recognition. This method has a success rate of 80% - 95%. Existing database was used to measure the success rate of RNN method. The new database was created using Indonesian language and then the success rate was compared with results from an existing database. Sound input from the microphone was processed on a DSP module with MFCC method to get the characteristic values. Then, the characteristic values were trained using the RNN which result was a command. The command became a control input to the single board computer (SBC) which result was the movement of the quadcopter. On SBC, we used robot operating system (ROS) as the kernel (Operating System).

  15. Multithread Face Recognition in Cloud

    Directory of Open Access Journals (Sweden)

    Dakshina Ranjan Kisku

    2016-01-01

    Full Text Available Faces are highly challenging and dynamic objects that are employed as biometrics evidence in identity verification. Recently, biometrics systems have proven to be an essential security tools, in which bulk matching of enrolled people and watch lists is performed every day. To facilitate this process, organizations with large computing facilities need to maintain these facilities. To minimize the burden of maintaining these costly facilities for enrollment and recognition, multinational companies can transfer this responsibility to third-party vendors who can maintain cloud computing infrastructures for recognition. In this paper, we showcase cloud computing-enabled face recognition, which utilizes PCA-characterized face instances and reduces the number of invariant SIFT points that are extracted from each face. To achieve high interclass and low intraclass variances, a set of six PCA-characterized face instances is computed on columns of each face image by varying the number of principal components. Extracted SIFT keypoints are fused using sum and max fusion rules. A novel cohort selection technique is applied to increase the total performance. The proposed protomodel is tested on BioID and FEI face databases, and the efficacy of the system is proven based on the obtained results. We also compare the proposed method with other well-known methods.

  16. Non Audio-Video gesture recognition system

    DEFF Research Database (Denmark)

    Craciunescu, Razvan; Mihovska, Albena Dimitrova; Kyriazakos, Sofoklis

    2016-01-01

    Gesture recognition is a topic in computer science and language technology with the goal of interpreting human gestures via mathematical algorithms. Gestures can originate from any bodily motion or state but commonly originate from the face or hand. Current research focus includes on the emotion...... recognition from the face and hand gesture recognition. Gesture recognition enables humans to communicate with the machine and interact naturally without any mechanical devices. This paper investigates the possibility to use non-audio/video sensors in order to design a low-cost gesture recognition device...

  17. Famous face recognition, face matching, and extraversion.

    Science.gov (United States)

    Lander, Karen; Poyarekar, Siddhi

    2015-01-01

    It has been previously established that extraverts who are skilled at interpersonal interaction perform significantly better than introverts on a face-specific recognition memory task. In our experiment we further investigate the relationship between extraversion and face recognition, focusing on famous face recognition and face matching. Results indicate that more extraverted individuals perform significantly better on an upright famous face recognition task and show significantly larger face inversion effects. However, our results did not find an effect of extraversion on face matching or inverted famous face recognition.

  18. Type I interferon production during herpes simplex virus infection is controlled by cell-type-specific viral recognition through Toll-like receptor 9, the mitochondrial antiviral signaling protein pathway, and novel recognition systems

    DEFF Research Database (Denmark)

    Rasmussen, Simon Brandtoft; Sørensen, Louise Nørgaard; Malmgaard, Lene

    2007-01-01

    Recognition of viruses by germ line-encoded pattern recognition receptors of the innate immune system is essential for rapid production of type I interferon (IFN) and early antiviral defense. We investigated the mechanisms of viral recognition governing production of type I IFN during herpes...... simplex virus (HSV) infection. We show that early production of IFN in vivo is mediated through Toll-like receptor 9 (TLR9) and plasmacytoid dendritic cells, whereas the subsequent alpha/beta IFN (IFN-alpha/beta) response is derived from several cell types and induced independently of TLR9...

  19. The coevolution of recognition and social behavior.

    Science.gov (United States)

    Smead, Rory; Forber, Patrick

    2016-05-26

    Recognition of behavioral types can facilitate the evolution of cooperation by enabling altruistic behavior to be directed at other cooperators and withheld from defectors. While much is known about the tendency for recognition to promote cooperation, relatively little is known about whether such a capacity can coevolve with the social behavior it supports. Here we use evolutionary game theory and multi-population dynamics to model the coevolution of social behavior and recognition. We show that conditional harming behavior enables the evolution and stability of social recognition, whereas conditional helping leads to a deterioration of recognition ability. Expanding the model to include a complex game where both helping and harming interactions are possible, we find that conditional harming behavior can stabilize recognition, and thereby lead to the evolution of conditional helping. Our model identifies a novel hypothesis for the evolution of cooperation: conditional harm may have coevolved with recognition first, thereby helping to establish the mechanisms necessary for the evolution of cooperation.

  20. Mechanisms of Expression and Internalisation of FIBCD1; a novel Pattern Recognition Receptor in the Gut Mucosa

    DEFF Research Database (Denmark)

    Hammond, Mark; Schlosser, Anders; Dubey, Lalit Kumar

    2012-01-01

    is a carbohydrate recognition domain also expressed by the ficolins, which are pattern recognition molecules that activate the complement system via the lectin pathway. Chitin is a highly ace¬tylated homopolymer of β-1,4-N-acetyl-glucosamine carbohydrate found abundantly in nature in organisms such as fungi...... pattern recognition receptor that binds chitin and directs acetylated structures for de¬gradation in the endosome via clathrin-mediated endocytosis. The localisation of FIBCD1 in the intestinal mucosal epithelia points towards a functional role in innate immunity and/or gut homeostasis....

  1. Vaccination inhibits TLR2 transcription via suppression of GR nuclear translocation and binding to TLR2 promoter in porcine lung infected with Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Sun, Zhiyuan; Liu, Maojun; Zou, Huafeng; Li, Xian; Shao, Guoqing; Zhao, Ruqian

    2013-12-27

    Toll-like receptors (TLRs) and glucocorticoid receptor (GR) act respectively as effectors of innate immune and stress responses. The crosstalk between them is critical for the maintenance of homeostasis during the immune response. Vaccination is known to boost adaptive immunity, yet it remains elusive whether vaccination may affect GR/TLR interactions following infection. Duroc×Meishan crossbred piglets were allocated to three groups. The control group (CC) received neither vaccination nor infection; the non-vaccinated infection group (NI) was artificially infected intratracheally with Mycoplasma hyopneumoniae (M. hyopneumoniae); while the vaccinated, infected group (VI) was vaccinated intramuscularly with inactivated M. hyopneumoniae one month before infection. The clinical signs and macroscopic lung lesions were significantly reduced by vaccination. However, vaccination did not affect the concentration of M. hyopneumoniae DNA in the lung. Serum cortisol was significantly decreased in both NI and VI pigs (Phyopneumoniae-induced lung lesions in the pig. Copyright © 2013 Elsevier B.V. All rights reserved.

  2. Exploring Cultural Differences in the Recognition of the Self-Conscious Emotions.

    Science.gov (United States)

    Chung, Joanne M; Robins, Richard W

    2015-01-01

    Recent research suggests that the self-conscious emotions of embarrassment, shame, and pride have distinct, nonverbal expressions that can be recognized in the United States at above-chance levels. However, few studies have examined the recognition of these emotions in other cultures, and little research has been conducted in Asia. Consequently the cross-cultural generalizability of self-conscious emotions has not been firmly established. Additionally, there is no research that examines cultural variability in the recognition of the self-conscious emotions. Cultural values and exposure to Western culture have been identified as contributors to variability in recognition rates for the basic emotions; we sought to examine this for the self-conscious emotions using the University of California, Davis Set of Emotion Expressions (UCDSEE). The present research examined recognition of the self-conscious emotion expressions in South Korean college students and found that recognition rates were very high for pride, low but above chance for shame, and near zero for embarrassment. To examine what might be underlying the recognition rates we found in South Korea, recognition of self-conscious emotions and several cultural values were examined in a U.S. college student sample of European Americans, Asian Americans, and Asian-born individuals. Emotion recognition rates were generally similar between the European Americans and Asian Americans, and higher than emotion recognition rates for Asian-born individuals. These differences were not explained by cultural values in an interpretable manner, suggesting that exposure to Western culture is a more important mediator than values.

  3. Exploring Cultural Differences in the Recognition of the Self-Conscious Emotions.

    Directory of Open Access Journals (Sweden)

    Joanne M Chung

    Full Text Available Recent research suggests that the self-conscious emotions of embarrassment, shame, and pride have distinct, nonverbal expressions that can be recognized in the United States at above-chance levels. However, few studies have examined the recognition of these emotions in other cultures, and little research has been conducted in Asia. Consequently the cross-cultural generalizability of self-conscious emotions has not been firmly established. Additionally, there is no research that examines cultural variability in the recognition of the self-conscious emotions. Cultural values and exposure to Western culture have been identified as contributors to variability in recognition rates for the basic emotions; we sought to examine this for the self-conscious emotions using the University of California, Davis Set of Emotion Expressions (UCDSEE. The present research examined recognition of the self-conscious emotion expressions in South Korean college students and found that recognition rates were very high for pride, low but above chance for shame, and near zero for embarrassment. To examine what might be underlying the recognition rates we found in South Korea, recognition of self-conscious emotions and several cultural values were examined in a U.S. college student sample of European Americans, Asian Americans, and Asian-born individuals. Emotion recognition rates were generally similar between the European Americans and Asian Americans, and higher than emotion recognition rates for Asian-born individuals. These differences were not explained by cultural values in an interpretable manner, suggesting that exposure to Western culture is a more important mediator than values.

  4. Exploring Cultural Differences in the Recognition of the Self-Conscious Emotions

    Science.gov (United States)

    Chung, Joanne M.; Robins, Richard W.

    2015-01-01

    Recent research suggests that the self-conscious emotions of embarrassment, shame, and pride have distinct, nonverbal expressions that can be recognized in the United States at above-chance levels. However, few studies have examined the recognition of these emotions in other cultures, and little research has been conducted in Asia. Consequently the cross-cultural generalizability of self-conscious emotions has not been firmly established. Additionally, there is no research that examines cultural variability in the recognition of the self-conscious emotions. Cultural values and exposure to Western culture have been identified as contributors to variability in recognition rates for the basic emotions; we sought to examine this for the self-conscious emotions using the University of California, Davis Set of Emotion Expressions (UCDSEE). The present research examined recognition of the self-conscious emotion expressions in South Korean college students and found that recognition rates were very high for pride, low but above chance for shame, and near zero for embarrassment. To examine what might be underlying the recognition rates we found in South Korea, recognition of self-conscious emotions and several cultural values were examined in a U.S. college student sample of European Americans, Asian Americans, and Asian-born individuals. Emotion recognition rates were generally similar between the European Americans and Asian Americans, and higher than emotion recognition rates for Asian-born individuals. These differences were not explained by cultural values in an interpretable manner, suggesting that exposure to Western culture is a more important mediator than values. PMID:26309215

  5. The Main Cognitive Model of Visual Recognition: Contour Recognition

    OpenAIRE

    Chen, YongHong

    2017-01-01

    In this paper, we will study the following pattern recognition problem: Every pattern is a 3-dimensional graph, its surface can be split up into some regions, every region is composed of the pixels with the approximately same colour value and the approximately same depth value that is distance to eyes, and there may also be some contours, e.g., literal contours, on a surface of every pattern. For this problem we reveal the inherent laws. Moreover, we establish a cognitive model to reflect the...

  6. ArtinM Mediates Murine T Cell Activation and Induces Cell Death in Jurkat Human Leukemic T Cells

    Science.gov (United States)

    Oliveira-Brito, Patrícia Kellen Martins; Gonçalves, Thiago Eleutério; Vendruscolo, Patrícia Edivânia; Roque-Barreira, Maria Cristina

    2017-01-01

    The recognition of cell surface glycans by lectins may be critical for the innate and adaptive immune responses. ArtinM, a d-mannose-binding lectin from Artocarpus heterophyllus, activates antigen-presenting cells by recognizing TLR2 N-glycans and induces Th1 immunity. We recently demonstrated that ArtinM stimulated CD4+ T cells to produce proinflammatory cytokines. Here, we further studied the effects of ArtinM on adaptive immune cells. We showed that ArtinM activates murine CD4+ and CD8+ T cells, augmenting their positivity for CD25, CD69, and CD95 and showed higher interleukin (IL)-2 and interferon (IFN)-γ production. The CD4+ T cells exhibited increased T-bet expression in response to ArtinM, and IL-2 production by CD4+ and CD8+ T cells depended on the recognition of CD3εγ-chain glycans by ArtinM. The ArtinM effect on aberrantly-glycosylated neoplastic lymphocytes was studied in Jurkat T cells, in which ArtinM induced IL-2, IFN-γ, and IL-1β production, but decreased cell viability and growth. A higher frequency of AnnexinV- and propidium iodide-stained cells demonstrated the induction of Jurkat T cells apoptosis by ArtinM, and this apoptotic response was reduced by caspases and protein tyrosine kinase inhibitors. The ArtinM effects on murine T cells corroborated with the immunomodulatory property of lectin, whereas the promotion of Jurkat T cells apoptosis may reflect a potential applicability of ArtinM in novel strategies for treating lymphocytic leukemia. PMID:28665310

  7. Lactoferricin mediates Anti-Inflammatory and Anti-Catabolic Effects via Inhibition of IL-1 and LPS Activity in the Intervertebral Disc†

    Science.gov (United States)

    Kim, Jae-Sung; Ellman, Michael B.; Yan, Dongyao; An, Howard S.; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Zabo, Gabriella; Hoskin, David W.; Buechter, D.D.; Van Wijnen, Andre J.; Im, Hee-Jeong

    2013-01-01

    The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. PMID:23460134

  8. Lactoferricin mediates anti-inflammatory and anti-catabolic effects via inhibition of IL-1 and LPS activity in the intervertebral disc.

    Science.gov (United States)

    Kim, Jae-Sung; Ellman, Michael B; Yan, Dongyao; An, Howard S; Kc, Ranjan; Li, Xin; Chen, Di; Xiao, Guozhi; Cs-Szabo, Gabriella; Hoskin, David W; Buechter, Doug D; Van Wijnen, Andre J; Im, Hee-Jeong

    2013-09-01

    The catabolic cytokine interleukin-1 (IL-1) and endotoxin lipopolysaccharide (LPS) are well-known inflammatory mediators involved in degenerative disc disease, and inhibitors of IL-1 and LPS may potentially be used to slow or prevent disc degeneration in vivo. Here, we elucidate the striking anti-catabolic and anti-inflammatory effects of bovine lactoferricin (LfcinB) in the intervertebral disc (IVD) via antagonism of both IL-1 and LPS-mediated catabolic activity using in vitro and ex vivo analyses. Specifically, we demonstrate the biological counteraction of LfcinB against IL-1 and LPS-mediated proteoglycan (PG) depletion, matrix-degrading enzyme production, and enzyme activity in long-term (alginate beads) and short-term (monolayer) culture models using bovine and human nucleus pulposus (NP) cells. LfcinB significantly attenuates the IL-1 and LPS-mediated suppression of PG production and synthesis, and thus restores PG accumulation and pericellular matrix formation. Simultaneously, LfcinB antagonizes catabolic factor mediated induction of multiple cartilage-degrading enzymes, including MMP-1, MMP-3, MMP-13, ADAMTS-4, and ADAMTS-5, in bovine NP cells at both mRNA and protein levels. LfcinB also suppresses the catabolic factor-induced stimulation of oxidative and inflammatory factors such as iNOS, IL-6, and toll-like receptor-2 (TLR-2) and TLR-4. Finally, the ability of LfcinB to antagonize IL-1 and LPS-mediated suppression of PG is upheld in an en bloc intradiscal microinjection model followed by ex vivo organ culture using both mouse and rabbit IVD tissue, suggesting a potential therapeutic benefit of LfcinB on degenerative disc disease in the future. Copyright © 2013 Wiley Periodicals, Inc.

  9. Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

    Science.gov (United States)

    Guan, Xiao-Feng; Chen, Qing-Jie; Zuo, Xiao-Cong; Guo, Ren; Peng, Xiang-Dong; Wang, Jiang-Lin; Yin, Wen-Jun; Li, Dai-Yang

    2017-01-01

    With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

  10. mediation: R package for causal mediation analysis

    OpenAIRE

    Tingley, Dustin; Yamamoto, Teppei; Hirose, Kentaro; Keele, Luke; Imai, Kosuke

    2012-01-01

    In this paper, we describe the R package mediation for conducting causal mediation analysis in applied empirical research. In many scientific disciplines, the goal of researchers is not only estimating causal effects of a treatment but also understanding the process in which the treatment causally affects the outcome. Causal mediation analysis is frequently used to assess potential causal mechanisms. The mediation package implements a comprehensive suite of statistical tools for conducting su...

  11. A new selective developmental deficit: Impaired object recognition with normal face recognition.

    Science.gov (United States)

    Germine, Laura; Cashdollar, Nathan; Düzel, Emrah; Duchaine, Bradley

    2011-05-01

    Studies of developmental deficits in face recognition, or developmental prosopagnosia, have shown that individuals who have not suffered brain damage can show face recognition impairments coupled with normal object recognition (Duchaine and Nakayama, 2005; Duchaine et al., 2006; Nunn et al., 2001). However, no developmental cases with the opposite dissociation - normal face recognition with impaired object recognition - have been reported. The existence of a case of non-face developmental visual agnosia would indicate that the development of normal face recognition mechanisms does not rely on the development of normal object recognition mechanisms. To see whether a developmental variant of non-face visual object agnosia exists, we conducted a series of web-based object and face recognition tests to screen for individuals showing object recognition memory impairments but not face recognition impairments. Through this screening process, we identified AW, an otherwise normal 19-year-old female, who was then tested in the lab on face and object recognition tests. AW's performance was impaired in within-class visual recognition memory across six different visual categories (guns, horses, scenes, tools, doors, and cars). In contrast, she scored normally on seven tests of face recognition, tests of memory for two other object categories (houses and glasses), and tests of recall memory for visual shapes. Testing confirmed that her impairment was not related to a general deficit in lower-level perception, object perception, basic-level recognition, or memory. AW's results provide the first neuropsychological evidence that recognition memory for non-face visual object categories can be selectively impaired in individuals without brain damage or other memory impairment. These results indicate that the development of recognition memory for faces does not depend on intact object recognition memory and provide further evidence for category-specific dissociations in visual

  12. Recognition memory span in autopsy-confirmed Dementia with Lewy Bodies and Alzheimer's Disease.

    Science.gov (United States)

    Salmon, David P; Heindel, William C; Hamilton, Joanne M; Vincent Filoteo, J; Cidambi, Varun; Hansen, Lawrence A; Masliah, Eliezer; Galasko, Douglas

    2015-08-01

    Evidence from patients with amnesia suggests that recognition memory span tasks engage both long-term memory (i.e., secondary memory) processes mediated by the diencephalic-medial temporal lobe memory system and working memory processes mediated by fronto-striatal systems. Thus, the recognition memory span task may be particularly effective for detecting memory deficits in disorders that disrupt both memory systems. The presence of unique pathology in fronto-striatal circuits in Dementia with Lewy Bodies (DLB) compared to AD suggests that performance on the recognition memory span task might be differentially affected in the two disorders even though they have quantitatively similar deficits in secondary memory. In the present study, patients with autopsy-confirmed DLB or AD, and Normal Control (NC) participants, were tested on separate recognition memory span tasks that required them to retain increasing amounts of verbal, spatial, or visual object (i.e., faces) information across trials. Results showed that recognition memory spans for verbal and spatial stimuli, but not face stimuli, were lower in patients with DLB than in those with AD, and more impaired relative to NC performance. This was despite similar deficits in the two patient groups on independent measures of secondary memory such as the total number of words recalled from long-term storage on the Buschke Selective Reminding Test. The disproportionate vulnerability of recognition memory span task performance in DLB compared to AD may be due to greater fronto-striatal involvement in DLB and a corresponding decrement in cooperative interaction between working memory and secondary memory processes. Assessment of recognition memory span may contribute to the ability to distinguish between DLB and AD relatively early in the course of disease. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. CELLULAR INTERACTIONS MEDIATED BY GLYCONECTIDS

    Directory of Open Access Journals (Sweden)

    O.Popescu

    1999-01-01

    Full Text Available Cellular interactions involve many types of cell surface molecules and operate via homophilic and/or heterophilic protein-protein and protein-carbohydrate binding. Our investigations in different model-systems (marine invertebrates and mammals have provided direct evidence that a novel class of primordial proteoglycans, named by us gliconectins, can mediate cell adhesion via a new alternative molecular mechanism of polyvalent carbohydrate-carbohydrate binding. Biochemical characterization of isolated and purified glyconectins revealed the presence of specific carbohydrate structures, acidic glycans, different from classical glycosaminoglycans. Such acidic glycans of high molecular weight containing fucose, glucuronic or galacturonic acids, and sulfate groups, originally found in sponges and sea urchin embryos, may represent a new class of carbohydrate carcino-embryonal antigens in mice and humans. Such interactions between biological macromolecules are usually investigated by kinetic binding studies, calorimetric methods, X-ray diffraction, nuclear magnetic resonance, and other spectroscopic analyses. However, these methods do not supply a direct estimation of the intermolecular binding forces that are fundamental for the function of the ligand-receptor association. Recently, we have introduced atomic force microscopy to quantify the binding strength between cell adhesion proteoglycans. Measurement of binding forces intrinsic to cell adhesion proteoglycans is necessary to assess their contribution to the maintenance of the anatomical integrity of multicellular organisms. As a model, we selected the glyconectin 1, a cell adhesion proteoglycan isolated from the marine sponge Microciona prolifera. This glyconectin mediates in vivo cell recognition and aggregation via homophilic, species-specific, polyvalent, and calcium ion-dependent carbohydrate-carbohydrate interactions. Under physiological conditions, an adhesive force of up to 400 piconewtons

  14. Speech Recognition for the iCub Platform

    Directory of Open Access Journals (Sweden)

    Bertrand Higy

    2018-02-01

    Full Text Available This paper describes open source software (available at https://github.com/robotology/natural-speech to build automatic speech recognition (ASR systems and run them within the YARP platform. The toolkit is designed (i to allow non-ASR experts to easily create their own ASR system and run it on iCub and (ii to build deep learning-based models specifically addressing the main challenges an ASR system faces in the context of verbal human–iCub interactions. The toolkit mostly consists of Python, C++ code and shell scripts integrated in YARP. As additional contribution, a second codebase (written in Matlab is provided for more expert ASR users who want to experiment with bio-inspired and developmental learning-inspired ASR systems. Specifically, we provide code for two distinct kinds of speech recognition: “articulatory” and “unsupervised” speech recognition. The first is largely inspired by influential neurobiological theories of speech perception which assume speech perception to be mediated by brain motor cortex activities. Our articulatory systems have been shown to outperform strong deep learning-based baselines. The second type of recognition systems, the “unsupervised” systems, do not use any supervised information (contrary to most ASR systems, including our articulatory systems. To some extent, they mimic an infant who has to discover the basic speech units of a language by herself. In addition, we provide resources consisting of pre-trained deep learning models for ASR, and a 2.5-h speech dataset of spoken commands, the VoCub dataset, which can be used to adapt an ASR system to the typical acoustic environments in which iCub operates.

  15. COMMERCIAL FUND, RECOGNITION AND ASSESSMENT

    Directory of Open Access Journals (Sweden)

    VIOREL TRIF

    2010-01-01

    Full Text Available The importance of the immaterial investments within companies nowadays urges the specialists in accounting to find the ways to present more in the elements. In their studies researchers face the controversy reinvestments, as an asset in the balance sheet or an expense in the profit or loss account. The main goal of this paper is to analyze the difficulties in commercial fund. In the first part we will analyze various definitions of the problems concerning the commercial fund’s recognition and assessment. The paper also suggests that investments are really social and economic problems.

  16. Introduction to radar target recognition

    CERN Document Server

    Tait, P

    2006-01-01

    This new text provides an overview of the radar target recognition process and covers the key techniques being developed for operational systems. It is based on the fundamental scientific principles of high resolution radar, and explains how the techniques can be used in real systems, taking into account the characteristics of practical radar system designs and component limitations. It also addresses operational aspects, such as how high resolution modes would fit in with other functions such as detection and tracking. Mathematics is kept to a minimum and the complex techniques and issues are

  17. Comparing word and face recognition

    DEFF Research Database (Denmark)

    Robotham, Ro Julia; Starrfelt, Randi

    2017-01-01

    included, as a control, which makes designing experiments all the more challenging. Three main strategies have been used to overcome this problem, each of which has limitations: 1) Compare performances on typical tests of the three stimulus types (e.g., a Face Memory Test, an Object recognition test...... this framework to classify tests and experiments aiming to compare processing across these categories, it becomes apparent that core differences in characteristics (visual and semantic) between the stimuli make the problem of designing comparable tests an insoluble conundrum. By analyzing the experimental...

  18. Psychophysiological indices of recognition memory

    OpenAIRE

    Heaver, Becky

    2012-01-01

    It has recently been found that during recognition memory tests participants’ pupils dilate more when they view old items compared to novel items. This thesis sought to replicate this novel ‘‘Pupil Old/New Effect’’ (PONE) and to determine its relationship to implicit and explicit mnemonic processes, the veracity of participants’ responses, and the analogous Event-Related Potential (ERP) old/new effect. Across 9 experiments, pupil-size was measured with a video-based eye-tracker during a varie...

  19. Face Recognition using Gabor Filters

    Directory of Open Access Journals (Sweden)

    Sajjad MOHSIN

    2011-01-01

    Full Text Available An Elastic Bunch Graph Map (EBGM algorithm is being proposed in this research paper that successfully implements face recognition using Gabor filters. The proposed system applies 40 different Gabor filters on an image. As aresult of which 40 images with different angles and orientation are received. Next, maximum intensity points in each filtered image are calculated and mark them as Fiducial points. The system reduces these points in accordance to distance between them. The next step is calculating the distances between the reduced points using distance formula. At last, the distances are compared with database. If match occurs, it means that the image is recognized.

  20. Micro dynamics in mediation

    OpenAIRE

    Boserup, Hans

    2014-01-01

    The author has identified a number of styles in mediation, which lead to different processes and different outcomes. Through discourse and conversation analysis he examines the micro dynamics in three of these, the postmodern styles: systemic, transformative and narrative mediation. The differences between the three mediation ideologies and practice is illustrated through role play scripts enacted in each style. Mediator and providers of mediation and trainers in mediation are encouraged to a...

  1. Nuclear DAMP complex-mediated RAGE-dependent macrophage cell death

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ruochan [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Fu, Sha; Fan, Xue-Gong [Department of Infectious Diseases and State Key Lab of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha, Hunan 410008 (China); Lotze, Michael T.; Zeh, Herbert J. [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Tang, Daolin, E-mail: tangd2@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States); Kang, Rui, E-mail: kangr@upmc.edu [Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15213 (United States)

    2015-03-13

    High mobility group box 1 (HMGB1), histone, and DNA are essential nuclear components involved in the regulation of chromosome structure and function. In addition to their nuclear function, these molecules act as damage-associated molecular patterns (DAMPs) alone or together when released extracellularly. The synergistic effect of these nuclear DNA-HMGB1-histone complexes as DAMP complexes (nDCs) on immune cells remains largely unexplored. Here, we demonstrate that nDCs limit survival of macrophages (e.g., RAW264.7 and peritoneal macrophages) but not cancer cells (e.g., HCT116, HepG2 and Hepa1-6). nDCs promote production of inflammatory tumor necrosis factor α (TNFα) release, triggering reactive oxygen species-dependent apoptosis and necrosis. Moreover, the receptor for advanced glycation end products (RAGE), but not toll-like receptor (TLR)-4 and TLR-2, was required for Akt-dependent TNFα release and subsequent cell death following treatment with nDCs. Genetic depletion of RAGE by RNAi, antioxidant N-Acetyl-L-cysteine, and TNFα neutralizing antibody significantly attenuated nDC-induced cell death. These findings provide evidence supporting novel signaling mechanisms linking nDCs and inflammation in macrophage cell death. - Highlights: • Nuclear DAMP complexes (nDCs) selectively induce cell death in macrophages, but not cancer cells. • TNFα-mediated oxidative stress is required for nDC-induced death. • RAGE-mediated Akt activation is required for nDC-induced TNFα release. • Blocking RAGE and TNFα inhibits nDC-induced macrophage cell death.

  2. Downregulation of toll-like receptor-mediated signalling pathways in oral lichen planus.

    Science.gov (United States)

    Sinon, Suraya H; Rich, Alison M; Parachuru, Venkata P B; Firth, Fiona A; Milne, Trudy; Seymour, Gregory J

    2016-01-01

    The objective of this study was to investigate the expression of Toll-like receptors (TLR) and TLR-associated signalling pathway genes in oral lichen planus (OLP). Initially, immunohistochemistry was used to determine TLR expression in 12 formalin-fixed archival OLP tissues with 12 non-specifically inflamed oral tissues as controls. RNA was isolated from further fresh samples of OLP and non-specifically inflamed oral tissue controls (n = 6 for both groups) and used in qRT(2)-PCR focused arrays to determine the expression of TLRs and associated signalling pathway genes. Genes with a statistical significance of ±two-fold regulation (FR) and a P-value < 0.05 were considered as significantly regulated. Significantly more TLR4(+) cells were present in the inflammatory infiltrate in OLP compared with the control tissues (P < 0.05). There was no statistically significant difference in the numbers of TLR2(+) and TLR8(+) cells between the groups. TLR3 was significantly downregulated in OLP (P < 0.01). TLR8 was upregulated in OLP, but the difference between the groups was not statistically significant. The TLR-mediated signalling-associated protein genes MyD88 and TIRAP were significantly downregulated (P < 0.01 and P < 0.05), as were IRAK1 (P < 0.05), MAPK8 (P < 0.01), MAP3K1 (P < 0.05), MAP4K4 (P < 0.05), REL (P < 0.01) and RELA (P < 0.01). Stress proteins HMGB1 and the heat shock protein D1 were significantly downregulated in OLP (P < 0.01). These findings suggest a downregulation of TLR-mediated signalling pathways in OLP lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. The relationship between protein synthesis and protein degradation in object recognition memory.

    Science.gov (United States)

    Furini, Cristiane R G; Myskiw, Jociane de C; Schmidt, Bianca E; Zinn, Carolina G; Peixoto, Patricia B; Pereira, Luiza D; Izquierdo, Ivan

    2015-11-01

    For decades there has been a consensus that de novo protein synthesis is necessary for long-term memory. A second round of protein synthesis has been described for both extinction and reconsolidation following an unreinforced test session. Recently, it was shown that consolidation and reconsolidation depend not only on protein synthesis but also on protein degradation by the ubiquitin-proteasome system (UPS), a major mechanism responsible for protein turnover. However, the involvement of UPS on consolidation and reconsolidation of object recognition memory remains unknown. Here we investigate in the CA1 region of the dorsal hippocampus the involvement of UPS-mediated protein degradation in consolidation and reconsolidation of object recognition memory. Animals with infusion cannulae stereotaxically implanted in the CA1 region of the dorsal hippocampus, were exposed to an object recognition task. The UPS inhibitor β-Lactacystin did not affect the consolidation and the reconsolidation of object recognition memory at doses known to affect other forms of memory (inhibitory avoidance, spatial learning in a water maze) while the protein synthesis inhibitor anisomycin impaired the consolidation and the reconsolidation of the object recognition memory. However, β-Lactacystin was able to reverse the impairment caused by anisomycin on the reconsolidation process in the CA1 region of the hippocampus. Therefore, it is possible to postulate a direct link between protein degradation and protein synthesis during the reconsolidation of the object recognition memory. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Age-related differences in emotion recognition ability: a cross-sectional study.

    Science.gov (United States)

    Mill, Aire; Allik, Jüri; Realo, Anu; Valk, Raivo

    2009-10-01

    Experimental studies indicate that recognition of emotions, particularly negative emotions, decreases with age. However, there is no consensus at which age the decrease in emotion recognition begins, how selective this is to negative emotions, and whether this applies to both facial and vocal expression. In the current cross-sectional study, 607 participants ranging in age from 18 to 84 years (mean age = 32.6 +/- 14.9 years) were asked to recognize emotions expressed either facially or vocally. In general, older participants were found to be less accurate at recognizing emotions, with the most distinctive age difference pertaining to a certain group of negative emotions. Both modalities revealed an age-related decline in the recognition of sadness and -- to a lesser degree -- anger, starting at about 30 years of age. Although age-related differences in the recognition of expression of emotion were not mediated by personality traits, 2 of the Big 5 traits, openness and conscientiousness, made an independent contribution to emotion-recognition performance. Implications of age-related differences in facial and vocal emotion expression and early onset of the selective decrease in emotion recognition are discussed in terms of previous findings and relevant theoretical models.

  5. The struggle for recognition online

    DEFF Research Database (Denmark)

    Christensen, Lars Holmgaard

    As a result of the democratization of media technologies new interactive media has opened up for alternative ways for people to express themselves in mediated spaces. It is an interactive space recognized by its cut and paste culture, where trust and ontological security emerges out of ‘folksonom...

  6. Exemplar Based Recognition of Visual Shapes

    DEFF Research Database (Denmark)

    Olsen, Søren I.

    2005-01-01

    This paper presents an approach of visual shape recognition based on exemplars of attributed keypoints. Training is performed by storing exemplars of keypoints detected in labeled training images. Recognition is made by keypoint matching and voting according to the labels for the matched keypoint....... The matching is insensitive to rotations, limited scalings and small deformations. The recognition is robust to noise, background clutter and partial occlusion. Recognition is possible from few training images and improve with the number of training images.......This paper presents an approach of visual shape recognition based on exemplars of attributed keypoints. Training is performed by storing exemplars of keypoints detected in labeled training images. Recognition is made by keypoint matching and voting according to the labels for the matched keypoints...

  7. Document recognition serving people with disabilities

    Science.gov (United States)

    Fruchterman, James R.

    2007-01-01

    Document recognition advances have improved the lives of people with print disabilities, by providing accessible documents. This invited paper provides perspectives on the author's career progression from document recognition professional to social entrepreneur applying this technology to help people with disabilities. Starting with initial thoughts about optical character recognition in college, it continues with the creation of accurate omnifont character recognition that did not require training. It was difficult to make a reading machine for the blind in a commercial setting, which led to the creation of a nonprofit social enterprise to deliver these devices around the world. This network of people with disabilities scanning books drove the creation of Bookshare.org, an online library of scanned books. Looking forward, the needs for improved document recognition technology to further lower the barriers to reading are discussed. Document recognition professionals should be proud of the positive impact their work has had on some of society's most disadvantaged communities.

  8. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

    Science.gov (United States)

    Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

    2015-10-27

    The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

  9. System of breast cancer recognition

    International Nuclear Information System (INIS)

    Rozhkova, N.I.

    1984-01-01

    The paper is concerned with the resUlts of the multimodality system of breast cancer recognition using methods, of clinical X-ray and cytological examinations. Altogether 1671 women were examined; breast cancer was detected in 165. Stage 1 was detected in 63 patients, Stage 2 in 34, Stage 3 in 34, and Stage 4 in 8. In 7% of the cases, tumors were inpalpable and could be detected by X-ray only. In 9.9% of the cases, the multicentric nature of tumor growth was established. In 71% tumors had a mixed histological structure. The system of breast cancer recognition provided for accurate diagnosis in 98% of the cases making it possible to avoid surgical intervention in 38%. Good diagnostic results are possible under conditions of a special mammology unit where a roentgenologist working in a close contact with surgeonns working in a close contact with surgeos and morphologists, performs the first stages of diagnosis beginning from clinical examination up to special methods that require X-ray control (paracentesis, ductography, pneumocystography, preoperative marking of the breast and marking of the remote sectors of the breast)

  10. Longitudinal study of fingerprint recognition.

    Science.gov (United States)

    Yoon, Soweon; Jain, Anil K

    2015-07-14

    Human identification by fingerprints is based on the fundamental premise that ridge patterns from distinct fingers are different (uniqueness) and a fingerprint pattern does not change over time (persistence). Although the uniqueness of fingerprints has been investigated by developing statistical models to estimate the probability of error in comparing two random samples of fingerprints, the persistence of fingerprints has remained a general belief based on only a few case studies. In this study, fingerprint match (similarity) scores are analyzed by multilevel statistical models with covariates such as time interval between two fingerprints in comparison, subject's age, and fingerprint image quality. Longitudinal fingerprint records of 15,597 subjects are sampled from an operational fingerprint database such that each individual has at least five 10-print records over a minimum time span of 5 y. In regard to the persistence of fingerprints, the longitudinal analysis on a single (right index) finger demonstrates that (i) genuine match scores tend to significantly decrease when time interval between two fingerprints in comparison increases, whereas the change in impostor match scores is negligible; and (ii) fingerprint recognition accuracy at operational settings, nevertheless, tends to be stable as the time interval increases up to 12 y, the maximum time span in the dataset. However, the uncertainty of temporal stability of fingerprint recognition accuracy becomes substantially large if either of the two fingerprints being compared is of poor quality. The conclusions drawn from 10-finger fusion analysis coincide with the conclusions from single-finger analysis.

  11. Ordinal measures for iris recognition.

    Science.gov (United States)

    Sun, Zhenan; Tan, Tieniu

    2009-12-01

    Images of a human iris contain rich texture information useful for identity authentication. A key and still open issue in iris recognition is how best to represent such textural information using a compact set of features (iris features). In this paper, we propose using ordinal measures for iris feature representation with the objective of characterizing qualitative relationships between iris regions rather than precise measurements of iris image structures. Such a representation may lose some image-specific information, but it achieves a good trade-off between distinctiveness and robustness. We show that ordinal measures are intrinsic features of iris patterns and largely invariant to illumination changes. Moreover, compactness and low computational complexity of ordinal measures enable highly efficient iris recognition. Ordinal measures are a general concept useful for image analysis and many variants can be derived for ordinal feature extraction. In this paper, we develop multilobe differential filters to compute ordinal measures with flexible intralobe and interlobe parameters such as location, scale, orientation, and distance. Experimental results on three public iris image databases demonstrate the effectiveness of the proposed ordinal feature models.

  12. Dynamic Features for Iris Recognition.

    Science.gov (United States)

    da Costa, R M; Gonzaga, A

    2012-08-01

    The human eye is sensitive to visible light. Increasing illumination on the eye causes the pupil of the eye to contract, while decreasing illumination causes the pupil to dilate. Visible light causes specular reflections inside the iris ring. On the other hand, the human retina is less sensitive to near infra-red (NIR) radiation in the wavelength range from 800 nm to 1400 nm, but iris detail can still be imaged with NIR illumination. In order to measure the dynamic movement of the human pupil and iris while keeping the light-induced reflexes from affecting the quality of the digitalized image, this paper describes a device based on the consensual reflex. This biological phenomenon contracts and dilates the two pupils synchronously when illuminating one of the eyes by visible light. In this paper, we propose to capture images of the pupil of one eye using NIR illumination while illuminating the other eye using a visible-light pulse. This new approach extracts iris features called "dynamic features (DFs)." This innovative methodology proposes the extraction of information about the way the human eye reacts to light, and to use such information for biometric recognition purposes. The results demonstrate that these features are discriminating features, and, even using the Euclidean distance measure, an average accuracy of recognition of 99.1% was obtained. The proposed methodology has the potential to be "fraud-proof," because these DFs can only be extracted from living irises.

  13. Chiral recognition in separation science: an overview.

    Science.gov (United States)

    Scriba, Gerhard K E

    2013-01-01

    Chiral recognition phenomena play an important role in nature as well as analytical separation sciences. In separation sciences such as chromatography and capillary electrophoresis, enantiospecific interactions between the enantiomers of an analyte and the chiral selector are required in order to observe enantioseparations. Due to the large structural variety of chiral selectors applied, different mechanisms and structural features contribute to the chiral recognition process. This chapter briefly illustrates the current models of the enantiospecific recognition on the structural basics of various chiral selectors.

  14. Employee Recognition and Performance: A Field Experiment

    OpenAIRE

    Bradler, Christiane; Dur, Robert; Neckermann, Susanne; Non, Arjan

    2014-01-01

    This discussion paper led to a publication in 'Management Science' . This paper reports the results from a controlled field experiment designed to investigate the causal effect of unannounced, public recognition on employee performance. We hired more than 300 employees to work on a three-hour data-entry task. In a random sample of work groups, workers unexpectedly received recognition after two hours of work. We find that recognition increases subsequent performance substantially, and particu...

  15. Artificial Neural Network Based Optical Character Recognition

    OpenAIRE

    Vivek Shrivastava; Navdeep Sharma

    2012-01-01

    Optical Character Recognition deals in recognition and classification of characters from an image. For the recognition to be accurate, certain topological and geometrical properties are calculated, based on which a character is classified and recognized. Also, the Human psychology perceives characters by its overall shape and features such as strokes, curves, protrusions, enclosures etc. These properties, also called Features are extracted from the image by means of spatial pixel-...

  16. Mathematical symbol hypothesis recognition with rejection option

    OpenAIRE

    Julca-Aguilar , Frank; Hirata , Nina ,; Viard-Gaudin , Christian; Mouchère , Harold; Medjkoune , Sofiane

    2014-01-01

    International audience; In the context of handwritten mathematical expressions recognition, a first step consist on grouping strokes (segmentation) to form symbol hypotheses: groups of strokes that might represent a symbol. Then, the symbol recognition step needs to cope with the identification of wrong segmented symbols (false hypotheses). However, previous works on symbol recognition consider only correctly segmented symbols. In this work, we focus on the problem of mathematical symbol reco...

  17. A Bayesian classifier for symbol recognition

    OpenAIRE

    Barrat , Sabine; Tabbone , Salvatore; Nourrissier , Patrick

    2007-01-01

    URL : http://www.buyans.com/POL/UploadedFile/134_9977.pdf; International audience; We present in this paper an original adaptation of Bayesian networks to symbol recognition problem. More precisely, a descriptor combination method, which enables to improve significantly the recognition rate compared to the recognition rates obtained by each descriptor, is presented. In this perspective, we use a simple Bayesian classifier, called naive Bayes. In fact, probabilistic graphical models, more spec...

  18. Object feature extraction and recognition model

    International Nuclear Information System (INIS)

    Wan Min; Xiang Rujian; Wan Yongxing

    2001-01-01

    The characteristics of objects, especially flying objects, are analyzed, which include characteristics of spectrum, image and motion. Feature extraction is also achieved. To improve the speed of object recognition, a feature database is used to simplify the data in the source database. The feature vs. object relationship maps are stored in the feature database. An object recognition model based on the feature database is presented, and the way to achieve object recognition is also explained

  19. MEMBRAIN NEURAL NETWORK FOR VISUAL PATTERN RECOGNITION

    Directory of Open Access Journals (Sweden)

    Artur Popko

    2013-06-01

    Full Text Available Recognition of visual patterns is one of significant applications of Artificial Neural Networks, which partially emulate human thinking in the domain of artificial intelligence. In the paper, a simplified neural approach to recognition of visual patterns is portrayed and discussed. This paper is dedicated for investigators in visual patterns recognition, Artificial Neural Networking and related disciplines. The document describes also MemBrain application environment as a powerful and easy to use neural networks’ editor and simulator supporting ANN.

  20. Dynamic Programming Algorithms in Speech Recognition

    Directory of Open Access Journals (Sweden)

    Titus Felix FURTUNA

    2008-01-01

    Full Text Available In a system of speech recognition containing words, the recognition requires the comparison between the entry signal of the word and the various words of the dictionary. The problem can be solved efficiently by a dynamic comparison algorithm whose goal is to put in optimal correspondence the temporal scales of the two words. An algorithm of this type is Dynamic Time Warping. This paper presents two alternatives for implementation of the algorithm designed for recognition of the isolated words.

  1. SURVEY OF BIOMETRIC SYSTEMS USING IRIS RECOGNITION

    OpenAIRE

    S.PON SANGEETHA; DR.M.KARNAN

    2014-01-01

    The security plays an important role in any type of organization in today’s life. Iris recognition is one of the leading automatic biometric systems in the area of security which is used to identify the individual person. Biometric systems include fingerprints, facial features, voice recognition, hand geometry, handwriting, the eye retina and the most secured one presented in this paper, the iris recognition. Biometric systems has become very famous in security systems because it is not possi...

  2. Context reinstatement in recognition: memory and beyond

    OpenAIRE

    Hanczakowski, M; Zawadzka, K; Coote, L

    2014-01-01

    Context effects in recognition tests are twofold. First, presenting familiar contexts at a test leads to an attribution of context familiarity to a recognition probe, which has been dubbed ‘context-dependent recognition’. Second, reinstating the exact study context for a particular target in a recognition test cues recollection of an item-context association, resulting in ‘context-dependent discrimination’. Here we investigated how these two context effects are expressed in metacognitive moni...

  3. Pedestrian recognition using automotive radar sensors

    OpenAIRE

    A. Bartsch; F. Fitzek; R. H. Rasshofer

    2012-01-01

    The application of modern series production automotive radar sensors to pedestrian recognition is an important topic in research on future driver assistance systems. The aim of this paper is to understand the potential and limits of such sensors in pedestrian recognition. This knowledge could be used to develop next generation radar sensors with improved pedestrian recognition capabilities. A new raw radar data signal processing algorithm is proposed that allows deep insight...

  4. Placental Trophoblast Responses to Porphyromonas gingivalis Mediated by Toll-like Receptor-2 and -4

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2013-09-01

    Full Text Available Trophoblast participates in preventing allorecognition and controlling pathogens that compromise fetal wellbeing. Toll-like receptors recognize conserved sequences on the pathogens surface and trigger effector cell functions. Porphyromonas gingivalis is thought to spread to the umbilical cord and cause fetal growth restriction. Objective: To characterize expression and function of TLR-2 and TLR-4 in trophoblast cells from Porphyromonas gingivalisinfected pregnant rats. Methods: Live Porphyromonas gingivalis were challenged into the maxillary first molar subgingival sulcus of female rats before and/or during pregnancy and sacrified on gestational day (GD 14 and 20. Porphyromonas gingivalis was detected by API-ZYM system in the maternal blood of the retro-orbital venous plexus and the umbilical cord. TLR-2 and TLR-4 expressions in trophoblast cells was detected by immunohistochemistry. Results: Porphyromonas gingivalis was first detected in the maternal blood and finally spread to the umbilical cord. Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell in treated groups had significantly higher expression of TLR-2 and TLR-4 than control group (p<0.05. Conclusion: Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell are able to recognize Porphyromonas gingivalis through TLR-2 and TLR-4 expression. The ligation of TLR-2 and TLR-4 promoted cytokine production and induced trophoblast cell death. These findings strengthen links between periodontal disease and fetal growth restriction.DOI: 10.14693/jdi.v20i2.150

  5. End-Stop Exemplar Based Recognition

    DEFF Research Database (Denmark)

    Olsen, Søren I.

    2003-01-01

    An approach to exemplar based recognition of visual shapes is presented. The shape information is described by attributed interest points (keys) detected by an end-stop operator. The attributes describe the statistics of lines and edges local to the interest point, the position of neighboring int...... interest points, and (in the training phase) a list of recognition names. Recognition is made by a simple voting procedure. Preliminary experiments indicate that the recognition is robust to noise, small deformations, background clutter and partial occlusion....

  6. Repetition and lag effects in movement recognition.

    Science.gov (United States)

    Hall, C R; Buckolz, E

    1982-03-01

    Whether repetition and lag improve the recognition of movement patterns was investigated. Recognition memory was tested for one repetition, two-repetitions massed, and two-repetitions distributed with movement patterns at lags of 3, 5, 7, and 13. Recognition performance was examined both immediately afterwards and following a 48 hour delay. Both repetition and lag effects failed to be demonstrated, providing some support for the claim that memory is unaffected by repetition at a constant level of processing (Craik & Lockhart, 1972). There was, as expected, a significant decrease in recognition memory following the retention interval, but this appeared unrelated to repetition or lag.

  7. Man machine interface based on speech recognition

    International Nuclear Information System (INIS)

    Jorge, Carlos A.F.; Aghina, Mauricio A.C.; Mol, Antonio C.A.; Pereira, Claudio M.N.A.

    2007-01-01

    This work reports the development of a Man Machine Interface based on speech recognition. The system must recognize spoken commands, and execute the desired tasks, without manual interventions of operators. The range of applications goes from the execution of commands in an industrial plant's control room, to navigation and interaction in virtual environments. Results are reported for isolated word recognition, the isolated words corresponding to the spoken commands. For the pre-processing stage, relevant parameters are extracted from the speech signals, using the cepstral analysis technique, that are used for isolated word recognition, and corresponds to the inputs of an artificial neural network, that performs recognition tasks. (author)

  8. Fusing Facial Features for Face Recognition

    Directory of Open Access Journals (Sweden)

    Jamal Ahmad Dargham

    2012-06-01

    Full Text Available Face recognition is an important biometric method because of its potential applications in many fields, such as access control, surveillance, and human-computer interaction. In this paper, a face recognition system that fuses the outputs of three face recognition systems based on Gabor jets is presented. The first system uses the magnitude, the second uses the phase, and the third uses the phase-weighted magnitude of the jets. The jets are generated from facial landmarks selected using three selection methods. It was found out that fusing the facial features gives better recognition rate than either facial feature used individually regardless of the landmark selection method.

  9. Face Recognition and Tracking in Videos

    Directory of Open Access Journals (Sweden)

    Swapnil Vitthal Tathe

    2017-07-01

    Full Text Available Advancement in computer vision technology and availability of video capturing devices such as surveillance cameras has evoked new video processing applications. The research in video face recognition is mostly biased towards law enforcement applications. Applications involves human recognition based on face and iris, human computer interaction, behavior analysis, video surveillance etc. This paper presents face tracking framework that is capable of face detection using Haar features, recognition using Gabor feature extraction, matching using correlation score and tracking using Kalman filter. The method has good recognition rate for real-life videos and robust performance to changes due to illumination, environmental factors, scale, pose and orientations.

  10. System for automatic crate recognition

    Directory of Open Access Journals (Sweden)

    Radovan Kukla

    2012-01-01

    Full Text Available This contribution describes usage of computer vision and artificial intelligence methods for application. The method solves abuse of reverse vending machine. This topic has been solved as innovation voucher for the South Moravian Region. It was developed by Mendel university in Brno (Department of informatics – Faculty of Business and Economics and Department of Agricultural, Food and Environmental Engineering – Faculty of Agronomy together with the Czech subsidiary of Tomra. The project is focused on a possibility of integration industrial cameras and computers to process recognition of crates in the verse vending machine. The aim was the effective security system that will be able to save hundreds-thousands financial loss. As suitable development and runtime platform there was chosen product ControlWeb and VisionLab developed by Moravian Instruments Inc.

  11. Recognition of Handwriting from Electromyography

    Science.gov (United States)

    Linderman, Michael; Lebedev, Mikhail A.; Erlichman, Joseph S.

    2009-01-01

    Ha