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Publications (25)166.52 Total impact
Article: PS1 - 10. Obesity induces CD11c+ macrophages in murine adipose tissue which are distinctive from, but resemble, dendritic cells[Show abstract] [Hide abstract]
ABSTRACT: During obesity, inflammatory 'M1' macrophages infiltrate adipose tissue (AT). These 'M1' AT macrophages (ATMs) express the dendritic cell marker CD11c. Dendritic cells are immune regulators that promote insulin resistance. However, it is unclear whether and how CD11c+ ATMs differ from dendritic cells and if they are activated by obesity.11/2015; 11(4):148-149. DOI:10.1007/s12467-013-0088-5
Article: Myeloid A Disintegrin and Metalloproteinase Domain 10 Deficiency Modulates Atherosclerotic Plaque Composition by Shifting the Balance from Inflammation toward Fibrosis[Show abstract] [Hide abstract]
ABSTRACT: A disintegrin and metalloproteinase domain 10 (ADAM10) is a metalloprotease involved in cleavage of various cell surface molecules, such as adhesion molecules, chemokines, and growth factor receptors. Although we have previously shown an association of ADAM10 expression with atherosclerotic plaque progression, a causal role of ADAM10 in atherosclerosis has not been investigated. Bone marrow from conditional knockout mice lacking Adam10 in the myeloid lineage or from littermate controls was transplanted into lethally irradiated Ldlr(-/-) mice on an atherogenic diet. Myeloid Adam10 deficiency did not affect plaque size, but it increased plaque collagen content. Matrix metalloproteinase 9 and 13 expression and matrix metalloproteinase 2 gelatinase activity were significantly impaired in Adam10-deficient macrophages, whereas their capacity to stimulate collagen production was unchanged. Furthermore, relative macrophage content in advanced atherosclerotic lesions was decreased. In vitro, Adam10-deficient macrophages showed reduced migration toward monocyte chemoattractant protein-1 and transmigration through collagen. In addition, Adam10-deficient macrophages displayed increased anti-inflammatory phenotype with elevated IL-10, and reduced production of proinflammatory tumor necrosis factor, IL-12, and nitric oxide in response to lipopolysaccharide. These data suggest a critical role of Adam10 for leukocyte recruitment, inflammatory mediator production, and extracellular matrix degradation. Thereby, myeloid ADAM10 may play a causal role in modulating atherosclerotic plaque stability. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.American Journal Of Pathology 02/2015; 185(4). DOI:10.1016/j.ajpath.2014.11.028
Article: Glyoxalase 1 overexpression does not affect atherosclerotic lesion size and severity in ApoE(-/-) mice with or without diabetes[Show abstract] [Hide abstract]
ABSTRACT: Advanced glycation endproducts (AGEs) and their precursors have been associated with the development of atherosclerosis. We recently discovered that glyoxalase 1 (GLO1), the major detoxifying enzyme for AGE-precursors, is decreased in ruptured human plaques and that levels of AGEs are higher in rupture-prone plaques. We here investigated whether overexpression of human GLO1 in ApoE(-/-) mice could reduce development of atherosclerosis METHODS AND RESULTS: We crossed C57Bl6 ApoE(-/-) mice with C57Bl6 GLO1 overexpressing mice (huGLO1(+/-)) to generate ApoE(-/-) (n=16) and ApoE(-/-) huGLO1(+/-) (n=20) mice. To induce diabetes, we injected a subset with streptozotocin to generate diabetic ApoE(-/-) (n=8) and ApoE(-/-) huGLO1(+/-) (n=13) mice. All mice were fed chow and sacrificed at 25 weeks of age. The GLO1 activity was threefold increased in huGLO1(+/-) aorta, but aortic root lesion size and phenotype did not differ between mice with- and without huGLO1(+/-) overexpression. We detected no differences in gene expression in aortic arches, in AGE levels and cytokines, in circulating cells and endothelial function between ApoE(-/-) mice with- and without huGLO1(+/-) overexpression. Although diabetic mice showed decreased GLO1 expression (p<0.05) and increased lesion size (p<0.05) in comparison to non-diabetic mice, GLO1 overexpression also did not affect the aortic root lesion size or inflammation in diabetic mice.Cardiovascular Research 08/2014; 104(1). DOI:10.1093/cvr/cvu189
Article: Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis[Show abstract] [Hide abstract]
ABSTRACT: Atherosclerosis is a lipid-driven inflammatory disease of the vessel wall, characterized by the chronic activation of macrophages. We investigated whether the helminth-derived antigens [soluble egg antigens (SEAs)] could modulate macrophage inflammatory responses and protect against atherosclerosis in mice. In bone marrow-derived macrophages, SEAs induce anti-inflammatory macrophages, typified by high levels of IL-10 and reduced secretion of proinflammatory mediators. In hyperlipidemic LDLR(-/-) mice, SEA treatment reduced plaque size by 44%, and plaques were less advanced compared with PBS-injected littermate controls. The atheroprotective effect of SEAs was found to be mainly independent of cholesterol lowering and T-lymphocyte responses but instead could be attributed to diminished myeloid cell activation. SEAs reduced circulating neutrophils and inflammatory Ly6C(high) monocytes, and macrophages showed high IL-10 production. In line with the observed systemic effects, atherosclerotic lesions of SEA-treated mice showed reduced intraplaque inflammation as inflammatory markers [TNF-α, monocyte chemotactic protein 1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and CD68], neutrophil content, and newly recruited macrophages were decreased. We show that SEA treatment protects against atherosclerosis development by dampening inflammatory responses. In the future, helminth-derived components may provide novel opportunities to treat chronic inflammatory diseases, as they diminish systemic inflammation and reduce the activation of immune cells.-Wolfs, I. M. J., Stöger, J. L., Goossens, P., Pöttgens, C., Gijbels, M. J. J., Wijnands, E., van der Vorst, E. P. C., van Gorp, P., Beckers, L., Engel, D., Biessen, E. A. L., Kraal, G., van Die, I., Donners, M. M. P. C., de Winther, M. P. J. Reprogramming macrophages to an anti-inflammatory phenotype by helminth antigens reduces murine atherosclerosis.The FASEB Journal 09/2013; 28(1). DOI:10.1096/fj.13-235911
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ABSTRACT: Cardiac hypertrophy and subsequent heart failure triggered by chronic hypertension represent major challenges for cardiovascular research. Beyond neurohormonal and myocyte signaling pathways, growing evidence suggests inflammatory signaling pathways as therapeutically targetable contributors to this process. We recently reported that microRNA-155 is a key mediator of cardiac inflammation and injury in infectious myocarditis. Here we investigated the impact of miRNA-155 manipulation in hypertensive heart disease. Genetic loss or pharmacological inhibition of the leukocyte-expressed microRNA-155 in mice markedly reduced cardiac inflammation, hypertrophy and dysfunction upon pressure overload. These alterations were macrophage-dependent, as in vivo cardiomyocyte-specific microRNA-155 manipulation did not affect cardiac hypertrophy or dysfunction, whereas bone marrow transplantation from wild type into microRNA-155 knockout animals rescued the cardiomyocytes' hypertrophic response and vice versa. In vitro, media from microRNA-155 knockout macrophages blocked the hypertrophic growth of stimulated cardiomyocytes, confirming that macrophages influence myocyte growth in a miR-155-dependent paracrine manner. These effects were at least partly mediated by the direct microRNA-155 target Suppressor of Cytokine Signaling 1 (Socs1), as Socs1 knockdown in microRNA-155 knockout macrophages largely restored their hypertrophy-stimulating potency. Our findings reveal that microRNA-155 expression in macrophages promotes cardiac inflammation, hypertrophy and failure in response to pressure overload. These data support the causative significance of inflammatory signaling in hypertrophic heart disease and demonstrate the feasibility of therapeutic microRNA targeting of inflammation in heart failure.Circulation 08/2013; 128(13). DOI:10.1161/CIRCULATIONAHA.112.001357
Article: Hematopoietic G-protein-coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor-knockout mice[Show abstract] [Hide abstract]
ABSTRACT: Leukocyte chemotaxis is deemed instrumental in initiation and progression of atherosclerosis. It is mediated by G-protein-coupled receptors (e.g., CCR2 and CCR5), the activity of which is controlled by G-protein-coupled receptor kinases (GRKs). In this study, we analyzed the effect of hematopoietic deficiency of a potent regulator kinase of chemotaxis (GRK2) on atherogenesis. LDL receptor-deficient (LDLr(-)(/)(-)) mice with heterozygous hematopoietic GRK2 deficiency, generated by bone marrow transplantation (n=15), displayed a dramatic attenuation of plaque development, with 79% reduction in necrotic core and increased macrophage content. Circulating monocytes decreased and granulocytes increased in GRK2(+/)(-) chimeras, which could be attributed to diminished granulocyte colony-forming units in bone marrow. Collectively, these data pointed to myeloid cells as major mediators of the impaired atherogenic response in GRK2(+/)(-) chimeras. LDLr(-)(/)(-) mice with macrophage/granulocyte-specific GRK2 deficiency (LysM-Cre GRK2(flox/flox); n=8) failed to mimic the aforementioned phenotype, acquitting these cells as major responsible subsets for GRK2 deficiency-associated atheroprotection. To conclude, even partial hematopoietic GRK2 deficiency prevents atherosclerotic lesion progression beyond the fatty streak stage, identifying hematopoietic GRK2 as a potential target for intervention in atherosclerosis.-Otten, J. J. T., de Jager, S. C. A., Kavelaars, A., Seijkens, T., Bot, I., Wijnands, E., Beckers, L., Westra, M. M., Bot, M., Busch, M., Bermudez, B., van Berkel, T. J. C., Heijnen, C. J., Biessen, E. A. L. Hematopoietic G-protein-coupled receptor kinase 2 deficiency decreases atherosclerotic lesion formation in LDL receptor-knockout mice.The FASEB Journal 10/2012; 27(1). DOI:10.1096/fj.12-205351
Article: MicroRNA Profiling Identifies MicroRNA-155 as an Adverse Mediator of Cardiac Injury and Dysfunction During Acute Viral Myocarditis[Show abstract] [Hide abstract]
ABSTRACT: Viral myocarditis results from an adverse immune response to cardiotropic viruses, which causes irreversible myocyte destruction and heart failure in previously healthy people. The involvement of microRNAs and their usefulness as therapeutic targets in this process are unknown. To identify microRNAs involved in viral myocarditis pathogenesis and susceptibility. Cardiac microRNAs were profiled in both human myocarditis and in Coxsackievirus B3-injected mice, comparing myocarditis-susceptible with nonsusceptible mouse strains longitudinally. MicroRNA responses diverged depending on the susceptibility to myocarditis after viral infection in mice. MicroRNA-155, -146b, and -21 were consistently and strongly upregulated during acute myocarditis in both humans and susceptible mice. We found that microRNA-155 expression during myocarditis was localized primarily in infiltrating macrophages and T lymphocytes. Inhibition of microRNA-155 by a systemically delivered LNA-anti-miR attenuated cardiac infiltration by monocyte-macrophages, decreased T lymphocyte activation, and reduced myocardial damage during acute myocarditis in mice. These changes were accompanied by the derepression of the direct microRNA-155 target PU.1 in cardiac inflammatory cells. Beyond the acute phase, microRNA-155 inhibition reduced mortality and improved cardiac function during 7 weeks of follow-up. Our data show that cardiac microRNA dysregulation is a characteristic of both human and mouse viral myocarditis. The inflammatory microRNA-155 is upregulated during acute myocarditis, contributes to the adverse inflammatory response to viral infection of the heart, and is a potential therapeutic target for viral myocarditis.Circulation Research 06/2012; 111(4):415-25. DOI:10.1161/CIRCRESAHA.112.267443
Article: Abrogated transforming growth factor beta receptor II (TGFβRII) signalling in dendritic cells promotes immune reactivity of T cells resulting in enhanced atherosclerosis[Show abstract] [Hide abstract]
ABSTRACT: AimsThe importance of transforming growth factor beta (TGFβ) as an immune regulatory cytokine in atherosclerosis has been established. However, the role of TGFβ signalling in dendritic cells (DCs) and in DC-mediated T cell proliferation and differentiation in atherosclerosis is unknown.Methods and resultsHere, we investigated the effect of disrupted TGFβ signalling in DCs on atherosclerosis by using mice carrying a transgene resulting in functional inactivation of TGFβ receptor II (TGFβRII) signalling in CD11c(+) cells (Apoe(-/-)CD11cDNR). Apoe(-/-)CD11cDNR mice exhibited an over two-fold increase in the plaque area compared with Apoe(-/-) mice. Plaques of Apoe(-/-)CD11cDNR mice showed an increase in CD45(+) leucocyte content, and specifically in CD3(+), CD4(+) and CD8(+) cells, whereas macrophage content was not affected. In lymphoid organs, Apoe(-/-)CD11cDNR mice had equal amounts of CD11c(+) cells, and CD11c(+)CD8(+) and CD11c(+)CD8(-) subsets, but showed a subtle shift in the CD11c(+)CD8(-) population towards the more inflammatory CD11c(+)CD8(-)CD4(-) DC subset. In addition, the number of plasmacytoid-DCs decreased. Maturation markers such as MHCII, CD86 and CD40 on CD11c(hi) cells did not change, but the CD11cDNR DCs produced more TNFα and IL-12. CD11c(+) cells from CD11cDNR mice strongly induced T-cell proliferation and activation, resulting in increased amounts of effector T cells producing high amounts of Th1 (IFN-γ), Th2 (IL-4, IL-10), Th17 (IL-17), and Treg (IL-10) cytokines.Conclusion Here, we show that loss of TGFβRII signalling in CD11c(+) cells induces subtle changes in DC subsets, which provoke uncontrolled T cell activation and maturation. This results in increased atherosclerosis and an inflammatory plaque phenotype during hypercholesterolaemia.European Heart Journal 05/2012; 34(48). DOI:10.1093/eurheartj/ehs106
Article: O14 Rôle du CD40 et des molécules adaptatrices TRAF dans le développement de l'obésité et de ses complications métaboliques[Show abstract] [Hide abstract]
ABSTRACT: Rationnel L'obésité constitue un facteur de risque pour les pathologies métaboliques et vasculaires telles que l'insulino-résistance, la stéatose hépatique ou l'athérosclérose. L'inflammation joue un rôle pivot dans le développement des désordres métaboliques. Il est clairement établi que les cellules immunitaires s'accumulent dans le tissu adipeux mais leurs interactions, entres elles ou avec les adipocytes, sont encore mal connues. Nous avons montré que la déficience en CD40 ligand améliore la prise de poids, l'inflammation adipeuse et la sensibilité à l'insuline chez la souris obèse. Notre objectif est ici d'étudier le rôle du récepteur CD40 et des molécules adaptatrices TRAF. Matériels et méthodes Des souris déficientes en CD40 re-exprimant ou non un CD40 présentant des mutations modifiant les sites de liaison aux TRAF (CD40-WT, CD40-TRAF2, CD40-TRAF6, CD40-TRAF2/6) ont reçu une alimentation hyperlipidique (18–20 semaines). Les paramètres inflammatoires et métaboliques ont été évalués. Résultats Contrairement au déficit en CD40L, celui en CD40 ne protège pas de la prise de poids, augmente l'infiltration des CD3+ dans le tissu adipeux et l'intolérance au glucose. Les souris déficientes pour la signalisation TRAF2/6 présentent un gain de poids accéléré comparées aux autres génotypes. À poids égal, ces souris sont plus fortement intolérantes au glucose et insulino-résistantes. L'infiltration de leur tissu adipeux par les lymphocytes T pro-inflammatoires est augmentée alors que celle des lymphocytes T régulateurs est réduite. La stéatose hépatique est nettement augmentée chez les souris CD40-TRAF2/6. Le phénotype des TRAF2 est similaire, bien que moins prononcé, tandis que celui des TRAF6 est peu ou pas modifié. Conclusion De façon inattendue, le déficit en CD40 aggrave les complications métaboliques et inflammatoires de l'obésité. L'absence de signalisation CD40-TRAF2/6 amplifie les effets délétères du régime gras, suggérant un rôle protecteur de cette voie inflammatoire. Sa modulation pourrait constituer une cible d'intérêt dans le traitement de l'obésité et complications associées.Diabetes & Metabolism 03/2012; 38:A4. DOI:10.1016/S1262-3636(12)70992-8
Article: CD40L Deficiency Ameliorates Adipose Tissue Inflammation and Metabolic Manifestations of Obesity in Mice[Show abstract] [Hide abstract]
ABSTRACT: Obese adipose tissue shows hallmarks of chronic inflammation, which promotes the development of metabolic disorders. The mechanisms by which immune cells interact with each other or with metabolism-associated cell types, and the players involved, are still unclear. The CD40-CD40L costimulatory dyad plays a pivotal role in immune responses and in diseases such as atherosclerosis and may therefore be a mediator of obesity. Here we investigated whether CD40L is involved in adipose tissue inflammation and its associated metabolic changes. To assess a putative role of CD40L in obesity in vivo, we evaluated metabolic and inflammatory consequences of 18 weeks of high-fat feeding in CD40L(+/+) and CD40L(-/-) mice. In addition, C57Bl6 mice were injected with neutralizing anti-CD40L (αCD40L) antibody for 12 weeks while being fed a high-fat diet. Genetic deficiency of CD40L attenuated the development of diet-induced obesity, hepatic steatosis, and increased systemic insulin sensitivity. In adipose tissue, it impaired obesity-induced immune cell infiltration and the associated deterioration of glucose and lipid metabolism. Accordingly, αCD40L treatment improved systemic insulin sensitivity, glucose tolerance, and CD4(+) T-cell infiltration in adipose tissue with limited effects on adipose tissue weight. CD40L plays a crucial role in the development of obesity-induced inflammation and metabolic complications.Arteriosclerosis Thrombosis and Vascular Biology 08/2011; 31(10):2251-60. DOI:10.1161/ATVBAHA.111.231357
Article: Caveolin-1 deficiency decreases atherosclerosis by hampering leukocyte influx into the arterial wall and generating a regulatory T-cell response[Show abstract] [Hide abstract]
ABSTRACT: Caveolin-1 plays a crucial role in atherosclerosis, which is mainly attributed to its effects on low-density-lipoprotein (LDL) transcytosis. However, caveolin-1 has also been implicated in the regulation of inflammation. We investigated the effects of caveolin-1 deficiency in atherosclerosis with its accompanying changes in plaque- and lymphoid-related immunology and inflammation. Cav1(-/-)Apoe(-/-) mice exhibited a 15-fold reduction in plaque size with plaques containing fewer macrophages, T cells, and neutrophils. Intravital microscopy revealed 83% less leukocyte adhesion to the vessel wall in Cav1(-/-)Apoe(-/-) mice, which could be attributed to reduced endothelial chemokine ligand-2 (CCL-2/MCP-1) and vascular cell adhesion molecule-1 (VCAM-1) expression. Caveolin-1 deficiency resulted in a 57% increase in regulatory T cells and a 4% decrease in CD4(+) effector T cells in lymphoid organs. Bone marrow transplantations revealed that Cav1(-/-)Apoe(-/-) mice receiving Cav1(+/+)Apoe(-/-) or Cav1(-/-)Apoe(-/-) bone marrow presented 4- to 4.5-fold smaller plaques with no additional phenotypic changes. In contrast, atherosclerosis was not affected in Cav1(+/+) Apoe(-/-) recipients receiving Cav1(-/-)Apoe(-/-) or Cav1(+/+) Apoe(-/-) bone marrow. However, the presence of Cav1(-/-) Apoe(-/-) bone marrow was associated with an anti-inflammatory T-cell profile. Our study reveals that nonhematopoietic caveolin-1 determines plaque size, whereas hematopoietic caveolin-1 regulates lymphoid immune-modulation. However, both are required for phenotypic modulation of plaques.The FASEB Journal 07/2011; 25(11):3838-48. DOI:10.1096/fj.11-183350
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ABSTRACT: CD40 ligand (CD40L), identified as a costimulatory molecule expressed on T cells, is also expressed and functional on platelets. We investigated the thrombotic and inflammatory contributions of platelet CD40L in atherosclerosis. Although CD40L-deficient (Cd40l(-/-)) platelets exhibited impaired platelet aggregation and thrombus stability, the effects of platelet CD40L on inflammatory processes in atherosclerosis were more remarkable. Repeated injections of activated Cd40l(-/-) platelets into Apoe(-/-) mice strongly decreased both platelet and leukocyte adhesion to the endothelium and decreased plasma CCL2 levels compared with wild-type platelets. Moreover, Cd40l(-/-) platelets failed to form proinflammatory platelet-leukocyte aggregates. Expression of CD40L on platelets was required for platelet-induced atherosclerosis as injection of Cd40l(-/-) platelets in contrast to Cd40l(+/+) platelets did not promote lesion formation. Remarkably, injection of Cd40l(+/+), but not Cd40l(-/-), platelets transiently decreased the amount of regulatory T cells (Tregs) in blood and spleen. Depletion of Tregs in mice injected with activated Cd40l(-/-) platelets abrogated the athero-protective effect, indicating that CD40L on platelets mediates the reduction of Tregs leading to accelerated atherosclerosis. We conclude that platelet CD40L plays a pivotal role in atherosclerosis, not only by affecting platelet-platelet interactions but especially by activating leukocytes, thereby increasing platelet-leukocyte and leukocyte-endothelium interactions.Blood 11/2010; 116(20):4317-27. DOI:10.1182/blood-2010-01-261206
Conference Paper: Deficiency of TGF-beta Signaling in CD11c+Cells Accelerates Atherosclerosis by Disrupting T-Cell HomeostasisScientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology; 11/2010
Conference Paper: Cell Type-Specific Modulation of the CD40-CD40L Costimulatory Dyad in AtherosclerosisScientific Sessions on Arteriosclerosis, Thrombosis and Vascular Biology; 11/2010
Article: W52 PROTECTION AGAINST ATHEROSCLEROSIS IN CAV1 IS DUE TO CAV1 −/− IN NON-HEMATOPOIETIC CELLSAtherosclerosis Supplements 06/2010; 11(2):11-12. DOI:10.1016/S1567-5688(10)70053-2
Article: W7 DEFICIENT CD40-TRAF6 SIGNALING IN LEUKOCYTES PREVENTS ATHEROSCLEROSIS BY SKEWING THE IMMUNE RESPONSE TOWARDS AN ANTI-INFLAMMATORY PROFILEAtherosclerosis Supplements 06/2010; 11(2):2-2. DOI:10.1016/S1567-5688(10)70008-8
Article: Low- but not high-dose FK506 treatment confers atheroprotection due to alternative macrophage activation and unaffected cholesterol levels[Show abstract] [Hide abstract]
ABSTRACT: Previous studies showed both pro- and anti-atherogenic effects of immunosuppressant drug FK506 on atherosclerosis. As these divergent/paradoxical results of FK506 may at least in part be attributable to differences in FK506 dosing, we have, in the current study, assessed dose-dependent effects of FK506 on atherosclerotic lesion formation as well as on inflammatory parameters relevant to atherosclerosis. Unlike low-dose FK506, high-dose FK506 did not protect against atherosclerosis in ApoE-/- mice. The high-dose induced hypercholesterolaemia, whereas the low-dose did not. Both low- and high-dose FK506 treatment significantly reduced systemic CD3+ and CD4+CD25+ T-cell populations, and showed similar suppression of FoxP3 regulatory T-cell populations. Increased IL-4+ CD4+ T-cells and decreased IgG-MDA-LDL antibody titres pointed to a selective, albeit modest Th2 skewing in the high-dose treatment group, despite the advanced stage of atherosclerosis. Low concentrations of FK506, however, skewed bone marrow-derived macrophage polarisation towards a M2 macrophage phenotype, whereas high concentration did not. A low-dose FK506 treatment regime protected against atherosclerosis by suppressing T-cell activation and favouring (M2) macrophage polarisation. Although a high-dose FK506 treatment effected a similar T-cell suppressive effect, with an even more pronounced shift towards Th2 type immune responses, this did not translate in atheroprotection due to the hypercholesterolaemia and absent M2 skewing.Thrombosis and Haemostasis 05/2010; 104(1):143-50. DOI:10.1160/TH09-07-0502
Article: Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile[Show abstract] [Hide abstract]
ABSTRACT: The CD40-CD40 ligand (CD40L) signaling axis plays an important role in immunological pathways. Consequently, this dyad is involved in chronic inflammatory diseases, including atherosclerosis. Inhibition of CD40L in apolipoprotein E (Apoe)-deficient (Apoe(-/-)) mice not only reduced atherosclerosis but also conferred a clinically favorable plaque phenotype that was low in inflammation and high in fibrosis. Blockade of CD40L may not be therapeutically feasible, as long-term inhibition will compromise systemic immune responses. Conceivably, more targeted intervention strategies in CD40 signaling will have less deleterious side effects. We report that deficiency in hematopoietic CD40 reduces atherosclerosis and induces features of plaque stability. To elucidate the role of CD40-tumor necrosis factor receptor-associated factor (TRAF) signaling in atherosclerosis, we examined disease progression in mice deficient in CD40 and its associated signaling intermediates. Absence of CD40-TRAF6 but not CD40-TRAF2/3/5 signaling abolishes atherosclerosis and confers plaque fibrosis in Apoe(-/-) mice. Mice with defective CD40-TRAF6 signaling display a reduced blood count of Ly6C(high) monocytes, an impaired recruitment of Ly6C(+) monocytes to the arterial wall, and polarization of macrophages toward an antiinflammatory regulatory M2 signature. These data unveil a role for CD40-TRAF6, but not CD40-TRAF2/3/5, interactions in atherosclerosis and establish that targeting specific components of the CD40-CD40L pathway harbors the potential to achieve therapeutic effects in atherosclerosis.Journal of Experimental Medicine 02/2010; 207(2):391-404. DOI:10.1084/jem.20091293
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ABSTRACT: Cathepsin K (catK), a lysosomal cysteine protease, exerts strong elastinolytic and collagenolytic activity and is implicated in a range of pathological disorders including cardiovascular disease. CatK expression was found to be elevated in human aortic aneurysm pointing to a role in this vasculopathy. In the angiotensin II (Ang II)-induced mouse model for aneurysm formation, catK, S and C expression was strongly upregulated. Therefore, we investigated the effect of catK deficiency on Ang II-induced aneurysm formation in the abdominal aorta of apoE-/- mice. Contrary to our expectations, catK deficiency did not protect against aneurysm formation, nor did it affect medial elastin breaks. Proteolytic activity in abdominal aortic lysates were comparable between apoE-/- and catK-//-apoE-/- mice. Adventitial presence of catS- and catC-expressing cells was significantly increased in catK-/-//apoE-/- versus apoE-/- mice, which might have compensated for the deficiency of catK-derived proteolysis in the aneurysm tissue of catK deficient apoE-/- mice. Circulating granulocytes and activated T cell numbers were significantly increased in Ang II-infused catK-/-//apoE-/- mice, which is consistent with the borderline significant increase in adventitial leukocyte content in catK-/-//apoE-/- compared to apoE-/- mice. Strikingly, despite unchanged proteolytic activity in AAA lesions, collagen content in the aneurysm was significantly increased in catK-//-apoE-/- mice. In conclusion, while catK deficiency has major impact on various vasculopathies, it did not affect murine aneurysm formation.Atherosclerosis 09/2009; 209(1):96-103. DOI:10.1016/j.atherosclerosis.2009.09.001
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ABSTRACT: Atherosclerosis is a chronic disease of the large arteries that is responsible for the majority of cardiovascular events. In its pathogenesis, the immune system plays a pivotal role. The effectuation of the immune response through interactions between immune cells that is mediated by co-stimulatory molecules, determine atherosclerosis severity. This review will highlight the role of one of the most powerful co-stimulatory dyads, the CD154 (also known as CD40 ligand, CD40L)-CD40 dyad, in atherosclerosis. Its cell-type specific actions, signal transduction cascades and its therapeutic potentials will be discussed.Seminars in Immunology 08/2009; 21(5):308-12. DOI:10.1016/j.smim.2009.06.004
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Maastricht Universitair Medisch Centrum
Maestricht, Limburg, Netherlands
- Central Diagnostic Laboratory
Maastricht University
Maestricht, Limburg, Netherlands
- • Department of Pathology
- • Department of Genetics and Molecular Cell Biology


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SeaSense announces the opening of its new research and design facility in Bonita Springs, Fla. In addition to a new research and design department, it also houses a state-of-the-art quality control testing center. The new research and design operation is dedicated to developing new technologies for the marine and trailer industries. The research and design facility is the third new plant to be opened by SeaSense's parent company, Unified Marine, Inc., since 2006 when it opened a 40,000 square-foot headquarters operation in Newport, Tenn. A new 20,000-square-foot warehouse and distribution center opened in 2009 just a few miles down the road.
GasLog Ltd. today announced that it has ordered two new 174,000 cubic meter LNG carriers from Hyundai Heavy Industries Co., Ltd. ("Hyundai") in South Korea.
Coast Guard, Seattle Police Department, Seattle Fire Department, King County Sheriff's Office and Washington Department of Fish and Wildlife personnel rescued
In line with LOC's continual global growth and strengthening of the senior management team, Britain has been appointed as Managing Director of the London operation.

subset: commoncrawl


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- While problems regarding exploitation of foreign workers are widespread across the country, grateful regional towns like Mundubbera in Queensland couldn't do without them; both in the orchard and on the footy field ...Thursday 14 May 2015
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- The undulating hills around the town of Childers in Queensland is a mix of colours; from the bright green of sugar cane fields, to the rich reddy brown of the volcanic soil. It is a far cry from the desert and dust of Iraq and Syria, but the two now share a common link - use of the name Isis. ...Monday 22 September 2014
- A central Queensland town is facing a rugby league renaissance....Wednesday 14 May 2014
- More than pride is on the line for players in the South and Central Burnett rugby league competitions, as they take to the field this weekend in the annual Mundubbera 'Clash for Cash'...Wednesday 12 March 2014
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How to bust your tomboy image around guys
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Pet Sitter — Shorewood, IL
I have been taking care of pets for neighbors and family for many years. Mainly experienced with dogs, cats and fish but willing to take care of all types of animals. I have personally owned 3 dogs, t...
7 yrs of exp.
Dog Walker - Pet Sitter — Shorewood, IL
I do not have any paid experience but have helped out many friends and neighbors with their dogs. I work in a school so I have my summers off. My children are grown so I am looking for something to ke...
0 yrs of exp.
Pet Sitting And Dog Walking — Shorewood, IL
I have a ton of personal pet care experience. Throughout my life, I've always had at least one pet. I've helped neighbors & friends with the care of their pets & homes. My schedule is flexible, which ...
10 yrs of exp.
Dog Walker/Pet Care — Shorewood, IL
I'm currently a college student home for the summer and I am looking for work. I love animals and I would love an opportunity to care for them over the summer.
0 yrs of exp.
Dog Lover Looking For Dog/ Pet Sitting Opportunities =) — Shorewood, IL
Hello! My name is Heather and I'd love to care for your pets. Dogs are definitely mans best friend! I have grown up with dogs my whole life and I currently have a 6-year-old boxer and a 12-year-old ro...
4 yrs of exp.
Seeking An Experienced Dog Owner? I'm Your Pick — Shorewood, IL
I have volunteered at shelters and I have worked as an adoption assistant, I even wake-up with my best friend at my side each day; a 2ft terrier full of love energy and attention, he is compatible wit...
2 yrs of exp.
Part-time Caregiver Available — Shorewood, IL
I love animals. I currently have and care for four dogs and one cat. I have cared for dogs of all sizes and breeds from 7-100 pounds. I have also cared for small animals such as rabbits, hamsters and ...
2 yrs of exp.
Dog Walker — Shorewood, IL
I have cared for many different breeds of dogs including beagles, corgis, cocker spaniels, labs and German shepherds. I grew up around dogs and I helped to take care of my family's dog for the past 14...
0 yrs of exp.
Shorewood, IL
My name is Rachel, and I am a loving dog and cat owner seeking employment as a pet sitter. I have been a dog owner for 15 years and a cat owner for 10 years. I have watched dogs at my house for a coup...
2 yrs of exp.
Shorewood, IL
My name is Paige and I'm currently in college studying to be a veterinarian. I love to help with animals or kids. I've been babysitting for as long as I can remember and I've had animals since the day...
6 yrs of exp.
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St. Louis Cardinals relief pitcher Mitch Harris is the first Naval Academy graduate to appear in the bigs in 94 years.
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The conferences get underway in September.
Michael Cuddyer was presented the 2014 American Legion Baseball Graduate of the Year award on June 11.
Kansas City Royals standout honored prior to June 6 game with Texas Rangers.
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Earl Scruggs Center in Shelby, N.C., will offer free admission for all active-duty military personnel and veterans during American Legion Baseball World Series.
Sean Breen from Brooklawn, N.J., met major-leaguers and Hall-of-Famer Rollie Fingers during trip to National Baseball Hall of Fame.
Official license partnership provides special rate for company's famous wood bats and other products.
Local television show highlights the American Legion World Series and all of its pageantries in special episode.
Robert O'Neill, decorated veteran and combat leader, will be guest of honor at National Commander's Reception during American Legion World Series.
Country music duo taking part in Celebration of Champions Aug. 12 at Keeter Stadium.
Country star's free concert set for Aug. 8 in Shelby, N.C., as part of the Annual 7th Inning Stretch Festival.
Scholarships for American Legion baseball players range from $500 to $5,000; applications due July 15.
Four days of pool play will be on ESPN3; semifinal and championship games will be aired live on ESPNU.
Several new rule changes are included in the book, including clarification to dual participation.
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Coaches can register teams online at www.baseball.legion.org; registration deadline is June 1.
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A blind drawing was conducted to identify the World Series division pairings and game times.
Legion Baseball champs from Brooklawn Post 72 honored on field before Game 2 of MLB's World Series.
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Brooklawn, N.J., Post 72 back at Major League Baseball's Fall Classic after another Legion Baseball World Series title.
Brooklawn, N.J., the back-to-back Legion World Series champs, are in Kansas City for Games 1 & 2 of Major League Baseball's World Series, will be honored on field before Game 2.
American Legion names Alex Gordon its 2015 Legion Baseball Graduate of the Year.
Defending champions Brooklawn, N.J., defeated Midland, Mich., 18-0 in seven innings; paid attendance record broken.
Brooklawn, N.J., and Midland, Mich., will play at 7 p.m. The game will be televised live on ESPNU.
Nine Legion Baseball players will receive a scholarship, sponsored by Diamond Sports, for their scholastic achievements.
New Jersey will play Hawaii at 5 p.m., and Nebraska will play Michigan at 8 p.m. Watch live on ESPN3.com.
Pool play wraps up Sunday with the top two teams from each pool advancing to the semifinals on Monday.
New Jersey and Nebraska are 2-0 in the pool play Series; Hawaii claims its first win of the tournament.
New Jersey, Nebraska and Michigan advance to Day 2 of the 2014 American Legion World Series with wins.
2013 champ Brooklawn, N.J., wins Game 1 of American Legion Baseball World Series.
The American Legion World Series begins Aug. 14 with live coverage from ESPN3 and ESPNU.
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A beautiful lakefront community, The Enclave at Lake Underhill demonstrates a commitment to craftsmanship, convenience, and lifestyle, rarely seen. With white-on-white color schemes, checkerboard flooring, fireplaces, and spacious closets, our attention to detail is unparalleled. Surrounded by mature, tropical landscaping, you're just minutes from downtown Orlando, Baldwin Park, Orlando International Airport, Orlando Regional Medical Center, Florida Hospital and the Fashion Square Mall. Wonderful apartment homes, outstanding customer service, and the greatest amenities you deserve-all at a location envied for its convenience and style.
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|By Marc Middleton | July 04, 2012 | Comments
- As seen on SmackDown, Zack Ryder won the Great American Bash Battle Royal and will be next week's SmackDown General Manager. Ryder reacted on Twitter:
"I just won the battle royal on SmackDown! I'm gonna be the General Manager next week! I'm serious bro! #WWWYKI The Broski is back! There is no stopping the Ryder Revolution!"
"Tonight I got my revenge on Eve & Kane yes this is a legit tweet. #WWWYKI"
- As noted before, Dustin "Goldust" Rhodes will return to the ring to face Vordell Walker at a NWA Ring Warriors event on July 14th in Hollywood, Florida. Dustin posted the following video on YouTube, responding to Walker:
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WWE Live Event Results From Ontario (8/1): Big Steel Cage Main Event, MizTV, Cesaro, Divas, More
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Rey Mysterio Talks Possible WWE Return, His Departure, Perro Aguayo, Vince McMahon, More
Ronda Rousey Brutally Knocks Out Bethe Correia, Thanks Rowdy Roddy Piper At UFC 190
WWE Star Takes Homeless Couple To Restaurant, Returns With Big Group Due To "Distant" Manager
Dana White Calls TNA Talent A Goofball Over "Fake" Comments, Bully Ray And Others Respond To White
Seth Rollins Fires Back At UFC President Dana White Over Wrestling Comments
Breaking News: "Rowdy" Roddy Piper Dead At 61
Rob Van Dam Confirms His WWE Status, Comments On Possibly Retiring From The Ring
WWE Officials Reportedly Want Tough Enough Competitor To Be Eliminated Next Tuesday
UFC 190: Rousey Vs. Correia Recap: Ronda Rousey Continues To Make History
Undertaker Rumor Killer, Early Brock Lesnar Vs. Undertaker Betting Odds, Mascot No-Sells Kevin Nash


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I changed my mind about asylum seekers. Here's why.
Why are we so indifferent about the plight of asylum seekers trying to reach Australia?
Immigrants do not threaten our jobs — on the contrary, they create new possibilities and demand in our economy.
Do you procrastinate about taking care of financial matters in your life?
The average American produces about 130 pounds of trash a month, and an article in the journal Nature estimates that global solid-waste generation will triple to...
After World War II, Dr Seuss dedicated himself to creating art that would speak to a sense of fairness and justice that he believed only children possessed.
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US President Barack Obama says his country's criminal justice system 'isn't as smart as it should be.' It's time to look at ours, too.
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This property allows you to book online with a credit card. After submitting a reservation request, the owner or manager has 24 hours to accept, at which time your card will be charged and you will receive an email confirmation
Other areas nearby to Toronto:
Recent Ontario reviews
"Carolyn was an extraordinary host. The place is so lovely. The cottage is perfectly well maintained and equipped. Everything has been taken care of. The bed is very soft (maybe too soft for some but perfect for others) :) Cathy was very nice with helping Carolyn to organise our stay. Thanks a lot!"Guest: Michael Date of Stay: July 2015 Review Submitted: July 16, 2015View listing
"The home is very nicely kept, very comfortable and very excellently located. With three rooms, two very nice bathrooms, a very functional kitchen and comfortable spaces for eating and hanging out you really couldn't need more. My parents, small child and I were traveling to the area for a family memorial and it was great to escape back to the house in the evenings and afternoons - with the great wifi we could get a little work done on the most magical porch and really relax. My parents and I were able to walk to many restaurants and through the town so quickly and easily. It felt safe and comfortable. We will definitely be back!!!!!"Guest: Jane B. Date of Stay: June 2015 Review Submitted: June 23, 2015View listing
"We booked last minute and had no expectations. Drove 90 minutes from Toronto and came to a beautiful secluded cottage that answered all our wishes :) We were three families with kids and all slept comfortably. We love to cook so the kitchen was beyond good. Women said it's a dread kitchen. Equipped with all we needed. Pool can be heated so the kids stayed in the water most of the day. Adults were in the hot tub. Grocery shopping is only 10 minutes away. View of the bay is breathtaking. No Wi-Fi and very low signal for Rogers customers which for some might be a good thing :) Overall, worth every penny. We had a great time and would like to go back next year."Guest: Family Man Date of Stay: August 2014 Review Submitted: September 2, 2014View listing
Featured Destinations: The Villages, Rosemary Beach, Destin Condo Rentals, Amelia Island, Myrtle Beach, Outer Banks


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Sort by: Viator Recommends | Traveler Rating | Most Recent
Moroccan Culture in Marrakech
By Viator, July 2015
From the bejeweled snake charmers and henna-painted fortune tellers that patrol the central square of Djeena El Fna, to the traditional dancing and rhythmic drumming of the Atlas mountains? Berber ... Read more
Fez Tours from Casablanca
By Viator, July 2015
With its historic architecture and rambling souks, the Imperial City of Fez is one of the country?s oldest and most unique cities, located a few hours northeast of Casablanca. Although it?s possible ... Read more
The Souks of Fez
By Viator, July 2015
Winding their way through the alleyways of the historic Fez Medina (Fez el-Bali), exploring the souks of Fez is like stepping into a world that time forgot, and the traditional markets are among the ... Read more
Fez Architecture Guide
By Viator, July 2015
As the original capital and the oldest of Morocco?s imperial cities, Fez is home to some of the country?s most important spiritual centers and a magnificent array of religious buildings and royal ... Read more
Exploring Northern Morocco
By Viator, July 2015
The majority of tourists might head straight for the cultural capital of Marrakech or the Atlantic resort of Essaouira, but Morocco?s real gems lie in the north ? grand imperial cities, bohemian ... Read more
3 Days in Fez: Suggested Itineraries
By Viator, July 2015
Morocco?s spiritual center is all-too-often relegated to a day trip, but the glorious Imperial City deserves much more attention than a whistle-stop tour. Spending 3 days in Fez means you can take ... Read more
Day Trips from Marrakech
By Viator, March 2015
If you?ve explored the Marrakech medina and haggled for bargains in the sprawling souk, heard storytellers weave their magic in the Djemaa el Fna square, and dined al fresco on Moroccan cuisine, it?s ... Read more
Marrakech Suggested Itineraries
By Viator, February 2015
The southern heart of Morocco, Marrakech has long been a magnet for travelers and trading. These days we?re more likely to arrive by plane than camel but the trading is just as fierce and wonderful. ... Read more
3 Days in Casablanca: Suggested Itineraries
By Viator, February 2015
The sprawling metropolis of Casablanca may seem overwhelming to first-time visitors, but with a little forward planning, you can easily taken in all the top sights in a short trip. Here are a ... Read more
Private 3 Days From Marrakech to Desert
By Moroccotours, December 2014
DAY One: Marrakech - Boumalne Dades: From Marrakech, we pick you up at the airport. We will cross the Atlas by the Tichka pass which has 2200m of altitude. We will continue by the Ourzazate ... Read more
Merzouga Camel Trekking Bivouc
By Moroccotours, December 2014
The dunes of Erg Chebbi is a strikingly strange natural formation. On the top of the flattest area you could imagine, suddenly a long mountain of sand rises. This mountain is surrounded by flat and ... Read more
Marrakech Tours from Casablanca
By Viator, July 2014
You can?t visit Morocco without paying a visit to the cultural capital of Marrakech, a city of contrasts that is as bewildering as it is enchanting. Less than 2.5 hours south of Casablanca, it?s ... Read more
Casablanca's Neighborhoods
By Viator, December 2013
From the ramshackle souks that sprawl through the Old Medina to the array of Mauresque and Art Deco style buildings constructed under General Lyautey's French rule, Morocco?s largest city is full of ... Read more
Romantic Things to Do in Marrakesh
By John Reality , Cambodia, December 2013
For a truly romantic twist on your holiday, Marrakesh offers loads of great options from its historic infrastructure, to tranquil restaurants, exotic palm groves and bazaars that are sure to make ... Read more
Relax at a Marrakech Hammam
By Viator, December 2013
Whether you opt for a traditional scrub down or luxury spa treatment in a five-star resort, no trip to Morocco is complete without experiencing the rituals of the hammam, or Turkish-style steam bath. ... Read more


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Dubai Investments sags on Q2 profit drop
MIDEAST STOCKS-Telecoms post poor Q2 results, but global background positive
Dubai's Aramex climbs on strong Q2 results
Gold wedged below $1,100 ahead of Fed meeting outcome
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UAE shifts fuel prices as the Gulf watches
UAE to raise gasoline price 24 pct, cut diesel 29 pct
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Gold stuck near 5-1/2-year low as Fed rate hike looms
The telecom industry may have weathered the financial storm better than most, but regional players may need to reinvent themselves to stay competitive, Part I.
April 19, 2009 7:35 by Ehtesham Shahid
It may have been called too early. The Gulf's telecommunications industry, which was euphorically deemed untouched by the global financial crisis, is realizing that 2009 will be a tougher year than it expected.
Some operators in the Gulf region that are undertaking ambitious overseas expansions may face rough weather as growth in those foreign countries wanes. The projected decline in the Gulf's population, on the back of an expatriate exodus, is sure to pose problems as well. On top of that, telecom operators will face challenges synergizing acquisitions and minimizing expenditure.
Since funding continues to be a problem both within and outside the industry, innovative solutions such as network sharing, are likely to get more attention as a way to reduce costs and generate new sources of revenue. Their focus is also likely to shift towards boosting the efficiency of business operations. All that should be music to the ears of end-users in the region who, for the first time, are beginning to look at the prospects of reduced tariffs and more value add-ons.
Mobile call charges in the Gulf region may drop by as much as 20 percent this year, mainly due to increasing competition. Customers may also benefit from technological innovation and declining project costs, says Booz & Company. If operators and vendors cling to their already fat purse, those at the receiving end of their products and services ought to benefit as well. Whether that will actually happen and when, however, still remains to be seen.
The crisis curse. As the aftershocks of the financial crisis continue to unfold, so do the vulnerabilities associated with it. An EFG-Hermes report on MENA economies says the expected population decline in some Gulf countries will affect the performance of a number of sectors, including telecommunications.
Kunal Bajaj, an analyst with HSBC Bank Middle East, says the impact of the crisis on Gulf telecom operators will be mainly on the number of subscribers, rather than usage rates. "Telco spend in consumer basket in Middle East is between 1-3 percent. However, because the region has a large number of expatriates, and should expatriates start to leave (which is starting to happen through job cuts), it will have negative impact on subscriber addition," he says. "However, we don't expect usage to go down."
Even if the subscriber numbers may shrink, the average revenue per user (ARPU, the industry measurement scale of profitability), is what matters to the telcos. These figures are rising, challenging those in mature telecoms markets elsewhere. Two examples are Zain and Qtel, both of which have now ranked in the top 20 global operators, with ARPUs exceeding $50, according to figures released at GSM Arab World.
Pages: 1 2
Piaget and the art of enamelling
April 19 2009
Do you think there is freedom of speech in the UAE?
April 19 2009


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Mango-Pecan Quick Bread
From EatingWell: October/November 2005
Mangos give a standard quick bread a lively flavor jolt.
Makes: 12 servings
Active Time:
Total Time:
Nutrition Profile
Low calorie | Low cholesterol | Low sodium | Healthy weight |View Our Nutrition Guidelines »
- Quick-Bread Dry Mix, (recipe follows)
- 2 large eggs
- 1 cup nonfat buttermilk, (see Tips)
- 2/3 cup brown sugar
- 2 tablespoons butter, melted
- 2 tablespoons canola oil
- 1 teaspoon vanilla extract
- 2 cups diced mango, (see Tips)
- 1/2 cup chopped toasted pecans, (see Tips), plus more for topping if desired
This recipe calls for:
- Preheat oven to 400°F for muffins, mini loaves and mini Bundts or 375°F for a large loaf. Coat pan(s) (see "Pan Options") with cooking spray.
- Prepare Quick-Bread Dry Mix.
- Whisk eggs, buttermilk, brown sugar, butter, oil and vanilla in a large bowl until well combined.
- Make a well in the center of the dry ingredients, pour in the wet ingredients and stir until just combined. Add mango and pecans. Stir just to combine; do not overmix. Transfer batter to the prepared pan(s). Top with additional pecans, if desired.
- Bake until golden brown and a wooden skewer inserted into the center comes out clean, 22 to 25 minutes for muffins or mini Bundts, 35 minutes for mini loaves, 1 hour 10 minutes for a large loaf. Let cool in the pan(s) for 10 minutes, then turn out onto a wire rack. Let muffins and mini Bundts cool for 5 minutes more, mini loaves for 30 minutes, large loaves for 40 minutes.
Tips & Notes
- Make Ahead Tip: Store, individually wrapped, at room temperature for up to 2 days or in the freezer for up to 1 month.
- Tips: No buttermilk? Mix 1 tablespoon lemon juice into 1 cup milk.
- To cut a mango: Slice both ends off the mango, revealing the long, slender seed inside. Set the fruit upright on a work surface and remove the skin with a sharp knife. With the seed perpendicular to you, slice the fruit from both sides of the seed, yielding two larger pieces. Turn the seed parallel to you and slice the two smaller pieces of fruit from each side. Cut the fruit into the desired shape.
- To toast walnuts, pecans or hazelnuts, spread nuts onto a baking sheet and bake at 350°F, stirring once, until fragrant, 7 to 9 minutes. To toast sliced almonds, cook in a small dry skillet over medium-low heat, stirring constantly, until fragrant and lightly browned, 2 to 4 minutes.
- Pan Options:
- Each of these recipes will make:
- 1 large loaf (9-by-5-inch pan)
- 3 mini loaves (6-by-3-inch pan, 2-cup capacity)
- 6 mini Bundt cakes (6-cup mini Bundt pan, scant 1-cup capacity per cake)
- 12 muffins (standard 12-cup, 2 1/2-inch muffin pan)
- Storage smarts: For long-term freezer storage, wrap your food in a layer of plastic wrap followed by a layer of foil. The plastic will help prevent freezer burn while the foil will help keep off-odors from seeping into the food.
Per serving: 230 calories; 9 g fat (2 g sat, 4 g mono); 41 mg cholesterol; 33 g carbohydrates; 5 g protein; 3 g fiber; 182 mg sodium; 104 mg potassium.
Carbohydrate Servings: 2
Exchanges: 1 starch, 1 other carb, 1.5 fat (mono)
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Recipe Categories
- Total Time
- More than 1 hour
- Servings
- 8 or more
- Preparation/ Technique
- Bake
- Type of Dish
- Baked Goods, quick breads & muffins
- Ethnic/Regional
- American
- Health & Diet Considerations
- Low calorie
- Low cholesterol
- Low sodium
- Healthy weight
- Ease of Preparation
- Easy
- Publication
- October/November 2005


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You are always welcome here at this site, where you can easily use hot ringtones for your Android smartphone. Today we have a ringtone of "Beyond the Sea" by Bobby Darin as well as 176 other ringtones by Bobby Darin. "Beyond the Sea" is a hit from the "The Very Best Of Bobby Darin (Remastered)" album that was made by Bobby Darin at their major label together with other 11 tracks. You can listen to all 58 Bobby Darin – "Beyond the Sea" ringtone variations available here and download it for free to your computer. You can also find other 20 albums produced by Bobby Darin for all time. "Beyond the Sea" is referred to Jazz, and Audiko offer a huge amount of Jazz ringtones absolutely for free. And finally, we have collected lyrics for this track and you can view it here as well. So feel free to browse, listen, download ringtones at Audiko.net. Make your phone sound cool!
Bobby Darin - Beyond the Sea
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Beyond the Sea 2:59
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30 Nov 2005
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Alaina Kaczmarski's Lincoln Park Apartment Tour #theeverygirl / whit all bookshelves full - good idea :D
Bar cart + books + neutrals + prints + gallery wall + flowers. It's like my personal heaven. // Alaina Kaczmarski's Lincoln Park Apartment Tour - The Everygirl
Glam white living space... white leather studded sofa, leopard print cushion, drinks cabinet, stack of books and scattering of art prints. *swoon*
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display your vintage bar glasses on a chic bar cart
Next time you visit me, can you help me do something like this bar cart?:) Again, my lack of organizational skill restricts me from accomplishing this shit.
The trolley looks the same as #IKEA Trendig 2013 Occasional table, but painted white. Article # 102.768.90. Price USD 99. Photo credits to | AMM blog


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Beverly Grant
Bad Ideas, Beverly Grant, Judge of the Day, State Judges, State Judges Are Clowns
Above the Law Judge of the Day: Beverly Grant
Who says going to court has to be so serious? Uh, the Washington State Commission on Judicial Conduct, that's who. They just admonished a judge for this behavior: Pierce County Superior Court Judge Beverly Grant asked about 100 people in court to say "Go Seahawks" before taking their seats on Feb. 3. Dissatisfied with the […]


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Pink Ribbon Women's Casual Shorts
Roll over image to zoom in
☆ Special Selection -- one of our favorites!
Soft and comfy, and sure to become a favorite for working out or relaxing. A slimming ladies' cut features a stretchy elastic waistband and drawstring.
- 100% cotton
- Embroidered pink ribbon
- Two pockets
- Machine wash cold; hang dry
- Made in & fairly traded from Bangladesh
|Sizing in inches / cm
|Waist (Relaxed and Stretched)
|26 - 42 / 66 - 106
|43 / 108
|5.5 / 14
|28 - 44 / 72 - 112
|44 / 112
|6 / 15
|30 - 46 / 76 - 118
|46 / 116
|6.25 / 16
|32 - 48 / 80 - 122
|50 / 128
|6.75 / 17
|33 - 50 / 84 - 128
|52 / 132
|7 / 18
|35 - 52 / 88 - 134
|55 / 140
|7.5 / 19
|36 - 54 / 92 - 140
|58 / 148
|8 / 20
Garment Measurements:
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Recent reviews:
July 20, 2015 - I bought 5 pair of different colors 2 in pin very comfortable and fit well I am normally a size 2x so I bought XXL and they fit great!
June 15, 2015 - Beautiful color (pink); comfortable; roomy.
November 8, 2014 - These shorts are awesome! Soft and so comfy, I just wish they had full length pants in my size (3x) like these. Just don't throw them in the dryer...they shrink.. bummer..
August 30, 2014 - I've been wearing these short casually at home and for sleeping for years now. Very soft, good quality and comfy!
July 17, 2014 - Love these shorts! Great fabric and fit!
Artisan: Aarong / BRAC
When you're a woman living in rural Bangladesh, your employment options are limited. In 1978 Aarong-BRAC stepped up to fill that gap. With a mission to be the best in the world in providing a unique Bangladeshi lifestyle experience, to empower people, and to promote Bangladesh while protecting the environment, their very name means "village fair." From those humble beginnings, Aarong/BRAC has grown into an cooperative that supports more than 65,000 artisans in 13 production centers and 647 sub-centers throughout 2,000 villages in Bangladesh. Offering more than mere jobs, they offer a future, one with skills training, medical benefits, day care center, and retirement benefits.
Established 1992 in Narayongonj, Bangladesh as one of Aarrong's production centers, Minar Ind. is a full-range apparel center. They knit, dye, assemble, and print all of their apparel on site, and will soon begin spinning their own cotton thread. They currently employ approximately 2,000 high and semi-skilled workers and have been certified by the Business Social Compliance Initiative, highlighting their commitment to bettering the wellbeing of their workers.
Minar Ind. training includes not only machine operation skills, but also quality control, first aid, fire prevention, and machine maintenance. A full health check-up and AIDS prevention and awareness are included as part of the training. While working, artisans have the benefit of a doctor and assistant with first aid stations on every floor, where signs of illness are treated immediately and any necessary medicine provided. They also receive mandatory rest periods, access to fresh water, a dining room, a day care center, safety equipment such as masks, ear protection, gloves, and boots, and clean, safe, well-lit work spaces.
Minar Ind. hosts an annual picnic for all employees and a organizes a worker participatory committee comprised of a number of employees on each floor who meet to discuss worker demands, legal rights, and dues with the management on a regular basis.
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Ruakura plea to council
'It feels like death by a thousand cuts'DANIEL ADAMS
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Ruakura residents have publicly condemned the lack of consultation with them by Hamilton City Council over Tainui Group Holdings' plans for a huge inland port neighbouring their properties.
The group today asked council to consider their plight before agreeing to publicly notify a draft district plan which includes zone changes clearing the path for the proposed freight hub.
Resident Derrick Marsters, one of about 30 adjacent ratepayers, said concessions changing the properties' zoning from logistics to large residential "seems to me a very clever way by council staff to end up with the same result. It feels like death by a thousand cuts. Nothing has really changed..where in ten or fifteen years we're going to become [zoned] logistics," said Mr Marsters.
The group had commissioned real estate appraisals and "there's no doubt there's a significant loss of value on our properties whereas Tainui will have massive equity growth overnight, at the stroke of a pen. Leave us out, deal with us, give us some sort of concession," he said.
"The gentlemen behind me, from Tainui, have had months, if not years of engagement."
"No resident I've spoken to is opposed to the plan. We want the best for Hamilton, we want the best for the community. We just want to retain what we have," said Mr Marsters.
The proposed zoning for the properties changes the rules for subdivision and includes a 40m building setback, while the residents want the current rules retained and a significant buffer belt or bunding.
Resident Peter Ryan said the council had missed a golden opportunity to modify the district plan prior to notification to lessen the impact of TGH's proposed port on neighbouring properties.
He said there had been a "deafening silence" from council and TGH on the propsal's impact.
"The purpose of this submission is to have the failure to consult entered in the council record."
Council staff said it was not correct to say subdivision was not possible for the residents under the proposed changes. Under the current country living provisions inherited from Waikato District subdivision in the area was a controlled activity down to 5000 sq m and for smaller lots sizes was discretionary. The proposed change in the district plan would make subdivision down to 2ha a limited discretionary activity, and smaller than that a restricted discretionary activity, they said.
A Tainui delegation led by TGH chief executive Mike Pohio talked up the economic impact of the inland port proposal and congratulated council for its work on the draft district plan.
"Today is core business. This sets the framework by which Hamilton City defines itself in New Zealand. What the project does is offer hope through jobs. Some 6-12,000 jobs, that's the essence of our proposal. TGH is fully committed, with all its resources, to the development of Ruakura," said Mr Pohio. Council will consider the draft district plan later today.
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This ticks all the boxes of a small family run Guest House and I wouldn't hesitate recommending. Staff were more than accommodating and gave a real personal service.
Offered a great traditional breakfast menu that was superb.
We probably waited too late to reserve our accommodations. The hotel was in a pretty setting but It is near "nowhere and nothing". We booked a double room for two people, at £80/night, $125. We got the attic family room with 1 small, hard double bed and two twins. The floors were so crooked that when I put a water...
Dear Barbjgladney
Thank you for taking time to review your recent stay at Dalshian House. Unfortunately, it would appear Dalshian has not met all/some of your expectations.
With regards to our location, we do not mislead or hide the fact of where we are situated (on the outskirts of Pitlochry, approx. 1 mile from town). Indeed, we find the majority...
We loved everything about the Dalshian House! Martin and Heather were very warm, welcoming, and friendly hosts; and their guest house is beautiful -- from the awesome grounds to the homey sitting/drawing room and the family room in which we stayed. Breakfast was very tasty and filling! Wish we could have had more time there; and if I ever visit...
The first thing to say about Dalshian House is that you are assured of a warm and friendly welcome. It is a small establishment, with ample parking directly in front of the main house and a small collection of lodges adjacent. We were shown to an ample bedroom with the largest bed I've ever seen (and at 6'4 bed size...
Everything about Dalshian House was fantastic.
Beautiful house & grounds, great rooms, wonderful breakfast.
Lovely hosts.
It is outside Pitlochry, not really walkable back to amenities.
Nice restaurant 100 yds away.
We stayed at Dalshian last year and couldn't wait to return. Driving up the hidden driveway surrounded by beautiful flowers and trees we knew we had arrived at our secluded destination and began to relax instantly. The owners are really lovely and very helpful. Lovely flower arrangements from the garden adorn the rooms and the house proudly emanates a faded...
After flying into Edinburgh, we chose Dalshian House for our first overnight stay. The lovely and quiet setting, the friendly and cheerful greeting from our hosts, the comfortable room, Michael's recommendation that we have dinner at nearby East Haugh Hotel, and the cooked-to-order breakfast all made for a terrific stay.
Dalshian House is an interesting old home with lots of character and antique furniture. Definitely a one-off and not corporate or chain hotel style.
It's set just off the A9 in a secluded and pretty grounds on the outskirts of Pitlochry. Our rooms were spacious and clean with good wi-fi, fluffy towels and plenty of useful tourist information. The owner...
I recently organised a tour of the UK for my Chinese friends and accompanied them on it. I booked two twin rooms at this residence as I wanted the experience to be fabulous as it was a special 50th wedding anniversary trip. The owner was delightful and the rooms were very nice and clean. The only gripe I did have...
Dear Julie N
Thank you for your recent review of Dalshian. We can only apologise again for the smell of cigarette smoke in one of the rooms. We do operate a non-smoking policy within Dalshian; however the guest occupying this room before your friends, chose to ignore this and it was only after their departure we discovered this issue. We...
We stayed at Dalshian House for 3 nights whilst the rest of the group we were with stayed in a local 5 star hotel. I was more than happy with our choice...A pretty, secluded location just outside Pitlochry but only minutes away by car from the centre. The house is delightful. It oozes charm, is comfortable, and the welcome you...


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World Bank's climate change envoy: 'We need to wean ourselves off coal' Bank has stopped funding new coal projects except in 'rare circumstances' The World Bank said coal was no cure for global poverty on Wednesday, rejecting a main industry argument for building new fossil fuel projects in developing countries. The Guardian – Suzanne Goldenberg @suzyji In a rebuff to coal, ... Read More »
China Answers Japan Oil Rig Concern With Joint-Development Offer
China repeated a call Friday for talks with Japan over joint development of gas and oil resources in contested waters in the East China Sea. BloombergBusiness – The offer comes days after Japan disclosed a map and photographs of what it said were 16 Chinese marine platforms close to Japan's side of a geographical median line that it contends should ... Read More »
Japan finds China's expansion in East China Sea 'extremely regrettable'
Japan warns China making new platform China warns those 'meddling' in the South China Sea The Age – Philip Wen, China correspondent for Fairfax Media Beijing: The Japanese government has released a map and aerial photos detailing Chinese oil and gas exploration platforms it said proved Beijing was accelerating plans to unilaterally exploit an oilfield that straddles disputed waters in the ... Read More »
Military ready to secure oil explorers
The Armed Forces of the Philippines (AFP) on Monday expressed its readiness to provide security to any group that will conduct deepwater oil exploration in the South China Sea (West Philippine Sea) as long as the activity is done within the country's exclusive economic zone (EEZ). Fernan Marasigan, | The Manila Times, Philippines Lt. Col.Noel Detoyato, chief of the AFP ... Read More »
Browse Basin deal relinquishes gas royalties worth $2 billion to WA Government
The Commonwealth has officially signed over ownership of 65 per cent of the largest gas field in the Browse Basin to the WA Government, relinquishing up to $2 billion in royalties. ABC - By Kathryn Diss A satellite sweep on the basin last year discovered three tiny rocky outcrops, 300 kilometres off the state's north-west coast. While they sit no ... Read More »
Proposed new political party in the Northern Territory reveals first policy: 'say no to fracking'
A new political party being formed in the Northern Territory has said it is opposed to hydraulic fracturing, or fracking. ABC Darwin – Emma Masters The controversial practice, which involves pumping water, sand and chemicals at high pressure to fracture rock layers to extract natural gas, has been criticised by some community and pastoral groups. The Northern Territory Government released ... Read More »
Beware permitting fracking, says farmer who allowed coal methane borehole
Paul Hickson says when he signed access agreement he had no idea of physical or psychological impact that gas drilling could have on him and his family The Guardian - John Vidal A farmer who gave an energy company permission to dig a test borehole for coal bed methane gas out of a sense of national duty has warned other ... Read More »
Can oil and gas fix Greece's economy?
Greece is turning to offshore oil and gas as a potential source of revenue, despite having almost no existing oil and gas production to begin with. The Christian Science Monitor – By Nick Cunningham, Oilprice.com Greece is in an economic depression. Whether or not it agrees to the ruinous terms imposed upon it by its creditors in order to obtain a ... Read More »
Mexico opens up oil industry for first time in 80 years
BBC – For the first time in nearly 80 years, Mexico has opened up its oil industry to foreign investors, selling off 14 exploration blocks in the Gulf of Mexico. However, only two of the blocks were sold in the auction, falling short of the government's expectations. Bidders were expected to sign new contracts with the Mexican state to explore, produce ... Read More »
Russia mulls direct energy supplies to Greece in near future – energy minister
RT – Moscow is considering direct energy supplies to Greece, Russia's Energy Minister Aleksandr Novak has said, adding that the country wants to help Greek recovery by expanding economic cooperation. "Russia intends to support the recovery of the Greek economy by increasing cooperation in the energy sector. Therefore we are looking into options for facilitating direct energy supplies to Greece ... Read More »


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Analysing Jack Wilshere's man of the match performance for Arsenal v Marseille [By Squawka Football]
- November 27, 2013
- Comments0
Since breaking into Arsenal's first team back in 2010, Jack Wilshere has been the focal point of the English media's gaze, under the spotlight of intense scrutiny. An extreme pressure cast upon the shoulders of a talented youngster, deemed a prospective saviour of English football and potential mainstay in the national team for the foreseeable future.
This screenshot is taken from the Squawka Football App – Download it here.
Viewed as a possible crock in the making, due to his unfortunate and ill-fated visits to the treatment table over the years, Wilshere shook off the cobwebs on Tuesday and displayed all of his attacking traits as Arsenal strolled to a 2-0 victory over Marseille in the Champions League.
Wilshere's heat map versus Marseille.
The 21-year-old midfielder ran the channels well, hugged the touchline when the team required extra width, darted into space beyond the opposition defence, and generally looked to penetrate Marseille's back four on a regular basis – more so than any other player.
Wilshere spent most of his time in front of Marseille's penalty box.
Wilshere frequently drifted inside too, linking intelligently with the likes of Aaron Ramsey and Mesut Özil as Arsenal maintained a level of creative fluidity that kept the French side on their toes, not knowing when a player in red would drift into space and take up a new position. Indeed, it only took 30 seconds from kick-off for Wilshere to scurry down the right flank into acres of space, cut inside onto his left foot and precisely lift the ball into the far corner past Steve Mandanda.
Two goals that won the game.
Marseille were shaken from then on, leaving pockets of space for Arsenal to probe and penetrate at will, with Wilshere remaining the epicentre of all things good for the hosts.
The most disappointing aspect, from Arsenal's standpoint, was their inability to pile on the pressure and see the game out following the early goal. They took the foot off the pedal and reduced the tempo, which in turn took the sting out of their own game.
Decisive passing, quicker tempo and horizontal passes to players in space had proven successful. It's just a shame they didn't pursue this strategy further, with more zest.
Wilshere completed 38 passes on the night from a variety of locations, including three goalscoring chances – one from the centre circle, and two within the opposition's 18-yard box. The total number of passes may be paltry when compared to Tomáš Rosický (79), Mathieu Flamini (90) and Ramsey (97), however Wilshere's role was to assist in patient build-up throughout central zones when needed, and dash into space beyond Olivier Giroud via the left and right channels.
Indeed, on one occasion the 27-year-old French striker was seen pointing to his feet (direction of passes), seemingly reluctant to break the offside trap – that was Wilshere's job.
Squawka's Man of the Match.
Two successful dribble attempts (100%) and two successful tackles (100%) only adds further emphasis that Wilshere performed at an impressive level in last night's clash with Marseille, picking up a Performance Score of 69 and the Squawka Man of the Match award in the process. Ever willing to advance into space, drop deep, switch sides, surge past opponents, and create chances for others, the England international capped his notable display with the game's only goals.
The opposition may have been lacklustre – personnel changes implying that Marseille were more concerned about resting key players than the score – however, you can only beat what's in front of you, and Wilshere unequivocally did that.
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