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Remels, A.H.V. (author), Derks, W.J.A. (author), Cillero-Pastor, B. (author), Verhees, K.J.P. (author), Kelders, M.C. (author), Heggermont, W. (author), Carai, P. (author), Summer, G. (author), Ellis, S.R. (author), de Theije, C.C. (author), Heeren, R.M.A. (author), Heymans, S. (author), Papageorgiou, A.P. (author), van Bilsen, M. (author)Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac...article 2018
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van Keulen, D. (author), Pouwer, M.G. (author), Pasterkamp, G. (author), van Gool, A.J. (author), Sollewijn Gelpke, M.D. (author), Princen, H.M.G. (author), Tempel, D. (author)Aims Endothelial activation is involved in many chronic inflammatory diseases, such as atherosclerosis, and is often initiated by cytokines. Oncostatin M (OSM) is a relatively unknown cytokine that has been suggested to play a role in both endothelial activation and atherosclerosis. We comprehensively investigated the effect of OSM on...article 2018
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Leist, M. (author), Ghallab, A. (author), Graepel, R. (author), Marchan, R. (author), Hassan, R. (author), Bennekou, S.H. (author), Limonciel, A. (author), Vinken, M. (author), Schildknecht, S. (author), Waldmann, T. (author), Danen, E. (author), van Ravenzwaay, B. (author), Kamp, H. (author), Gardner, I. (author), Godoy, P. (author), Bois, F.Y. (author), Braeuning, A. (author), Reif, R. (author), Oesch, F. (author), Drasdo, D. (author), Höhme, S. (author), Schwarz, M. (author), Hartung, T. (author), Braunbeck, T. (author), Beltman, J. (author), Vrieling, H. (author), Sanz, F. (author), Forsby, A. (author), Gadaleta, D. (author), Fisher, C. (author), Kelm, J. (author), Fluri, D. (author), Ecker, G. (author), Zdrazil, B. (author), Terron, A. (author), Jennings, P. (author), van der Burg, B. (author), Dooley, S. (author), Meijer, A.H. (author), Willighagen, E. (author), Martens, M. (author), Evelo, C. (author), Mombelli, E. (author), Taboureau, O. (author), Mantovani, A. (author), Hardy, B. (author), Koch, B. (author), Escher, S. (author), van Thriel, C. (author), Cadenas, C. (author), Kroese, D. (author), van de Water, B. (author), Hengstler, J.G. (author)Adverse outcome pathways (AOPs) are a recent toxicological construct that connects, in a formalized, transparent and quality-controlled way, mechanistic information to apical endpoints for regulatory purposes. AOP links a molecular initiating event (MIE) to the adverse outcome (AO) via key events (KE), in a way specified by key event...article 2017
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Derous, D. (author), Kelder, T. (author), van Schothorst, E.M. (author), van Erk, M. (author), Voigt, A. (author), Klaus, S. (author), Keijer, J. (author), Radonjic, M. (author)Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing...article 2015
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Busnadiego, O. (author), Gorbenko del Blanco, D. (author), González-Santamaría, J. (author), Habashi, J.P. (author), Calderon, J.F. (author), Sandoval, P. (author), Bedja, D. (author), Guinea-Viniegra, J. (author), Lopez-Cabrera, M. (author), Rosell-Garcia, T. (author), Snabel, J.M. (author), Hanemaaijer, R. (author), Forteza, A. (author), Dietz, H.C. (author), Egea, G. (author), Rodriguez-Pascual, F. (author)Patients with Marfan syndrome (MFS) are at high risk of life-threatening aortic dissections. The condition is caused by mutations in the gene encoding fibrillin-1, an essential component in the formation of elastic fibers. While experimental findings in animal models of the disease have shown the involvement of transforming growth factor-β (TGF...article 2015
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Raiten, D.J. (author), Sakr Ashour, F.A. (author), Ross, A.C. (author), Meydani, S.N. (author), Dawson, H.D. (author), Stephensen, C.B. (author), Brabin, B.J. (author), Suchdev, P.S. (author), van Ommen, B. (author), Ahluwalia, N. (author), Ahmed, T. (author), Allen, L. (author), Beck, M. (author), Blanchard, H. (author), Brindle, E. (author), Brown, K. (author), Calder, P. (author), Checkley, W. (author), Claycombe, K. (author), Coles, C. (author), Esamai, F. (author), Friis, H. (author), Gardner, E. (author), Grinspoon, S. (author), Guerrant, R. (author), Hellerstein, M. (author), Hunt, J. (author), King, J. (author), Klasing, K. (author), Kramer, B. (author), Koski, K. (author), Northrop-Clewes, C. (author), Pfeiffer, C. (author), Prentice, A. (author), Ramirez-Zea, M. (author), van Rheenan, P. (author), Rink, L. (author), Srinivasa, S. (author), Benn, C.S. (author), Stephensen, C. (author), Suchdev, P. (author), Sullivan, K. (author), Thurnham, D. (author), Varadhan, R. (author), Van Der Ven, A. (author), Walston, J. (author), Xia, J. (author)An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and...article 2015
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Mariman, R. (author), Kremer, S.H.A. (author), Koning, F. (author), Nagelkerken, L. (author)Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...article 2014
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Kooijman, S. (author), Boon, M.R. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van de Pol, V. (author), Romijn, J.A. (author), Havekes, L.M. (author), Meurs, I. (author), Rensen, P.C.N. (author)The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...article 2014
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Abhyankar, W. (author), Beek, A.T. (author), Dekker, H. (author), Kort, R. (author), Brul, S. (author), de Koster, C.G. (author)Species from the genus Bacillus have the ability to form endospores, dormant cellular forms that are able to survive heat and acid preservation techniques commonly used in the food industry. Resistance characteristics of spores towards various environmental stresses are in part attributed to their coat proteins. Previously, 70 proteins have been...article 2011
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Gaubius Instituut TNO (author), Coomans, C.P. (author), Geerling, J.J. (author), Guigas, B. (author), van den Hoek, A.M. (author), Parlevliet, E.T. (author), Ouwens, D.M. (author), Pijl, H. (author), Voshol, P.J. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Romijn, J.A. (author)Insulin signaling in the central nervous system (CNS) is required for the inhibitory effect of insulin on glucose production. Our aim was to determine whether the CNS is also involved in the stimulatory effect of circulating insulin on the tissue-specific retention of fatty acid (FA) from plasma. In wild-type mice, hyperinsulinemic-euglycemic...article 2011
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Coomans, C.P. (author), Biermasz, N.R. (author), Geerling, J.J. (author), Guigas, B. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), Romijn, J.A. (author)OBJECTIVE - Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake. RESEARCH DESIGN...article 2011
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Bsibsi, M. (author), Bajramovic, J.J. (author), Vogt, M.H. (author), van Duijvenvoorden, E. (author), Baghat, A. (author), Persoon-Deen, C. (author), Tielen, F. (author), Verbeek, R. (author), Huitinga, I. (author), Ryffel, B. (author), Kros, A. (author), Gerritsen, W.H. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne...article 2010
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van Delft, J.H.M. (author), Mathijs, K. (author), Staal, Y.C.M. (author), van Herwijnen, M.H.M. (author), Brauers, K.J.J. (author), Boorsma, A. (author), Kleinjans, J.C.S. (author), TNO Kwaliteit van Leven (author)Chemical carcinogens may cause a multitude of effects inside cells, thereby affecting transcript levels of genes by direct activation of transcription factors (TF) or indirectly through the formation of DNA damage. As the temporal profiles of these responses may be profoundly different, examining time-dependent changes may provide new insights...article 2010
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TNO Kwaliteit van Leven (author), Berbé, J.F.P. (author), Coomans, C.P. (author), Westerterp, M. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Timely sensing of lipopolysaccharide (LPS) is critical for the host to fight invading Gram-negative bacteria. We recently showed that apolipoprotein CI (apoCI) (apoCI1-57) avidly binds to LPS, involving an LPS-binding motif (apoCI48-54), and thereby enhances the LPS-induced inflammatory response. Our current aim was to further elucidate the...article 2010
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van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...article 2009
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TNO Defensie en Veiligheid (author), Molhoek, E.M. (author), den Hertog, A.L. (author), de Vries, A.M.B.C. (author), Nazmi, K. (author), Veerman, E.C.I. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), Bikker, F.J. (author), van der Kleij, D. (author)Cathelicidins are effector molecules of the innate host defense system that establish an antimicrobial barrier at epithelial interfaces. The human cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits immunomodulatory effects, such as inhibition of pro-inflammatory responses to bacterial LPS in human monocytic cells. In...article 2009
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Lu, Z.F. (author), Doulabi, B.Z. (author), Huang, C.L. (author), Bank, R.A. (author), Helder, M.N. (author), TNO Kwaliteit van Leven (author)β1 integrins play a controversial role during chondrogenesis. Since the maturation of chondrocytes relies on a signaling switch from cell-cell to cell-matrix interactions, we hypothesized that β1 integrins play a different role at the earlier (mainly cell-cell interaction) from the later stage (mainly cell-matrix interaction) of chondrogenesis....article 2008
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Molecular characterization of trimellitic anhydride-induced respiratory allergy in Brown Norway ratsKuper, C.F. (author), Heijne, W.H. (author), Dansen, M. (author), Verhoeckx, K.C. (author), Boorsma, A. (author), Radonjic, M. (author), Bruijntjes, J. (author), Stierum, R. (author), Muijser, H. (author), Arts, J.H. (author), TNO Kwaliteit van Leven (author)To contribute to the hazard identification of low molecular weight (LMW) respiratory allergens, respiratory allergy induced by trimellitic anhydride (TMA) was characterized by whole genome analysis of lung tissue and blood proteomics in Brown Norway rats. Dermal sensitization (50% and 25% w/v) with TMA and an inhalation challenge of 15 mg/m(3)...article 2008
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de Ruiter, M.C. (author), Alkemade, F.E. (author), de Gittenberger - Groot, A.C. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)In this review, we briefly summarize the possible signals crossing the placental barrier and discuss the molecular mechanisms of epigenetic programming in the developing fetus leading to increased athero-susceptibility of the vessel wall. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.article 2008
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Kleemann, R. (author), Zadelaar, A.S.M. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are...article 2008