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Offringa, A. (author), Montijn, R. (author), Singh, S. (author), Paul, M. (author), Pinto, Y.M. (author), Pinto-Sietsma, S.J. (author)
The SARS-CoV-2 pandemic is a healthcare crisis caused by insufficient knowledge applicable to effectively combat the virus. Therefore, different scientific discovery strategies need to be connected, to generate a rational treatment which can be made available as rapidly as possible. This relies on a solid theoretical understanding of the...
article 2020
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Venema, K. (author)
article 2012
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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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Kleemann, R. (author), Bucala, R. (author), TNO Kwaliteit van Leven (author)
Obesity is associated with insulin resistance, disturbed glucose homeostasis, low grade inflammation, and comorbidities such as type 2 diabetes and cardiovascular disease. The cytokine macrophage migration inhibitory factor (MIF) is an ubiquitously expressed protein that plays a crucial role in many inflammatory and autoimmune disorders....
article 2010
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Venema, K. (author), TNO Kwaliteit van Leven (author)
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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Kienhuis, A.S. (author), van de Poll, M.C.G. (author), Wortelboer, H. (author), van Herwijnen, M. (author), Gottschalk, R. (author), de Jong, C.H.C. (author), Boorsma, A. (author), Paules, R.S. (author), Kleinjans, J.C.S. (author), Stierum, R.H. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)
The frequent use of rodent hepatic in vitro systems in pharmacological and toxicological investigations challenges extrapolation of in vitro results to the situation in vivo and interspecies extrapolation from rodents to humans. The toxicogenomics approach may aid in evaluating relevance of these model systems for human risk assessment by direct...
article 2009
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Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)
Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...
article 2009
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Schaafsma, G. (author), Kroese, E.D. (author), Tielemans, E.L.J.P. (author), van de Sandt, J.J.M. (author), van Leeuwen, C.J. (author), TNO Kwaliteit van Leven (author)
The objectives of REACH cannot be achieved under the current risk assessment approach. A change in mind set among all the relevant stakeholders is needed: risk assessment should move away from a labor-intensive and animal-consuming approach to intelligent and pragmatic testing, by combining exposure and hazard data effectively and trying to...
article 2009
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Madsen, C.B. (author), Hattersley, S. (author), Buck, J. (author), Gendel, S.M. (author), Houben, G.F. (author), Hourihane, J.OB. (author), Mackie, A. (author), Mills, E.N.C. (author), Nørhede, P. (author), Taylor, S.L. (author), Crevel, R.W.R. (author), TNO Kwaliteit van Leven (author)
A workshop was organised to investigate whether risk assessment strategies and methodologies used in classical/conventional toxicology may be used for risk assessment of allergenic foods, to discuss the advantages and limitations of different approaches and to determine the research needed to move the area forward. Three possible approaches to...
article 2009
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Kersten, S. (author), Lichtenstein, L. (author), Steenbergen, E. (author), Mudde, K. (author), Hendriks, H.F.J. (author), Hesselink, M.K. (author), Schrauwen, P. (author), Müller, M. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human....
article 2009
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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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Schutte, M.E. (author), Alink, G.M. (author), Freidig, A.P. (author), Spenkelink, B. (author), Vaessen, J.C.H. (author), van de Sandt, J.J.M. (author), Groten, J.P. (author), Rietjens, I.M.C.M. (author), TNO Kwaliteit van Leven (author), KvL (author)
This study investigates whether the previous observation that quercetin increases the transport of PhIP through Caco-2 monolayers in vitro could be confirmed in an in vivo rat model. Co-administration of 1.45 μmol PhIP/kg bw and 30 μmol quercetin/kg bw significantly increased the blood AUC(0-8 h) of PhIP in rats to 131 ± 14% of the AUC(0-8 h)...
article 2008
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Groux-Degroote, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), Neumann, S. (author), Theos, A.C. (author), de Mazière, A.M. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)
Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1)...
article 2008
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Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)
Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...
article 2008
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van Weel, V. (author), van Tongeren, R.B. (author), van Hinsbergh, V.W.M. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)
Stimulation of vascular growth to treat limb ischemia is promising, and early results obtained from uncontrolled clinical trials using angiogenic agents, e.g., vascular endothelial growth factor, led to high expectations. However, negative results from recent placebo-controlled trials warrant further research. Here, current insights into...
article 2008
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Fabriek, B.O. (author), Møller, H.J. (author), Vloet, R.P.M. (author), van Winsen, L.M. (author), Hanemaaijer, R. (author), Teunissen, C.E. (author), Uitdehaag, B.M.J. (author), van den Berg, T.K. (author), Dijkstra, C.D. (author), TNO Kwaliteit van Leven (author)
The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present...
article 2007
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Hissink, A.M. (author), Krüse, J. (author), Kulig, B.M. (author), Verwei, M. (author), Muijser, H. (author), Salmon, F. (author), Leenheers, L.H. (author), Owen, D.E. (author), Lammers, J.H.C.M. (author), Freidig, A.P. (author), McKee, R.H. (author), TNO Kwaliteit van Leven (author)
As part of a project designed to develop a framework for extrapolating acute central nervous system (CNS) effects of hydrocarbon solvents in animals to humans, experimental studies were conducted in rats and human volunteers in which acute CNS effects were measured and toxicokinetic data were collected. A complex hydrocarbon solvent, white...
article 2007
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Alkemade, F.E. (author), de Gittenberger-Groot, A.C. (author), Schiel, A.E. (author), van Munsteren, J.C. (author), Hogers, B. (author), van Vliet, L.S.J. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), de Ruiter, M.C. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE - Maternal hypercholesterolemia is associated with a higher incidence and faster progression of atherosclerotic lesions in neonatal offspring. We aimed to determine whether an in utero environment exposing a fetus to maternal hypercholesterolemia and associated risk factors can prime the murine vessel wall to accelerated development of...
article 2007
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Halter, D. (author), Neumann, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), de Mazière, A.M. (author), Vieira, O.V. (author), Mattjus, P. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)
Glycosphingolipids are controlled by the spatial organization of their metabolism and by transport specificity. Using immunoelectron microscopy, we localize to the Golgi stack the glycosyltransferases that produce glucosylceramide (GlcCer), lactosylceramide (LacCer), and GM3. GlcCer is synthesized on the cytosolic side and must translocate...
article 2007
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