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Sample records for distinguish monocyte-derived fibrocytes

  1. Role of neoplastic monocyte-derived fibrocytes in primary myelofibrosis.

    PubMed

    Verstovsek, Srdan; Manshouri, Taghi; Pilling, Darrell; Bueso-Ramos, Carlos E; Newberry, Kate J; Prijic, Sanja; Knez, Liza; Bozinovic, Ksenija; Harris, David M; Spaeth, Erika L; Post, Sean M; Multani, Asha S; Rampal, Raajit K; Ahn, Jihae; Levine, Ross L; Creighton, Chad J; Kantarjian, Hagop M; Estrov, Zeev

    2016-08-22

    Primary myelofibrosis (PMF) is a fatal neoplastic disease characterized by clonal myeloproliferation and progressive bone marrow (BM) fibrosis thought to be induced by mesenchymal stromal cells stimulated by overproduced growth factors. However, tissue fibrosis in other diseases is associated with monocyte-derived fibrocytes. Therefore, we sought to determine whether fibrocytes play a role in the induction of BM fibrosis in PMF. In this study, we show that BM from patients with PMF harbors an abundance of clonal, neoplastic collagen- and fibronectin-producing fibrocytes. Immunodeficient mice transplanted with myelofibrosis patients' BM cells developed a lethal myelofibrosis-like phenotype. Treatment of the xenograft mice with the fibrocyte inhibitor serum amyloid P (SAP; pentraxin-2) significantly prolonged survival and slowed the development of BM fibrosis. Collectively, our data suggest that neoplastic fibrocytes contribute to the induction of BM fibrosis in PMF, and inhibiting fibrocyte differentiation with SAP may interfere with this process. PMID:27481130

  2. Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina

    PubMed Central

    O’Koren, E. G.; Mathew, R.; Saban, D. R.

    2016-01-01

    The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap of microglia with monocyte-derived macrophages. The latter are differentiated from recruited monocytes in neuroinflammation, including retina. Here we demonstrate the use of fate mapping wherein microglia and monocyte-derived cells are endogenously labeled with different fluorescent reporters. Combining this method with 12-color flow cytometry, we show that these two populations are definitively distinguishable by phenotype in retina. We prove that retinal microglia have a unique CD45lo CD11clo F4/80lo I-A/I-E− signature, conserved in the steady state and during retinal injury. The latter was observed in the widely used light-induced retinal degeneration model and corroborated in other models, including whole-body irradiation/bone-marrow transplantation. The literature contains conflicting observations about whether microglia, including in the retina, increase expression of these markers in neuroinflammation. We show that monocyte-derived macrophages have elevated expression of these surface markers, not microglia. Our resolution of such phenotypic differences may serve as a robust way to help characterize isolated roles of these cells in retinal neuroinflammation and possibly elsewhere in CNS. PMID:26856416

  3. Fate mapping reveals that microglia and recruited monocyte-derived macrophages are definitively distinguishable by phenotype in the retina.

    PubMed

    O'Koren, E G; Mathew, R; Saban, D R

    2016-01-01

    The recent paradigm shift that microglia are yolk sac-derived, not hematopoietic-derived, is reshaping our knowledge about the isolated role of microglia in CNS diseases, including degenerative conditions of the retina. However, unraveling microglial-specific functions has been hindered by phenotypic overlap of microglia with monocyte-derived macrophages. The latter are differentiated from recruited monocytes in neuroinflammation, including retina. Here we demonstrate the use of fate mapping wherein microglia and monocyte-derived cells are endogenously labeled with different fluorescent reporters. Combining this method with 12-color flow cytometry, we show that these two populations are definitively distinguishable by phenotype in retina. We prove that retinal microglia have a unique CD45(lo) CD11c(lo) F4/80(lo) I-A/I-E(-) signature, conserved in the steady state and during retinal injury. The latter was observed in the widely used light-induced retinal degeneration model and corroborated in other models, including whole-body irradiation/bone-marrow transplantation. The literature contains conflicting observations about whether microglia, including in the retina, increase expression of these markers in neuroinflammation. We show that monocyte-derived macrophages have elevated expression of these surface markers, not microglia. Our resolution of such phenotypic differences may serve as a robust way to help characterize isolated roles of these cells in retinal neuroinflammation and possibly elsewhere in CNS. PMID:26856416

  4. TNF-α–stimulated fibroblasts secrete lumican to promote fibrocyte differentiation

    PubMed Central

    Pilling, Darrell; Vakil, Varsha; Cox, Nehemiah; Gomer, Richard H.

    2015-01-01

    In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis. PMID:26351669

  5. TNF-α-stimulated fibroblasts secrete lumican to promote fibrocyte differentiation.

    PubMed

    Pilling, Darrell; Vakil, Varsha; Cox, Nehemiah; Gomer, Richard H

    2015-09-22

    In healing wounds and fibrotic lesions, fibroblasts and monocyte-derived fibroblast-like cells called fibrocytes help to form scar tissue. Although fibrocytes promote collagen production by fibroblasts, little is known about signaling from fibroblasts to fibrocytes. In this report, we show that fibroblasts stimulated with the fibrocyte-secreted inflammatory signal tumor necrosis factor-α secrete the small leucine-rich proteoglycan lumican, and that lumican, but not the related proteoglycan decorin, promotes human fibrocyte differentiation. Lumican competes with the serum fibrocyte differentiation inhibitor serum amyloid P, but dominates over the fibroblast-secreted fibrocyte inhibitor Slit2. Lumican acts directly on monocytes, and unlike other factors that affect fibrocyte differentiation, lumican has no detectable effect on macrophage differentiation or polarization. α2β1, αMβ2, and αXβ2 integrins are needed for lumican-induced fibrocyte differentiation. In lung tissue from pulmonary fibrosis patients with relatively normal lung function, lumican is present at low levels throughout the tissue, whereas patients with advanced disease have pronounced lumican expression in the fibrotic lesions. These data may explain why fibrocytes are increased in fibrotic tissues, suggest that the levels of lumican in tissues may have a significant effect on the decision of monocytes to differentiate into fibrocytes, and indicate that modulating lumican signaling may be useful as a therapeutic for fibrosis. PMID:26351669

  6. Monocyte Heterogeneity: Consequences for Monocyte-Derived Immune Cells

    PubMed Central

    de Vries, Teun J.; Everts, Vincent

    2016-01-01

    Blood monocytes are precursors of dendritic cells, macrophages, and osteoclasts. They are a heterogeneous cell population with differences in size, phenotype, and function. Although monocytes maintain several tissue-specific populations of immune cells in homeostasis, their contribution to populations of dendritic cells, macrophages, and osteoclasts is significantly increased in inflammation. Identification of a growing number of functionally different subsets of cells within populations of monocyte-derived immune cells has recently put monocyte heterogeneity into sharp focus. Here, we summarize recent findings in monocyte heterogeneity and their differentiation into dendritic cells, macrophages, and osteoclasts. We also discuss these advances in the context of the formation of functionally different monocyte-derived subsets of dendritic cells, macrophages, and osteoclasts. PMID:27478854

  7. Antigen Presentation by Monocytes and Monocyte-derived Cells

    PubMed Central

    Randolph, Gwendalyn J.; Jakubzick, Claudia; Qu, Chunfeng

    2008-01-01

    Summary Monocytes are circulating mononuclear phagocytes with a fundamental capacity to differentiate into macrophages. This differentiation can, in the presence of the right environmental cues, be re-directed instead to dendritic cells (DCs). Recent advances have been made in understanding the role of monocytes and their derivatives in presenting antigen to drive immune responses, and we review this topic herein. We briefly discuss the heterogeneity of monocytes in the blood and subsequently raise the possibility that one of the major monocyte phenotypes in the blood corresponds with a population of “blood DCs” previously proposed to drive T-independent antibody reactions in the spleen. Then we evaluate the role of monocytes in T-dependent immunity, considering their role in acquiring antigens for presentation prior to exiting the bloodstream and their ability to differentiate into macrophages versus antigen-presenting DCs. Finally, we review recent literature on the role of monocyte-derived cells in cross-presentation and discuss the possibility that monocyte-derived cells participate critically in processing antigen for cross-priming, even if they do not present that antigen to T cells themselves. PMID:18160272

  8. Differential Responses Between Monocytes and Monocyte-Derived Macrophages for Lipopolysaccharide Stimulation of Calves

    PubMed Central

    Guo, Yijie; Zhao, Guoqi; Tanaka, Sachi; Yamaguchi, Takahiro

    2009-01-01

    In this experiment Toll-like receptor expression pattern in monocytes and monocyte-derived macrophages by lipopolysaccharide (LPS) stimulation was examined. Jugular venous blood was collected from four Japanese calves, and the peripheral blood mononuclear cells (PBMCs) were isolated. The cells were directly used for collecting monocytes by magnetic cell sorting or cultured for 7 days to collect monocyte-derived macrophages in Repcell. Then we analyzed the mRNA expression pattern of TLRs and cytokines in monocytes and monocyte-derived macrophages after LPS stimulation for 24 h. LPS stimulation of both monocytes and monocyte-derived macrophages resulted in an increase in the levels of mRNA transcripts for TNF-α, IL-6 and IL-8. Moreover, TNF-α and IL-6 mRNA expressions were significantly augmented by LPS stimulation in monocyte-derived macrophages. TLRs mRNA expressions were unchanged after LPS stimulation of monocytes, while TLRs mRNA expressions in monocyte-derived macrophages were complicated. TLR1, 3, 5, 8 and 10 were significantly decreased after LPS stimulation and there were no differences in the mRNA expressions of TLR2, 4, 6 and 7 between the groups of control and LPS stimulation. Besides, no expression of TLR9 was found. As antigen presenting cells, monocytes and monocyte-derived macrophages respond differently to LPS, so they may have different functions in the innate immune system. PMID:19567206

  9. Fibrocytes: emerging effector cells in chronic inflammation

    PubMed Central

    Reilkoff, Ronald A.; Bucala, Richard; Herzog, Erica L.

    2013-01-01

    Fibrocytes are mesenchymal cells that arise from monocyte precursors. They are present in injured organs and have both the inflammatory features of macrophages and the tissue remodelling properties of fibroblasts. Chronic inflammatory stimuli mediate the differentiation, trafficking and accumulation of these cells in fibrosing conditions associated with autoimmunity, cardiovascular disease and asthma. This Opinion article discusses the immunological mediators controlling fibrocyte differentiation and recruitment, describes the association of fibrocytes with chronic inflammatory diseases and compares the potential roles of fibrocytes in these disorders with those of macrophages and fibroblasts. It is hoped that this information prompts new opportunities for the study of these unique cells. PMID:21597472

  10. Inhibition of the Differentiation of Monocyte-Derived Dendritic Cells by Human Gingival Fibroblasts

    PubMed Central

    Séguier, Sylvie; Tartour, Eric; Guérin, Coralie; Couty, Ludovic; Lemitre, Mathilde; Lallement, Laetitia; Folliguet, Marysette; Naderi, Samah El; Terme, Magali; Badoual, Cécile; Lafont, Antoine; Coulomb, Bernard

    2013-01-01

    We investigated whether gingival fibroblasts (GFs) can modulate the differentiation and/or maturation of monocyte-derived dendritic cells (DCs) and analyzed soluble factors that may be involved in this immune modulation. Experiments were performed using human monocytes in co-culture with human GFs in Transwell® chambers or using monocyte cultures treated with conditioned media (CM) from GFs of four donors. The four CM and supernatants from cell culture were assayed by ELISA for cytokines involved in the differentiation of dendritic cells, such as IL-6, VEGF, TGFβ1, IL-13 and IL-10. The maturation of monocyte-derived DCs induced by LPS in presence of CM was also studied. Cell surface phenotype markers were analyzed by flow cytometry. In co-cultures, GFs inhibited the differentiation of monocyte-derived DCs and the strength of this blockade correlated with the GF/monocyte ratio. Conditioned media from GFs showed similar effects, suggesting the involvement of soluble factors produced by GFs. This inhibition was associated with a lower stimulatory activity in MLR of DCs generated with GFs or its CM. Neutralizing antibodies against IL-6 and VEGF significantly (P<0.05) inhibited the inhibitory effect of CM on the differentiation of monocytes-derived DCs and in a dose dependent manner. Our data suggest that IL-6 is the main factor responsible for the inhibition of DCs differentiation mediated by GFs but that VEGF is also involved and constitutes an additional mechanism. PMID:23936476

  11. Non-identical twins - microglia and monocyte-derived macrophages in acute injury and autoimmune inflammation.

    PubMed

    Jung, Steffen; Schwartz, Michal

    2012-01-01

    The brain has been commonly regarded as a "tissue behind walls." Appearance of immune cells in the brain has been taken as a sign of pathology. Moreover, since infiltrating monocyte-derived macrophages and activated resident microglia were indistinguishable by conventional means, both populations were considered together as inflammatory cells that should be mitigated. Yet, because the microglia permanently reside in the brain, attributing to them negative properties evoked an ongoing debate; why cells that are supposed to be the brain guardians acquire only destructive potential? Studies over the last two decades in the immune arena in general, and in the context of central nervous system pathology in particular, have resulted in a paradigm shift toward a more balanced appreciation of the contributions of immune cells in the context of brain maintenance and repair, and toward the recognition of distinct roles of resident microglia and infiltrating monocyte-derived macrophages. PMID:22566968

  12. The effect of short-chain fatty acids on human monocyte-derived dendritic cells.

    PubMed

    Nastasi, Claudia; Candela, Marco; Bonefeld, Charlotte Menné; Geisler, Carsten; Hansen, Morten; Krejsgaard, Thorbjørn; Biagi, Elena; Andersen, Mads Hald; Brigidi, Patrizia; Ødum, Niels; Litman, Thomas; Woetmann, Anders

    2015-01-01

    The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions. PMID:26541096

  13. Differential Activation of Infiltrating Monocyte-Derived Cells After Mild and Severe Traumatic Brain Injury.

    PubMed

    Trahanas, Diane M; Cuda, Carla M; Perlman, Harris; Schwulst, Steven J

    2015-03-01

    Microglia are the resident innate immune cells of the brain. Although embryologically and functionally distinct, they are morphologically similar to peripheral monocyte-derived cells, resulting in a poor ability to discriminate between the two cell types. The purpose of this study was to develop a rapid and reliable method to simultaneously characterize, quantify, and discriminate between whole populations of myeloid cells from the brain in a murine model of traumatic brain injury. Male C57BL/6 mice underwent traumatic brain injury (n = 16) or sham injury (n = 14). Brains were harvested at 24 h after injury. Multiparameter flow cytometry and sequential gating analysis were performed, allowing for discrimination between microglia and infiltrating leukocytes as well as for the characterization and quantification of individual subtypes within the infiltrating population. The proportion of infiltrating leukocytes within the brain increased with the severity of injury, and the predominant cell types within the infiltrating population were monocyte derived (P = 0.01). In addition, the severity of injury altered the overall makeup of the infiltrating monocyte-derived cells. In conclusion, we describe a flow cytometry-based technique for gross discrimination between infiltrating leukocytes and microglia as well as the ability to simultaneously characterize and quantify individual myeloid subtypes and their maturation states within these populations. PMID:26091024

  14. Differential activation of infiltrating monocyte-derived cells after mild and severe traumatic brain injury

    PubMed Central

    Trahanas, Diane M.; Cuda, Carla M.; Perlman, Harris; Schwulst, Steven J.

    2014-01-01

    Microglia are the resident innate immune cells of the brain. Although embryologically and functionally distinct, they are morphologically similar to peripheral monocyte-derived cells resulting in a poor ability to discriminate between the two cell types. The purpose of this study was to develop a rapid and reliable method to simultaneously characterize, quantify, and discriminate between whole populations of myeloid cells from the brain in a murine model of traumatic brain injury (TBI). Male C57BL/6 mice underwent TBI (n=16) or sham injury (n=14). Brains were harvested at 24 hours post injury. Multiparameter flow cytometry and sequential gating analysis was performed allowing for discrimination between microglia and infiltrating leukocytes as well as for the characterization and quantification of individual subtypes within the infiltrating population. The proportion of infiltrating leukocytes within the brain increased with the severity of injury and the predominate cell types within the infiltrating population were monocyte-derived (p=0.01). Additionally, the severity of injury altered the overall makeup of the infiltrating monocyte-derived cells. In conclusion, we describe a flow cytometry based technique for gross discrimination between infiltrating leukocytes and microglia as well as the ability to simultaneously characterize and quantify individual myeloid subtypes and their maturation states within these populations. PMID:26091024

  15. Fibrocytes in the Pathogenesis of Chronic Fibrotic Lung Disease

    PubMed Central

    Loomis-King, Hillary; Moore, Bethany B.

    2016-01-01

    Fibrocytes were initially described in 1999 and since that time there has been a growing body of literature to suggest their importance in a number of chronic lung diseases. It is now well established that fibrocytes derive from the bone marrow and circulate within the peripheral blood. However, when injury occurs, fibrocytes can travel to the site of damage via chemokine-mediated recruitment. Recent studies suggest that fibrocyte numbers increase within the lung or circulation during numerous disease processes. Although fibrocytes readily differentiate into fibroblasts in vitro, whether they do so in vivo is still unknown. The variety of pro-fibrotic mediators that are secreted by fibrocytes makes it likely that they act via paracrine functions to influence the behavior of resident lung cells. This review summarizes recent insights regarding fibrocytes in asthma, scleroderma and IPF.

  16. Altered monocyte and fibrocyte phenotype and function in scleroderma interstitial lung disease: reversal by caveolin-1 scaffolding domain peptide.

    PubMed

    Tourkina, Elena; Bonner, Michael; Oates, James; Hofbauer, Ann; Richard, Mathieu; Znoyko, Sergei; Visconti, Richard P; Zhang, Jing; Hatfield, Corey M; Silver, Richard M; Hoffman, Stanley

    2011-01-01

    Interstitial lung disease (ILD) is a major cause of morbidity and mortality in scleroderma (systemic sclerosis, or SSc). Fibrocytes are a monocyte-derived cell population implicated in the pathogenesis of fibrosing disorders. Given the recently recognized importance of caveolin-1 in regulating function and signaling in SSc monocytes, in the present study we examined the role of caveolin-1 in the migration and/or trafficking and phenotype of monocytes and fibrocytes in fibrotic lung disease in human patients and an animal model. These studies fill a gap in our understanding of how monocytes and fibrocytes contribute to SSc-ILD pathology. We found that C-X-C chemokine receptor type 4-positive (CXCR4+)/collagen I-positive (ColI+), CD34+/ColI+ and CD45+/ColI+ cells are present in SSc-ILD lungs, but not in control lungs, with CXCR4+ cells being most prevalent. Expression of CXCR4 and its ligand, stromal cell-derived factor 1 (CXCL12), are also highly upregulated in SSc-ILD lung tissue. SSc monocytes, which lack caveolin-1 and therefore overexpress CXCR4, exhibit almost sevenfold increased migration toward CXCL12 compared to control monocytes. Restoration of caveolin-1 function by administering the caveolin scaffolding domain (CSD) peptide reverses this hypermigration. Similarly, transforming growth factor β-treated normal monocytes lose caveolin-1, overexpress CXCR4 and exhibit 15-fold increased monocyte migration that is CSD peptide-sensitive. SSc monocytes exhibit a different phenotype than normal monocytes, expressing high levels of ColI, CD14 and CD34. Because ColI+/CD14+ cells are prevalent in SSc blood, we looked for such cells in lung tissue and confirmed their presence in SSc-ILD lungs but not in normal lungs. Finally, in the bleomycin model of lung fibrosis, we show that CSD peptide diminishes fibrocyte accumulation in the lungs. Our results suggest that low caveolin-1 in SSc monocytes contributes to ILD via effects on cell migration and phenotype and that the

  17. Fibrocytes are associated with the fibrosis of coronary heart disease.

    PubMed

    Lei, Pu-Ping; Qu, Yong-Qiang; Shuai, Qun; Tao, Si-Ming; Bao, Yu-Xia; Wang, Yu; Wang, Shang-Wen; Wang, Dian-Hua

    2013-01-15

    Fibrocytes contribute significantly to fibrosis in many cardiac diseases. However, it is not clear whether fibrocytes are associated with the fibrosis in coronary heart disease (CHD). The aim of this study was to determine whether fibrocytes are involved in cardiac fibrosis in CHD. We identified the presence of fibrocytes in CHD heart by immunofluorescence and confocal microscopy, examined the collagen volume fraction by Masson's Trichrome staining, and evaluated the correlation between fibrocytes and cardiac fibrosis. In conjunction, we examined the location of CXCL12, a homing factor and specific ligand for CXCR4, by immunohistochemistry. Fibrocytes were identified in 26 out of 27 CHD hearts and in 10 out of 11 normal hearts. Combinations, including CD34/αSMA, CD34/procollagen-I, CD45/αSMA, CXCR4/procollagen-I and CXCR4/αSMA, stained significantly more fibrocytes in CHD hearts as compared with those in normal hearts (p<0.05). There were positive correlations between the collagen volume fraction and the amount of fibrocytes (r=0.558; p=0.003<0.01) and between the number of CXCR4(+) fibrocytes and the CXCL12(+) cells (r=0.741; p=0.000<0.01) in CHD hearts. Based upon these findings, we conclude that fibrocytes, likely recruited through the CXCR4/CXCL12 axis, may contribute to the increase in the fibroblast population in CHD heart. PMID:23177618

  18. Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma-bearing mice.

    PubMed

    Ricard, Clément; Tchoghandjian, Aurélie; Luche, Hervé; Grenot, Pierre; Figarella-Branger, Dominique; Rougon, Geneviève; Malissen, Marie; Debarbieux, Franck

    2016-01-01

    Inflammatory cells, an integral component of tumor evolution, are present in Glioblastomas multiforme (GBM). To address the cellular basis and dynamics of the inflammatory microenvironment in GBM, we established an orthotopic syngenic model by grafting GL261-DsRed cells in immunocompetent transgenic LysM-EGFP//CD11c-EYFP reporter mice. We combined dynamic spectral two-photon imaging with multiparametric cytometry and multicolor immunostaining to characterize spatio-temporal distribution, morphology and activity of microglia and blood-derived infiltrating myeloid cells in live mice. Early stages of tumor development were dominated by microglial EYFP(+) cells invading the tumor, followed by massive recruitment of circulating LysM-EGFP(+) cells. Fluorescent invading cells were conventional XCR1(+) and monocyte-derived dendritic cells distributed in subpopulations of different maturation stages, located in different areas relative to the tumor core. The lethal stage of the disease was characterized by the progressive accumulation of EGFP(+)/EYFP(+) monocyte-derived dendritic cells. This local phenotypic regulation of monocyte subtypes marked a transition in the immune response. PMID:27193333

  19. Human Monocyte-Derived Osteoclasts Are Targeted by Staphylococcal Pore-Forming Toxins and Superantigens.

    PubMed

    Flammier, Sacha; Rasigade, Jean-Philippe; Badiou, Cédric; Henry, Thomas; Vandenesch, François; Laurent, Frédéric; Trouillet-Assant, Sophie

    2016-01-01

    Staphylococcus aureus is the leading cause of bone and joint infections (BJIs). Staphylococcal pathogenesis involves numerous virulence factors including secreted toxins such as pore-forming toxins (PFTs) and superantigens. The role of these toxins on BJI outcome is largely unknown. In particular, few studies have examined how osteoclasts, the bone-resorbing cells, respond to exposure to staphylococcal PFTs and superantigens. We investigated the direct impact of recombinant staphylococcal toxins on human primary mature monocyte-derived osteoclasts, in terms of cytotoxicity and cell activation with cell death and bone resorption assays, using macrophages of the corresponding donors as a reference. Monocyte-derived osteoclasts displayed similar toxin susceptibility profiles compared to macrophages. Specifically, we demonstrated that the Panton-Valentine leukocidin, known as one of the most powerful PFT which lyses myeloid cells after binding to the C5a receptor, was able to induce the death of osteoclasts. The archetypal superantigen TSST-1 was not cytotoxic but enhanced the bone resorption activity of osteoclasts, suggesting a novel mechanism by which superantigen-producing S. aureus can accelerate the destruction of bone tissue during BJI. Altogether, our data indicate that the diverse clinical presentations of BJIs could be related, at least partly, to the toxin profiles of S. aureus isolates involved in these severe infections. PMID:26934588

  20. Phenotypic dynamics of microglial and monocyte-derived cells in glioblastoma-bearing mice

    PubMed Central

    Ricard, Clément; Tchoghandjian, Aurélie; Luche, Hervé; Grenot, Pierre; Figarella-Branger, Dominique; Rougon, Geneviève; Malissen, Marie; Debarbieux, Franck

    2016-01-01

    Inflammatory cells, an integral component of tumor evolution, are present in Glioblastomas multiforme (GBM). To address the cellular basis and dynamics of the inflammatory microenvironment in GBM, we established an orthotopic syngenic model by grafting GL261-DsRed cells in immunocompetent transgenic LysM-EGFP//CD11c-EYFP reporter mice. We combined dynamic spectral two-photon imaging with multiparametric cytometry and multicolor immunostaining to characterize spatio-temporal distribution, morphology and activity of microglia and blood-derived infiltrating myeloid cells in live mice. Early stages of tumor development were dominated by microglial EYFP+ cells invading the tumor, followed by massive recruitment of circulating LysM-EGFP+ cells. Fluorescent invading cells were conventional XCR1+ and monocyte-derived dendritic cells distributed in subpopulations of different maturation stages, located in different areas relative to the tumor core. The lethal stage of the disease was characterized by the progressive accumulation of EGFP+/EYFP+ monocyte-derived dendritic cells. This local phenotypic regulation of monocyte subtypes marked a transition in the immune response. PMID:27193333

  1. Monocyte-derived extracellular Nampt-dependent biosynthesis of NAD(+) protects the heart against pressure overload.

    PubMed

    Yano, Masamichi; Akazawa, Hiroshi; Oka, Toru; Yabumoto, Chizuru; Kudo-Sakamoto, Yoko; Kamo, Takehiro; Shimizu, Yu; Yagi, Hiroki; Naito, Atsuhiko T; Lee, Jong-Kook; Suzuki, Jun-ichi; Sakata, Yasushi; Komuro, Issei

    2015-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) catalyzes the rate-limiting step in the salvage pathway for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and thereby regulates the deacetylase activity of sirtuins. Here we show accommodative regulation of myocardial NAD(+) by monocyte-derived extracellular Nampt (eNampt), which is essential for hemodynamic compensation to pressure overload. Although intracellular Nampt (iNampt) expression was decreased in pressure-overloaded hearts, myocardial NAD(+) concentration and Sirt1 activity were preserved. In contrast, iNampt was up-regulated in spleen and monocytes, and circulating eNampt protein and nicotinamide mononucleotide (NMN), a key precursor of NAD(+), were significantly increased. Pharmacological inhibition of Nampt by FK866 or depletion of monocytes/macrophages by clodronate liposomes disrupted the homeostatic mechanism of myocardial NAD(+) levels and NAD(+)-dependent Sirt1 activity, leading to susceptibility to cardiomyocyte apoptosis and cardiac decompensation in pressure-overloaded mice. These biochemical and hemodynamic defects were prevented by systemic administration of NMN. Our studies uncover a crucial role of monocyte-derived eNampt in myocardial adaptation to pressure overload, and highlight a potential intervention controlling myocardial NAD(+) against heart failure. PMID:26522369

  2. Mycobacterium leprae upregulates IRGM expression in monocytes and monocyte-derived macrophages.

    PubMed

    Yang, Degang; Chen, Jia; Zhang, Linglin; Cha, Zhanshan; Han, Song; Shi, Weiwei; Ding, Ru; Ma, Lan; Xiao, Hong; Shi, Chao; Jing, Zhichun; Song, Ningjing

    2014-08-01

    Leprosy is caused by the infection of Mycobacterium leprae, which evokes a strong inflammatory response and leads to nerve damage. Immunity-related GTPase family M protein (IRGM) plays critical roles in controlling inflammation. The objective of the study was to investigate whether IRGM is involved in the infection of M. leprae. Levels of IRGM were assessed in M. leprae-infected CD4(+) T cells, monocytes, and monocyte-derived macrophages. Data revealed that both protein and mRNA levels of IRGM were increased in monocytes after M. leprae infection. Interestingly, monocyte-derived macrophages showed more prominent IRGM expression with M. leprae infection, whereas the bacteria did not affect IRGM in CD4(+) T cells. Furthermore, we assessed levels of IRGM in CD4(+) T cells and monocytes from 78 leprosy patients and 40 healthy controls, and observed upregulated protein level of IRGM in the monocytes from leprosy patients. Also, IRGM expression was inversely correlated with the severity of the disease. These findings suggested a close involvement of IRGM in M. leprae infection and indicated a potential mechanism of defending M. leprae infection. PMID:24469081

  3. Human Monocyte-Derived Osteoclasts Are Targeted by Staphylococcal Pore-Forming Toxins and Superantigens

    PubMed Central

    Flammier, Sacha; Rasigade, Jean-Philippe; Badiou, Cédric; Henry, Thomas; Vandenesch, François; Laurent, Frédéric; Trouillet-Assant, Sophie

    2016-01-01

    Staphylococcus aureus is the leading cause of bone and joint infections (BJIs). Staphylococcal pathogenesis involves numerous virulence factors including secreted toxins such as pore-forming toxins (PFTs) and superantigens. The role of these toxins on BJI outcome is largely unknown. In particular, few studies have examined how osteoclasts, the bone-resorbing cells, respond to exposure to staphylococcal PFTs and superantigens. We investigated the direct impact of recombinant staphylococcal toxins on human primary mature monocyte-derived osteoclasts, in terms of cytotoxicity and cell activation with cell death and bone resorption assays, using macrophages of the corresponding donors as a reference. Monocyte-derived osteoclasts displayed similar toxin susceptibility profiles compared to macrophages. Specifically, we demonstrated that the Panton-Valentine leukocidin, known as one of the most powerful PFT which lyses myeloid cells after binding to the C5a receptor, was able to induce the death of osteoclasts. The archetypal superantigen TSST-1 was not cytotoxic but enhanced the bone resorption activity of osteoclasts, suggesting a novel mechanism by which superantigen-producing S. aureus can accelerate the destruction of bone tissue during BJI. Altogether, our data indicate that the diverse clinical presentations of BJIs could be related, at least partly, to the toxin profiles of S. aureus isolates involved in these severe infections. PMID:26934588

  4. Uptake of exogenous free cholesterol induces upregulation of tissue factor expression in human monocyte-derived macrophages.

    PubMed Central

    Lesnik, P; Rouis, M; Skarlatos, S; Kruth, H S; Chapman, M J

    1992-01-01

    Lipid-laden macrophages present as foam cells may contribute to the hyperthrombotic state of human atherosclerotic lesions by the production of tissue factor (TF). We investigated the effect of exogenous nonlipoprotein cholesterol on the expression of TF by human monocyte-derived macrophages in culture. Nonlipoprotein cholesterol at 50 micrograms/ml increased TF activity 4-fold; TF induction was dose- and time-dependent. Expression of TF activity was positively correlated with the free cholesterol content of monocyte-derived macrophages, was increased upon inhibition of cholesterol esterification, and reflected de novo synthesis of TF protein. TF expression in cholesterol-loaded macrophages remained sensitive to stimulation (approximately 12-fold) by bacterial lipopolysaccharide, indicating that intracellular free cholesterol and lipopolysaccharide act by distinct mechanisms in inducing TF procoagulant activity. Our results suggest that loading human monocyte-derived macrophages with free cholesterol induces upregulation of TF expression, thereby contributing to thrombus formation at sites of plaque rupture. Images PMID:1438222

  5. Circulating Fibrocytes Are Increased in Neonates with Bronchopulmonary Dysplasia

    PubMed Central

    Li, Chun; Li, Xiaoyu; Deng, Chun; Guo, Chunbao

    2016-01-01

    Background Bronchopulmonary dysplasia (BPD) is characterized by the aberrant remodeling of the lung parenchyma, resulting from accumulation of fibroblasts or myofibroblasts. Circulating fibrocytes are implied in pulmonary fibrosis, but whether these cells are associated with the development of BPD or the progressive fibrosis is unknown. The aim of the present study was to investigate the occurrence of fibrocytes in peripheral venous blood and explore whether these cells might be associated with severity of BPD. Methods We investigated circulating fibrocytes in 66 patients with BPD, 23 patients with acute respiratory distress syndrome(ARDS) and 11 normal subjects. Circulating fibrocytes were defined and quantified as cells positive for CD45 andcollagen-1 by flow cytometry. Furthermore, serum SDF-1/CXCL12 and TGF-β1 were evaluated using ELISA methods. We also investigated the clinical value of fibrocyte counts by comparison with standard clinical parameters. Results The patients with BPD had significantly increased numbers of fibrocytes compared to the controls (p < 0.01). Patients with ARDS were not different from healthy control subjects. There was a correlation between the number of fibrocytes and pulmonary hypertension or oxygen saturation (p < 0.05). Fibrocyte numbers were not correlated with other clinical or functional variables or radiologic severity scores. The fibrocyte attractant chemokine CXCL12 increased in plasma (p < 0.05) and was detectable in the bronchoalveolar lavage fluid of 40% of the patients but not in controls. Conclusion These findings indicate that circulating fibrocytes are increased in patients with BPD and may contribute to pulmonary fibrosis in BPD. Circulating fibrocytes, likely recruited through the CXCR4/CXCL12 axis, might contribute to the production of TGF-β1 for the expansion of fibroblast/myofibroblast population in BPD. PMID:27309347

  6. In vitro interaction of Stenotrophomonas maltophilia with human monocyte-derived dendritic cells

    PubMed Central

    Roscetto, Emanuela; Vitiello, Laura; Muoio, Rosa; Soriano, Amata A.; Iula, Vita D.; Vollaro, Antonio; Gregorio, Eliana De; Catania, Maria R.

    2015-01-01

    Stenotrophomonas maltophilia is increasingly identified as an opportunistic pathogen in immunocompromised, cancer and cystic fibrosis (CF) patients. Knowledge on innate immune responses to S. maltophilia and its potential modulation is poor. The present work investigated the ability of 12 clinical S. maltophilia strains (five from CF patients, seven from non-CF patients) and one environmental strain to survive inside human monocyte-derived dendritic cells (DCs). The effects of the bacteria on maturation of and cytokine secretion by DCs were also measured. S. maltophilia strains presented a high degree of heterogeneity in internalization and intracellular replication efficiencies as well as in the ability of S. maltophilia to interfere with normal DCs maturation. By contrast, all S. maltophilia strains were able to activate DCs, as measured by increase in the expression of surface maturation markers and proinflammatory cytokines secretion. PMID:26236302

  7. Oxidative metabolism in cord blood monocytes and monocyte-derived macrophages.

    PubMed Central

    Speer, C P; Ambruso, D R; Grimsley, J; Johnston, R B

    1985-01-01

    Little is known about phagocytosis-associated oxidative metabolism in mononuclear phagocytes from the human neonate. We investigated this phenomenon in monocytes from the cord blood of term newborn infants by measuring generation of superoxide anion (O2-) and hydroxyl radical (X OH) after stimulation with opsonized zymosan or phorbol myristate acetate. Production of these microbicidal oxygen metabolites by monocytes from neonates and healthy adult volunteers was equivalent. When cultured in the presence of the macrophage activator lipopolysaccharide or muramyl dipeptide, monocytes from neonates and adults differentiated into cells with the appearance of macrophages and with an enhanced capacity to release O2- compared with cells cultured in the absence of an activator. Monocyte-derived macrophages from neonates produced only slightly less O2- than did adult cells. Thus, unlike the cord blood neutrophil, which exhibits abnormalities in oxidative metabolism, the cord blood mononuclear phagocyte has a respiratory burst that is quantitatively comparable to that of the adult cell. PMID:2999001

  8. Divergent JAM-C Expression Accelerates Monocyte-Derived Cell Exit from Atherosclerotic Plaques

    PubMed Central

    Miljkovic-Licina, Marijana; Lee, Boris P.; Fischer, Nicolas; Fish, Richard J.; Kwak, Brenda; Fisher, Edward A.; Imhof, Beat A.

    2016-01-01

    Atherosclerosis, caused in part by monocytes in plaques, continues to be a disease that afflicts the modern world. Whilst significant steps have been made in treating this chronic inflammatory disease, questions remain on how to prevent monocyte and macrophage accumulation in atherosclerotic plaques. Junctional Adhesion Molecule C (JAM-C) expressed by vascular endothelium directs monocyte transendothelial migration in a unidirectional manner leading to increased inflammation. Here we show that interfering with JAM-C allows reverse-transendothelial migration of monocyte-derived cells, opening the way back out of the inflamed environment. To study the role of JAM-C in plaque regression we used a mouse model of atherosclerosis, and tested the impact of vascular JAM-C expression levels on monocyte reverse transendothelial migration using human cells. Studies in-vitro under inflammatory conditions revealed that overexpression or gene silencing of JAM-C in human endothelium exposed to flow resulted in higher rates of monocyte reverse-transendothelial migration, similar to antibody blockade. We then transplanted atherosclerotic, plaque-containing aortic arches from hyperlipidemic ApoE-/- mice into wild-type normolipidemic recipient mice. JAM-C blockade in the recipients induced greater emigration of monocyte-derived cells and further diminished the size of atherosclerotic plaques. Our findings have shown that JAM-C forms a one-way vascular barrier for leukocyte transendothelial migration only when present at homeostatic copy numbers. We have also shown that blocking JAM-C can reduce the number of atherogenic monocytes/macrophages in plaques by emigration, providing a novel therapeutic strategy for chronic inflammatory pathologies. PMID:27442505

  9. Expression and Function of Semaphorin 3A and Its Receptors in Human Monocyte-derived Macrophages

    PubMed Central

    Ji, Jong-Dae; Park-Min, Kyung-Hyun; Ivashkiv, Lionel B.

    2016-01-01

    Semaphorins are a large family of secreted and membrane-bound proteins. Recently, several roles of semaphorins in the immune system have emerged. Several semaphorins and their receptors are expressed in a variety of lymphoid and myeloid cells and affect immune cell functions, including cell proliferation, differentiation, chemotaxis, and cytokine production. However, the roles of class 3 semaphorins in human myeloid cells are not well known. Here we examined the regulation of expression of class 3 semaphorins and their receptors by inflammatory stimuli and their function in human macrophages. We show that the expression of Sema3A receptors (neuropilin-1 (NRP-1), NRP-2, plexin A1, plexin A2 and plexin A3) significantly increased during M-CSF-mediated differentiation of monocytes into macrophages under conditions that promote an M2 alternatively activated macrophage phenotype. Consistent with increased NRP-1 expression, cell surface binding of Sema3A increased during M2 differentiation. IFN-γ and LPS that promote classical M1 macrophage activation affected expression of NRP-1, NRP-2 and plexin A1. IFN-γ decreased NRP-1 expression and LPS suppressed NRP-2 and plexin A1 expression. Furthermore we show that Sema3A induced apoptosis in monocyte-derived macrophages, and cooperated with anti-Fas CH11 antibody to augment apoptosis. Our results suggest Sema3A plays a role in induction of apoptosis in monocyte-derived macrophages that are resistant to Fas-induced apoptosis and that its function can be modulated in inflammatory conditions. PMID:19480842

  10. Increased CD40+ fibrocytes in patients with idiopathic orbital inflammation

    PubMed Central

    Lee, Brian J; Atkins, Stephen; Ginter, Anna; Elner, Victor M; Nelson, Christine C; Douglas, Raymond S

    2014-01-01

    Objective To investigate the phenotypic and functional characteristics of peripheral and tissue-infiltrating stem cells, called fibrocytes in patients with idiopathic orbital inflammation (IOI). Methods Seven patients with IOI were studied. In the three patients requiring orbital biopsy, fibrocytes were identified in orbital tissue from patients with IOI compared to healthy controls using immunohistochemistry. Fibrocytes from the peripheral blood of all seven patients and controls were quantified and phenotyped by flow cytometry and immunofluorescence for expression of CD34, alpha smooth muscle actin, CD40 and Collagen 1. Quantitation of CD40-mediated IL-6 production was measured using ELISA. Results Orbital biopsy specimens from patients with IOI demonstrate tissue infiltration by fibrocytes (n=3). Fibrocytes are present in the peripheral blood of IOI patients (n= 7) but are scarce in healthy donors (n=19). Fibrocytes from IOI patients express substantial levels of CD40 and ligation of CD40 increases IL-6 expression. Conclusions Fibrocytes are present in the peripheral blood and orbital tissues of patients with IOI and constitutively express CD40 and express IL-6 in response to ligation. This site-specific predilection of CD34+ fibrocytes to sites of orbital inflammation and fibrosis may suggest a role in IOI. Moreover CD40-mediated activation cytokine production may contribute to the proinflammatory and profibrotic features of IOI and may provide a mechanism for future targeted therapy. PMID:25098443

  11. TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy.

    PubMed

    Smith, Terry J

    2015-03-01

    Thyroid-associated ophthalmopathy (TAO) is a vexing and undertreated ocular component of Graves disease in which orbital tissues undergo extensive remodelling. My colleagues and I have introduced the concept that fibrocytes expressing the haematopoietic cell antigen CD34 (CD34(+) fibrocytes), which are precursor cells of bone-marrow-derived monocyte lineage, express the TSH receptor (TSHR). These cells also produce several other proteins whose expression was traditionally thought to be restricted to the thyroid gland. TSHR-expressing fibrocytes in which the receptor is activated by its ligand generate extremely high levels of several inflammatory cytokines. Acting in concert with TSHR, the insulin-like growth factor 1 receptor (IGF-1R) expressed by orbital fibroblasts and fibrocytes seems to be necessary for TSHR-dependent cytokine production, as anti-IGF-1R blocking antibodies attenuate these proinflammatory actions of TSH. Furthermore, circulating fibrocytes are highly abundant in patients with TAO and seem to infiltrate orbital connective tissues, where they might transition to CD34(+) fibroblasts. My research group has postulated that the infiltration of fibrocytes into the orbit, their unique biosynthetic repertoire and their proinflammatory and profibrotic phenotype account for the characteristic properties exhibited by orbital connective tissues that underlie susceptibility to TAO. These insights, which have emerged in the past few years, might be of use in therapeutically targeting pathogenic orbit-infiltrating fibrocytes selectively by utilizing novel biologic agents that interfere with TSHR and IGF-1R signalling. PMID:25560705

  12. Circulating fibrocytes stabilize blood vessels during angiogenesis in a paracrine manner.

    PubMed

    Li, Jinqing; Tan, Hong; Wang, Xiaolin; Li, Yuejun; Samuelson, Lisa; Li, Xueyong; Cui, Caibin; Gerber, David A

    2014-02-01

    Accumulating evidence supports that circulating fibrocytes play important roles in angiogenesis. However, the specific role of fibrocytes in angiogenesis and the underlying mechanisms remain unclear. In this study, we found that fibrocytes stabilized newly formed blood vessels in a mouse wound-healing model by inhibiting angiogenesis during the proliferative phase and inhibiting blood vessel regression during the remodeling phase. Fibrocytes also inhibited angiogenesis in a Matrigel mouse model. In vitro study showed that fibrocytes inhibited both the apoptosis and proliferation of vascular endothelial cells (VECs) in a permeable support (Transwell) co-culture system. In a three-dimensional collagen gel, fibrocytes stabilized the VEC tubes by decreasing VEC tube density on stimulation with growth factors and preventing VEC tube regression on withdrawal of growth factors. Further mechanistic investigation revealed that fibrocytes expressed many prosurvival factors that are responsible for the prosurvival effect of fibrocytes on VECs and blood vessels. Fibrocytes also expressed angiogenesis inhibitors, including thrombospondin-1 (THBS1). THBS1 knockdown partially blocked the fibrocyte-induced inhibition of VEC proliferation in the Transwell co-culture system and recovered the fibrocyte-induced decrease of VEC tube density in collagen gel. Purified fibrocytes transfected with THBS1 siRNA partially recovered the fibrocyte-induced inhibition of angiogenesis in both the wound-healing and Matrigel models. In conclusion, our findings reveal that fibrocytes stabilize blood vessels via prosurvival factors and anti-angiogenic factors, including THBS1. PMID:24300950

  13. Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A.

    PubMed

    Salvatore, Giulia; Bernoud-Hubac, Nathalie; Bissay, Nathalie; Debard, Cyrille; Daira, Patricia; Meugnier, Emmanuelle; Proamer, Fabienne; Hanau, Daniel; Vidal, Hubert; Aricò, Maurizio; Delprat, Christine; Mahtouk, Karène

    2015-06-01

    Interleukin 17A (IL-17A) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases. In the field of immunometabolism, we have studied the impact of IL-17A on the lipid metabolism of human in vitro-generated monocyte-derived dendritic cells (DCs). Microarrays and lipidomic analysis revealed an intense remodeling of lipid metabolism induced by IL-17A in DCs. IL-17A increased 2-12 times the amounts of phospholipids, cholesterol, triglycerides, and cholesteryl esters in DCs. Palmitic (16:0), stearic (18:0), and oleic (18:ln-9c) acid were the main fatty acid chains present in DCs. They were strongly increased in response to IL-17A while their relative proportion remained unchanged. Capture of extracellular lipids was the major mechanism of lipid droplet accumulation, visualized by electron microscopy and Oil Red O staining. Besides this foamy phenotype, IL-17A induced a mixed macrophage-DC phenotype and expression of the nuclear receptor NR1H3/liver X receptor-α, previously identified in the context of atherosclerosis as the master regulator of cholesterol homeostasis in macrophages. These IL-17A-treated DCs were as competent as untreated DCs to stimulate allogeneic naive T-cell proliferation. Following this first characterization of lipid-rich DCs, we propose to call these IL-17A-dependent cells "foamy DCs" and discuss the possible existence of foamy DCs in atherosclerosis, a metabolic and inflammatory disorder involving IL-17A. PMID:25833686

  14. Hyperbaric oxygen enhances neutrophil apoptosis and their clearance by monocyte-derived macrophages.

    PubMed

    Almzaiel, Anwar J; Billington, Richard; Smerdon, Gary; Moody, A John

    2015-08-01

    Neutrophil apoptosis and clearance by macrophages are essential for wound healing. Evidence suggests that hyperbaric oxygen (HBO) exposure may enhance neutrophil apoptosis, but HBO effects leading to neutrophil clearance by macrophages are still unclear. In the current study, bovine neutrophils and monocyte-derived macrophages (MDMΦ) were co-cultured under HBO (97.9% O2, 2.1% CO2 at 2.4 atm absolute (ATA)) (1 atm = 101.325 kPa), hyperbaric normoxia (8.8% O2 at 2.4 ATA), normobaric hyperoxia (95% O2, 5% CO2), normoxia (air), and normobaric hypoxia (5% O2, 5% CO2). Phagocytosis of fresh and 22 h aged neutrophils by MDMΦ was increased after HBO pre-treatment, assessed using flow cytometry and light microscopy. Enhanced clearance of neutrophils was accompanied by an increase in H2O2 levels following HBO pre-treatment with upregulation of IL-10 (anti-inflammatory cytokine) mRNA expression in LPS-stimulated MDMΦ that had ingested aged neutrophils. TNF-α (pro-inflammatory cytokine) gene expression did not change in LPS-stimulated MDMΦ that had ingested fresh or aged neutrophils after HBO, pressure, and hyperoxia. These findings suggest that HBO-activated MDMΦ participate in the clearance of apoptotic cells. Uptake of neutrophils by MDMΦ exposed to HBO may contribute to resolution of inflammation, because HBO induced up-regulation of IL-10 mRNA expression. PMID:26194051

  15. Expression of ESE-3 Isoforms in Immunogenic and Tolerogenic Human Monocyte-Derived Dendritic Cells

    PubMed Central

    Sprater, Florian; Hovden, Arnt-Ove; Appel, Silke

    2012-01-01

    Dendritic cells (DC) are the only hematopoietic cells expressing the epithelial specific Ets transcription factor ESE-3. Here we analyzed presence and quantity of isoforms ESE-3a, ESE-3b and ESE-3j in various immunogenic and tolerogenic human monocyte-derived DC (moDC) and blood DC populations using quantitative real time PCR and immunoblot analyses. ESE-3a and ESE-3b were detectable in all moDC populations with ESE-3b being the main transcript. ESE-3b expression was upregulated in immunogenic moDC and downregulated in tolerogenic moDC compared to immature moDC. ESE-3a had similar transcript levels in immature and immunogenic moDC and had very low levels in tolerogenic moDC. In blood DC populations only splice variant ESE-3b was detectable. ESE-3j was not detectable in any of the DC populations. These findings suggest that ESE-3b is the functionally most important ESE-3 isoform in DC. PMID:23185370

  16. Expression of ESE-3 isoforms in immunogenic and tolerogenic human monocyte-derived dendritic cells.

    PubMed

    Sprater, Florian; Hovden, Arnt-Ove; Appel, Silke

    2012-01-01

    Dendritic cells (DC) are the only hematopoietic cells expressing the epithelial specific Ets transcription factor ESE-3. Here we analyzed presence and quantity of isoforms ESE-3a, ESE-3b and ESE-3j in various immunogenic and tolerogenic human monocyte-derived DC (moDC) and blood DC populations using quantitative real time PCR and immunoblot analyses. ESE-3a and ESE-3b were detectable in all moDC populations with ESE-3b being the main transcript. ESE-3b expression was upregulated in immunogenic moDC and downregulated in tolerogenic moDC compared to immature moDC. ESE-3a had similar transcript levels in immature and immunogenic moDC and had very low levels in tolerogenic moDC. In blood DC populations only splice variant ESE-3b was detectable. ESE-3j was not detectable in any of the DC populations. These findings suggest that ESE-3b is the functionally most important ESE-3 isoform in DC. PMID:23185370

  17. Distinct Transcriptional Programs Control Cross-Priming in Classical and Monocyte-Derived Dendritic Cells.

    PubMed

    Briseño, Carlos G; Haldar, Malay; Kretzer, Nicole M; Wu, Xiaodi; Theisen, Derek J; Kc, Wumesh; Durai, Vivek; Grajales-Reyes, Gary E; Iwata, Arifumi; Bagadia, Prachi; Murphy, Theresa L; Murphy, Kenneth M

    2016-06-14

    Both classical DCs (cDCs) and monocyte-derived DCs (Mo-DCs) are capable of cross-priming CD8(+) T cells in response to cell-associated antigens. We found that Ly-6C(hi)TREML4(-) monocytes can differentiate into Zbtb46(+) Mo-DCs in response to granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) but that Ly-6C(hi)TREML4(+) monocytes were committed to differentiate into Ly-6C(lo)TREML4(+) monocytes. Differentiation of Zbtb46(+) Mo-DCs capable of efficient cross-priming required both GM-CSF and IL-4 and was accompanied by the induction of Batf3 and Irf4. However, monocytes require IRF4, but not BATF3, to differentiate into Zbtb46(+) Mo-DCs capable of cross-priming CD8(+) T cells. Instead, Irf4(-/-) monocytes differentiate into macrophages in response to GM-CSF and IL-4. Thus, cDCs and Mo-DCs require distinct transcriptional programs of differentiation in acquiring the capacity to prime CD8(+) T cells. These differences may be of consideration in the use of therapeutic DC vaccines based on Mo-DCs. PMID:27264183

  18. Constraints for monocyte-derived dendritic cell functions under inflammatory conditions.

    PubMed

    Fekete, Tünde; Szabo, Attila; Beltrame, Luca; Vivar, Nancy; Pivarcsi, Andor; Lanyi, Arpad; Cavalieri, Duccio; Rajnavölgyi, Eva; Rethi, Bence

    2012-02-01

    The activation of TLRs expressed by macrophages or DCs, in the long run, leads to persistently impaired functionality. TLR signals activate a wide range of negative feedback mechanisms; it is not known, however, which of these can lead to long-lasting tolerance for further stimulatory signals. In addition, it is not yet understood how the functionality of monocyte-derived DCs (MoDCs) is influenced in inflamed tissues by the continuous presence of stimulatory signals during their differentiation. Here we studied the role of a wide range of DC-inhibitory mechanisms in a simple and robust model of MoDC inactivation induced by early TLR signals during differentiation. We show that the activation-induced suppressor of cytokine signaling 1 (SOCS1), IL-10, STAT3, miR146a and CD150 (SLAM) molecules possessed short-term inhibitory effects on cytokine production but did not induce persistent DC inactivation. On the contrary, the LPS-induced IRAK-1 downregulation could alone lead to persistent MoDC inactivation. Studying cellular functions in line with the activation-induced negative feedback mechanisms, we show that early activation of developing MoDCs allowed only a transient cytokine production that was followed by the downregulation of effector functions and the preservation of a tissue-resident non-migratory phenotype. PMID:22057588

  19. The Salmonella virulence plasmid spv genes are required for cytopathology in human monocyte-derived macrophages.

    PubMed

    Libby, S J; Lesnick, M; Hasegawa, P; Weidenhammer, E; Guiney, D G

    2000-02-01

    The pathogenesis of serious systemic Salmonella infections is characterized by survival and proliferation of bacteria inside macrophages. Infection of human monocyte-derived macrophages in vitro with S. typhimurium or S. dublin produces cytopathology characterized by detachment of cells that contain large numbers of proliferating bacteria. This cytopathology is dependent on the expression of the bacterial spv genes, a virulence locus previously shown to markedly enhance the ability of Salmonella to produce systemic disease. After 24 h of infection, macrophage cultures contain two populations of bacteria: (i) proliferating organisms present in a detached cell fraction; and (ii) a static bacterial population in macrophages remaining attached to the culture well. Mutations in either the essential transcriptional activator SpvR or the key SpvB protein markedly reduce the cytopathic effect of Salmonella infection. The spv-dependent cytopathology in macrophages exhibits characteristics of apoptosis, with release of nucleosomes into the cytoplasm, nuclear condensation and DNA fragmentation. The current findings suggest that the mechanism of the spv effect is through induction of increased cytopathology in host macrophages. PMID:11207562

  20. Innate Allorecognition Results in Rapid Accumulation of Monocyte-Derived Dendritic Cells.

    PubMed

    Chow, Kevin V; Delconte, Rebecca B; Huntington, Nicholas D; Tarlinton, David M; Sutherland, Robyn M; Zhan, Yifan; Lew, Andrew M

    2016-09-01

    Although the mechanisms governing the innate recognition of pathogen-associated molecular patterns have been well defined, how allogeneic cellular stimuli evoke innate responses remains less so. In this article, we report that upon i.v. transfer (to avoid major iatrogenic interference), allogeneic but not syngeneic leukocytes could induce a rapid (after 1 d) accumulation of host monocyte-derived dendritic cells (moDCs) without any increase in conventional DCs. This occurred in various donor-host strain combinations, did not require MHC mismatch, and could be induced by various donor cell types including B cells, T cells, or NK cells. Using RAG(-/-)γc(-/-) and scid γc(-/-)mice with different MHC, we found that the presence of either donor or host lymphoid cells was required. Alloinduced moDC accumulation was significantly reduced when splenocytes from mice deficient in NK cells by genetic ablation were used as donors. A major component of this moDC accumulation appears to be recruitment. Our findings provide new insights into how the innate and adaptive immune system may interact during allogeneic encounters and thus transplant rejection. PMID:27474076

  1. Differential phagocytosis of Leishmania mexicana promastigotes and amastigotes by monocyte-derived dendritic cells.

    PubMed

    Argueta-Donohué, Jesús; Wilkins-Rodríguez, Arturo A; Aguirre-García, Magdalena; Gutiérrez-Kobeh, Laila

    2016-06-01

    Leishmania species are dimorphic protozoan parasites that live and replicate in the gut of sand flies as promastigotes or in mammalian hosts as amastigotes. Different immune cells, including DCs, and receptors differ in their involvement in phagocytosis of promastigotes and amastigotes and in recognition of different Leishmania species. In the case of L. mexicana, differences in phagocytosis of promastigotes and amastigotes by DCs and participation of C-type lectin receptors (CLRs) have not been established. In the present study, flow cytometry and confocal microscopy were used to investigate the phagocytosis by monocyte-derived dendritic cells (moDCs) of L. mexicana promastigotes and amastigotes in the presence or absence of immune serum during various periods of time. Blocking antibodies against mannose receptors and DC-SIGN were used to explore the participation of these receptors in the phagocytosis of L. mexicana by moDC. The major differences in interactions of L. mexicana promastigotes and amastigotes with moDC were found to occur within the first 3 hr, during which phagocytosis of promastigotes predominated as compared with opsonization of promastigotes and amastigotes. However, after 6 hr of incubation, opsonized promastigotes were preferentially phagocytosed as compared with unopsonized promastigotes and amastigotes and after 24 hr of incubation there were no differences in the phagocytosis of promastigotes and amastigotes. Finally, after 3 hr incubation, DC-SIGN was involved in the phagocytosis of promastigotes, but not of amastigotes. PMID:26399218

  2. Monocyte-derived dendritic cell subpopulations use different types of matrix metalloproteinases inhibited by GM6001.

    PubMed

    Kis-Toth, Katalin; Bacskai, Ildiko; Gogolak, Peter; Mazlo, Anett; Szatmari, Istvan; Rajnavolgyi, Eva

    2013-11-01

    Matrix metalloproteinases (MMPs) are endopeptidases with the potential to cleave extracellular matrix, support tissue renewal and regulate cell migration. Functional activities of MMPs are regulated by tissue inhibitors of MMPs (TIMPs) and disruption of the MMP-TIMP balance has pathological consequences. Here we studied the expression and secretion of MMPs and TIMPs in CD1a(-) and CD1a(+) monocyte-derived dendritic cell (DC) subpopulations. Our results showed that monocytes express TIMPs but lack MMPs, whereas upon differentiation to moDCs and in response to activation signals the expression of MMPs is increased and that of TIMPs is decreased. MMP-9 is expressed dominantly in the CD1a(-) subpopulation, while MMP-12 is preferentially expressed in CD1a(+) cells. Experiments performed with the synthetic MMP inhibitor GM6001 revealed that this drug efficiently inhibits the migration of moDCs through inactivation of MMPs. We conclude that modulation of MMP activity by GM6001 emerges as a novel approach to manipulate DC migration under inflammatory conditions. PMID:23870824

  3. Metabolic profiling during HIV-1 and HIV-2 infection of primary human monocyte-derived macrophages

    PubMed Central

    Hollenbaugh, Joseph A.; Montero, Catherine; Schinazi, Raymond F.; Munger, Joshua; Kim, Baek

    2016-01-01

    We evaluated cellular metabolism profiles of HIV-1 and HIV-2 infected primary human monocyte-derived macrophages (MDMs). First, HIV-2 GL-AN displays faster production kinetics and greater amounts of virus as compared to HIV-1s: YU-2, 89.6 and JR-CSF. Second, quantitative LC–MS/MS metabolomics analysis demonstrates very similar metabolic profiles in glycolysis and TCA cycle metabolic intermediates between HIV-1 and HIV-2 infected macrophages, with a few notable exceptions. The most striking metabolic change in MDMs infected with HIV-2 relative to HIV-1-infected MDMs was the increased levels of quinolinate, a metabolite in the tryptophan catabolism pathway that has been linked to HIV/AIDS pathogenesis. Third, both HIV-1 and HIV-2 infected MDMs showed elevated levels of ribose-5-phosphate, a key metabolic component in nucleotide biosynthesis. Finally, HIV-2 infected MDMs display increased dNTP concentrations as predicted by Vpx-mediated SAMHD1 degradation. Collectively, these data show differential metabolic changes during HIV-1 and HIV-2 infection of macrophages. PMID:26895248

  4. Fibrocytes and the tissue niche in lung repair.

    PubMed

    Andersson-Sjöland, Annika; Nihlberg, Kristian; Eriksson, Leif; Bjermer, Leif; Westergren-Thorsson, Gunilla

    2011-01-01

    Human fibrocytes are bone marrow-derived mesenchymal progenitor cells that express a variety of markers related to leukocytes, hematopoietic stem cells and a diverse set of fibroblast phenotypes. Fibrocytes can be recruited from the circulation to the tissue where they further can differentiate and proliferate into various mesenchymal cell types depending on the tissue niche. This local tissue niche is important because it modulates the fibrocytes and coordinates their role in tissue behaviour and repair. However, plasticity of a niche may be co-opted in chronic airway diseases such as asthma, idiopathic pulmonary fibrosis and obliterative bronchiolitis. This review will therefore focus on a possible role of fibrocytes in pathological tissue repair processes in those diseases. PMID:21658209

  5. BM-derived fibrocytes contribute to liver fibrosis

    PubMed Central

    2016-01-01

    Chronic liver injury often leads to hepatic fibrosis, a condition associated with increased levels of circulating TGF-β1 and lipopolysaccharide (LPS), activation of myofibroblasts, and extensive deposition of extracellular matrix, mostly collagen type I. Hepatic stellate cells (HSCs) are considered to be the major [1] but not the only source of myofibroblasts in the injured liver [2]. Hepatic myofibroblasts may also originate from portal fibroblasts, mesenchymal cells and fibrocytes [3]. Since the discovery of fibrocytes in 1994 by Dr. Bucala and colleagues, these bone marrow (BM)-derived collagen Type I-producing CD45+ cells remain the most fascinating cells of the hematopoietic system. Due to the ability to differentiate into collagen Type I producing cells/myofibroblasts, fibrocytes were implicated in the pathogenesis of liver, skin, lung, and kidney fibrosis. However, studies of different organs often contain controversial results on the number of fibrocytes recruited to the site of injury, and their biological function. Furthermore, fibrocytes were implicated in pathogenesis of sepsis, and were shown to possess anti-microbial activity. Finally, in response to specific stimuli, fibrocytes can give rise to fully differentiated macrophages, suggesting that in concurrence with high plasticity of hematopoietic cells, fibrocytes exhibit progenitor properties. Here we summarize our current understanding of the role of CD45+Collagen Type I+ BM-derived cells in response to fibrogenic liver injury and septicemia and discuss the most recent evidence supporting the critical role of fibrocytes in the mediation of pro-fibrogenic and/or pro-inflammatory responses. PMID:25966982

  6. cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells.

    PubMed

    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-04-01

    Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID:27058035

  7. cGAS Senses Human Cytomegalovirus and Induces Type I Interferon Responses in Human Monocyte-Derived Cells

    PubMed Central

    Paijo, Jennifer; Döring, Marius; Spanier, Julia; Grabski, Elena; Nooruzzaman, Mohammed; Schmidt, Tobias; Witte, Gregor; Messerle, Martin; Hornung, Veit; Kaever, Volkhard; Kalinke, Ulrich

    2016-01-01

    Human cytomegalovirus (HCMV) infections of healthy individuals are mostly unnoticed and result in viral latency. However, HCMV can also cause devastating disease, e.g., upon reactivation in immunocompromised patients. Yet, little is known about human immune cell sensing of DNA-encoded HCMV. Recent studies indicated that during viral infection the cyclic GMP/AMP synthase (cGAS) senses cytosolic DNA and catalyzes formation of the cyclic di-nucleotide cGAMP, which triggers stimulator of interferon genes (STING) and thus induces antiviral type I interferon (IFN-I) responses. We found that plasmacytoid dendritic cells (pDC) as well as monocyte-derived DC and macrophages constitutively expressed cGAS and STING. HCMV infection further induced cGAS, whereas STING expression was only moderately affected. Although pDC expressed particularly high levels of cGAS, and the cGAS/STING axis was functional down-stream of STING, as indicated by IFN-I induction upon synthetic cGAMP treatment, pDC were not susceptible to HCMV infection and mounted IFN-I responses in a TLR9-dependent manner. Conversely, HCMV infected monocyte-derived cells synthesized abundant cGAMP levels that preceded IFN-I production and that correlated with the extent of infection. CRISPR/Cas9- or siRNA-mediated cGAS ablation in monocytic THP-1 cells and primary monocyte-derived cells, respectively, impeded induction of IFN-I responses following HCMV infection. Thus, cGAS is a key sensor of HCMV for IFN-I induction in primary human monocyte-derived DC and macrophages. PMID:27058035

  8. Flow Cytometric Identification of Fibrocytes in the Human Circulation.

    PubMed

    Hu, Xinyuan; DeBiasi, Erin M; Herzog, Erica L

    2015-01-01

    Because the incidence of organ fibrosis increases with age, various fibrosing disorders are projected to account for significant increases in morbidity, mortality, and healthcare costs in the years to come. Treatments for these diseases are scarce and better understanding of the immunopathogenesis of fibrosis and its relationship to aging are sorely needed. One area of interest in this field is the role that fibrocytes might play in the development of tissue remodeling and fibrosis. Fibrocytes are mesenchymal progenitor cells presumed to be of monocyte origin that possess the tissue remodeling properties of tissue resident fibroblasts such as extracellular matrix production and α-SMA-related contractile properties, as well as the immunologic functions typically attributed to macrophages including production of cytokines and chemokines, antigen presentation, regulation of leukocyte trafficking, and modulation of angiogenesis. Fibrocytes could participate in the development of age-related fibrosing disorders through any or all of these functions. This chapter presents methods that have been developed for the study of circulating human fibrocytes. Protocols for the quantification of fibrocytes in the human circulation will be presented along with discussion of the technical challenges that are frequently encountered in this field. It is hoped that this information will facilitate further investigation of the relationship between fibrocytes, aging, and fibrosis, and perhaps uncover new areas of study in these difficult-to-treat and deadly diseases. PMID:26420706

  9. Bacterial Ghosts of Escherichia coli Drive Efficient Maturation of Bovine Monocyte-Derived Dendritic Cells

    PubMed Central

    Hajam, Irshad Ahmed; Dar, Pervaiz Ahmad; Appavoo, Elamurugan; Kishore, Subodh; Bhanuprakash, Veerakyathappa; Ganesh, Kondabattula

    2015-01-01

    Bacterial ghosts (BGs) are empty cell envelopes derived from Gram-negative bacteria. They not only represent a potential platform for development of novel vaccines but also provide a tool for efficient adjuvant and antigen delivery system. In the present study, we investigated the interaction between BGs of Escherichia coli (E. coli) and bovine monocyte-derived dendritic cells (MoDCs). MoDCs are highly potent antigen-presenting cells and have the potential to act as a powerful tool for manipulating the immune system. We generated bovine MoDCs in vitro from blood monocytes using E. coli expressed bovine GM-CSF and IL-4 cytokines. These MoDCs displayed typical morphology and functions similar to DCs. We further investigated the E. coli BGs to induce maturation of bovine MoDCs in comparison to E. coli lipopolysaccharide (LPS). We observed the maturation marker molecules such as MHC-II, CD80 and CD86 were induced early and at higher levels in BG stimulated MoDCs as compared to the LPS stimulated MoDCs. BG mediated stimulation induced significantly higher levels of cytokine expression in bovine MoDCs than LPS. Both pro-inflammatory (IL-12 and TNF-α) and anti-inflammatory (IL-10) cytokines were induced in MoDCs after BGs stimulation. We further analysed the effects of BGs on the bovine MoDCs in an allogenic mixed lymphocyte reaction (MLR). We found the BG-treated bovine MoDCs had significantly (p<0.05) higher capacity to stimulate allogenic T cell proliferation in MLR as compared to the LPS. Taken together, these findings demonstrate the E. coli BGs induce a strong activation and maturation of bovine MoDCs. PMID:26669936

  10. No impairment of monocyte-derived Langerhans cell phenotype or function in early-onset psoriasis

    PubMed Central

    Shaw, F L; Kimber, I; Begum, R; Cumberbatch, M; Dearman, R J; Griffiths, C E M

    2012-01-01

    Background Migration of epidermal Langerhans cells (LCs) in response to the cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α is impaired in uninvolved skin of patients with early-onset psoriasis. Aim To investigate whether this impairment is a reflection of a systemic defect in dendritic cells (DCs), using an established model of monocyte-derived LC-like cells (mLCs). Methods CD14+ monocytes isolated from both patients with psoriasis and healthy control volunteers were cultured in a cytokine cocktail for 5 days to promote their differentiation into mLCs, then stimulated for 24 h with TNF-α, IL-1β (both 100 ng/mL) or medium alone. Cellular surface protein expression was quantified by flow cytometry, and the ability of cells to migrate to media supplemented with C-C motif ligand (CCL)19 was assessed using a Transwell migration assay. The cytokine and chemokine content of supernatants was analysed by cytokine array. Results CD14+ cells acquired an LC-like phenotype with high expression of CD1a and major histocompatibility complex (MHC) class II. There were no differences in the expression of activation markers or in the secretion of cytokines by mLCs isolated from patients with psoriasis and those isolated from healthy controls. Moreover, mLCs isolated from both groups displayed comparable ability to migrate in vitro. Conclusions These data suggest that the failure of LCs to migrate in response to stimulation in patients with psoriasis is not attributable to a systemic defect in DC function, but is rather a reflection of local changes in the epidermal microenvironment. PMID:21933242

  11. Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages.

    PubMed

    Lathrop, Stephanie K; Binder, Kelsey A; Starr, Tregei; Cooper, Kendal G; Chong, Audrey; Carmody, Aaron B; Steele-Mortimer, Olivia

    2015-07-01

    Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages. PMID:25895967

  12. Characterization of a receptor for human monocyte-derived neutrophil chemotactic factor/interleukin-8

    SciTech Connect

    Grob, P.M.; David, E.; Warren, T.C.; DeLeon, R.P.; Farina, P.R.; Homon, C.A. )

    1990-05-15

    Monocyte-derived neutrophil chemotactic factor/interleukin-8 (MDNCF/IL-8) is an 8,000-dalton protein produced by monocytes which exhibits activity as a chemoattractant for neutrophils with maximal activity achieved at a concentration of 50 ng/ml. This polypeptide has been iodinated by chloramine-T methodology (350 Ci/mM), and specific receptors for MDNCF/IL-8 have been detected on human neutrophils, U937 cells, THP-1 cells, and dimethyl sulfoxide-differentiated HL-60 cells. The binding of MDNCF/IL-8 to human neutrophils is not inhibited by interleukin-1 alpha, tumor necrosis factor-alpha, insulin, or epidermal growth factor. In addition, chemoattractants such as C5a, fMet-Leu-Phe, leukotriene B4, and platelet-activating factor fail to inhibit binding, suggesting that MDNCF/IL-8 utilizes a unique receptor. The receptor for MDNCF/IL-8 is apparently glycosylated since ligand binding is inhibited by the presence of wheat germ agglutinin, a lectin with a binding specificity for N-acetylglucosamine and neuraminic acid. Steady state binding experiments indicate Kd values of 4 and 0.5 nM and receptor numbers of 75,000 and 7,400 for human neutrophils and differentiated HL-60 cells, respectively. 125I-MDNCF/IL-8 bound to human neutrophils is rapidly internalized and subsequently released from cells as trichloroacetic acid-soluble radioactivity. Affinity labeling experiments suggest that the human neutrophil MDNCF/IL-8 receptor exhibits a mass of approximately 58,000 daltons.

  13. HIV Infection of Monocytes-Derived Dendritic Cells Inhibits Vγ9Vδ2 T Cells Functions

    PubMed Central

    Sacchi, Alessandra; Rinaldi, Alessandra; Tumino, Nicola; Casetti, Rita; Agrati, Chiara; Turchi, Federica; Bordoni, Veronica; Cimini, Eleonora; Martini, Federico

    2014-01-01

    DCs act as sentinel cells against incoming pathogens and represent the most potent antigen presenting cells, having the unique capability to prime naïve T cells. In addition to their role in induction of adaptive immune responses, DC are also able to activate innate cells as γδ T cells; in particular, a reciprocal crosstalk between DC and γδ T cells was demonstrated. However, whether HIV infection may alter DC-Vγ9Vδ2 T cells cross-talk was not yet described. To clarify this issue, we cultured activated Vγ9Vδ2 T cells with HIV infected monocyte derived DC (MoDC). After 5 days we evaluated MoDC phenotype, and Vγ9Vδ2 T cells activation and proliferation. In our model, Vγ9Vδ2 T cells were not able to proliferate in response to HIV-infected MoDC, although an up-regulation of CD69 was observed. Upon phosphoantigens stimulation, Vγ9Vδ2 T cells proliferation and cytokine production were inhibited when cultured with HIV-infected MoDC in a cell-contact dependent way. Moreover, HIV-infected MoDC are not able to up-regulate CD86 molecules when cultured with activated Vγ9Vδ2 T cells, compared with uninfected MoDC. Further, activated Vγ9Vδ2 T cells are not able to induce HLA DR up-regulation and CCR5 down-regulation on HIV-infected MoDC. These data indicate that HIV-infected DC alter the capacity of Vγ9Vδ2 T cells to respond to their antigens, pointing out a new mechanisms of induction of Vγ9Vδ2 T cells anergy carried out by HIV, that could contribute to immune evasion. PMID:25340508

  14. Cocaine Enhances HIV-1 Infectivity in Monocyte Derived Dendritic Cells by Suppressing microRNA-155

    PubMed Central

    Napuri, Jessica; Pilakka-Kanthikeel, Sudheesh; Raymond, Andrea; Agudelo, Marisela; Yndart-Arias, Adriana; Saxena, Shailendra K.; Nair, Madhavan

    2013-01-01

    Cocaine and other drugs of abuse increase HIV-induced immunopathogenesis; and neurobiological mechanisms of cocaine addiction implicate a key role for microRNAs (miRNAs), single-stranded non-coding RNAs that regulate gene expression and defend against viruses. In fact, HIV defends against miRNAs by actively suppressing the expression of polycistronic miRNA cluster miRNA-17/92, which encodes miRNAs including miR-20a. IFN-g production by natural killer cells is regulated by miR-155 and this miRNA is also critical to dendritic cell (DC) maturation. However, the impact of cocaine on miR-155 expression and subsequent HIV replication is unknown. We examined the impact of cocaine on two miRNAs, miR-20a and miR-155, which are integral to HIV replication, and immune activation. Using miRNA isolation and analysis, RNA interference, quantitative real time PCR, and reporter assays we explored the effects of cocaine on miR-155 and miR-20 in the context of HIV infection. Here we demonstrate using monocyte-derived dendritic cells (MDCCs) that cocaine significantly inhibited miR-155 and miR-20a expression in a dose dependent manner. Cocaine and HIV synergized to lower miR-155 and miR-20a in MDDCs by 90%. Cocaine treatment elevated LTR-mediated transcription and PU.1 levels in MDCCs. But in context of HIV infection, PU.1 was reduced in MDDCs regardless of cocaine presence. Cocaine increased DC-SIGN and and decreased CD83 expression in MDDC, respectively. Overall, we show that cocaine inhibited miR-155 and prevented maturation of MDDCs; potentially, resulting in increased susceptibility to HIV-1. Our findings could lead to the development of novel miRNA-based therapeutic strategies targeting HIV infected cocaine abusers. PMID:24391808

  15. Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells.

    PubMed

    Moutaftsi, Magdalena; Mehl, Anja M; Borysiewicz, Leszek K; Tabi, Zsuzsanna

    2002-04-15

    Dendritic cells (DCs) play a pivotal role in the generation of virus-specific cytotoxic T-cell responses, but some viruses can render DCs inefficient in stimulating T cells. We studied whether infection of DCs with human cytomegalovirus (HCMV) results in a suppression of DC function which may assist HCMV in establishing persistence. The effect of HCMV infection on the phenotype and function of monocyte-derived DCs and on their ability to mature following infection with an endothelial cell-adapted clinical HCMV isolate were studied. HCMV infection induced no maturation of DCs; instead, it efficiently down-regulated the expression of surface major histocompatibility complex (MHC) class I, CD40, and CD80 molecules. Slight down-regulation of MHC class II and CD86 molecules was also observed. Lipopolysaccharide (LPS)-induced maturation of infected DCs was strongly inhibited, as indicated by lower levels of surface expression of MHC class I, class II, costimulatory, and CD83 molecules. The down-regulation or inhibition of these surface markers occurred only in HCMV antigen-positive DCs. DCs produced no interleukin 12 (IL-12) and only low levels of tumor necrosis factor alpha (TNF-alpha) upon HCMV infection. Furthermore, cytokine production upon stimulation with LPS or CD40L was significantly impaired. Inhibition of cytokine production did not depend on viral gene expression as UV-irradiated HCMV resulted in the same effect. Proliferation and cytotoxicity of T cells specific to a recall antigen presented by DCs were also reduced when DCs were HCMV infected. This study shows that HCMV inhibits DC function, revealing a powerful viral strategy to delay or prevent the generation of virus-specific cytotoxic T cells. PMID:11929782

  16. Replication of Salmonella enterica Serovar Typhimurium in Human Monocyte-Derived Macrophages

    PubMed Central

    Lathrop, Stephanie K.; Binder, Kelsey A.; Starr, Tregei; Cooper, Kendal G.; Chong, Audrey; Carmody, Aaron B.

    2015-01-01

    Salmonella enterica serovar Typhimurium is a common cause of food-borne gastrointestinal illness, but additionally it causes potentially fatal bacteremia in some immunocompromised patients. In mice, systemic spread and replication of the bacteria depend upon infection of and replication within macrophages, but replication in human macrophages is not widely reported or well studied. In order to assess the ability of Salmonella Typhimurium to replicate in human macrophages, we infected primary monocyte-derived macrophages (MDM) that had been differentiated under conditions known to generate different phenotypes. We found that replication in MDM depends greatly upon the phenotype of the cells, as M1-skewed macrophages did not allow replication, while M2a macrophages and macrophages differentiated with macrophage colony-stimulating factor (M-CSF) alone (termed M0) did. We describe how additional conditions that alter the macrophage phenotype or the gene expression of the bacteria affect the outcome of infection. In M0 MDM, the temporal expression of representative genes from Salmonella pathogenicity islands 1 and 2 (SPI1 and SPI2) and the importance of the PhoP/Q two-component regulatory system are similar to what has been shown in mouse macrophages. However, in contrast to mouse macrophages, where replication is SPI2 dependent, we observed early SPI2-independent replication in addition to later SPI2-dependent replication in M0 macrophages. Only SPI2-dependent replication was associated with death of the host cell at later time points. Altogether, our results reveal a very nuanced interaction between Salmonella and human macrophages. PMID:25895967

  17. SAMHD1 Limits HIV-1 Antigen Presentation by Monocyte-Derived Dendritic Cells

    PubMed Central

    Bruel, Timothée; Cardinaud, Sylvain; Porrot, Françoise; Prado, Julia G.; Moris, Arnaud

    2015-01-01

    ABSTRACT Monocyte-derived dendritic cells (MDDC) stimulate CD8+ cytotoxic T lymphocytes (CTL) by presenting endogenous and exogenous viral peptides via major histocompatibility complex class I (MHC-I) molecules. MDDC are poorly susceptible to HIV-1, in part due to the presence of SAMHD1, a cellular enzyme that depletes intracellular deoxynucleoside triphosphates (dNTPs) and degrades viral RNA. Vpx, an HIV-2/SIVsm protein absent from HIV-1, antagonizes SAMHD1 by inducing its degradation. The impact of SAMHD1 on the adaptive cellular immune response remains poorly characterized. Here, we asked whether SAMHD1 modulates MHC-I-restricted HIV-1 antigen presentation. Untreated MDDC or MDDC pretreated with Vpx were exposed to HIV-1, and antigen presentation was examined by monitoring the activation of an HIV-1 Gag-specific CTL clone. SAMHD1 depletion strongly enhanced productive infection of MDDC as well as endogenous HIV-1 antigen presentation. Time-lapse microscopy analysis demonstrated that in the absence of SAMHD1, the CTL rapidly killed infected MDDC. We also report that various transmitted/founder (T/F) HIV-1 strains poorly infected MDDC and, as a consequence, did not stimulate CTL. Vesicular stomatitis virus glycoprotein (VSV-G) pseudotyping of T/F alleviated a block in viral entry and induced antigen presentation only in the absence of SAMHD1. Furthermore, by using another CTL clone that mostly recognizes incoming HIV-1 antigens, we demonstrate that SAMHD1 does not influence exogenous viral antigen presentation. Altogether, our results demonstrate that the antiviral activity of SAMHD1 impacts antigen presentation by DC, highlighting the link that exists between restriction factors and adaptive immune responses. IMPORTANCE Upon viral infection, DC may present antigens derived from incoming viral material in the absence of productive infection of DC or from newly synthesized viral proteins. In the case of HIV, productive infection of DC is blocked at an early

  18. Matrix metalloproteinase-12 gene regulation by a PPAR alpha agonist in human monocyte-derived macrophages

    SciTech Connect

    Souissi, Imen Jguirim; Billiet, Ludivine; Cuaz-Perolin, Clarisse; Rouis, Mustapha

    2008-11-01

    MMP-12, a macrophage-specific matrix metalloproteinase with large substrate specificity, has been reported to be highly expressed in mice, rabbits and human atherosclerotic lesions. Increased MMP-12 from inflammatory macrophages is associated with several degenerative diseases such as atherosclerosis. In this manuscript, we show that IL-1{beta}, a proinflammatory cytokine found in atherosclerotic plaques, increases both mRNA and protein levels of MMP-12 in human monocyte-derived macrophages (HMDM). Since peroxisome proliferator-activated receptors (PPARs), such as PPAR{alpha} and PPAR{gamma}, are expressed in macrophages and because PPAR activation exerts an anti-inflammatory effect on vascular cells, we have investigated the effect of PPAR{alpha} and {gamma} isoforms on MMP-12 regulation in HMDM. Our results show that MMP-12 expression (mRNA and protein) is down regulated in IL-1{beta}-treated macrophages only in the presence of a specific PPAR{alpha} agonist, GW647, in a dose-dependent manner. In contrast, this inhibitory effect was abolished in IL-1{beta}-stimulated peritoneal macrophages isolated from PPAR{alpha}{sup -/-} mice and treated with the PPAR{alpha} agonist, GW647. Moreover, reporter gene transfection experiments using different MMP-12 promoter constructs showed a reduction of the promoter activities by {approx} 50% in IL-1{beta}-stimulated PPAR{alpha}-pre-treated cells. However, MMP-12 promoter analysis did not reveal the presence of a PPRE response element. The IL-1{beta} effect is known to be mediated through the AP-1 binding site. Mutation of the AP-1 site, located at - 81 in the MMP-12 promoter region relative to the transcription start site, followed by transfection analysis, gel shift and ChIP experiments revealed that the inhibitory effect was the consequence of the protein-protein interaction between GW 647-activated PPAR{alpha} and c-Fos or c-Jun transcription factors, leading to inhibition of their binding to the AP-1 motif. These studies

  19. Superinduction of interleukin 8 mRNA in activated monocyte derived macrophages from rheumatoid arthritis patients

    PubMed Central

    Rodenburg, R.; van den Hoogen, F. H J; Barrera, P.; van Venrooij, W. J; van de Putte, L. B A

    1999-01-01

    OBJECTIVE—Synovial inflammation in patients with rheumatoid arthritis (RA) is characterised by the presence of large numbers of highly activated monocytes and macrophages. The importance of these cells in the aethiopathogenesis and prognosis of RA is increasingly recognised. The object of this report is to determine whether monocytes and monocyte derived macrophages of RA patients produce increased cytokine mRNA levels.
METHODS—Monocyte derived macrophages from RA patients and healthy controls were cultured either in the absence or presence of lipopolysaccharide. The expression levels of the mRNAs encoding GAPDH, interleukin 1β (IL1β), IL8, and α2 macroglobulin in these cells were analysed by reverse transcriptase-polymerase chain reaction (RT-PCR).
RESULTS—Activated monocyte derived macrophages from RA patients produce significantly higher IL8 mRNA levels than activated macrophages from healthy controls. By contrast, resting RA and control macrophages produce similar levels of IL8 mRNA. Culturing of activated macrophages in the presence of RA or control sera has no effect on the expression levels of IL8 mRNA. No significant differences between RA and control macrophages were observed in the expression levels of IL1β and α2 macroglobulin mRNAs.
CONCLUSION—These data indicate that the increased IL8 mRNA production capacity of RA macrophages upon activation is an intrinsic property of these cells, and is not attributable to factors present in the circulation. Based on these observations, it is postulated that this innate hyper-responsiveness of RA macrophages contributes to the high IL8 levels present in the synovial fluid of rheumatoid joints, and is implicated in the chemotactic gradient leading to the homing of leucocytes to the joints.

 PMID:10491366

  20. Biphasic Presence of Fibrocytes in a Porcine Hypertrophic Scar Model

    PubMed Central

    Travis, Taryn E.; Mino, Matthew J.; Moffatt, Lauren T.; Mauskar, Neil A.; Prindeze, Nicholas J.; Ghassemi, Pejhman; Ramella-Roman, Jessica C.; Jordan, Marion H.; Shupp, Jeffrey W.

    2014-01-01

    Objective The duroc pig has been described as a promising animal model for use in the study of human wound healing and scar formation. However little is known about the presence and chronology of the fibrocyte cell population in the healing process of these animals. Methods Wounds known to form scar were created on red duroc swine (3“ × 3”) with a dermatome to a total depth of either 0.06“ or 0.09”. These wounds were allowed to heal completely and were biopsied at scheduled time points during the healing process. Biopsies were formalin-fixed and paraffin embedded for immunohistochemical analysis. Porcine-reactive antibodies to CD-45 and procollagen-1 and a human-reactive antibody to LSP-1 were used to detect the presence of fibrocytes in immunohistochemistry an immunocytochemistry. Results Initial immunohistochemical studies showed evidence of a biphasic presence of fibrocytes. Pigs with 0.06“ deep wounds showed positive staining for CD-45 and LSP-1 within highly cellular areas at days 2 and 4 after wounding. Additional animals with 0.09” deep wounds showed positive staining within similar areas at days 56, 70, and 113 after wounding. There was no immunohistochemical evidence of fibrocytes in skin biopsies taken at days 14, 28, or 42. Procollagen-1 staining was diffuse in all samples. Cultured cells stained for CD-45, LSP-1, and procollagen-1 by immunocytochemistry. Conclusions These data confirm that fibrocytes are indeed present in this porcine model. We conclude that these cells are present after initial wounding and later during scar formation and remodeling. We believe that this is evidence of a biphasic presence of fibrocytes, first as an acute response to skin wounding followed by later involvement in the remodeling process, prompted by continued inflammation in a deep partial thickness wound. PMID:25051518

  1. Activated Human Mast Cells Induce LOX-1-Specific Scavenger Receptor Expression in Human Monocyte-Derived Macrophages

    PubMed Central

    Alanne-Kinnunen, Mervi; Lappalainen, Jani; Öörni, Katariina; Kovanen, Petri T.

    2014-01-01

    Objective Activated mast cells in atherosclerotic lesions degranulate and release bioactive compounds capable of regulating atherogenesis. Here we examined the ability of activated human primary mast cells to regulate the expression of the major scavenger receptors in cultured human primary monocyte-derived macrophages (HMDMs). Results Components released by immunologically activated human primary mast cells induced a transient expression of lectin-like oxidized LDL receptor (LOX-1) mRNA in HMDMs, while the expression of two other scavenger receptors, MSR1 and CD36, remained unaffected. The LOX-1-inducing secretory components were identified as histamine, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta (TGF-β1), which exhibited a synergistic effect on LOX-1 mRNA expression. Histamine induced a transient expression of LOX-1 protein. Mast cell –induced increase in LOX-1 expression was not associated with increased uptake of oxidized LDL by the macrophages. Conclusions Mast cell-derived histamine, TNF-α, and TGF-β1 act in concert to induce a transient increase in LOX-1 expression in human primary monocyte-derived macrophages. The LOX-1-inducing activity potentially endows mast cells a hitherto unrecognized role in the regulation of innate immune reactions in atherogenesis. PMID:25250731

  2. Laricitrin suppresses increased benzo(a)pyrene-induced lung tumor-associated monocyte-derived dendritic cell cancer progression

    PubMed Central

    CHANG, WEI-AN; HUNG, JEN-YU; TSAI, YING-MING; HSU, YA-LING; CHIANG, HUNG-HSING; CHOU, SHAH-HWA; HUANG, MING-SHYAN; KUO, PO-LIN

    2016-01-01

    Benzo(a)pyrene (BaP) stimulates lung cancer cells, promoting monocyte-derived dendritic cells to secrete soluble factors, including heparin binding-epidermal growth factor and C-X-C motif chemokine 5. The secretions from monocyte-derived dendritic cells stimulate the progression of lung cancer cells, including the migration and invasion of cells. To the best of our knowledge, these secretions remain unknown, and require additional study. The present study identified that treatment with BaP-H1395-tumor-associated dendritic cell-conditioned medium had the most marked effect on cell migration and invasion. This result may be associated with the female gender, stage 2 adenocarcinoma or mutation of the proto-oncogene B-Raf (BRAF), according to the cell line background. Laricitrin, a dietary flavonoid derivative present in grapes and red wine, suppresses certain factors and decreases the progression of lung cancer cells that are promoted by BaP in the lung cancer tumor microenvironment. The results of the present study suggest that prolonged exposure to BaP exacerbates lung cancer, particularly in female lung cancer patients with the BRAF mutation, but that laricitrin may ameliorate this effect. PMID:26998077

  3. TLR8 agonists stimulate newly recruited monocyte-derived cells into potent APCs that enhance HBsAg immunogenicity

    PubMed Central

    Du, Jun; Wu, Zhiyuan; Ren, Shurong; Wei, Yong; Gao, Meihua; Randolph, Gwendalyn J.; Qu, Chunfeng

    2011-01-01

    We previously reported that synthetic or natural Toll-like receptor (TLR) 7/8 agonists present within dead cells enhanced cell-associated antigen presentation both in vitro and in vivo. Here, we investigated the immunopotency of different chemically synthesized TLR7/8 agonists, Resiquimod, Gardiquimod, CL075, and CL097, on HBsAg immunogenicity. These agonists stimulated inflammatory monocyte-derived cells to become potent antigen-presenting dendritic cells (DCs), which augmented HBsAg specific T cell proliferation after they were conditioned with HBsAg. The TLR8 agonist CL075 and the TLR7/8 dual agonist CL097 showed more potent effects than the TLR7 agonist. Compared with alum adjuvant, when HBsAg mixed with CL075 was injected intramuscularly into mice, more monocyte-derived DCs carried antigens into draining lymph nodes and spleens. Specific Abs, particularly IgG2a, were significantly increased, and more IL-5 and IFN-γ were produced by splenocytes and intrahepatic immunocytes in mice that received HBsAg mixed with CL075 and CL097. These results suggest that TLR8 agonists are good candidates to enhance recombinant HBsAg immunogenicity to induce specific humoral and cellular immune responses. PMID:20637759

  4. Gene expression profiling of the host response to HIV-1 B, C, or A/E infection in monocyte-derived dendritic cells

    SciTech Connect

    Solis, Mayra; Wilkinson, Peter; Romieu, Raphaelle; Hernandez, Eduardo; Wainberg, Mark A.; Hiscott, John . E-mail: john.hiscott@mcgill.ca

    2006-08-15

    Dendritic cells (DC) are among the first targets of human immunodeficiency virus type-1 (HIV-1) infection and in turn play a crucial role in viral transmission to T cells and in the regulation of the immune response. The major group of HIV-1 has diversified genetically based on variation in env sequences and comprise at least 11 subtypes. Because little is known about the host response elicited against different HIV-1 clade isolates in vivo, we sought to use gene expression profiling to identify genes regulated by HIV-1 subtypes B, C, and A/E upon de novo infection of primary immature monocyte-derived DC (iMDDCs). A total of 3700 immune-related genes were subjected to a significance analysis of microarrays (SAM); 656 genes were selected as significant and were further divided into 8 functional categories. Regardless of the time of infection, 20% of the genes affected by HIV-1 were involved in signal transduction, followed by 14% of the genes identified as transcription-related genes, and 7% were classified as playing a role in cell proliferation and cell cycle. Furthermore, 7% of the genes were immune response genes. By 72 h postinfection, genes upregulated by subtype B included the inhibitor of the matrix metalloproteinase TIMP2 and the heat shock protein 40 homolog (Hsp40) DNAJB1, whereas the IFN inducible gene STAT1, the MAPK1/ERK2 kinase regulator ST5, and the chemokine CXCL3 and SHC1 genes were induced by subtypes C and A/E. These analyses distinguish a temporally regulated host response to de novo HIV-1 infection in primary dendritic cells.

  5. Effect of cytokines on Siglec-1 and HIV-1 entry in monocyte-derived macrophages: the importance of HIV-1 envelope V1V2 region.

    PubMed

    Jobe, Ousman; Trinh, Hung V; Kim, Jiae; Alsalmi, Wadad; Tovanabutra, Sodsai; Ehrenberg, Philip K; Peachman, Kristina K; Gao, Guofen; Thomas, Rasmi; Kim, Jerome H; Michael, Nelson L; Alving, Carl R; Rao, Venigalla B; Rao, Mangala

    2016-06-01

    Monocytes and monocyte-derived macrophages express relatively low levels of CD4. Despite this, macrophages can be effectively infected with human immunodeficiency virus type 1. Macrophages have a critical role in human immunodeficiency virus type 1 transmission; however, the mechanism or mechanisms of virus infection are poorly understood. We report that growth factors, such as granulocyte macrophage colony-stimulating factor and macrophage colony-stimulating factor affect the phenotypic profile and permissiveness of macrophages to human immunodeficiency virus type 1. Human immunodeficiency virus type 1 infection of monocyte-derived macrophages derived from granulocyte macrophage and macrophage colony-stimulating factors was predominantly facilitated by the sialic acid-binding immunoglobulin-like lectin-1. The number of sialic acid-binding immunoglobulin-like lectin receptors on macrophage colony-stimulating factor-derived monocyte-derived macrophages was significantly greater than on granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages, and correspondingly, human immunodeficiency virus type 1 infection was greater in the macrophage colony-stimulating factor-derived monocyte-derived macrophages. Single-genome analysis and quantitative reverse transcriptase-polymerase chain reaction revealed that the differences in infectivity was not due to differences in viral fitness or in viral variants with differential infectivity but was due to reduced viral entry into the granulocyte macrophage colony-stimulating factor-derived monocyte-derived macrophages. Anti-sialic acid-binding immunoglobulin-like lectin, trimeric glycoprotein 145, and scaffolded V1V2 proteins were bound to sialic acid-binding immunoglobulin-like lectin and significantly reduced human immunodeficiency virus type 1 entry and infection. Furthermore, sialic acid residues present in the V1V2 region of the envelope protein mediated human immunodeficiency virus type 1

  6. Effect of a standardized liver and spleen fraction of peptides on the differentiation of human monocyte-derived macrophages.

    PubMed

    Spessotto, P; Bulla, R; Mittenzwei, H; Dri, P

    1994-06-01

    The effect of Factor AF2 (AF2), a standardized fraction of peptides with a molecular weight of < 10,000 Dalton obtained from livers and spleens of newborn lambs, on the differentiation of human monocyte-derived macrophages was studied, in view of the central role played by these cells in inflammation and tumor cytotoxicity. The results show that the drug 1. increases the cell density of cultures, 2. favours the morphologic differentiation of monocytes into macrophages, and 3. increases the macrophages phagocytic capacity. The first two effects are observed when monocytes are cultured in 1% serum but not in 10% serum while the enhancement of phagocytic activity is detected at both serum concentrations. PMID:8053979

  7. Equine herpesvirus type 1 (EHV1) induces alterations in the immunophenotypic profile of equine monocyte-derived dendritic cells.

    PubMed

    Claessen, Christophe; De Lange, Valérie; Huang, Teng; Ma, Guanggang; Osterrieder, Nikolaus; Favoreel, Herman; Van de Walle, Gerlinde R

    2016-04-01

    Equine herpesvirus 1 (EHV1) is an α-herpesvirus that can infect a variety of different cells in vitro and in vivo, including dendritic cells (DC) which are essential in the immune response against EHV1. Infection of equine monocyte-derived DC (MDDC) with EHV1 induced down-regulation of major histocompatibility complex I (MHCI), CD83, CD86, CD206, CD29 and CD172a, but not of CD11a/CD18 and MHCII. This down-regulation was not mediated by the virion host-shutoff (VHS) protein or pUL49.5. Interestingly, down-regulation of CD83 and CD86 was in part mediated by pUL56. Taken together, these data indicate that EHV1 employs different and still unresolved mechanisms to induce down-regulation of several functionally important cell surface proteins on equine DC. PMID:26920348

  8. Nanoparticle based galectin-1 gene silencing, implications in methamphetamine regulation of HIV-1 infection in monocyte derived macrophages.

    PubMed

    Reynolds, Jessica L; Law, Wing Cheung; Mahajan, Supriya D; Aalinkeel, Ravikumar; Nair, Bindukumar; Sykes, Donald E; Yong, Ken-Tye; Hui, Rui; Prasad, Paras N; Schwartz, Stanley A

    2012-09-01

    Galectin-1, an adhesion molecule, is expressed in macrophages and implicated in human immunodeficiency virus (HIV-1) viral adsorption. In this study, we investigated the effects of methamphetamine on galectin-1 production in human monocyte derived macrophages (MDM) and the role of galectin-1 in methamphetamine potentiation of HIV-1 infection. Herein we show that levels of galectin-1 gene and protein expression are significantly increased by methamphetamine. Furthermore, concomitant incubation of MDM with galectin-1 and methamphetamine facilitates HIV-1 infection compared to galectin-1 alone or methamphetamine alone. We utilized a nanotechnology approach that uses gold nanorod (GNR)-galectin-1 siRNA complexes (nanoplexes) to inhibit gene expression for galectin-1. Nanoplexes significantly silenced gene expression for galectin-1 and reversed the effects of methamphetamine on galectin-1 gene expression. Moreover, the effects of methamphetamine on HIV-1 infection were attenuated in the presence of the nanoplex in MDM. PMID:22689223

  9. MicroRNA-155 modulates the interleukin-1 signaling pathway in activated human monocyte-derived dendritic cells

    PubMed Central

    Ceppi, Maurizio; Pereira, Patricia M.; Dunand-Sauthier, Isabelle; Barras, Emmanuèle; Reith, Walter; Santos, Manuel A.; Pierre, Philippe

    2009-01-01

    In response to inflammatory stimulation, dendritic cells (DCs) have a remarkable pattern of differentiation (maturation) that exhibits specific mechanisms to control immunity. Here, we show that in response to Lipopolysaccharides (LPS), several microRNAs (miRNAs) are regulated in human monocyte-derived dendritic cells. Among these miRNAs, miR-155 is highly up-regulated during maturation. Using LNA silencing combined to microarray technology, we have identified the Toll-like receptor/interleukin-1 (TLR/IL-1) inflammatory pathway as a general target of miR-155. We further demonstrate that miR-155 directly controls the level of TAB2, an important signal transduction molecule. Our observations suggest, therefore, that in mature human DCs, miR-155 is part of a negative feedback loop, which down-modulates inflammatory cytokine production in response to microbial stimuli. PMID:19193853

  10. Patient specific proteolytic activity of monocyte-derived macrophages and osteoclasts predicted with temporal kinase activation states during differentiation

    PubMed Central

    Park, Keon-Young; Li, Weiwei A.; Platt, Manu O.

    2012-01-01

    Patient-to-patient variability in disease progression continues to complicate clinical decisions of treatment regimens for cardiovascular diseases, metastatic cancers and osteoporosis. Here, we investigated if monocytes, circulating white blood cells that enter tissues and contribute to disease progression by differentiating into macrophages or osteoclasts, could be useful in understanding this variability. Monocyte-derived macrophages and osteoclasts produce cysteine cathepsins, powerful extracellular matrix proteases which have been mechanistically linked to accelerated atherosclerotic, osteoporotic, and tumor progression. We hypothesized that multivariate analysis of temporal kinase activation states during monocyte differentiation could predict cathepsin proteolytic responses of monocyte-derived macrophages and osteoclasts in a patient-specific manner. Freshly isolated primary monocytes were differentiated with M-CSF or RANKL into macrophages or osteoclasts, respectively, and phosphorylation of ERK1/2, Akt, p38 MAPK, JNK, c-jun, and IκB-α were measured at days 1, 3, 6, and 9. In parallel, cell diameters and numbers of nuclei were measured, and multiplex cathepsin zymography was used to quantify cathepsins K, L, S, and V activity from cell extracts and conditioned media. There was extensive patient-to-patient variability in temporal kinase activation states, cell morphologies, and cathepsin K, L, S, and V proteolytic activity. Partial least squares regression models trained with temporal kinase activation states successfully predicted patient-specific morphological characteristics (mean cell diameter and number of nuclei) and patient-specific cathepsin proteolytic activity with predictability as high as 95%, even with the challenge of incorporating the complex, unknown cues from individual patients’ unique genetic and biochemical backgrounds. This personalized medicine approach considers patient variability in kinase signals to predict cathepsin activity

  11. Establishing Porcine Monocyte-Derived Macrophage and Dendritic Cell Systems for Studying the Interaction with PRRSV-1

    PubMed Central

    Singleton, Helen; Graham, Simon P.; Bodman-Smith, Katherine B.; Frossard, Jean-Pierre; Steinbach, Falko

    2016-01-01

    Monocyte-derived macrophages (MoMØ) and monocyte-derived dendritic cells (MoDC) are two model systems well established in human and rodent systems that can be used to study the interaction of pathogens with host cells. Porcine reproductive and respiratory syndrome virus (PRRSV) is known to infect myeloid cells, such as macrophages (MØ) and dendritic cells (DC). Therefore, this study aimed to establish systems for the differentiation and characterization of MoMØ and MoDC for subsequent infection with PRRSV-1. M-CSF differentiated MoMØ were stimulated with activators for classical (M1) or alternative (M2) activation. GM-CSF and IL-4 generated MoDC were activated with the well established maturation cocktail containing PAMPs and cytokines. In addition, MoMØ and MoDC were treated with dexamethasone and IL-10, which are known immuno-suppressive reagents. Cells were characterized by morphology, phenotype, and function and porcine MØ subsets highlighted some divergence from described human counterparts, while MoDC, appeared more similar to mouse and human DCs. The infection with PRRSV-1 strain Lena demonstrated different replication kinetics between MoMØ and MoDC and within subsets of each cell type. While MoMØ susceptibility was significantly increased by dexamethasone and IL-10 with an accompanying increase in CD163/CD169 expression, MoDC supported only a minimal replication of PRRSV These findings underline the high variability in the susceptibility of porcine myeloid cells toward PRRSV-1 infection. PMID:27313573

  12. Peripheral blood fibrocytes: new information to explain the dynamics of Leishmania infection

    PubMed Central

    Macedo-Silva, Roger Magno; dos Santos, Carina de Lima Pereira; Diniz, Vanessa Alvaro; de Carvalho, Jorge José; Guerra, Camila; Côrte-Real, Suzana

    2013-01-01

    Fibrocytes are important for understanding the progression of many diseases because they are present in areas where pathogenic lesions are generated. However, the morphology of fibrocytes and their interactions with parasites are poorly understood. In this study, we examined the morphology of peripheral blood fibrocytes and their interactions with Leishmania (L.) amazonensis . Through ultrastructural analysis, we describe the details of fibrocyte morphology and how fibrocytes rapidly internalise Leishmania promastigotes. The parasites differentiated into amastigotes after 2 h in phagolysosomes and the infection was completely resolved after 72 h. Early in the infection, we found increased nitric oxide production and large lysosomes with electron-dense material. These factors may regulate the proliferation and death of the parasites. Because fibrocytes are present at the infection site and are directly involved in developing cutaneous leishmaniasis, they are targets for effective, non-toxic cell-based therapies that control and treat leishmaniasis. PMID:24626303

  13. IL-13 REPLACES IL-4 IN DEVELOPMENT OF MONOCYTE DERIVED DENDRITIC CELLS (MODC) OF SWINE; THE INNATE IMMUNE RESPONSE OF MODC TO TOLL-LIKE RECEPTOR AGONISTS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dendritic cells (DCs) are a critical aspect of innate immune responses in addition to initiating adaptive immunity. In vitro generation of monocyte derived dendritic cells (MoDC) by culturing cells in IL-4 and GM-CSF has been reported for multiple species including swine. However, IL-4 is not a prom...

  14. Killing of Escherichia coli by Crohn's Disease Monocyte-derived Macrophages and Its Enhancement by Hydroxychloroquine and Vitamin D

    PubMed Central

    Flanagan, Paul K.; Chiewchengchol, Direkrit; Wright, Helen L.; Edwards, Steven W.; Alswied, Abdullah; Satsangi, Jack; Subramanian, Sreedhar; Rhodes, Jonathan M.

    2015-01-01

    Background: Crohn's disease (CD) is associated with defective innate immunity, including impaired neutrophil chemotaxis, and mucosal invasion by bacteria, particularly adherent and invasive Escherichia coli that replicate inside macrophage phagolysosomes. We compared CD and healthy control (HC) macrophages for their abilities to kill E. coli and generate neutrophil chemoattractants and also assessed the effects of hydroxychloroquine (HCQ) and vitamin D on killing of phagocytosed E. coli. Methods: Peripheral blood monocyte-derived macrophages from CD and HC were compared for bacterial killing and generation of neutrophil chemoattractants in response to CD-derived E. coli. Escherichia coli replication was also assessed in the presence and absence of HCQ, alone and with antibiotics, and vitamin D. Results: Monocyte-derived macrophages from patients with CD were similar to HC in allowing replication of phagocytosed CD-derived E. coli: HM605 {CD: N = 10, mean fold replication in 3 hr = 1.08 (95% confidence interval [CI], 0.39–1.78); HC: N = 9, 1.50 (95% CI, 1.02–1.97); P = 0.15} and also in generation of neutrophil chemoattractants in response to E. coli (mean fold chemotaxis relative to control: CD = 2.55 [95% CI, 2.31–2.80]; HC = 2.65 [95% CI, 2.46–2.85], P = 0.42). HCQ and 1,25 OH2-vitamin D3 both caused dose-dependent inhibition of intramacrophage E. coli replication 3-hour postinfection; HCQ: 73.9% inhibition (P < 0.001) at 1 μg/mL, accompanied by raised intraphagosomal pH, and 1,25 OH2-vitamin D3: 80.7% inhibition (P < 0.05) at 80 nM. HCQ had synergistic effects with doxycycline and ciprofloxacin. Conclusions: CD and HC macrophages perform similarly in allowing replication of phagocytosed E. coli and generating neutrophil chemoattractants. Replication of phagocytosed E. coli was substantially decreased by HCQ and vitamin D. These warrant further therapeutic trials in CD in combination with relevant antibiotics. PMID:25839777

  15. Effect of size of man-made and natural mineral fibers on chemiluminescent response in human monocyte-derived macrophages.

    PubMed Central

    Ohyama, M; Otake, T; Morinaga, K

    2001-01-01

    Fiber size is an important factor in the tumorigenicity of various mineral fibers and asbestos fibers in animal experiments. We examined the time course of the ability to induce lucigenin-dependent chemiluminescence (CL) from human monocyte-derived macrophages exposed to Japan Fibrous Material standard reference samples (glass wool, rock wool, micro glass fiber, two types of refractory ceramic fiber, refractory mullite fiber, potassium titanium whisker, silicon carbide whisker, titanium oxide whisker, and wollastonite). We determined how fiber length or width might modify the response of cells. We found that the patterns of time-dependent increase of CL (sigmoid type) were similar for each sample except wollastonite. We observed a strong correlation between geometric-mean length and ability to induce CL in seven samples > 6 microm in length over the time course (largest r(2) = 0.9760). Although we also observed a close positive correlation between geometric-mean width and the ability to induce CL in eight samples < 1.8 microm in width at 15 min (r(2) = 0.8760), a sample of 2.4 microm in width had a low ability to induce CL. Moreover, the relationship between width and the rate of increase in ability to induce CL had a negative correlation at 30-60 min (largest r(2) = 0.7473). Our findings suggest that the release of superoxide from macrophages occurs nonspecifically for various types of mineral fibers depending on fiber length. PMID:11675268

  16. SAMHD1 Restricts HIV-1 Cell-to-Cell Transmission and Limits Immune Detection in Monocyte-Derived Dendritic Cells

    PubMed Central

    Puigdomènech, Isabel; Casartelli, Nicoletta; Porrot, Françoise

    2013-01-01

    SAMHD1 is a viral restriction factor expressed in dendritic cells and other cells, inhibiting infection by cell-free human immunodeficiency virus type 1 (HIV-1) particles. SAMHD1 depletes the intracellular pool of deoxynucleoside triphosphates, thus impairing HIV-1 reverse transcription and productive infection in noncycling cells. The Vpx protein from HIV-2 or simian immunodeficiency virus (SIVsm/SIVmac) antagonizes the effect of SAMHD1 by triggering its degradation. A large part of HIV-1 spread occurs through direct contacts between infected cells and bystander target cells. Here, we asked whether SAMHD1 impairs direct HIV-1 transmission from infected T lymphocytes to monocyte-derived dendritic cells (MDDCs). HIV-1-infected lymphocytes were cocultivated with MDDCs that have been pretreated or not with Vpx or with small interfering RNA against SAMHD1. We show that in the cocultures, SAMHD1 significantly inhibits productive cell-to-cell transmission to target MDDCs and prevents the type I interferon response and expression of the interferon-stimulated gene MxA. Therefore, SAMHD1, by controlling the sensitivity of MDDCs to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response. PMID:23269793

  17. Equine monocyte-derived macrophage cultures and their applications for infectivity and neutralization studies of equine infectious anemia virus.

    PubMed

    Raabe, M R; Issel, C J; Montelaro, R C

    1998-03-01

    Equine infectious anemia virus (EIAV) has been shown to infect cells of monocyte/macrophage lineage. These primary cells are intrinsically difficult to obtain, to purify and to culture in vitro for extended periods of time. As a result, most in vitro studies concerning this lentivirus make use of primary equine fibroblasts or transformed canine or feline cell lines. We describe methods that yield reproducibly pure cultures of equine blood monocytes from peripheral blood mononuclear cells. The in vitro differentiation of these cells into mature equine macrophage was verified using various cytochemical staining methods. The equine monocyte-derived macrophage (MDM) cultures were found to replicate cell-adapted and field strains of EIAV more efficiently than cultures of fully differentiated equine splenic macrophage. Having established reproducible and fully differentiated cultures of equine macrophage, in vitro assays of virus infectivity and serum neutralization were developed using the in vivo target cell of EIAV. These procedures, while developed for the EIAV system, should be equally useful for in vitro cultures of other macrophage-tropic pathogens of horses. PMID:9628225

  18. Leishmania donovani infection drives the priming of human monocyte-derived dendritic cells during Plasmodium falciparum co-infections.

    PubMed

    van den Bogaart, E; de Bes, H M; Balraadjsing, P P S; Mens, P F; Adams, E R; Grobusch, M P; van Die, I; Schallig, H D F H

    2015-09-01

    Functional impairment of dendritic cells (DCs) is part of a survival strategy evolved by Leishmania and Plasmodium parasites to evade host immune responses. Here, the effects of co-exposing human monocyte-derived DCs to Leishmania donovani promastigotes and Plasmodium falciparum-infected erythrocytes were investigated. Co-stimulation resulted in a dual, dose-dependent effect on DC differentiation which ranged from semi-mature cells, secreting low interleukin(-12p70 levels to a complete lack of phenotypic maturation in the presence of high parasite amounts. The effect was mainly triggered by the Leishmania parasites, as illustrated by their ability to induce semi-mature, interleukin-10-producing DCs, that poorly responded to lipopolysaccharide stimulation. Conversely, P. falciparum blood-stage forms failed to activate DCs and only slightly interfered with lipopolysaccharide effects. Stimulation with high L. donovani concentrations triggered phosphatidylserine translocation, whose onset presented after initiating the maturation impairment process. When added in combination, the two parasites could co-localize in the same DCs, confirming that the leading effects of Leishmania over Plasmodium may not be due to mutual exclusion. Altogether, these results suggest that in the presence of visceral leishmaniasis-malaria co-infections, Leishmania-driven effects may overrule the more silent response elicited by P. falciparum, shaping host immunity towards a regulatory pattern and possibly delaying disease resolution. PMID:26173941

  19. Monocyte-Derived Dendritic Cells Are Essential for CD8+ T Cell Activation and Antitumor Responses After Local Immunotherapy

    PubMed Central

    Kuhn, Sabine; Yang, Jianping; Ronchese, Franca

    2015-01-01

    Tumors harbor several populations of dendritic cells (DCs) with the ability to prime tumor-specific T cells. However, these T cells mostly fail to differentiate into armed effectors and are unable to control tumor growth. We have previously shown that treatment with immunostimulatory agents at the tumor site can activate antitumor immune responses and is associated with the appearance of a population of monocyte-derived DCs (moDCs) in the tumor and tumor-draining lymph node (dLN). Here, we use depletion of DCs or monocytes and monocyte transfer to show that these moDCs are critical to the activation of antitumor immune responses. Treatment with the immunostimulatory agents monosodium urate crystals and Mycobacterium smegmatis induced the accumulation of monocytes in the dLN, their upregulation of CD11c and MHCII, and expression of iNOS, TNFα, and IL12p40. Blocking monocyte entry into the lymph node and tumor through neutralization of the chemokine CCL2 or inhibition of colony-stimulating factor-1 receptor signaling prevented the generation of moDCs, the infiltration of tumor-specific T cells into the tumor, and antitumor responses. In a reciprocal fashion, monocytes transferred into mice depleted of CD11c+ cells were sufficient to rescue CD8+ T cell priming in lymph node and delay tumor growth. Thus, monocytes exposed to the appropriate conditions become powerful activators of tumor-specific CD8+ T cells and antitumor immunity. PMID:26635798

  20. Expression of CD1a and Type-1 Polarization Are Dissociated in Human Monocyte-Derived Dendritic Cells.

    PubMed

    Mester, Brigitta; Bauer, Evelyn; Wood, Catherine E; Hermans, Ian F; Gasser, Olivier

    2015-01-01

    Ex vivo generated monocyte-derived dendritic cell (moDC)-vaccines have long been touted as promising immunotherapeutic agents for cancer treatment, although the response rate generally remains low. The reasons for this are still unclear and confounded by the diversity in manufacturing protocols that may affect moDC function. Preclinical studies have shown that the stimulatory function of dendritic cells can be improved by engaging invariant NKT cells in vivo through the presentation of the glycolipid alpha-galactosylceramide via CD1d. However, expression of CD1d on moDC has been shown to be negatively correlated with expression of CD1a, which in turn has been suggested to be a surrogate marker for IL-12 secreting type-1 polarized moDC, the preferred functional characteristics for cancer vaccines. Here we challenge this notion by showing that plasma-derived lipids drive functional levels of CD1d expression, while CD1a expression can vary considerably in these cells without being correlated with a loss of polarization or immunogenicity. PMID:26460687

  1. Microglia and monocyte-derived macrophages: functionally distinct populations that act in concert in CNS plasticity and repair

    PubMed Central

    London, Anat; Cohen, Merav; Schwartz, Michal

    2013-01-01

    Functional macrophage heterogeneity is recognized outside the central nervous system (CNS), where alternatively activated macrophages can perform immune-resolving functions. Such functional heterogeneity was largely ignored in the CNS, with respect to the resident microglia and the myeloid-derived cells recruited from the blood following injury or disease, previously defined as blood-derived microglia; both were indistinguishably perceived detrimental. Our studies have led us to view the myeloid-derived infiltrating cells as functionally distinct from the resident microglia, and accordingly, to name them monocyte-derived macrophages (mo-MΦ). Although microglia perform various maintenance and protective roles, under certain conditions when they can no longer provide protection, mo-MΦ are recruited to the damaged CNS; there, they act not as microglial replacements but rather assistant cells, providing activities that cannot be timely performed by the resident cells. Here, we focus on the functional heterogeneity of microglia/mo-MΦ, emphasizing that, as opposed to the mo-MΦ, microglia often fail to timely acquire the phenotype essential for CNS repair. PMID:23596391

  2. Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4(+) T cells.

    PubMed

    Kok, Yik Lim; Vongrad, Valentina; Shilaih, Mohaned; Di Giallonardo, Francesca; Kuster, Herbert; Kouyos, Roger; Günthard, Huldrych F; Metzner, Karin J

    2016-01-01

    The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4(+) T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4(+) T cells were over-represented in gene hotspots identified in CD4(+) T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4(+) T cells. PMID:27067385

  3. Annexin 2: a novel human immunodeficiency virus type 1 Gag binding protein involved in replication in monocyte-derived macrophages.

    PubMed

    Ryzhova, Elena V; Vos, Robin M; Albright, Andrew V; Harrist, Alexia V; Harvey, Thomas; González-Scarano, Francisco

    2006-03-01

    Human immunodeficiency virus (HIV) replication in the major natural target cells, CD4+ T lymphocytes and macrophages, is parallel in many aspects of the virus life cycle. However, it differs as to viral assembly and budding, which take place on plasma membranes in T cells and on endosomal membranes in macrophages. It has been postulated that cell type-specific host factors may aid in directing viral assembly to distinct destinations. In this study we defined annexin 2 (Anx2) as a novel HIV Gag binding partner in macrophages. Anx2-Gag binding was confined to productively infected macrophages and was not detected in quiescently infected monocyte-derived macrophages (MDM) in which an HIV replication block was mapped to the late stages of the viral life cycle (A. V. Albright, R. M. Vos, and F. Gonzalez-Scarano, Virology 325:328-339, 2004). We demonstrate that the Anx2-Gag interaction likely occurs at the limiting membranes of late endosomes/multivesicular bodies and that Anx2 depletion is associated with a significant decline in the infectivity of released virions; this coincided with incomplete Gag processing and inefficient incorporation of CD63. Cumulatively, our data suggest that Anx2 is essential for the proper assembly of HIV in MDM. PMID:16501079

  4. Immunomodulatory effects of adult Haemonchus contortus excretory/secretory products on human monocyte-derived dendritic cells.

    PubMed

    Rehman, Z U; Knight, J S; Koolaard, J; Simpson, H V; Pernthaner, A

    2015-12-01

    The levels of expression of surface molecules and release of cytokines and chemokines of human monocyte-derived dendritic cells were determined after their exposure to adult H. contortus excretory/secretory (ES) products or a combination of ES products and bacterial lipopolysaccharide (LPS). Worm products provoked a weak response and only partial maturation of the dendritic cells, consistent with the hyporesponsiveness and more tolerogenic immune environment present in parasitized animals and humans. Co-stimulation with LPS demonstrated that H. contortus secretions, like those of other helminths, contain immunomodulators capable of reducing some aspects of the strong T(H)1/T(H)2 response evoked by bacterial LPS. There were significant reductions in the release of some cytokine/chemokines by LPS-stimulated mdDCs and a trend (although not significant at P < 0.05) for reduced expression levels of CD40, CD80 and HLA-DR. A prominent feature was the variability in responses of dendritic cells from the four donors, even on different days in repeat experiments, suggesting that generalized conclusions may be difficult to make, except in genetically related animals. Such observations may therefore be applicable only to restricted populations. In addition, previous exposure to parasites in a target population for immunomodulatory therapy may be an important factor in assessing the likelihood of adverse reactions or failures in the treatment to worm therapy. PMID:26457886

  5. Collagen Induces Maturation of Human Monocyte-Derived Dendritic Cells by Signaling through Osteoclast-Associated Receptor

    PubMed Central

    Schultz, Heidi S.; Nitze, Louise M.; Zeuthen, Louise H.; Keller, Pernille; Gruhler, Albrecht; Pass, Jesper; Chen, Jianhe; Guo, Li; Fleetwood, Andrew J.; Hamilton, John A.; Berchtold, Martin W.

    2015-01-01

    Osteoclast-associated receptor (OSCAR) is widely expressed on human myeloid cells. Collagen types (Col)I, II, and III have been described as OSCAR ligands, and ColII peptides can induce costimulatory signaling in receptor activator for NF-κB–dependent osteoclastogenesis. In this study, we isolated collagen as an OSCAR-interacting protein from the membranes of murine osteoblasts. We have investigated a functional outcome of the OSCAR–collagen interaction in human monocyte-derived dendritic cells (DCs). OSCAR engagement by ColI/II-induced activation/maturation of DCs is characterized by upregulation of cell surface markers and secretion of cytokines. These collagen-matured DCs (Col-DCs) were efficient drivers of allogeneic and autologous naive T cell proliferation. The T cells expanded by Col-DCs secreted cytokines with no clear T cell polarization pattern. Global RNA profiling revealed that multiple proinflammatory mediators, including cytokines and cytokine receptors, components of the stable immune synapse (namely CD40, CD86, CD80, and ICAM-1), as well as components of TNF and TLR signaling, are transcriptional targets of OSCAR in DCs. Our findings indicate the existence of a novel pathway by which extracellular matrix proteins locally drive maturation of DCs during inflammatory conditions, for example, within synovial tissue of rheumatoid arthritis patients, where collagens become exposed during tissue remodeling and are thus accessible for interaction with infiltrating precursors of DCs. PMID:25725106

  6. Serum IL-10 from systemic lupus erythematosus patients suppresses the differentiation and function of monocyte-derived dendritic cells

    PubMed Central

    Sun, Zhida; Zhang, Rong; Wang, Huijuan; Jiang, Pengtao; Zhang, Jiangquan; Zhang, Mingshun; Gu, Lei; Yang, Xiaofan; Zhang, Miaojia; Ji, Xiaohui

    2012-01-01

    The role played by cytokines, other than interferon (IFN)-α, in the differentiation and function of dendritic cells (DCs) in systemic lupus erythematosus (SLE), remains unclear. Serum interleukin-10 (IL-10) levels are generally elevated in SLE patients, which might modulate the differentiation of DCs. In this study, DCs were induced from monocytes either by transendothelial trafficking or by culture with granulocyte-macrophage colony-stimulating factor (GM-CSF) + IL-4 + tumor necrosis factor (TNF)-α. Both systems were used to investigate the effects of elevated serum IL-10 level on DC differentiation in SLE patients. The results showed that monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the expression of human leukocyte antigen (HLA)-DR and CD80, decreased IL-12p40 level, and increased IL-10 level, and exhibited an impaired capacity to stimulate allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved in the pathogenesis of SLE by modulating the differentiation and function of DCs. PMID:23554785

  7. Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses.

    PubMed

    Della Chiesa, Mariella; Romagnani, Chiara; Thiel, Andreas; Moretta, Lorenzo; Moretta, Alessandro

    2006-12-01

    During innate immune responses, natural killer (NK) cells may interact with both plasmacytoid dendritic cells (pDCs) and monocyte-derived dendritic cells (MDDCs). We show that freshly isolated NK cells promote the release by pDCs of IFN-alpha, in a CpG-dependent manner, whereas they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN-alpha up-regulates NK-mediated killing, whereas IL-6 could promote B-cell differentiation. We also show that exposure to exogenous IL-12 or coculture with maturing MDDCs up-regulates the NK-cell-dependent IFN-alpha production by pDCs. On the other hand, NK cells cocultured with pDCs acquire the ability to kill immature MDDCs, thus favoring their editing process. Finally, we show that activated NK cells are unable to lyse pDCs because these cells display an intrinsic resistance to lysis. The exposure of pDCs to IL-3 increased their susceptibility to NK-cell cytotoxicity resulting from a de novo expression of ligands for activating NK-cell receptors, such as the DNAM-1 ligand nectin-2. Thus, different cell-to-cell interactions and various cytokines appear to control a multidirectional network between NK cells, MDDCs, and pDCs that is likely to play an important role during the early phase of innate immune responses to viral infections and to tumors. PMID:16873676

  8. Pericellular mobilization of the tissue-destructive cysteine proteinases, cathepsins B, L, and S, by human monocyte-derived macrophages.

    PubMed Central

    Reddy, V Y; Zhang, Q Y; Weiss, S J

    1995-01-01

    Human macrophages are believed to damage host tissues in chronic inflammatory disease states, but these cells have been reported to express only modest degradative activity in vitro. However, while examining the ability of human monocytes to degrade the extracellular matrix component elastin, we identified culture conditions under which the cells matured into a macrophage population that displayed a degradative phenotype hundreds of times more destructive than that previously ascribed to any other cell population. The monocyte-derived macrophages synthesized elastinolytic matrix metalloproteinases (i.e., gelatinase B and matrilysin) as well as cysteine proteinases (i.e., cathepsins B, L, and S), but only the cathepsins were detected in the extracellular milieu as fully processed, mature enzymes by either vital fluorescence or active-site labeling. Consistent with these observations, macrophage-mediated elastinolytic activity was not affected by matrix metalloproteinase inhibitors but could be almost completely abrogated by inhibiting cathepsins L and S. These data demonstrate that human macrophages mobilize cysteine proteinases to arm themselves with a powerful effector mechanism that can participate in the pathophysiologic remodeling of the extracellular matrix. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:7731994

  9. Monocyte-derived macrophages exhibit distinct and more restricted HIV-1 integration site repertoire than CD4+ T cells

    PubMed Central

    Kok, Yik Lim; Vongrad, Valentina; Shilaih, Mohaned; Di Giallonardo, Francesca; Kuster, Herbert; Kouyos, Roger; Günthard, Huldrych F.; Metzner, Karin J.

    2016-01-01

    The host genetic landscape surrounding integrated HIV-1 has an impact on the fate of the provirus. Studies analysing HIV-1 integration sites in macrophages are scarce. We studied HIV-1 integration site patterns in monocyte-derived macrophages (MDMs) and activated CD4+ T cells derived from seven antiretroviral therapy (ART)-treated HIV-1-infected individuals whose cells were infected ex vivo with autologous HIV-1 isolated during the acute phase of infection. A total of 1,484 unique HIV-1 integration sites were analysed. Their distribution in the human genome and genetic features, and the effects of HIV-1 integrase polymorphisms on the nucleotide selection specificity at these sites were indistinguishable between the two cell types, and among HIV-1 isolates. However, the repertoires of HIV-1-hosting gene clusters overlapped to a higher extent in MDMs than in CD4+ T cells. The frequencies of HIV-1 integration events in genes encoding HIV-1-interacting proteins were also different between the two cell types. Lastly, HIV-1-hosting genes linked to clonal expansion of latently HIV-1-infected CD4+ T cells were over-represented in gene hotspots identified in CD4+ T cells but not in those identified in MDMs. Taken together, the repertoire of genes targeted by HIV-1 in MDMs is distinct from and more restricted than that of CD4+ T cells. PMID:27067385

  10. Comparison of small interfering RNA (siRNA) delivery into bovine monocyte-derived macrophages by transfection and electroporation

    PubMed Central

    Jensen, Kirsty; Anderson, Jennifer A.; Glass, Elizabeth J.

    2014-01-01

    The manipulation of the RNA interference pathway using small interfering RNA (siRNA) has become the most frequently used gene silencing method. However, siRNA delivery into primary cells, especially primary macrophages, is often considered challenging. Here we report the investigation of the suitability of two methodologies: transient transfection and electroporation, to deliver siRNA targeted against the putative immunomodulatory gene Mediterranean fever (MEFV) into primary bovine monocyte-derived macrophages (bMDM). Eleven commercial transfection reagents were investigated with variable results with respect to siRNA uptake, target gene knock-down, cell toxicity and type I interferon (IFN) response induction. Three transfection reagents: Lipofectamine 2000, Lipofectamine RNAiMAX and DharmaFECT 3, were found to consistently give the best results. However, all the transfection reagents tested induced an IFN response in the absence of siRNA, which could be minimized by reducing the transfection reagent incubation period. In addition, optimized siRNA delivery into bMDM by electroporation achieved comparable levels of target gene knock-down as transient transfection, without a detectable IFN response, but with higher levels of cell toxicity. The optimized transient transfection and electroporation methodologies may provide a starting point for optimizing siRNA delivery into macrophages derived from other species or other cells considered difficult to investigate with siRNA. PMID:24598124

  11. Fibrocytes in the fibrotic lung: altered phenotype detected by flow cytometry.

    PubMed

    Reese, Charles; Lee, Rebecca; Bonner, Michael; Perry, Beth; Heywood, Jonathan; Silver, Richard M; Tourkina, Elena; Visconti, Richard P; Hoffman, Stanley

    2014-01-01

    Fibrocytes are bone marrow hematopoietic-derived cells that also express a mesenchymal cell marker (commonly collagen I) and participate in fibrotic diseases of multiple organs. Given their origin, they or their precursors must be circulating cells before recruitment into target tissues. While most previous studies focused on circulating fibrocytes, here we focus on the fibrocyte phenotype in fibrotic tissue. The study's relevance to human disease is heightened by use of a model in which bleomycin is delivered systemically, recapitulating several features of human scleroderma including multi-organ fibrosis not observed when bleomycin is delivered directly into the lungs. Using flow cytometry, we find in the fibrotic lung a large population of CD45(high) fibrocytes (called Region I) rarely found in vehicle-treated control mice. A second population of CD45+ fibrocytes (called Region II) is observed in both control and fibrotic lung. The level of CD45 in circulating fibrocytes is far lower than in either Region I or II lung fibrocytes. The chemokine receptors CXCR4 and CCR5 are expressed at higher levels in Region I than in Region II and are present at very low levels in all other lung cells including CD45+/collagen I- leucocytes. The collagen chaperone HSP47 is present at similar high levels in both Regions I and II, but at a higher level in fibrotic lung than in control lung. There is also a major population of HSP47(high)/CD45- cells in fibrotic lung not present in control lung. CD44 is present at higher levels in Region I than in Region II and at much lower levels in all other cells including CD45+/collagen I- leucocytes. When lung fibrosis is inhibited by restoring caveolin-1 activity using a caveolin-1 scaffolding domain peptide (CSD), a strong correlation is observed between fibrocyte number and fibrosis score. In summary, the distinctive phenotype of fibrotic lung fibrocytes suggests that fibrocyte differentiation occurs primarily within the target organ. PMID

  12. IRF5 Risk Polymorphisms Contribute to Inter-Individual Variance in Pattern-Recognition Receptor-Mediated Cytokine Secretion in Human Monocyte-Derived Cells

    PubMed Central

    Hedl, Matija; Abraham, Clara

    2012-01-01

    Monocyte-derived cells display highly variable cytokine secretion upon pattern-recognition receptor (PRR) stimulation across individuals; such variability likely affects inter-individual inflammatory/autoimmune disease susceptibility. To define mechanisms for this heterogeneity, we examined pattern recognition receptor (PRR)-induced monocyte-derived-cell cytokine secretion from a large cohort healthy individuals. Although cytokine secretion ranged widely among individuals, the magnitude of cytokine induction after individual Nod2 and TLR2 stimulation (a cohort of 86 individuals) or stimulation of multiple TLRs (a cohort of 77 individuals), either alone or in combination with Nod2, was consistent intra-individually across these stimuli. Nod2 and TLRs signal through interferon-regulatory-factor-5 (IRF5) and common IRF5 polymorphisms confer risk for autoimmunity. We find that cells from rs2004640 IRF5 risk-associated allele carriers secrete increased cytokines upon individual or synergistic PRR stimulation in a gene dose- and ligand dose-dependent manner in both monocyte-derived dendritic cells and macrophages. IRF5 expression knockdown in IRF5-risk-allele carrier cells significantly decreases PRR-induced cytokines. Moreover, we find that IRF5 knockdown profoundly decreases Nod2-mediated MAPK and NF-κB pathway activation, whereas the PI3K and mTOR pathways are not impaired. Finally, the IRF5 rs2004640 polymorphism is a major determinant of the variance (r2=0.53) in Nod2-induced cytokine secretion by monocyte-derived cells from different individuals. We therefore show a profound contribution of a single gene to the variance in inter-individual PRR-induced cytokines. The hyper-responsiveness of IRF5 disease-associated polymorphisms to a wide spectrum of microbial triggers has broad implications on global immunological responses, host defenses against pathogens and inflammatory/autoimmune disease susceptibility. PMID:22544929

  13. Expression and regulation of Schlafen (SLFN) family members in primary human monocytes, monocyte-derived dendritic cells and T cells

    PubMed Central

    Puck, Alexander; Aigner, Regina; Modak, Madhura; Cejka, Petra; Blaas, Dieter; Stöckl, Johannes

    2015-01-01

    Schlafen (SLFN/Slfn) family members have been investigated for their involvement in fundamental cellular processes including growth regulation, differentiation and control of viral replication. However, most research has been focused on the characterization of Slfns within the murine system or in human cell lines. Since little is known about SLFNs in primary human immune cells, we set out to analyze the expression and regulation of the six human SLFN genes in monocytes, monocyte-derived dendritic cells (moDCs) and T cells. Comparison of SLFN gene expression across these three cell types showed high mRNA expression of SLFN11 in monocytes and moDCs and high SLFN5 expression in T cells, indicating functional importance within these cell types. Differentiation of monocytes to moDCs leads to the gradual upregulation of SLFN12L and SLFN13 while SLFN12 levels were decreased by differentiation stimuli. Stimulation of moDCs via human rhinovirus, lipopolysaccharide, or IFN-α lead to strong upregulation of SLFN gene expression, while peptidoglycan poorly stimulated regulation of both SLFNs and the classical interferon-stimulated gene MxA. T cell activation was found to downregulate the expression of SLFN5, SLFN12 and SLFN12L, which was reversible upon addition of exogenous IFN-α. In conclusion, we demonstrate, that SLFN gene upregulation is mainly dependent on autocrine type I interferon signaling in primary human immune cells. Rapid decrease of SLFN expression levels following T cell receptor stimulation indicates a role of SLFNs in the regulation of human T cell quiescence. PMID:26623250

  14. Triggering of B7h by the ICOS modulates maturation and migration of monocyte-derived dendritic cells.

    PubMed

    Occhipinti, Sergio; Dianzani, Chiara; Chiocchetti, Annalisa; Boggio, Elena; Clemente, Nausicaa; Gigliotti, Casimiro Luca; Soluri, Maria Felicia; Minelli, Rosalba; Fantozzi, Roberto; Yagi, Jungi; Rojo, Josè Maria; Sblattero, Daniele; Giovarelli, Mirella; Dianzani, Umberto

    2013-02-01

    B7h, expressed by several cell types, binds ICOS expressed by activated T cells. We have previously shown that B7h triggering by ICOS-Fc inhibits human endothelial cell adhesiveness. This work investigated the effect of ICOS-Fc on human monocyte-derived dendritic cells (DCs). We found that DCs matured with LPS in the presence of ICOS-Fc (mDCs(ICOS)) produced greater amounts of IL-23 and IL-10, and promoted a higher secretion of IL-17A and IL-17F in MLCs than did those DCs matured with LPS alone (mDCs). Moreover, mDCs(ICOS) pulsed with the keyhole limpet hemocyanin Ag during the maturation phase were better stimulators of Ag-specific MHC class I-, but not class II-restricted T cells than mDCs. This was probably due to promotion of cross-presentation because it was not detected when the Flu-MA(58-66) Ag was directly loaded on already matured DCs and mDCs(ICOS). Finally, ICOS-Fc inhibited the adhesion of both immature DCs and mDCs to vascular and lymphoid endothelial cells, their migratory activity, and the expression of the Rac-1 activator β-Pix involved in cell motility. These data suggest that B7h stimulation modulates DC function with effects on their maturation and recruitment into tissues. This opens a novel view on the use of interactors of the ICOS:B7h system as immunomodulatory drugs. PMID:23275603

  15. Extracellular nucleotides regulate CCL20 release from human primary airway epithelial cells, monocytes and monocyte-derived dendritic cells.

    PubMed

    Marcet, Brice; Horckmans, Michael; Libert, Frédérick; Hassid, Sergio; Boeynaems, Jean-Marie; Communi, Didier

    2007-06-01

    Extracellular nucleotides regulate ion transport and mucociliary clearance in human airway epithelial cells (HAECs) via the activation of P2 receptors, especially P2Y(2). Therefore, P2Y(2) receptor agonists represent potential pharmacotherapeutic agents to treat cystic fibrosis (CF). Nucleotides also modulate inflammatory properties of immune cells like dendritic cells (DCs), which play an important role in mucosal immunity. Using DNA-microarray experiments, quantitative RT-PCR and cytokine measurements, we show here that UTP up-regulated approximately 2- to 3-fold the antimicrobial chemokine CCL20 expression and release in primary HAECs cultured on permeable supports at an air-liquid interface (ALI). Both P2Y(2) (ATPgammaS, UTP, INS365) and P2Y(6) (UDP, INS48823) agonists increased CCL20 release. UTP-induced CCL20 release was insensitive to NF-kappaB pathway inhibitors but sensitive to inhibitors of ERK1/2 and p38/MAPK pathways. Furthermore, UTP had no effect on interleukin-(IL)-8 release and reduced the release of both CCL20 and IL-8 induced by TNF-alpha and LPS. Accordingly, UTP reduced the capacity of basolateral supernatants of HAECs treated with TNF-alpha or LPS to induce the chemoattraction of both CD4(+) T lymphocytes and neutrophils. In addition, we show that, in monocyte-derived DCs, ATPgammaS, and UDP but not UTP/INS365-stimulated CCL20 release. Likewise, UDP but not ATPgammaS was also able to increase CCL20 release from monocytes. Pharmacological experiments suggested an involvement of P2Y(11) or P2Y(6) receptors through NF-kappaB, ERK1/2, and p38/MAPK pathways. Altogether, our data demonstrate that nucleotides may modulate chemokine release and leukocyte recruitment in inflamed airways by acting on both epithelial and immune cells. Our results could be relevant for further clinical investigations in CF. PMID:17295217

  16. The Complement Inhibitor Factor H Generates an Anti-Inflammatory and Tolerogenic State in Monocyte-Derived Dendritic Cells.

    PubMed

    Olivar, Rut; Luque, Ana; Cárdenas-Brito, Sonia; Naranjo-Gómez, Mar; Blom, Anna M; Borràs, Francesc E; Rodriguez de Córdoba, Santiago; Zipfel, Peter F; Aran, Josep M

    2016-05-15

    The activation of the complement system is a key initiating step in the protective innate immune-inflammatory response against injury, although it may also cause harm if left unchecked. The structurally related soluble complement inhibitors C4b-binding protein (C4BP) and factor H (FH) exert a tight regulation of the classical/lectin and alternative pathways of complement activation, respectively, attenuating the activity of the C3/C5 convertases and, consequently, avoiding serious damage to host tissues. We recently reported that the acute-phase C4BP isoform C4BP lacking the β-chain plays a pivotal role in the modulation of the adaptive immune responses. In this study, we demonstrate that FH acts in the early stages of monocyte to dendritic cell (DC) differentiation and is able to promote a distinctive tolerogenic and anti-inflammatory profile on monocyte-derived DCs (MoDCs) challenged by a proinflammatory stimulus. Accordingly, FH-treated and LPS-matured MoDCs are characterized by altered cytoarchitecture, resembling immature MoDCs, lower expression of the maturation marker CD83 and the costimulatory molecules CD40, CD80, and CD86, decreased production of key proinflammatory Th1-cytokines (IL-12, TNF-α, IFN-γ, IL-6, and IL-8), and preferential production of immunomodulatory mediators (IL-10 and TGF-β). Moreover, FH-treated MoDCs show low Ag uptake and, when challenged with LPS, display reduced CCR7 expression and chemotactic migration, impaired CD4(+) T cell alloproliferation, inhibition of IFN-γ secretion by the allostimulated T cells, and, conversely, induction of CD4(+)CD127(low/negative)CD25(high)Foxp3(+) regulatory T cells. Thus, this novel noncanonical role of FH as an immunological brake able to directly affect the function of MoDCs in an inflammatory environment may exhibit therapeutic potential in hypersensitivity, transplantation, and autoimmunity. PMID:27076676

  17. Human monocyte-derived cells with individual hepatocyte characteristics: a novel tool for personalized in vitro studies.

    PubMed

    Benesic, Andreas; Rahm, Nora L; Ernst, Samuel; Gerbes, Alexander L

    2012-06-01

    Gender, ethnicity and individual differences in hepatic metabolism have major impact on individual drug response, adverse events and attrition rate during drug development. Therefore, there is an urgent need for reliable test systems based on human cells. Yet, the use of primary human hepatocytes (PHHs) is restricted by limited availability, invasive preparation and short-term stability in culture. All other cellular approaches proposed so far have major disadvantages. We investigated whether peripheral human monocytes after cultivation according to our novel protocol (monocyte-derived hepatocyte-like cells (MH cells)) can serve as an in vitro model for hepatocyte metabolism. Enzyme activities, synthesis parameters (coagulation factor VII and urea) and cytochrome (CY) P450 activities and induction were investigated. Furthermore, MH cells were compared with PHH from the same donor. Using our protocol, we could generate cells that exhibit hepatocyte-like properties: These cells show 71±9% of specific ALT activity, 41±3% of CYP3A4 activity and 65±13% of factor VII secretion when compared with PHHs. Consequently, CYP-mediated acetaminophen toxicity and drug interactions could be shown. Moreover, the investigated parameters were stable in culture over at least 4 weeks. Furthermore, MH cells retain gender-specific and donor-specific CYP activities and toxicity profiles, respectively. MH cells show quantitative and qualitative approximation to human hepatocytes concerning CYP-metabolism and toxicity. Our data support individual prediction of toxicity and CYP metabolism. MH cells are a novel tool to investigate long-term hepatic toxicity, metabolism and drug interactions. PMID:22469698

  18. Alcohol and Cannabinoids Differentially Affect HIV Infection and Function of Human Monocyte-Derived Dendritic Cells (MDDC)

    PubMed Central

    Agudelo, Marisela; Figueroa, Gloria; Yndart, Adriana; Casteleiro, Gianna; Muñoz, Karla; Samikkannu, Thangavel; Atluri, Venkata; Nair, Madhavan P.

    2015-01-01

    During human immunodeficiency virus (HIV) infection, alcohol has been known to induce inflammation while cannabinoids have been shown to have an anti-inflammatory role. For instance cannabinoids have been shown to reduce susceptibility to HIV-1 infection and attenuate HIV replication in macrophages. Recently, we demonstrated that alcohol induces cannabinoid receptors and regulates cytokine production by monocyte-derived dendritic cells (MDDC). However, the ability of alcohol and cannabinoids to alter MDDC function during HIV infection has not been clearly elucidated yet. In order to study the potential impact of alcohol and cannabinoids on differentiated MDDC infected with HIV, monocytes were cultured for 7 days with GM-CSF and IL-4, differentiated MDDC were infected with HIV-1Ba-L and treated with EtOH (0.1 and 0.2%), THC (5 and 10 μM), or JWH-015 (5 and 10 μM) for 4–7 days. HIV infection of MDDC was confirmed by p24 and Long Terminal Repeats (LTR) estimation. MDDC endocytosis assay and cytokine array profiles were measured to investigate the effects of HIV and substances of abuse on MDDC function. Our results show the HIV + EtOH treated MDDC had the highest levels of p24 production and expression when compared with the HIV positive controls and the cannabinoid treated cells. Although both cannabinoids, THC and JWH-015 had lower levels of p24 production and expression, the HIV + JWH-015 treated MDDC had the lowest levels of p24 when compared to the HIV + THC treated cells. In addition, MDDC endocytic function and cytokine production were also differentially altered after alcohol and cannabinoid treatments. Our results show a differential effect of alcohol and cannabinoids, which may provide insights into the divergent inflammatory role of alcohol and cannabinoids to modulate MDDC function in the context of HIV infection. PMID:26733986

  19. Cooperation between Monocyte-Derived Cells and Lymphoid Cells in the Acute Response to a Bacterial Lung Pathogen

    PubMed Central

    Brown, Andrew S.; Yang, Chao; Fung, Ka Yee; Bachem, Annabell; Bourges, Dorothée; Bedoui, Sammy; Hartland, Elizabeth L.; van Driel, Ian R.

    2016-01-01

    Legionella pneumophila is the causative agent of Legionnaires’ disease, a potentially fatal lung infection. Alveolar macrophages support intracellular replication of L. pneumophila, however the contributions of other immune cell types to bacterial killing during infection are unclear. Here, we used recently described methods to characterise the major inflammatory cells in lung after acute respiratory infection of mice with L. pneumophila. We observed that the numbers of alveolar macrophages rapidly decreased after infection coincident with a rapid infiltration of the lung by monocyte-derived cells (MC), which, together with neutrophils, became the dominant inflammatory cells associated with the bacteria. Using mice in which the ability of MC to infiltrate tissues is impaired it was found that MC were required for bacterial clearance and were the major source of IL12. IL12 was needed to induce IFNγ production by lymphoid cells including NK cells, memory T cells, NKT cells and γδ T cells. Memory T cells that produced IFNγ appeared to be circulating effector/memory T cells that infiltrated the lung after infection. IFNγ production by memory T cells was stimulated in an antigen-independent fashion and could effectively clear bacteria from the lung indicating that memory T cells are an important contributor to innate bacterial defence. We also determined that a major function of IFNγ was to stimulate bactericidal activity of MC. On the other hand, neutrophils did not require IFNγ to kill bacteria and alveolar macrophages remained poorly bactericidal even in the presence of IFNγ. This work has revealed a cooperative innate immune circuit between lymphoid cells and MC that combats acute L. pneumophila infection and defines a specific role for IFNγ in anti-bacterial immunity. PMID:27300652

  20. Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells.

    PubMed

    Gosset, P; Charbonnier, A S; Delerive, P; Fontaine, J; Staels, B; Pestel, J; Tonnel, A B; Trottein, F

    2001-10-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the nuclear receptor superfamily, has recently been described as a modulator of macrophage functions and as an inhibitor of T cell proliferation. Here, we investigated the role of PPARgamma in dendritic cells (DC), the most potent antigen-presenting cells. We showed that PPARgamma is highly expressed in immature human monocyte-derived DC (MDDC) and that it may affect the immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist rosiglitazone (as well as pioglitazone and troglitazone) significantly increases on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and 104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L-stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha, IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by 49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage-derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17), in mature MDDC. Taken together, our data suggest that activation of PPARgamma in human DC may have an impact in the orientation of primary and secondary immune responses by favoring type 2 responses. PMID:11592060

  1. The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages.

    PubMed

    Daigneault, Marc; Preston, Julie A; Marriott, Helen M; Whyte, Moira K B; Dockrell, David H

    2010-01-01

    Differentiated macrophages are the resident tissue phagocytes and sentinel cells of the innate immune response. The phenotype of mature tissue macrophages represents the composite of environmental and differentiation-dependent imprinting. Phorbol-12-myristate-13-acetate (PMA) and 1,25-dihydroxyvitamin D3 (VD(3)) are stimuli commonly used to induce macrophage differentiation in monocytic cell lines but the extent of differentiation in comparison to primary tissue macrophages is unclear. We have compared the phenotype of the promonocytic THP-1 cell line after various protocols of differentiation utilising VD(3) and PMA in comparison to primary human monocytes or monocyte-derived macrophages (MDM). Both stimuli induced changes in cell morphology indicative of differentiation but neither showed differentiation comparable to MDM. In contrast, PMA treatment followed by 5 days resting in culture without PMA (PMAr) increased cytoplasmic to nuclear ratio, increased mitochondrial and lysosomal numbers and altered differentiation-dependent cell surface markers in a pattern similar to MDM. Moreover, PMAr cells showed relative resistance to apoptotic stimuli and maintained levels of the differentiation-dependent anti-apoptotic protein Mcl-1 similar to MDM. PMAr cells retained a high phagocytic capacity for latex beads, and expressed a cytokine profile that resembled MDM in response to TLR ligands, in particular with marked TLR2 responses. Moreover, both MDM and PMAr retained marked plasticity to stimulus-directed polarization. These findings suggest a modified PMA differentiation protocol can enhance macrophage differentiation of THP-1 cells and identify increased numbers of mitochondria and lysosomes, resistance to apoptosis and the potency of TLR2 responses as important discriminators of the level of macrophage differentiation for transformed cells. PMID:20084270

  2. Human monocyte-derived dendritic cells turn into foamy dendritic cells with IL-17A1[S

    PubMed Central

    Salvatore, Giulia; Bernoud-Hubac, Nathalie; Bissay, Nathalie; Debard, Cyrille; Daira, Patricia; Meugnier, Emmanuelle; Proamer, Fabienne; Hanau, Daniel; Vidal, Hubert; Aricò, Maurizio; Delprat, Christine; Mahtouk, Karène

    2015-01-01

    Interleukin 17A (IL-17A) is a proinflammatory cytokine involved in the pathogenesis of chronic inflammatory diseases. In the field of immunometabolism, we have studied the impact of IL-17A on the lipid metabolism of human in vitro-generated monocyte-derived dendritic cells (DCs). Microarrays and lipidomic analysis revealed an intense remodeling of lipid metabolism induced by IL-17A in DCs. IL-17A increased 2–12 times the amounts of phospholipids, cholesterol, triglycerides, and cholesteryl esters in DCs. Palmitic (16:0), stearic (18:0), and oleic (18:ln-9c) acid were the main fatty acid chains present in DCs. They were strongly increased in response to IL-17A while their relative proportion remained unchanged. Capture of extracellular lipids was the major mechanism of lipid droplet accumulation, visualized by electron microscopy and Oil Red O staining. Besides this foamy phenotype, IL-17A induced a mixed macrophage-DC phenotype and expression of the nuclear receptor NR1H3/liver X receptor-α, previously identified in the context of atherosclerosis as the master regulator of cholesterol homeostasis in macrophages. These IL-17A-treated DCs were as competent as untreated DCs to stimulate allogeneic naive T-cell proliferation. Following this first characterization of lipid-rich DCs, we propose to call these IL-17A-dependent cells “foamy DCs” and discuss the possible existence of foamy DCs in atherosclerosis, a metabolic and inflammatory disorder involving IL-17A. PMID:25833686

  3. Role of cytomegalovirus on the maturation and function of monocyte derived dendritic cells of liver transplant patients

    PubMed Central

    Karimi, Mohammad Hossein; Shariat, Afsoon; Yaghobi, Ramin; Mokhtariazad, Talat; Moazzeni, Seyed Mohammad

    2016-01-01

    AIM: To study the impact of association between cytomegalovirus (CMV) pathogenesis with dendritic cell (DC) maturation and function was evaluated in CMV reactivated liver transplanted patients in comparing with non-reactivated ones, and healthy controls. METHODS: Monocyte derived dendritic cells (MoDCs) was generated from collected ethylenediaminetetraacetic acid-treated blood samples from patient groups and controls. In these groups, expression rates and mean fluorescent intensity of DC markers were evaluated using flowcytometry technique. Secretion of cytokines including: interleukin (IL)-6, IL-12 and IL-23 were determined using enzyme-linked immunosorbent assay methods. The gene expression of toll-like receptor 2 (TLR2), TLR4 and IL-23 were analyzed using in-house real-time polymerase chain reaction protocols. RESULTS: Results have been shown significant decreases in: Expression rates of MoDC markers including CD83, CD1a and human leukocyte antigen DR (HLA-DR), the mean fluorescence intensitys for CD1a and HLA-DR, and secretion of IL-12 in CMV reactivated compared with non-reactivated liver transplanted patients. On the other hand, significant increases have been shown in the secretions of IL-6 and IL-23 and gene expression levels of TLR2, TLR4 and IL-23 from MoDCs in CMV reactivated compared with non-reactivated liver transplanted recipients. CONCLUSION: DC functional defects in CMV reactivated recipients, such as decrease in expression of DC maturation markers, increase in secretion of proinflammatory cytokines, and TLRs can emphasize on the importance of CMV infectivity in development of liver rejection in transplanted patients. PMID:27358779

  4. Gene Expression Profiling of Human Monocyte-derived Dendritic Cells – Searching for Molecular Regulators of Tolerogenicity

    PubMed Central

    Schinnerling, Katina; García-González, Paulina; Aguillón, Juan Carlos

    2015-01-01

    The ability of dendritic cells (DCs) to initiate and modulate antigen-specific immune responses has made them attractive targets for immunotherapy. Since DC research in humans is limited by the scarcity of DC populations in the blood circulation, most of our knowledge about DC biology and function has been obtained in vitro from monocyte-derived DCs (moDCs), which can be readily generated in sufficient numbers and are able to differentiate into distinct functional subsets depending on the nature of stimulus. In particular, moDCs with tolerogenic properties (tolDCs) possess great therapeutic potential for the treatment of autoimmune diseases. Several protocols have been developed to generate tolDCs in vitro, able to reinstruct auto-reactive T cells and to promote regulatory cells. While ligands and soluble mediators, by which DCs shape immune responses, have been vastly studied, the intracellular pathways and transcriptional regulators that govern tolDC differentiation and function are poorly understood. Whole-genome microarrays and proteomics provide useful strategies to dissect the complex molecular processes that promote tolerogenicity. Only few attempts have been made to understand tolDC biology through a global view on “omics” profiles. So far, the identification of a common regulator of tolerogenicity has been hampered by the fact that each protocol, used for tolDC generation, targets distinct signaling pathways. Here, we review the progress in understanding the transcriptional regulation of moDC differentiation, with a special focus on tolDCs, and highlight candidate molecules that might be associated with DC tolerogenicity. PMID:26539195

  5. Fibrocytes contribute to the myofibroblast population in wounded skin and originate from the bone marrow

    SciTech Connect

    Mori, Luca; Bellini, Alberto; Stacey, Martin A.; Schmidt, Matthias; Mattoli, Sabrina . E-mail: smattoli@avail-research.com

    2005-03-10

    Myofibroblasts play a key role in wound closure but their origin is poorly understood. To investigate whether fibrocytes contribute to myofibroblast population, we examined the phenotype of fibrocytes and myofibroblasts present in the wounded skin of BALB/c mice. During wound healing, there was a marked increase in the number of cells expressing the myofibroblast marker {alpha}-smooth muscle actin in the granulation tissue. Between 4 and 7 days post-wounding, more than 50% of these cells also expressed the CD13 antigen. CD13{sup +}/collagen I{sup +} fibrocytes could be isolated at an early stage of the healing process from digested fragments of wounded tissue by fluorescence-activated cell sorting. Like authentic fibrocytes, these cells were also CD45{sup +}/CD34{sup +}/CD14{sup -}. Between 4 and 7 days post-injury, 61.4% of the isolated fibrocytes were found to express {alpha}-smooth muscle actin gene and protein. We repeated similar experiments in female mice that had received a male whole bone marrow transplant after total body irradiation. By in situ hybridization, we identified the Y chromosome in the nuclei of the majority of fibrocytes isolated from the wounded tissue of these animals. Our data indicate that circulating fibrocytes contribute to the myofibroblast population in the wounded skin and that they originate from the bone marrow.

  6. Fibrocyte and T cell interactions promote disease pathogenesis in rheumatoid arthritis.

    PubMed

    Galligan, Carole L; Keystone, Edward C; Fish, Eleanor N

    2016-05-01

    Rheumatoid arthritis (RA) is a systemic autoimmune disease. We previously identified a circulating cell population, fibrocytes, which is activated early in disease. As RA is characterized by the formation of autoantibodies and autoreactive T cells, which often precede symptom onset, the objective of these studies was to characterize fibrocyte activation in the context of T cell activation. Multidimensional flow cytometry was used to characterize the activation status of peripheral blood (PB) fibrocytes and T cells derived from RA patients with different levels of disease activity. Compared to healthy controls, fibrocytes from RA patients exhibited increased activation, denoted as elevated levels of phosphorylation of STAT3 and NF-κB. RA patients had higher numbers of circulating activated Th17 cells and Tregs compared with healthy controls, Th17 cell numbers being higher in patients with moderate to high disease activity. Additionally, increased numbers of FOXP3+ RORγt+ double positive CD4+ T cells were observed in RA patients with more severe disease. Our data confirm that circulating fibrocytes are expanded in RA and that there is a direct correlation between the increase in number of activated fibrocytes and increased number of CD4+ T cells. Moreover, our data suggest that interactions between circulating fibrocytes and activated T cells may promote disease activity. Specifically, we provide in vitro evidence that mouse-derived CD4+ T cells produce GM-CSF which induces fibrocyte proliferation. In turn, activated fibrocytes produce IL-6, promoting Th17 polarization. PMID:26948996

  7. Mesenchymal Stem Cells Derived from Human Exfoliated Deciduous Teeth (SHEDs) Induce Immune Modulatory Profile in Monocyte-Derived Dendritic Cells

    PubMed Central

    Silva, Fernando de Sá; Ramos, Rodrigo Nalio; de Almeida, Danilo Candido; Bassi, Enio Jose; Gonzales, Roberto Pereira; Miyagi, Sueli Patricia Harumi; Maranduba, Claudinéia Pereira; Sant'Anna, Osvaldo Augusto Brazil Esteves; Marques, Márcia Martins; Barbuto, José Alexandre Marzagão; Câmara, Niels Olsen Saraiva; da Costa Maranduba, Carlos Magno

    2014-01-01

    Background Mesenchymal stem cells have prominent immune modulatory properties, which may have clinical applications; however their major source, bone marrow, is of limited availability. On the other hand, mesenchymal stem cells derived from human exfoliated deciduous teeth (SHEDs) are readily accessible, but their immune regulatory properties have not been completely investigated. This study was designed, therefore, to evaluate the SHEDs influence on DCs differentiation, maturation, ability to activate T cells and to expand CD4+Foxp3+ T cells. Methodology/Principal Findings The experiments were based in cellular co-culture during differentiation and maturation of monocyte derived-DCs (moDCs), with, or not, presence of SHEDs. After co-culture with SHEDs, (moDCs) presented lower expression of BDCA-1 and CD11c, in comparison to DC cultivated without SHEDs. CD40, CD80, CD83 and CD86 levels were also decreased in mature DCs (mDCs) after co-cultivation with SHEDs. To assess the ability of SHEDs-exposed moDCs to modulate T cell responses, the former were separated from SHEDs, and co-cultured with peripheral blood lymphocytes. After 5 days, the proliferation of CD4+ and CD8+ T cells was evaluated and found to be lower than that induced by moDCs cultivated without SHEDs. In addition, an increase in the proportion of CD4+Foxp3+IL-10+ T cells was observed among cells stimulated by mature moDCs that were previously cultivated with SHEDs. Soluble factors released during co-cultures also showed a reduction in the pro-inflammatory cytokines (IL-2, TNF-α and IFN-γ), and an increase in the anti-inflammatory molecule IL-10. Conclusion/Significance This study shows that SHEDs induce an immune regulatory phenotype in moDCs cells, evidenced by changes in maturation and differentiation rates, inhibition of lymphocyte stimulation and ability to expand CD4+Foxp3+ T cells. Further characterization and validation of this phenomenon could support the use of SHEDs, directly or indirectly

  8. Activation of p38 Mitogen-Activated Protein Kinase Promotes Peritoneal Fibrosis by Regulating Fibrocytes

    PubMed Central

    Kokubo, Satoshi; Sakai, Norihiko; Furuichi, Kengo; Toyama, Tadashi; Kitajima, Shinji; Okumura, Toshiya; Matsushima, Kouji; Kaneko, Shuichi; Wada, Takashi

    2012-01-01

    ♦ Background: Peritoneal fibrosis is a serious complication of long-term peritoneal dialysis, and yet the precise pathogenic mechanisms of peritoneal fibrosis remain unknown. Fibrocytes participate in tissue fibrosis and express chemokine receptors that are necessary for migration. The p38 mitogen-activated protein kinase (MAPK) pathway regulates the production of chemokines and has been demonstrated to contribute to the pathogenesis of various fibrotic conditions. Accordingly, we used an experimental mouse model of peritoneal fibrosis to examine the dependency of fibrocytes on p38MAPK signaling. ♦ Methods: Peritoneal fibrosis was induced in mice by the injection of 0.1% chlorhexidine gluconate (CG) into the abdominal cavity. Mice were treated with FR167653, a specific inhibitor of p38MAPK, and immunohistochemical studies were performed to detect fibrocytes and cells positive for phosphorylated p38MAPK. The involvement of p38MAPK in the activation of fibrocytes also was also investigated in vitro. ♦ Results: Fibrocytes infiltrated peritoneum in response to CG, and that response was accompanied by progressive peritoneal fibrosis. The phosphorylation of p38MAPK, as defined by CD45+ spindle-shaped cells, was detected both in peritoneal mesothelial cells and in fibrocytes. The level of peritoneal expression of CCL2, a chemoattractant for fibrocytes, was upregulated by CG injection, and treatment with FR167653 reduced the number of cells positive for phosphorylated p38MAPK, the peritoneal expression of CCL2, and the extent of peritoneal fibrosis. Pretreatment with FR167653 inhibited the expression of procollagen type I α1 induced by transforming growth factor-β1. ♦ Conclusions: Our results suggest that p38MAPK signaling contributes to peritoneal fibrosis by regulating fibrocyte function. PMID:21719683

  9. Expression of fibrocyte markers by keloid fibroblasts: an insight into fibrosis during burn wound healing - a preliminary study

    PubMed Central

    Mathangi Ramakrishnan, K.; Meenakshi Janakiraman, M.; Babu, M.

    2012-01-01

    Summary In extensive burns it becomes difficult for fibroblasts to migrate from the periphery of the healthy tissue and colonize the injured area. Even under such circumstances healing takes place, and this is attributed to the differentiation of circulating fibrocytes which enter the wound site. This normal cell type is identified in keloid fibroblasts: it expresses fibrocyte markers and secretes extra cellular matrix proteins. In-vitro collagen contraction assay reveals that fibrocytes contract collagen gels with an efficacy similar to normal fibroblasts. The contribution of fibrocytes to the formation of keloid fibroblasts in post-burn healing is discussed. PMID:23467263

  10. An in vitro model to assess the immunosuppressive effect of tick saliva on the mobilization of inflammatory monocyte-derived cells.

    PubMed

    Vachiery, Nathalie; Puech, Carinne; Cavelier, Patricia; Rodrigues, Valérie; Aprelon, Rosalie; Lefrançois, Thierry; Martinez, Dominique; Epardaud, Mathieu

    2015-01-01

    Tick-borne pathogens cause potent infections. These pathogens benefit from molecules contained in tick saliva that have evolved to modulate host innate and adaptive immune responses. This is called "saliva-activated transmission" and enables tick-borne pathogens to evade host immune responses. Ticks feed on their host for relatively long periods; thus, mechanisms counteracting the inflammation-driven recruitment and activation of innate effector cells at the bite site, are an effective strategy to escape the immune response. Here, we developed an original in vitro model to evaluate and to characterize the immunomodulatory effects of tick saliva that prevent the establishment of a local inflammatory immune response. This model mimics the tick bite and enables the assessment of the effect of saliva on the inflammatory-associated dynamic recruitment of cells from the mononuclear phagocyte system. Using this model, we were able to recapitulate the dual effect of tick saliva on the mobilization of inflammatory monocyte-derived cells, i.e. (i) impaired recruitment of monocytes from the blood to the bite wound; and (ii) poor mobilization of monocyte-derived cells from the skin to the draining lymph node. This simple tool reconstitutes the effect of tick saliva in vivo, which we characterized in the mouse, and should enable the identification of important factors facilitating pathogen infection. Furthermore, this model may be applied to the characterization of any pathogen-derived immunosuppressive molecule affecting the establishment of the inflammatory immune response. PMID:26412247

  11. The TLR7/8 ligand resiquimod targets monocyte-derived dendritic cell differentiation via TLR8 and augments functional dendritic cell generation.

    PubMed

    Hackstein, Holger; Knoche, Angela; Nockher, Angelika; Poeling, Jochen; Kubin, Thomas; Jurk, Marion; Vollmer, Jörg; Bein, Gregor

    2011-01-01

    Imidazoquinolone compounds, such as resiquimod are Toll-like receptor (TLR) 7/8 ligands representing novel immune response modifiers undergoing clinical testing. Resiquimod has been reported to modulate conventional human monocyte-derived DC (moDC) differentiation, but the role of TLR7 and TLR8 is unclear. We directly dissected the TLR7- and TLR8-dependency by employing selective TLR7 ligands and resiquimod-coculture experiments with inhibitory oligonucleotides (iODN) suppressing TLR7, TLR7+8 or TLR7+8+9. Selective TLR7 ligands did not affect conventional moDC differentiation as analyzed by CD14/CD1a expression. iODN experiments confirmed that resiquimod's effects during DC differentiation were antagonized only with TLR8 iODNs. Direct comparison of resiquimod DC with TLR7- and control-DC revealed significantly higher T-cell costimulatory molecule and MHC class II expression. Resiquimod DC promoted significantly stronger allogeneic T-cell proliferation and stronger naïve CD4(+) T-cell proliferation. These results indicate the relevance of TLR8 for human monocyte-derived DC differentiation and maturation and may be relevant for clinical trials employing resiquimod. PMID:21889130

  12. In vitro suppression of immune responses using monocyte-derived tolerogenic dendritic cells from patients with primary Sjögren's syndrome

    PubMed Central

    2013-01-01

    Introduction Therapeutic vaccination with antigen-specific tolerogenic dendritic cells (tolDC) might become a future option of individualized therapy for patients with autoimmune diseases. In this study, we tested the possibility of generating monocyte-derived tolDC from patients with primary Sjögren's syndrome (pSS). We analyzed phenotype, cytokine production and ability to suppress Ro/La-specific immune responses. Methods Monocyte-derived tolDC from patients with pSS were generated in the presence of dexamethasone, vitamin D3 and lipopolysaccharide (DexVD3 DC). The phenotype was analyzed by flow cytometry and the cytokine profile was investigated using a 25-plex Luminex assay and ELISA. The capacity to both stimulate Ro/La-specific T cells and suppress this response was evaluated by autologous mixed lymphocyte reaction (MLR). Results DC generated from patients with pSS had a similar phenotype and cytokine profile to those from healthy controls. DexVD3 DC from pSS patients induced little antigen-specific T cell proliferation, but DexVD3 DC-primed lymphocytes successfully suppressed Ro/La-specific T cell responses. Conclusions DexVD3 DC presenting Ro/La antigens might be a promising new therapeutic option for patients with pSS. PMID:24025795

  13. Serum opsonin ficolin-A enhances host-fungal interactions and modulates cytokine expression from human monocyte-derived macrophages and neutrophils following Aspergillus fumigatus challenge.

    PubMed

    Bidula, Stefan; Sexton, Darren W; Schelenz, Silke

    2016-04-01

    Invasive aspergillosis is a devastating invasive fungal disease associated with a high mortality rate in the immunocompromised, such as leukaemia patients, transplant patients and those with HIV/AIDS. The rodent serum orthologue of human L-ficolin, ficolin-A, can bind to and opsonize Aspergillus fumigatus, the pathogen that causes invasive aspergillosis, and may participate in fungal defence. Using human monocyte-derived macrophages and neutrophils isolated from healthy donors, we investigated conidial association and fungal viability by flow cytometry and microscopy. Additionally, cytokine production was measured via cytometric bead arrays. Ficolin-A opsonization was observed to significantly enhance association of conidia, while also inhibiting hyphal growth and contributing to increased fungal killing following incubation with monocyte-derived macrophages and neutrophils. Additionally, ficolin-A opsonization was capable of manifesting a decrease in IL-8, IL-1β, IL-6, IL-10 and TNF-α production from MDM and IL-1β, IL-6 and TNF-α from neutrophils 24 h post-infection. In conclusion, rodent ficolin-A is functionally comparable to human L-ficolin and is capable of modulating the innate immune response to A. fumigatus, down-regulating cytokine production and could play an important role in airway immunity. PMID:26337048

  14. Maturation of the viral core enhances the fusion of HIV-1 particles with primary human T cells and monocyte-derived macrophages

    SciTech Connect

    Jiang Jiyang; Aiken, Christopher . E-mail: chris.aiken@vanderbilt.edu

    2006-03-15

    HIV-1 infection requires fusion of viral and cellular membranes in a reaction catalyzed by the viral envelope proteins gp120 and gp41. We recently reported that efficient HIV-1 particle fusion with target cells is linked to maturation of the viral core by an activity of the gp41 cytoplasmic domain. Here, we show that maturation enhances the fusion of a variety of recombinant viruses bearing primary and laboratory-adapted Env proteins with primary human CD4{sup +} T cells. Overall, HIV-1 fusion was more dependent on maturation for viruses bearing X4-tropic envelope proteins than for R5-tropic viruses. Fusion of HIV-1 with monocyte-derived macrophages was also dependent on particle maturation. We conclude that the ability to couple fusion to particle maturation is a common feature of HIV-1 Env proteins and may play an important role during HIV-1 replication in vivo.

  15. Distinguished Books.

    ERIC Educational Resources Information Center

    Marles, Daisy; Ink, Gary

    1999-01-01

    Presents the following lists of distinguished books: "Best Books of 1998"; "Best Young Adult Books"; "Notable Children's Videos"; "Best Children's Books"; "Notable Recordings for Children"; "Notable Software and Web Sites for Children"; "Quick Picks for Reluctant Young Adult Readers"; "Bestsellers of 1998"; and "Literary Prizes, 1998." (AEF)

  16. Immunomodulatory effects of human umbilical cord Wharton's jelly-derived mesenchymal stem cells on differentiation, maturation and endocytosis of monocyte-derived dendritic cells.

    PubMed

    Saeidi, Mohsen; Masoud, Ahmad; Shakiba, Yadollah; Hadjati, Jamshid; Mohyeddin Bonab, Mandana; Nicknam, Mohammad Hossein; Latifpour, Mostafa; Nikbin, Behrooz

    2013-03-01

    The Wharton's jelly of the umbilical cord is believed to be a source of mesenchymal stem cells (MSCs) which can be therapeutically applied in degenerative diseases.In this study, we investigated the immunomodulatory effect of umbilical cord derived-mesenchymal stem cells (UC-MSCs) and bone marrow-derived-mesenchymal stem cells (BM-MSCs) on differentiation, maturation, and endocytosis of monocyte-derived dendritic cells in a transwell culture system under laboratory conditions. Monocytes were differentiated into immature dendritic cells (iDCs) in the presence of GM-CSF and IL-4 for 6 days and then differentiated into mature dendritic cells (mDCs) in the presence of TNF-α for 2 days. In every stage of differentiation, immature and mature dendritic cells were separately co-cultured with UC-MSCs and BM-MSCs. The findings showed that UC-MSCs and BM-MSCs inhibited strongly differentiation and maturation of dendritic cells at higher dilution ratios (1:1). The BM-MSCs and UC-MSCs showed more inhibitory effect on CD1a, CD83, CD86 expression, and dendritic cell endocytic activity, respectively. On the other hand, these cells severely up-regulated CD14 marker expression. We concluded that UC-MSCs and BM-MSCs could inhibit differentiation, maturation and endocytosis in monocyte-derived DCs through the secreted factors and free of any cell-cell contacts under laboratory conditions. As DCs are believed to be the main antigen presenting cells for naïve T cells in triggering immune responses, it would be logical that their inhibitory effect on differentiation, maturation and function can decrease or modulate immune and inflammatory responses. PMID:23454777

  17. Regulatory T cells reduce acute lung injury fibroproliferation by decreasing fibrocyte recruitment.

    PubMed

    Garibaldi, Brian T; D'Alessio, Franco R; Mock, Jason R; Files, D Clark; Chau, Eric; Eto, Yoshiki; Drummond, M Bradley; Aggarwal, Neil R; Sidhaye, Venkataramana; King, Landon S

    2013-01-01

    Acute lung injury (ALI) causes significant morbidity and mortality. Fibroproliferation in ALI results in worse outcomes, but the mechanisms governing fibroproliferation remain poorly understood. Regulatory T cells (Tregs) are important in lung injury resolution. Their role in fibroproliferation is unknown. We sought to identify the role of Tregs in ALI fibroproliferation, using a murine model of lung injury. Wild-type (WT) and lymphocyte-deficient Rag-1(-/-) mice received intratracheal LPS. Fibroproliferation was characterized by histology and the measurement of lung collagen. Lung fibrocytes were measured by flow cytometry. To dissect the role of Tregs in fibroproliferation, Rag-1(-/-) mice received CD4(+)CD25(+) (Tregs) or CD4(+)CD25(-) Tcells (non-Tregs) at the time of LPS injury. To define the role of the chemokine (C-X-C motif) ligand 12 (CXCL12)-CXCR4 pathway in ALI fibroproliferation, Rag-1(-/-) mice were treated with the CXCR4 antagonist AMD3100 to block fibrocyte recruitment. WT and Rag-1(-/-) mice demonstrated significant collagen deposition on Day 3 after LPS. WT mice exhibited the clearance of collagen, but Rag-1(-/-) mice developed persistent fibrosis. This fibrosis was mediated by the sustained epithelial expression of CXCL12 (or stromal cell-derived factor 1 [SDF-1]) that led to increased fibrocyte recruitment. The adoptive transfer of Tregs resolved fibroproliferation by decreasing CXCL12 expression and subsequent fibrocyte recruitment. Blockade of the CXCL12-CXCR4 axis with AMD3100 also decreased lung fibrocytes and fibroproliferation. These results indicate a central role for Tregs in the resolution of ALI fibroproliferation by reducing fibrocyte recruitment along the CXCL12-CXCR4 axis. A dissection of the role of Tregs in ALI fibroproliferation may inform the design of new therapeutic tools for patients with ALI. PMID:23002097

  18. Role of platelet-derived growth factor/platelet-derived growth factor receptor axis in the trafficking of circulating fibrocytes in pulmonary fibrosis.

    PubMed

    Aono, Yoshinori; Kishi, Masami; Yokota, Yuki; Azuma, Momoyo; Kinoshita, Katsuhiro; Takezaki, Akio; Sato, Seidai; Kawano, Hiroshi; Kishi, Jun; Goto, Hisatsugu; Uehara, Hisanori; Izumi, Keisuke; Nishioka, Yasuhiko

    2014-12-01

    Circulating fibrocytes have been reported to migrate into the injured lungs, and contribute to fibrogenesis via CXCL12-CXCR4 axis. In contrast, we report that imatinib mesylate prevented bleomycin (BLM)-induced pulmonary fibrosis in mice by inhibiting platelet-derived growth factor receptor (PDGFR), even when it was administered only in the early phase. The goal of this study was to test the hypothesis that platelet-derived growth factor (PDGF) might directly contribute to the migration of fibrocytes to the injured lungs. PDGFR expression in fibrocytes was examined by flow cytometry and RT-PCR. The migration of fibrocytes was evaluated by using a chemotaxis assay for human fibrocytes isolated from peripheral blood. The numbers of fibrocytes triple-stained for CD45, collagen-1, and CXCR4 were also examined in lung digests of BLM-treated mice. PDGFR mRNA levels in fibrocytes isolated from patients with idiopathic pulmonary fibrosis were investigated by real-time PCR. Fibrocytes expressed both PDGFR-α and -β, and migrated in response to PDGFs. PDGFR inhibitors (imatinib, PDGFR-blocking antibodies) suppressed fibrocyte migration in vitro, and reduced the number of fibrocytes in the lungs of BLM-treated mice. PDGF-BB was a stronger chemoattractant than the other PDGFs in vitro, and anti-PDGFR-β-blocking antibody decreased the numbers of fibrocytes in the lungs compared with anti-PDGFR-α antibody in vivo. Marked expression of PDGFR-β was observed in fibrocytes from patients with idiopathic pulmonary fibrosis compared with healthy subjects. These results suggest that PDGF directly functions as a strong chemoattractant for fibrocytes. In particular, the PDGF-BB-PDGFR-β biological axis might play a critical role in fibrocyte migration into the fibrotic lungs. PMID:24885373

  19. Monocyte-Derived Dendritic Cells Exhibit Increased Levels of Lysosomal Proteolysis as Compared to Other Human Dendritic Cell Populations

    PubMed Central

    McCurley, Nathanael; Mellman, Ira

    2010-01-01

    Background Fine control of lysosomal degradation for limited processing of internalized antigens is a hallmark of professional antigen presenting cells. Previous work in mice has shown that dendritic cells (DCs) contain lysosomes with remarkably low protease content. Combined with the ability to modulate lysosomal pH during phagocytosis and maturation, murine DCs enhance their production of class II MHC-peptide complexes for presentation to T cells. Methodology/Principal Findings In this study we extend these findings to human DCs and distinguish between different subsets of DCs based on their ability to preserve internalized antigen. Whereas DCs derived in vitro from CD34+ hematopoietic progenitor cells or isolated from peripheral blood of healthy donors are protease poor, DCs derived in vitro from monocytes (MDDCs) are more similar to macrophages (MΦs) in protease content. Unlike other DCs, MDDCs also fail to reduce their intralysosomal pH in response to maturation stimuli. Indeed, functional characterization of lysosomal proteolysis indicates that MDDCs are comparable to MΦs in the rapid degradation of antigen while other human DC subtypes are attenuated in this capacity. Conclusions/Significance Human DCs are comparable to murine DCs in exhibiting a markedly reduced level of lysosomal proteolysis. However, as an important exception to this, human MDDCs stand apart from all other DCs by a heightened capacity for proteolysis that resembles that of MΦs. Thus, caution should be exercised when using human MDDCs as a model for DC function and cell biology. PMID:20689855

  20. Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab

    PubMed Central

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Saijo, Atsuro; Trung, Van The; Aono, Yoshinori; Ogino, Hirokazu; Kuramoto, Takuya; Tabata, Sho; Uehara, Hisanori; Izumi, Keisuke; Yoshida, Mitsuteru; Kobayashi, Hiroaki; Takahashi, Hidefusa; Gotoh, Masashi; Kakiuchi, Soji; Hanibuchi, Masaki; Yano, Seiji; Yokomise, Hiroyasu; Sakiyama, Shoji; Nishioka, Yasuhiko

    2015-01-01

    Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy. PMID:26635184

  1. Fibrocyte-like cells mediate acquired resistance to anti-angiogenic therapy with bevacizumab.

    PubMed

    Mitsuhashi, Atsushi; Goto, Hisatsugu; Saijo, Atsuro; Trung, Van The; Aono, Yoshinori; Ogino, Hirokazu; Kuramoto, Takuya; Tabata, Sho; Uehara, Hisanori; Izumi, Keisuke; Yoshida, Mitsuteru; Kobayashi, Hiroaki; Takahashi, Hidefusa; Gotoh, Masashi; Kakiuchi, Soji; Hanibuchi, Masaki; Yano, Seiji; Yokomise, Hiroyasu; Sakiyama, Shoji; Nishioka, Yasuhiko

    2015-01-01

    Bevacizumab exerts anti-angiogenic effects in cancer patients by inhibiting vascular endothelial growth factor (VEGF). However, its use is still limited due to the development of resistance to the treatment. Such resistance can be regulated by various factors, although the underlying mechanisms remain incompletely understood. Here we show that bone marrow-derived fibrocyte-like cells, defined as alpha-1 type I collagen-positive and CXCR4-positive cells, contribute to the acquired resistance to bevacizumab. In mouse models of malignant pleural mesothelioma and lung cancer, fibrocyte-like cells mediate the resistance to bevacizumab as the main producer of fibroblast growth factor 2. In clinical specimens of lung cancer, the number of fibrocyte-like cells is significantly increased in bevacizumab-treated tumours, and correlates with the number of treatment cycles, as well as CD31-positive vessels. Our results identify fibrocyte-like cells as a promising cell biomarker and a potential therapeutic target to overcome resistance to anti-VEGF therapy. PMID:26635184

  2. Comparison of alpha-Type-1 polarizing and standard dendritic cell cytokine cocktail for maturation of therapeutic monocyte-derived dendritic cell preparations from cancer patients.

    PubMed

    Trepiakas, Redas; Pedersen, Anders Elm; Met, Ozcan; Hansen, Morten H; Berntsen, Annika; Svane, Inge Marie

    2008-06-01

    The current "gold standard" for generation of dendritic cell (DC) used in DC-based cancer vaccine studies is maturation of monocyte-derived DCs with tumor necrosis factor-alpha (TNF-alpha)/IL-1beta/IL-6 and prostaglandin E(2) (PGE(2)). Recently, a protocol for producing so-called alpha-Type-1 polarized dendritic cells (alphaDC1) in serum-free medium was published based on maturation of monocyte-derived DCs with TNF-alpha/IL-1-beta/polyinosinic:polycytidylic acid (poly-I:C)/interferon (IFN)-alpha and IFN-gamma. This DC maturation cocktail was described to fulfill the criteria for optimal DC generation and to be superior to the standard DC (sDC) cocktail as it induced fully mature DCs with potent IL-12p70 secretion together with CCR7 expression which is necessary for priming of a TH1 response and for migration to the draining lymph node, respectively. In this study, we tested the adaptation of alphaDC1 maturation cocktail to a protocol for clinical grade DC generation from cancer patients performed in X-VIVO 15 medium. We showed that alphaDC1 in this protocol induce lower up-regulation of CD83 and several other maturation markers, co-stimulatory molecules and CCR7 together with higher up-regulation of inhibitory molecules such as PD-L1, ILT2, ILT3 as compared to sDC. Although alphaDC1 matured DCs secreted more IL-12p70 and IL-23 these DCs had lower or similar stimulatory capacity compared to sDCs when used as stimulating cells in mixed lymphocyte reaction (MLR) or for induction of autologous influenza antigen specific T lymphocytes. Thus, our observations underline that alphaDC1 maturation cannot be directly adapted to alternative protocols for DC generation. Also, this study indicates the necessity for further investigation of correlation between in vitro DC parameters and their in vivo efficacy in clinical vaccination trials. PMID:18450338

  3. Modern Lineages of Mycobacterium tuberculosis Exhibit Lineage-Specific Patterns of Growth and Cytokine Induction in Human Monocyte-Derived Macrophages

    PubMed Central

    Sarkar, Rajesh; Lenders, Laura; Wilkinson, Katalin A.; Wilkinson, Robert J.; Nicol, Mark P.

    2012-01-01

    Background Strains of Mycobacterium tuberculosis vary in virulence. Strains that have caused outbreaks in the United States and United Kingdom have been shown to subvert the innate immune response as a potential immune evasion mechanism. There is, however, little information available as to whether these patterns of immune subversion are features of individual strains or characteristic of broad clonal lineages of M. tuberculosis. Methods Strains from two major modern lineages (lineage 2 [East-Asian] and lineage 4 [Euro-American]) circulating in the Western Cape in South Africa as well as a comparator modern lineage (lineage 3 [CAS/Delhi]) were identified. We assessed two virulence associated characteristics: mycobacterial growth (in liquid broth and monocyte derived macrophages) and early pro-inflammatory cytokine induction. Results In liquid culture, Lineage 4 strains grew more rapidly and reached higher plateau levels than other strains (lineage 4 vs. lineage 2 p = 0.0024; lineage 4 vs. lineage 3 p = 0.0005). Lineage 3 strains were characterized by low and early plateau levels, while lineage 2 strains showed an intermediate growth phenotype. In monocyte-derived macrophages, lineage 2 strains grew faster than lineage 3 strains (p<0.01) with lineage 4 strains having an intermediate phenotype. Lineage 2 strains induced the lowest levels of pro-inflammatory TNF and IL-12p40 as compared to other lineages (lineage 2: median TNF 362 pg/ml, IL-12p40 91 pg/ml; lineage 3: median TNF 1818 pg/ml, IL-12p40 123 pg/ml; lineage 4: median TNF 1207 pg/ml, IL-12p40 205 pg/ml;). In contrast, lineage 4 strains induced high levels of IL-12p40 and intermediate level of TNF. Lineage 3 strains induced high levels of TNF and intermediate levels of IL-12p40. Conclusions Strains of M. tuberculosis from the three major modern strain lineages possess distinct patterns of growth and cytokine induction. Rapid growth and immune subversion may be key characteristics to the success of

  4. Pentraxin-3 Is a TSH-Inducible Protein in Human Fibrocytes and Orbital Fibroblasts.

    PubMed

    Wang, Hao; Atkins, Stephen J; Fernando, Roshini; Wei, Rui-Li; Smith, Terry J

    2015-11-01

    CD34(+) fibrocytes are bone marrow-derived monocyte progenitor cells that traffic to sites of tissue injury and repair. They putatively infiltrate the orbit in thyroid-associated ophthalmopathy where they appear to transition into CD34(+) orbital fibroblasts (OFs) that interact with residential CD34(-) fibroblasts. A unique phenotypic attribute of fibrocytes and CD34(+) OFs is their expression of the functional thyrotropin receptor (TSHR) and other "thyroid-specific" proteins. When activated through TSHR, fibrocytes express a number of cytokines and other inflammatory genes. Here we sought to determine whether pentraxin-3 (PTX-3), an acute-phase protein involved in inflammation and autoimmunity, might be induced by TSH in fibrocytes and OFs. These cells were collected from patients with Graves disease and healthy individuals. PTX-3 mRNA levels were determined by real-time PCR, protein was determined by ELISA and Western blot, and PTX-3 gene promoter activity was assessed with reporter assays. PTX-3 expression was induced by TSH in both cell types, regardless of the health status of the donor and was a consequence of increased steady-state PTX-3 mRNA levels. M22, a TSHR-activating monoclonal antibody, also induced PTX-3. The induction could be attenuated by dexamethasone and by IGF-I receptor-blocking antibodies, teprotumumab and 1H7. TSH effects were mediated through phosphatidylinositol 3-kinase/AKT, mammalian target of rapamycin/p70(s6k), Janus tyrosine kinase 2 pathways, and enhanced PTX-3 mRNA stability. These findings indicate that PTX-3 is a TSH target gene, the expression of which can be induced in fibrocytes and OFs. They suggest that PTX-3 might represent a previously unidentified nexus between the thyroid axis and the mechanisms involved in tissue remodeling. PMID:26287404

  5. Leishmania mexicana promastigotes down regulate JNK and p-38 MAPK activation: Role in the inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.

    PubMed

    Rodríguez-González, Jorge; Wilkins-Rodríguez, Arturo; Argueta-Donohué, Jesús; Aguirre-García, Magdalena; Gutiérrez-Kobeh, Laila

    2016-04-01

    Dendritic cells (DC) are one of the principal host cells of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a strategy employed by multiple pathogens to ensure their survival in the infected cell. We have previously shown that the infection of monocyte-derived dendritic cells (moDC) with Leishmania mexicana inhibits campthotecin-induced apoptosis. Nevertheless, the mechanisms involved in the inhibition of apoptosis of dendritic cells by Leishmania have not been established. Mitogen-activated protein kinases (MAPK) are key participants in the process of apoptosis and different species of Leishmania have been shown to regulate these kinases. In the present study, we analyzed the effect of L. mexicana promastigotes in the activation of JNK and p38 MAP kinase and their participation in the inhibition of apoptosis. The infection of moDC with L. mexicana promastigotes diminished significantly the phosphorylation of the MAP kinases JNK and p38. The inhibition of both kinases diminished DNA fragmentation, but in a major extent was the reduction of DNA fragmentation when JNK was inhibited. The capacity of L. mexicana promastigotes to diminish MAP kinases activation is probably one of the strategies employed to delay apoptosis induction in the infected moDC and may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells. PMID:26777406

  6. Paradigm Shift in Dendritic Cell-Based Immunotherapy: From in vitro Generated Monocyte-Derived DCs to Naturally Circulating DC Subsets

    PubMed Central

    Wimmers, Florian; Schreibelt, Gerty; Sköld, Annette E.; Figdor, Carl G.; De Vries, I. Jolanda M.

    2014-01-01

    Dendritic cell (DC)-based immunotherapy employs the patients’ immune system to fight neoplastic lesions spread over the entire body. This makes it an important therapy option for patients suffering from metastatic melanoma, which is often resistant to chemotherapy. However, conventional cellular vaccination approaches, based on monocyte-derived DCs (moDCs), only achieved modest response rates despite continued optimization of various vaccination parameters. In addition, the generation of moDCs requires extensive ex vivo culturing conceivably hampering the immunogenicity of the vaccine. Recent studies, thus, focused on vaccines that make use of primary DCs. Though rare in the blood, these naturally circulating DCs can be readily isolated and activated thereby circumventing lengthy ex vivo culture periods. The first clinical trials not only showed increased survival rates but also the induction of diversified anti-cancer immune responses. Upcoming treatment paradigms aim to include several primary DC subsets in a single vaccine as pre-clinical studies identified synergistic effects between various antigen-presenting cells. PMID:24782868

  7. Comparative analysis of the early transcriptome of Brucella abortus - infected monocyte-derived macrophages from cattle naturally resistant or susceptible to brucellosis

    PubMed Central

    Rossetti, C.A.; Galindo, C.L.; Everts, R.E.; Lewin, H.A.; Garner, H.R.; Adams, L.G.

    2010-01-01

    Brucellosis is a worldwide zoonotic infectious disease that has a significant economic impact on animal production and human public health. We characterized the gene expression profile of B. abortus-infected monocyte-derived macrophages (MDMs) from naïve cattle naturally resistant (R) or susceptible (S) to brucellosis using a cDNA microarray technology. Our data indicate that 1) B. abortus induced a slightly increased genome activation in R MDMs and a down-regulated transcriptome in S MDMs, during the onset of infection, 2) R MDMs had the ability to mount a type 1 immune response against B. abortus infection which was impaired in S cells, and 3) the host cell activity was not altered after 12h post-B. abortus infection in R MDMs while the cell cycle was largely arrested in infected S MDMs at 12h p.i. These results contribute to understand of how host responses may be manipulated to prevent infection by brucellae. PMID:20932540

  8. High Intracellular Concentrations of Posaconazole Do Not Impact on Functional Capacities of Human Polymorphonuclear Neutrophils and Monocyte-Derived Macrophages In Vitro.

    PubMed

    Farowski, Fedja; Cornely, Oliver A; Hartmann, Pia

    2016-06-01

    Posaconazole is a commonly used antifungal for the prophylaxis and treatment of invasive fungal infections. We previously demonstrated that the intracellular concentration of posaconazole in peripheral blood mononuclear cells (PBMCs) and polymorphonuclear neutrophils (PMNs) was greatly increased compared to the plasma concentration. As these professional phagocytes are crucial to combat fungal infections, we set out to investigate if and how, beneficial or deleterious, this high loading of intracellular posaconazole impacts the functional capacities of these cells. Here, we show that high intracellular concentrations of posaconazole do not significantly impact PMN and monocyte-derived macrophage function in vitro In particular, killing capacity and cytoskeletal features of PMN, such as migration, are not affected, indicating that these cells serve as vehicles for posaconazole to the site of infection. Moreover, since posaconazole as such slowed the germination of Aspergillus fumigatus conidia, infected neutrophils released less reactive oxygen species (ROS). Based on these findings, we propose that the delivery of posaconazole by neutrophils to the site of Aspergillus species infection warrants control of the pathogen and preservation of tissue integrity at the same time. PMID:27021317

  9. Toll-like receptor 3 (TLR3): a new marker of canine monocytes-derived dendritic cells (cMo-DC).

    PubMed

    Bonnefont-Rebeix, Catherine; Marchal, Thierry; Bernaud, Janine; Pin, Jean-Jacques; Leroux, Caroline; Lebecque, Serge; Chabanne, Luc; Rigal, Dominique

    2007-07-15

    Toll-like receptors (TLRs) are a family of functionally important receptors for recognition of pathogen-associated molecular pattern (PAMP) since they trigger the pro-inflammatory response and upregulation of costimulatory molecules, linking the rapid innate response to adaptative immunity. In human leukocytes, TLR3 has been found to be specifically expressed in dendritic cells (DC). This study examined the expression of TLR3 in canine monocytes-derived DC (cMo-DC) and PBMC using three new anti-TLR3 mAbs (619F7, 722E2 and 713E4 clones). The non-adherent cMo-DC generated after culture in canine IL-4 plus canine GM-CSF were labelled with the three anti-TLR3 clones by flow cytometry, with a strong expression shown for 619F7 and 722E2 clones. By contrast, TLR3 expression was low to moderate in canine monocytes and lymphocytes. These results were confirmed by Western blot using 619F7 and 722E2 clones and several polypeptide bands were observed, suggesting a possible cleavage of TLR3 molecule or different glycosylation states. In addition, TLR3 was detectable in immunocytochemistry by using 722E2 clone. In conclusion, this first approach to study canine TLR3 protein expression shows that three anti-TLR3 clones detect canine TLR3 and can be used to better characterize canine DC and the immune system of dogs. PMID:17521746

  10. The Role of Porcine Monocyte Derived Dendritic Cells (MoDC) in the Inflammation Storm Caused by Streptococcus suis Serotype 2 Infection

    PubMed Central

    Liu, Jin; Tian, Zhong-Yuan; Xiao, Yun-Cai; Wang, Xi-Liang; Jin, Mei-Lin; Shi, De-Shi

    2016-01-01

    Background Streptococcus suis is an important swine pathogen and zoonotic agent. Infection with this highly pathogenic strain can cause streptococcal toxic shock-like syndrome (STSLS), characterized by a Th-1 inflammatory cytokine storm, and a high mortality rate. Monocyte derived dendritic cells (MoDCs) are known to stimulate Th-1 cell differentiation, but the role of MoDCs in STSLS remains to be elucidated. Methodology and Findings Porcine CD14-positive monocytes, purified from peripheral blood mononuclear cells (PBMCs), were used to generate MoDCs using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). Highly pure MoDCs were generated, as proved by their morphology, phenotype analysis, phagocytic ability, and induction of T cells proliferation. The MoDCs were further stimulated by the virulent S. suis serotype 2 (SS2) SC19 strain which triggered a strong release of several pro-inflammatory cytokines, including IL-1β, IL-8, TNF-α, IFN-γ, and IL-12. Furthermore, the stimulated MoDCs induced CD4+ T cell differentiation towards Th-1 cells in vitro. Conclusions The results of this study indicated that the porcine MoDCs stimulated by SS2 could release high levels of Th-1 inflammatory cytokines and induce CD4+ T cell differentiation towards Th-1 cells. Hence, it is likely that porcine MoDCs play an important role in the STSLS caused by SS2. PMID:26974437

  11. Elevated level of pro inflammatory cytokine and chemokine expression in chicken bone marrow and monocyte derived dendritic cells following LPS induced maturation.

    PubMed

    Kalaiyarasu, Semmannan; Bhatia, Sandeep; Mishra, Niranjan; Sood, Richa; Kumar, Manoj; SenthilKumar, D; Bhat, Sushant; Dass Prakash, M

    2016-09-01

    The study was designed to characterize and compare chicken bone marrow and peripheral blood monocyte derived dendritic cells (chBM-DC and chMoDC) and to evaluate inflammatory cytokine and chemokine alterations in response upon LPS stimulation. Typical morphology was observed in DCs from 48h of culture using recombinant chicken GM-CSF and IL-4. Maturation of DCs with LPS (1μg/ml) showed significant up regulation of mRNA of surface markers (CD40, CD80, CD83, CD86, MHC-II and DC-LAMP (CD208)), pro-inflammatory cytokines (IL-1β, IL-6, TNF-α (LITAF)), iNOS, chemokine CXCli2 and TLRs4 and 15. Basal level of TLR1 mRNA expression was higher followed by TLR15 in both DCs irrespective of their origin. Expression of iNOS and CXCLi2 mRNA in mature DCs of both origins were higher than other surface molecules and cytokines studied. Hence, its level of expression can also be used as an additional maturation marker for LPS induced chicken dendritic cell maturation along with CD83 and CD40. LPS matured DCs of both origins upregulated IL-12 and IFN-γ. Based on CD40 and CD83 mRNA expression, it was observed that LPS induced the maturation in both DCs, but chMoDCs responded better in expression of surface markers and inflammatory mediator genes. PMID:27344111

  12. Gallic Acid Is the Major Active Component of Cortex Moutan in Inhibiting Immune Maturation of Human Monocyte-Derived Dendritic Cells.

    PubMed

    Chan, Ben Chung Lap; Li, Long Fei; Hu, Shui Qing; Wat, Elaine; Wong, Eric Chun Wai; Zhang, Vanilla Xin; Lau, Clara Bik San; Wong, Chun Kwok; Hon, Kam Lun Ellis; Hui, Patrick Chi Leung; Leung, Ping Chung

    2015-01-01

    Atopic dermatitis (AD) is a widely prevalent and chronically relapsing inflammatory skin disease. Penta Herbs Formula (PHF) is efficacious in improving the quality of life and reducing topical corticosteroid used in children with AD and one of the active herbs it contains is Cortex Moutan. Recent studies showed that altered functions of dendritic cells (DC) were observed in atopic individuals, suggesting that DC might play a major role in the generation and maintenance of inflammation by their production of pro-inflammatory cytokines. Hence, the aims of the present study were to identify the major active component(s) of Cortex Moutan, which might inhibit DC functions and to investigate their possible interactions with conventional corticosteroid on inhibiting the development of DC from monocytes. Monocyte-derived dendritic cells (moDC) culture model coupled with the high-speed counter-current chromatography (HSCCC), high pressure liquid chromatography (HPLC) and Liquid Chromatography-Mass Spectrometry (LCMS) analyses were used. Gallic acid was the major active component from Cortex Moutan which could dose dependently inhibit interleukin (IL)-12 p40 and the functional cluster of differentiation (CD) surface markers CD40, CD80, CD83 and CD86 expression from cytokine cocktail-activated moDC. Gallic acid could also lower the concentration of hydrocortisone required to inhibit the activation of DC. PMID:26378505

  13. Activation of peroxisome proliferator-activated receptor gamma leads to upregulation of ESE-3 expression in human monocyte-derived dendritic cells.

    PubMed

    Sprater, F; Azeem, W; Appel, S

    2014-01-01

    The transcription factor ESE-3 has been suggested to be involved in regulating the immunogenicity of human monocyte-derived dendritic cells (moDCs). While ESE-3 is not expressed in monocytes, it is upregulated during the differentiation of monocytes into dendritic cells (DCs) and highly expressed in immunogenic DCs while downregulated in tolerogenic DCs. Activation of peroxisome proliferator-activated receptor gamma (PPAR-γ) during DC development has been shown to result in a rather tolerogenic cell population. In this study, we identified eight PPAR-γ binding sites upstream of the ESE-3 gene. Activation of the PPAR-γ pathway with synthetic PPAR-γ ligands during moDC generation resulted in upregulation of ESE-3b expression on mRNA and protein level, phenotypic alterations and reduced capacity of the cells to stimulate allogeneic T cells. This could be inhibited by blocking the PPAR-γ pathway with specific antagonists. Our results suggest PPAR-γ to be involved in the regulation of ESE-3b expression during moDC development and that ESE-3 expression is not correlated with the immunogenicity of DCs. PMID:24219556

  14. Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity.

    PubMed

    Bol, Kalijn F; Aarntzen, Erik H J G; Pots, Jeanette M; Olde Nordkamp, Michel A M; van de Rakt, Mandy W M M; Scharenborg, Nicole M; de Boer, Annemiek J; van Oorschot, Tom G M; Croockewit, Sandra A J; Blokx, Willeke A M; Oyen, Wim J G; Boerman, Otto C; Mus, Roel D M; van Rossum, Michelle M; van der Graaf, Chantal A A; Punt, Cornelis J A; Adema, Gosse J; Figdor, Carl G; de Vries, I Jolanda M; Schreibelt, Gerty

    2016-03-01

    Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail. PMID:26861670

  15. Nonopsonic phagocytosis of nonmucoid Pseudomonas aeruginosa by human neutrophils and monocyte-derived macrophages is correlated with bacterial piliation and hydrophobicity.

    PubMed Central

    Speert, D P; Loh, B A; Cabral, D A; Salit, I E

    1986-01-01

    We have shown previously that some strains of Pseudomonas aeruginosa from patients with cystic fibrosis are phagocytized by human polymorphonuclear leukocytes in the absence of serum opsonins. The purpose of this study was to identify the bacterial features which render certain strains susceptible to nonopsonic phagocytosis. Three strains were phagocytized by human neutrophils and monocyte-derived macrophages, and two were not, as determined by luminol-enhanced chemiluminescence, visual inspection of stained smears, and bactericidal assay. Strains that were phagocytized formed pellicles when grown in static broth, but the phagocytosis-resistant strains did not. The phagocytosis-susceptible strains were more heavily piliated and more hydrophobic than the resistant strains. Bacteria exposed to heat (60 degrees C) or UV irradiation were depiliated, as assessed by electron microscopy, and rendered resistant to phagocytosis. When P. aeruginosa was grown on agar, it was piliated, hydrophobic, and susceptible to nonopsonic phagocytosis, but when grown to stationary phase in shaken broth, it was nonpiliated, less hydrophobic, and resistant to phagocytosis. It appears that nonopsonic phagocytosis of certain P. aeruginosa strains by human polymorphonuclear leukocytes and macrophages is facilitated by hydrophobic interactions which may be determined in part by pili. PMID:2873104

  16. Human monocyte-derived macrophages infected with virulent Shigella flexneri in vitro undergo a rapid cytolytic event similar to oncosis but not apoptosis.

    PubMed Central

    Fernandez-Prada, C M; Hoover, D L; Tall, B D; Venkatesan, M M

    1997-01-01

    Infection of human monocyte-derived macrophages in vitro with virulent Shigella flexneri resulted in cell death which involved rupture of the plasma membrane, cell swelling, disintegration of ultrastructure, and generalized karyolysis. These features bore resemblance to oncosis and are in striking contrast to previously described observations of mouse macrophages, where a similar infection by virulent Shigella resulted in cell death by apoptosis. Cell death by oncosis in human macrophages was confirmed by lactate dehydrogenase release, light microscopy, electron microscopy, terminal deoxynucleotidyltransferase end labeling of DNA ends, DNA fragmentation assays, and fluorescence-activated cell sorter analysis of propidium-labeled nuclei. Thus, the phenomena of cell death induced by virulent Shigella in human and mouse macrophages reflect different biochemical pathways. Interleukin-1beta (IL-1beta) was released in culture supernatants of human macrophages infected with virulent bacteria. Inhibition with IL-1beta-converting enzyme inhibitors indicated, however, that this release occurred as a passive event of cell lysis. The patterns of intracellular survival of Shigella strains within human and mouse macrophages reflect differences that exist not only between Shigella serotypes but also between the two different macrophage cell types. PMID:9119491

  17. Anti-CSF-1 treatment is effective to prevent carcinoma invasion induced by monocyte-derived cells but scarcely by microglia

    PubMed Central

    Rietkötter, Eva; Bleckmann, Annalen; Bayerlová, Michaela; Menck, Kerstin; Chuang, Han-Ning; Wenske, Britta; Schwartz, Hila; Erez, Neta; Binder, Claudia; Hanisch, Uwe-Karsten; Pukrop, Tobias

    2015-01-01

    The mononuclear phagocytic system is categorized in three major groups: monocyte-derived cells (MCs), dendritic cells and resident macrophages. During breast cancer progression the colony stimulating factor 1 (CSF-1) can reprogram MCs into tumor-promoting macrophages in the primary tumor. However, the effect of CSF-1 during colonization of the brain parenchyma is largely unknown. Thus, we analyzed the outcome of anti-CSF-1 treatment on the resident macrophage population of the brain, the microglia, in comparison to MCs, alone and in different in vitro co-culture models. Our results underline the addiction of MCs to CSF-1 while surprisingly, microglia were not affected. Furthermore, in contrast to the brain, the bone marrow did not express the alternative ligand, IL-34. Yet treatment with IL-34 and co-culture with carcinoma cells partially rescued the anti-CSF-1 effects on MCs. Further, MC-induced invasion was significantly reduced by anti-CSF-1 treatment while microglia-induced invasion was reduced to a lower extend. Moreover, analysis of lung and breast cancer brain metastasis revealed significant differences of CSF-1 and CSF-1R expression. Taken together, our findings demonstrate not only differences of anti-CSF-1 treatment on MCs and microglia but also in the CSF-1 receptor and ligand expression in brain and bone marrow as well as in brain metastasis. PMID:26098772

  18. Middle East respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells.

    PubMed

    Tynell, Janne; Westenius, Veera; Rönkkö, Esa; Munster, Vincent J; Melén, Krister; Österlund, Pamela; Julkunen, Ilkka

    2016-02-01

    In this study we assessed the ability of Middle East respiratory syndrome coronavirus (MERS-CoV) to replicate and induce innate immunity in human monocyte-derived macrophages and dendritic cells (MDDCs), and compared it with severe acute respiratory syndrome coronavirus (SARS-CoV). Assessments of viral protein and RNA levels in infected cells showed that both viruses were impaired in their ability to replicate in these cells. Some induction of IFN-λ1, CXCL10 and MxA mRNAs in both macrophages and MDDCs was seen in response to MERS-CoV infection, but almost no such induction was observed in response to SARS-CoV infection. ELISA and Western blot assays showed clear production of CXCL10 and MxA in MERS-CoV-infected macrophages and MDDCs. Our data suggest that SARS-CoV and MERS-CoV replicate poorly in human macrophages and MDDCs, but MERS-CoV is nonetheless capable of inducing a readily detectable host innate immune response. Our results highlight a clear difference between the viruses in activating host innate immune responses in macrophages and MDDCs, which may contribute to the pathogenesis of infection. PMID:26602089

  19. Analysis of histone post translational modifications in primary monocyte derived macrophages using reverse phase×reverse phase chromatography in conjunction with porous graphitic carbon stationary phase.

    PubMed

    Minshull, Thomas C; Cole, Joby; Dockrell, David H; Read, Robert C; Dickman, Mark J

    2016-07-01

    A two dimensional-liquid chromatography (2D-LC) based approach was developed for the identification and quantification of histone post translational modifications in conjunction with mass spectrometry analysis. Using a bottom-up strategy, offline 2D-LC was developed using reverse phase chromatography. A porous graphitic carbon stationary phase in the first dimension and a C18 stationary phase in the second dimension interfaced with mass spectrometry was used to analyse global levels of histone post translational modifications in human primary monocyte-derived macrophages. The results demonstrated that 84 different histone peptide proteoforms, with modifications at 18 different sites including combinatorial marks were identified, representing an increase in the identification of histone peptides by 65% and 51% compared to two different 1D-LC approaches on the same mass spectrometer. The use of the porous graphitic stationary phase in the first dimension resulted in efficient separation of histone peptides across the gradient, with good resolution and is orthogonal to the online C18 reverse phase chromatography. Overall, more histone peptides were identified using the 2D-LC approach compared to conventional 1D-LC approaches. In addition, a bioinformatic pipeline was developed in-house to enable the high throughput efficient and accurate quantification of fractionated histone peptides. The automation of a section of the downstream analysis pipeline increased the throughput of the 2D-LC-MS/MS approach for the quantification of histone post translational modifications. PMID:27260198

  20. Results of a phase 1 study utilizing monocyte-derived dendritic cells pulsed with tumor RNA in children and young adults with brain cancer1

    PubMed Central

    Caruso, Denise A.; Orme, Lisa M.; Neale, Alana M.; Radcliff, Fiona J.; Amor, Gerlinda M.; Maixner, Wirginia; Downie, Peter; Hassall, Timothy E.; Tang, Mimi L.K.; Ashley, David M.

    2004-01-01

    We conducted a phase 1 study of 9 pediatric patients with recurrent brain tumors using monocyte-derived dendritic cells pulsed with tumor RNA to produce antitumor vaccine (DCRNA) preparations. The objectives of this study included (1) establishing safety and feasibility and (2) measuring changes in general, antigen-specific, and tumor-specific immune responses after DCRNA. Dendritic cells were derived from freshly isolated monocytes after 7 days of culture with IL-4 and granulocyte-macrophage colony–stimulating factor, pulsed with autologous tumor RNA, and then cryopreserved. Patients received at least 3 vaccines, each consisting of an intravenous and an intra-dermal administration at biweekly intervals. The study showed that this method for producing and administering DCRNA from a single leukapheresis product was both feasible and safe in this pediatric brain tumor population. Immune function at the time of enrollment into the study was impaired in all patients tested. While humoral responses to recall antigens (diphtheria and tetanus) were intact in all patients, cellular responses to mitogen and recall antigens were below normal. Following DCRNA vaccine, 2 of 7 patients showed stable clinical disease and 1 of 7 showed a partial response. Two of 7 patients who were tested showed a tumor-specific immune response to DCRNA. This study showed that DCRNA vaccines are both safe and feasible in children with tumors of the central nervous system with a single leukapheresis. PMID:15279716

  1. Evaluation of an optimized protocol using human peripheral blood monocyte derived dendritic cells for the in vitro detection of sensitizers: Results of a ring study in five laboratories.

    PubMed

    Reuter, Hendrik; Gerlach, Silke; Spieker, Jochem; Ryan, Cindy; Bauch, Caroline; Mangez, Claire; Winkler, Petra; Landsiedel, Robert; Templier, Marie; Mignot, Aurelien; Gerberick, Frank; Wenck, Horst; Aeby, Pierre; Schepky, Andreas

    2015-08-01

    Allergic contact dermatitis is a delayed T-cell mediated allergic response associated with relevant social and economic impacts. Animal experiments (e.g. the local lymph node assay) are still supplying most of the data used to assess the sensitization potential of new chemicals. However, the 7th amendment to the EU Cosmetic Directive have introduced a testing ban for cosmetic ingredients after March 2013. We have developed and optimized a stable and reproducible in vitro protocol based on human peripheral blood monocyte derived dendritic cells to assess the sensitization potential of chemicals. To evaluate the transferability and the predictivity of this PBMDCs based test protocol, a ring study was organized with five laboratories using seven chemicals with a known sensitization potential (one none-sensitizer and six sensitizers, including one pro-hapten). The results indicated that this optimized test protocol could be successfully transferred to all participating laboratories and allowed a correct assessment of the sensitization potential of the tested set of chemicals. This should allow a wider acceptance of PBMDCs as a reliable test system for the detection of human skin sensitizers and the inclusion of this protocol in the toolbox of in vitro methods for the evaluation of the skin sensitization potential of chemicals. PMID:25868915

  2. Monocyte-Derived Dendritic Cells from Patients with Dermatophytosis Restrict the Growth of Trichophyton rubrum and Induce CD4-T Cell Activation

    PubMed Central

    Santiago, Karla; Bomfim, Gisele Facholi; Criado, Paulo Ricardo; Almeida, Sandro Rogerio

    2014-01-01

    Dermatophytes are the most common agents of superficial mycoses that are caused by mold fungi. Trichophyton rubrum is the most common pathogen causing dermatophytosis. The immunology of dermatophytosis is currently poorly understood. Recently, our group investigated the interaction of T. rubrum conidia with peritoneal mouse macrophages. We found that macrophages phagocytose T. rubrum conidia resulted in a down-modulation of class II major histocompatibility complex (MHC) antigens and in the expression of co-stimulatory molecules. Furthermore, it induced the production of IL-10, and T. rubrum conidia differentiated into hyphae that grew and killed the macrophages after 8 hrs of culture. This work demonstrated that dendritic cells (DCs) and macrophages, from patients or normal individuals, avidly interact with pathogenic fungus T. rubrum. The dermatophyte has two major receptors on human monocyte-derived DC: DC-SIGN and mannose receptor. In contrast macrophage has only mannose receptor that participates in the phagocytosis or bound process. Another striking aspect of this study is that unlike macrophages that permit rapid growth of T. rubrum, human DC inhibited the growth and induces Th activation. The ability of DC from patients to interact and kill T. rubrum and to present Ags to T cells suggests that DC may play an important role in the host response to T. rubrum infection by coordinating the development of cellular immune response. PMID:25372145

  3. The role of the fibrocyte, a bone marrow-derived mesenchymal progenitor, in reactive and reparative fibroses.

    PubMed

    Bellini, Alberto; Mattoli, Sabrina

    2007-09-01

    Human fibrocytes are mesenchymal progenitors that exhibit mixed morphological and molecular characteristics of hematopoietic stem cells, monocytes and fibroblasts. They likely represent the obligate intermediate stage of differentiation into mature mesenchymal cells of a bone marrow-derived precursor of the monocyte lineage under permissive conditions. On in vitro stimulation with pro-fibrotic cytokines and growth factors, human fibrocytes produce large quantities of extracellular matrix components and further differentiate into cells identical to the contractile myofibroblasts that emerge at the tissue sites during repair processes and in some fibrotic lesions. Studies in various animal models of wound healing or fibrotic diseases have confirmed the ability of fibrocytes to differentiate into mature mesenchymal cells in vivo and have suggested a causal link between fibrocyte accumulation and ongoing tissue fibrogenesis or vascular remodeling in response to tissue damage or hypoxia. Fibrocytes synthesizing new collagen or acquiring myofibroblast markers have been detected in human hypertrophic scars, in the skin of patients affected by nephrogenic systemic fibrosis, in human atherosclerotic lesions, and in pulmonary diseases characterized by repeated cycles of inflammation and repair, like asthma. The presence of fibrocyte-like cells has been reported in human chronic pancreatitis and chronic cystitis. Similar cells also populate the stroma surrounding human benign tumors. The available data indicate that human fibrocytes serve as a source of mature mesenchymal cells during reparative processes and in fibrotic disorders or stromal reactions predominantly associated with a persistent inflammatory infiltrate or with the selective recruitment of monocytes induced by ischemic changes and tumor development. A deeper understanding of the mechanisms involved in fibrocyte differentiation in these pathological conditions may lead to the development of novel therapies for

  4. Recognizing the Putative Role for TSH Receptor Expressing Fibrocytes in Thyroid-Associated Ophthalmopathy may solve several mysteries

    PubMed Central

    Smith, Terry J.

    2015-01-01

    Thyroid-associated ophthalmopathy (TAO) remains the vexing and undertreated ocular component of Graves’ disease where orbital tissues undergo extensive remodeling. We have recently introduced the concept that CD34+ fibrocytes, bone marrow derived monocyte lineage precursor cells express the thyrotropin receptor (TSHR) and several other proteins traditionally thought to be expressed uniquely in the thyroid. TSHR-engaged fibrocytes generate extremely high levels of several inflammatory cytokines. Acting in concert with TSHR, the insulin-like growth factor 1 receptor (IGF-1R) expressed by fibrocytes appears to be necessary for TSHR-dependent cytokine production since anti-IGF-1R blocking antibodies attenuate these actions of TSH. Further, circulating fibrocytes become more abundant and appear to infiltrate orbital connective tissues in TAO where they may transition to CD34+ fibroblasts. We currently postulate that the infiltration of fibrocytes into the orbit and their unique biosynthetic repertoire and proinflammatory/profibrotic phenotype account for the characteristic properties exhibited by orbital connective tissues that render them susceptible to TAO. Further, it may be possible to utilize these very recent insights to therapeutically target pathogenic orbital fibrocytes selectively utilizing recently developed biologic agents which interfere with TSHR and IGF-1R signaling. PMID:25560705

  5. Cooperation between human fibrocytes and endothelial colony-forming cells increases angiogenesis via the CXCR4 pathway.

    PubMed

    Smadja, David M; Dorfmüller, Peter; Guerin, Coralie L; Bieche, Ivan; Badoual, Cécile; Boscolo, Elisa; Kambouchner, Marianne; Cazes, Aurélie; Mercier, Olaf; Humbert, Marc; Gaussem, Pascale; Bischoff, Joyce; Israël-Biet, Dominique

    2014-11-01

    Fibrotic diseases of the lung are associated with a vascular remodelling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that co-express haematopoietic cell antigens and fibroblast markers, and have been shown to contribute to organ fibrosis. The purpose of this study was to determine whether fibrocytes cooperate with endothelial colony-forming cells (ECFC) to induce angiogenesis. We isolated fibrocytes from blood of patient with idiopathic pulmonary fibrosis (IPF) and characterised them by flow cytometry, quantitative reverse transcriptase PCR (RTQ-PCR), and confocal microscopy. We then investigated the angiogenic interaction between fibrocytes and cord-blood-derived ECFC, both in vitro and in an in vivo Matrigel implant model. Compared to fibroblast culture medium, fibrocyte culture medium increased ECFC proliferation and differentiation via the SDF-1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in Matrigel plugs in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after two weeks revealed an extensive network of erythrocyte-containing blood vessels. CXCR4 blockade significantly inhibited this blood vessel formation. The clinical relevance of these data was confirmed by strong CXCR4 expression in vessels close to fibrotic areas in biopsy specimens from patients with IPF, by comparison with control lungs. In conclusion, circulating fibrocytes might contribute to the intense remodelling of the pulmonary vasculature in patients with idiopathic pulmonary fibrosis. PMID:25103869

  6. Alternative strategies to manipulate fibrocyte involvement in the fibrotic tissue response: pharmacokinetic inhibition and the feasibility of directed-adipogenic differentiation

    PubMed Central

    Baker, David W; Tsai, Yi-Ting; Weng, Hong; Tang, Liping

    2014-01-01

    Fibrocytes have previously been identified as important mediators in several inflammatory and fibrotic diseases. However, there is no effective treatment thus far to reduce fibrotic tissue responses without affecting wound healing reactions. Here we investigate two strategies to alleviate fibrocyte interactions at the biomaterial interface reducing collagen production and scar tissue formation. First, in an indirect approach, TGF-β inhibitor-SB431542 and IL-1β/TNF-α inhibitor SB203580 were locally released from scaffold implants to block their respective signaling pathways. We show that inhibition of IL-1β/TNF-α has no influence on overall fibrotic tissue reactions to the implants. However, the reduction of localized TGF-β significantly decreases the fibrocyte accumulation and myofibroblast activation while reducing the fibrotic tissue formation. Since fibrocytes can be differentiated into non-fibrotic cell types, such as adipocytes, we further sought a more direct approach to reduce fibrocyte responses by directing fibrocyte differentiation into adipocytes. Interestingly, by initiating fibrocyte-to-adipocyte differentiation through sustained differentiation cocktail release, we find that adipogentic differentiation forces incoming fibrocytes away from the traditional myofibroblast lineage leading to a substantial reduction in the collagen formation and fibrotic response. Our results support a novel and effective strategy to improve implant safety by reducing implant-associated fibrotic tissue reactions via directing non-fibrotic differentiation of fibrocytes. PMID:24657674

  7. Alternative strategies to manipulate fibrocyte involvement in the fibrotic tissue response: pharmacokinetic inhibition and the feasibility of directed-adipogenic differentiation.

    PubMed

    Baker, David W; Tsai, Yi-Ting; Weng, Hong; Tang, Liping

    2014-07-01

    Fibrocytes have previously been identified as important mediators in several inflammatory and fibrotic diseases. However, there is no effective treatment thus far to reduce fibrotic tissue responses without affecting wound healing reactions. Here we investigate two strategies to alleviate fibrocyte interactions at the biomaterial interface, reducing collagen production and scar tissue formation. First, in an indirect approach, TGF-β inhibitor-SB431542 and IL-1β/TNF-α inhibitor SB203580 were locally released from scaffold implants to block their respective signaling pathways. We show that the inhibition of IL-1β/TNF-α has no influence on overall fibrotic tissue reactions to the implants. However, the reduction of localized TGF-β significantly decreases the fibrocyte accumulation and myofibroblast activation while reducing the fibrotic tissue formation. Since fibrocytes can be differentiated into non-fibrotic cell types, such as adipocytes, we further sought a more direct approach to reduce fibrocyte responses by directing fibrocyte differentiation into adipocytes. Interestingly, by initiating fibrocyte-to-adipocyte differentiation through sustained differentiation cocktail release, we find that adipogenic differentiation forces incoming fibrocytes away from the traditional myofibroblast lineage, leading to a substantial reduction in the collagen formation and fibrotic response. Our results support a novel and effective strategy to improve implant safety by reducing implant-associated fibrotic tissue reactions via directing non-fibrotic differentiation of fibrocytes. PMID:24657674

  8. Bacillus anthracis capsule activates caspase-1 and induces interleukin-1beta release from differentiated THP-1 and human monocyte-derived dendritic cells.

    PubMed

    Cho, Min-Hee; Ahn, Hae-Jeong; Ha, Hyun-Joon; Park, Jungchan; Chun, Jeong-Hoon; Kim, Bong-Su; Oh, Hee-Bok; Rhie, Gi-Eun

    2010-01-01

    The poly-gamma-d-glutamic acid (PGA) capsule is one of the major virulence factors of Bacillus anthracis, which causes a highly lethal infection. The antiphagocytic PGA capsule disguises the bacilli from immune surveillance and allows unimpeded growth of bacilli in the host. Recently, efforts have been made to include PGA as a component of anthrax vaccine; however, the innate immune response of PGA itself has been poorly investigated. In this study, we characterized the innate immune response elicited by PGA in the human monocytic cell line THP-1, which was differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA) and human monocyte-derived dendritic cells (hMoDCs). PGA capsules were isolated from the culture supernatant of either the pXO1-cured strain of B. anthracis H9401 or B. licheniformis ATCC 9945a. PGA treatment of differentiated THP-1 cells and hMoDCs led to the specific extracellular release of interleukin-1beta (IL-1beta) in a dose-dependent manner. Evaluation of IL-1beta processing by Western blotting revealed that cleaved IL-1beta increased in THP-1 cells and hMoDCs after PGA treatment. Enhanced processing of IL-1beta directly correlated with increased activation of its upstream regulator, caspase-1, also known as IL-1beta-converting enzyme (ICE). The extracellular release of IL-1beta in response to PGA was ICE dependent, since the administration of an ICE inhibitor prior to PGA treatment blocked induction of IL-1beta. These results demonstrate that B. anthracis PGA elicits IL-1beta production through activation of ICE in PMA-differentiated THP-1 cells and hMoDCs, suggesting the potential for PGA as a therapeutic target for anthrax. PMID:19737897

  9. Comparative DNA microarray analysis of human monocyte derived dendritic cells and MUTZ-3 cells exposed to the moderate skin sensitizer cinnamaldehyde

    SciTech Connect

    Python, Francois; Goebel, Carsten; Aeby, Pierre

    2009-09-15

    The number of studies involved in the development of in vitro skin sensitization tests has increased since the adoption of the EU 7th amendment to the cosmetics directive proposing to ban animal testing for cosmetic ingredients by 2013. Several studies have recently demonstrated that sensitizers induce a relevant up-regulation of activation markers such as CD86, CD54, IL-8 or IL-1{beta} in human myeloid cell lines (e.g., U937, MUTZ-3, THP-1) or in human peripheral blood monocyte-derived dendritic cells (PBMDCs). The present study aimed at the identification of new dendritic cell activation markers in order to further improve the in vitro evaluation of the sensitizing potential of chemicals. We have compared the gene expression profiles of PBMDCs and the human cell line MUTZ-3 after a 24-h exposure to the moderate sensitizer cinnamaldehyde. A list of 80 genes modulated in both cell types was obtained and a set of candidate marker genes was selected for further analysis. Cells were exposed to selected sensitizers and non-sensitizers for 24 h and gene expression was analyzed by quantitative real-time reverse transcriptase-polymerase chain reaction. Results indicated that PIR, TRIM16 and two Nrf2-regulated genes, CES1 and NQO1, are modulated by most sensitizers. Up-regulation of these genes could also be observed in our recently published DC-activation test with U937 cells. Due to their role in DC activation, these new genes may help to further refine the in vitro approaches for the screening of the sensitizing properties of a chemical.

  10. Porcine reproductive and respiratory syndrome virus activates the transcription of interferon alpha/beta (IFN-α/β) in monocyte-derived dendritic cells (Mo-DC).

    PubMed

    Zhang, Hanmo; Guo, Xueshui; Nelson, Eric; Christopher-Hennings, Jane; Wang, Xiuqing

    2012-10-12

    Porcine reproductive and respiratory syndrome virus (PRRSV) is known to be a poor inducer of interferon alpha/beta (IFN-α/β), which may contribute to the delayed development of adaptive immunity and the resultant viral persistence. However, the exact mechanism by which PRRSV inhibits the induction of IFN-α/β during infection of its natural host cells remains less well defined. Here, we show that PRRSV efficiently activates the transcription of IFN-α/β in porcine monocyte-derived dendritic cells (Mo-DC) in a time-dependent and transient manner; and this effect is dependent on the activation of phosphatidylinositol 3-kinase (PI3K). Despite the abundant IFN-α transcripts detected in PRRSV-infected Mo-DC, little or no detectable IFN-α is found in the supernatants and cell lysates of PRRSV-infected Mo-DC, suggesting that PRRSV either blocks the translation of IFN-α or inhibits the RNA processing and transport. Furthermore, we observed that PRRSV infection significantly reduced the induction of IFN-α by Poly I:C treatment; and virus replication is essential to the effect since heat-inactivated PRRSV has no effect on IFN-α induction by Poly I:C. Overall, our data provide evidence for the possible role of PI3K in the activation of the transcription of IFN-α/β by PRRSV. We conclude that PRRSV inhibits the induction of IFN-α in Mo-DC by as yet undefined post-transcriptional mechanisms. PMID:22592217

  11. PD-L1 expression is increased in monocyte derived dendritic cells in response to porcine circovirus type 2 and porcine reproductive and respiratory syndrome virus infections.

    PubMed

    Richmond, O; Cecere, T E; Erdogan, E; Meng, X J; Piñeyro, P; Subramaniam, S; Todd, S M; LeRoith, T

    2015-11-15

    Host immune system suppression is thought to be crucial in the development of porcine circovirus associated diseases (PCVAD). Many immune suppressive mechanisms have been studied in cases of PCVAD, however, the role of programmed death ligand-1 (PD-L1) during porcine circovirus type 2 (PCV2) infection and PCVAD development has yet to be determined. PD-L1 has become an important research target because of its ability to interfere with effective T-cell activity and proliferation during the course of an immune response. In this study, porcine monocyte derived dendritic cells (MoDC) were infected with different combinations of PCV2 and porcine reproductive and respiratory syndrome virus (PRRSV) and evaluated for expression levels of PD-L1, as well as the expression levels of swine major histocompatibility complexes 1 and 2 (SLA-1 and SLA-2) as a measure of MoDC stimulatory capacity. PD-L1 expression levels were also tested in MoDCs after treatment with interferon alpha (IFN-α) and beta (IFN-β). The results showed that the expression levels of PD-L1 were increased in PCV2-infected MoDCs, as well as in PCV2 and PRRSV co-infected MoDCs. The MoDCs infected with PRRSV only also showed a strain-dependent increase in PD-L1 expression. Both IFN-α and IFN-β treatment also increased the expression levels of PD-L1 in MoDCs. SLA-1 and 2 expression levels were increased by PCV2 infection, and altered in the PRRSV, and PCV2+PRRSV co-infected MoDCs in a strain-dependent manner. These results indicate a potential immuno-suppressive role for dendritic cells during PCV2 infection and the development of PCVAD and will be helpful in more fully elucidating the underlying mechanisms leading to clinical PCVAD. PMID:26553563

  12. Th2 polarization by Der p 1--pulsed monocyte-derived dendritic cells is due to the allergic status of the donors.

    PubMed

    Hammad, H; Charbonnier, A S; Duez, C; Jacquet, A; Stewart, G A; Tonnel, A B; Pestel, J

    2001-08-15

    The polarization of the immune response toward a Th2 or a Th1 profile can be mediated by dendritic cells (DCs) following antigen presentation and interaction with T cells. Costimulatory molecules such as CD80 and CD86 expressed by DCs, the polarizing cytokine environment during DC--T-cell interaction, and also the nature of the antigen are critical in the orientation of the immune response. In this study, the effect of the cysteine protease Der p 1, one of the major allergens of the house dust mite Dermatophagoides pteronyssinus, on these different parameters was evaluated comparatively on monocyte-derived DCs obtained from healthy donors, from pollen-sensitive patients, or from patients sensitive to Dermatophagoides pteronyssinus. Results showed that Der p 1 induced an increase in CD86 expression only on DCs from house dust mite--sensitive patients. This was also associated with a higher capacity to induce T-cell proliferation, a rapid increase in the production of proinflammatory cytokines, tumor necrosis factor--alpha and interleukin (IL)-1 beta, and the type 2 cytokine IL-10. No changes in the release of IL-12 p70 were induced by Der p 1. Finally, purified T cells from house dust mite-sensitive patients stimulated by autologous Der p 1--pulsed DCs preferentially produced IL-4 rather than interferon-gamma. These effects were abolished in the presence of the inactive precursor of Der p 1 (ProDer p 1). Taken together, these data suggest that DCs from house dust mite--sensitive patients, in contrast to DCs from healthy donors and from pollen-sensitive patients, exposed to Der p 1 play a pivotal role in the enhancement of the Th2 response associated with the allergic reaction developed in response to house dust mite exposure. (Blood. 2001;98:1135-1141) PMID:11493462

  13. Dendritic Cell (DC) Vaccine in Mouse Lung Cancer Minimal Residual Model; Comparison of Monocyte-derived DC vs. Hematopoietic Stem Cell Derived-DC.

    PubMed

    Baek, Soyoung; Lee, Seog Jae; Kim, Myoung Joo; Lee, Hyunah

    2012-12-01

    The anti-tumor effect of monocyte-derived DC (MoDC) vaccine was studied in lung cancer model with feasible but weak Ag-specific immune response and incomplete blocking of tumor growth. To overcome this limitation, the hematopoietic stem cell-derived DC (SDC) was cultured and the anti-tumor effect of MoDC & SDC was compared in mouse lung cancer minimal residual model (MRD). Therapeutic DCs were cultured from either CD34(+) hematopoietic stem cells with GM-CSF, SCF and IL-4 for 14 days (SDC) or monocytes with GM-CSF and IL-4 for 7 days (MoDC). DCs were injected twice by one week interval into the peritoneum of mice that are inoculated with Lewis Lung Carcinoma cells (LLC) one day before the DC injection. Anti-tumor responses and the immune modulation were observed 3 weeks after the final DC injection. CD11c expression, IL-12 and TGF-β secretion were higher in SDC but CCR7 expression, IFN-γ and IL-10 secretion were higher in MoDC. The proportion of CD11c(+)CD8a(+) cells was similar in both DC cultures. Although both DC reduced the tumor burden, histological anti-tumor effect and the frequencies of IFN-γ secreting CD8(+) T cells were higher in SDC treated group than in MoDC. Conclusively, although both MoDC and SDC can induce the anti-tumor immunity, SDC may be better module as anti-tumor vaccine than MoDC in mouse lung cancer. PMID:23396889

  14. Interleukin-12 gene expression in human monocyte-derived macrophages stimulated with Mycobacterium bovis BCG: cytokine regulation and effect of NK cells.

    PubMed Central

    Matsumoto, H; Suzuki, K; Tsuyuguchi, K; Tanaka, E; Amitani, R; Maeda, A; Yamamoto, K; Sasada, M; Kuze, F

    1997-01-01

    Macrophage-derived interleukin-12 (IL-12) is essential for the activation of a protective immune response against intracellular pathogens. In this study, we examined the regulation of IL-12 mRNA expression by monocyte-derived macrophages (MDM) in response to Mycobacterium bovis BCG stimulation. A reverse transcription-PCR assay detected p40 mRNA of IL-12 at 3 h and showed a peak at 6 to 12 h with a subsequent decline. Semiquantitation of mRNA levels by competitive PCR revealed that pretreatment with gamma interferon (IFN-gamma) amplified the expression approximately 100-fold, while pretreatment with tumor necrosis factor alpha (TNF-alpha) or granulocyte-macrophage colony-stimulating factor augmented this expression about 10-fold. In contrast, pretreatment with IL-10 and IL-4 inhibited IL-12 mRNA expression. These results were further confirmed by measuring the p70 bioactive protein level in each conditioned medium by an enzyme-linked immunosorbent assay. Since IL-12 mRNA expression was weak without cytokine pretreatment and IFN-gamma strongly augmented production, we speculated that IFN-gamma might have a role in BCG stimulation of IL-12 mRNA expression. Unexpectedly, the addition of three different kinds of anti-IFN-gamma antibodies and anti-IFN-gamma receptor antibody and the coaddition of anti-TNF-alpha antibody with anti-IFN-gamma receptor antibody all failed to inhibit IL-12 mRNA expression. However, the MiniMACS method used to remove NK cells from a mononuclear cell suspension inhibited the expression of p40 mRNA but not the expression of mRNA of TNF-alpha or IL-1beta. We concluded that the coexistence of NK cells was essential for the induction of IL-12 in MDM stimulated with BCG rather than through the secretion of IFN-gamma. PMID:9353012

  15. Exposure to Δ9-Tetrahydrocannabinol Impairs the Differentiation of Human Monocyte-derived Dendritic Cells and their Capacity for T cell Activation

    PubMed Central

    Castaneda, Julie T.; Kiertscher, Sylvia M.

    2015-01-01

    The capacity for human monocytes to differentiate into antigen-presenting dendritic cells (DC) can be influenced by a number of immune modulating signals. Monocytes express intracellular cannabinoid type 1 (CB1) and 2 (CB2) receptors and we demonstrate that exposure to Δ9-tetrahydrocannabinol (THC) inhibits the forskolin-induced generation of cyclic adenosine monophosphate in a CB2-specific manner. In order to examine the potential impact of cannabinoids on the generation of monocyte-derived DC, monocytes were cultured in vitro with differentiation medium alone [containing granulocyte/macrophage-colony stimulating factor (GM-CSF) and Interleukin-4 (IL-4)] or in combination with THC. The presence of THC (0.25–1.0 μg/ml) altered key features of DC differentiation, producing a concentration-dependent decrease in surface expression of CD11c, HLA-DR and costimulatory molecules (CD40 and CD86), less effective antigen uptake, and signs of functional skewing with decreased production of IL-12 but normal levels of IL-10. When examined in a mixed leukocyte reaction, DC that had been generated in the presence of THC were poor T cell activators as evidenced by their inability to generate effector/memory T cells or to stimulate robust IFN-γ responses. Some of these effects were partially restored by exposure to exogenous IL-7 and bacterial superantigen (S. aureus Cowans strain). These studies demonstrate that human monocytes express functional cannabinoid receptors and suggest that exposure to THC can alter their differentiation into functional antigen presenting cells; an effect that may be counter-balanced by the presence of other immunoregulatory factors. The impact of cannabinoids on adaptive immune responses in individuals with frequent drug exposure remains to be determined. PMID:25614186

  16. Binding immunoglobulin protein-treated peripheral blood monocyte-derived dendritic cells are refractory to maturation and induce regulatory T-cell development.

    PubMed

    Corrigall, Valerie M; Vittecoq, Olivier; Panayi, Gabriel S

    2009-10-01

    Binding immunoglobulin protein (BiP) has been shown previously to have immunomodulatory functions. Herein we investigated whether BiP could affect the differentiation of monocytes into dendritic cells (DCs) and thence the development of regulatory T cells. Peripheral blood monocyte-derived DCs were matured with lipopolysaccharide in the presence or absence of BiP. DC development and T-cell changes were monitored by flow cytometry and regulatory T-cell function was measured by uptake of tritiated thymidine. More BiP-treated DCs (DC((BiP))s) expressed amounts of intracellular indoleamine 2,3-dioxygenase (IDO) and cell surface leucocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1), retained CD14 expression but down-regulated expression of human leucocyte antigen (HLA)-DR and CD86, and produced copious amounts of interleukin (IL)-10, when compared with control DCs. T cells co-cultured with DC((BiP))s developed regulatory function with increased surface expression of CD4(+) CD25(hi) CD27(hi) but with no concomitant increase in forkhead box P3 (Foxp3). These T cells also showed significantly higher levels of intracellular cytotoxic T-lymphocyte antigen (CTLA)-4. The latter could be inhibited by the presence of the IDO inhibitor 1 methyl tryptophan. The addition of neutralizing anti-IL-10 antibody or the specific mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580 reversed the inhibition of DC differentiation by BiP. In conclusion, BiP is an immunomodulator able to arrest inflammation through induction of tolerogenic DCs and subsequent generation of T regulatory cells. PMID:19740378

  17. Peroxisome Proliferator-activated Receptor γ Induces Apoptosis and Inhibits Autophagy of Human Monocyte-derived Macrophages via Induction of Cathepsin L

    PubMed Central

    Mahmood, Dler Faieeq Darweesh; Jguirim-Souissi, Imene; Khadija, El-Hadri; Blondeau, Nicolas; Diderot, Vimala; Amrani, Souliman; Slimane, Mohamed-Naceur; Syrovets, Tatiana; Simmet, Thomas; Rouis, Mustapha

    2011-01-01

    Macrophages play a pivotal role in the pathophysiology of atherosclerosis. These cells express cathepsin L (CatL), a cysteine protease that has been implicated in atherogenesis and the associated arterial remodeling. In addition, macrophages highly express peroxisome proliferator-activated receptor (PPAR) γ, a transcription factor that regulates numerous genes important for lipid and lipoprotein metabolism, for glucose homeostasis, and inflammation. Hence, PPARγ might affect macrophage function in the context of chronic inflammation such as atherogenesis. In the present study, we examined the effect of PPARγ activation on the expression of CatL in human monocyte-derived macrophages (HMDM). Activation of PPARγ by the specific agonist GW929 concentration-dependently increased the levels of CatL mRNA and protein in HMDM. By promoter analysis, we identified a functional PPAR response element-like sequence that positively regulates CatL expression. In addition, we found that PPARγ-induced CatL promotes the degradation of Bcl2 without affecting Bax protein levels. Consistently, degradation of Bcl2 could be prevented by a specific CatL inhibitor, confirming the causative role of CatL. PPARγ-induced CatL was found to decrease autophagy through reduction of beclin 1 and LC3 protein levels. The reduction of these proteins involved in autophagic cell death was antagonized either by the CatL inhibitor or by CatL knockdown. In conclusion, our data show that PPARγ can specifically induce CatL, a proatherogenic protease, in HMDM. In turn, CatL inhibits autophagy and induces apoptosis. Thus, the proatherogenic effect of CatL could be neutralized by apoptosis, a beneficial phenomenon, at least in the early stages of atherosclerosis. PMID:21700710

  18. Bordetella pertussis Proteins Dominating the Major Histocompatibility Complex Class II-Presented Epitope Repertoire in Human Monocyte-Derived Dendritic Cells

    PubMed Central

    Stenger, Rachel M.; Meiring, Hugo D.; Kuipers, Betsy; Poelen, Martien; van Gaans-van den Brink, Jacqueline A. M.; Boog, Claire J. P.; de Jong, Ad P. J. M.

    2014-01-01

    Knowledge of naturally processed Bordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4+ T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4+ T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the natural B. pertussis epitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition of B. pertussis. A more complete understanding of hallmarks in B. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies. PMID:24599530

  19. Bordetella pertussis proteins dominating the major histocompatibility complex class II-presented epitope repertoire in human monocyte-derived dendritic cells.

    PubMed

    Stenger, Rachel M; Meiring, Hugo D; Kuipers, Betsy; Poelen, Martien; van Gaans-van den Brink, Jacqueline A M; Boog, Claire J P; de Jong, Ad P J M; van Els, Cécile A C M

    2014-05-01

    Knowledge of naturally processed Bordetella pertussis-specific T cell epitopes may help to increase our understanding of the basis of cell-mediated immune mechanisms to control this reemerging pathogen. Here, we elucidate for the first time the dominant major histocompatibility complex (MHC) class II-presented B. pertussis CD4(+) T cell epitopes, expressed on human monocyte-derived dendritic cells (MDDC) after the processing of whole bacterial cells by use of a platform of immunoproteomics technology. Pertussis epitopes identified in the context of HLA-DR molecules were derived from two envelope proteins, i.e., putative periplasmic protein (PPP) and putative peptidoglycan-associated lipoprotein (PAL), and from two cytosolic proteins, i.e., 10-kDa chaperonin groES protein (groES) and adenylosuccinate synthetase (ASS). No epitopes were detectable from known virulence factors. CD4(+) T cell responsiveness in healthy adults against peptide pools representing epitope regions or full proteins confirmed the immunogenicity of PAL, PPP, groES, and ASS. Elevated lymphoproliferative activity to PPP, groES, and ASS in subjects within a year after the diagnosis of symptomatic pertussis suggested immunogenic exposure to these proteins during clinical infection. The PAL-, PPP-, groES-, and ASS-specific responses were associated with secretion of functional Th1 (tumor necrosis factor alpha [TNF-α] and gamma interferon [IFN-γ]) and Th2 (interleukin 5 [IL-5] and IL-13) cytokines. Relative paucity in the natural B. pertussis epitope display of MDDC, not dominated by epitopes from known protective antigens, can interfere with the effectiveness of immune recognition of B. pertussis. A more complete understanding of hallmarks in B. pertussis-specific immunity may advance the design of novel immunological assays and prevention strategies. PMID:24599530

  20. Enterovirus-71 Virus-Like Particles Induce the Activation and Maturation of Human Monocyte-Derived Dendritic Cells through TLR4 Signaling

    PubMed Central

    Lin, Yu-Li; Hu, Yu-Chen; Liang, Cheng-Chao; Lin, Shih-Yeh; Liang, Yu-Chih; Yuan, Hui-Ping; Chiang, Bor-Luen

    2014-01-01

    Enterovirus 71 (EV71) causes seasonal epidemics of hand-foot-and-mouth disease and has a high mortality rate among young children. We recently demonstrated potent induction of the humoral and cell-mediated immune response in monkeys immunized with EV71 virus-like particles (VLPs), with a morphology resembling that of infectious EV71 virions but not containing a viral genome, which could potentially be safe as a vaccine for EV71. To elucidate the mechanisms through which EV71 VLPs induce cell-mediated immunity, we studied the immunomodulatory effects of EV71 VLPs on human monocyte-derived dendritic cells (DCs), which bind to and incorporate EV71 VLPs. DC treatment with EV71 VLPs enhanced the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR on the cell surface; increased the production of interleukin (IL)-12 p40, IL-12 p70, and IL-10 by DCs; and suppressed the capacity of DCs for endocytosis. Treatment with EV71 VLPs also enhanced the ability of DCs to stimulate naïve T cells and induced secretion of interferon (IFN)-γ by T cells and Th1 cell responses. Neutralization with antibodies against Toll-like receptor (TLR) 4 suppressed the capacity of EV71 VLPs to induce the production of IL-12 p40, IL-12 p70, and IL-10 by DCs and inhibited EV71 VLPs binding to DCs. Our study findings clarified the important role for TLR4 signaling in DCs in response to EV71 VLPs and showed that EV71 VLPs induced inhibitor of kappaB alpha (IκBα) degradation and nuclear factor of kappaB (NF-κB) activation. PMID:25360749

  1. Validation of efficient high-throughput plasmid and siRNA transfection of human monocyte-derived dendritic cells without cell maturation.

    PubMed

    Bowles, Robert; Patil, Sonali; Pincas, Hanna; Sealfon, Stuart C

    2010-12-15

    Transfection of primary immune cells is difficult to achieve at high efficiency and without cell activation and maturation. Dendritic cells (DCs) represent a key link between the innate and adaptive immune systems. Delineating the signaling pathways involved in the activation of human primary DCs and reverse engineering cellular inflammatory pathways have been challenging tasks. We optimized and validated an effective high-throughput transfection protocol, allowing us to transiently express DNA in naïve primary DCs, as well as investigate the effect of gene silencing by RNA interference. Using a high-throughput nucleofection system, monocyte-derived DCs were nucleoporated with a plasmid expressing green fluorescent protein (GFP), and transfection efficiency was determined by flow cytometry, based on GFP expression. To evaluate the effect of nucleoporation on DC maturation, the expression of cell surface markers CD86 and MHCII in GFP-positive cells was analyzed by flow cytometry. We established optimal assay conditions with a cell viability reaching 70%, a transfection efficiency of over 50%, and unchanged CD86 and MHCII expression. We examined the impact of small interfering RNA (siRNA)-mediated knockdown of RIG-I, a key viral recognition receptor, on the induction of the interferon (IFN) response in DCs infected with Newcastle disease virus. RIG-I protein was undetectable by Western blot in siRNA-treated cells. RIG-I knockdown caused a 75% reduction in the induction of IFNβ mRNA compared with the negative control siRNA. This protocol should be a valuable tool for probing the immune response pathways activated in human DCs. PMID:20875421

  2. Evaluation of the sensitizing potential of antibiotics in vitro using the human cell lines THP-1 and MUTZ-LC and primary monocyte-derived dendritic cells.

    PubMed

    Sebastian, Katrin; Ott, Hagen; Zwadlo-Klarwasser, Gabriele; Skazik-Voogt, Claudia; Marquardt, Yvonne; Czaja, Katharina; Merk, Hans F; Baron, Jens Malte

    2012-08-01

    Since the 7th amendment to the EU cosmetics directive foresees a complete ban on animal testing, alternative in vitro methods have been established to evaluate the sensitizing potential of small molecular weight compounds. To find out whether these novel in vitro assays are also capable to predict the sensitizing potential of small molecular weight drugs, model compounds such as beta-lactams and sulfonamides - which are the most frequent cause of adverse drug reactions - were co-incubated with THP-1, MUTZ-LC, or primary monocyte-derived dendritic cells for 48 h and subsequent expression of selected marker genes (IL-8, IL-1β, CES1, NQO1, GCLM, PIR and TRIM16) was studied by real time PCR. Benzylpenicillin and phenoxymethylpenicillin were recognized as sensitizing compounds because they are capable to induce the mRNA expression of these genes in moDCs and, except for IL-8, in THP-1 cells but not in MUTZ-LC. Ampicillin stimulated the expression of some marker genes in moDCs and THP-1 cells. SMX did not affect the expression of these genes in THP-1, however, in moDCs, at least PIR was enhanced and there was an increase of the release of IL-8. These data reveal that novel in vitro DC based assays might play a role in the evaluation of the allergenic potential of novel drug compounds, but these systems seem to lack the ability to detect the sensitizing potential of prohaptens that require metabolic activation prior to sensitization and moDCs seem to be superior with regard to the sensitivity compared with THP-1 and MUTZ-3 cell lines. PMID:22609641

  3. IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma

    SciTech Connect

    Bianchetti, Lorenza; Marini, Maurizio A.; Isgro, Mirko; Bellini, Alberto; Schmidt, Matthias; Mattoli, Sabrina

    2012-09-14

    Highlights: Black-Right-Pointing-Pointer IL-33 is considered a new therapeutic target for reducing inflammation in asthma. Black-Right-Pointing-Pointer This study shows that IL-33 is a potent chemoattractant for fibrocytes in asthma. Black-Right-Pointing-Pointer IL-33 also promotes fibrocyte proliferation without reducing collagen production. Black-Right-Pointing-Pointer The study uncovers a novel non-inflammatory, profibrotic function of IL-33. -- Abstract: The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.

  4. Investigating the Role of Surface Materials and Three Dimensional Architecture on In Vitro Differentiation of Porcine Monocyte-Derived Dendritic Cells

    PubMed Central

    Hartmann, Sofie Bruun; Mohanty, Soumyaranjan; Skovgaard, Kerstin; Brogaard, Louise; Flagstad, Frederikke Bjergvang; Emnéus, Jenny; Wolff, Anders; Summerfield, Artur; Jungersen, Gregers

    2016-01-01

    In vitro generation of dendritic-like cells through differentiation of peripheral blood monocytes is typically done using two-dimensional polystyrene culture plates. In the process of optimising cell culture techniques, engineers have developed fluidic micro-devises usually manufactured in materials other than polystyrene and applying three-dimensional structures more similar to the in vivo environment. Polydimethylsiloxane (PDMS) is an often used polymer for lab-on-a-chip devices but not much is known about the effect of changing the culture surface material from polystyrene to PDMS. In the present study the differentiation of porcine monocytes to monocyte-derived dendritic cells (moDCs) was investigated using CD172apos pig blood monocytes stimulated with GM-CSF and IL-4. Monocytes were cultured on surfaces made of two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS and carbonised three-dimensional PDMS. Cells cultured conventionally (on two-dimensional polystyrene) differentiated into moDCs as expected. Interestingly, gene expression of a wide range of cytokines, chemokines, and pattern recognition receptors was influenced by culture surface material and architecture. Distinct clustering of cells, based on similar expression patterns of 46 genes of interest, was seen for cells isolated from two- and three-dimensional polystyrene as well as two- and three-dimensional PDMS. Changing the material from polystyrene to PDMS resulted in cells with expression patterns usually associated with macrophage expression (upregulation of CD163 and downregulation of CD1a, FLT3, LAMP3 and BATF3). However, this was purely based on gene expression level, and no functional assays were included in this study which would be necessary in order to classify the cells as being macrophages. When changing to three-dimensional culture the cells became increasingly activated in terms of IL6, IL8, IL10 and CCR5 gene expression. Further stimulation with LPS resulted

  5. Proteomic analyses of monocyte-derived macrophages infected with human immunodeficiency virus type 1 primary isolates from Hispanic women with and without cognitive impairment

    PubMed Central

    Toro-Nieves, DM; Rodriguez, Y; Plaud, M; Ciborowski, P; Duan, F; Laspiur, J Pérez; Wojna, V; Meléndez, LM

    2009-01-01

    The signature for human immunodeficiency virus type 1 (HIV-1) neurovirulence remains a subject of intense debate. Macrophage viral tropism is one prerequisite but others, including virus-induced alterations in innate and adaptive immunity, remain under investigation. HIV-1–infected mononuclear phagocytes (MPs; perivascular macrophages and microglia) secrete toxins that affect neurons. The authors hypothesize that neurovirulent HIV-1 variants affect the MP proteome by inducing a signature of neurotoxic proteins and thus affect cognitive function. To test this hypothesis, HIV-1 isolates obtained from peripheral blood of women with normal cognition (NC) were compared to isolates obtained from women with cognitive impairment (CI) and to the laboratory adapted SF162, a spinal fluid R5 isolate from a patient with HIV-1–associated dementia. HIV-1 isolates were used to infect monocyte-derived macrophages (MDMs) and infection monitored by secreted HIV-1 p24 by enzyme-linked immunosorbent assay (ELISA). Cell lysates of uninfected and HIV-1–infected MDMs at 14 days post infection were fractionated by cationic exchange chromatography and analyzed by surface enhanced laser desorption ionization time of flight (SELDI-TOF) using generalized estimating equations statistics. Proteins were separated by one-dimensional sodium dodecyl sulfate–polyacrylamide gel electrophoresis (1D SDS-PAGE) and identified by tandem mass spectrometry. Levels of viral replication were similar amongst the HIV-1 isolates, although higher levels were obtained from one viral strain obtained from a patient with CI. Significant differences were found in protein profiles between virus-infected MDMs with NC, CI, and SF162 isolates (adjusted P value after multiple testing corrections, or q value < .10). The authors identified 6 unique proteins in NC, 7 in SF162, and 20 in CI. Three proteins were common to SF162 and CI strains. The MDM proteins linked to infection with CI strains were related to apoptosis

  6. The effect of bovine viral diarrhea virus (BVDV) strains on bovine monocyte-derived dendritic cells (Mo-DC) phenotype and capacity to produce BVDV

    PubMed Central

    2014-01-01

    Background Dendritic cells (DC) are important antigen presentation cells that monitor, process, and present antigen to T cells. Viruses that infect DC can have a devastating impact on the immune system. In this study, the ability of bovine viral diarrhea virus (BVDV) to replicate and produce infectious virus in monocyte-derived dendritic cells (Mo-DC) and monocytes was studied. The study also examined the effect of BVDV infection on Mo-DC expression of cell surface markers, including MHCI, MHCII, and CD86, which are critical for DC function in immune response. Methods Peripheral blood mononuclear cells (PBMCs) were isolated from bovine blood through gradient centrifugation. The adherent monocytes were isolated from PBMCs and differentiated into Mo-DC using bovine recombinant interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GMCSF). To determine the effect of BVDV on Mo-DC, four strains of BVDV were used including the severe acute non-cytopathic (ncp) BVDV2a-1373; moderate acute ncp BVDV2a 28508-5; and a homologous virus pair [i.e., cytopathic (cp) BVDV1b TGAC and ncp BVDV1b TGAN]. The Cooper strain of bovine herpesvirus 1 (BHV1) was used as the control virus. Mo-DC were infected with one of the BVDV strains or BHV-1 and were subsequently examined for virus replication, virus production, and the effect on MHCI, MHCII, and CD86 expression. Results The ability of monocytes to produce infectious virus reduced as monocytes differentiated to Mo-DC, and was completely lost at 120 hours of maturation. Interestingly, viral RNA increased throughout the course of infection in Mo-DC, and the viral non-structural (NS5A) and envelope (E2) proteins were expressed. The ncp strains of BVDV down-regulated while cp strain up-regulated the expression of the MHCI, MHCII, and CD86 on Mo-DC. Conclusions The study revealed that the ability of Mo-DC to produce infectious virus was reduced with its differentiation from monocytes to Mo-DC. The inability to produce

  7. Binding of the 68-kilodalton protein of Mycobacterium avium to alpha(v)beta3 on human monocyte-derived macrophages enhances complement receptor type 3 expression.

    PubMed Central

    Hayashi, T; Rao, S P; Catanzaro, A

    1997-01-01

    Attachment to and uptake by host cells are important early events in the pathogenesis of intracellular organisms such as Mycobacterium avium. Monocyte-derived macrophages (MDM) are known to express multiple surface receptors that play a role in binding to and uptake of M. avium. These include complement receptor type 3 (CR3), fibronectin receptor, mannose receptor, and transferrin receptor. In addition to these, we have previously reported that the integrin receptor alpha(v)beta3 also plays a role in binding to M. avium in a nonopsonic environment. Further, we have shown that a 68-kDa surface protein of M. avium binds to human monocytes and plays a role in attachment of M. avium to MDM. The present study provides direct evidence that this protein mediates attachment of M. avium to MDM by binding to alpha(v)beta3. Using the technique of cell surface enzyme-linked immunosorbent assay, we have shown that the M. avium 68-kDa protein inhibits the binding of monoclonal antibodies (MAb) against alpha(v)beta3 to MDM compared to control proteins such as ovalbumin and laminin (P < 0.05). Dual-labeling studies were performed to demonstrate that after phagocytosis, alpha(v)beta3 is present along with M. avium in phagosomes of M. avium-infected MDM. In addition, we have demonstrated that this interaction between alpha(v)beta3 and the M. avium 68-kDa protein resulted in enhancement of CR3 expression, which is known to play a role in complement-mediated uptake of M. avium. Attachment of MDM to wells coated with the M. avium 68-kDa protein resulted in a twofold increase in CR3 expression compared to attachment of MDM to wells coated with ovalbumin. This enhancement was completely inhibited by pretreatment of MDM with MAb against alpha(v)beta3. In summary, M. avium binds to MDM via alpha(v)beta3 with the help of the M. avium 68-kDa protein, and this ligation enhanced the expression of CR3 on MDM. Since CR3 has been known to play a role in M. avium uptake, enhanced expression of

  8. Cancer associated fibroblasts have phenotypic and functional characteristics similar to the fibrocytes that represent a novel MDSC subset

    PubMed Central

    Gunaydin, Gurcan; Kesikli, S Altug; Guc, Dicle

    2015-01-01

    Circulating fibrocytes were reported to represent a novel myeloid-derived suppressor cell (MDSC) subset and they were also proposed to be involved in the tumor immune escape. This novel fibrocyte subset had a surface phenotype resembling non-monocytic MDSCs (CD14−CD11chiCD123−) and exhibited immunomodulatory roles. Most effector functions of fibrocytes (circulating fibroblast-progenitors) are accomplished as tissue fibroblasts, likewise in the tumor microenvironment. Therefore, fibroblasts at tumor tissues should be evaluated whether they display similar molecular/gene expression patterns and functional roles to the blood-borne fibrocytes. A chemically induced rat breast carcinogenesis model was utilized to obtain cancer associated fibroblasts (CAFs). CAFs and normal tissue fibroblasts (NFs) were isolated from cancerous and healthy breast tissues, respectively, using a previously described enzymatic protocol. Both CAFs and NFs were analyzed for cell surface phenotypes by flow cytometry and for gene expression profiles by gene set enrichment analysis (GSEA). PBMCs were cocultured with either NFs or CAFs and proliferations of PBMCs were assessed by CFSE assays. Morphological analyses were performed by immunocytochemistry stainings with vimentin. CAFs were spindle shaped cells unlike their blood-borne counterparts. They did not express CD80 and their MHC-II expression was lower than NFs. Although CAFs expressed the myeloid marker CD11b/c, its expression was lower than that on the circulating fibrocytes. CAFs did not express granulocytic/neutrophilic markers and they seemed to have developed in an environment containing THELPER2-like cytokines. They also showed immunosuppressive effects similar to their blood-borne counterparts. In summary, CAFs showed similar phenotypic and functional characteristics to the circulating fibrocytes that were reported to represent a unique MDSC subset. PMID:26405600

  9. Human fibrocyte-derived exosomes accelerate wound healing in genetically diabetic mice.

    PubMed

    Geiger, Adolf; Walker, Audrey; Nissen, Erwin

    2015-11-13

    Diabetic ulcers represent a substantial societal and healthcare burden worldwide and scarcely respond to current treatment strategies. This study was addressed to evaluate the therapeutic potential of exosomes secreted by human circulating fibrocytes, a population of mesenchymal progenitors involved in normal wound healing via paracrine signaling. The exosomes released from cells sequentially stimulated with platelet-derived growth factor-BB and transforming growth factor-β1, in the presence of fibroblast growth factor 2, did not show potential immunogenicity. These exosomes exhibited in-vitro proangiogenic properties, activated diabetic dermal fibroblasts, induced the migration and proliferation of diabetic keratinocytes, and accelerated wound closure in diabetic mice in vivo. Important components of the exosomal cargo were heat shock protein-90α, total and activated signal transducer and activator of transcription 3, proangiogenic (miR-126, miR-130a, miR-132) and anti-inflammatory (miR124a, miR-125b) microRNAs, and a microRNA regulating collagen deposition (miR-21). This proof-of-concept study demonstrates the feasibility of the use of fibrocytes-derived exosomes for the treatment of diabetic ulcers. PMID:26454169

  10. Bromelain treatment leads to maturation of monocyte-derived dendritic cells but cannot replace PGE2 in a cocktail of IL-1β, IL-6, TNF-α and PGE2.

    PubMed

    Karlsen, M; Hovden, A-O; Vogelsang, P; Tysnes, B B; Appel, S

    2011-08-01

    Immunotherapy using dendritic cells (DC) has shown promising results. However, the use of an appropriate DC population is critical for the outcome of this treatment, and the search for an optimal DC subset is still ongoing. The DC used in immunotherapy today are usually matured with a cytokine cocktail consisting of TNF-α, IL-1β, IL-6 and PGE(2). These cells have deficits in their cytokine production, particularly IL-12p70, mainly because of the presence of PGE(2). Bromelain is a pineapple stem extract containing a mixture of proteases that has been used clinically in adjuvant cancer treatment. In this study, we analysed the effect of bromelain on human monocyte-derived DC. We added bromelain to the cytokine cocktail and modified cytokine cocktails with either no PGE(2) or reduced amounts of PGE(2), respectively. Combining bromelain with the cytokine cocktails containing PGE(2) resulted in an increased surface expression of CD83, CD80 and CD86. The chemokine receptor CCR7 was also considerably upregulated in these DC populations compared with DC treated with the cytokine cocktail alone. Removal or reduction of PGE(2) from the cytokine cocktail did not increase the IL-12p70 secretion from stimulated DC, and addition of bromelain to the different cytokine cocktails resulted in only a minor increase in IL-12p70 production. Moreover, combining bromelain with the cytokine cocktails did not improve the T cell stimulatory capacity of the generated DC populations. In conclusion, bromelain treatment of monocyte-derived DC does not improve the functional quality compared with the standard cytokine cocktail. PMID:21449940

  11. Another Piece in the Fibrotic Puzzle: TSLP as a Novel Ligand for Fibrocyte Activation.

    PubMed

    Christmann, Romy Beatriz

    2016-02-01

    Thymic stromal lymphopoietin (TSLP) has emerged as an important cytokine in the pathogenesis of nonallergic diseases, especially in diseases that include fibrosis. It has been shown to be upregulated in both cutaneous and lung fibrotic conditions. Shin et al. report that TSLP may also play a role in the pathogenesis of keloids. The main mechanism of TSLP profibrotic effects is not as yet fully understood, although the data suggest that it involves collagen production through transforming growth factor-β, at least in the case of dermal fibroblasts. The authors also report that TSLP is able to activate fibrocytes, probably by inducing stromal cell-derived factor-1 (also termed CXCL12), one of its main ligands. These findings support the concept that TSLP plays a role in the development of fibrosis, and they should lead to mechanistic studies on TSLP profibrotic signaling. PMID:26802232

  12. Tanshinone IIA Attenuates Renal Fibrosis after Acute Kidney Injury in a Mouse Model through Inhibition of Fibrocytes Recruitment

    PubMed Central

    Jiang, Chunming; Shao, Qiuyuan; Jin, Bo; Zhang, Miao

    2015-01-01

    Acute kidney injury (AKI) is associated with an increased risk of developing advanced chronic kidney disease (CKD). Yet, effective interventions to prevent this conversion are unavailable for clinical practice. In this study, we examined the beneficial effects of Tanshinone IIA on renal fibrosis in a mouse model of folic acid induced AKI. We found that Tanshinone IIA treatment significantly attenuated the folic acid elicited kidney dysfunction on days 3, 14, and 28. This effect was concomitant with a much lessened accumulation of fibronectin and collagen in tubulointerstitium 28 days after folic acid injury, denoting an ameliorated renal fibrosis. The kidney protective and antifibrotic effect of Tanshinone IIA was likely attributable to an early inhibition of renal recruitment of fibrocytes positive for both CD45 and collagen I. Mechanistically, Tanshinone IIA treatment not only markedly diminished renal expression of chemoattractants for fibrocytes such as TGFβ1 and MCP-1, but also significantly reduced circulating fibrocytes at the acute phase of kidney injury. These data suggested that Tanshinone IIA might be a novel therapy for preventing progression of CKD after AKI. PMID:26885500

  13. The unique ion permeability profile of cochlear fibrocytes and its contribution to establishing their positive resting membrane potential.

    PubMed

    Yoshida, Takamasa; Nin, Fumiaki; Murakami, Shingo; Ogata, Genki; Uetsuka, Satoru; Choi, Samuel; Nakagawa, Takashi; Inohara, Hidenori; Komune, Shizuo; Kurachi, Yoshihisa; Hibino, Hiroshi

    2016-09-01

    Eukaryotic cells exhibit negative resting membrane potential (RMP) owing to the high K(+) permeability of the plasma membrane and the asymmetric [K(+)] between the extracellular and intracellular compartments. However, cochlear fibrocytes, which comprise the basolateral surface of a multilayer epithelial-like tissue, exhibit a RMP of +5 to +12 mV in vivo. This positive RMP is critical for the formation of an endocochlear potential (EP) of +80 mV in a K(+)-rich extracellular fluid, endolymph. The epithelial-like tissue bathes fibrocytes in a regular extracellular fluid, perilymph, and apically faces the endolymph. The EP, which is essential for hearing, represents the potential difference across the tissue. Using in vivo electrophysiological approaches, we describe a potential mechanism underlying the unusual RMP of guinea pig fibrocytes. The RMP was +9.0 ± 3.7 mV when fibrocytes were exposed to an artificial control perilymph (n = 28 cochleae). Perilymphatic perfusion of a solution containing low [Na(+)] (1 mM) markedly hyperpolarized the RMP to -31.1 ± 11.2 mV (n = 10; p < 0.0001 versus the control, Tukey-Kramer test after one-way ANOVA). Accordingly, the EP decreased. Little change in RMP was observed when the cells were treated with a high [K(+)] of 30 mM (+10.4 ± 2.3 mV; n = 7; p = 0.942 versus the control). During the infusion of a low [Cl(-)] solution (2.4 mM), the RMP moderately hyperpolarized to -0.9 ± 3.4 mV (n = 5; p < 0.01 versus the control), although the membranes, if governed by Cl(-) permeability, should be depolarized. These observations imply that the fibrocyte membranes are more permeable to Na(+) than K(+) and Cl(-), and this unique profile and [Na(+)] gradient across the membranes contribute to the positive RMP. PMID:27344659

  14. Cooperation between human fibrocytes and endothelial colony forming cells increases angiogenesis via CXCR4 pathway

    PubMed Central

    Smadja, David M.; Dorfmüller, Peter; Bieche, Ivan; Guerin, Coralie; Badoual, Cécile; Boscolo, Elisa; Kambouchner, Marianne; Cazes, Aurélie; Mercier, Olaf; Humbert, Marc; Gaussem, Pascale; Bischoff, Joyce; Israël-Biet, Dominique

    2016-01-01

    Background Fibrotic diseases of the lung are associated with a vascular remodeling process. Fibrocytes (Fy) are a distinct population of blood-borne cells that coexpress hematopoietic cell antigens and fibroblast markers, which have been shown to contribute to organ fibrosis. The purpose of this study was to test the hypothesis that Fy might cooperate with endothelial colony forming cells to induce angiogenesis. Methods/Results We successfully isolated Fy from blood of idiopathic pulmonary fibrosis (IPF) patients, which were further characterized by flow cytometry, Reverse Transcriptase quantitative-PCR (RTQ-PCR), and confocal analysis. We investigated the interaction between Fy and cord blood derived endothelial colony forming cells (ECFC) angiogenic potential in vitro and in vivo in a Matrigel implant model. Compared to fibroblast culture media, secreted media from Fy increase ECFC proliferation and their differentiation ability via SDF-1/CXCR4 pathway. IPF-Fy co-implanted with human ECFC in a matrigel plug in immunodeficient mice formed functional microvascular beds, whereas fibroblasts did not. Evaluation of implants after 2 weeks revealed an extensive network of blood vessels containing erythrocytes. CXCR4 blockade significantly inhibited blood vessel formation in the implants. The clinical relevance of these data was confirmed by the high expression level of CXCR4 in vessels close to fibrotic areas in biopsy specimens from patients with IPF, in contrast to control lungs. Conclusions Circulating Fy might be contribute to the intense remodeling of the pulmonary vasculature in patients with IPF. PMID:25103869

  15. Physiological function and inflamed-brain migration of mouse monocyte-derived macrophages following cellular uptake of superparamagnetic iron oxide nanoparticles-Implication of macrophage-based drug delivery into the central nervous system.

    PubMed

    Tong, Hsin-I; Kang, Wen; Shi, Yingli; Zhou, Guangzhou; Lu, Yuanan

    2016-05-30

    This study was designed to use superparamagnetic iron oxide nanoparticles (SPIONs) as evaluating tools to study monocyte-derived macrophages (MDM)-mediated delivery of small molecular agents into the diseased brains. MDM were tested with different-configured SPIONs at selected concentrations for their impacts on carrier cells' physiological and migratory properties, which were found to depend largely on particle size, coating, and treatment concentrations. SHP30, a SPION of 30-nm core size with oleic acids plus amphiphilic polymer coating, was identified to have high cellular uptake efficiency and cause little cytotoxic effects on MDM. At lower incubation dose (25μg/mL), few alteration was observed in carrier cells' physiological and in vivo migratory functions, as tested in a lipopolysaccharide-induced acute neuroinflammation mouse model. Nevertheless, significant increase in monocyte-to-macrophage differentiation, and decrease in in vivo carrier MDM inflamed-brain homing ability were found in groups treated with a higher dose of SHP30at 100μg/mL. Overall, our results have identified MDM treatment at 25μg/mL SHP30 resulted in little functional changes, provided valuable parameters for using SPIONs as evaluating tools to study MDM-mediated therapeutics carriage and delivery, and supported the concepts of using monocytes-macrophages as cellular vehicles to transport small molecular agents to the brain. PMID:27001531

  16. Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy.

    PubMed

    Braga, André Flores; Moretto, Daniela Ferraz; Gigliotti, Patrícia; Peruchi, Mariela; Vilani-Moreno, Fátima Regina; Campanelli, Ana Paula; Latini, Ana Carla Pereira; Iyer, Anand; Das, Pranab Kumar; Souza, Vânia Nieto Brito de

    2015-08-01

    Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy. PMID:26222022

  17. Differential regulatory activities of viral protein X for anti-viral efficacy of nucleos(t)ide reverse transcriptase inhibitors in monocyte-derived macrophages and activated CD4(+) T cells.

    PubMed

    Hollenbaugh, Joseph A; Schader, Susan M; Schinazi, Raymond F; Kim, Baek

    2015-11-01

    Vpx encoded by HIV-2 and SIVsm enhances retroviral reverse transcription in macrophages in vitro by mediating the degradation of the host SAMHD1 protein that hydrolyzes dNTPs and by elevating cellular dNTP levels. Here we employed RT-SHIV constructs (SIV encoding HIV-1 RT) to investigate the contribution of Vpx to the potency of NRTIs, which compete against dNTPs, in monocyte-derived macrophages (MDMs) and activated CD4(+) T cells. Relative to HIV-1, both SIV and RT-SHIV exhibited reduced sensitivities to AZT, 3TC and TDF in MDMs but not in activated CD4(+) T cells. However, when SIV and RT-SHIV constructs not coding for Vpx were utilized, we observed greater sensitivities to all NRTIs tested using activated CD4(+) T cells relative to the Vpx-coding counterparts. This latter phenomenon was observed for AZT only when using MDMs. Our data suggest that Vpx in RT-SHIVs may underestimate the antiviral efficacy of NRTIs in a cell type dependent manner. PMID:26319213

  18. Activation and cytokine profile of monocyte derived dendritic cells in leprosy: in vitro stimulation by sonicated Mycobacterium leprae induces decreased level of IL-12p70 in lepromatous leprosy

    PubMed Central

    Braga, André Flores; Moretto, Daniela Ferraz; Gigliotti, Patrícia; Peruchi, Mariela; Vilani-Moreno, Fátima Regina; Campanelli, Ana Paula; Latini, Ana Carla Pereira; Iyer, Anand; Das, Pranab Kumar; de Souza, Vânia Nieto Brito

    2015-01-01

    Dendritic cells (DCs) play a pivotal role in the connection of innate and adaptive immunity of hosts to mycobacterial infection. Studies on the interaction of monocyte-derived DCs (MO-DCs) using Mycobacterium leprae in leprosy patients are rare. The present study demonstrated that the differentiation of MOs to DCs was similar in all forms of leprosy compared to normal healthy individuals. In vitro stimulation of immature MO-DCs with sonicated M. leprae induced variable degrees of DC maturation as determined by the increased expression of HLA-DR, CD40, CD80 and CD86, but not CD83, in all studied groups. The production of different cytokines by the MO-DCs appeared similar in all of the studied groups under similar conditions. However, the production of interleukin (IL)-12p70 by MO-DCs from lepromatous (LL) leprosy patients after in vitro stimulation with M. leprae was lower than tuberculoid leprosy patients and healthy individuals, even after CD40 ligation with CD40 ligand-transfected cells. The present cumulative findings suggest that the MO-DCs of LL patients are generally a weak producer of IL-12p70 despite the moderate activating properties ofM. leprae. These results may explain the poor M. leprae-specific cell-mediated immunity in the LL type of leprosy. PMID:26222022

  19. Plasma visfatin levels and mRNA expression of visfatin in peripheral blood mononuclear cells and peripheral blood monocyte-derived macrophages from normal weight females with polycystic ovary syndrome

    PubMed Central

    ZHANG, JING; ZHOU, LINGLING; TANG, LIULIN; XU, LIANGZHI

    2014-01-01

    Polycystic ovary syndrome (PCOS) is a common reproductive endocrinology disease, however, an explicit etiology is not known. Insulin resistance (IR) appears to be central to the pathogenesis of PCOS and inflammation may be significant in the pathogenesis of IR in PCOS. The aims of the present study were to investigate the plasma visfatin level and the gene expression of visfatin in peripheral blood mononuclear cells (PBMCs) and peripheral blood monocyte-derived macrophages (PBMMs) from PCOS patients, in addition to investigating the association between PCOS and IR. A total of 21 PCOS patients and 21 control subjects were enrolled in the study; the homeostasis model assessment of insulin resistance (HOMA-IR) was considered to be a stratified method for establishing the subgroups. Fasting blood samples were collected and the levels of sex hormones, insulin, glucose, blood lipids and visfatin were measured. In addition, visfatin gene expression levels in PBMCs and PBMMs were assessed using quantitative polymerase chain reaction. The plasma visfatin and gene expression levels of visfatin in PBMCs and PBMMs were not observed to increase in the normal weight PCOS and normal weight IR patients. Furthermore, plasma visfatin levels did not correlate with the normal weight PCOS patients or the normal weight IR patients per se. Further investigation into the role of visfatin in the pathogenesis of PCOS or IR should examine macrophages in the tissues, rather than macrophages in the peripheral blood. PMID:24940414

  20. Myofibroblasts in proliferative diabetic retinopathy can originate from infiltrating fibrocytes and through endothelial-to-mesenchymal transition (EndoMT).

    PubMed

    Abu El-Asrar, Ahmed M; De Hertogh, Gert; van den Eynde, Kathleen; Alam, Kaiser; Van Raemdonck, Katrien; Opdenakker, Ghislain; Van Damme, Jo; Geboes, Karel; Struyf, Sofie

    2015-03-01

    Myofibroblasts expressing α-smooth muscle actin (α-SMA) are the key cellular mediator of fibrosis. Fibrovascular epiretinal membranes from patients with proliferative diabetic retinopathy (PDR) are characterized by the accumulation of a large number of myofibroblasts. We explored the hypothesis that proliferating endothelial cells via endothelial-to-mesenchymal transition (EndoMT) and/or bone marrow-derived circulating fibrocytes contribute to the myofibroblast population present in PDR epiretinal membranes. Epiretinal membranes from 14 patients with PDR were studied by immunohistochemistry. All membranes contained neovessels expressing the endothelial cell marker CD31. CD31(+) endothelial cells co-expressed the fibroblast/myofibroblast markers fibroblast-specific protein-1 (FSP-1) and α-SMA, indicative for the occurrence of endoMT. In the stroma, cells expressing FSP-1, α-SMA, the leukocyte common antigen CD45, and the myelomonocytic marker CD11b were detected. Double labeling showed co-localization of CD45 with FSP-1 and α-SMA and co-localization of CD11b with α-SMA and matrix metalloproteinase-9, demonstrating the presence of infiltrating fibrocytes. In addition, we investigated the phenotypic changes that take place in human retinal microvascular endothelial cells following exposure to transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF) and the proinflammatory cytokines interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Retinal microvascular endothelial cells changed morphology upon cytokine exposure, lost the expression of endothelial cell markers (endothelial nitric oxide synthase and vascular endothelial-cadherin) and started to express mesenchymal markers (calponin, snail, transgelin and FSP-1). These results suggest that endothelial cells as well as circulating fibrocytes may differentiate into myofibroblasts in the diabetic eye and contribute to pathologic fibrosis in PDR. PMID:25637870

  1. Distinguished Cooperating Teacher Program.

    ERIC Educational Resources Information Center

    Chicago State Univ., IL.

    The Distinguished Cooperating Teacher Program at Chicago State University was developed to train cooperating teachers to supervise student teachers. The program departs from traditional practice by changing the roles of the classroom teacher and the university field supervisor. The supervisor's role becomes that of coordinator while the teacher…

  2. Single point mutations in the helicase domain of the NS3 protein enhance dengue virus replicative capacity in human monocyte-derived dendritic cells and circumvent the type I interferon response.

    PubMed

    Silveira, G F; Strottmann, D M; de Borba, L; Mansur, D S; Zanchin, N I T; Bordignon, J; dos Santos, C N Duarte

    2016-01-01

    Dengue is the most prevalent arboviral disease worldwide. The outcome of the infection is determined by the interplay of viral and host factors. In the present study, we evaluated the cellular response of human monocyte-derived DCs (mdDCs) infected with recombinant dengue virus type 1 (DV1) strains carrying a single point mutation in the NS3hel protein (L435S or L480S). Both mutated viruses infect and replicate more efficiently and produce more viral progeny in infected mdDCs compared with the parental, non-mutated virus (vBACDV1). Additionally, global gene expression analysis using cDNA microarrays revealed that the mutated DVs induce the up-regulation of the interferon (IFN) signalling and pattern recognition receptor (PRR) canonical pathways in mdDCs. Pronounced production of type I IFN were detected specifically in mdDCs infected with DV1-NS3hel-mutated virus compared with mdDCs infected with the parental virus. In addition, we showed that the type I IFN produced by mdDCs is able to reduce DV1 infection rates, suggesting that cytokine function is effective but not sufficient to mediate viral clearance of DV1-NS3hel-mutated strains. Our results demonstrate that single point mutations in subdomain 2 have important implications for adenosine triphosphatase (ATPase) activity of DV1-NS3hel. Although a direct functional connection between the increased ATPase activity and viral replication still requires further studies, these mutations speed up viral RNA replication and are sufficient to enhance viral replicative capacity in human primary cell infection and circumvent type I IFN activity. This information may have particular relevance for attenuated vaccine protocols designed for DV. PMID:26340409

  3. Addition of CpG ODN and Poly (I:C) to a standard maturation cocktail generates monocyte-derived dendritic cells and induces a potent Th1 polarization with migratory capacity

    PubMed Central

    Zhu, Mei; Xu, Wei; Su, Hong; Huang, Qiong; Wang, Baolong

    2015-01-01

    Monocyte-derived dendritic cells (DCs) are used as immunoadjuvant cells in cancer vaccines and have made great progress. However, an optimal DCs subset is vital for this treatment effect, the current ′gold standard′ cytokine cocktail DCs have a shortcoming in their cytokines secretion, especially IL-12p70, mainly because of the existence of PGE2. Therefore, it is necessary to find an appropriate DCs-based immunotherapeutic protocol. In this study, we compared a novel ′improved′ maturation cytokine cocktail with the current ′gold standard′ maturation cytokine cocktail used for generating standard DCs. The ′improved′ maturation cytokine cocktail DCs showed a higher levels surface markers expression (CD80, CD83, CD86 and HLA-DR), the chemokine receptors CXCR4 and CCR7 and chemokine CCL19, CCL21 and CXCL21, whereas CCR5 expression was reduced. Most importantly, in contrast to ′gold standard′ DCs, which secrete little IL-12p70 and as a result induce mainly Th2 immunity, ′improved′ cytokine cocktail DCs secreted higher levels IL-12p70 and also secreted similar concentration IL-10. To removal of PGE2 from the ′improved′ DCs did increase the IL-12p70 production. In conclusion, we here present the ′improved′ DCs, as an optimal maturation cocktail protocol, can induce high migratory potential, generate immunostimulatory DCs, produce higher levels IL-12p70 with superior capacity to induce Th1 immunity, when compared with the ′gold standard′ DCs. PMID:26039883

  4. Psychedelic N,N-Dimethyltryptamine and 5-Methoxy-N,N-Dimethyltryptamine Modulate Innate and Adaptive Inflammatory Responses through the Sigma-1 Receptor of Human Monocyte-Derived Dendritic Cells

    PubMed Central

    Szabo, Attila; Kovacs, Attila

    2014-01-01

    The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor. PMID:25171370

  5. Psychedelic N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine modulate innate and adaptive inflammatory responses through the sigma-1 receptor of human monocyte-derived dendritic cells.

    PubMed

    Szabo, Attila; Kovacs, Attila; Frecska, Ede; Rajnavolgyi, Eva

    2014-01-01

    The orphan receptor sigma-1 (sigmar-1) is a transmembrane chaperone protein expressed in both the central nervous system and in immune cells. It has been shown to regulate neuronal differentiation and cell survival, and mediates anti-inflammatory responses and immunosuppression in murine in vivo models. Since the details of these findings have not been elucidated so far, we studied the effects of the endogenous sigmar-1 ligands N,N-dimethyltryptamine (NN-DMT), its derivative 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) and the synthetic high affinity sigmar-1 agonist PRE-084 hydrochloride on human primary monocyte-derived dendritic cell (moDCs) activation provoked by LPS, polyI:C or pathogen-derived stimuli to induce inflammatory responses. Co-treatment of moDC with these activators and sigma-1 receptor ligands inhibited the production of pro-inflammatory cytokines IL-1β, IL-6, TNFα and the chemokine IL-8, while increased the secretion of the anti-inflammatory cytokine IL-10. The T-cell activating capacity of moDCs was also inhibited, and dimethyltryptamines used in combination with E. coli or influenza virus as stimulators decreased the differentiation of moDC-induced Th1 and Th17 inflammatory effector T-cells in a sigmar-1 specific manner as confirmed by gene silencing. Here we demonstrate for the first time the immunomodulatory potential of NN-DMT and 5-MeO-DMT on human moDC functions via sigmar-1 that could be harnessed for the pharmacological treatment of autoimmune diseases and chronic inflammatory conditions of the CNS or peripheral tissues. Our findings also point out a new biological role for dimethyltryptamines, which may act as systemic endogenous regulators of inflammation and immune homeostasis through the sigma-1 receptor. PMID:25171370

  6. Phenotypic and functional activation of hyporesponsive KIRnegNKG2Aneg human NK-cell precursors requires IL12p70 provided by Poly(I:C)-matured monocyte-derived dendritic cells.

    PubMed

    Curran, Shane A; Romano, Emanuela; Kennedy, Michael G; Hsu, Katharine C; Young, James W

    2014-10-01

    A functionally responsive natural killer (NK)-cell repertoire requires the acquisition of inhibitory NKG2A and killer immunoglobulin-like receptors (KIR) through pathways that remain undefined. Functional donor NK cells expressing KIRs for non-self class I MHC ligands contribute to a positive outcome after allogeneic hematopoietic stem cell transplantation (alloHSCT) by targeting HLA-matched recipient leukemic cells. Insofar as circulating donor conventional dendritic cells (DC) reconstitute with comparable kinetics with donor NK cells after alloHSCT, we used hyporesponsive KIRnegNKG2Aneg precursor cells to evaluate how specific DC subtypes generate a functionally active NK-cell repertoire. Both monocyte-derived DCs (moDC) and Langerhans-type DCs (LC) induce KIRnegNKG2Aneg precursor cells to express the inhibitory receptors NKG2A and KIR, without requiring cell proliferation. Poly(I:C)-matured moDCs significantly augmented the expression of NKG2A, but not KIR, in an IL12p70-dependent manner. Although all DC-stimulated KIRnegNKG2Aneg cells were able to acquire cytolytic activity against class I MHC-negative targets, the ability to secrete IFNγ was restricted to cells that were stimulated by IL12p70-producing, poly(I:C)-matured moDCs. This critical ability of poly(I:C)-matured moDCs to provide IL12p70 to developing KIRnegNKG2Aneg precursors results in a dom4inant, multifunctional, NKG2Apos NK-cell population that is capable of both cytolysis and IFNγ production. Poly(I:C)-matured moDCs are, therefore, the most effective conventional DC subtype for generating a functionally competent NK-cell repertoire by an IL12p70-dependent mechanism. PMID:25023628

  7. Inhibition of TNF-α, IL-1α, and IL-1β by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro.

    PubMed

    Pan, Min-Hsiung; Maresz, Katarzyna; Lee, Pei-Sheng; Wu, Jia-Ching; Ho, Chi-Tang; Popko, Janusz; Mehta, Dilip S; Stohs, Sidney J; Badmaev, Vladimir

    2016-07-01

    Circulatory markers of low-grade inflammation such as tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1β) positively correlate with endothelial damage, atheroma formation, cardiovascular disease, and aging. The natural vitamin K2-menaquinone-7 (MK-7) added to the cell culture of human monocyte-derived macrophages (hMDMs) at the same time as toll-like receptor (TLR) agonists did not influence the production of TNF-α. When the cells were pretreated up to 6 h with MK-7 before treatment with TLR agonists, MK-7 did not inhibit significantly the production of TNF-α after the TLR activation. However, 30 h pretreatment of hMDMs with at least 10 μM of MK-7 effectively and dose dependently inhibited the proinflammatory function of hMDMs. Pretreatment of hMDMs with 10 μM of MK-7 for 30 h resulted in 20% inhibition of TNF-α production after lipopolysaccharide (LPS) activation (P < .05) and 43% inhibition after macrophage-activating lipopeptide (MALP) activation (P < .001). Pathogen-associated molecular pattern (PMPP) activation was inhibited by 20% with MK-7 pretreatment; however, this inhibition was not statistically significant. The 30 h pretreatment of a THP-1-differentiated monocyte cell line with MK-7 resulted in a dose-dependent downregulation of TNFα, IL-1α, and IL-1β gene expression as evaluated by RNA semiquantitative reverse transcription polymerase chain reaction (RT-PCR). MK-7 is able to modulate immune and inflammatory reactions in the dose-response inhibition of TNF-α, IL-1α, and IL-1β gene expression and protein production by the healthy hMDMs in vitro. PMID:27200471

  8. Analysis of proteomic profiles and functional properties of human peripheral blood myeloid dendritic cells, monocyte-derived dendritic cells and the dendritic cell-like KG-1 cells reveals distinct characteristics

    PubMed Central

    2007-01-01

    Background Dendritic cells (DCs) are specialized antigen presenting cells that play a pivotal role in bridging innate and adaptive immune responses. Given the scarcity of peripheral blood myeloid dendritic cells (mDCs) investigators have used different model systems for studying DC biology. Monocyte-derived dendritic cells (moDCs) and KG-1 cells are routinely used as mDC models, but a thorough comparison of these cells has not yet been carried out, particularly in relation to their proteomes. We therefore sought to run a comparative study of the proteomes and functional properties of these cells. Results Despite general similarities between mDCs and the model systems, moDCs and KG-1 cells, our findings identified some significant differences in the proteomes of these cells, and the findings were confirmed by ELISA detection of a selection of proteins. This was particularly noticeable with proteins involved in cell growth and maintenance (for example, fibrinogen γ chain (FGG) and ubiquinol cytochrome c) and cell-cell interaction and integrity (for example, fascin and actin). We then examined the surface phenotype, cytokine profile, endocytic and T-cell-activation ability of these cells in support of the proteomic data, and obtained confirmatory evidence for differences in the maturation status and functional attributes between mDCs and the two DC models. Conclusion We have identified important proteomic and functional differences between mDCs and two DC model systems. These differences could have major functional implications, particularly in relation to DC-T cell interactions, the so-called immunological synapse, and, therefore, need to be considered when interpreting data obtained from model DC systems. PMID:17331236

  9. The abcEDCBA-Encoded ABC Transporter and the virB Operon-Encoded Type IV Secretion System of Brucella ovis Are Critical for Intracellular Trafficking and Survival in Ovine Monocyte-Derived Macrophages

    PubMed Central

    Macedo, Auricelio A.; Silva, Ana P. C.; Mol, Juliana P. S.; Costa, Luciana F.; Garcia, Luize N. N.; Araújo, Marcio S.; Martins Filho, Olindo A.; Paixão, Tatiane A.; Santos, Renato L.

    2015-01-01

    Brucella ovis infection is associated with epididymitis, orchitis and infertility in rams. Most of the information available on B. ovis and host cell interaction has been generated using murine macrophages or epithelial cell lines, but the interaction between B. ovis and primary ovine macrophages has not been studied. The aim of this study was to evaluate the role of the B. ovis abcEDCBA-encoded ABC transporter and the virB operon-encoded Type IV Secretion System (T4SS) during intracellular survival of B. ovis in ovine peripheral blood monocyte-derived macrophages. ΔabcBA and ΔvirB2 mutant strains were unable to survive in the intracellular environment when compared to the WT B. ovis at 48 hours post infection (hpi). In addition, these mutant strains cannot exclude the lysosomal marker LAMP1 from its vacuolar membrane, and their vacuoles do not acquire the endoplasmic reticulum marker calreticulin, which takes place in the WT B. ovis containing vacuole. Higher levels of nitric oxide production were observed in macrophages infected with WT B. ovis at 48 hpi when compared to macrophages infected with the ΔabcBA or ΔvirB2 mutant strains. Conversely, higher levels of reactive oxygen species were detected in macrophages infected with the ΔabcBA or ΔvirB2 mutant strains at 48 hpi when compared to macrophages infected with the WT strain. Our results demonstrate that B. ovis is able to persist and multiply in ovine macrophages, while ΔabcBA and ΔvirB2 mutations prevent intracellular multiplication, favor phagolysosome fusion, and impair maturation of the B. ovis vacuole towards an endoplasmic reticulum-derived compartment. PMID:26366863

  10. Distinguishing Radiculopathies from Mononeuropathies

    PubMed Central

    Robblee, Jennifer; Katzberg, Hans

    2016-01-01

    Identifying “where is the lesion” is particularly important in the approach to the patient with focal dysfunction where a peripheral localization is suspected. This article outlines a methodical approach to the neuromuscular patient in distinguishing focal neuropathies versus radiculopathies, both of which are common presentations to the neurology clinic. This approach begins with evaluation of the sensory examination to determine whether there are irritative or negative sensory signs in a peripheral nerve or dermatomal distribution. This is followed by evaluation of deep tendon reflexes to evaluate if differential hyporeflexia can assist in the two localizations. Finally, identification of weak muscle groups unique to a nerve or myotomal pattern in the proximal and distal extremities can most reliably assist in a precise localization. The article concludes with an application of the described method to the common scenario of distinguishing radial neuropathy versus C7 radiculopathy in the setting of a wrist drop and provides additional examples for self-evaluation and reference. PMID:27468275

  11. Early exposure of interferon-γ inhibits signal transducer and activator of transcription-6 signalling and nuclear factor κB activation in a short-term monocyte-derived dendritic cell culture promoting ‘FAST’ regulatory dendritic cells

    PubMed Central

    Rojas-Canales, D; Krishnan, R; Jessup, C F; Coates, P T

    2012-01-01

    Interferon (IFN)-γ is a cytokine with immunomodulatory properties, which has been shown previously to enhance the generation of tolerogenic dendritic cells (DC) when administered early ex vivo in 7-day monocyte-derived DC culture. To generate tolerogenic DC rapidly within 48 h, human monocytes were cultured for 24 h with interleukin (IL)-4 and granulocyte–macrophage colony-stimulating factor (GM-CSF) in the presence (IFN-γ-DC) or absence of IFN-γ (500 U/ml) (UT-DC). DC were matured for 24 h with TNF-α and prostaglandin E2 (PGE2). DC phenotype, signal transducer and activator of transcription-6 (STAT-6) phosphorylation and promotion of CD4+CD25+CD127neg/lowforkhead box P3 (FoxP3)hi T cells were analysed by flow cytometry. DC nuclear factor (NF)-κB transcription factor reticuloendotheliosis viral oncogene homologue B (RELB) and IL-12p70 protein expression were also determined. Phenotypically, IFN-γ-DC displayed reduced DC maturation marker CD83 by 62% and co-stimulation molecules CD80 (26%) and CD86 (8%). IFN-γ treatment of monocytes inhibited intracellular STAT6, RELB nuclear translocation and IL-12p70 production. IFN-γ-DC increased the proportion of CD4+CD25+CD127neg/lowfoxp3hi T cells compared to UT-DC from 12 to 23%. IFN-γ-DC primed T cells inhibited antigen-specific, autologous naive T cell proliferation by 70% at a 1:1 naive T cells to IFN-γ-DC primed T cell ratio in suppression assays. In addition, we examined the reported paradoxical proinflammatory effects of IFN-γ and confirmed in this system that late IFN-γ exposure does not inhibit DC maturation marker expression. Early IFN-γ exposure is critical in promoting the generation of regulatory DC. Early IFN-γ modulated DC generated in 48 h are maturation arrested and promote the generation of antigen-specific regulatory T cells, which may be clinically applicable as a novel cellular therapy for allograft rejection. PMID:22288588

  12. Effects of T cell immunoglobulin and mucin domain-containing molecule-3 signaling molecule on human monocyte-derived dendritic cells with hepatitis B virus surface antigen stimulation in vitro.

    PubMed

    Yu, Zhenjun; Jiang, Ting; Zhu, Min; Pan, Kechuan; Yan, Fei; Zhu, Jiansheng

    2016-03-01

    The aim of the present study was to investigate the in vitro effects of hepatitis B virus surface antigen (HBsAg) on the immune function of human monocyte-derived dendritic cells (MD‑DCs), and the moderating role of T cell immunoglobulin and mucin domain‑containing molecule‑3 (Tim‑3) signaling molecule. The monocytes, obtained from healthy adult peripheral blood, were incubated with recombinant human granulocyte‑macrophage colony‑stimulating factor and interleukin (IL)‑4 to induce DCs. DC‑associated cell markers were detected using flow cytometry. MD‑DCs were treated with HBsAg (5 µg/ml) in vitro for 48 h and subsequently, cell markers, lymphocyte stimulatory capacity, signaling protein and downstream cytokines were assessed. In addition, a Tim‑3 monoclonal antibody was used to inhibit the Tim‑3 signaling pathway, and subsequently the immune responses of MD‑DCs to HBsAg stimulation were determined using the aforementioned method. The cell phenotype expressions of MD‑DCs were all significantly increased with cluster of differentiation (CD)11c at 70.09±0.57%, human leukocyte antigen‑DR at 79.83±2.12%, CD80 at 48.33±7.34% and CD86 at 44.21±5.35%. The treatment of MD‑DCs with HBsAg resulted in a CD80 and CD86 enhanced expression, enhanced lymphocyte stimulatory capacity, upregulated expression of Tim‑3 and nuclear factor‑κB (NF‑κB), as well as enhanced cytokine secretion of IL‑6, IL‑10 and interferon (IFN)‑γ. However, a reduced immune response of MD‑DCs in response to HBsAg stimulation was observed when the Tim‑3 signaling pathway was inhibited prior to stimulation. The expression of NF‑κB was decreased and the cytokine secretion level of IL‑6, IL‑10 and IFN‑γ were downregulated. The treatment with HBsAg in vitro resulted in an enhanced immune response of MD‑DCs, which may be positively regulated by the Tim-3 signaling molecule. PMID:26820685

  13. Distinguishing heroes from celebrities.

    PubMed

    North, Adrian C; Bland, Victoria; Ellis, Nicky

    2005-02-01

    Although numerous studies have concerned both 'greatness' and 'celebrity worship,' little previous research has overtly investigated the psychological bases for distinguishing 'heroes' from 'celebrities'. Study 1 indicated that, in response to 13 attitudinal measures, participants' responses to heroes could be summarized in terms of emotional attachment, drive for affiliation, and ordinariness, whereas the corresponding factors for celebrities were drive for affiliation, disdain, and ordinariness. Study 2 investigated how certain individuals might come to be perceived as producing 'great' outputs. Using a vignette, manipulations of 'dead versus alive,' and 'good conduct versus bad conduct' mediated perceptions of the emotional significance of a pop song. The results are used to generate some tentative theoretical explanations for the differences between heroism and celebrity. PMID:15826323

  14. A novel interaction between megakaryocytes and activated fibrocytes increases TGF-β bioavailability in the Gata1low mouse model of myelofibrosis

    PubMed Central

    Zingariello, Maria; Ruggeri, Alessandra; Martelli, Fabrizio; Marra, Manuela; Sancillo, Laura; Ceglia, Ilaria; Rana, Rosa Alba; Migliaccio, Anna Rita

    2015-01-01

    Despite numerous circumstantial evidences, the pathogenic role of TGF-β in primary myelofibrosis (PMF), the most severe of the Philadelphia-negative myeloproliferative neoplasms, is still unclear because of the modest (2-fold) increases in its plasma levels observed in PMF patients and in the Gata1low mouse model. Whether myelofibrosis is associated with increased bioavailability of TGF-β bound to fibrotic fibres is unknown. Transmission electron-microscopy (TEM) observations identified that spleen from PMF patients and Gata1low mice contained megakaryocytes with abnormally high levels of TGF-β and collagen fibres embedded in their cytoplasm. Additional immuno-TEM observations of spleen from Gata1low mice revealed the presence of numerous activated fibrocytes establishing with their protrusions a novel cellular interaction, defined as peripolesis, with megakaryocytes. These protrusions infiltrated the megakaryocyte cytoplasm releasing collagen that was eventually detected in its mature polymerized form. Megakaryocytes, engulfed with mature collagen fibres, acquired the morphology of para-apoptotic cells and, in the most advanced cases, were recognized as polylobated heterochromatic nuclei surrounded by collagen fibres strictly associated with TGF-β. These areas contained concentrations of TGF-β-gold particles ~1000-fold greater than normal and numerous myofibroblasts, an indication that TGF-β was bioactive. Loss-of-function studies indicated that peripolesis between megakaryocytes and fibrocytes required both TGF-β, possibly for inducing fibrocyte activation, and P-selectin, possibly for mediating interaction between the two cell types. Loss-of-function of TGF-β and P-selectin also prevented fibrosis. These observations identify that myelofibrosis is associated with pathological increases of TGF-β bioavailability and suggest a novel megakaryocyte-mediated mechanism that may increase TGF-β bioavailability in chronic inflammation. PMID:27069753

  15. IL-10/HMOX1 signaling modulates cochlear inflammation via negative regulation of MCP-1/CCL2 expression in cochlear fibrocytes.

    PubMed

    Woo, Jeong-Im; Kil, Sung-Hee; Oh, Sejo; Lee, Yoo-Jin; Park, Raekil; Lim, David J; Moon, Sung K

    2015-04-15

    Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aimed to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on IL-10 and hemoxygenase-1 (HMOX1) signaling. We demonstrated that IL-10Rs are expressed in the cochlear lateral wall of mice and rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell line was found to inhibit nontypeable Haemophilus influenzae (NTHi)-induced upregulation of monocyte chemotactic protein-1 (MCP-1; CCL2) in response to IL-10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by cobalt Protoporphyrin IX and CO-releasing molecule-2. In addition, IL-10 appeared to suppress monocyte recruitment through reduction of NTHi-induced rat SLF cell line-derived chemoattractants. Silencing of HMOX1 was found to attenuate the inhibitory effect of IL-10 on NTHi-induced MCP-1/CCL2 upregulation. Chromatin immunoprecipitation assays showed that IL-10 inhibits NTHi-induced binding of p65 NF-κB to the distal motif in the promoter region of MCP-1/CCL2, resulting in suppression of NTHi-induced NF-κB activation. Furthermore, IL-10 deficiency appeared to significantly affect cochlear inflammation induced by intratympanic injections of NTHi. Taken together, our results suggest that IL-10/HMOX1 signaling is involved in modulation of cochlear inflammation through inhibition of MCP-1/CCL2 regulation in SLFs, implying a therapeutic potential for a CO-based approach for inflammation-associated cochlear diseases. PMID:25780042

  16. IL-10/HMOX1 signaling modulates cochlear inflammation via negative regulation of MCP-1/CCL2 expression in cochlear fibrocytes

    PubMed Central

    Woo, Jeong-Im; Kil, Sung-Hee; Oh, Sejo; Lee, Yoo-Jin; Park, Raekil; Lim, David J.; Moon, Sung K.

    2015-01-01

    Cochlear inflammatory diseases such as tympanogenic labyrinthitis are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aim to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on interleukin-10 (IL-10) and hemoxygenase-1 (HMOX1) signaling. We demonstrated that IL-10 receptors (IL-10Rs) are expressed in the cochlear lateral wall of mice and rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell line (RSL) was found to inhibit nontypeable H. influenzae (NTHi)-induced up-regulation of monocyte chemotactic protein-1 (MCP-1/CCL2) in response to IL-10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by cobalt protoporphyrin IX (CoPP) and carbon monoxide-releasing molecule-2 (CORM-2). In addition, IL-10 appeared to suppress monocyte recruitment through reduction of NTHi-induced RSL-derived chemoattractants. Silencing of HMOX1 was found to attenuate the inhibitory effect of IL-10 on NTHi-induced MCP-1/CCL2 up-regulation. Chromatin immunoprecipitation (ChIP) assays showed that IL-10 inhibits NTHi-induced binding of p65 NF-κB to the distal motif in the promoter region of MCP-1/CCL2, resulting in suppression of NTHi-induced NF-κB activation. Furthermore, IL-10 deficiency appeared to significantly affect cochlear inflammation induced by intratympanic injections of NTHi. Taken together, our results suggest that IL-10/HMOX1 signaling is involved in modulation of cochlear inflammation through inhibition of MCP-1/CCL2 regulation in SLFs, implying therapeutic potential of a carbon monoxide (CO)-based approach for inflammation-associated cochlear diseases. PMID:25780042

  17. Angiotensin-(1-7) suppresses the number and function of the circulating fibrocytes by upregulating endothelial nitric oxide synthase expression.

    PubMed

    Wang, Kan; Hu, Xiaosheng; Du, Changqing; Tu, Shike; Zhang, Furong; Xie, Xudong

    2012-06-01

    There is growing evidence suggesting that circulating fibrocytes (CFs) play a pivotal role in tissue repair and fibrosis. In contrast, in recent studies, angiotensin-(1-7) [Ang-(1-7)] has been shown to antagonize fibrosis. The purpose of this study was to examine the direct effect of Ang-(1-7) on CFs. Total mononuclear cells (MNCs) were isolated from peripheral blood by Ficoll density gradient centrifugation. Using laser scanning confocal microscopy, CFs were identified as adherent cells that stained positive for both CD34 and collagen-I. After 14 days of culture, CFs were stimulated with Ang-(1-7) at concentrations of 10 nM, 100 nM, 1 μM or 10 μM, in the absence and presence of pretreatment with A-779, N(G)-nitro-L-arginine methyl ester (L-NAME) or both, for 24, 48 or 72 h. The number of cells, cellular proliferation, and level of apoptosis were determined by hematoxylin and eosin staining, the Cell Counting Kit-8 (CCK8) assay and the annexin V/propidium iodide binding assay, respectively. The collagen content of CFs was measured by the concentration of hydroxyproline, which was detected using the enzymatic digestion method. The expression of endothelial nitric oxide synthase (eNOS) was assayed by western Blot analysis, while nitric oxide (NO) generation was detected using the Griess method. We found that Ang-(1-7) increases apoptosis and eNOS/NO production in CFs. In addition, Ang-(1-7) decreases the number, proliferative capacity and collagen-secretion of CFs in a concentration- and time-dependent manner. These data suggest that Ang-(1-7) suppresses the both the number and function of CFs possibly by increasing eNOS/NO production in the CFs. PMID:22456996

  18. Heme Oxygenase-1 Induction Prevents Autoimmune Diabetes in Association With Pancreatic Recruitment of M2-Like Macrophages, Mesenchymal Cells, and Fibrocytes.

    PubMed

    Husseini, Mahmoud; Wang, Gen-Sheng; Patrick, Christopher; Crookshank, Jennifer A; MacFarlane, Amanda J; Noel, J Ariana; Strom, Alexander; Scott, Fraser W

    2015-11-01

    Immunoregulatory and regenerative processes are activated in the pancreas during the development of type 1 diabetes (T1D) but are insufficient to prevent the disease. We hypothesized that the induction of cytoprotective heme oxygenase-1 (HO-1) by cobalt protophoryrin (CoPP) would prevent T1D by promoting anti-inflammatory and pro-repair processes. Diabetes-prone BioBreeding rats received ip CoPP or saline twice per week for 3 weeks, starting at 30 days and were monitored for T1D. Immunohistochemistry, confocal microscopy, quantitative RT-PCR, and microarrays were used to evaluate postinjection pancreatic changes at 51 days, when islet inflammation is first visible. T1D was prevented in CoPP-treated rats (29% vs 73%). Pancreatic Hmox1 was up-regulated along with islet-associated CD68(+)HO-1(+) cells, which were also observed in a striking peri-lobular interstitial infiltrate. Most interstitial cells expressed the mesenchymal marker vimentin and the hematopoietic marker CD34. Spindle-shaped, CD34(+)vimentin(+) cells coexpressed collagen V, characteristic of fibrocytes. M2 macrophage factors Krüppel-like factor 4, CD163, and CD206 were expressed by interstitial cells, consistent with pancreatic upregulation of several M2-associated genes. CoPP upregulated islet-regenerating REG genes and increased neogenic REG3β(+) and insulin(+) clusters. Thus, short-term induction of HO-1 promoted a protective M2-like milieu in the pancreas and recruited mesenchymal cells, M2 macrophages, and fibrocytes that imparted immunoregulatory and pro-repair effects, preventing T1D. PMID:26252059

  19. Nephrogenic systemic fibrosis: evidence for oxidative stress and bone marrow-derived fibrocytes in skin, liver, and heart lesions using a 5/6 nephrectomy rodent model.

    PubMed

    Wagner, Brent; Tan, Chunyan; Barnes, Jeffrey L; Ahuja, Seema; Davis, Thomas L; Gorin, Yves; Jimenez, Fabio

    2012-12-01

    Nephrogenic systemic fibrosis (NSF) is associated with gadolinium-based magnetic resonance imaging (MRI) contrast exposure in the setting of acute or chronic renal compromise. It has been proposed that circulating fibrocytes mediate the disease. A study was conducted to determine whether bone marrow-derived fibroblast precursors are involved in contributing to organ fibrosis in MRI contrast-treated rodents with renal insufficiency. Rats status post 5/6 nephrectomy underwent bone marrow transplant from human placental alkaline phosphatase (hPAP)-expressing donors. After engraftment, animals were treated with gadolinium-based MRI contrast (2.5 mmol/kg IP), during weekdays for 4 weeks, or an equivalent volume of normal saline. Dermal cellularity in the contrast-treated group was fourfold that of control. Skin cells from the contrast-treated group demonstrated greater hPAP expression with co-expression of pro-collagen I and α-smooth muscle actin-positive stress fibers. Donor and host cells expressed CD34. Dihydroethidium staining of skin was greater in the contrast-treated animals, indicating oxidative stress. This was abrogated when the animals were co-administered the superoxide dismutase mimetic tempol. In conclusion, a bone marrow-derived cell population is increased in the dermis of MRI contrast-treated rodents. The cell markers are consistent with fibrocytes mediating the disease. These changes correlate with oxidative stress and expression of Nox4, suggestive of a novel therapeutic target. Elucidation of the mechanisms of MRI contrast-induced fibrosis may aid in discovering therapies to this devastating disease. PMID:23041060

  20. Wigner-Araki-Yanase theorem on distinguishability

    SciTech Connect

    Miyadera, Takayuki; Imai, Hideki

    2006-08-15

    The presence of an additive-conserved quantity imposes a limitation on the measurement process. According to the Wigner-Araki-Yanase theorem, perfect repeatability and distinguishability of the apparatus cannot be attained simultaneously. Instead of repeatability, in this paper, the distinguishability in both systems is examined. We derive a trade-off inequality between the distinguishability of the final states on the system and the one on the apparatus. An inequality shows that perfect distinguishability of both systems cannot be attained simultaneously.

  1. Distinguishability of generic quantum states

    NASA Astrophysics Data System (ADS)

    Puchała, Zbigniew; Pawela, Łukasz; Życzkowski, Karol

    2016-06-01

    Properties of random mixed states of dimension N distributed uniformly with respect to the Hilbert-Schmidt measure are investigated. We show that for large N , due to the concentration of measure, the trace distance between two random states tends to a fixed number D ˜=1 /4 +1 /π , which yields the Helstrom bound on their distinguishability. To arrive at this result, we apply free random calculus and derive the symmetrized Marchenko-Pastur distribution, which is shown to describe numerical data for the model of coupled quantum kicked tops. Asymptotic value for the root fidelity between two random states, √{F }=3/4 , can serve as a universal reference value for further theoretical and experimental studies. Analogous results for quantum relative entropy and Chernoff quantity provide other bounds on the distinguishablity of both states in a multiple measurement setup due to the quantum Sanov theorem. We study also mean entropy of coherence of random pure and mixed states and entanglement of a generic mixed state of a bipartite system.

  2. Distinguishing cell type using epigenotype

    NASA Astrophysics Data System (ADS)

    Wytock, Thomas; Motter, Adilson E.

    Recently, researchers have proposed that unique cell types are attractors of their epigenetic dynamics including gene expression and chromatin conformation patterns. Traditionally, cell types have been classified by their function, morphology, cytochemistry, and other macroscopically observable properties. Because these properties are the result of many proteins working together, it should be possible to predict cell types from gene expression or chromatin conformation profiles. In this talk, I present a maximum entropy approach to identify and distinguish cell type attractors on the basis of correlations within these profiles. I will demonstrate the flexibility of this method through its separate application to gene expression and chromatin conformation datasets. I show that our method out-performs other machine-learning techniques and uncorrelated benchmarks. We adapt our method to predict growth rate from gene expression in E. coli and S. cerevisiae and compare our predictions with those from metabolic models. In addition, our method identifies a nearly convex region of state-space associated with each cell type attractor basin. Estimates of the growth rate and attractor basin make it possible to rationally control gene regulatory networks independent of a model. This research was supported by NSF-GRFP, NSF-GK12, GAANN, and Northwestern's NIH-NIGMS Molecular Biophysics Training Grant.

  3. Distinguishing psychogenic and essential tremor.

    PubMed

    Kenney, Christopher; Diamond, Alan; Mejia, Nicte; Davidson, Anthony; Hunter, Christine; Jankovic, Joseph

    2007-12-15

    In contrast to essential tremor (ET), psychogenic tremor (PT) is often manifested by shaking with variable amplitude and frequency, distractibility, suggestibility, and entrainment. The sensitivity and specificity of these findings in differentiating PT and ET have not been systematically examined. In order to determine clinical features that reliably distinguish PT from ET, we collected patient information regarding tremor onset, spontaneous remissions, family history, and employment history. A "blinded" rater evaluated video segments of subjects using a standardized protocol with special attention to distractibility, suggestibility, or entrainment. A total of 45 subjects with ET or PT were enrolled in this study: 33 met clinical criteria for ET with a mean age of 56.8+/-17.0 years and 12 met clinical criteria for PT with a mean age of 42.5+/-11.0 years. PT subjects were significantly more likely to relay a history of sudden onset (p=0.03), spontaneous remissions (p=0.03), and shorter duration of tremor (p=0.001). Family history of tremor was significantly more common in the ET group (p=0.001). A moderate-to-marked degree of distraction with alternate finger tapping (p=0.01) and mental concentration on serial 7 s (p=0.01) was more common in PT. Furthermore, suggestibility with a tuning fork (p=0.04) and exacerbation with hyperventilation (p=0.06) seemed predictive of PT. Entrainment was not different in the two groups. In conclusion, a history of tremor with sudden onset and spontaneous remissions along with distractibility and suggestibility on examination are good predictors of PT and help differentiate it from ET. PMID:17604055

  4. Dysregulation of lipid metabolism in Tangier monocyte-derived macrophages.

    PubMed

    Schmitz, G; Fischer, H; Beuck, M; Hoecker, K P; Robenek, H

    1990-01-01

    The cellular defect in Tangier mononuclear phagocytes (MNP) was shown to be associated with significant abnormalities in cellular phospholipid, triglyceride, and cholesteryl ester metabolism by using various radiolabeled precursors (32Pi, 3H-serine, 3H-choline, 14C-acetate, and 14C-oleic acid). Tangier MNP expressed increased rates of synthesis for phospholipids (twofold), triglycerides (fivefold), and cholesteryl esters (threefold) as compared to normal MNP when incubated in McCoy's medium containing 0.2% human serum albumin. The turnover rate of cellular phospholipids was also enhanced, while the turnover rates for triglycerides and cholesteryl esters were normal, thus leading to the accumulation of a larger pool of labeled triglycerides and cholesteryl esters in Tangier MNP. The individual phospholipid classes, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine were similarly affected. Cholesterol loading led to approximately 30% down-regulation of phospholipid synthesis in normal cells, but Tangier MNP showed a smaller response. When nonloaded normal MNP were exposed to high density lipoprotein3 (HDL3), they diminished cellular cholesterol esterification mediated by acyl-CoA:cholesterol acyltransferase (ACAT); in Tangier MNP, ACAT activity increased in the presence of HDL3. When cholesterol-loaded normal and Tangier MNP were treated with HDL3, an up-regulation of phospholipid synthesis was observed in both cell types, but Tangier MNP showed a smaller response. We conclude that the defect in Tangier disease, which we recently described as a "disorder of intracellular traffic" (Schmitz et al. Proc Natl Acad Sci USA 1985;82:6305-6309), is associated with a dysregulation of cellular lipid metabolism, leading to an overproduction of triglycerides and esterified cholesterol and to enhanced synthesis and catabolism of phospholipids. PMID:2244850

  5. Bovine viral diarrhea virus modulations of monocyte derived macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine viral diarrhea virus (BVDV) is a single stranded, positive sense RNA virus and is the causative agent of bovine viral diarrhea (BVD). Disease can range from persistently infected (PI) animals displaying no clinical symptoms of disease to an acute, severe disease. Presently, limited studies ha...

  6. Bovine Viral Diarrhea Virus Modulation of Monocyte Derived Macrophage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bovine Viral Diarrhea Virus (BVDV) is a single stranded, positive sense virus of the Flaviviridae family and is the causative agent of the disease known as Bovine Viral Diarrhea (BVD). Disease can range from persistently infected (PI) animals displaying no clinical symptoms of disease to an acute, s...

  7. CD34+ stromal cells/fibroblasts/fibrocytes/telocytes as a tissue reserve and a principal source of mesenchymal cells. Location, morphology, function and role in pathology.

    PubMed

    Díaz-Flores, L; Gutiérrez, R; García, M P; Sáez, F J; Díaz-Flores, L; Valladares, F; Madrid, J F

    2014-07-01

    We review the morphofunctional characteristics of CD34+ stromal fibroblastic/fibrocytic cells (CD34+ SFCs) and report our observations. We consider the following aspects of CD34+ SFCs: A) The confusing terms applied to this cell type, often combining the prefix CD34 with numerous names, including fibroblasts, fibrocytes, dendrocytes, keratocytes, telocytes and stromal, dendritic, adventitial, supraadventitial, perivascular, paravascular and delimiting cells; B) Changes in their immunophenotype, e.g., loss of CD34 expression and gain of other markers, such as those defining mesenchymal and derivate cells (myofibroblasts, osteoblasts, chondroblasts, adipocytes); C) Morphology (elongated or triangular cell body and thin, moniliform, bipolar or multipolar cytoplasmic processes), immunohistochemistry (co-expression of and changes in molecular expression) and structure (characteristics of nucleus and cytoplasmic organelles, and points of contact and junctions in quiescent and activated stages by light and electron microscopy); D) Location and distribution in the vessels (adventitia or external layer), in the tissues (connective, adipose, blood, muscle and nervous) and in the organs and systems (skin, oral cavity and oropharynx, respiratory, digestive, urinary, male, female, endocrine and lymphoid systems, serosal and synovial membranes, heart, eye and meninges); E) Origin from the mesoderm and cranial neural crest in the embryo, and from stem cells (themselves or other cells) and/or peripheral blood pluripotent stem cells (circulating progenitor cells) in post-natal life; F) Functions, such as synthesis of different molecules, progenitor of mesenchymal cells, immunomodulation, parenchymal regulation (growth, maturation and differentiation of adjacent cells), induction of angiogenesis, scaffolding support of other cells and phagocytic properties. Since CD34+ SFCs are the main reservoir of tissue mesenchymal cells (great mesenchymal potential, probably higher than that

  8. RESTRICTION FRAGMENT LENGTH POLYMORPHISMS DISTINGUISH ECTOMYCORRHIZAL FUNGI

    EPA Science Inventory

    Basidiomycetous fungi, two saprophytes and three mycorrhizal, were used to assess the specificity of DNA hybridization for distinguishing genera from one another. nterspecific comparisons were done with several isolates of mycorrhizal fungi, Laccaria bicolor and L. laccata, colle...

  9. CD4+CD25+FoxP3+ Regulatory Tregs inhibit fibrocyte recruitment and fibrosis via suppression of FGF-9 production in the TGF-β1 exposed murine lung

    PubMed Central

    Peng, Xueyan; Moore, Meagan W.; Peng, Hong; Sun, Huanxing; Gan, Ye; Homer, Robert J.; Herzog, Erica L.

    2014-01-01

    Pulmonary fibrosis is a difficult to treat, often fatal disease whose pathogenesis involves dysregulated TGF-β1 signaling. CD4+CD25+FoxP3+ Regulatory T cells (“Tregs”) exert important effects on host tolerance and arise from naïve CD4+ lymphocytes in response to TGF-β1. However, the precise contribution of Tregs to experimentally induced murine lung fibrosis remains unclear. We sought to better understand the role of Tregs in this context. Using a model of fibrosis caused by lung specific, doxycycline inducible overexpression of the bioactive form of the human TGF-β1 gene we find that Tregs accumulate in the lung parenchyma within 5 days of transgene activation and that this enhancement persists to at least 14 days. Anti-CD25 Antibody mediated depletion of Tregs causes increased accumulation of soluble collagen and of intrapulmonary CD45+Col Iα1 fibrocytes. These effects are accompanied by enhanced local concentrations of the classical inflammatory mediators CD40L, TNF-α, and IL-1α, along with the neuroimmune molecule fibroblast growth factor 9 (FGF-9, also known as “glial activating factor”). FGF-9 expression localizes to parenchymal cells and alveolar macrophages in this model and antibody mediated neutralization of FGF-9 results in attenuated detection of intrapulmonary collagen and fibrocytes without affecting Treg quantities. These data indicate that CD4+CD25+FoxP3+ Tregs attenuate TGF-β1 induced lung fibrosis and fibrocyte accumulation in part via suppression of FGF-9. PMID:24904415

  10. Stanislas Dehaene: Award for Distinguished Scientific Contributions.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2015 award winners is Stanislas Dehaene, who received this award for "outstanding empirical and theoretical contributions to not just one but three fields that are central to the enterprises of psychology and cognitive neuroscience." Dehaene's award citation, biography, and a selected bibliography are presented here. PMID:26618941

  11. Orthogonality and distinguishability: Criterion for local distinguishability of arbitrary orthogonal states

    SciTech Connect

    Chen Pingxing; Li Chengzu

    2003-12-01

    We consider the relation between the orthogonality and the distinguishability of a set of arbitrary states (including multipartite states). It is shown that if a set of arbitrary states can be distinguished by local operations and classical communication (LOCC), each of the states can be written as a linear combination of product vectors such that all product vectors of one of the states are orthogonal to the other states. With this result we then prove a simple necessary condition for LOCC distinguishability of a class of orthogonal states. These conclusions may be useful in discussing the distinguishability of orthogonal quantum states further, understanding the essence of nonlocality and discussing the distillation of entanglement.

  12. Children distinguish between positive pride and hubris.

    PubMed

    Nelson, Nicole L; Russell, James A

    2015-11-01

    Adults distinguish expressions of hubris from those of positive pride. To determine whether children (N = 183; 78-198 months old) make a similar distinction, we asked them to attribute emotion labels and a variety of social characteristics to dynamic expressions intended to convey hubris and positive pride. Like adults, children attributed different emotion labels to the expressions, and this tendency increased with age. Girls were more likely to distinguish between the expressions than boys were. Children also associated more positive social characteristics with the expression of positive pride and more negative characteristics with the expression of hubris. PMID:26347987

  13. Beyond Benford's Law: Distinguishing Noise from Chaos.

    PubMed

    Li, Qinglei; Fu, Zuntao; Yuan, Naiming

    2015-01-01

    Determinism and randomness are two inherent aspects of all physical processes. Time series from chaotic systems share several features identical with those generated from stochastic processes, which makes them almost undistinguishable. In this paper, a new method based on Benford's law is designed in order to distinguish noise from chaos by only information from the first digit of considered series. By applying this method to discrete data, we confirm that chaotic data indeed can be distinguished from noise data, quantitatively and clearly. PMID:26030809

  14. Beyond Benford's Law: Distinguishing Noise from Chaos

    PubMed Central

    Li, Qinglei; Fu, Zuntao; Yuan, Naiming

    2015-01-01

    Determinism and randomness are two inherent aspects of all physical processes. Time series from chaotic systems share several features identical with those generated from stochastic processes, which makes them almost undistinguishable. In this paper, a new method based on Benford's law is designed in order to distinguish noise from chaos by only information from the first digit of considered series. By applying this method to discrete data, we confirm that chaotic data indeed can be distinguished from noise data, quantitatively and clearly. PMID:26030809

  15. Michael Tomasello: Award for Distinguished Scientific Contributions.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2015 award winners is Michael Tomasello, who received this award for "outstanding empirical and theoretical contributions to understanding what makes the human mind unique. Michael Tomasello's pioneering research on the origins of social cognition has led to revolutionary insights in both developmental psychology and primate cognition." Tomasello's award citation, biography, and a selected bibliography are presented here. PMID:26618943

  16. 10 CFR 1002.22 - Use of distinguishing flag.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Use of distinguishing flag. 1002.22 Section 1002.22 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG Distinguishing Flag § 1002.22 Use of distinguishing flag. (a) DOE distinguishing flags may be used only: (1) In the offices of...

  17. 10 CFR 1002.22 - Use of distinguishing flag.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Use of distinguishing flag. 1002.22 Section 1002.22 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG Distinguishing Flag § 1002.22 Use of distinguishing flag. (a) DOE distinguishing flags may be used only: (1) In the offices of...

  18. 10 CFR 1002.22 - Use of distinguishing flag.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Use of distinguishing flag. 1002.22 Section 1002.22 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG Distinguishing Flag § 1002.22 Use of distinguishing flag. (a) DOE distinguishing flags may be used only: (1) In the offices of...

  19. 10 CFR 1002.22 - Use of distinguishing flag.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Use of distinguishing flag. 1002.22 Section 1002.22 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG Distinguishing Flag § 1002.22 Use of distinguishing flag. (a) DOE distinguishing flags may be used only: (1) In the offices of...

  20. 10 CFR 1002.22 - Use of distinguishing flag.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Use of distinguishing flag. 1002.22 Section 1002.22 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG Distinguishing Flag § 1002.22 Use of distinguishing flag. (a) DOE distinguishing flags may be used only: (1) In the offices of...

  1. Repetitive sequence environment distinguishes housekeeping genes

    PubMed Central

    Eller, C. Daniel; Regelson, Moira; Merriman, Barry; Nelson, Stan; Horvath, Steve; Marahrens, York

    2007-01-01

    Housekeeping genes are expressed across a wide variety of tissues. Since repetitive sequences have been reported to influence the expression of individual genes, we employed a novel approach to determine whether housekeeping genes can be distinguished from tissue-specific genes their repetitive sequence context. We show that Alu elements are more highly concentrated around housekeeping genes while various longer (>400-bp) repetitive sequences ("repeats"), including Long Interspersed Nuclear Element 1 (LINE-1) elements, are excluded from these regions. We further show that isochore membership does not distinguish housekeeping genes from tissue-specific genes and that repetitive sequence environment distinguishes housekeeping genes from tissue-specific genes in every isochore. The distinct repetitive sequence environment, in combination with other previously published sequence properties of housekeeping genes, were used to develop a method of predicting housekeeping genes on the basis of DNA sequence alone. Using expression across tissue types as a measure of success, we demonstrate that repetitive sequence environment is by far the most important sequence feature identified to date for distinguishing housekeeping genes. PMID:17141428

  2. Children Distinguish between Positive Pride and Hubris

    ERIC Educational Resources Information Center

    Nelson, Nicole L.; Russell, James A.

    2015-01-01

    Adults distinguish expressions of hubris from those of positive pride. To determine whether children (N = 183; 78-198 months old) make a similar distinction, we asked them to attribute emotion labels and a variety of social characteristics to dynamic expressions intended to convey hubris and positive pride. Like adults, children attributed…

  3. Characteristics of Distinguished Programs of Agricultural Education

    ERIC Educational Resources Information Center

    Birkenholz, Robert J.; Simonsen, Jon C.

    2011-01-01

    Academic program rankings are highly anticipated by many university administrators, faculty, and alumni. This study analyzed the perceptions of agricultural education departmental contact persons to identify esteemed post-secondary agricultural education programs and the distinguishing characteristics of each program. The ten most distinguished…

  4. Entropy of Mixing of Distinguishable Particles

    ERIC Educational Resources Information Center

    Kozliak, Evguenii I.

    2014-01-01

    The molar entropy of mixing yields values that depend only on the number of mixing components rather than on their chemical nature. To explain this phenomenon using the logic of chemistry, this article considers mixing of distinguishable particles, thus complementing the well-known approach developed for nondistinguishable particles, for example,…

  5. Distinguishing the Spending Preferences of Seniors.

    ERIC Educational Resources Information Center

    Zimmer, Zachary; Chappell, Neena L.

    1996-01-01

    The consumer spending preferences of 1,406 senior Canadians were surveyed. Age distinguished those who had product-specific preferences. Income and health status separated those interested in recreational spending from those more interested in basic needs. Diversity of health and social characteristics in this population extends to their…

  6. The Humanity of English. 1972 Distinguished Lectures.

    ERIC Educational Resources Information Center

    National Council of Teachers of English, Urbana, IL.

    This is a collection of lectures by distinguished members of the English profession who were invited to lecture to schools located far from large urban and cultural centers. Included are papers by: John H. Fisher, "Truth Versus Beauty: An Inquiry into the Function of Language and Literature in an Articulate Society"; Walter Loban, "The Green…

  7. Distinguishing Disability: Parents, Privilege, and Special Education

    ERIC Educational Resources Information Center

    Ong-Dean, Colin

    2009-01-01

    Students in special education programs can have widely divergent experiences. For some, special education amounts to a dumping ground where schools unload their problem students, while for others, it provides access to services and accommodations that drastically improve chances of succeeding in school and beyond. "Distinguishing Disability"…

  8. Local distinguishability of generic unentangled orthonormal bases

    NASA Astrophysics Data System (ADS)

    Lebl, Jiří; Shakeel, Asif; Wallach, Nolan

    2016-01-01

    An orthonormal basis consisting of unentangled (pure tensor) elements in a tensor product of Hilbert spaces is an unentangled orthonormal basis (UOB). In general, for n qubits, we prove that in its natural structure as a real variety, the space of UOB is a bouquet of products of Riemann spheres parametrized by a class of edge colorings of hypercubes. Its irreducible components of maximum dimension are products of 2n-1 two spheres. Using a theorem of Walgate and Hardy, we observe that the UOB whose elements are distinguishable by local operations and classical communication (called locally distinguishable or LOCC distinguishable UOB) are exactly those in the maximum dimensional components. Bennett et al. [Phys. Rev. A 59, 1070 (1999)., 10.1103/PhysRevA.59.1070], in their in-depth study of quantum nonlocality without entanglement, include a specific three-qubit example UOB which is not LOCC distinguishable; we construct certain generalized counterparts of this UOB in n qubits.

  9. The ambiguity of "distinguishability" in statistical mechanics

    NASA Astrophysics Data System (ADS)

    Swendsen, Robert H.

    2015-06-01

    Differences of opinion concerning fundamental issues in statistical mechanics directly related to the thermodynamic entropy have persisted through more than a century of debate. One reason is the lack of consensus on the definitions of key terms, especially the terms "distinguishable," "indistinguishable," and "identical." Several definitions occur in the literature, but are not always made explicit. The multiplicity of definitions has created confusion about the basic conditions under which entropy is to be defined. In this paper, I present an overview of definitions in current use for terms associated with distinguishability and relate them to various definitions that have been suggested for entropy. My hope is that consensus will be achievable if the definitions are clarified and agreed upon.

  10. Distinguishing Provenance Equivalence of Earth Science Data

    NASA Technical Reports Server (NTRS)

    Tilmes, Curt; Yesha, Ye; Halem, M.

    2010-01-01

    Reproducibility of scientific research relies on accurate and precise citation of data and the provenance of that data. Earth science data are often the result of applying complex data transformation and analysis workflows to vast quantities of data. Provenance information of data processing is used for a variety of purposes, including understanding the process and auditing as well as reproducibility. Certain provenance information is essential for producing scientifically equivalent data. Capturing and representing that provenance information and assigning identifiers suitable for precisely distinguishing data granules and datasets is needed for accurate comparisons. This paper discusses scientific equivalence and essential provenance for scientific reproducibility. We use the example of an operational earth science data processing system to illustrate the application of the technique of cascading digital signatures or hash chains to precisely identify sets of granules and as provenance equivalence identifiers to distinguish data made in an an equivalent manner.

  11. Distinguishing between applied research and practice

    PubMed Central

    Johnston, James M.

    1996-01-01

    Behavior-analytic research is often viewed along a basic—applied continuum of research goals and methods. The applied portion of this continuum has evolved in ways that combine applied research and service delivery. Although these two facets of applied behavior analysis should be closely related, more clearly distinguishing between them, particularly in how we conceptualize and conduct applied research, may enhance the continuing development of each. This differentiation may improve the recruitment and training of graduate students. PMID:22478238

  12. Familial Identification: Population Structure and Relationship Distinguishability

    PubMed Central

    Rohlfs, Rori V.; Fullerton, Stephanie Malia; Weir, Bruce S.

    2012-01-01

    With the expansion of offender/arrestee DNA profile databases, genetic forensic identification has become commonplace in the United States criminal justice system. Implementation of familial searching has been proposed to extend forensic identification to family members of individuals with profiles in offender/arrestee DNA databases. In familial searching, a partial genetic profile match between a database entrant and a crime scene sample is used to implicate genetic relatives of the database entrant as potential sources of the crime scene sample. In addition to concerns regarding civil liberties, familial searching poses unanswered statistical questions. In this study, we define confidence intervals on estimated likelihood ratios for familial identification. Using these confidence intervals, we consider familial searching in a structured population. We show that relatives and unrelated individuals from population samples with lower gene diversity over the loci considered are less distinguishable. We also consider cases where the most appropriate population sample for individuals considered is unknown. We find that as a less appropriate population sample, and thus allele frequency distribution, is assumed, relatives and unrelated individuals become more difficult to distinguish. In addition, we show that relationship distinguishability increases with the number of markers considered, but decreases for more distant genetic familial relationships. All of these results indicate that caution is warranted in the application of familial searching in structured populations, such as in the United States. PMID:22346758

  13. Quantum correlations and distinguishability of quantum states

    SciTech Connect

    Spehner, Dominique

    2014-07-15

    A survey of various concepts in quantum information is given, with a main emphasis on the distinguishability of quantum states and quantum correlations. Covered topics include generalized and least square measurements, state discrimination, quantum relative entropies, the Bures distance on the set of quantum states, the quantum Fisher information, the quantum Chernoff bound, bipartite entanglement, the quantum discord, and geometrical measures of quantum correlations. The article is intended both for physicists interested not only by collections of results but also by the mathematical methods justifying them, and for mathematicians looking for an up-to-date introductory course on these subjects, which are mainly developed in the physics literature.

  14. Distinguishing ankle and knee articular cartilage.

    PubMed

    Cole, Ada A; Margulis, Arkady; Kuettner, Klaus E

    2003-06-01

    Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee. PMID:12911243

  15. Can cosmic parallax distinguish between anisotropic cosmologies?

    SciTech Connect

    Fontanini, Michele; West, Eric J.; Trodden, Mark

    2009-12-15

    In an anisotropic universe, observers not positioned at a point of special symmetry should observe cosmic parallax--the relative angular motion of test galaxies over cosmic time. It was recently argued that the nonobservance of this effect in upcoming precision astrometry missions such as GAIA may be used to place strong bounds on the position of off-center observers in a void-model universe described by the Lemaitre-Tolman-Bondi metric. We consider the analogous effect in anisotropic cosmological models described by an axisymmetric homogeneous Bianchi type I metric and discuss whether any observation of cosmic parallax would distinguish between different anisotropic evolutions.

  16. Techniques to Distinguish Apoptosis from Necroptosis.

    PubMed

    Feoktistova, Maria; Wallberg, Fredrik; Tenev, Tencho; Geserick, Peter; Leverkus, Martin; Meier, Pascal

    2016-04-01

    The processes by which cells die are as tightly regulated as those that govern cell growth and proliferation. Recent studies of the molecular pathways that regulate and execute cell death have uncovered a plethora of signaling cascades that lead to distinct modes of cell death, including "apoptosis," "necrosis," "autophagic cell death," and "mitotic catastrophe." Cells can readily switch from one form of death to another; therefore, it is vital to have the ability to monitor the form of death that cells are undergoing. A number of techniques are available that allow the detection of cell death and when combined with either knockdown approaches or inhibitors of specific signaling pathways, such as caspase or RIP kinase pathways, they allow the rapid dissection of divergent cell death pathways. However, techniques that reveal the end point of cell death cannot reconstruct the sequence of events that have led to death; therefore, they need to be complemented with methods that can distinguish all forms of cell death. Apoptotic cells frequently undergo secondary necrosis under in vitro culture conditions; therefore, novel methods relying on high-throughput time-lapse fluorescence video microscopy are necessary to provide temporal resolution to cell death events. Further, visualizing the assembly of multiprotein signaling hubs that can execute apoptosis or necroptosis helps to explore the underlying processes. Here we introduce a suite of techniques that reliably distinguish necrosis from apoptosis and secondary necrosis, and that enable investigation of signaling platforms capable of instructing apoptosis or necroptosis. PMID:27037077

  17. Do open clusters have distinguishable chemical signatures?

    NASA Astrophysics Data System (ADS)

    Blanco-Cuaresma, S.; Soubiran, C.; Heiter, U.

    2014-07-01

    Past studies have already shown that stars in open clusters are chemically homogeneous (e.g. De Silva et al. 2006, 2007 and 2009). These results support the idea that stars born from the same giant molecular cloud should have the same chemical composition. In this context, the chemical tagging technique was proposed by Freeman et al. (2002). The principle is to recover disrupted stellar clusters by looking only to the stellar chemical composition. In order to evaluate the feasibility of this approach, it is necessary to test if we can distinguish between stars born from different molecular clouds. For this purpose, we studied the chemical composition of stars in 32 old and intermediate-age open clusters, and we applied machine learning algorithms to recover the original cluster by only considering the chemical signatures.

  18. Distinguishing Feedback Mechanisms in Clock Models

    NASA Astrophysics Data System (ADS)

    Golden, Alexander; Lubensky, David

    Biological oscillators are very diverse but can be classified based on dynamical motifs such as type of feedback. The S. Elongatus circadian oscillator is a novel circadian oscillator that can operate at constant protein number by modifying covalent states. It can be reproduced in vitro with only 3 different purified proteins: KaiA, KaiB, and KaiC. We use computational and analytic techniques to compare models of the S. Elongatus post-translational oscillator that rely on positive feedback with models that rely on negative feedback. We show that introducing a protein that binds competitively with KaiA to the KaiB-KaiC complex can distinguish between positive and negative feedback as the primary driver of the rhythm, which has so far been difficult to address experimentally. NSF Grant DMR-1056456.

  19. Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

    PubMed

    Howard, Rebecca; Rattray, Magnus; Prosperi, Mattia; Custovic, Adnan

    2015-07-01

    Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as 'asthma endotypes'. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies. PMID:26143394

  20. Inequality indicators and distinguishability in economics

    NASA Astrophysics Data System (ADS)

    Rosenblatt, J.; Martinás, K.

    2008-03-01

    Money has a material counterpart, such as banknotes or coins, and an ideal expression, monetary units. In the latter case, it is boson-like: individual incomes have no a priori limit, and their units are not distinguishable from each other in economic processes. Individuals, on the other hand, usually occupy one job at a time which makes them akin to fermions. We apply to individual incomes down-to-earth statistical calculations, similar to those for quantum particles, and obtain expressions for the cumulative distribution function, probability density and Lorenz function resulting from the simultaneous use of both statistics. They provide extremely good fits to corresponding data on French income distributions. On this basis, we propose a new entropic inequality indicator.

  1. Distinguishing Solar Cycle Effects in Planetary Atmospheres

    NASA Astrophysics Data System (ADS)

    Aplin, K. L.; Harrison, R. G.

    2008-12-01

    As solar radiation decreases with distance from the Sun, other sources of energy, such as ionization from galactic cosmic rays (GCR), assume a greater relative importance than at the terrestrial planets. Charged particle effects could therefore be more relevant to the formation of clouds and haze at the outer planets. The long-term solar modulation of Neptune's albedo is thought to be caused by either ion-induced nucleation of cloud-forming particles, or ultraviolet (UV) radiation effects on the colour of the clouds. On the basis of the 11 year solar cycle, the statistical evidence was slightly in favour of the UV mechanism, however distinguishing unambiguously between the two mechanisms will require more than the solar cycle variation alone. A 1.68 year quasi-periodicity, uniquely present at some times from heliospheric modulation of GCR, has previously been used to discriminate between solar UV and GCR effects in terrestrial data. The cosmic ray proton monitor data from both the Voyager spacecraft show this 1.68 year modulation during the 1980s when the spacecraft were close to the outer planets, indicating the possibility for applying a similar technique as far out as Neptune.

  2. LDRD 149045 final report distinguishing documents.

    SciTech Connect

    Mitchell, Scott A.

    2010-09-01

    This LDRD 149045 final report describes work that Sandians Scott A. Mitchell, Randall Laviolette, Shawn Martin, Warren Davis, Cindy Philips and Danny Dunlavy performed in 2010. Prof. Afra Zomorodian provided insight. This was a small late-start LDRD. Several other ongoing efforts were leveraged, including the Networks Grand Challenge LDRD, and the Computational Topology CSRF project, and the some of the leveraged work is described here. We proposed a sentence mining technique that exploited both the distribution and the order of parts-of-speech (POS) in sentences in English language documents. The ultimate goal was to be able to discover 'call-to-action' framing documents hidden within a corpus of mostly expository documents, even if the documents were all on the same topic and used the same vocabulary. Using POS was novel. We also took a novel approach to analyzing POS. We used the hypothesis that English follows a dynamical system and the POS are trajectories from one state to another. We analyzed the sequences of POS using support vector machines and the cycles of POS using computational homology. We discovered that the POS were a very weak signal and did not support our hypothesis well. Our original goal appeared to be unobtainable with our original approach. We turned our attention to study an aspect of a more traditional approach to distinguishing documents. Latent Dirichlet Allocation (LDA) turns documents into bags-of-words then into mixture-model points. A distance function is used to cluster groups of points to discover relatedness between documents. We performed a geometric and algebraic analysis of the most popular distance functions and made some significant and surprising discoveries, described in a separate technical report.

  3. How do recovery definitions distinguish recovering individuals?

    PubMed Central

    Witbrodt, Jane; Kaskutas, Lee Ann; Grella, Christine E.

    2015-01-01

    Background Six percent of American adults say they are “in recovery” from an alcohol or drug problem yet only a scant emergent literature has begun to ask how they define “recovery” or explored whether there is heterogeneity among their definitions. Methods Secondary analysis of the What Is Recovery? online survey employed Latent Class Analysis (LCA) to identify typologies of study participants based on their actual endorsement of 39 recovery elements and to compare the composition of these typologies in terms of distinguishing personal characteristics. Results A 5-class solution provided the best fit and conceptual representation for the recovery definitions. Classes were labeled 12-Step Traditionalist (n=4912); 12-Step Enthusiast (n=2014); Secular (n=980); Self-Reliant (n=1040); and Atypical (n=382) based on patterns of endorsement of the recovery elements. Abstinence, spiritual, and social interaction elements differentiated the classes most (as did age and recovery duration but to a lesser extent). Although levels and patterns of endorsement to the elements varied by class, a rank-ordering of the top 10 elements indicated that four elements were endorsed by all five classes: being honest with myself, handling negative feelings without using, being able to enjoy life, and process of growth and development. Conclusions The results of the LCA demonstrate the diversity of meanings, and varying degrees of identification with, specific elements of recovery. As others have found, multiple constituents are invested in how recovery is defined and this has ramifications for professional, personal, and cultural processes related to how strategies to promote recovery are implemented. PMID:25630961

  4. Liberating the Publications of a Distinguished Scholar: A Pilot Project

    ERIC Educational Resources Information Center

    Kelly, Julie

    2014-01-01

    Many distinguished scholars published the primary corpus of their work before the advent of online journals, which makes it more challenging to access. Upon being approached by a distinguished Emeritus Professor seeking advice about getting his work posted online, librarians at the University of Minnesota worked to gain copyright permissions to…

  5. Excellence in Teacher Education. 1973 Distinguished Achievement Awards Program.

    ERIC Educational Resources Information Center

    American Association of Colleges for Teacher Education, Washington, DC.

    The State University of New York College of Cortland received the 1973 Distinguished Achievement Award for its Project Change, a performance-based early childhood teacher education program. Also cited for distinguished achievement were a) Teachers College of Ball State University, Indiana for an experimental program designed to include…

  6. 28 CFR 301.318 - Civilian compensation laws distinguished.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Civilian compensation laws distinguished... Civilian compensation laws distinguished. The Inmate Accident Compensation system is not obligated to... under civilian workmen's compensation laws in that hospitalization is usually completed prior to...

  7. 29 CFR 779.328 - Retail and wholesale distinguished.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Retail and wholesale distinguished. 779.328 Section 779.328... AS APPLIED TO RETAILERS OF GOODS OR SERVICES Exemptions for Certain Retail or Service Establishments ârecognizedâ As Retail âin the Particular Industryâ § 779.328 Retail and wholesale distinguished. (a)...

  8. John Glenn: Presented with NASA Distinguished Service Medal

    NASA Technical Reports Server (NTRS)

    1963-01-01

    John Glenn tours with his family, meets JFK and is presented with the NASA distinguished Service Medal. From: The John Glenn Story: Summary of astronaut John Glenn's flying career, from naval aviation training to space flight. The Mercury project is featured as John Glenn flies the Friendship 7 spacecraft. President John F. Kennedy presents the NASA Distinguished service Medal to Astronaut John Glenn.

  9. 32 CFR 22.205 - Distinguishing assistance from procurement.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Distinguishing assistance from procurement. 22... Instrument § 22.205 Distinguishing assistance from procurement. Before using a grant or cooperative agreement... procurement contract, is the appropriate instrument, based on the following: (a) Purpose. (1) The...

  10. Charles L. Brewer Award for Distinguished Teaching of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    The American Psychological Foundation (APF) Charles L. Brewer Distinguished Teaching of Psychology Award recognizes an outstanding career contribution to the teaching of psychology. The 2009 recipient of the Distinguished Teaching Award is William Buskist. Dorothy W. Cantor, president of the APF, will present the APF Teaching Award at the 117th…

  11. Distinguishability of Biological Material Using Ultraviolet Multi-Spectral Fluorescence

    SciTech Connect

    Gray, P.C.; Heinen, R.J.; Rigdon, L.D.; Rosenthal, S.E.; Shokair, I.R.; Siragusa, G.R.; Tisone, G.C.; Wagner, J.S.

    1998-10-14

    Recent interest in the detection and analysis of biological samples by spectroscopic methods has led to questions concerning the degree of distinguishability and biological variability of the ultraviolet (W) fluorescent spectra from such complex samples. We show that the degree of distinguishability of such spectra is readily determined numerically.

  12. Charles L. Brewer Award for Distinguished Teaching of Psychology.

    PubMed

    2008-01-01

    The American Psychological Foundation (APF) Charles L. Brewer Distinguished Teaching of Psychology Award recognizes an outstanding career contribution to the teaching of psychology. The 2008 recipient of the Distinguished Teaching Award is Scott Plous. A citation, biography, and selected bibliography for Scott Plous are provided in this article. (PsycINFO Database Record (c) 2008 APA, all rights reserved). PMID:18665671

  13. Distinguishability of countable quantum states and von Neumann lattice

    NASA Astrophysics Data System (ADS)

    Kawakubo, Ryûitirô; Koike, Tatsuhiko

    2016-07-01

    The condition for distinguishability of a countably infinite number of pure states by a single measurement is given. Distinguishability is to be understood as the possibility of an unambiguous measurement. For a finite number of states, it is known that the necessary and sufficient condition of distinguishability is that the states are linearly independent. For an infinite number of states, several natural classes of distinguishability can be defined. We give a necessary and sufficient condition for a system of pure states to be distinguishable. It turns out that each level of distinguishability naturally corresponds to one of the generalizations of linear independence to families of infinite vectors. As an important example, we apply the general theory to von Neumann’s lattice, a subsystem of coherent states which corresponds to a lattice in the classical phase space. We prove that the condition for distinguishability is that the area of the fundamental region of the lattice is greater than the Planck constant, and also find subtle behavior on the threshold. These facts reveal the measurement theoretical meaning of the Planck constant and give a justification for the interpretation that it is the smallest unit of area in the phase space. The cases of uncountably many states and of mixed states are also discussed.

  14. Strain gage network distinguishes between thermal and mechanical deformations

    NASA Technical Reports Server (NTRS)

    Cepollina, F. J.

    1966-01-01

    Strain gage network measures the thermal coefficient of linear expansion of composite metal structures. The network consists of a test gage and two dummy gages arranged to distinguish thermally induced deformation from mechanical strain.

  15. Charles L. Brewer Award for Distinguished Teaching of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2007

    2007-01-01

    This article announces the 2007 recipient of the Charles L. Brewer Award for Distinguished Teaching of Psychology: Baron Perlman. A brief biography, highlighting areas of special focus in Perlman's work, is provided.

  16. Edna B. Foa: Award for Distinguished Scientific Contributions.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2015 award winners is Edna B. Foa, who received this award for "her outstanding and innovative research on the nature, measurement, and treatment of anxiety." Foa's award citation, biography, and a selected bibliography are presented here. PMID:26618942

  17. Carol A. Barnes: Award for Distinguished Scientific Contributions.

    PubMed

    2014-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2014 award winners is Carol A. Barnes, who received this award for her "groundbreaking work on the neurobiological mechanisms underlying memory changes in normal aging." Barnes' award citation, biography, and a selected bibliography are presented here. PMID:25486138

  18. Richard N. Aslin: Award for Distinguished Scientific Contributions.

    PubMed

    2014-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2014 award winners is Richard N. Aslin, who received this award for "elegance of thought in providing new ways to think about the relationships among learning, development, and biology." Aslin's award citation, biography, and a selected bibliography are presented here. PMID:25486136

  19. John A. Bargh: Award for Distinguished Scientific Contributions.

    PubMed

    2014-11-01

    The APA Awards for Distinguished Scientific Contributions are presented to persons who, in the opinion of the Committee on Scientific Awards, have made distinguished theoretical or empirical contributions to basic research in psychology. One of the 2014 award winners is John A. Bargh, who received this award for his "groundbreaking work on the automaticity of social cognition, emotion, motivation, and behavior." Bargh's award citation, biography, and a selected bibliography are presented here. PMID:25486137

  20. G. Terence Wilson: Award for Distinguished Scientific Applications of Psychology.

    PubMed

    2014-11-01

    The APA Award for Distinguished Scientific Applications of Psychology is presented to a person who, in the opinion of the Committee on Scientific Awards, has made distinguished theoretical or empirical advances leading to the understanding or amelioration of important practical problems. The 2014 recipient is G. Terence Wilson, who received the award for "his outstanding contributions to the nature and theory of behavior therapy." Wilson's award citation, biography, and a selected bibliography are presented here. PMID:25486140

  1. Distinguishing grammatical constructions with fMRI pattern analysis.

    PubMed

    Allen, Kachina; Pereira, Francisco; Botvinick, Matthew; Goldberg, Adele E

    2012-12-01

    All linguistic and psycholinguistic theories aim to provide psychologically valid analyses of particular grammatical patterns and the relationships that hold among them. Until recently, no tools were available to distinguish neural correlates of particular grammatical constructions that shared the same content words, propositional meaning, and degree of surface complexity, such as the dative (e.g., Sally gave the book to Joe) and the ditransitive (e.g., Sally gave Joe a book). We report the first fMRI data that distinguish such closely related, abstract grammatical patterns. Multi-voxel pattern analysis (MVPA) proved capable of discriminating at above-chance levels between activity patterns arising during reading of dative and ditransitive sentences. Region-of-interest analyses reveal that the union of certain language-relevant areas, anterior and posterior BA22, BA44/45 and BA47, yield classification accuracy above chance and above that of control conditions in the left hemisphere but not in the right. Looking more closely at the LH ROIs, we find that the combination of areas aBA22 and BA47 is sufficient to distinguish the two constructions better than the controls and better than chance. The fact that both of these areas-particularly BA47-have been implicated in semantics, lends support to claims that the two constructions are distinguishable semantically. More generally, the ability to distinguish closely related grammatical constructions using MVPA offers the promise of addressing traditional theoretical questions on a neuroscientifically grounded basis. PMID:23010489

  2. Two-Year-Olds Distinguish Pretending and Joking.

    PubMed

    Hoicka, Elena; Martin, Catriona

    2016-05-01

    Although children understand intentions to joke and pretend by 2 or 3 years, it is unclear whether they distinguish these intentional acts. Using a normativity paradigm, this study found (N = 72) 2-year-olds protest against jokes more than pretending, suggesting, for the first time, they distinguish these acts. Furthermore, toddlers protested more generally after pretend than literal or joke contexts but only if intentional cues were used. Additionally, children objected more to joking than pretending after pretend and literal contexts but not after joke contexts. Thus, toddlers distinguish the intentional nature of pretending and joking. Furthermore, a pretend intentional context establishes specific rules to be followed, whereas a joke intentional context allows an open space to perform various types of acts. PMID:27170036

  3. Entanglement as a resource to distinguish orthogonal product states

    PubMed Central

    Zhang, Zhi-Chao; Gao, Fei; Cao, Tian-Qing; Qin, Su-Juan; Wen, Qiao-Yan

    2016-01-01

    It is known that there are many sets of orthogonal product states which cannot be distinguished perfectly by local operations and classical communication (LOCC). However, these discussions have left the following open question: What entanglement resources are necessary and/or sufficient for this task to be possible with LOCC? In m ⊗ n, certain classes of unextendible product bases (UPB) which can be distinguished perfectly using entanglement as a resource, had been presented in 2008. In this paper, we present protocols which use entanglement more efficiently than teleportation to distinguish some classes of orthogonal product states in m ⊗ n, which are not UPB. For the open question, our results offer rather general insight into why entanglement is useful for such tasks, and present a better understanding of the relationship between entanglement and nonlocality. PMID:27458034

  4. The distinguishable cluster approach from a screened Coulomb formalism.

    PubMed

    Kats, Daniel

    2016-01-28

    The distinguishable cluster doubles equations have been derived starting from an effective screened Coulomb formalism and a particle-hole symmetric formulation of the Fock matrix. A perturbative triples correction to the distinguishable cluster with singles and doubles (DCSD) has been introduced employing the screened integrals. It is shown that the resulting DCSD(T) method is more accurate than DCSD for reaction energies and is less sensitive to the static correlation than coupled cluster with singles and doubles with a perturbative triples correction. PMID:26827197

  5. Distinguishing succulent plants from crop and woody plants

    NASA Technical Reports Server (NTRS)

    Gausman, H. W.; Escobar, D. E.; Everitt, J. H.; Richardson, A. J.; Rodriguez, R. R.

    1978-01-01

    We compared laboratory spectrophotometrically measured leaf reflectances of six succulents (peperomia, possum-grape, prickly pear, spiderwort, Texas tuberose, wolfberry) with those of four nonsucculents (cenizo, honey mesquite, cotton, sugarcane) for plant species discrimination. Succulents (average leaf water content of 92.2 percent) could be distinguished from nonsucculents (average leaf water content of 71.2 percent) within the near-infrared water absorption waveband (1.35 to 2.5 microns). This was substantiated by field spectrophotometric reflectances of plant canopies. Sensor bands encompassing either the 1.6- or 2.2-wavelengths may be useful to distinguish succulent from nonsucculent plant species.

  6. Award for Distinguished Scientific Contributions: Susan E. Carey

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Susan E. Carey, winner of the 2009 Award for Distinguished Scientific Contributions, is cited for groundbreaking studies of the nature of concepts and conceptual change. Her research deepens understanding of the development of concepts, and of the belief systems in which they are embedded, over human childhood, over the history of science, and…

  7. The Identification of Conductor-Distinguished Functions of Conducting

    ERIC Educational Resources Information Center

    Gumm, Alan J.; Battersby, Sharyn L.; Simon, Kathryn L.; Shankles, Andrew E.

    2011-01-01

    The purpose of the present study was to identify whether conductors distinguish functions of conducting similarly to functions implied in previous research. A sample of 84 conductors with a full range of experience levels (M = 9.8) and of a full range of large ensemble types and ensemble age levels rated how much they pay attention to 82…

  8. Distinguishing between Realistic and Fantastical Figures in Iran

    ERIC Educational Resources Information Center

    Davoodi, Telli; Corriveau, Kathleen H.; Harris, Paul L.

    2016-01-01

    Children in the United States come to distinguish historical from fictional story figures between the ages of 3 and 5 years, guided by the plausibility of the story events surrounding the figure (Corriveau, Kim, Schwalen, & Harris, 2009; Woolley & Cox, 2007). However, U.S. children vary in their reactions to stories that include…

  9. Distinguishing between Dirac and Majorana neutrinos withtwo-particle interferometry

    SciTech Connect

    Gutierrez, Thomas D.

    2006-03-02

    Two-particle interferometry, a second-order interferenceeffect, is explored as another possible tool to distinguish betweenmassive Dirac and Majorana neutrinos. A simple theoretical framework isdiscussed in the context of several gedanken experiments. The method canin principle provide both the mass scale and the quantum nature of theneutrino for a certain class of incoherent left-handed sourcecurrents.

  10. Daniel L. Schacter: Award for Distinguished Scientific Contributions

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents Daniel L. Schacter as one of the winners of the American Psychological Association's Award for Distinguished Scientific Contributions (2012). Daniel L. Schacter's major theoretical and empirical contributions include groundbreaking research on the psychological and neural foundations of implicit and explicit memory, memory distortions and…

  11. Edward F. Diener: Award for Distinguished Scientific Contributions

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents Edward F. Diener as one of the winners of the American Psychological Association's Award for Distinguished Scientific Contributions (2012). Edward F. Diener has been a leader in every aspect of well-being research. He provided an influential conception of well-being as consisting of cognitive and emotional elements. A citation, biography,…

  12. Award for Distinguished Scientific Contributions: Steven F. Maier

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Steven F. Maier, winner of the Award for Distinguished Scientific Contributions, is cited for his work in the fields of learned helplessness; cytokines, depressed mood, and cognitive interference; and the brain structures that produce and counteract learned helplessness. In addition to the citation, a biography and selected bibliography of Maier's…

  13. Distinguishing Grammatical Constructions with fMRI Pattern Analysis

    ERIC Educational Resources Information Center

    Allen, Kachina; Pereira, Francisco; Botvinick, Matthew; Goldberg, Adele E.

    2012-01-01

    All linguistic and psycholinguistic theories aim to provide psychologically valid analyses of particular grammatical patterns and the relationships that hold among them. Until recently, no tools were available to distinguish neural correlates of particular grammatical constructions that shared the same content words, propositional meaning, and…

  14. Distinguishing between Poor/Dysfunctional Parenting and Child Emotional Maltreatment

    ERIC Educational Resources Information Center

    Wolfe, David A.; McIsaac, Caroline

    2011-01-01

    Objective: This paper was intended to distinguish between poor parenting and child emotional maltreatment (CEM), to inform child welfare and public health policymakers of the need for differentiated responses. Methods: Scientific literature was integrated with current practice and assumptions relating to poor/dysfunctional parenting and child…

  15. Award for Distinguished Scientific Contributions: Alice H. Eagly

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Alice H. Eagly, winner of the Award for Distinguished Scientific Contributions, is cited for her work in the field of social psychology, the psychology of gender, and the use of meta-analytic techniques. She envisions a psychology that extends from individual cognitions to societal structures. In addition to the citation, a biography and selected…

  16. A Conceptual and Psychometric Framework for Distinguishing Categories and Dimensions

    ERIC Educational Resources Information Center

    De Boeck, Paul; Wilson, Mark; Acton, G. Scott

    2005-01-01

    An important, sometimes controversial feature of all psychological phenomena is whether they are categorical or dimensional. A conceptual and psychometric framework is described for distinguishing whether the latent structure behind manifest categories (e.g., psychiatric diagnoses, attitude groups, or stages of development) is category-like or…

  17. A Tribute to My Ag Teacher: 2011 AAAE Distinguished Lecture

    ERIC Educational Resources Information Center

    Barrick, R. Kirby

    2012-01-01

    The author is a product of school-based agricultural education. In a way, this distinguished lecture could also be called a tribute to his high school ag teacher, John Stimpert. Mr. Stimpert was a true professional and an excellent teacher. He changed and he changed the program with the changing school and community. The more the author became…

  18. Award for Distinguished Scientific Applications of Psychology: Nancy E. Adler

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Nancy E. Adler, winner of the Award for Distinguished Scientific Applications of Psychology, is cited for her research on reproductive health examining adolescent decision making with regard to contraception, conscious and preconscious motivations for pregnancy, and perception of risk for sexually transmitted diseases, and for her groundbreaking…

  19. Elliptic cylinder geometry for distinguishability analysis in impedance tomography.

    PubMed

    Saka, Birsen; Yilmaz, Atila

    2004-01-01

    Electrical impedance tomography (EIT) is a technique that computes the cross-sectional impedance distribution within the body by using current and voltage measurements made on the body surface. It has been reported that the image reconstruction is distorted considerably when the boundary shape is considered to be more elliptical than circular as a more realistic shape for the measurement boundary. This paper describes an alternative framework for determining the distinguishability region with a finite measurement precision for different conductivity distributions in a body modeled by elliptic cylinder geometry. The distinguishable regions are compared in terms of modeling error for predefined inhomogeneities with elliptical and circular approaches for a noncircular measurement boundary at the body surface. Since most objects investigated by EIT are noncircular in shape, the analytical solution for the forward problem for the elliptical cross section approach is shown to be useful in order to reach a better assessment of the distinguishability region defined in a noncircular boundary. This paper is concentrated on centered elliptic inhomogeneity in the elliptical boundary and an analytic solution for this type of forward problem. The distinguishability performance of elliptical cross section with cosine injected current patterns is examined for different parameters of elliptical geometry. PMID:14723501

  20. 32 CFR 22.205 - Distinguishing assistance from procurement.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... research and development, the appropriate use of grants and cooperative agreements therefore is almost exclusively limited to the performance of selected basic, applied, and advanced research projects. Development... 32 National Defense 1 2013-07-01 2013-07-01 false Distinguishing assistance from procurement....

  1. 32 CFR 22.205 - Distinguishing assistance from procurement.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... research and development, the appropriate use of grants and cooperative agreements therefore is almost exclusively limited to the performance of selected basic, applied, and advanced research projects. Development... 32 National Defense 1 2014-07-01 2014-07-01 false Distinguishing assistance from procurement....

  2. 32 CFR 22.205 - Distinguishing assistance from procurement.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... research and development, the appropriate use of grants and cooperative agreements therefore is almost exclusively limited to the performance of selected basic, applied, and advanced research projects. Development... 32 National Defense 1 2012-07-01 2012-07-01 false Distinguishing assistance from procurement....

  3. 32 CFR 22.205 - Distinguishing assistance from procurement.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... research and development, the appropriate use of grants and cooperative agreements therefore is almost exclusively limited to the performance of selected basic, applied, and advanced research projects. Development... 32 National Defense 1 2011-07-01 2011-07-01 false Distinguishing assistance from procurement....

  4. Bifunctional mesoporous silicas with clearly distinguished localization of grafted groups

    NASA Astrophysics Data System (ADS)

    Roik, N. V.; Belyakova, L. A.

    2013-12-01

    Bifunctional mesoporous silicas with clearly distinguished localization of grafted groups on the surface of particles and inside their pores were obtained by means of sol-gel synthesis with postsynthetic vapor-phase treatment in vacuum. It was found that the synthesized materials have the hexagonally ordered porous structure typical of MCM-41 type silica.

  5. Optimal amount of entanglement to distinguish quantum states instantaneously

    NASA Astrophysics Data System (ADS)

    Groisman, Berry; Strelchuk, Sergii

    2015-11-01

    We introduce an aspect of nonlocality which arises when the task of quantum states distinguishability is considered under local operations and shared entanglement in the absence of classical communication. We find the optimal amount of entanglement required to accomplish the task perfectly for sets of orthogonal states and argue that it quantifies information nonlocality.

  6. Recent Detrimental and Distinguished Books about Hispanic People and Cultures.

    ERIC Educational Resources Information Center

    Schon, Isabel

    1981-01-01

    The article discusses nine detrimental and six distinguished books about Hispanic people and cultures, published since 1979 for young readers. It is suggested that many recent books that depict Hispanic people and cultures repeat the same stereotypes, misconceptions and insensibilities that were prevalent in books published in the 1960s and early…

  7. Distinguishing Schemes and Tasks in Children's Development of Multiplicative Reasoning

    ERIC Educational Resources Information Center

    Tzur, Ron; Johnson, Heather L.; McClintock, Evan; Kenney, Rachael H.; Xin, Yan P.; Si, Luo; Woordward, Jerry; Hord, Casey; Jin, Xianyan

    2013-01-01

    We present a synthesis of findings from constructivist teaching experiments regarding six schemes children construct for reasoning multiplicatively and tasks to promote them. We provide a task-generating platform game, depictions of each scheme, and supporting tasks. Tasks must be distinguished from children's thinking, and learning situations…

  8. Michael J. Meaney: Award for Distinguished Scientific Contributions

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents Michael J. Meaney as one of the winners of the American Psychological Association's Award for Distinguished Scientific Contributions (2012). Michael J. Meaney has taken the phenomenon of "handling" of newborn rats and opened a new area of investigation that has given new meaning to epigenetics via his work demonstrating transgenerational…

  9. Martin E. P. Seligman: 2006 award for distinguished scientific contributions.

    PubMed

    2006-11-01

    Presents the citation for Martin E. P. Seligman, who received the Award for Distinguished Scientific Contributions "for a career spent charging creatively ahead of his field and then pulling his colleagues along." A brief profile and a selected bibliography, as well as the award address, Positive Psychotherapy, accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115809

  10. Marcia K. Johnson: 2006 award for distinguished scientific contributions.

    PubMed

    2006-11-01

    Presents the citation to Marcia K. Johnson, who received the Award for Distinguished Scientific Contributions "for raising and illuminating fundamental questions about the cognitive and neural processes that constitute the subjective experience of mental life." A brief profile and a selected bibliography, as well as Johnson's award address, entitled Memory and Reality, accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115807

  11. John P. Campbell: award for distinguished scientific applications of psychology.

    PubMed

    2006-11-01

    Presents the citation for John P. Campbell who received Award for Distinguished Scientific Applications of Psychology "for his many different contributions to the field of industrial and organizational (I/O) psychology." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115812

  12. Kelly D. Brownell: Award for Distinguished Scientific Applications of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of Kelly D. Brownwell, winner of the American Psychological Association's Award for Distinguished Scientific Applications of Psychology (2012). He won the award for outstanding contributions to our understanding of the etiology and management of obesity and the crisis it poses for the modern world. A seminal thinker in…

  13. Survival of Mycobacterium avium subsp. paratuberculosis in bovine monocyte-derived macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Johne’s disease is a significant problem in many North American cattle herds. The efficacy of currently available vaccines is questionable. There is a need to develop efficacious vaccines and strains of Mycobacterium avium subsp. paratuberculosis (MAPTB) that could serve as potential candidates for ...

  14. Exposure to Bacillus anthracis Capsule Results in Suppression of Human Monocyte-Derived Dendritic Cells

    PubMed Central

    Chabot, Donald J.; Bozue, Joel A.; Tobery, Steven A.; West, Michael W.; Moody, Krishna; Yang, De; Oppenheim, Joost J.

    2014-01-01

    The antiphagocytic capsule of Bacillus anthracis is a major virulence factor. We hypothesized that it may also mediate virulence through inhibition of the host's immune responses. During an infection, the capsule exists attached to the bacterial surface but also free in the host tissues. We sought to examine the impact of free capsule by assessing its effects on human monocytes and immature dendritic cells (iDCs). Human monocytes were differentiated into iDCs by interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) over 7 days in the presence of capsule derived from wild-type encapsulated B. anthracis Ames (WT) or a control preparation from an isogenic B. anthracis Ames strain that produces only 2% of the capsule of the WT (capA mutant). WT capsule consistently induced release of IL-8 and IL-6 while the capA mutant control preparation elicited either no response or only a minimal release of IL-8. iDCs that were differentiated in the presence of WT capsule had increased side scatter (SSC), a measure of cellular complexity, when assessed by flow cytometry. iDCs differentiated in the presence of WT capsule also matured less well in response to subsequent B. anthracis peptidoglycan (Ba PGN) exposure, with reduced upregulation of the chemokine receptor CCR7, reduced CCR7-dependent chemotaxis, and reduced release of certain cytokines. Exposure of naive differentiated control iDCs to WT capsule did not alter cell surface marker expression but did elicit IL-8. These results indicate that free capsule may contribute to the pathogenesis of anthrax by suppressing the responses of immune cells and interfering with the maturation of iDCs. PMID:24891109

  15. Human SOCS1 Controls Immunostimulatory Activity of Monocyte-derived Dendritic Cells

    PubMed Central

    Hong, Bangxing; Ren, Wenhong; Song, Xiao-Tong; Evel-Kabler, Kevin; Chen, Si-Yi; Huang, Xue F

    2009-01-01

    Dendritic cell (DC)-based tumor vaccines have only achieved limited clinical efficacy, underscoring the limitation of stimulatory strategies to elicit effective cytotoxic T lymphocyte (CTL) responses against self tumor-associated antigens. Here we investigate the role of human suppressor of cytokine signaling (SOCS) 1, a feedback inhibitor of the JAK/STAT signaling pathway, in regulating antigen presentation by human DCs. We find that human SOCS1-silenced DCs have an enhanced stimulatory ability to prime self antigen-specific CTLs in vitro and in an SCID-hu mouse model. Human CTLs activated by SOCS1-silenced DCs, but not wild-type DCs, have an active lytic activity to natural antigen-expressing tumor cells. We further find that the capacity of human DCs to prime CTLs is likely controlled by SOCS1 restricted production and signaling of proinflammatory cytokines such as IL-12. These results indicate a critical role of human SOCS1 in negatively regulating the immunostimulatory capacity of DCs and imply a translational potential of this alternative, SOCS1 silencing strategy to develop effective DC vaccines. PMID:19789342

  16. The effect of human immunodeficiency virus-1 on monocyte-derived dendritic cell maturation and function

    PubMed Central

    Fairman, P; Angel, J B

    2012-01-01

    Dendritic cells (DC) are mediators of the adaptive immune response responsible for antigen presentation to naive T cells in secondary lymph organs. Human immunodeficiency virus (HIV-1) has been reported to inhibit the maturation of DC, but a clear link between maturation and function has not been elucidated. To understand further the effects of HIV-1 on DC maturation and function, we expanded upon previous investigations and assessed the effects of HIV-1 infection on the expression of surface molecules, carbohydrate endocytosis, antigen presentation and lipopolysaccharide (LPS) responsiveness over the course of maturation. In vitro infection with HIV-1 resulted in an increase in the expression of DC-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) as well as decreases in maturation-induced CCR7 and major histocompatibility complex (MHC)-II expression. Retention of endocytosis that normally occurs with DC maturation as well as inhibition of antigen presentation to CD8+ T cells was also observed. Mitogen-activated protein kinase (MAPK) responsiveness to LPS as measured by phosphorylation of p38, c-Jun N-terminal kinase (JNK) and extracellular-regulated kinase (ERK)1/2 was not affected by HIV-1 infection. In summary, in-vitro HIV-1 impairs DC maturation, as defined by cell surface protein expression, with selective alterations in mature DC function. Understanding the mechanisms of DC dysfunction in HIV infection will provide further insight into HIV immune pathogenesis. PMID:22943206

  17. Characterization of the porcine monocyte-derived cell lines Cdelta2- and Cdelta2+

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cell lines Cdelta2- and Cdelta2+ were developed from monocytes obtained from a 10-month-old, crossbred, female pig at the U.S. Meat Animal Research Center, Clay Center, NE. These cells have macrophage morphology, stain positively for alpha-naphthyl esterase and negatively for peroxidase. Additiona...

  18. Combination strategies to enhance the potency of monocyte-derived dendritic cell-based cancer vaccines.

    PubMed

    Fecek, Ronald J; Storkus, Walter J

    2016-10-01

    Dendritic cells (DCs) are potent inducers of adaptive immunity and their clinical use in cancer vaccine formulations remains an area of active translational and clinical investigation. Although cancer vaccines applied as monotherapies have had a modest history of clinical success, there is great enthusiasm for novel therapeutic strategies combining DC-based cancer vaccines with agents that 'normalize' immune function in the tumor microenvironment (TME). Broadly, these combination vaccines are designed to antagonize/remove immunosuppressive networks within the TME that serve to limit the antitumor action of vaccine-induced T cells and/or to condition the TME to facilitate the recruitment and optimal function and durability of vaccine-induced T cells. Such combination regimens are expected to dramatically enhance the clinical potency of DC-based cancer vaccine platforms. PMID:27605069

  19. Radiation effects on cultured human monocytes and on monocyte-derived macrophages

    SciTech Connect

    Buescher, E.S.; Gallin, J.I.

    1984-06-01

    Prior to administration, leukocyte transfusions are commonly irradiated with up to 5,000 R to eliminate lymphocytes and thereby prevent graft-versus-host disease in the recipient. It has been widely believed that phagocytes are resistant to this irradiation. In a recent report, it was noted that phagocyte oxidative metabolism was compromised during preparation of white cells for transfusion. As part of the effort to examine the basis for this inhibition of phagocyte function during white cell preparation, an assessment was made of the effects of irradiation on the long-lived monocytes that have been shown to persist at inflammatory foci posttransfusion. Human monocytes were irradiated for up to 3 min, receiving 2,500-5,000 R. This irradiation damaged human monocytes, significantly decreasing their in vitro survival for the first 3 wk of culture, and growth as assessed by two-dimensional cell size measurements during the first 2 wk of culture. Despite smaller cell size, total cell protein was significantly increased over time in irradiated cultures. Extracellular release of lysozyme and beta-glucuronidase per cell was not affected by irradiation, but extracellular lactate dehydrogenase (LDH) release was significantly increased after irradiation. Irradiated monocytes killed Listeria monocytogenes at a slower rate than the nonirradiated controls. Thus, the data indicate that irradiation in doses used to prevent graft-versus-host disease in leukocyte transfusion recipients has a deleterious effect on in vitro human monocyte survival and function.

  20. Development and characterization of two porcine monocyte-derived macrophage cell lines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cell lines Cdelta2+ and Cdelta2- were developed from monocytes obtained from a 10-month-old, crossbred, female pig. These cells morphologically resembled macrophages, stained positively for a-naphthyl esterase and negatively for peroxidase. The cell lines were bactericidal and highly phagocytic. ...

  1. Responsiveness of human monocyte-derived dendritic cells to thimerosal and mercury derivatives

    SciTech Connect

    Migdal, C.; Tailhardat, M.; Courtellemont, P.; Haftek, M.; Serres, M.

    2010-07-15

    Several cases of skin sensitization have been reported following the application of thimerosal, which is composed of ethyl mercury and thiosalicylic acid (TSA). However, few in vitro studies have been carried out on human dendritic cells (DCs) which play an essential role in the initiation of allergic contact dermatitis. The aim of the present study was to identify the effect of thimerosal and other mercury compounds on human DCs. To address this purpose, DCs derived from monocytes (mono-DCs) were used. Data show that thimerosal and mercury derivatives induced DC activation, as monitored by CD86 and HLA-DR overexpression associated with the secretion of tumor necrosis factor {alpha} and interleukin 8, similarly to lipopolysaccharide and the sensitizers, 1-chloro-2,4-dinitrobenzene (DNCB) and nickel sulfate, which were used as positive controls. In contrast, TSA, the non-mercury part of thimerosal, as well as dichloronitrobenzene, a DNCB negative control, and the irritant, sodium dodecyl sulfate, had no effect. Moreover, oxidative stress, monitored by ROS induction and depolarization of the mitochondrial membrane potential, was induced by thimerosal and mercury compounds, as well as DNCB, in comparison with hydrogen peroxide, used as a positive control. The role of thiol oxidation in the initiation of mono-DC activation was confirmed by a pre-treatment with N-acetyl-L-cysteine which strongly decreased chemical-induced CD86 overexpression. These data are in agreement with several clinical observations of the high relevance of thimerosal in patch-test reactions and prove that human mono-DCs are useful in vitro tools for determining the allergenic potency of chemicals.

  2. Chrysin suppresses human CD14(+) monocyte-derived dendritic cells and ameliorates experimental autoimmune encephalomyelitis.

    PubMed

    Zhang, Kai; Ge, Zhenzhen; Xue, Zhenyi; Huang, Wenjing; Mei, Mei; Zhang, Qi; Li, Yan; Li, Wen; Zhang, Zhihui; Zhang, Zimu; Zhang, Lijuan; Wang, Huafeng; Cai, Jinzhen; Yao, Zhi; Zhang, Rongxin; Da, Yurong

    2015-11-15

    Chrysin, a naturally flavonoid of plant, has various biological activities. However, the effects of chrysin on dendritic cells (DCs) and multiple sclerosis (MS) remain unknown. In this study, we demonstrate that chrysin inhibited human DC differentiation, maturation, function and the expression of the Th1 cells polarizing cytokines IFN-γ and IL-12p35 form DCs. In addition, chrysin ameliorated experimental autoimmune encephalomyelitis (EAE), an animal model of MS, by reducing CNS inflammation and demyelination. Furthermore, chrysin suppressed DCs and Th1 cells in the EAE mice. Taken together, chrysin exerts anti-inflammatory and immune suppressive effects, and suggests a possible therapeutic application of chrysin in MS. PMID:26531689

  3. Multiscale entropy to distinguish physiologic and synthetic RR time series.

    PubMed

    Costa, M; Goldberger, A L; Peng, C-K

    2002-01-01

    We address the challenge of distinguishing physiologic interbeat interval time series from those generated by synthetic algorithms via a newly developed multiscale entropy method. Traditional measures of time series complexity only quantify the degree of regularity on a single time scale. However, many physiologic variables, such as heart rate, fluctuate in a very complex manner and present correlations over multiple time scales. We have proposed a new method to calculate multiscale entropy from complex signals. In order to distinguish between physiologic and synthetic time series, we first applied the method to a learning set of RR time series derived from healthy subjects. We empirically established selected criteria characterizing the entropy dependence on scale factor for these datasets. We then applied this algorithm to the CinC 2002 test datasets. Using only the multiscale entropy method, we correctly classified 48 of 50 (96%) time series. In combination with Fourier spectral analysis, we correctly classified all time series. PMID:14686448

  4. Pores with longitudinal irregularities distinguish objects by shape.

    PubMed

    Qiu, Yinghua; Hinkle, Preston; Yang, Crystal; Bakker, Henriette E; Schiel, Matthew; Wang, Hong; Melnikov, Dmitriy; Gracheva, Maria; Toimil-Molares, Maria Eugenia; Imhof, Arnout; Siwy, Zuzanna S

    2015-04-28

    The resistive-pulse technique has been used to detect and size objects which pass through a single pore. The amplitude of the ion current change observed when a particle is in the pore is correlated with the particle volume. Up to date, however, the resistive-pulse approach has not been able to distinguish between objects of similar volume but different shapes. In this manuscript, we propose using pores with longitudinal irregularities as a sensitive tool capable of distinguishing spherical and rod-shaped particles with different lengths. The ion current modulations within resulting resistive pulses carry information on the length of passing objects. The performed experiments also indicate the rods rotate while translocating, and displace an effective volume that is larger than their geometrical volume, and which also depends on the pore diameter. PMID:25787224

  5. Improving text recognition by distinguishing scene and overlay text

    NASA Astrophysics Data System (ADS)

    Quehl, Bernhard; Yang, Haojin; Sack, Harald

    2015-02-01

    Video texts are closely related to the content of a video. They provide a valuable source for indexing and interpretation of video data. Text detection and recognition task in images or videos typically distinguished between overlay and scene text. Overlay text is artificially superimposed on the image at the time of editing and scene text is text captured by the recording system. Typically, OCR systems are specialized on one kind of text type. However, in video images both types of text can be found. In this paper, we propose a method to automatically distinguish between overlay and scene text to dynamically control and optimize post processing steps following text detection. Based on a feature combination a Support Vector Machine (SVM) is trained to classify scene and overlay text. We show how this distinction in overlay and scene text improves the word recognition rate. Accuracy of the proposed methods has been evaluated by using publicly available test data sets.

  6. Michael E. Lamb: Award for Distinguished Scientific Applications of Psychology.

    PubMed

    2015-11-01

    The APA Award for Distinguished Scientific Applications of Psychology is presented to a person who, in the opinion of the Committee on Scientific Awards, has made distinguished theoretical or empirical advances leading to the understanding or amelioration of important practical problems. The 2015 recipient is Michael E. Lamb, who "has significantly advanced understanding of the developmental and contextual factors affecting the delivery and impact of child care in the early years of life; the role of parent-child relationships in development; and the cognitive, emotional, and social factors affecting the quality of children's testimony, especially in cases of sexual and physical abuse." award citation, biography, and a selected bibliography are presented here. PMID:26618945

  7. Primary structure -- An important concept to distinguish primary stresses

    SciTech Connect

    Lu Mingwan |; Li Jianguo

    1996-12-01

    A new Chinese design code JB 4732-95, Steel Pressure Vessels -- Design by Analysis, was issued in March 1995. In this paper the authors discuss some concepts and ideas which formed in the introduction and application of the design by analysis approach in China. They are: multi-possibility of stress decomposition, self-limiting stress, classification of constraints, and finally an important concept to distinguish primary stress -- primary structures.

  8. Criteria for two distinguishable fermions to form a boson

    SciTech Connect

    Ramanathan, Ravishankar; Chuan, Tan Kok; Kurzynski, Pawel; Santos, Marcelo F.; Kaszlikowski, Dagomir

    2011-09-15

    We study the necessary conditions for systems composed of two distinguishable fermions to exhibit bosonic behavior. We base our analysis on tools of quantum information theory such as entanglement, local operations and classical communication and the majorization criterion for probability distributions. Introduction of these tools yields new insights into the old and important problem of identifying the conditions for existence of composite bosons. We precisely identify the role entanglement plays in the formation and behavior of such composite particles.

  9. The TCICA Test for Distinguishing Primary and Secondary Alcohols

    NASA Astrophysics Data System (ADS)

    Hiegel, Gene A.; Chaharmohal, Afshin K.

    1997-04-01

    Simple primary and secondary alcohols can easily be distinguished by their rate of oxidation with trichloroisocyanuric acid (TCICA).1,2 The TCICA test is conducted by adding the unknown to a solution of TCICA in acetonitrile3 containing hydrochloric acid4 and measuring the time for a precipitate5 to form. Primary alcohols react slowly and secondary alcohols react rapidly. To generate comparison data for primary and secondary alcohols, tests should be first carried out using ethanol and 2-propanol.6

  10. Michael Davis: 2006 award for distinguished scientific contributions.

    PubMed

    2006-11-01

    Presents the citation for Michael Davis, who received the Award for Distinguished Scientific Contributions "for his major discoveries about the brain circuits underlying basic aspects of behavioral plasticity and learning." A brief profile and a selected bibliography, as well as Davis' award address, entitled Neural Systems Involved in Fear and Anxiety Measured With Fear-Potentiated Startle, accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115805

  11. Complementarity and path distinguishability: Some recent results concerning photon pairs

    NASA Technical Reports Server (NTRS)

    Shimony, Abner; Jaeger, Gregg

    1994-01-01

    Two results concerning photon pairs, one previously reported and one new, are summarized. It was previously shown that if the two photons are prepared in a quantum state formed from bar-A and bar-A' for photon 1 and bar-B and bar-B' for photon 2, then both one- and two-particle interferometry can be studied. If upsilon(sub i) is the visibility of one-photon interference fringes (i = 1,2) and upsilon(sub 12) is the visibility of two-photon fringes (a concept which we explicitly define), then upsilon(sub i) squared + upsilon(sub 12) squared is less than or equal to 1. The second result concerns the distinguishability of the paths of photon 2, using the known 2-photon state. A proposed measure E for path distinguishability is based upon finding an optimum strategy for betting on the outcome of a path measurement. Mandel has also proposed a measure of distinguishability P(sub D), defined in terms of the density operator rho of photon 2. We show that E is greater than or equal to P(sub D) and that upsilon(sub 2) = (1 - E(exp 2))exp 1/2.

  12. Reversible or not? Distinguishing agglomeration and aggregation at the nanoscale.

    PubMed

    Sokolov, Stanislav V; Tschulik, Kristina; Batchelor-McAuley, Christopher; Jurkschat, Kerstin; Compton, Richard G

    2015-10-01

    Nanoparticles are prone to clustering either via aggregation (irreversible) or agglomeration (reversible) processes. It is exceedingly difficult to distinguish the two via conventional techniques such as dynamic light scattering (DLS), nanoparticle tracking analysis (NTA), or electron microscopy imaging (scanning electron microscopy (SEM), transmission electron microscopy (TEM)) as such techniques only generally confirm the presence of large particle clusters. Herein we develop a joint approach to tackle the issue of distinguishing between nanoparticle aggregation vs agglomeration by characterizing a colloidal system of Ag NPs using DLS, NTA, SEM imaging and the electrochemical nanoimpacts technique. In contrast to the conventional techniques which all reveal the presence of large clusters of particles, electrochemical nanoimpacts provide information regarding individual nanoparticles in the solution phase and reveal the presence of small nanoparticles (<30 nm) even in high ionic strength (above 0.5 M KCl) and allow a more complete analysis. The detection of small nanoparticles in high ionic strength media evidence the clustering to be a reversible process. As a result it is concluded that agglomeration rather than irreversible aggregation takes place. This observation is of general importance for all colloids as it provides a feasible analysis technique for a wide range of systems with an ability to distinguish subtly different processes. PMID:26352558

  13. Identifying Distinguishing Characteristics of Secondary Pyroclastic Density Currents

    NASA Astrophysics Data System (ADS)

    Isom, S. L.; Brand, B. D.

    2014-12-01

    Pyroclastic density currents (PDCs) are ground-hugging mixtures of volcanic particles and gas that travel down the slopes of erupting volcanoes. The combination of high velocities, high bulk densities (due to particles in the current) and high temperatures make PDCs the most dangerous and deadly hazard associated with explosive volcanism. Secondary explosive phenomenon associated with PDCs, such as inland-directed surges (e.g., Montserrat, 2003) and phreatic explosions (e.g., Mt St Helens 1980) can increase the area affected and duration of the hazard. However, little work has been done on distinguishing the deposits of secondary explosive phenomenon from primary phenomenon. Samples have been acquired from the 1980 Mt St Helens phreatic explosion crater deposits and the 2003 eruptive event at Montserrat where a PDC flowed into the ocean, causing an inland-directed surge (Edmonds and Herd, 2005. Geology 33.4:245-248). The samples will be analyzed via depositional characteristics, granulometry, componentry, microscopic analysis and scanning electron microscope imaging. We hypothesize that thermal cracking or vesicle distortion (e.g., compression or hindered expansion) may occur in hot pyroclasts that enter a body of water, leading to a difference between the ash textures of primary PDCs, phreatic surges and inland-directed surge deposits. Analyzing granulometry and componentry from parent flows and secondary flows may also reveal distinguishing characteristics that will allow us to constrain differences in segregation mechanisms of particles for each phenomenon. Determining distinguishing depositional characteristics of these secondary phenomena is important for assessing their occurrence during past eruptions and identifying conditions conducive to the formation of secondary explosions. This will result in the ability to make more accurate hazard maps for volcanoes prone to explosive activity.

  14. Ratios of Biogenic Elements for Distinguishing Recent from Fossil Microorganisms

    NASA Technical Reports Server (NTRS)

    Hoover, Richard B.

    2007-01-01

    The ability to distinguish possible microfossils from recent biological contaminants is of great importance to Astrobiology. In this paper we discuss the application of the ratios of life critical biogenic elements (C/O; C/N; and C/S) as determined by Energy Dispersive X-ray Spectroscopy (EDS) to this problem. Biogenic element ratios will be provided for a wide variety of living cyanobacteria and other microbial extremophiles, preserved herbarium materials, and ancient biota from the Antarctic Ice Cores and Siberian and Alaskan Permafrost for comparison with megafossils and microfossils in ancient terrestrial rocks and carbonaceous meteorites.

  15. HIC1 Expression Distinguishes Intestinal Carcinomas Sensitive to Chemotherapy12

    PubMed Central

    Janeckova, Lucie; Kolar, Michal; Svec, Jiri; Lanikova, Lucie; Pospichalova, Vendula; Baloghova, Nikol; Vojtechova, Martina; Sloncova, Eva; Strnad, Hynek; Korinek, Vladimir

    2016-01-01

    Neoplastic growth is frequently associated with genomic DNA methylation that causes transcriptional silencing of tumor suppressor genes. We used a collection of colorectal polyps and carcinomas in combination with bioinformatics analysis of large datasets to study the expression and methylation of Hypermethylated in cancer 1 (HIC1), a tumor suppressor gene inactivated in many neoplasms. In premalignant stages, HIC1 expression was decreased, and the decrease was linked to methylation of a specific region in the HIC1 locus. However, in carcinomas, the HIC1 expression was variable and, in some specimens, comparable to healthy tissue. Importantly, high HIC1 production distinguished a specific type of chemotherapy-responsive tumors. PMID:27084425

  16. Distinguishing Between Supra-Arcade Downflows and Plasmoids

    NASA Technical Reports Server (NTRS)

    Savage, Sabrina

    2014-01-01

    Supra-arcade downflows (SADs) observed above flaring active regions during long-duration events are theorized to be signatures of magnetic reconnection. Observations of SADs strongly indicate an association with shrinking reconnected flux tubes characterized by a specific magnetic topology. Plasmoids comprise another proposed group of observational reconnection signatures. While some plasmoids occur under nearly the same conditions as SADs, the magnetic configuration of the two phenomena are quite incongruous, yet they are often categorized together. We present distinguishing characteristics between SADs and plasmoids and indicate how their respective observations may yield insight into the conditions within the current sheet above eruptive active regions.

  17. Ratios of biogenic elements for distinguishing recent from fossil microorganisms

    NASA Astrophysics Data System (ADS)

    Hoover, Richard B.

    2007-09-01

    The ability to distinguish possible microfossils from recent biological contaminants is of great importance to Astrobiology. In this paper we discuss the application of the ratios of life critical biogenic elements (C/O; C/N; and C/S) as determined by Energy Dispersive X-ray Spectroscopy (EDS) to this problem. Biogenic element ratios are provided for a wide variety of living cyanobacteria and other microbial extremophiles, preserved herbarium materials, and ancient biota from the Antarctic Ice Cores and Siberian and Alaskan Permafrost for comparison with macrofossils and microfossils in ancient terrestrial rocks and carbonaceous meteorites.

  18. Distinguishing Cancerous Liver Cells Using Surface-Enhanced Raman Spectroscopy.

    PubMed

    Huang, Jing; Liu, Shupeng; Chen, Zhenyi; Chen, Na; Pang, Fufei; Wang, Tingyun

    2016-02-01

    Raman spectroscopy has been widely used in biomedical research and clinical diagnostics. It possesses great potential for the analysis of biochemical processes in cell studies. In this article, the surface-enhanced Raman spectroscopy (SERS) of normal and cancerous liver cells incubated with SERS active substrates (gold nanoparticle) was measured using confocal Raman microspectroscopy technology. The chemical components of the cells were analyzed through statistical methods for the SERS spectrum. Both the relative intensity ratio and principal component analysis (PCA) were used for distinguishing the normal liver cells (QSG-7701) from the hepatoma cells (SMMC-7721). The relative intensity ratio of the Raman spectra peaks such as I937/I1209, I1276/I1308, I1342/I1375, and I1402/I1435 was set as the judge boundary, and the sensitivity and the specificity using PCA method were calculated. The results indicated that the surface-enhanced Raman spectrum could provide the chemical information for distinguishing the normal cells from the cancerous liver cells and demonstrated that SERS technology possessed the possible applied potential for the diagnosis of liver cancer. PMID:25432931

  19. Methods to distinguish various types of protein phosphatase activity

    SciTech Connect

    Brautigan, D.L.; Shriner, C.L.

    1988-01-01

    To distinguish the action of protein Tyr(P) and protein Ser(P)/Thr(P) phosphatases on /sup 32/P-labeled phosphoproteins in subcellular fractions different inhibitors and activators are utilized. Comparison of the effects of added compounds provides a convenient, indirect method to characterize dephosphorylation reactions. Protein Tyr(P) phosphatases are specifically inhibited by micromolar Zn2+ or vanadate, and show maximal activity in the presence of EDTA. The other class of cellular phosphatases, specific for protein Ser(P) and Thr(P) residues, are inhibited by fluoride and EDTA. In this class of enzymes two major functional types can be distinguished: those sensitive to inhibition by the heat-stable protein inhibitor-2 and not stimulated by polycations, and those not sensitive to inhibition and stimulated by polycations. Preparation of /sup 32/P-labeled Tyr(P) and Ser(P) phosphoproteins also is presented for the direct measurement of phosphatase activities in preparations by the release of acid-soluble (/sup 32/P)phosphate.

  20. Distinguishing suspicious actions in long-distance surveillance

    NASA Astrophysics Data System (ADS)

    Hebe, Guy; Chen, Eli; Yitzhaky, Yitzhak

    2014-10-01

    Human action classification distinguishes different human behaviors at a video signal. Suspicious behavior can be defined by the user, and in long distance imaging it may include bending the body during walking or crawling, in contrast to regular walking for instance. When imaging is performed through relatively long distance, some difficulties occur which affect the performances regular action recognition tasks. The degradation sources that include turbulence and aerosols in the atmosphere cause blur and spatiotemporal-varying distortions (image dancing). These effects become more significant as the imaging distance increases and as the sizes of the objects of interest in the image are smaller. The process of action recognition is usually a part of surveillance system that naturally includes a detection of the moving objects as a first step, followed by tracking them in the video sequence. In this study, we first detect and track moving objects in long-distance horizontal imaging, and then we examine dynamic spatio-temporal (motion and shape) characteristics of correctly detected moving objects. According to such characteristics. We construct features that characterize different actions for such imaging conditions, and distinguish suspicious from non-suspicious actions, based on these characteristics.

  1. Closed time like curves enable perfect state distinguishability

    SciTech Connect

    Harrington, James William; Wilde, Mark M; Brun, Todd A

    2008-01-01

    The causal self-consistency condition for closed timelike curves can give rise to nonlinear interactions on chronology-respecting qubits. We demonstrate that particular unitary interactions between closed timelike curve qubits and chronology-respecting qubits allow perfect distinguishability of nonorthogonal states, and provide a constructive proof for an arbitrary number of nonorthogonal states. This has a number of highly significant consequences. For example, an adversary with access to closed timelike curves can break the B92, BB84, and SARG04 quantum key distribution protocols, or any prepare-and-measure quantum key distribution scheme. Our result also implies that a party with access to closed timelike curves can violate the Holevo bound by accessing more than log(N) bits of information from an N-dimensional quantum state. In principle, he can transmit an arbitrarily large amount of classical information with a quantum system of fixed size. We discuss the implications of this for quantum cloning.

  2. Asymptotic state discrimination and a strict hierarchy in distinguishability norms

    NASA Astrophysics Data System (ADS)

    Chitambar, Eric; Hsieh, Min-Hsiu

    2014-11-01

    In this paper, we consider the problem of discriminating quantum states by local operations and classical communication (LOCC) when an arbitrarily small amount of error is permitted. This paradigm is known as asymptotic state discrimination, and we derive necessary conditions for when two multipartite states of any size can be discriminated perfectly by asymptotic LOCC. We use this new criterion to prove a gap in the LOCC and separable distinguishability norms. We then turn to the operational advantage of using two-way classical communication over one-way communication in LOCC processing. With a simple two-qubit product state ensemble, we demonstrate a strict majorization of the two-way LOCC norm over the one-way norm.

  3. Distinguishing short and long Fermi gamma-ray bursts

    NASA Astrophysics Data System (ADS)

    Tarnopolski, M.

    2015-11-01

    Two classes of gamma-ray bursts (GRBs), short and long, have been determined without any doubts, and are usually ascribed to different progenitors, yet these classes overlap for a variety of descriptive parameters. A subsample of 46 long and 22 short Fermi GRBs with estimated Hurst Exponents (HEs), complemented by minimum variability time-scales (MVTS) and durations (T90) is used to perform a supervised machine learning and Monte Carlo simulation using a support vector machine algorithm. It is found that while T90 itself performs very well in distinguishing short and long GRBs, the overall success ratio is higher when the training set is complemented by MVTS and HE. These results may allow us to introduce a new (non-linear) parameter that might provide less ambiguous classification of GRBs.

  4. Distinguishing clonal apple rootstocks by isozymes banding patterns.

    PubMed

    Kaushal, K; Modgil, M; Sharma, D R

    2001-11-01

    Molecular characterisation of clonal apple rootstocks using isozymes was carried out to identify isozyme polymorphism in seven clonal apple rootstocks and to identify the most characteristic and stable enzyme markers for each individual rootstock. Five enzyme systems were studied out of which polyphenol oxidase, malate dehydrogenase, acid phosphatase and peroxidase were useful in discriminating among the rootstocks. The peroxidase enzyme system showed maximum variation and esterase showed the least variation among the rootstocks. Out of seven rootstocks, three were distinguished on the basis of one enzyme system only (M.3 with MDH or PER, M.7 with PPO or PER and MM. 111 with MDH). Out of the sixteen loci studied seven were found to be polymorphic. Genetic variation among the rootstocks was explained on the basis of various parameters. The percentage of polymorphic loci varied from 13.33 to 35.71 per cent. PMID:11906109

  5. Mathematically guided approaches to distinguish models of periodic patterning

    PubMed Central

    Hiscock, Tom W.; Megason, Sean G.

    2015-01-01

    How periodic patterns are generated is an open question. A number of mechanisms have been proposed – most famously, Turing's reaction-diffusion model. However, many theoretical and experimental studies focus on the Turing mechanism while ignoring other possible mechanisms. Here, we use a general model of periodic patterning to show that different types of mechanism (molecular, cellular, mechanical) can generate qualitatively similar final patterns. Observation of final patterns is therefore not sufficient to favour one mechanism over others. However, we propose that a mathematical approach can help to guide the design of experiments that can distinguish between different mechanisms, and illustrate the potential value of this approach with specific biological examples. PMID:25605777

  6. Chamber catalogues of optical and fluorescent signatures distinguish bioaerosol classes

    NASA Astrophysics Data System (ADS)

    Hernandez, Mark; Perring, Anne E.; McCabe, Kevin; Kok, Greg; Granger, Gary; Baumgardner, Darrel

    2016-07-01

    Rapid bioaerosol characterization has immediate applications in the military, environmental and public health sectors. Recent technological advances have facilitated single-particle detection of fluorescent aerosol in near real time; this leverages controlled ultraviolet exposures with single or multiple wavelengths, followed by the characterization of associated fluorescence. This type of ultraviolet induced fluorescence has been used to detect airborne microorganisms and their fragments in laboratory studies, and it has been extended to field studies that implicate bioaerosol to compose a substantial fraction of supermicron atmospheric particles. To enhance the information yield that new-generation fluorescence instruments can provide, we report the compilation of a referential aerobiological catalogue including more than 50 pure cultures of common airborne bacteria, fungi and pollens, recovered at water activity equilibrium in a mesoscale chamber (1 m3). This catalogue juxtaposes intrinsic optical properties and select bandwidths of fluorescence emissions, which manifest to clearly distinguish between major classes of airborne microbes and pollens.

  7. Dual-axes confocal reflectance microscope for distinguishing colonic neoplasia

    PubMed Central

    Liu, Jonathan T. C.; Mandella, Michael J.; Friedland, Shai; Soetikno, Roy; Crawford, James M.; Contag, Christopher H.; Kino, Gordon S.; Wang, Thomas D.

    2007-01-01

    A dual-axes confocal reflectance microscope has been developed that utilizes a narrowband laser at 1310 nm to achieve high axial resolution, image contrast, field of view, and tissue penetration for distinguishing among normal, hyperplastic, and dysplastic colonic mucosa ex vivo. Light is collected off-axis using a low numerical aperture objective to obtain vertical image sections, with 4- to 5-μm resolution, at tissue depths up to 610 μm. Post-objective scanning enables a large field of view (610 × 640 μm), and balanced-heterodyne detection provides sensitivity to collect vertical sections at one frame per second. System optics are optimized to effectively reject out-of-focus scattered light without use of a low-coherence gate. This design is scalable to millimeter dimensions, and the results demonstrate the potential for a miniature instrument to detect precancerous tissues, and hence to perform in vivo histopathology. PMID:17092168

  8. Distinguishing time-delayed causal interactions using convergent cross mapping

    PubMed Central

    Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

    2015-01-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

  9. Distinguishing fiction from non-fiction with complex networks

    NASA Astrophysics Data System (ADS)

    Larue, David M.; Carr, Lincoln D.; Jones, Linnea K.; Stevanak, Joe T.

    2014-03-01

    Complex Network Measures are applied to networks constructed from texts in English to demonstrate an initial viability in textual analysis. Texts from novels and short stories obtained from Project Gutenberg and news stories obtained from NPR are selected. Unique word stems in a text are used as nodes in an associated unweighted undirected network, with edges connecting words occurring within a certain number of words somewhere in the text. Various combinations of complex network measures are computed for each text's network. Fisher's Linear Discriminant analysis is used to build a parameter optimizing the ability to separate the texts according to their genre. Success rates in the 70% range for correctly distinguishing fiction from non-fiction were obtained using edges defined as within four words, using 400 word samples from 400 texts from each of the two genres with some combinations of measures such as the power-law exponents of degree distributions and clustering coefficients.

  10. Distinguishing between R2-inflation and Higgs-inflation

    NASA Astrophysics Data System (ADS)

    Bezrukov, F. L.; Gorbunov, D. S.

    2012-07-01

    We present three features which can be used to distinguish the R2-inflation Higgs-inflation from with ongoing, upcoming and planned experiments, assuming no new physics (apart form sterile neutrinos) up to inflationary scale. (i) Slightly different tilt of the scalar perturbation spectrum ns and ratio r of scalar-to-tensor perturbation amplitudes. (ii) Gravity waves produced within R2-model by collapsing, merging and evaporating scalaron clumps formed in the post-inflationary Universe. (iii) Different ranges of the possible Standard Model Higgs boson masses, where the electroweak vacuum remains stable while the Universe evolves after inflation. Specifically, in the R2-model Higgs boson can be as light as 116 GeV. These effects mainly rely on the lower reheating temperature in the R2-inflation.

  11. Asymptotic state discrimination and a strict hierarchy in distinguishability norms

    SciTech Connect

    Chitambar, Eric; Hsieh, Min-Hsiu

    2014-11-15

    In this paper, we consider the problem of discriminating quantum states by local operations and classical communication (LOCC) when an arbitrarily small amount of error is permitted. This paradigm is known as asymptotic state discrimination, and we derive necessary conditions for when two multipartite states of any size can be discriminated perfectly by asymptotic LOCC. We use this new criterion to prove a gap in the LOCC and separable distinguishability norms. We then turn to the operational advantage of using two-way classical communication over one-way communication in LOCC processing. With a simple two-qubit product state ensemble, we demonstrate a strict majorization of the two-way LOCC norm over the one-way norm.

  12. Distinguishing time-delayed causal interactions using convergent cross mapping.

    PubMed

    Ye, Hao; Deyle, Ethan R; Gilarranz, Luis J; Sugihara, George

    2015-01-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains. PMID:26435402

  13. Distinguishing time-delayed causal interactions using convergent cross mapping

    NASA Astrophysics Data System (ADS)

    Ye, Hao; Deyle, Ethan R.; Gilarranz, Luis J.; Sugihara, George

    2015-10-01

    An important problem across many scientific fields is the identification of causal effects from observational data alone. Recent methods (convergent cross mapping, CCM) have made substantial progress on this problem by applying the idea of nonlinear attractor reconstruction to time series data. Here, we expand upon the technique of CCM by explicitly considering time lags. Applying this extended method to representative examples (model simulations, a laboratory predator-prey experiment, temperature and greenhouse gas reconstructions from the Vostok ice core, and long-term ecological time series collected in the Southern California Bight), we demonstrate the ability to identify different time-delayed interactions, distinguish between synchrony induced by strong unidirectional-forcing and true bidirectional causality, and resolve transitive causal chains.

  14. Kelly D. Brownell: Award for Distinguished Scientific Applications of Psychology.

    PubMed

    2012-11-01

    Presents a short biography of Kelly D. Brownwell, winner of the American Psychological Association's Award for Distinguished Scientific Applications of Psychology (2012). He won the award for outstanding contributions to our understanding of the etiology and management of obesity and the crisis it poses for the modern world. A seminal thinker in the field, Kelly D. Brownell has been a persuasive proponent of the view that the surge in obesity is attributable to a 'toxic food environment' that includes easy access to abundant but energy-dense and aggressively marketed food. An exemplary leader, he has inspired students and colleagues alike through his tenacious advocacy of the social and behavioral sciences in the public interest. Brownwell's Award citation and a selected bibliography are also presented here. (PsycINFO Database Record (c) 2012 APA, all rights reserved). PMID:23163440

  15. Distinguishing high surf from volcanic long-period earthquakes

    NASA Astrophysics Data System (ADS)

    Lyons, John J.; Haney, Matthew M.; Fee, David; Paskievitch, John F.

    2014-02-01

    Repeating long-period (LP) earthquakes are observed at active volcanoes worldwide and are typically attributed to unsteady pressure fluctuations associated with fluid migration through the volcanic plumbing system. Nonvolcanic sources of LP signals include ice movement and glacial outburst floods, and the waveform characteristics and frequency content of these events often make them difficult to distinguish from volcanic LP events. We analyze seismic and infrasound data from an LP swarm recorded at Pagan volcano on 12-14 October 2013 and compare the results to ocean wave data from a nearby buoy. We demonstrate that although the events show strong similarity to volcanic LP signals, the events are not volcanic but due to intense surf generated by a passing typhoon. Seismo-acoustic methods allow for rapid distinction of volcanic LP signals from those generated by large surf and other sources, a critical task for volcano monitoring.

  16. A method for distinguishing between propagons, diffusions, and locons

    NASA Astrophysics Data System (ADS)

    Seyf, Hamid Reza; Henry, Asegun

    2016-07-01

    The majority of intuition on phonon transport has been derived from studies of homogenous crystalline solids, where the atomic composition and structure are periodic. For this specific class of materials, the solutions to the equations of motions for the atoms (in the harmonic limit) result in plane wave modulated velocity fields for the normal modes of vibration. However, it has been known for several decades that whenever a system lacks periodicity, either compositional or structural, the normal modes of vibration can still be determined (in the harmonic limit), but the solutions take on different characteristics and many modes may not be plane wave modulated. Previous work has classified the types of vibrations into three primary categories, namely, propagons, diffusions, and locons. One can use the participation ratio to distinguish locons, from propagons and diffusons, which measures the extent to which a mode is localized. However, distinguishing between propagons and diffusons has remained a challenge, since both are spatially delocalized. Here, we present a new method that quantifies the extent to which a mode's character corresponds to a propagating mode, e.g., exhibits plane wave modulation. This then allows for clear and quantitative distinctions between propagons and diffusons. By resolving this issue quantitatively, one can now automate the classification of modes for any arbitrary material or structure, subject to a single constraint that the atoms must vibrate stably around their respective equilibrium sites. Several example test cases are studied including crystalline silicon and germanium, crystalline silicon with different defect concentrations, as well as amorphous silicon, germanium, and silica.

  17. Using MT2 to distinguish dark matter stabilization symmetries

    NASA Astrophysics Data System (ADS)

    Agashe, Kaustubh; Kim, Doojin; Walker, Devin G. E.; Zhu, Lijun

    2011-09-01

    We examine the potential of using colliders to distinguish models with parity (Z2) stabilized dark matter (DM) from models in which the DM is stabilized by other symmetries, taking the latter to be a Z3 symmetry for illustration. The key observation is that a heavier mother particle charged under a Z3 stabilization symmetry can decay into one or two DM particles along with standard model particles. This can be contrasted with the decay of a mother particle charged under a parity symmetry; typically, only one DM particle appears in the decay chain. The arXiv:1003.0899 studied the distributions of visible invariant mass from the decay of a single such mother particle in order to highlight the resulting distinctive signatures of Z3 symmetry versus parity symmetry stabilized dark matter candidates. We now describe a complementary study which focuses on decay chains of the two mother particles which are necessarily present in these events. We also include in our analysis the missing energy/momentum in the event. For the Z3 symmetry stabilized mothers, the resulting inclusive final state can have two, three or four DM particles. In contrast, models with Z2 symmetry can have only two. We show that the shapes and edges of the distribution of MT2-type variables, along with ratio of the visible momentum/energy on the two sides of the event, are powerful in distinguishing these different scenarios. Finally we conclude by outlining future work which focuses on reducing combinatoric ambiguities from reconstructing multijet events. Increasing the reconstruction efficiency can allow better reconstruction of events with two or three dark matter candidates in the final state.

  18. Distinguishing cirrus cloud presence in autonomous lidar measurements

    NASA Astrophysics Data System (ADS)

    Campbell, J. R.; Vaughan, M. A.; Oo, M.; Holz, R. E.; Lewis, J. R.; Welton, E. J.

    2014-07-01

    Level 2 Cloud Aerosol Lidar with Orthogonal Polarization (CALIOP) satellite-based cloud datasets from 2012 are investigated for metrics that help distinguish the cirrus cloud presence of in autonomous lidar measurements, using temperatures, heights, optical depth and phase. A thermal threshold, proposed by Sassen and Campbell (2001; SC2001) for cloud top temperature Ttop ≤ -37 °C, is evaluated vs. CALIOP algorithms that identify ice-phase cloud layers alone using depolarized backscatter. Global mean cloud top heights (11.15 vs. 10.07 km a.m.s.l.), base heights (8.76 vs. 7.95 km a.m.s.l.), temperatures (-58.48 °C vs. -52.18 °C and -42.40 °C vs. -38.13 °C, respectively for tops and bases) and optical depths (1.18 vs. 1.23) reflect the sensitivity to these competing constraints. Over 99% of all Ttop ≤ -37 °C clouds are classified as ice by CALIOP Level 2 algorithms. Over 81% of all ice clouds correspond with Ttop ≤ -37 °C. For instruments lacking polarized measurements, and thus practical phase estimates, Ttop ≤ -37 °C proves stable for distinguishing cirrus, as opposed to the risks of glaciated liquid water cloud contamination occurring in a given sample from clouds identified at warmer temperatures. Uncertainties in temperature profiles use to collocate with lidar data (i.e., model reanalyses/sondes) may justifiably relax the Ttop ≤ -37 °C threshold to include warmer cases. The ambiguity of "warm" (Ttop > -37 °C) ice cloud genus cannot be reconciled completely with available measurements, however, conspicuously including phase. Cloud top heights and optical depths are evaluated as potential constraints, as functions of CALIOP-retrieved phase. However, these data provide, at best, additional constraint in regional samples, compared with temperature alone, and may exacerbate classification uncertainties overall globally.

  19. Distinguishing cirrus cloud presence in autonomous lidar measurements

    NASA Astrophysics Data System (ADS)

    Campbell, J. R.; Vaughan, M. A.; Oo, M.; Holz, R. E.; Lewis, J. R.; Welton, E. J.

    2015-01-01

    2012 Level-2 Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP) satellite-based cloud data sets are investigated for thresholds that distinguish the presence of cirrus clouds in autonomous lidar measurements, based on temperatures, heights, optical depth and phase. A thermal threshold, proposed by Sassen and Campbell (2001) for cloud top temperature Ttop ≤ -37 °C, is evaluated versus CALIOP algorithms that identify ice-phase cloud layers using polarized backscatter measurements. Derived global mean cloud top heights (11.15 vs. 10.07 km above mean sea level; a.m.s.l.), base heights (8.76 km a.m.s.l. vs. 7.95 km a.m.s.l.), temperatures (-58.48 °C vs. -52.18 °C and -42.40 °C vs. -38.13 °C, respectively, for tops and bases) and optical depths (1.18 vs. 1.23) reflect the sensitivity to this constraint. Over 99 % of all Ttop ≤ -37 °C clouds are classified as ice by CALIOP Level-2 algorithms. Over 81 % of all ice clouds correspond with Ttop ≤ -37 °C. For instruments lacking polarized measurements, and thus practical estimates of phase, Ttop ≤ -37 °C provides sufficient justification for distinguishing cirrus, as opposed to the risks of glaciated liquid-water cloud contamination occurring in a given sample from clouds identified at relatively "warm" (Ttop > -37 °C) temperatures. Although accounting for uncertainties in temperatures collocated with lidar data (i.e., model reanalyses/sondes) may justifiably relax the threshold to include warmer cases, the ambiguity of "warm" ice clouds cannot be fully reconciled with available measurements, conspicuously including phase. Cloud top heights and optical depths are investigated, and global distributions and frequencies derived, as functions of CALIOP-retrieved phase. These data provide little additional information, compared with temperature alone, and may exacerbate classification uncertainties overall.

  20. For Distinguished Public Service: Medical Library Association Honors FNLM and NIH MedlinePlus Magazine | NIH ...

    MedlinePlus

    ... page please turn Javascript on. For Distinguished Public Service: Medical Library Association Honors FNLM and NIH MedlinePlus ... Dr. Donald West King with the Distinguished Public Service Award at the MLA’s recent national conference. Let ...

  1. 78 FR 12329 - Distinguishing Medical Device Recalls From Product Enhancements; Reporting Requirements; Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-22

    ... HUMAN SERVICES Food and Drug Administration Distinguishing Medical Device Recalls From Product... Device Recalls From Product Enhancements; Reporting Requirements.'' This draft guidance intends to clarify for industry when a potential change to a device is a medical device recall, distinguish...

  2. Distinguishing Candida Species by β-N-Acetylhexosaminidase Activity

    PubMed Central

    Niimi, Kyoko; Shepherd, Maxwell G.; Cannon, Richard D.

    2001-01-01

    A variety of fungi produce the hydrolytic enzyme β-N-acetylhexosaminidase (HexNAcase), which can be readily detected in assays by using p-nitrophenyl-N-acetyl-β-d-glucosaminide as a substrate. In the present study we developed a microtiter plate-based HexNAcase assay for distinguishing Candida albicans and Candida dubliniensis strains from other yeast species. HexNAcase activity was detected in 89 of 92 (97%) C. albicans strains and 4 of 4 C. dubliniensis strains but not in 28 strains of eight other Candida species, 4 Saccharomyces cerevisiae strains, or 2 Cryptococcus neoformans strains. The HexNAcase activity in C. albicans and C. dubliniensis was strain specific. All except three clinical C. albicans isolates among the C. albicans strains tested produced enzyme activity within 24 h. These strains did produce enzyme activity, however, after a prolonged incubation period. For two of these atypical strains, genomic DNA at the C. albicans HEX1 gene locus, which encodes HexNAcase, showed nucleotide differences from the sequence of control strains. Among the other Candida species tested, only C. dubliniensis had a DNA sequence that hybridized with the HEX1 probe under low-stringency conditions. The microtiter plate-based assay used in the present study for the detection of HexNAcase activity is a simple, relatively inexpensive method useful for the presumptive identification of C. albicans and C. dubliniensis. PMID:11376040

  3. TRPA channels distinguish gravity sensing from hearing in Johnston's organ

    PubMed Central

    Sun, Yishan; Liu, Lei; Ben-Shahar, Yehuda; Jacobs, Julie S.; Eberl, Daniel F.; Welsh, Michael J.

    2009-01-01

    Although many animal species sense gravity for spatial orientation, the molecular bases remain uncertain. Therefore, we studied Drosophila melanogaster, which possess an inherent upward movement against gravity-negative geotaxis. Negative geotaxis requires Johnston's organ, a mechanosensory structure located in the antenna that also detects near-field sound. Because channels of the transient receptor potential (TRP) superfamily can contribute to mechanosensory signaling, we asked whether they are important for negative geotaxis. We identified distinct expression patterns for 5 TRP genes; the TRPV genes nanchung and inactive were present in most Johnston's organ neurons, the TRPN gene nompC and the TRPA gene painless were localized to 2 subpopulations of neurons, and the TRPA gene pyrexia was expressed in cap cells that may interact with the neurons. Likewise, mutating specific TRP genes produced distinct phenotypes, disrupting negative geotaxis (painless and pyrexia), hearing (nompC), or both (nanchung and inactive). Our genetic, physiological and behavioral data indicate that the sensory component of negative geotaxis involves multiple TRP genes. The results also distinguish between different mechanosensory modalities and set the stage for understanding how TRP channels contribute to mechanosensation. PMID:19666538

  4. Can we distinguish early dark energy from a cosmological constant?

    NASA Astrophysics Data System (ADS)

    Shi, Difu; Baugh, Carlton M.

    2016-04-01

    Early dark energy (EDE) models are a class of quintessence dark energy with a dynamically evolving scalar field which display a small but non-negligible amount of dark energy at the epoch of matter-radiation equality. Compared with a cosmological constant, the presence of dark energy at early times changes the cosmic expansion history and consequently the shape of the linear theory power spectrum and potentially other observables. We constrain the cosmological parameters in the EDE cosmology using recent measurements of the cosmic microwave background and baryon acoustic oscillations. The best-fitting models favour no EDE; here we consider extreme examples which are in mild tension with current observations in order to explore the observational consequences of a maximally allowed amount of EDE. We study the non-linear evolution of cosmic structure in EDE cosmologies using large volume N-body simulations. Many large-scale structure statistics are found to be very similar between the Λ cold dark matter (ΛCDM) and EDE models. We find that EDE cosmologies predict fewer massive halos in comparison to ΛCDM, particularly at high redshifts. The most promising way to distinguish EDE from ΛCDM is to measure the power spectrum on large scales, where differences of up to 15% are expected.

  5. Method for distinguishing multiple targets using time-reversal acoustics

    DOEpatents

    Berryman, James G.

    2004-06-29

    A method for distinguishing multiple targets using time-reversal acoustics. Time-reversal acoustics uses an iterative process to determine the optimum signal for locating a strongly reflecting target in a cluttered environment. An acoustic array sends a signal into a medium, and then receives the returned/reflected signal. This returned/reflected signal is then time-reversed and sent back into the medium again, and again, until the signal being sent and received is no longer changing. At that point, the array has isolated the largest eigenvalue/eigenvector combination and has effectively determined the location of a single target in the medium (the one that is most strongly reflecting). After the largest eigenvalue/eigenvector combination has been determined, to determine the location of other targets, instead of sending back the same signals, the method sends back these time reversed signals, but half of them will also be reversed in sign. There are various possibilities for choosing which half to do sign reversal. The most obvious choice is to reverse every other one in a linear array, or as in a checkerboard pattern in 2D. Then, a new send/receive, send-time reversed/receive iteration can proceed. Often, the first iteration in this sequence will be close to the desired signal from a second target. In some cases, orthogonalization procedures must be implemented to assure the returned signals are in fact orthogonal to the first eigenvector found.

  6. Distinguishing Intrapsychic From Interpersonal Motives in Psychological Theory and Research.

    PubMed

    Leary, Mark R; Raimi, Kaitlin Toner; Jongman-Sereno, Katrina P; Diebels, Kate J

    2015-07-01

    Many psychological phenomena have been explained primarily in terms of intrapsychic motives to maintain particular cognitive or affective states--such as motives for consistency, self-esteem, and authenticity--whereas other phenomena have been explained in terms of interpersonal motives to obtain tangible resources, reactions, or outcomes from other people. In this article, we describe and contrast intrapsychic and interpersonal motives, and we review evidence showing that these two distinct sets of motives are sometimes conflated and confused in ways that undermine the viability of motivational theories. Explanations that invoke motives to maintain certain intrapsychic states offer a dramatically different view of the psychological foundations of human behavior than those that posit motives to obtain desired interpersonal outcomes. Several phenomena are examined as exemplars of instances in which interpersonal and intrapsychic motives have been inadequately distinguished, if not directly confounded, including cognitive dissonance, the self-esteem motive, biases in judgment and decision making, posttransgression accounts, authenticity, and self-conscious emotions. Our analysis of the literature suggests that theorists and researchers should consider the relative importance of intrapsychic versus interpersonal motives in the phenomena they study and that they should make a concerted effort to deconfound intrapsychic and interpersonal influences in their research. PMID:26177950

  7. Distinguishing between microscale gaseous bubbles and liquid drops

    NASA Astrophysics Data System (ADS)

    Tan, Beng Hau; An, Hongjie; Chan, Chon U.; Ohl, Claus-Dieter

    2015-11-01

    In recent years, there has been strong research interest in decorating surfaces with tiny bubbles and drops due to their potential applications in reducing slippage in micro and nanofluidic devices. Both nanobubbles and nanodrops are typically nucleated by exchanging fluids over a suitable substrate. However, the nucleation experiments present many challenges, such as reproducibility and the possibility of contamination. The use of one-use plastic syringes and needle cannulas in nucleation experiments can introduce polymeric contamination. A contaminated experiment may nucleate bubbles, drops or both. Moreover, it is surprisingly difficult to distinguish between bubbles and drops under the usual atomic force microscopy or optical techniques. Here we present an experimental study comparing bubbles and oil (PDMS) drops on an atomically smooth surface (HOPG). Instead of nucleating the objects via solvent exchange, we directly introduced bubbles via electrolysis, and oil drops by injecting a dilute solution. Contrary to previous reports, we find that under careful AFM characterisation, liquid drops and gaseous bubbles respond differently to a change in imaging force, and moreover present different characteristic force curves.

  8. Alienation appraisals distinguish adults diagnosed with DID from PTSD.

    PubMed

    DePrince, Anne P; Huntjens, Rafaële J C; Dorahy, Martin J

    2015-11-01

    Studies are beginning to show the importance of appraisals to different types and severities of psychiatric disorders. Yet, little work in this area has assessed whether trauma-related appraisals can differentiate complex trauma-related disorders, such as posttraumatic stress disorder (PTSD) and dissociative identity disorder (DID). The current study evaluated whether any of 6 trauma-related appraisals distinguished adults diagnosed with DID from those diagnosed with PTSD. To accomplish this, we first examined the basic psychometric properties of a Dutch-translated short-form of the Trauma Appraisals Questionnaire (TAQ) in healthy control (n = 57), PTSD (n = 27) and DID (n = 12) samples. The short-form Dutch translation of the TAQ showed good internal reliability and criterion-related validity for all 6 subscales (betrayal, self-blame, fear, alienation, shame, anger). Of the 6 subscales, the alienation appraisal subscale specifically differentiated DID from PTSD, with the former group reporting more alienation. Abuse-related appraisals that emphasize disconnection from self and others may contribute to reported problems of memory and identity common in DID. The current findings suggest that addressing experiences of alienation may be particularly important in treatment for clients diagnosed with DID. PMID:26168348

  9. Distinguishing the Photothermal and Photoinjection Effects in Vanadium Dioxide Nanowires

    NASA Astrophysics Data System (ADS)

    Wang, Xi; Gao, Hanwei

    Vanadium dioxide (VO2) has drawn significant attention for its unique metal-to-insulator transition. The high electrical resistivity below the transition temperature is a result of the strong electron correlation with the assistance of lattice distortion. Theoretical calculations indicated that the strong inter-electron interactions might induce intriguing optoelectronic phenomena, such as the multiple exciton generation. However, the resistivity of VO2 is temperature sensitive. Therefore, the light-induced conductivity in VO2 has often been attributed to the photothermal effects. In this work, we distinguished the photothermal and photoinjection effects in VO2 nanowires by varying the chopping frequency of the optical illumination. In our VO2 nanowires, the relatively slow photothermal processes can be well suppressed when the chopping frequency >2 kHz, whereas the fast photoinjection component (direct photo-excitation of charge carriers) remains constant at all chopping frequencies. By separating the photothermal and photoinjection processes, our work set the basis for further studies of carrier dynamics under optical excitations in strongly correlated materials. This work is supported by the Start-Up Funds and the First-Year Assistant Professor Award from the Florida State University.

  10. Distinguishing genetics and eugenics on the basis of fairness.

    PubMed Central

    Ledley, F D

    1994-01-01

    There is concern that human applications of modern genetic technologies may lead inexorably to eugenic abuse. To prevent such abuse, it is essential to have clear, formal principles as well as algorithms for distinguishing genetics from eugenics. This work identifies essential distinctions between eugenics and genetics in the implied nature of the social contract and the importance ascribed to individual welfare relative to society. Rawls's construction of 'justice as fairness' is used as a model for how a formal systems of ethics can be used to proscribe eugenic practices. Rawls's synthesis can be applied to this problem if it is assumed that in the original condition all individuals are ignorant of their genetic constitution and unwilling to consent to social structures which may constrain their own potential. The principles of fairness applied to genetics requires that genetic interventions be directed at extending individual liberties and be applied to the greatest benefit of individuals with the least advantages. These principles are incompatible with negative eugenics which would further penalize those with genetic disadvantage. These principles limit positive eugenics to those practices which are designed to provide absolute benefit to those individuals with least advantage, are acceptable to its subjects, and further a system of basic equal liberties. This analysis also illustrates how simple deviations from first principles in Rawls's formulation could countenance eugenic applications of genetic technologies. PMID:7996561

  11. Can we distinguish early dark energy from a cosmological constant?

    NASA Astrophysics Data System (ADS)

    Shi, Difu; Baugh, Carlton M.

    2016-07-01

    Early dark energy (EDE) models are a class of quintessence dark energy with a dynamically evolving scalar field which display a small but non-negligible amount of dark energy at the epoch of matter-radiation equality. Compared with a cosmological constant, the presence of dark energy at early times changes the cosmic expansion history and consequently the shape of the linear theory power spectrum and potentially other observables. We constrain the cosmological parameters in the EDE cosmology using recent measurements of the cosmic microwave background and baryon acoustic oscillations. The best-fitting models favour no EDE; here we consider extreme examples which are in mild tension with current observations in order to explore the observational consequences of a maximally allowed amount of EDE. We study the non-linear evolution of cosmic structure in EDE cosmologies using large-volume N-body simulations. Many large-scale structure statistics are found to be very similar between the Λ cold dark matter (ΛCDM) and EDE models. We find that EDE cosmologies predict fewer massive haloes in comparison to ΛCDM, particularly at high redshifts. The most promising way to distinguish EDE from ΛCDM is to measure the power spectrum on large scales, where differences of up to 15 per cent are expected.

  12. Distinguishing human cell types based on housekeeping gene signatures.

    PubMed

    Oyolu, Chuba; Zakharia, Fouad; Baker, Julie

    2012-03-01

    'In this report, we use single cell gene expression to identify transcriptional patterns emerging during the differentiation of human embryonic stem cells (hESCs) into the endodermal lineage. Endoderm-specific transcripts are highly variable between individual CXCR4(+) endodermal cells, suggesting that either the cells generated from in vitro differentiation are distinct or that these embryonic cells tolerate a high degree of transcript variability. Housekeeping transcripts, on the other hand, are far more consistently expressed within the same cellular population. However, when we compare the levels of housekeeping transcripts between hESCs and derived endoderm, patterns emerge that can be used to clearly separate the two embryonic cell types. We further compared four additional human cell types, including 293T, induced pluripotent stem cell (iPSC), HepG2, and endoderm-derived iPSC. In each case, the relative levels of housekeeping transcripts defined a particular cell fate. Interestingly, we find that three transcripts, LDHA, NONO, and ACTB, contribute the most to this diversity and together serve to segregate all six cell types. Overall, this suggests that levels of housekeeping transcripts, which are expressed within all cells, can be leveraged to distinguish between human cell types and thus may serve as important biomarkers for stem cell biology and other disciplines. PMID:22162332

  13. Adaptive inference for distinguishing credible from incredible patterns in nature

    USGS Publications Warehouse

    Holling, Crawford S.; Allen, C.R.

    2002-01-01

    Strong inference is a powerful and rapid tool that can be used to identify and explain patterns in molecular biology, cell biology, and physiology. It is effective where causes are single and separable and where discrimination between pairwise alternative hypotheses can be determined experimentally by a simple yes or no answer. But causes in ecological systems are multiple and overlapping and are not entirely separable. Frequently, competing hypotheses cannot be distinguished by a single unambiguous test, but only by a suite of tests of different kinds, that produce a body of evidence to support one line of argument and not others. We call this process "adaptive inference". Instead of pitting each member of a pair of hypotheses against each other, adaptive inference relies on the exuberant invention of multiple, competing hypotheses, after which carefully structured comparative data are used to explore the logical consequences of each. Herein we present an example that demonstrates the attributes of adaptive inference that have developed out of a 30-year study of the resilience of ecosystems.

  14. Distinguishing two Population Processes with Identical Equilibrium Densities

    NASA Astrophysics Data System (ADS)

    Jakeman, E.; Hopcraft, K. I.; Matthews, J. O.

    2003-04-01

    We analyze the relationship between the evolution of simple population processes and the rate of emigration of individuals. An external monitoring scheme is defined by counting the number leaving the population in fixed time intervals. This is the analogue of photon counting in quantum optics. It is a reasonable measurement in many situations of interest and also has the merit of being analytically tractable. The formalism we develop is used to investigate the statistical and correlation properties of two stochastic population models that give rise to identical first order probability densities. The first is the birth-death- immigration process for which many well-known results can be found in the literature. The second is based on a population sustained by multiple immigration. This model is a generalization of the pair process investigated previously [1]. It can be used to generate populations with a range of equilibrium densities including those with power law tails to be described in a companion paper. Here we show that, in the case of a geometric distribution of multiples, the equilibrium density is negative binomial and higher order joint statistical properties must be used to distinguish the model from the conventional birth-death-immigration process. Formulae characterizing the integrated counting statistics of the two models are derived and it is shown how they may be exploited to achieve this objective.

  15. Cues used for distinguishing African American and European American voices

    NASA Astrophysics Data System (ADS)

    Thomas, Erik R.; Lass, Norman J.

    2005-04-01

    Past studies have shown that listeners can distinguish most African American and European American voices, but how they do so is poorly understood. Three experiments were designed to investigate this problem. Recordings of African American and European American college students performing various reading tasks were used as the basis for stimuli in all three. In the first experiment, stimuli were subjected to monotonization, lowpass filtering at 660 Hz, and no modification. In the second, stimuli featuring certain ethnically diagnostic vowels and control stimuli were subjected to monotonization, conversion of vowels to schwa, or no modification. In the third, stimuli featuring diagnostic vowels and control stimuli were modified so that the intonation of paired African American and European American speakers was swapped. In all three experiments, African American and European American listeners in North Carolina and European American listeners in West Virginia identified the ethnicity of the speaker of each stimulus. Vowel quality emerged as the most consistent cue for identifications. However, listeners accessed other cues differently for male and female speakers. Breathiness was correlated with identifications of male speakers but not of female speakers. F0-related factors proved more important for female speakers than for male speakers. [Work supported by NSF.

  16. 2015 Distinguished career award: Reflections on a career in science.

    PubMed

    Stricker, Edward M

    2016-08-01

    I was very pleased to receive the 2015 Distinguished Career Award from SSIB. This brief manuscript contains reminisces that might stir up pleasant memories in the older members of SSIB and also some general thoughts that I hope will be of value to the younger investigators who are closer to the beginning of their scientific careers. Although the organization has chosen to honor me with this special award, my own career was shaped by a great many people who have influenced my scientific career and I want to acknowledge them. They include Neal Miller, my doctoral mentor at Yale; Joe Holmes and Alan Epstein, my postdoctoral mentors; George Wolf and Reed Hainsworth, graduate student colleagues; John Brobeck, Paul Rozin, and Phil Teitelbaum, Michael Zigmond, Joe Verbalis, Jim Smith, and Alan Sved, faculty colleagues; Derek Denton, Paul McHugh, and James Fitzsimons, scientific role models; John Bruno, Steve Fluharty, and Linda Rinaman, post-doctoral trainees at Pitt; and Lori Flanagan, Kath Curtis, Michael Bushey, Mike Bykowski, Reza Manesh, Carrie Smith, Jennifer Vaughan, and Myriam Stricker, student trainees at Pitt. I thank them all and also my colleagues in SSIB not only for the honor of this award but for providing an abundant supply of insights and discoveries that have stimulated me throughout my adult life, in addition to being an attentive community in supporting my own work. PMID:26434784

  17. The role of orbital ultrasonography in distinguishing papilledema from pseudopapilledema

    PubMed Central

    Carter, S B; Pistilli, M; Livingston, K G; Gold, D R; Volpe, N J; Shindler, K S; Liu, G T; Tamhankar, M A

    2014-01-01

    Purpose To determine the sensitivity and specificity of orbital ultrasonography in distinguishing papilledema from pseudopapilledema in adult patients. Methods The records of all adult patients referred to the neuro-ophthalmology service who underwent orbital ultrasonography for the evaluation of suspected papilledema were reviewed. The details of history, ophthalmologic examination, and results of ancillary testing including orbital ultrasonography, MRI, and lumbar puncture were recorded. Results of orbital ultrasonography were correlated with the final diagnosis of papilledema or pseudopapilledema on the basis of the clinical impression of the neuro-ophthalmologist. Ultrasound was considered positive when the optic nerve sheath diameter was ≥3.3 mm along with a positive 30° test. Results The sensitivity of orbital ultrasonography for detection of papilledema was 90% (CI: 80.2–99.3%) and the specificity in detecting pseudopapilledema was 79% (CI: 67.7–90.7%). Conclusions Orbital ultrasonography is a rapid and noninvasive test that is highly sensitive, but less specific in differentiating papilledema from pseudopapilledema in adult patients, and can be useful in guiding further management of patients in whom the diagnosis is initially uncertain. PMID:25190532

  18. Fimbriae have distinguishable roles in Proteus mirabilis biofilm formation.

    PubMed

    Scavone, Paola; Iribarnegaray, Victoria; Caetano, Ana Laura; Schlapp, Geraldine; Härtel, Steffen; Zunino, Pablo

    2016-07-01

    Proteus mirabilis is one of the most common etiological agents of complicated urinary tract infections, especially those associated with catheterization. This is related to the ability of P. mirabilis to form biofilms on different surfaces. This pathogen encodes 17 putative fimbrial operons, the highest number found in any sequenced bacterial species so far. The present study analyzed the role of four P. mirabilis fimbriae (MR/P, UCA, ATF and PMF) in biofilm formation using isogenic mutants. Experimental approaches included migration over catheter, swimming and swarming motility, the semiquantitative assay based on adhesion and crystal violet staining, and biofilm development by immunofluorescence and confocal microscopy. Different assays were performed using LB or artificial urine. Results indicated that the different fimbriae contribute to the formation of a stable and functional biofilm. Fimbriae revealed particular associated roles. First, all the mutants showed a significantly reduced ability to migrate across urinary catheter sections but neither swimming nor swarming motility were affected. However, some mutants formed smaller biofilms compared with the wild type (MRP and ATF) while others formed significantly larger biofilms (UCA and PMF) showing different bioarchitecture features. It can be concluded that P. mirabilis fimbriae have distinguishable roles in the generation of biofilms, particularly in association with catheters. PMID:27091004

  19. Distinguishing k-defects from their canonical twins

    SciTech Connect

    Andrews, Melinda; Lewandowski, Matt; Trodden, Mark; Wesley, Daniel

    2010-11-15

    We study k-defects--topological defects in theories with more than two derivatives and second-order equations of motion--and describe some striking ways in which these defects both resemble and differ from their analogues in canonical scalar field theories. We show that, for some models, the homotopy structure of the vacuum manifold is insufficient to establish the existence of k-defects, in contrast to the canonical case. These results also constrain certain families of Dirac-Born-Infeld instanton solutions in the 4-dimensional effective theory. We then describe a class of k-defect solutions, which we dub ''doppelgaengers,'' that precisely match the field profile and energy density of their canonical scalar field theory counterparts. We give a complete characterization of Lagrangians which admit doppelgaenger domain walls. By numerically computing the fluctuation eigenmodes about domain wall solutions, we find different spectra for doppelgaengers and canonical walls, allowing us to distinguish between k-defects and the canonical walls they mimic. We search for doppelgaengers for cosmic strings by numerically constructing solutions of Dirac-Born-Infeld and canonical scalar field theories. Despite investigating several examples, we are unable to find doppelgaenger cosmic strings, hence the existence of doppelgaengers for defects with codimension >1 remains an open question.

  20. Mid-infrared diagnostics to distinguish AGNs from starbursts

    NASA Astrophysics Data System (ADS)

    Laurent, O.; Mirabel, I. F.; Charmandaris, V.; Gallais, P.; Madden, S. C.; Sauvage, M.; Vigroux, L.; Cesarsky, C.

    2000-07-01

    We present new mid-infrared (MIR) diagnostics to distinguish emission of active galactic nuclei (AGN) from that originating in starburst regions. Our method uses empirical spectroscopic criteria based on the fact that MIR emission from star forming or active galaxies arises mostly from HII regions, photo-dissociation regions (PDRs) and AGNs. The analysis of the strength of the 6.2 mu m Unidentified Infrared Band (UIB) and the MIR continuum shows that UIBs are very faint or absent in regions harboring the intense and hard radiation fields of AGNs and pure HII regions, where the UIB carriers could be destroyed. The MIR signature of AGNs is the presence of an important continuum in the 3-10 mu m band which originates from very hot dust heated by the intense AGN radiation field. Using these two distinct spectral properties found in our MIR templates, we build diagnostic diagrams which provide quantitative estimates of the AGN, PDR and HII region contribution in a given MIR spectrum. This new MIR classification can be used to reveal the presence of AGNs highly obscured by large columns of dust. Based on observations made with ISO, an ESA project with instruments funded by ESA Member States (especially the PI countries: France, Germany, the Netherlands and the United Kingdom) and with the participation of ISAS and NASA.

  1. 10 CFR 1002.3 - Custody of official seal and distinguishing flags.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Custody of official seal and distinguishing flags. 1002.3 Section 1002.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG General § 1002.3 Custody of official seal and distinguishing flags. The Secretary or his designee...

  2. 10 CFR 1002.3 - Custody of official seal and distinguishing flags.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Custody of official seal and distinguishing flags. 1002.3 Section 1002.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG General § 1002.3 Custody of official seal and distinguishing flags. The Secretary or his designee...

  3. 10 CFR 1002.3 - Custody of official seal and distinguishing flags.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Custody of official seal and distinguishing flags. 1002.3 Section 1002.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG General § 1002.3 Custody of official seal and distinguishing flags. The Secretary or his designee...

  4. 10 CFR 1002.3 - Custody of official seal and distinguishing flags.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Custody of official seal and distinguishing flags. 1002.3 Section 1002.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG General § 1002.3 Custody of official seal and distinguishing flags. The Secretary or his designee...

  5. 10 CFR 1002.3 - Custody of official seal and distinguishing flags.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Custody of official seal and distinguishing flags. 1002.3 Section 1002.3 Energy DEPARTMENT OF ENERGY (GENERAL PROVISIONS) OFFICIAL SEAL AND DISTINGUISHING FLAG General § 1002.3 Custody of official seal and distinguishing flags. The Secretary or his designee...

  6. Charles L. Brewer Award for Distinguished Teaching of Psychology: Neil Lutsky

    ERIC Educational Resources Information Center

    American Psychologist, 2011

    2011-01-01

    The American Psychological Foundation (APF) Charles L. Brewer Award for Distinguished Teaching of Psychology recognizes an outstanding career contribution to the teaching of psychology. The 2011 recipient of the Distinguished Teaching Award is Neil Lutsky. Dorothy W. Cantor, president of the APF, will present the APF Distinguished Teaching Award…

  7. Value of distinguishing differentiated thyroid carcinoma by miRNA

    PubMed Central

    XU, JIANLIN; ZHANG, DING; NIU, QIAN; NAN, YONGGANG; SHI, CHANGBEI; ZHAO, HUA; LIANG, XIAOYAN

    2016-01-01

    Current methods for diagnosing thyroid carcinoma are time consuming or expensive. Thus, alternative approaches are required. In the present study, microRNAs (miRNAs) with higher sensitivity and specificity were screened while distinguishing between differentiated thyroid carcinoma (DTC) and subtype papillary thyroid carcinoma (PTC). A total of 120 cases suspected of having thyroid carcinoma were selected and examined using clinical color Doppler ultrasound, and computed tomography scan at the same time. The tissue specimens were obtained with fine needle aspiration, multiphase biopsy and surgical resection. The expression of miR146b, miR221 and miR222 was detected uisng the RT-quantitative polymerase chain reaction method. The receiver operating characteristic curve was used to obtain the cut-off value. Pathological examination identified 8 cases of normal thyroid tissue; 9 cases of hyperplastic nodules; 12 cases of thyroid adenoma; and 91 cases of thyroid carcinoma, of which 59 cases were DTC, 15 cases were follicular carcinoma and 17 cases were undifferentiated carcinoma. In the thyroid carcinoma, the expression levels of miR146b, miR221 and miR222 were significantly higher than those of other tissues (P<0.05). The expression levels of these miRNAs in the differentiated type were also significantly higher than those in the undifferentiated type (P<0.05). A comparison of the differentiated subunit identified no statistically significant difference (P>0.05). Following diagnosis of DTC, the area under curve (AUC) of miR146b, miR221 and miR222 was 0.832, 0.806 and 0.745, respectively; the cut-off values were 1.346, 1.213 and 1.425, respectively; susceptibility was 72.8, 71.5 and 68.7%, respectively; and specificity was 62.3, 60.9 and 59.3%, respectively. The AUC of the combined miR-146b and −221 following diagnosis of PTC was 0.695; the cut-off values were 1.506 and 1.462, respectively; susceptibility was 78.9%; and specificity was 68.5%. The AUC of the combined mi

  8. Distinguishing bias from sensitivity effects in multialternative detection tasks

    PubMed Central

    Sridharan, Devarajan; Steinmetz, Nicholas A.; Moore, Tirin; Knudsen, Eric I.

    2014-01-01

    Studies investigating the neural bases of cognitive phenomena increasingly employ multialternative detection tasks that seek to measure the ability to detect a target stimulus or changes in some target feature (e.g., orientation or direction of motion) that could occur at one of many locations. In such tasks, it is essential to distinguish the behavioral and neural correlates of enhanced perceptual sensitivity from those of increased bias for a particular location or choice (choice bias). However, making such a distinction is not possible with established approaches. We present a new signal detection model that decouples the behavioral effects of choice bias from those of perceptual sensitivity in multialternative (change) detection tasks. By formulating the perceptual decision in a multidimensional decision space, our model quantifies the respective contributions of bias and sensitivity to multialternative behavioral choices. With a combination of analytical and numerical approaches, we demonstrate an optimal, one-to-one mapping between model parameters and choice probabilities even for tasks involving arbitrarily large numbers of alternatives. We validated the model with published data from two ternary choice experiments: a target-detection experiment and a length-discrimination experiment. The results of this validation provided novel insights into perceptual processes (sensory noise and competitive interactions) that can accurately and parsimoniously account for observers' behavior in each task. The model will find important application in identifying and interpreting the effects of behavioral manipulations (e.g., cueing attention) or neural perturbations (e.g., stimulation or inactivation) in a variety of multialternative tasks of perception, attention, and decision-making. PMID:25146574

  9. T-Cell Immunophenotyping Distinguishes Active From Latent Tuberculosis

    PubMed Central

    Pollock, Katrina M.; Whitworth, Hilary S.; Montamat-Sicotte, Damien J.; Grass, Lisa; Cooke, Graham S.; Kapembwa, Moses S.; Kon, Onn M.; Sampson, Robert D.; Taylor, Graham P.; Lalvani, Ajit

    2013-01-01

    Background. Changes in the phenotype and function of Mycobacterium tuberculosis (M. tuberculosis)-specific CD4+ and CD8+ T-cell subsets in response to stage of infection may allow discrimination between active tuberculosis and latent tuberculosis infection. Methods. A prospective comparison of M. tuberculosis-specific cellular immunity in subjects with active tuberculosis and latent tuberculosis infection, with and without human immunodeficiency virus (HIV) coinfection. Polychromatic flow cytometry was used to measure CD4+ and CD8+ T-cell subset phenotype and secretion of interferon γ (IFN-γ), interleukin 2 (IL-2), and tumor necrosis factor α (TNF-α). Results. Frequencies of CD4+ and CD8+ cells secreting IFN-γ-only, TNF-α-only and dual IFN-γ/TNF-α were greater in active tuberculosis vs latent tuberculosis infection. All M. tuberculosis-specific CD4+ subsets, with the exception of IL-2-only cells, switched from central to effector memory phenotype in active tuberculosis vs latent tuberculosis infection, accompanied by a reduction in IL-7 receptor α (CD127) expression. The frequency of PPD-specific CD4+ TNF-α-only-secreting T cells with an effector phenotype accurately distinguished active tuberculosis from latent tuberculosis infection with an area under the curve of 0.99, substantially more discriminatory than measurement of function alone. Conclusions. Combined measurement of T-cell phenotype and function defines a highly discriminatory biomarker of tuberculosis disease activity. Unlocking the diagnostic and monitoring potential of this combined approach now requires validation in large-scale prospective studies. PMID:23966657

  10. Distinguishing between gaming and gambling activities in addiction research

    PubMed Central

    King, Daniel L.; Gainsbury, Sally M.; Delfabbro, Paul H.; Hing, Nerilee; Abarbanel, Brett

    2015-01-01

    Background and Aims Gambling and gaming activities have become increasingly recognised as sharing many common features at a structural and aesthetic level. Both have also been implicated as contributing to harm through excessive involvement. Despite this, relatively little attention has been given to the fundamental characteristics that differentiate these two classes of activity, especially in situations where the boundaries between them may be particularly hard to distinguish. This is evident, for example, in digital games that incorporate free and paid virtual currencies or items, as well as the capacity for wagering. Such overlaps create problems for regulatory classifications, screening, diagnosis and treatment. Is the problem related to the gambling or gaming content? Methods In this paper, we review the principal sources of overlap between the activity classes in terms of several dimensions: interactivity, monetisation, betting and wagering, types of outcomes, structural fidelity, context and centrality of content, and advertising. Results We argue that gaming is principally defined by its interactivity, skill-based play, and contextual indicators of progression and success. In contrast, gambling is defined by betting and wagering mechanics, predominantly chance-determined outcomes, and monetisation features that involve risk and payout to the player. A checklist measure is provided, with practical examples, to examine activities according to features of design and function, which may inform guidelines for policy makers, researchers and treatment providers. Discussion and conclusions We suggest that, in some instances, using category-based nomenclature (e.g., “gambling-like game”) may be too vague or cumbersome to adequately organise our understanding of new gaming/gambling hybrid activities. PMID:26690615

  11. Distinguishing Biotic from Abiotic Phosphate Oxygen Isotopic Signatures

    NASA Astrophysics Data System (ADS)

    Blake, R.; Moyer, C.; Colman, A.; Liang, Y.; Dogru, D.

    2006-05-01

    On earth, phosphate has a strong biological oxygen isotope signature due to its concentration and intense cycling by living organisms as an essential nutrient. Phosphate does not undergo oxygen isotope exchange with water at low temperature without enzymatic catalysis, making the oxygen isotope ratio (18O/16O) of phosphate, δ18OP, an attractive biosignature in the search for early and extraterrestrial life. Recent laboratory and field studies have demonstrated that the δ18OP value of dissolved inorganic phosphate (PO4) records specific microbial activity and enzymatic reaction pathways in both laboratory cultures and natural waters/sediments (Blake et al., 2005; Colman et al 2005; Liang and Blake, 2005). Phosphate oxygen isotope biosignatures may be distinguished from abiotic signatures by: (1) evaluating the degree of temperature-dependent PO4-water oxygen isotope exchange in aqueous systems and deviation from equilibrium; and (2) evolution from an abiotic P reservoir signature towards a biotic P reservoir signature. Important abiotic processes potentially affecting phosphate δ18OP values include dissolution/precipitation, adsorption/desorption, recrystallization of PO4 mineral phases, diagenesis and metamorphism. For most of these processes, the recording, retention and alteration of δ18OP biosignatures have not been evaluated. Deep-sea hydrothermal vent fields are an ideal system in which to study the preservation and alteration of δ18OP biosignatures, as well as potential look-alikes produced by heat-promoted PO4 -water oxygen isotope exchange. Results from recent studies of δ18OP biosignatures in hydrothermal deposits near 9 and 21 degrees N. EPR and at Loihi seamount will be presented.

  12. Distinguishing Morphotypes of Foraminifera Orbulina Universa Using Shell Morphometrics

    NASA Astrophysics Data System (ADS)

    Marshall, B. J.; Thunell, R.

    2014-12-01

    Several recent genetic studies have revealed that many morphologically defined planktonic foraminiferal species contain multiple distinct cryptic or pseudocryptic genetic variants. In some cases, such as with the genetic variants of Globigerinoides ruber, past taxonomic "lumping" may be easily revised within the framework of the morphospecies concept. However, some planktonic foraminiferal cryptic species are not easily differentiated from one another based on identifiable morphological differences, as is the case with Orbulina universa cryptic species (Morard et al., 2009). Based on recent findings, it is believed that several of these O. universa cryptic species differ in their habitat preferences (Darling et al., 1999,2000; de Vargas et al., 1999, 2001), and the lumping of these cryptic species could possibly account for a significant amount of the noise observed in various paleoclimate records derived from this species (Kucera and Darling, 2002). The current study uses foraminiferal morphometrics (area density, Marshall et al., 2013, thickness and weight-diameter realtionships) to identify distinct groupings of individual Orbulina universa specimens collected from sediment trap samples in the Cariaco Basin, Venezuela. The study reveals three distinct groups of individuals, varying in their test thicknesses and pore space distribution, which likely correspond to the previously identified cryptic species of O. universa. We find significant differences in the isotopic compositions of these groupings - suggesting that the identified morphotypes differ in their habitat preferences. These morphotypes also exhibit different relationships with the measured hydrographic parameters and their relative distribution can be linked to changes in upwelling and non-upwelling hydrographic regimes. We agree with the results of previous studies that suggest different cryptic species should not be treated as ecophenotypic variants and need to be distinguished from one another

  13. Mesiodistal odontometrics as a distinguishing trait: A comparative preliminary study

    PubMed Central

    Sravya, Taneeru; Dumpala, Rakesh Kumar; Guttikonda, Venkateswara Rao; Manchikatla, Praveen Kumar; Narasimha, Vanajakshi China

    2016-01-01

    Introduction: Sex determination is a vital step in reconstructing an individual profile from unidentified skeletal remnants. Variations in tooth size are influenced by genetic and environmental factors. Tooth size variations have been reported among different populations. Aim: To identify the sex by determining the mesiodistal (MD) dimensions of maxillary canines. Objectives: (1) To compare the MD diameter of all maxillary canines — (a) in the entire urban and tribal population, (b) in urban male and urban female populations, (c) in tribal male and tribal female populations, and (d) in the entire male and female populations and (2) To estimate the percentage of sexual dimorphism individually in urban and tribal populations. Materials and Methods: Fifty subjects each from urban and tribal populations in equal gender ratio were selected in Khammam district, Telangana, for the purpose of this study. After obtaining informed consent, maxillary study models of the selected subjects were made. MD diameters of left and right maxillary canines were measured on casts using vernier calipers. The obtained data were subjected to statistical analysis. Results: (1) The total tribal population showed a greater MD diameter of maxillary canines than the total urban population, (2) Urban males showed a greater MD diameter of maxillary canines than urban females, (3) Tribal males showed a greater MD diameter of maxillary canines than tribal females, (4) The entire male population showed a greater MD diameter of maxillary canines than the entire female population, and (5) The percentage of dimorphism between males and females in individual groups was found to be significant. Conclusion: The study showed maxillary canines exhibiting significant sexual dimorphism and can be used as a distinguishing trait for sex determination along with other procedures. PMID:27555727

  14. Mapping groundwater quality distinguishing geogenic and anthropogenic contribution using NBL

    NASA Astrophysics Data System (ADS)

    Preziosi, Elisabetta; Ducci, Daniela; Condesso de Melo, Maria Teresa; Parrone, Daniele; Sellerino, Mariangela; Ghergo, Stefano; Oliveira, Joana; Ribeiro, Luis

    2015-04-01

    Groundwaters are threatened by anthropic activities and pollution is interesting a large number of aquifers worldwide. Qualitative and quantitative monitoring is required to assess the status and track its evolution in time and space especially where anthropic pressures are stronger. Up to now, groundwater quality mapping has been performed separately from the assessment of its natural status, i.e. the definition of the natural background level of a particular element in a particular area or groundwater body. The natural background level (NBL) of a substance or element allows to distinguish anthropogenic pollution from contamination of natural origin in a population of groundwater samples. NBLs are the result of different atmospheric, geological, chemical and biological interaction processes during groundwater infiltration and circulation. There is an increasing need for the water managers to have sound indications on good quality groundwater exploitation. Indeed the extension of a groundwater body is often very large, in the order of tens or hundreds of square km. How to select a proper location for good quality groundwater abstraction is often limited to a question of facility for drilling (access, roads, authorizations, etc.) or at the most related to quantitative aspects driven by geophysical exploration (the most promising from a transmissibility point of view). So how to give indications to the administrators and water managers about the exploitation of good quality drinking water? In the case of anthropic contamination, how to define which area is to be restored and to which threshold (e.g. background level) should the concentration be lowered through the restoration measures? In the framework of a common project between research institutions in Italy (funded by CNR) and Portugal (funded by FCT), our objective is to establish a methodology aiming at merging together 1) the evaluation of NBL and 2) the need to take into account the drinking water standards

  15. Tissue cytokine patterns distinguish variants of rheumatoid synovitis.

    PubMed Central

    Klimiuk, P. A.; Goronzy, J. J.; Björ nsson, J.; Beckenbaugh, R. D.; Weyand, C. M.

    1997-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disease with primary manifestations in the synovial membrane. Tissue infiltrates are composed of T cells, B cells, and macrophages, but histopathological appearances vary widely and are rarely pathognomonic. Mechanisms underlying the phenotypic heterogeneity of rheumatoid synovitis are not known. To explore whether a correlation exists between the microscopic patterns of rheumatoid synovitis and in situ production of cytokines, tissue samples from 21 consecutive patients with clinically active RA were examined. Based upon the organization of the lymphocyte infiltrate, the synovial biopsies were categorized into three distinct subsets. Ten samples were characterized by diffuse lymphoid infiltrates without further microarrangement. In seven samples, lymphoid follicles with germinal center formation were detected, and in four specimens, granuloma formation was identified. In all specimens, cytokine transcription of interferon (IFN)-gamma, interleukin (IL)-4, IL-1 beta, tumor necrosis factor (TNF)-alpha, IL-10, and transforming growth factor-beta 1 was semiquantified with polymerase chain reaction and liquid phase hybridization. Each of the morphologically defined variants of synovitis displayed a unique cytokine profile. Low-level transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha was typical of diffuse synovitis. In follicular synovitis, IFN-gamma was the dominant cytokine, IL-4 was virtually undetectable, and IL-10 was abundant. Granulomatous synovitis demonstrated high transcription of IFN-gamma, IL-4, IL-1 beta, and TNF-alpha and could be clearly distinguished from the other phenotypes. To investigate whether differences in the synovial lesions were related to host factors, patients were compared for clinical parameters. Diffuse synovitis was seen in most of the patients with seronegative RA, the mildest form of the disease. In contrast, extra-articular spreading of RA with nodule formation was typically

  16. Dissecting Childhood Asthma with Nasal Transcriptomics Distinguishes Subphenotypes of Disease

    PubMed Central

    Poole, Alex; Urbanek, Cydney; Eng, Celeste; Schageman, Jeoffrey; Jacobson, Sean; O’Connor, Brian P.; Galanter, Joshua M.; Gignoux, Christopher R.; Roth, Lindsey A.; Kumar, Rajesh; Lutz, Sharon; Liu, Andrew H.; Fingerlin, Tasha; Setterquist, Robert A.; Burchard, Esteban G.; Rodriguez-Santana, Jose; Seibold, Max A.

    2014-01-01

    Background Bronchial airway expression profiling has identified inflammatory subphenotypes of asthma, but invasiveness of this technique has limited its application to childhood asthma. Objectives To determine if the nasal transcriptome can proxy expression changes in the lung airway transcriptome in asthma. To determine if the nasal transcriptome can distinguish subphenotypes of asthma. Methods Whole transcriptome RNA-sequencing (RNA-seq) was performed on nasal airway brushings from 10 controls and 10 subjects with asthma, which was compared to established bronchial and small airway transcriptomes. Targeted RNA-seq nasal expression analysis was used to profile 105 genes in 50 subjects with asthma and 50 controls for differential expression and clustering analyses. Results We found 90.2% overlap in expressed genes and strong correlation in gene expression (ρ=0.87) between the nasal and bronchial transcriptomes. Previously observed asthmatic bronchial differential expression was strongly correlated with asthmatic nasal differential expression (ρ=0.77, p=5.6×10−9). Clustering analysis identified Th2-high and Th2-low subjects differentiated by expression of 70 genes including IL-13, IL-5, POSTN, CLCA1, and SERPINB2. Th2-high subjects were more likely to have atopy (O.R.=10.3, p=3.5×10−6), atopic asthma (OR=32.6, p=6.9×10−7), high blood eosinophils (OR=9.1, 2.6×10−6), and rhinitis (OR=8.3, p=4.1×10−6) compared to Th2-low subjects. Nasal IL-13 expression levels were 3.9-fold higher in asthmatic participants who experienced asthma exacerbation in the past year (p=0.01). Several differentially expressed nasal genes were specific to asthma and independent of atopic status. Conclusion Nasal airway gene expression profiles largely recapitulate expression profiles in the lung airways. Nasal expression profiling can be used to identify individuals with IL13-driven asthma and a Th2-skewed systemic immune response. Clinical Implications Nasal airway gene

  17. Distinguishing resuspension and advection signals in a hypertidal estuary

    NASA Astrophysics Data System (ADS)

    Todd, David; Souza, Alex; Jago, Colin

    2015-04-01

    Terrestrial material is supplied to an estuary system by the river, while marine material is supplied by the sea. Whether the estuary acts as a trap or a bypass zone for SPM (suspended particulate matter) depends upon the properties and dynamics of both the estuary, including the tidal and residual behaviour of the currents, and the SPM, including particle sizes and settling velocities and concentration gradients, which together control the dynamics, such as the trapping efficiency, of the estuary. Whether an SPM signal is regarded as being one of resuspension or advection depends upon the area of interest, and therefore distinguishing between resuspension and advection can be complex. Material that is resuspended within the area of study is regarded as resuspension, while that which is resuspended outside, but passes through, the area of interest, is regarded as advection. The results of a measurement campaign undertaken in a hypertidal UK estuary during the pre-spring bloom February-March and post-spring bloom May-June are presented utilising a combination of acoustic and optical instruments, moorings, and CTD stations. A characteristic asymmetric "twin peak" signal is present during both time periods, implying the presence of both resuspension and advection. This is confirmed through the use of harmonic analysis. A seasonal variation in the relative importance of the resuspension and advection components is seen between the two observation periods, with the small (<122µm) and large (>122µm) particles displaying different behaviours and providing a strong indication of the presence of flocculation. Approximate point flux calculations showed a reduction in the horizontal gradient of concentration, and subsequently the flood dominance of sediment transport, between May-June and February-March. This has been attributed to changes in biological activity and atmospheric forcing between the two observational periods. Ebb-dominant concentrations brought about by the

  18. Distinguishing "new" from "old" carbon in post mining soils

    NASA Astrophysics Data System (ADS)

    Vindušková, Olga; Frouz, Jan

    2014-05-01

    Introduction Soils developing on heaped overburden after open pit coal mining near Sokolov, Czech Republic, provide an exceptional opportunity to study sites of different ages (0-70 years) developing on similar substrate under relatively well-known conditions. Soil organic carbon (SOC) is an useful indicator of soil quality and represents an important global carbon pool. Post-mining soils would be a perfect model for long-term study of carbon dynamics. Unfortunately, quantifying SOC in Sokolov post-mining soils is quite complicated, since conventional quantification methods cannot distinguish between SOC derived from plant residues and fossil organic carbon derived from coal and kerogen present in the overburden. Moreover, also inorganic carbon may sometimes bias SOC quantification. Up to now, the only way to directly estimate recently derived SOC in these soils is radiocarbon dating (Rumpel et al. 1999; Karu et al. 2009). However, this method is costly and thus cannot be used routinely. The aim of our study is to find an accessible method to quantify recently derived SOC. We would highly appreciate ideas of other soil scientists, organic geochemists and sedimentologists on how to solve this challenge. Methods and hypotheses A set of 14 soil samples were analysed by radiocarbon (14C-AMS) analysis, near-infrared spectroscopy (NIRS), 13C CPMAS NMR spectroscopy, Rock-Eval and XRD. For calibration of NIRS, also 125 artificial mixtures were produced by mixing different amounts of claystone, coal and partially decomposed litter. NIRS (1000-2500 nm) as well as younger mid-infrared spectroscopy has been widely applied to soils (Janik et al. 2007; Vasques et al. 2009; Michel et al. 2009). When combined with multivariate chemometric techniques, it can be used to predict concentration of different compounds. No study has yet focused on NIRS application to soils where fossil carbon is found in two chemically different forms - whereas coal is rather aromatic, kerogen in our

  19. The Effect of Distinguished Educators on Academic Gain of Louisiana Academically Unacceptable Schools

    ERIC Educational Resources Information Center

    Scroggins, Ruby C.

    2012-01-01

    The purpose of this study was to examine the degree of academic growth of Academically Unacceptable schools in Louisiana which have been assigned a Distinguished Educator. Distinguished Educators are external change agents who are placed in Academically Unacceptable schools in Louisiana. The data were generated from the Louisiana Department of…

  20. Daniel Landis: Award for Distinguished Contributions to the International Advancement of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the co-recipients of the American Psychological Association's Award for Distinguished Contributions to the International Advancement of Psychology. One of the 2012 winners is Daniel Landis for his unparalleled contribution to the field of intercultural research in a distinguished academic career spanning almost…

  1. 29 CFR 778.207 - Other types of contract premium pay distinguished.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Other types of contract premium pay distinguished. 778.207....207 Other types of contract premium pay distinguished. (a) Overtime premiums are those defined by the statute. The various types of contract premium rates which provide extra compensation qualifying...

  2. Award for Distinguished Senior Career Contributions to Psychology in the Public Interest: Beverly Greene

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Beverly Greene, recipient of the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest, has a long history of distinguished contributions in the public interest through her research, scholarship, teaching, practice, and consultation. Her work raises the visibility of many populations that have been overlooked and…

  3. Concurrence as a measure of Markovianity: concurrence versus distinguishability and divisibility

    NASA Astrophysics Data System (ADS)

    Gao, Ze-Yu; Ren, Yu-Kun; Zeng, Hao-Sheng

    2016-07-01

    We examine the measure of Markovianity based on entanglement through two typical dynamical models in qubit systems and compare it with the measures of Markovianity based on state distinguishability and dynamical divisibility. We find that divisible dynamics always leads to the monotonic decrease in concurrence, but distinguishability does not constrain its behavior in the same way.

  4. Distinguishing Features in Scoring L2 Chinese Speaking Performance: How Do They Work?

    ERIC Educational Resources Information Center

    Jin, Tan; Mak, Barley

    2013-01-01

    For Chinese as a second language (L2 Chinese), there has been little research into "distinguishing features" (Fulcher, 1996; Iwashita et al., 2008) used in scoring L2 Chinese speaking performance. The study reported here investigates the relationship between the distinguishing features of L2 Chinese spoken performances and the scores awarded by…

  5. Award for Distinguished Professional Contributions to Independent Practice: Jeffrey E. Barnett

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Jeffrey E. Barnett, recipient of the Award for Distinguished Professional Contributions to Independent Practice, is cited for outstanding, distinguished, and meritorious service in several areas of professional practice, especially professional ethics and psychotherapy treatment. Barnett has produced hundreds of high-quality publications,…

  6. Michael E. Barnes: Award for Distinguished Professional Contributions to Institutional Practice

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography on the winner of the American Psychological Association's Award for Distinguished Professional Contributions to Institutional Practice. The 2012 winner is Michael E. Barnes for his pioneering leadership, dedication, and distinguished contributions to juvenile justice. As chief psychologist of the Superior Court of the…

  7. Distinguishing attack and second-preimage attack on encrypted message authentication codes (EMAC)

    NASA Astrophysics Data System (ADS)

    Ariwibowo, Sigit; Windarta, Susila

    2016-02-01

    In this paper we show that distinguisher on CBC-MAC can be applied to Encrypted Message Authentication Code (EMAC) scheme. EMAC scheme in general is vulnerable to distinguishing attack and second preimage attack. Distinguishing attack simulation on AES-EMAC using 225 message modifications, no collision have been found. According to second preimage attack simulation on AES-EMAC no collision found between EMAC value of S1 and S2, i.e. no second preimage found for messages that have been tested. Based on distinguishing attack simulation on truncated AES-EMAC we found collision in every message therefore we cannot distinguish truncated AES-EMAC with random function. Second-preimage attack is successfully performed on truncated AES-EMAC.

  8. FABP4-mediated homocysteine-induced cholesterol accumulation in THP-1 monocyte-derived macrophages and the potential epigenetic mechanism.

    PubMed

    Jiang, Yideng; Ma, Shengchao; Zhang, Huiping; Yang, Xiaoling; Lu, Guan Jun; Zhang, Hui; He, Yangyang; Kong, Fanqi; Yang, Anning; Xu, Hua; Zhang, Minghao; Jiao, Yun; Li, Guizhong; Cao, Jun; Jia, Yuexia; Jin, Shaoju; Wei, Jun; Shi, Yingkang

    2016-07-01

    Hyperhomocysteinemia (HHcy) is an independent risk factor for the development of atherosclerosis (AS), according to overwhelming number of clinical and epidemiological studies. However, the underlying pathogenic molecular mechanisms by which HHcy promotes AS remain to be fully elucidated. Fatty acid binding protein 4 (FABP4) has been shown to be important in macrophage cholesterol trafficking. The objective of the present study was to determine whether homocysteine (Hcy) accelerates AS through regulating FABP4, and then mediates cholesterol accumulation in macrophages. Hcy concentrations of 0, 50, 100, 200 and 500 µM, and 100 µM Hcy+30 µM vitamin B12 (VB12)+30 µM folic acid (FA) were respectively added to cultured THP‑1 monocyte‑derived macrophages for 24 h. The levels of FABP4, which acts as a key factor connecting cellular lipid accumulation to inflammation, were determined using reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blot analyses in the macrophages. The present study used a nested touchdown methylation‑specific PCR assay to detect the DNA methylation status of the FABP4 promoter region. In addition, the FABP4 gene fragment was inserted into the cloning vector, pcDNA3.1‑EGFP, to construct the recombinant plasmid, pcDNA3.1‑EGFP/FABP4, which was identified using restriction endonuclease digestion analysis and DNA sequencing. The pcDNA3.1‑EGFP/FABP4 expression plasmid was transfected into THP‑1 monocyte‑derived macrophages, mediated by liposome reagent, following which the expression levels of FABP4 were detected using RT‑qPCR and western blot analyses. The present study also determined the intracellular accumulation of total cholesterol in the macrophages. The results indicated that Hcy decreased the levels of FABP4 promoter methylation, but increased the mRNA and protein expression levels of FABP4 in the macrophages, compared with the control group (0 µM Hcy). However, no dose‑dependent changes were observed with increasing concentrations of Hcy. The recombinant fluorescent eukaryotic expression vector, pcDNA3.1‑EGFP/FABP4, was successfully constructed and effectively expressed in the THP‑1 macrophages. The results also showed that FABP4 accelerated the accumulation of cholesterol in the macrophages. Taken together, the results of the present study suggested that FABP4 DNA hypomethylation induced by Hcy may be involved in the overexpression of FABP4, thereby inducing cholesterol accumulation in macrophages. PMID:27221153

  9. Glucose levels affect LL-37 expression in monocyte-derived macrophages altering the Mycobacterium tuberculosis intracellular growth control.

    PubMed

    Montoya-Rosales, Alejandra; Castro-Garcia, Pamela; Torres-Juarez, Flor; Enciso-Moreno, Jose Antonio; Rivas-Santiago, Bruno

    2016-08-01

    Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non-infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients. PMID:27263098

  10. Effects of inactivated porcine epidemic diarrhea virus on porcine monocyte-derived dendritic cells and intestinal dendritic cells.

    PubMed

    Gao, Qi; Zhao, Shanshan; Qin, Tao; Yin, Yinyan; Yu, Qinghua; Yang, Qian

    2016-06-01

    Porcine epidemic diarrhea (PED) is a serious infection in neonatal piglets. As the causative agent of PED, porcine epidemic diarrhea virus (PEDV) results in acute diarrhea and dehydration with high mortality rates in swine. Dendritic cells (DCs) are highly effective antigen-presenting cells to uptake and present viral antigens to T cells, which then initiate a distinct immune response. In this study, our results show that the expression of Mo-DCs surface markers such as SWC3a(+)CD1a(+), SWC3a(+)CD80/86(+) and SWC3a(+)SLA-II-DR(+) is increased after incubation with UV-PEDV for 24h. Mo-DCs incubated with UV-PEDV produce higher levels of IL-12 and INF-γ compared to mock-infected Mo-DCs. Interactions between Mo-DCs and UV-PEDV significantly stimulate T-cell proliferation in vitro. Consistent with these results, there is an enhancement in the ability of porcine intestinal DCs to activate T-cell proliferation in vivo. We conclude that UV-PEDV may be a useful and safe vaccine to trigger adaptive immunity. PMID:27234553

  11. Monocyte-derived macrophage assisted breast cancer cell invasion as a personalized, predictive metric to score metastatic risk

    PubMed Central

    Park, Keon-Young; Li, Gande; Platt, Manu O.

    2015-01-01

    Patient-to-patient variability in breast cancer progression complicates clinical treatment decisions. Of women undergoing prophylactic mastectomies, many may not have progressed to indolent forms of disease and could have benefited from milder, localized therapy. Tumor associated macrophages contribute significantly to tumor invasion and metastasis, with cysteine cathepsin proteases as important contributors. Here, a method is demonstrated by which variability in macrophage expression of cysteine cathepsins, their inhibitor cystatin C, and kinase activation can be used to train a multivariate model and score patients for invasion risk. These enzymatic profiles were used to predict macrophage-assisted MCF-7 breast cancer cell invasion in the trained computational model. To test these predictions, a priori, signals from monocytes isolated from women undergoing mastectomies were input to score their cancer invasion potential in a patient-specific manner, and successfully predicted that patient monocytes with highest predicted invasion indices matched those with more invasive initial diagnoses of the nine patients tested. Together this establishes proof-of-principle that personalized information acquired from minimally invasive blood draws may provide useful information to inform oncologists and patients of invasive/metastatic risk, helping to make decisions regarding radical mastectomy or milder, conservative treatments to save patients from hardship and surgical recovery. PMID:26349896

  12. Differential expression of HIV-1 interfering factors in monocyte-derived macrophages stimulated with polarizing cytokines or interferons

    NASA Astrophysics Data System (ADS)

    Jiménez, Viviana Cobos; Booiman, Thijs; de Taeye, Steven W.; van Dort, Karel A.; Rits, Maarten A. N.; Hamann, Jörg; Kootstra, Neeltje A.

    2012-10-01

    HIV-1 replication in macrophages can be regulated by cytokines and infection is restricted in macrophages activated by type I interferons and polarizing cytokines. Here, we observed that the expression levels of the cellular factors Trim5α, CypA, APOBEC3G, SAMHD-1, Trim22, tetherin and TREX-1, and the anti-HIV miRNAs miR-28, miR-150, miR-223 and miR-382 was upregulated by IFN-α and IFN-β in macrophages, which may account for the inhibiting effect on viral replication and the antiviral state of these cells. Expression of these factors was also increased by IFN-γ +/- TNF-α, albeit to a lesser extent; yet, HIV-1 replication in these cells was not restricted at the level of proviral synthesis, indicating that these cellular factors only partially contribute to the observed restriction. IL-4, IL-10 or IL-32 polarization did not affect the expression of cellular factors and miRNAs, suggesting only a limited role for these cellular factors in restricting HIV-1 replication in macrophages.

  13. Identification and characterization of a monocyte-derived neutrophil-activating factor in corticosteroid-resistant bronchial asthma.

    PubMed Central

    Wilkinson, J R; Crea, A E; Clark, T J; Lee, T H

    1989-01-01

    Peripheral blood mononuclear cells (PBMC) were isolated from seven normal subjects, eight asthmatic subjects clinically sensitive to corticosteroids (CS), and eight asthmatic subjects clinically resistant to corticosteroids (CR). PBMC were cultured at 37 degrees C for 24 h in the absence or presence of 10(-16) to 10(-4) M hydrocortisone. Calcium ionophore (A23187)-activated neutrophils (PMN) primed by supernatants of PBMC from asthmatic subjects cultured in the absence of hydrocortisone generated approximately threefold more leukotriene B4 than PMN primed by supernatants of PBMC from normal subjects (P less than 0.05). Incubation of PBMC derived from CS subjects with 10(-8) M hydrocortisone completely inhibited the production of the enhancing activity (P less than 0.01), whereas in CR subjects hydrocortisone at concentrations up to 10(-4) M did not suppress the release of enhancing activity. The enhancing activity was produced by monocytes. Enhancing activity eluted with an Mr of 3,000 D and a pI of 7.1. It eluted at 10% acetonitrile after reverse-phase HPLC. The activity was destroyed by heating to 60 degrees C for 60 min and was sensitive to pronase treatment. The purified factor also enhanced superoxide generation by PMN which had been stimulated submaximally by phorbol myristate acetate. Images PMID:2556450

  14. Screening of Mycobacterium avium subsp. paratuberculosis mutants for attenuation in a bovine monocyte-derived macrophage model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccination remains a major tool for prevention and progression of Johne’s disease, a chronic enteritis of ruminants worldwide. Currently there is only one licensed vaccine within the United States and two vaccines licensed internationally against Johne’s disease. All licensed vaccines reduce fecal...

  15. Mesenchymal Stromal Cell-Like Cells Set the Balance of Stimulatory and Inhibitory Signals in Monocyte-Derived Dendritic Cells.

    PubMed

    Bacskai, Ildikó; Mázló, Anett; Kis-Tóth, Katalin; Szabó, Attila; Panyi, György; Sarkadi, Balázs; Apáti, Ágota; Rajnavölgyi, Éva

    2015-08-01

    The major reservoir of human multipotent mesenchymal stem/stromal cells (MSCs) is the bone marrow (BM) with the capability to control hematopoietic stem cell development. The regenerative potential of MSCs is associated with enhanced endogenous repair and healing mechanisms that modulate inflammatory responses. Our previous results revealed that MSC-like (MSCl) cells derived from pluripotent human embryonic stem cells resemble BM-derived MSCs in morphology, phenotype, and differentiating potential. In this study, we investigated the effects of MSCl cells on the phenotype and functions of dendritic cells (DCs). To assess how antiviral immune responses could be regulated by intracellular pattern recognition receptors of DCs in the presence of MSCl cells, we activated DCs with the specific ligands of retinoic acid-inducible gene-I (RIG-I) helicases and found that activated DCs cocultured with MSCl cells exhibited reduced expression of CD1a and CD83 cell surface molecules serving as phenotypic indicators of DC differentiation and activation, respectively. However, RIG-I-mediated stimulation of DCs through specific ligands in the presence of MSCl cells resulted in significantly higher expression of the costimulatory molecules, CD80 and CD86, than in the presence of BM-MSCs. In line with these results, the concentration of IL-6, IL-10, and CXCL8 was increased in the supernatant of the DC-MSCl cocultures, while the secretion of TNF-α, CXCL10, IL-12, and IFNγ was reduced. Furthermore, the concerted action of mechanisms involved in the regulation of DC migration resulted in the blockade of cell migration, indicating altered DC functionality mediated by MSCl cell-derived signals and mechanisms resulting in a suppressive microenvironment. PMID:25808140

  16. Bjcul, a snake venom lectin, modulates monocyte-derived macrophages to a pro-inflammatory profile in vitro.

    PubMed

    Dias-Netipanyj, M F; Boldrini-Leite, L M; Trindade, E S; Moreno-Amaral, A N; Elifio-Esposito, S

    2016-06-01

    Macrophages are cells of high plasticity and can act in different ways to ensure that the appropriate immune response remains controlled. This study shows the effects of the C-type Bothrops jararacussu venom lectin (BJcuL) on the activation of human macrophages derived from the U937 cell line. BJcuL binds on the cell surface, and this event is inhibited by its specific carbohydrate. It induced phagocytosis and production of H2O2, and expression of antigen presentation molecules. It also enhanced the production of TNF-α, GM-CSF and IL-6 by macrophages and indirectly induced T cells to an increased production of TNF-α, IFN-γ and IL-6 in the presence of LPS. Our results suggest that BJcuL can modulate macrophage functional activation towards an M1 state. PMID:26944802

  17. Comparative analysis of signature genes in PRRSV-infected porcine monocyte-derived dendritic cells at differential activation statuses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Activation statuses of monocytic cells including monocytes, macrophages and dendritic cells (DCs) are critically important for antiviral immunity. In particular, some devastating viruses, including porcine reproductive and respiratory syndrome virus (PRRSV), are capable of directly infecting these c...

  18. Plasmacytoid, conventional, and monocyte-derived dendritic cells undergo a profound and convergent genetic reprogramming during their maturation

    PubMed Central

    Vu Manh, Thien-Phong; Alexandre, Yannick; Baranek, Thomas; Crozat, Karine; Dalod, Marc

    2013-01-01

    DCs express receptors sensing microbial, danger or cytokine signals, which when triggered in combination drive DC maturation and functional polarization. Maturation was proposed to result from a discrete number of modifications in conventional DCs (cDCs), in contrast to a cell-fate conversion in plasmacytoid DCs (pDCs). cDC maturation is generally assessed by measuring cytokine production and membrane expression of MHC class II and co-stimulation molecules. pDC maturation complexity was demonstrated by functional genomics. Here, pDCs and cDCs were shown to undergo profound and convergent changes in their gene expression programs in vivo during viral infection. This observation was generalized to other stimulation conditions and DC subsets, by public microarray data analyses, PCR confirmation of selected gene expression profiles, and gene regulatory sequence bioinformatics analyses. Thus, maturation is a complex process similarly reshaping all DC subsets, including through the induction of a core set of NF-κB- or IFN-stimulated genes irrespective of stimuli. PMID:23553052

  19. Distinguishing between Higher and Lower Risk Youth Offenders: Applications for Practice

    ERIC Educational Resources Information Center

    Coll, Kenneth M.; Stewart, Roger A.; Juhnke, Gerald A.; Thobro, Patti; Haas, Robin

    2009-01-01

    The authors report the development of an assessment process for distinguishing between higher and lower risk youth offenders through the use of 3 measures. Preliminary results and applications for practice are included. (Contains 2 tables.)

  20. Use and abuse of the distinguished-coordinate method for transition-state structure searching

    NASA Astrophysics Data System (ADS)

    Williams, Ian H.; Maggiora, Gerald M.

    Exploration of potential-energy surfaces for reacting systems is often expedited by selection of a distinguished coordinate, to measure progress between reactants and products, at each value of which the remaining coordinates are optimized by constrained energy-minimization. A classification of surfaces is suggested according to the number of energy minima in thesubspace excluding the distinguished coordinate in the saddle region. Type S surfaces are well behaved in the distinguished-coordinate method but type D surfaces are not. In general, reaction paths and energy profiles generated by this method for type D surfaces are discontinuous and cannot be used to locate transition-state structures precisely. An extension of the method using two distinguished coordinates is discussed in relation to the example of formaldehyde hydration but is found to suffer from the same pathological condition in two dimensions as does the standard method in one dimension.

  1. For Distinguished Public Service: Medical Library Association Honors FNLM and NIH MedlinePlus Magazine | NIH ...

    MedlinePlus

    ... turn Javascript on. For Distinguished Public Service: Medical Library Association Honors FNLM and NIH MedlinePlus Magazine Past ... hearing from you. The Friends of the National Library of Medicine has a warm and mutually appreciative ...

  2. Distinguishing of tumor cell-targeting peptide ligands through a color-encoding microarray.

    PubMed

    Wang, Zihua; Wang, Weizhi; Geng, Lingling; Hu, Zhiyuan

    2015-12-21

    A silicon-based microarray system was constructed to discover the affinity peptides and to distinguish the specific peptides from a high throughput library. Using a color-encoding strategy, in situ peptide distinguishing between HER1 ligands and HER2 ligands was achieved. Novel affinity peptide sequences H1P (HER1 ligand) and H2P (HER2 ligand) were determined with nmol affinity. PMID:26530232

  3. Mark D. Cunningham: award for distinguished contributions to research in public policy.

    PubMed

    2006-11-01

    Presents a citation for Mark D. Cunningham, who received the Award for Distinguished Contributions to Research in Public Policy "for his highly distinguished contributions to research on death-sentenced inmates, capital sentencing determinations, and law." Accompanying the citation are a brief profile and a selected bibliography, as well as Cunningham's award address, entitled Dangerousness and Death: A Nexus in Search of Science and Reason. ((c) 2006 APA, all rights reserved). PMID:17115826

  4. McCay Vernon: award for distinguished senior career contributions to psychology in the public interest.

    PubMed

    2006-11-01

    Presents a citation for McCay Vernon, who received the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest "for fifty-five years of distinguished contributions toward improving the lives of both deaf and deaf-blind individuals." Accompanying the citation are a brief profile and a selected bibliography, as well as Vernon's award address, The APA and Deafness. ((c) 2006 APA, all rights reserved). PMID:17115822

  5. Distinguishing Bonds.

    PubMed

    Rahm, Martin; Hoffmann, Roald

    2016-03-23

    The energy change per electron in a chemical or physical transformation, ΔE/n, may be expressed as Δχ̅ + Δ(VNN + ω)/n, where Δχ̅ is the average electron binding energy, a generalized electronegativity, ΔVNN is the change in nuclear repulsions, and Δω is the change in multielectron interactions in the process considered. The last term can be obtained by the difference from experimental or theoretical estimates of the first terms. Previously obtained consequences of this energy partitioning are extended here to a different analysis of bonding in a great variety of diatomics, including more or less polar ones. Arguments are presented for associating the average change in electron binding energy with covalence, and the change in multielectron interactions with electron transfer, either to, out, or within a molecule. A new descriptor Q, essentially the scaled difference between the Δχ̅ and Δ(VNN + ω)/n terms, when plotted versus the bond energy, separates nicely a wide variety of bonding types, covalent, covalent but more correlated, polar and increasingly ionic, metallogenic, electrostatic, charge-shift bonds, and dispersion interactions. Also, Q itself shows a set of interesting relations with the correlation energy of a bond. PMID:26910496

  6. Distinguished Books.

    ERIC Educational Resources Information Center

    Maryles, Daisy; Ink, Gary

    1998-01-01

    Lists best books by the American Library Association for the general reader, best young adult books, notable children's films and videos, best children's books, notable recordings for children, notable children's software and Web sites, quick picks for reluctant young adult readers, bestsellers of 1997, and literary prizes, 1997. (PEN)

  7. Distinguished Books.

    ERIC Educational Resources Information Center

    Maryles, Daisy; Roback, Diane; Ink, Gary

    2001-01-01

    Includes 12 articles that list notable books for college-bound youth, young adults, and children; paperbacks for young adults; audiobooks for young adults; children's videos; recordings for children; software and Web sites for children; bestsellers of 2000; and literary prizes that were awarded in 2000. (LRW)

  8. Distinguished Books.

    ERIC Educational Resources Information Center

    Bowker Annual Library and Book Trade Almanac, 1994

    1994-01-01

    This section includes lists compiled by the American Library Association (ALA) of the best adult books of 1993, including fiction, poetry, and nonfiction; the best young adult books; the best children's books; best sellers; and recipients of literary prizes. (LRW)

  9. Distinguished Practices of Distinguished Schools.

    ERIC Educational Resources Information Center

    Council for American Private Education, Germantown, MD.

    The Blue Ribbon Schools (BRS) program was designed in 1982 with three purposes in mind: to identify and recognize outstanding schools; to provide schools a tool and criteria for self-assessment and improvement; and to facilitate the sharing of best practices among schools. This book presents profiles and best practices of 12 elementary, 2 middle,…

  10. Parents Produce Explicit Cues That Help Toddlers Distinguish Joking and Pretending.

    PubMed

    Hoicka, Elena; Butcher, Jessica

    2016-05-01

    While separate pieces of research found parents offer toddlers cues to express that they are (1) joking and (2) pretending, and that toddlers and preschoolers understand intentions to (1) joke and (2) pretend, it is not yet clear whether parents and toddlers consider joking and pretending to be distinct concepts. This is important as distinguishing these two forms of non-literal acts could open a gateway to understanding the complexities of the non-literal world, as well as the complexities of intentions in general. Two studies found parents offer explicit cues to help 16- to 24-month-olds distinguish pretending and joking. Across an action play study (n = 25) and a verbal play study (n = 40) parents showed more disbelief and less belief through their actions and language when joking versus pretending. Similarly, toddlers showed less belief through their actions, and older toddlers showed less belief through their language. Toddlers' disbelief could be accounted for by their response to parents' language and actions. Thus, these studies reveal a mechanism by which toddlers learn to distinguish joking and pretending. Parents offer explicit cues to distinguish these intentions, and toddlers use these cues to guide their own behaviors, which in turn allows toddlers to distinguish these intentional contexts. PMID:26194014

  11. Identification of immunohistochemical markers for distinguishing lung adenocarcinoma from squamous cell carcinoma

    PubMed Central

    Zhan, Cheng; Yan, Li; Wang, Lin; Sun, Yang; Wang, Xingxing; Lin, Zongwu; Zhang, Yongxing; Wang, Qun

    2015-01-01

    Background Immunohistochemical staining has been widely used in distinguishing lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC), which is of vital importance for the diagnosis and treatment of lung cancer. Due to the lack of a comprehensive analysis of different lung cancer subtypes, there may still be undiscovered markers with higher diagnostic accuracy. Methods Herein first, we systematically analyzed high-throughput data obtained from The Cancer Genome Atlas (TCGA) database. Combining differently expressed gene screening and receiver operating characteristic (ROC) curve analysis, we attempted to identify the genes which might be suitable as immunohistochemical markers in distinguishing LUAD from LUSC. Then we detected the expression of six of these genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in lung cancer sections using immunohistochemical staining. Results A number of genes were identified as candidate immunohistochemical markers with high sensitivity and specificity in distinguishing LUAD from LUSC. Then the staining results confirmed the potentials of the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) in distinguishing LUAD from LUSC, and their sensitivity and specificity were not less than many commonly used markers. Conclusions The results revealed that the six genes (MLPH, TMC5, SFTA3, DSG3, DSC3 and CALML3) might be suitable markers in distinguishing LUAD from LUSC, and also validated the feasibility of our methods for identification of candidate markers from high-throughput data. PMID:26380766

  12. Distinguishing Features and Similarities Between Descriptive Phenomenological and Qualitative Description Research.

    PubMed

    Willis, Danny G; Sullivan-Bolyai, Susan; Knafl, Kathleen; Cohen, Marlene Z

    2016-09-01

    Scholars who research phenomena of concern to the discipline of nursing are challenged with making wise choices about different qualitative research approaches. Ultimately, they want to choose an approach that is best suited to answer their research questions. Such choices are predicated on having made distinctions between qualitative methodology, methods, and analytic frames. In this article, we distinguish two qualitative research approaches widely used for descriptive studies: descriptive phenomenological and qualitative description. Providing a clear basis that highlights the distinguishing features and similarities between descriptive phenomenological and qualitative description research will help students and researchers make more informed choices in deciding upon the most appropriate methodology in qualitative research. We orient the reader to distinguishing features and similarities associated with each approach and the kinds of research questions descriptive phenomenological and qualitative description research address. PMID:27106878

  13. Charles L. Brewer Award for Distinguished Teaching of Psychology: Sue Frantz.

    PubMed

    2016-01-01

    The American Psychological Foundation (APF) Charles L. Brewer Distinguished Teaching of Psychology Award recognizes an outstanding career contribution to the teaching of psychology. The 2016 recipient of the Distinguished Teaching Award is Sue Frantz. Dorothy W. Cantor, president of the APF, will present the Distinguished Teaching Award at the 124th Annual Convention of the American Psychological Association on August 5, 2016, at 4:00 p.m. Members of the 2016 APF Board of Trustees are Dorothy W. Cantor, president; David H. Barlow, vice president; Melba J. T. Vasquez, secretary; Richard C. McCarty, treasurer; Elisabeth R. Straus, executive vice president/executive director; Cynthia Belar; Camilla Benbow; Rosie Phillips Bingham; Connie S. Chan; Anthony Jackson; Terence M. Keane; Archie L. Turner; W. Bruce Walsh; and Bonnie Markham and Rick McGraw, APA Board of Directors liaisons. (PsycINFO Database Record PMID:27504572

  14. Method and apparatus for distinguishing actual sparse events from sparse event false alarms

    DOEpatents

    Spalding, Richard E.; Grotbeck, Carter L.

    2000-01-01

    Remote sensing method and apparatus wherein sparse optical events are distinguished from false events. "Ghost" images of actual optical phenomena are generated using an optical beam splitter and optics configured to direct split beams to a single sensor or segmented sensor. True optical signals are distinguished from false signals or noise based on whether the ghost image is presence or absent. The invention obviates the need for dual sensor systems to effect a false target detection capability, thus significantly reducing system complexity and cost.

  15. Candice L. Odgers: Awards for Distinguished Early Career Contributions to Psychology in the Public Interest.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Contributions to Psychology in the Public Interest recognize persons who have advanced psychology as a science and/or profession by a single extraordinary achievement or a lifetime of outstanding contributions in the public interest. The 2015 co-recipient of the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest is Candice L. Odgers. Odgers's work addressing the developmental course of externalizing and conduct disorders and substance use yielded key insights into genetic and environmental variations in risk, leading to policy recommendations regarding how best to target interventions." Odgers's award citation, biography, and a selected bibliography are presented here. PMID:26618956

  16. Gary B. Melton: Award for Distinguished Senior Career Contributions to Psychology in the Public Interest.

    PubMed

    2014-11-01

    The APA Awards for Distinguished Contributions to Psychology in the Public Interest recognize persons who have advanced psychology as a science and/or profession by a single extraordinary achievement or a lifetime of outstanding contributions in the public interest. The 2014 recipient of the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest is Gary B. Melton. Melton was selected for his "influential scholarship on critical topics in psychology in the public interest, especially child and family law and policy, forensic mental health services, child advocacy, rural psychology, research ethics, and child abuse and neglect." Melton's award citation, biography, and a selected bibliography are presented here. PMID:25486149

  17. Michael E. Lamb: Award for Distinguished Senior Career Contributions to Psychology in the Public Interest.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Contributions to Psychology in the Public Interest recognize persons who have advanced psychology as a science and/or profession by a single extraordinary achievement or a lifetime of outstanding contributions in the public interest. The 2015 co-recipient of the Award for Distinguished Senior Career Contributions to Psychology in the Public Interest is Michael E. Lamb. Lamb was selected because his "work profoundly shaped the fields of developmental psychology, social welfare, child and family policy, and law." Lamb's award citation, biography, and a selected bibliography are presented here. PMID:26618955

  18. Award for Distinguished Scientific Early Career Contributions to Psychology: Daniel J. Bauer

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Daniel J. Bauer, winner of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for the creative integration of sophisticated quantitative methods with empirical research in the psychological sciences. Bauer draws on his joint training as a developmental and quantitative psychologist to pursue the design,…

  19. Charles L. Brewer Award for Distinguished Teaching in Psychology: G. William Hill IV.

    ERIC Educational Resources Information Center

    American Psychologist, 2004

    2004-01-01

    The 2004 Distinguished Teaching Award is awarded to G. William Hill IV. He is recognized as a superb teacher who has helped the Kennesaw State University faculty through ambitious programs in the Center for Excellence in Teaching and Learning, built and sustained a regional psychology community through the vibrant Southeastern Conference on the…

  20. Influences on Counselor Race Preferences: Distinguishing Black Racial Attitudes from Black Racial Identity

    ERIC Educational Resources Information Center

    Ferguson, Tara M.; Leach, Mark M.; Levy, Jacob J.; Nicholson, Bonnie C.; Johnson, James D.

    2008-01-01

    The authors examined differential contributions of Black racial identity and racial attitudes toward Whites in determining counselor preferences. Results indicated that racial attitudes accounted for a significant portion of the variance in same-race counselor preference. In addition, Black racial attitudes were distinguished from racial identity…

  1. A Developmental Framework for Distinguishing Disruptive Behavior from Normative Misbehavior in Preschool Children

    ERIC Educational Resources Information Center

    Wakschlag, Lauren S.; Briggs-Gowan, Margaret J.; Carter, Alice S.; Hill, Carri; Danis, Barbara; Keenan, Kate; McCarthy, Kimberly J.; Leventhal, Bennett L.

    2007-01-01

    Background: Attaining a developmentally sensitive nosology for preschool disruptive behavior requires characterization of the features that distinguish it from the normative misbehavior of this developmental period. We hypothesize that "quality of behavior and its pervasiveness across contexts" are critical dimensions for clinical discrimination…

  2. Accuracy of radionuclide imaging in distinguishing renal masses from normal variants

    SciTech Connect

    Older, R.A.; Korobkin, M.; Workman, J.; Cleeve, D.M.; Cleeve, L.K.; Sullivan, D.; Webster, G.D.

    1980-08-01

    To determine the accuracy of scintigraphy in distinguishing true renal masses from normal variants, 40 patients with excretory urographic findings indicating a possible, but not definite, mass lesion were studied. Scintigraphy correctly identified 17 true masses and 17 normal variants. Four false positive and two false negative results were obtained.

  3. W. Gregory Keilin: Award for Distinguished Contributions to Education and Training in Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the 2012 winner of the American Psychological Association's Award for Distinguished Contributions to Education and Training in Psychology. W. Gregory Keilin has spent the majority of his professional career providing training and administration for psychology doctoral internship programs as well as leadership service…

  4. Distinguishing Themes of Cultural Responsiveness: A Study of Document-Based Learning

    ERIC Educational Resources Information Center

    Swartz, Ellen E.

    2012-01-01

    This qualitative study examines the distinguishing themes of cultural responsiveness in state- and federally-derived document-based learning materials. Two data sources--"Teaching with Documents" articles in Social Education and Document Based Questions on New York State 11th-grade U.S. History and Government Regents exams--were examined using…

  5. Understanding How Thriving Internet Quasi-Communities Work: Distinguishing between Learning About and Learning To Be.

    ERIC Educational Resources Information Center

    Hung, David; Chen, Der-Thanq

    2002-01-01

    Discusses learning within the context of communities of practice, analyzes Internet-based communities to discover why some online communities thrive and why members are motivated to participate in them, distinguishes quasi-communities from communities, and suggests future directions. (LRW)

  6. Distinguishing Perceived Competence and Self-Efficacy: An Example from Exercise

    ERIC Educational Resources Information Center

    Rodgers, Wendy M.; Markland, David; Selzler, Anne-Marie; Murray, Terra C.; Wilson, Philip M.

    2014-01-01

    This article examined the conceptual and statistical distinction between perceived competence and self-efficacy. Although they are frequently used interchangeably, it is possible that distinguishing them might assist researchers in better understanding their roles in developing enduring adaptive behavior patterns. Perceived competence is conceived…

  7. Nonlinear forecasting as a way of distinguishing chaos from measurement error in time series

    NASA Astrophysics Data System (ADS)

    Sugihara, George; May, Robert M.

    1990-04-01

    An approach is presented for making short-term predictions about the trajectories of chaotic dynamical systems. The method is applied to data on measles, chickenpox, and marine phytoplankton populations, to show how apparent noise associated with deterministic chaos can be distinguished from sampling error and other sources of externally induced environmental noise.

  8. Friederike Range: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Friederike Range for outstanding contributions to the understanding of the complex social minds of nonhuman animals. Through ingenious experimental approaches,…

  9. Distinguishing between Causes and Enabling Conditions--Through Mental Models or Linguistic Cues?

    ERIC Educational Resources Information Center

    Kuhnmunch, Gregory; Beller, Sieghard

    2005-01-01

    The mental model theory of naive causal understanding and reasoning (Goldvarg & Johnson-Laird, 2001, Cognitive Science, 25, 565-610) claims that people distinguish between causes and enabling conditions on the basis of sets of models that represent possible causal situations. In the tasks used to test this hypothesis, however, the proposed set of…

  10. Melissa L. Anderson: APA/APAGS Award for Distinguished Graduate Student in Professional Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the winner of the American Psychological Association/American Psychological Association of Graduate Students Award for Distinguished Graduate Student in Professional Psychology. The 2012 winner is Melissa L. Anderson for her ongoing commitment to understanding, treating, and preventing domestic violence in Deaf women…

  11. Award for Distinguished Contributions to Research in Public Policy: Laurence Steinberg

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Laurence Steinberg, recipient of the Award for Distinguished Contributions to Research in Public Policy, is cited for his extraordinary impact on policy in juvenile justice and child labor and on research into the role of parent and peer relationships in the development of children and adolescents. His groundbreaking research is marked by a…

  12. Award for Distinguished Contributions to the International Advancement of Psychology: Judith V. Torney-Purta

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Judith V. Torney-Purta, recipient of the Award for Distinguished Contributions to the International Advancement of Psychology, is cited for leadership of rigorous research on the development of democratic attitudes and civic knowledge among adolescents from more than 30 countries that has served as a catalyst for education and youth policy reform.…

  13. Using Tractography to Distinguish SWEDD from Parkinson's Disease Patients Based on Connectivity

    PubMed Central

    Kim, Mansu

    2016-01-01

    Background. It is critical to distinguish between Parkinson's disease (PD) and scans without evidence of dopaminergic deficit (SWEDD), because the two groups are different and require different therapeutic approaches. Objective. The aim of this study was to distinguish SWEDD patients from PD patients using connectivity information derived from diffusion tensor imaging tractography. Methods. Diffusion magnetic resonance images of SWEDD (n = 37) and PD (n = 40) were obtained from a research database. Tractography, the process of obtaining neural fiber information, was performed using custom software. Group-wise differences between PD and SWEDD patients were quantified using the number of connected fibers between two regions, and correlation analyses were performed based on clinical scores. A support vector machine classifier (SVM) was applied to distinguish PD and SWEDD based on group-wise differences. Results. Four connections showed significant group-wise differences and correlated with the Unified Parkinson's Disease Rating Scale sponsored by the Movement Disorder Society. The SVM classifier attained 77.92% accuracy in distinguishing between SWEDD and PD using these identified connections. Conclusions. The connections and regions identified represent candidates for future research investigations. PMID:27034889

  14. Distinguished-Level Learning Online: Support Materials from LangNet and RussNet

    ERIC Educational Resources Information Center

    Leaver, Betty Lou; Ehrman, Madeline; Lekic, Maria

    2004-01-01

    This article introduces the reader to two online sources of materials for working on improving listening and reading skills. The materials are intended for learners already at Interagency Language Roundtable (ILR) Level 3 (Superior) proficiency in Arabic, Chinese, Hindi, Korean, Russian, and Spanish, who desire to reach Level 4 (Distinguished, or…

  15. Volatile-sulfur-compound profile distinguishes Burkholderia pseudomallei from Burkholderia thailandensis.

    PubMed

    Inglis, Timothy J J; Hahne, Dorothee R; Merritt, Adam J; Clarke, Michael W

    2015-03-01

    Solid-phase microextraction gas chromatography-mass spectrometry (SPME-GCMS) was used to show that dimethyl sulfide produced by Burkholderia pseudomallei is responsible for its unusual truffle-like smell and distinguishes the species from Burkholderia thailandensis. SPME-GCMS can be safely used to detect dimethyl sulfide produced by agar-grown B. pseudomallei. PMID:25568444

  16. Can Young Children Distinguish Abstract Expressionist Art from Superficially Similar Works by Preschoolers and Animals?

    ERIC Educational Resources Information Center

    Nissel, Jenny; Hawley-Dolan, Angelina; Winner, Ellen

    2016-01-01

    While it is sometimes claimed that abstract art requires little skill and is indistinguishable from the scribbles of young children, recent research has shown that even adults with no training in art can distinguish works by abstract expressionists from superficially similar works by children and even elephants, monkeys, and apes (Hawley-Dolan…

  17. 77 FR 3233 - National Policy for Distinguishing Serious From Non-Serious Injuries of Marine Mammals

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-01-23

    ... [Federal Register Volume 77, Number 14 (Monday, January 23, 2012)] [Notices] [Page 3233] [FR Doc..., 2012. James H. Lecky, Director, Office of Protected Resources, National Marine Fisheries Service. [FR... National Policy for Distinguishing Serious From Non-Serious Injuries of Marine Mammals AGENCY:...

  18. Award for Distinguished Scientific Early Career Contributions to Psychology: Ahmad R. Hariri

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Ahmad R. Hariri, recipient of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for pioneering contributions to understanding the neurobiological mechanisms driving individual differences in complex behavior traits. Hariri has integrated molecular genetics, neuropharmacology, neuroimaging, and psychology in…

  19. Angela J. Grippo: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Angela J. Grippo for her creative contributions in investigating the association between depression and cardiovascular disease in preclinical animal models.…

  20. Bethany Ann Teachman: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Bethany Ann Teachman for transformative, translational research integrating social cognition, life-span, and perceptual approaches to investigating clinical…

  1. Laurie R. Santos: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Laurie R. Santos for creative and insightful investigations of cognition across a broad range of species and psychological domains, illuminating cognitive…

  2. Fanny M. Cheung: Award for Distinguished Contributions to the International Advancement of Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the co-recipients of the American Psychological Association's Award for Distinguished Contributions to the International Advancement of Psychology. One of the 2012 winners is Fanny M. Cheung for her outstanding contributions to the assessment of cross-cultural psychopathology, personality psychology, and gender…

  3. Distinguishing Science from Pseudoscience in School Psychology: Science and Scientific Thinking as Safeguards against Human Error

    ERIC Educational Resources Information Center

    Lilienfeld, Scott O.; Ammirati, Rachel; David, Michal

    2012-01-01

    Like many domains of professional psychology, school psychology continues to struggle with the problem of distinguishing scientific from pseudoscientific and otherwise questionable clinical practices. We review evidence for the scientist-practitioner gap in school psychology and provide a user-friendly primer on science and scientific thinking for…

  4. Volatile-Sulfur-Compound Profile Distinguishes Burkholderia pseudomallei from Burkholderia thailandensis

    PubMed Central

    Hahne, Dorothee R.; Merritt, Adam J.; Clarke, Michael W.

    2015-01-01

    Solid-phase microextraction gas chromatography-mass spectrometry (SPME-GCMS) was used to show that dimethyl sulfide produced by Burkholderia pseudomallei is responsible for its unusual truffle-like smell and distinguishes the species from Burkholderia thailandensis. SPME-GCMS can be safely used to detect dimethyl sulfide produced by agar-grown B. pseudomallei. PMID:25568444

  5. Distinguishing boron desorption from mineral dissolution in arid-zone soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Boron release from six arid-zone soils from the San Joaquin Valley of California was investigated as a function of reaction time, solution pH, and suspension density. A multiple batch extraction experiment was carried out for 362 days to distinguish B desorption from mineral dissolution. Amounts o...

  6. Leslie S. Greenberg: Award for Distinguished Professional Contributions to Applied Research

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the 2012 winner of the American Psychological Association's Award for Distinguished Professional Contributions to Applied Research. Leslie S. Greenberg is an exemplary scientist-practitioner whose pioneering work has significantly altered the landscape of the field of psychotherapy research and practice. His seminal…

  7. Development of the Ability to Distinguish Communicative Intention and Literal Message Meaning.

    ERIC Educational Resources Information Center

    Beal, Carole R.; Flavell, John H.

    1984-01-01

    Investigates children's ability to distinguish the literal meaning of a message and a speaker's communicative intent. Either knowing or not knowing the speaker's intended referent, first- and second-grade children evaluated brief referential communication messages for ambiguity. In the first experiment, messages were written on cards and read to…

  8. Factors Distinguishing between Achievers and At Risk Students: A Qualitative and Quantitative Synthesis

    ERIC Educational Resources Information Center

    Eiselen, R.; Geyser, H.

    2003-01-01

    The purpose of this article is to identify factors that distinguish between Achievers and At Risk Students in Accounting 1A, and to explore how qualitative and quantitative research methods complement each other. Differences between the two groups were explored from both a quantitative and a qualitative perspective, focusing on study habits,…

  9. The use of dynamic thermal analysis to distinguish between genuine and counterfeit drugs.

    PubMed

    Wilczyński, Sławomir

    2015-07-25

    WHO estimates that 10% of drugs are falsified. Economic and health factors arising from the use of counterfeit drugs lead to the development of new methods for distinguishing genuine medicines from falsified ones. The purpose of this study was to develop a new, fast, and inexpensive method to distinguish between original and fake drugs. 10 counterfeit Viagra(®) tablets were compared to 4 original pills (Pfizer). The drugs - both original and fake - were heated to 60°C and then the dynamics of their temperature changes at ambient conditions was tested using a thermal imaging camera. The time constants τ showing the dynamics of temperature changes for Viagra(®) and the falsified drug were determined. The thermokinetic parameters of drugs were determined in the temperature range of 60-22.2°C. Both original and counterfeit tablets had different time constants: 171.44 ± 4.62s and 182.71 ± 4.05 s, respectively. Differences in the dynamics of temperature changes as a function of time are particularly pronounced in the range of t+2 to t+7 min. The comparison of the time constants τ enables to distinguish between genuine and counterfeit drugs. The proposed new method which uses dynamic thermal analysis is an effective, cheap and fast technique to distinguish genuine drugs from counterfeit ones. PMID:25975231

  10. Distinguishing Features of Cuban Children Referred for Professional Help Because of ADHD: Looking beyond the Symptoms

    ERIC Educational Resources Information Center

    Schneider, Barry H.; Normand, Sebastien; Sotares deToro, Maria del Pilar; Santana Gonzalez, Yorkys; Guilarte Tellez, Jorge Antonio; Carbonell Naranjo, Migdalia; Musle, Miriam; Diaz Socarras, Felix Javier; Robaey, Philippe

    2011-01-01

    Objective: To distinguish Cuban children clinically referred because of ADHD from an at-risk community sample and a community control group in terms of symptoms, associated difficulties and impairment of family and peer relations. Method: Parents and teachers of 1,036 children (6-8 years old) completed an established ADHD rating scale and a…

  11. Variables Distinguishing Between Effective and Ineffective Writers in the Tenth Grade.

    ERIC Educational Resources Information Center

    Donelson, Kenneth L.

    1967-01-01

    To provide data for examining the variables that distinguish effective writers from ineffective ones, 1821 mid-west 10th-grade students wrote three themes at 3-week intervals. From a first reading of these papers, the sets of three themes from 432 pupils, which were judged strong or weak in effective writing, were submitted to four judges for…

  12. Comments on "Distinguishing Science from Pseudoscience in School Psychology:" Evidence-Based Interventions for Grandiose Bragging

    ERIC Educational Resources Information Center

    Kratochwill, Thomas R.

    2012-01-01

    The purpose of this article is to provide some perspectives on Lilienfeld, Ammirati, and David's (2012) paper on distinguishing science from pseudoscience in school psychology. In many respects their work represents an intervention for "grandiose bragging," a problem that has occasionally occurred when various non-evidence-based or discredited…

  13. Using Airborne and Satellite Imagery to Distinguish and Map Black Mangrove

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This paper reports the results of studies evaluating color-infrared (CIR) aerial photography, CIR aerial true digital imagery, and high resolution QuickBird multispectral satellite imagery for distinguishing and mapping black mangrove [Avicennia germinans (L.) L.] populations along the lower Texas g...

  14. Award for Distinguished Professional Contributions to Applied Research: Luciano L'Abate

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Luciano L'Abate, recipient of the Award for Distinguished Professional Contributions to Applied Research, contributed to applied research through the introduction of the laboratory method in clinical psychology assessment and intervention, leading to the development of the first automated playroom, linking play therapy with research in child…

  15. Do You "Want" to Play? Distinguishing between Conflicted Shyness and Social Disinterest in Early Childhood

    ERIC Educational Resources Information Center

    Coplan, Robert J.; Prakash, Kavita; O'Neil, Kim; Armer, Mandana

    2004-01-01

    This study attempted to distinguish two types of social withdrawal in early childhood: (a) one based on social fear and anxiety despite a desire to interact socially (conflicted shyness) and (b) one based on the lack of a strong motivation to engage in social interaction (social disinterest). Two samples of preschoolers (n = 119 and n = 127) 3-5…

  16. Award for Distinguished Early Career Contributions to Psychology in the Public Interest: Keith Humphreys

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Keith Humphreys, recipient of the Award for Distinguished Early Career Contributions to Psychology in the Public Interest, is cited for creatively combining a scientist's commitment to rigor, a clinician's emphasis on high-quality mental health care, and a policy analyst's understanding of how to address and resolve social problems. His work as a…

  17. Are Children Able to Distinguish among the Concepts of Aloneness, Loneliness, and Solitude?

    ERIC Educational Resources Information Center

    Galanaki, Evangelia

    2004-01-01

    School-age children's ability to distinguish among the concepts of aloneness, loneliness, and solitude was the focus of this study. This ability has been largely neglected by researchers. Also, the relation of this ability with self-reported loneliness was examined. Individual interviews were conducted with 180 second, fourth, and sixth graders…

  18. Children's Ability to Distinguish between Enjoyment and Non-Enjoyment Smiles

    ERIC Educational Resources Information Center

    Gosselin, Pierre; Perron, Melanie; Maassarani, Reem

    2010-01-01

    Children's ability to distinguish between enjoyment and non-enjoyment smiles was investigated by presenting participants with short video excerpts of smiles. Enjoyment smiles differed from non-enjoyment smiles by greater symmetry and by appearance changes produced in the eye region by the Cheek Raiser action. The results indicate that 6- and…

  19. USING QUICKBIRD SATELLITE IMAGERY TO DISTINGUISH TWO AQUATIC WEEDS IN SOUTH TEXAS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    QuickBird false color satellite imagery was evaluated for distinguishing waterhyacinth [Eichhornia crassipes (Mort.) Solms] and waterlettuce (Pistia stratiotes L.) infestations in a large reservoir in south Texas. The imagery had three bands (green, red, and near-infrared) and contained 11-bit data...

  20. Award for Distinguished Scientific Early Career Contributions to Psychology: Christian N. L. Olivers

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Christian N. L. Olivers, winner of the Award for Distinguished Scientific Early Career Contributions to Psychology, is cited for outstanding research on visual attention and working memory. Olivers uses classic experimental designs in an innovative and sophisticated way to determine underlying mechanisms. He has formulated important theoretical…

  1. Distinguishing among models of strong WL WL scattering at the LHC

    SciTech Connect

    Kilgore, W.B.

    1997-01-01

    Using a multi-channel analysis of strong W{sub L} W{sub L} scattering signals, I study the LHC`s ability to distinguish among various models of strongly interacting electroweak symmetry breaking sectors. 9 refs., 1 fig., 3 tabs.

  2. A National Analysis of Endowed Chairs and Distinguished Professors in the Field of Education

    ERIC Educational Resources Information Center

    Hartlep, Nicholas Daniel; Ball, Daisy; Theodosopoulos, Kendra; Wells, Kevin; Morgan, Grant B.

    2016-01-01

    Noting a gap in the literature, this study examines how race, gender, and prestige are related to endowed and distinguished faculty of education. Specifically, this study seeks to ascertain the makeup of higher education with regard to faculty diversity: what processes are at work that serve to recreate the "status quo" in terms of…

  3. Distinguished Educators on Reading: Contributions That Have Shaped Effective Literacy Instruction.

    ERIC Educational Resources Information Center

    Padak, Nancy D., Ed.; Rasinski, Timothy V., Ed.; Peck, Jacqueline K., Ed.; Church, Brenda Weible, Ed.; Fawcett, Gay, Ed.; Hendershot, Judith M., Ed.; Henry, Justina M., Ed.; Moss, Barbara G., Ed.; Pryor, Elizabeth, Ed.; Roskos, Kathleen A., Ed.; Baumann, James F., Ed.; Dillon, Deborah R., Ed.; Hopkins, Carol J., Ed.; Humphrey, Jack W., Ed.; O'Brien, David G., Ed.

    Drawing from the popular "Distinguished Educator" series of articles in the journal "The Reading Teacher," this book presents 33 essays by respected scholars in nearly every field of reading research and instruction. In addition to the original articles, almost all featured educators have included a professional biography written especially for…

  4. Bob McMurray: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology. The 2012 winner is Bob McMurray for pioneering research on speech and language processing in infants and adults. McMurray has conducted influential work on the graded nature of…

  5. Anthony D. Wagner: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Anthony D. Wagner, who received the Award for Distinguished Scientific Early Career Contributions to Psychology (cognition and human learning) "for outstanding and innovative research on the neural basis of memory and executive control." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115819

  6. Mona M. Amer: APA/APAGS award for distinguished graduate student in professional psychology.

    PubMed

    2006-11-01

    Presents the citation of Mona M. Amer, who received the APA/APAGS Award for Distinguished Graduate Student in Professional Psychology "for her outstanding and innovative leadership in addressing the mental health needs of Muslim and Arab Americans." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115845

  7. Seth D. Pollak: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Seth D. Pollak, who received the Award for Distinguished Scientific Early Career Contributions to Psychology (developmental psychology) "for his research on the mechanisms of emotional development using an innovative combination of methods from psychophysics, neuroscience, and behavioral endocrinology." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115817

  8. APA/APAGS Award for Distinguished Graduate Student in Professional Psychology: Julie E. Braciszewski

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Julie E. Braciszewski, recipient of the APA/APAGS Award for Distinguished Graduate Student in Professional Psychology, is cited for her noteworthy efforts to decrease mental health and academic service disparities among low-income, urban African American youth. Braciszewski recognizes that educational achievement is the clearest and most reliable…

  9. Thomas J. Fagan: award for distinguished professional contributions to practice in the public sector.

    PubMed

    2006-11-01

    Presents the citation for Thomas J. Fagan, who received the Award for Distinguished Professional Contributions to Practice in the Public Sector "for his service as a leader in correctional psychology." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115843

  10. Angela Bryan: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Angela Bryan, who received the Award for Distinguished Scientific Early Career Contributions to Psychology (health psychology) "for her outstanding theoretical and applied research on health behavior change." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115816

  11. Brian J. Scholl: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Brian J. Scholl, who received the Award for Distinguished Scientific Early Career Contributions to Psychology "for his brilliantly creative and sweepingly broad research program that addresses the hard questions in cognitive science." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115818

  12. Stephen M. Weiss: award for distinguished professional contributions to applied research.

    PubMed

    2006-11-01

    Presents the citation for Stephen M. Weiss, who received the Award for Distinguished Professional Contributions to Applied Research "for his work as an internationally recognized leader in the fields of health psychology and behavioral medicine." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115838

  13. Award for Distinguished Contributions to Research in Public Policy: Charlotte J. Patterson

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Charlotte J. Patterson, winner of the Award for Distinguished Contributions to Research in Public Policy, is cited as the world's expert on psychological research on children and youths raised by lesbian and gay parents. Her early analytic syntheses of the literature on the subject greatly influenced other researchers in child and family…

  14. Information-Theoretic Latent Distribution Modeling: Distinguishing Discrete and Continuous Latent Variable Models

    ERIC Educational Resources Information Center

    Markon, Kristian E.; Krueger, Robert F.

    2006-01-01

    Distinguishing between discrete and continuous latent variable distributions has become increasingly important in numerous domains of behavioral science. Here, the authors explore an information-theoretic approach to latent distribution modeling, in which the ability of latent distribution models to represent statistical information in observed…

  15. Bernice Lott: Award for Distinguished Senior Career Contributions to Psychology in the Public Interest

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the winner of the American Psychological Association's Award for Distinguished Senior Career Contributions to Psychology in the Public Interest. The 2012 winner is Bernice Lott. Lott's commitment to the public interest has always guided her career, as her groundbreaking research on gender, ethnicity, and race…

  16. Award for Distinguished Professional Contributions to Institutional Practice: Eduardo S. Morales

    ERIC Educational Resources Information Center

    American Psychologist, 2009

    2009-01-01

    Eduardo S. Morales, recipient of the Award for Distinguished Professional Contributions to Institutional Practice, is cited for his leadership in and contributions to institutional practice through obtaining and implementing research and service grants and creating agencies and programs for Latinos, lesbian, gay, bisexual, and transgender persons,…

  17. Dan Olweus: Award for Distinguished Contributions to Research in Public Policy

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the winner of the American Psychological Association's Award for Distinguished Contributions to Research in Public Policy. The 2012 winner is Dan Olweus for his rigorous scientific research on bullying among children and youth and his early and tireless attention to its public policy implications. Dan Olweus's…

  18. Thomas L. Griffiths: Award for Distinguished Scientific Early Career Contributions to Psychology

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of one of the winners of the American Psychological Association's Award for Distinguished Scientific Early Career Contributions to Psychology (2012). Thomas L. Griffiths won the award for bringing mathematical precision to the deepest questions in human learning, reasoning, and concept formation. In his pioneering work,…

  19. Marguerita Lightfoot: Award for Distinguished Early Career Contributions to Psychology in the Public Interest

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the winner of the American Psychological Association's Award for Distinguished Early Career Contributions to Psychology in the Public Interest. The 2012 winner is Marguerita Lightfoot for her leadership, innovation, and commitment to applying psychological principles to develop behavioral health interventions for…

  20. Sandra L. Shullman: Award for Distinguished Professional Contributions to Independent Practice

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the winner of the American Psychological Association's Award for Distinguished Professional Contributions to Independent Practice. The 2012 winner is Sandra L. Shullman for her outstanding contributions and leadership as an independent practitioner in the fields of counseling and consulting psychology. Through her…

  1. C. Cybele Raver: Award for Distinguished Contributions of Applications of Psychology to Education and Training

    ERIC Educational Resources Information Center

    American Psychologist, 2012

    2012-01-01

    Presents a short biography of the 2012 winner of the American Psychological Association's Award for Distinguished Contributions of Applications of Psychology to Education and Training. C. Cybele Raver is a prolific and award-winning writer who has published widely and served as a reviewer on many high-quality journals. Her publications are well…

  2. Distinguishing Bark Beetle-infested Vegetation by Tree Species Types and Stress Levels using Landsat Data

    NASA Astrophysics Data System (ADS)

    Sivanpillai, R.; Ewers, B. E.; Speckman, H. N.; Miller, S. N.

    2015-12-01

    In the Western United States, more than 3 million hectares of lodgepole pine forests have been impacted by the Mountain pine beetle outbreak, while another 166,000 hectares of spruce-fir forests have been attacked by Spruce beetle. Following the beetle attack, the trees lose their hydraulic conductivity thus altering their carbon and water fluxes. These trees go through various stages of stress until mortality, described by color changes in their needles prior to losing them. Modeling the impact of these vegetation types require thematically precise land cover data that distinguishes lodgepole pine and spruce-fir forests along with the stage of impact since the ecosystem fluxes are different for these two systems. However, the national and regional-scale land cover datasets derived from remotely sensed data do not have this required thematic precision. We evaluated the feasibility of multispectral data collected by Landsat 8 to distinguish lodgepole pine and spruce fir, and subsequently model the different stages of attack using field data collected in Medicine Bow National Forest (Wyoming, USA). Operational Land Imager, onboard Landsat 8 has more spectral bands and higher radiometric resolution (12 bit) in comparison to sensors onboard earlier Landsat missions which could improve the ability to distinguish these vegetation types and their stress conditions. In addition to these characteristics, its repeat coverage, rigorous radiometric calibration, wide swath width, and no-cost data provide unique advantages to Landsat data for mapping large geographic areas. Initial results from this study highlight the importance of SWIR bands for distinguishing different levels of stress, and the need for ancillary data for distinguishing species types. Insights gained from this study could lead to the generation of land cover maps with higher thematic precision, and improve the ability to model various ecosystem processes as a result of these infestations.

  3. Comparison of candidate methods to distinguish noise modes from system modes in structural identification

    NASA Technical Reports Server (NTRS)

    Longman, Richard W.; Lew, Jiann-Shiun; Juang, Jer-Nan

    1992-01-01

    In modal identification, nonphysical noise or computation modes always appear to help match the input-output data. This paper studies the ability of four criteria to distinguish which modes in a model are noise modes: (1) modal amplitude coherency, (2) the relative contribution of each mode to the pulse response indicated by the mode singular value, (3) the variances of the mode frequencies and damping factors produced by a chosen measurement noise level, and (4) identification of the backward-time in order to let the shift from positive to negative damping of the true system modes distinguish these modes from noise modes. Both simulated and experimental data are used to study the four criteria.

  4. Equilibration of isolated many-body quantum systems with respect to general distinguishability measures

    NASA Astrophysics Data System (ADS)

    Balz, Ben N.; Reimann, Peter

    2016-06-01

    We demonstrate equilibration of isolated many-body systems in the sense that, after initial transients have died out, the system behaves practically indistinguishable from a time-independent steady state, i.e., non-negligible deviations are unimaginably rare in time. Measuring the distinguishability in terms of quantum mechanical expectation values, results of this type have been previously established under increasingly weak assumptions about the initial disequilibrium, the many-body Hamiltonian, and the considered observables. Here, we further extend these results with respect to generalized distinguishability measures which fully take into account the fact that the actually observed, primary data are not expectation values but rather the probabilistic occurrence of different possible measurement outcomes.

  5. Belief in a just what? Demystifying just world beliefs by distinguishing sources of justice.

    PubMed

    Stroebe, Katherine; Postmes, Tom; Täuber, Susanne; Stegeman, Alwin; John, Melissa-Sue

    2015-01-01

    People's Belief in a Just World (BJW) plays an important role in coping with misfortune and unfairness. This paper demonstrates that understanding of the BJW concept, and its consequences for behavior, is enhanced if we specify what (or who) the source of justice might be. We introduce a new scale, the 5-Dimensional Belief in a Just Treatment Scale (BJT5), which distinguishes five causal dimensions of BJW (God, Nature, Other People, Self, Chance). We confirm the 5-factor structure of the BJT5. We then address whether the BJW should be considered a uni- and/or multi-dimensional construct and find support for our multi-dimensional approach. Finally, we demonstrate convergent and discriminant validity with respect to important correlates of BJW as well as action in response to important negative life events and societal attitudes. This work illustrates the importance of distinguishing causal dimensions with regard to who distributes justice. PMID:25803025

  6. Jon Carlson: Award for Distinguished Career Contributions to Education and Training in Psychology.

    PubMed

    2011-11-01

    Presents Jon Carlson as the 2011 winner of the American Psychological Association Award for Distinguished Career Contributions to Education and Training in Psychology. "For his contributions in creating educational and training materials in psychology for instruction and the public. Jon Carlson has a distinguished career in higher education, maintained an active private practice, served 34 years as a school psychologist/counselor, is a prolific author and scholar, and is an innovator in the development of media-based training materials. His contribution to education and training is noteworthy for the volume of his professional production, the scope of topics addressed, and his ability to provide meaningful tools to change how psychologists are trained. His audiovisual work documents the profession of psychology in terms of research and practice for current scholars and for future generations." (PsycINFO Database Record (c) 2011 APA, all rights reserved). PMID:22082400

  7. Distinguishing between a true period and its alias, and other tasks of model discrimination

    NASA Astrophysics Data System (ADS)

    Baluev, Roman V.

    2012-05-01

    We consider the task of distinguishing between two different alternative models that can explain observed time-series data roughly equally, mainly focusing on the period-ambiguity case (aliasing). We propose a test for checking whether the rival models are observationally equivalent for now or are already distinguishable: the Vuong closeness test, which is based on the Kullback-Leibler information criterion. It is asymptotically normal and can work (in a certain sense) even in a misspecified case in which both proposed alternatives are actually wrong. This test is also very simple for practical use. We apply it to several known extrasolar planetary systems and find that our method often helps to resolve various model ambiguities emerging in astronomical practice, but prevents us from hasty conclusions in other cases.

  8. Distinguishability and chiral stability in solution: Effects of decoherence and intermolecular interactions

    SciTech Connect

    Han, Heekyung; Wardlaw, David M.; Frolov, Alexei M.

    2014-05-28

    We examine the effect of decoherence and intermolecular interactions (chiral discrimination energies) on the chiral stability and the distinguishability of initially pure versus mixed states in an open chiral system. Under a two-level approximation for a system, intermolecular interactions are introduced by a mean-field theory, and interaction between a system and an environment is modeled by a continuous measurement of a population difference between the two chiral states. The resultant equations are explored for various parameters, with emphasis on the combined effects of the initial condition of the system, the chiral discrimination energies, and the decoherence in determining: the distinguishability as measured by a population difference between the initially pure and mixed states, and the decoherence process; the chiral stability as measured by the purity decay; and the stationary state of the system at times long relative to the time scales of the system dynamics and of the environmental effects.

  9. Belief in a Just What? Demystifying Just World Beliefs by Distinguishing Sources of Justice

    PubMed Central

    Stroebe, Katherine; Postmes, Tom; Täuber, Susanne; Stegeman, Alwin; John, Melissa-Sue

    2015-01-01

    People’s Belief in a Just World (BJW) plays an important role in coping with misfortune and unfairness. This paper demonstrates that understanding of the BJW concept, and its consequences for behavior, is enhanced if we specify what (or who) the source of justice might be. We introduce a new scale, the 5-Dimensional Belief in a Just Treatment Scale (BJT5), which distinguishes five causal dimensions of BJW (God, Nature, Other People, Self, Chance). We confirm the 5-factor structure of the BJT5. We then address whether the BJW should be considered a uni- and/or multi-dimensional construct and find support for our multi-dimensional approach. Finally, we demonstrate convergent and discriminant validity with respect to important correlates of BJW as well as action in response to important negative life events and societal attitudes. This work illustrates the importance of distinguishing causal dimensions with regard to who distributes justice. PMID:25803025

  10. Multicolored Silver Nanoparticles for Multiplexed Disease Diagnostics: Distinguishing Dengue, Yellow Fever, and Ebola Viruses

    PubMed Central

    Yen, Chun-Wan; de Puig, Helena; Tam, Justina; Gómez-Márquez, José; Bosch, Irene; Hamad-Schifferli, Kimberly; Gehrke, Lee

    2015-01-01

    Rapid point-of-care (POC) diagnostic devices are needed for field-forward screening of severe acute systemic febrile illnesses. Multiplexed rapid lateral flow diagnostics have the potential to distinguish among multiple pathogens, thereby facilitating diagnosis and improving patient care. Here, we present a platform for multiplexed pathogen detection using multi-colored silver nanoplates. This design requires no external excitation source and permits multiplexed analysis in a single channel, facilitating integration and manufacturing. PMID:25672590

  11. Fluorescence from Pearls to Distinguish Mother Oysters Used in Pearl Culture

    NASA Astrophysics Data System (ADS)

    Miyoshi, Tadaki; Matsuda, Yasunori; Komatsu, Hiroshi

    1987-04-01

    The fluorescence spectra of pearls and shells of Pteria penguin (mabe), Pinctada fucata (Japan’s Akoya oyster) and Pinctada maxima (yellow lip oyster) have been measured in order to distinguish species of the mother oyster which produce that pearl. A distinction is possible for these pearls using differences in the fluorescence spectra. The spectral difference has been attributable to colouring matter or screloprotain in pearls and shells.

  12. Rose L. Clark: award for distinguished early career contributions to psychology in the public interest.

    PubMed

    2006-11-01

    Presents a citation for Rose L. Clark, who received the Award for Distinguished Early Career Contributions to Psychology in the Public Interest "for her leadership and contributions to the field of psychology in the awareness and advancement of research, practice, and policy on behalf of American Indian/Alaska Native (AI/AN) children, families, and communities." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115824

  13. Mark G. Baxter: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Mark G. Baxter, who received the Award for Distinguished Scientific Early Career Contributions to Psychology (animal learning and behavior, comparative) "for insightful and incisive contributions in studies of learning, memory, attentional processing, executive function, and goal-directed behavior in work that has translated across species." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115814

  14. Michael C. Roberts: award for distinguished contributions to education and training in psychology.

    PubMed

    2006-11-01

    Presents a citation for Michael C. Roberts, who received the Award for Distinguished Contributions to Education and Training in Psychology "for his dedication to the education, training, and mentoring of psychologists from undergraduate study through professional career." Accompanying the citation are a brief profile and a selected bibliography, as well as Roberts' award address, entitled Essential Tension: Specialization With Broad and General Training in Psychology. ((c) 2006 APA, all rights reserved). PMID:17115832

  15. Rosie Phillips Bingham: Award for Distinguished Professional Contributions to Institutional Practice.

    PubMed

    2015-11-01

    The APA Awards for Distinguished Professional Contributions to Institutional Practice are intended to recognize outstanding practitioners in psychology. One of the 2015 award winners is Rosie Phillips Bingham, who received this award for being "an extraordinary psychologist and dedicated, visionary leader who has made a tremendous difference in psychology and in the institutions in which she has worked." Rosie's award citation, biography, and a selected bibliography are presented here. PMID:26618973

  16. Theodore P. Beauchaine: award for distinguished scientific early career contributions to psychology.

    PubMed

    2006-11-01

    Presents the citation for Theodore P. Beauchaine, who received the Award for Distinguished Scientific Early Career Contributions to Psychology (psychopathology) "for core contributions in developmental psychopathology, especially related to the biological underpinnings of various mental disorders among children, sophisticated and elegant quantitative approaches to these issues, and exemplary work on the prevention of such conditions." A brief profile and a selected bibliography accompany the citation. ((c) 2006 APA, all rights reserved). PMID:17115815

  17. Janet E. Helms: award for distinguished contributions to education and training in psychology.

    PubMed

    2006-11-01

    Presents a citation for Janet E. Helms, who received the Award for Distinguished Contributions to Education and Training in Psychology "for her remarkable contribution to a conceptual and reiterative empirical base that has transformed the study of racism in our time." Accompanying the citation are a brief profile and a selected bibliography, as well as Helms' award address, entitled Fairness Is Not Validity or Cultural Bias in Racial-Group Assessment: A Quantitative Perspective. ((c) 2006 APA, all rights reserved). PMID:17115830

  18. Michael Cole: award for distinguished contributions to the international advancement of psychology.

    PubMed

    2006-11-01

    Presents the citation for Michael Cole, who received the Award for Distinguished Contributions to the International Advancement of Psychology "for his significant and influential contributions to understanding the cultural and historical construction of human life and the implications of collective social practices for human development." Accompanying the citation are a brief profile and a selected bibliography, as well as Cole's award address, entitled Internationalism in Psychology: We Need It Now More Than Ever. ((c) 2006 APA, all rights reserved). PMID:17115848

  19. Predictive Ability of Galilei to Distinguish Subclinical Keratoconus and Keratoconus from Normal Corneas

    PubMed Central

    Feizi, Sepehr; Yaseri, Mehdi; Kheiri, Bahareh

    2016-01-01

    Purpose: To determine the predictive ability of different data measured by the Galilei dual Scheimpflug analyzer in differentiating subclinical keratoconus and keratoconus from normal corneas. Methods: This prospective comparative study included 136 normal eyes, 23 eyes with subclinical keratoconus, and 51 keratoconic eyes. In each eye, keratometric values, pachymetry, elevation parameters and surface indices were evaluated. Receiver operating characteristic (ROC) curves were calculated and quantified by using the area under the curve (AUC) to compare the sensitivity and specificity of the measured parameters and to identify optimal cutoff points for differenciating subclinical keratoconus and keratoconus from normal corneas. Several model structures including keratometric, pachymetric, elevation parameters and surface indices were analyzed to find the best model for distinguishing subclinical and clinical keratoconus. The data sets were also examined using the non-parametric “classification and regression tree” (CRT) technique for the three diagnostic groups. Results: Nearly all measured parameters were strong enough to distinguish keratoconus. However, only the radius of best fit sphere and keratometry readings had an acceptable predictive accuracy to differentiate subclinical keratoconus. Elevation parameters and surface indices were able to differentiate keratoconus from normal corneas in 100% of eyes. Meanwhile, none of the parameter sets could effectively discriminate subclinical keratoconus; a 3-factor model including keratometric variables, elevation data and surface indices provided the highest predictive ability for this purpose. Conclusion: Surface indices measured by the Galilei analyzer can effectively differentiate keratoconus from normal corneas. However, a combination of different data is required to distinguish subclinical keratoconus. PMID:27195079

  20. Beating the Shot-Noise Limit with Partially-Distinguishable Photons

    NASA Astrophysics Data System (ADS)

    Birchall, Patrick M.; Sabines-Chesterking, Javier; O'Brien, Jeremy L.; Cable, Hugo; Matthews, Jonathan C. F.

    Quantum metrology promises high-precision measurements beyond the capability of any classical techniques. This has the potential to be an integral part of investigative techniques, utilised across all areas of science and technology. However, all sensors must be able to operate despite imperfections to be of practical use. Proposals for photonic quantum sensors typically exploit quantum interference between photons which are perfectly indistinguishable, but achieving this indistinguishability can be a major technical challenge in practice, in particular with immature but promising approaches to photon sources. Here we show that highly indistinguishable photons are not required for quantum-enhanced measurements, nor do partially distinguishable photons have to be engineered to mitigate the effects of distinguishability. We conduct an experiment to verify the utility of two- and four-photon states containing partially distinguishable particles by performing quantum-enhanced measurements with low-visibility quantum interference. This demonstrates that sources producing spectrally-mixed single photons can be readily applied in quantum metrology systems.