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Pouwer, M.G. (author), Pieterman, E.J. (author), Worms, N. (author), Keijzer, N. (author), Jukema, J.W. (author), Gromada, J. (author), Gusarova, V. (author), Princen, H.M.G. (author)Atherosclerosis-related cardiovascular disease causes nearly 20 million deaths annually. Most patients are treated after plaques develop, so therapies must regress existing lesions. Current therapies reduce plaque volume, but targeting all apoB-containing lipoproteins with intensive combinations that include alirocumab or evinacumab-monoclonal...article 2020
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Oosterman, J.E. (author), Wopereis, S. (author), Kalsbeek, A. (author)Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony...article 2020
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Schuster, S. (author), Rubil, S. (author), Endres, M. (author), Princen, H.M.G. (author), Boeckel, J.N. (author), Winter, K. (author), Werner, C. (author), Laufs, U. (author)LDL-cholesterol (LDL-C) is a causal pathogenic factor in atherosclerosis. Monoclonal anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) neutralizing antibodies are novel potent LDL-lowering drugs which reduce cardiovascular events. To characterize their effect on atherogenesis, APOE*3Leiden.CETP mice were fed a high cholesterol/high fat...article 2019
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Verhoeckx, K. (author), Bogh, K.L. (author), Dupont, D. (author), Egger, L. (author), Gadermaier, G. (author), Larre, C. (author), Mackie, A. (author), Menard, O. (author), Adel-Patient, K. (author), Picariello, G. (author), Portmann, R. (author), Smit, J. (author), Turner, P. (author), Untersmayr, E. (author), Epstein, M.M. (author)The current allergenicity assessment of novel proteins is based on the EFSA GMO guidance. Recently, EFSA launched a new guidance document on allergenicity assessment of GM plants (2017). This document describes, amongst other topics, the new scientific and regulatory developments on in vitro protein digestibility tests. The EFSA GMO Panel stated...article 2019
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Fu, J. (author), van Wietmarschen, H.A. (author), van der Kooij, A. (author), Cuppen, B.V.J. (author), Schroën, Y. (author), Marijnissen, A.K. (author), Meulman, J.J. (author), Lafeber, F.P.J.G. (author), van der Greef, J. (author)Introduction: Biological therapies have greatly improved the treatment efficacy in rheumatoid arthritis (RA). However, in clinical practice a significant proportion of patients experience an inadequate response to treatment. The aim of this study is to classify responding and non-responding rheumatoid arthritis patients treated with biological...article 2018
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de Jong, G.A.H. (author), Jayasena, S. (author), Johnson, P. (author), Marsh, J. (author), Apostolovic, D. (author), van Hage, M. (author), Nordlee, J. (author), Baumert, J. (author), Taylor, S.L. (author), Roucairol, C. (author), de Jongh, H. (author), Koppelman, S.J. (author)The 2S albumin Ara h 6 is one of the most important peanut allergens. A post-translationally cleaved Ara h 6 (pAra h 6) was purified from Virginia type peanuts, and the cleavage site was mapped using high-resolution mass spectrometry. Compared to intact Ara h 6, pAra h 6 lacks a 5-amino acid stretch, resembling amino acids 43-47 (UniProt...article 2018
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Verhoeckx, K.C.M. (author), Vissers, Y.M. (author), Baumert, J.L. (author), Faludi, R. (author), Feys, M. (author), Flanagan, S. (author), Herouet-Guicheney, C. (author), Holzhauser, T. (author), Shimojo, R. (author), van der Bolt, N. (author), Wichers, H. (author), Kimber, I. (author)Food processing can have many beneficial effects. However, processing may also alter the allergenic properties of food proteins. A wide variety of processing methods is available and their use depends largely on the food to be processed. In this review the impact of processing (heat and non-heat treatment) on the allergenic potential of proteins...article 2015
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Zune, Q. (author), Delepierre, A. (author), Gofflot, S. (author), Bauwens, J. (author), Twizere, J.C. (author), Punt, P.J. (author), Francis, F. (author), Toye, D. (author), Bawin, T. (author), Delvigne, F. (author)Fungal biofilm is known to promote the excretion of secondary metabolites in accordance with solid-staterelated physiological mechanisms. This work is based on the comparative analysis of classical submerged fermentation with a fungal biofilmreactor for the production of a Gla::green fluorescent protein (GFP) fusion protein by Aspergillus oryzae...article 2015
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van Uhm, J.I.M. (author), Visser, G.W.M. (author), van der Schans, M.J. (author), Geldof, A.A. (author), Meuleman, E.J.H. (author), Nieuwenhuijzen, J.A. (author)Background: Botulinum neurotoxin A (BoNT-A) is a highly neurotoxic drug and frequently used in patients. Knowledge on the optimal way of administration of BoNT-A and its subsequent distribution is still rather limited. An accurate method for monitoring these processes might be the use of radiolabelled BoNT-A. In this paper, we report our...article 2015
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Wagner, A. (author), Cohen, N. (author), Kelder, T. (author), Amit, U. (author), Liebman, E. (author), Steinberg, D.M. (author), Radonjic, M. (author), Ruppin, E. (author)High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...article 2015
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Wouters, D. (author), Wolbink, G.J. (author), Hart, M.H.L. (author), Rispens, T. (author), Ganderup, N.C. (author), Kuper, C.F. (author), Aarden, L. (author), Penninks, A.H. (author)Immunogenicity is a major issue of concern for monoclonal antibodies used in human diseases and is by default mainly determined in non-human primates (NHP), as target molecules are considered most similar in NHP compared to human. In this manuscript the predictive value of immunogenicity testing in minipigs for human safety is evaluated, as the...article 2014
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Vogt, L.M. (author), Meyer, D. (author), Pullens, G. (author), Faas, M.M. (author), Venema, K. (author), Ramasamy, U. (author), Schols, H.A. (author), de Vos, P. (author)Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear.We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether β2→1-fructan chain...article 2014
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Bereszczak, J.Z. (author), Havlik, M. (author), Weiss, V.U. (author), Marchetti-Deschmann, M. (author), van Duijn, E. (author), Watts, N.R. (author), Wingfield, P.T. (author), Allmaier, G. (author), Steven, A.C. (author), Heck, A.J.R. (author)The capsid of hepatitis B virus (HBV) is a major viral antigen and important diagnostic indicator. HBV capsids have prominent protrusions ('spikes') on their surface and are unique in having either T = 3 or T = 4 icosahedral symmetry. Mouse monoclonal and also human polyclonal antibodies bind either near the spike apices (historically the 'α...article 2014
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Ason, B. (author), van der Hoorn, J.W.A. (author), Chan, J. (author), Lee, E. (author), Pieterman, E.J. (author), Nguyen, K.K. (author), Di, M. (author), Shetterly, S. (author), Tang, J. (author), Yeh, W.C. (author), Schwarz, M. (author), Jukema, J.W. (author), Scott, R. (author), Wasserman, S.M. (author), Princen, H.M.G. (author), Jackson, S. (author)LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower...article 2014
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van Mierlo, G.J.D. (author), Cnubben, N.H.P. (author), Kuper, C.F. (author), Wolthoorn, J. (author), van Meeteren-Kreikamp, A.P. (author), Nagtegaal, M.M. (author), Doornbos, R. (author), Ganderup, N.-C. (author), Penninks, A.H. (author)The use of recombinant human proteins for the treatment of several diseases has increased considerably during the last decades. A major safety and efficacy issue of biopharmaceuticals is their potential immunogenicity. To prevent immunogenicity, biotechnology-derived proteins are engineered to be as human-like as possible. Immunogenicity is...article 2013
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van den Broek, I. (author), Niessen, W.M.A. (author), van Dongen, W.D. (author)Biotechnology increasingly delivers highly promising protein-based biopharmaceutical candidates to the drug development funnel. For successful biopharmaceutical drug development, reliable bioanalytical methods enabling quantification of drugs in biological fluids (plasma, urine, tissue, etc.) are required to generate toxicokinetic (TK),...article 2013
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- Sauerborn, M. (author) article 2013
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Rose, R.J. (author), Thompson, N.J. (author), Van Duijn, E. (author), Damoc, E. (author), Denisov, E. (author), Makarov, A. (author), Heck, A.J.R. (author)Monoclonal antibodies (mAbs) represent a major class of therapeutic biomolecules being developed by the biopharmaceutical industry, their popularity largely being a result of their high specificity towards targets. Therapeutic mAbs are being developed for various diseases, with a strong focus on cancer and immunological disorders.[1] All...article 2012
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van Noort, J.M. (author), Bsibsi, M. (author), Gerritsen, W.H. (author), van der Valk, P. (author), Bajramovic, J.J. (author), Steinman, L. (author), Amor, S. (author), TNO Kwaliteit van Leven (author)We present the first comparative analysis of serum immunoglobulinG reactivity profiles against the full spectrum of human myelin-associated proteins in multiple sclerosis patients and healthy control subjects. In both groups, serum antibodies display a consistent and prominent reaction to αB-crystallin (CRYAB) versus other myelin proteins. As an...article 2010
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Tonk, E.C.M. (author), de Groot, D.M.G. (author), Penninks, A.H. (author), Waalkens - Berendsen, I.D.H. (author), Wolterbeek, A.P.M. (author), Slob, W. (author), Piersma, A.H. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...article 2010