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Activity based protein profiling leads to identification of novel protein targets for nerve agent VXCarmany, D. (author), Walz, A.J. (author), Hsu, F.L. (author), Benton, B. (author), Burnett, D. (author), Gibbons, J. (author), Noort, D. (author), Glaros, T. (author), Sekowski, J.W. (author)Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt...article 2017
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Zeegers, M.P. (author), Nekeman, D. (author), Khan, H.S. (author), van Dijk, B.A.C. (author), Goldbohm, R.A. (author), Schalken, J. (author), Shajahan, S. (author), Pearlman, A. (author), Oddoux, C. (author), van den Brandt, P.A. (author), Schouten, L.J. (author), Ostrer, H. (author), TNO Preventie en Gezondheid (author)Background:Prostate cancer is the most commonly diagnosed cancer in men in Europe and the United States. Numerous studies have indicated genetics to have a major role in the aetiology of this disease; as much as 42% of the risk may be explained by heritable factors. Genome-wide association studies have detected an association between prostate...article 2013
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Georgiadi, A. (author), Wang, Y. (author), Stienstra, R. (author), Tjeerdema, N. (author), Janssen, A. (author), Stalenhoef, A. (author), van der Vliet, J.A. (author), de Roos, A. (author), Tamsma, J.T. (author), Smit, J.W. (author), Tan, N.S. (author), Müller, M. (author), Rensen, P.C. (author), Kersten, S. (author)Objective: Macrophage foam cells play a crucial role in several pathologies including multiple sclerosis, glomerulosclerosis, and atherosclerosis. Angiopoietin-like protein 4 (Angptl4) was previously shown to inhibit chyle-induced foam cell formation in mesenteric lymph nodes. Here we characterized the regulation of Angptl4 expression in...article 2013
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Abrahamse, E. (author), Minekus, M. (author), van Aken, G.A. (author), van de Heijning, B. (author), Knol, J. (author), Bartke, N. (author), Oozeer, R. (author), van der Beek, E.M. (author), Ludwig, T. (author)At least during the first 6 months after birth, the nutrition of infants should ideally consist of human milk which provides 40-60 % of energy from lipids. Beyond energy, human milk also delivers lipids with a specific functionality, such as essential fatty acids (FA), phospholipids, and cholesterol. Healthy development, especially of the...article 2012
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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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TNO Kwaliteit van Leven (author), Bijland, S. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W.A. (author), van Erk, M.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are...article 2010
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Voshol, P.J. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the...article 2009
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Henneman, P. (author), van der Sman-de Beer, F. (author), Moghaddam, P.H. (author), Huijts, P. (author), Stalenhoef, A.F.H. (author), Kastelein, J.J.P. (author), van Duijn, C.M. (author), Havekes, L.M. (author), Frants, R.R. (author), van Dijk, K.W. (author), Smelt, A.H.M. (author), TNO Kwaliteit van Leven (author)Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In...article 2009
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TNO Kwaliteit van Leven (author), van Schalkwijk, D.B. (author), de Graaf, A.A. (author), van Ommen, B. (author), van Bochove, K. (author), Rensen, P.C.N. (author), Havekes, L.M. (author), van de Pas, N.C.A. (author), Hoefsloot, H.C.J. (author), van der Greef, J. (author), Freidig, A.P. (author)Increased plasma cholesterol is a known risk factor for cardiovascular disease. Lipoprotein particles transport both cholesterol and triglycerides through the blood. It is thought that the size distribution of these particles codetermines cardiovascular disease risk. New types of measurements can determine the concentration of many lipoprotein...article 2009
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TNO Kwaliteit van Leven (author), Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...article 2008
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TNO Kwaliteit van Leven (author), Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...article 2008
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Henneman, P. (author), Schaap, F.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Frants, R.R. (author), van Tol, A. (author), Hattori, H. (author), Smelt, A.H.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Objective: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation....article 2007
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...article 2007
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TNO Kwaliteit van Leven (author), Moen, C.J.A. (author), Tholens, A.P. (author), Voshol, P.J. (author), de Haan, W. (author), Havekes, L.M. (author), Gargalovic, P. (author), Lusis, A.J. (author), van Dyk, K.W. (author), Frants, R.R. (author), Hofker, M.H. (author), Rensen, P.C.N. (author)The Hyplip2 congenic mouse strain contains part of chromosome 15 from MRL/MpJ on the BALB/cJ background. Hyplip2 mice show increased plasma levels of cholesterol and predominantly triglycerides (TGs) and are susceptible to diet-induced atherosclerosis. This study aimed at elucidation of the mechanism(s) explaining the hypertriglyceridemia....article 2007
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Primo-Martín, C. (author), Hamer, R.J. (author), de Jongh, H.H.J. (author), TNO Kwaliteit van Leven (author)Gas cell stability during bread making is controlled by both surface and bulk properties. This paper is focused on studying the surface properties of the water-soluble phase of the dough, the dough liquor (with and without lipids), as well as the composition of the air/water interface. Using infrared reflection measurements, we showed that in...article 2006
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den Boer, M.A.M. (author), Berbée, J.F.P. (author), Reiss, P. (author), van der Valk, M. (author), Voshol, P.J. (author), Kuipers, F. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Romijn, J.A. (author), Gaubius Instituut TNO (author)Objective - The use of the HIV protease inhibitor ritonavir (RTV) is frequently associated with hypertriglyceridemia and lipodystrophy. The aim of our study was to determine the mechanism underlying the observed hypertriglyceridemia. Methods and Results - Feeding female APOE*3-Leiden transgenic mice a Western-type diet supplemented with RTV (35...article 2006
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TNO Kwaliteit van Leven (author), Westerterp, M. (author), de Haan, W. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma lipid levels independently of effects of apoE on...article 2006
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Rensen, P.C.N. (author), van Dijk, K.W. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)Chemicals / CAS: lipoprotein lipase, 83137-80-8, 9004-02-8; APOA5 protein, human; Apolipoproteins A; Apolipoproteins; Triglyceridesarticle 2005
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TNO Kwaliteit van Leven (author), Gerritsen, G. (author), Rensen, P.C.N. (author), Kypreos, K.E. (author), Zannis, V.I. (author), Havekes, L.M. (author), van Dijk, K.W. (author)Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by...article 2005
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TNO Kwaliteit van Leven (author), Espirito Santo, S.M.S. (author), Rensen, P.C.N. (author), Goudriaan, J.R. (author), Bensadoun, A. (author), Bovenschen, N. (author), Voshol, P.J. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author)The very low density lipoprotein receptor (VLDLR), low density lipoprotein receptor (LDLR), and low density lipoprotein receptor-related protein (LRP) are the three main apolipoprotein E-recognizing endocytic receptors involved in the clearance of triglyceride (TG)-rich lipoproteins from plasma. Whereas LDLR deficiency in mice results in the...article 2005