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Macrophage low-density lipoprotein receptor-related protein deficiency enhances atherosclerosis in apoE/LDLR double knockout mice

Hu, L. (author), Boesten, L.S.M. (author), May, P. (author), Herz, J. (author), Bovenschen, N. (author), Huisman, M.V. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Tamsma, J.T. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. METHODS AND RESULTS - We generated...

article 2006

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Chronic quercetin exposure affects fatty acid catabolism in rat lung

de Boer, V.C.J. (author), van Schothorst, E.M. (author), Dihal, A.A. (author), van der Woude, H. (author), Arts, I.C.W. (author), Rietjens, I.M.C.M. (author), Hollman, P.C.H. (author), Keijer, J. (author), TNO Kwaliteit van Leven (author)

Dietary quercetin intake is suggested to be health promoting, but this assumption is mainly based on mechanistic studies performed in vitro. Previously, we identified rat lung as a quercetin target tissue. To assess relevant in vivo health effects of quercetin, we analyzed mechanisms of effect in rat lungs of a chronic (41 weeks) 1% quercetin...

article 2006

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Cholesterol 7α-hydroxylase deficiency in mice on an APOE*3-Leiden background increases hepatic ABCA1 mRNA expression and HDL-cholesterol

Post, S.M. (author), Groenendijk, M. (author), van der Hoogt, C.C. (author), Fievet, C. (author), Luc, G. (author), Hoekstra, M. (author), Princen, H.M.G. (author), Staels, B. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7α-hydroxylase (Cyp7a1) catalyzes the rate-limiting step...

article 2006

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Mdm2, but not Mdm4, protects terminally differentiated smooth muscle cells from p53-mediated caspase-3-independent cell death

TNO Kwaliteit van Leven (author), Boesten, L.S.M. (author), Zadelaar, A.S.M. (author), de Clercq, S. (author), Francoz, S. (author), van Nieuwkoop, A. (author), Biessen, E.A.L. (author), Hofmann, F. (author), Feil, S. (author), Feil, R. (author), Jochemsen, A.G. (author), Zurcher, C. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Marine, J.C. (author)

p53 is a potent inhibitor of cell growth and an inducer of apoptosis. During embryonic development, Mdm2 and Mdm4 inhibit the growth suppressive activities of p53. However, whether tight surveillance of p53 activity is required in quiescent cells is unknown. To test this, conditional inactivation of mdm2 and mdm4 was carried out in smooth muscle...

article 2006

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Unlocking Streptomyces spp. for use as sustainable industrial production platforms by morphological engineering

TNO Kwaliteit van Leven (author), van Wezel, G.P. (author), Krabben, P. (author), Traag, B.A. (author), Keijser, B.J.F. (author), Kerste, R. (author), Vijgenboom, E. (author), Heijnen, J.J. (author), Kraal, B. (author)

Filamentous actinomycetes are commercially widely used as producers of natural products (in particular antibiotics) and of industrial enzymes. However, the mycelial lifestyle of actinomycetes, resulting in highly viscous broths and unfavorable pellet formation, has been a major bottleneck in their commercialization. Here we describe the...

article 2006

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Modulation of the cytokine network in human adult astrocytes by human herpesvirus-6A

Meeuwsen, S. (author), Persoon-Deen, C. (author), Bsibsi, M. (author), Bajramovic, J.J. (author), Ravid, R. (author), de Bolle, L. (author), van Noort, J.M. (author), Gaubius Instituut TNO (author)

Human herpesvirus-6A (HHV-6A) is a common pathogen whose role in CNS disorders including multiple sclerosis remains controversial. To understand how HHV-6A could influence inflammatory pathways in the CNS, we infected cultured human adult astrocytes and examined the expression of 268 cytokines, chemokines, growth factors and their receptors by...

article 2005

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Nutrigenomics: The impact of biomics technology on nutrition research

Corthésy-Theulaz, I. (author), den Dunnen, J.T. (author), Ferré, P. (author), Geurts, J.M.W. (author), Müller, M. (author), van Belzen, N. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)

The interaction between the human body and nutrition is an extremely complex process involving multi-organ physiology with molecular mechanisms on all levels of regulation (genes, gene expression, proteins, metabolites). Only with the recent technology push have nutritional scientists been able to address this complexity. Both the challenges and...

article 2005

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Optimization of biomass, vitamins, and carotenoid yield on light energy in a flat-panel reactor using the A-stat technique

Barbosa, M.J. (author), Zijffers, J.W. (author), Nisworo, A. (author), Vaes, W. (author), van Schoonhoven, J. (author), Wijffels, R.H. (author), TNO Kwaliteit van Leven (author)

Acceleration-stat (A-stat) cultivations in which the dilution rate is continuously changed at a constant acceleration rate, leading to different average light intensities inside the photobioreactor, can supply more information and reduce experimental time compared with chemostat cultivations. The A-stat was used to optimize the biomass and...

article 2005

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Toxicogenomic analysis of gene expression changes in rat liver after a 28-day oral benzene exposure

Heijne, W.H.M. (author), Jonker, D. (author), Stierum, R.H. (author), van Ommen, B. (author), Groten, J.P. (author), TNO Kwaliteit van Leven (author)

Benzene is an industrial chemical, component of automobile exhaust and cigarette smoke. After hepatic bioactivation benzene induces bone marrow, blood and hepatic toxicity. Using a toxicogenomics approach this study analysed the effects of benzene at three dose levels on gene expression in the liver after 28 daily doses. NMR based metabolomics...

article 2005

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The Aspergillus niger MADS-box transcription factor RlmA is required for cell wall reinforcement in response to cell wall stress

Damveld, R.A. (author), Arentshorst, M. (author), Franken, A. (author), van Kuyk, P.A. (author), Klis, F.M. (author), van den Hondel, C.A.M.J.J. (author), Ram, A.F.J. (author), TNO Kwaliteit van Leven (author)

In Aspergillus niger, the genes coding for glutamine:fructose-6-phosphate amidotransferase (gfaA) and α-1,3-glucan synthase (agsA) are induced in response to cell wall stress. In silico analysis of the promoter region of the two genes revealed the presence of putative DNA binding sites for transcription factors involved in stress responses,...

article 2005

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Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus

Meeuwsen, S. (author), Bsibsi, M. (author), Persoon-Deen, C. (author), Ravid, R. (author), van Noort, J.M. (author), TNO Preventie en Gezondheid (author)

Objectives: Brain microglia are highly responsive cells in the central nervous system that exert key functions in host defense as well as in neuroprotection and regeneration. In this study the gene expression profiles for 268 cytokines, chemokines, growth factors and their receptors were examined in cultures of purified human adult microglia,...

article 2005

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Minoxidil exerts different inhibitory effects on gene expression of lysyl hydroxylase 1, 2, and 3: Implications for collagen cross-linking and treatment of fibrosis

Zuurmond, A.M. (author), Slot van der-Verhoeven, A.J. (author), van Dura, E.A. (author), de Groot, J. (author), Bank, R.A. (author), TNO Kwaliteit van Leven (author)

Collagen deposits in fibrotic lesions often display elevated levels of hydroxyallysine (pyridinoline) cross-links. The relation between the occurrence of pyridinoline cross-links and the irreversibility of fibrosis suggests that these cross-links contribute to the aberrant accumulation of collagen. Based on its inhibitory effect on lysyl...

article 2005

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Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced lysyl hydroxylase 2b levels

van der Slot, A.J. (author), van Dura, E.A. (author), de Wit, E.C. (author), de Groot, J. (author), Huizinga, T.W.J. (author), Bank, R.A. (author), Zuurmond, A.M. (author), TNO Preventie en Gezondheid (author)

The hallmark of fibrosis is the excessive accumulation of collagen. The deposited collagen contains increased pyridinoline cross-link levels due to an overhydroxylation of lysine residues within the collagen telopeptides. Lysyl hydroxylase 2b (LH2b) is the only lysyl hydroxylase consistently up-regulated in several forms of fibrosis, suggesting...

article 2005

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Different control mechanisms regulate glucoamylase and protease gene transcription in Aspergillus oryzae in solid-state and submerged fermentation

te Biesebeke, R. (author), van Biezen, N. (author), de Vos, W.M. (author), van den Hondel, C.A.M.J.J. (author), Punt, P.J. (author), TNO Kwaliteit van Leven (author)

Solid-state fermentation (SSF) with Aspergillus oryzae results in high levels of secreted protein. However, control mechanisms of gene expression in SSF have been only poorly studied. In this study we show that both glucoamylase (glaB) and protease (alpA, nptB) genes are highly expressed during surface cultivation on wheat-based solid medium,...

article 2005

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Androgenic switch: An example of plant embryogenesis from the male gametophyte perspective

Maraschin, S.F. (author), de Priester, W. (author), Spaink, H.P. (author), Wang, M. (author)

Embryogenesis in plants is a unique process in the sense that it can be initiated from a wide range of cells other than the zygote. Upon stress, microspores or young pollen grains can be switched from their normal pollen development towards an embryogenic pathway, a process called androgenesis. Androgenesis represents an important tool for...

article 2005

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Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro

van Erk, M.J. (author), Roepman, P. (author), van der Lende, T.R. (author), Stierum, R.H. (author), Aarts, J.M.M.J.G. (author), van Bladeren, P.J. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)

Background: Many different mechanisms are involved in nutrient-related prevention of colon cancer. In this study, a comprehensive assessment of the spectrum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid that can inhibit proliferation of tumor cells and...

article 2005

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Expression profiling of colon cancer cell lines and colon biopsies: Towards a screening system for potential cancer-preventive compounds

van Erk, M.J. (author), Krul, C.A.M. (author), Caldenhoven, E. (author), Stierum, R.H. (author), Peters, W.H. (author), Woutersen, R.A. (author), van Ommen, B. (author), TNO Kwaliteit van Leven TNO Voeding (author)

Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived from colonic tissue were measured using cDNA...

article 2005

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Agrobacterium-mediated transformation as a tool for functional genomics in fungi

Michielse, C.B. (author), Hooykaas, P.J.J. (author), van den Hondel, C.A.M.J.J. (author), Ram, A.F.J. (author), TNO Kwaliteit van Leven (author)

In the era of functional genomics, the need for tools to perform large-scale targeted and random mutagenesis is increasing. A potential tool is Agrobacterium-mediated fungal transformation. A. tumefaciens is able to transfer a part of its DNA (transferred DNA; T-DNA) to a wide variety of fungi and the number of fungi that can be transformed by...

article 2005

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Tumor necrosis factor-α plays an important role in restenosis development

Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...

article 2005

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Identification of growth phenotype-related genes in Aspergillus oryzae by heterologous macroarray and suppression subtractive hybridization

te Biesebeke, R. (author), Levin, A. (author), Sagt, C. (author), Bartels, J. (author), Goosen, T. (author), Ram, A. (author), van den Hondel, C. (author), Punt, P. (author), TNO Kwaliteit van Leven (author)

Aspergillus oryzae requires polarized growth for colonization of solid substrates, and this growth phenotype differs from that seen in liquid medium. Various experimental approaches were used to identify genes that are differentially expressed when A. oryzae is grown on wheat kernels and in a wheat-based liquid medium. Hybridization of A. oryzae...

article 2005