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A framework to identify physiological responses in microarray-based gene expression studies: Selection and interpretation of biologically relevant genes

Rodenburg, W. (author), Heidema, A.G. (author), Boer, J.M.A. (author), Bovee-Oudenhoven, I.M.J. (author), Feskens, E.J.M. (author), Mariman, E.C.M. (author), Keijer, J. (author), TNO Kwaliteit van Leven (author)

In whole genome microarray studies major gene expression changes are easily identified, but it is a challenge to capture small, but biologically important, changes. Pathway-based programs can capture small effects but may have the disadvantage of being restricted to functionally annotated genes. A structured approach toward the identification of...

article 2008

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Genomic analysis suggests higher susceptibility of children to air pollution

van Leeuwen, D.M. (author), Pedersen, M. (author), Hendriksen, P.J.M. (author), Boorsma, A. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), Kirsch-Volders, M. (author), Knudsen, L.E. (author), Šrám, R.J. (author), Bajak, E. (author), van Delft, J.H.M. (author), Kleinjans, J.C.S. (author), TNO Kwaliteit van Leven (author)

Differences in biological responses to exposure to hazardous airborne substances between children and adults have been reported, suggesting children to be more susceptible. Aim of this study was to improve our understanding of differences in susceptibility in cancer risk associated with air pollution by comparing genome-wide gene expression...

article 2008

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Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...

article 2008

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Endothelium specific matrilysin (MMP-7) expression in human cancers

Sier, C.F.M. (author), Hawinkels, L.J.A.C. (author), Zijlmans, H.J.M.A.A. (author), Zuidwijk, K. (author), Muller, E.S.M. (author), Ferreira, V. (author), Hanemaaijer, R. (author), Mulder-Stapel, A.A. (author), Kenter, G.G. (author), Verspaget, H.W. (author), Gorter, A. (author), TNO Kwaliteit van Leven (author)

Over-expression of matrilysin (MMP-7) is predominantly associated with epithelial (pre)malignant cells. In the present study MMP-7 expression is also found in endothelial cells in various human cancer types. Endothelial MMP-7 was associated with CD34 and/or CD105 expression. These immunohistochemical data were confirmed by RT-PCR on VEGF...

article 2008

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Nur77 modulates hepatic lipid metabolism through suppression of SREBP1c activity

Pols, T.W.H. (author), Ottenhoff, R. (author), Vos, M. (author), Levels, J.H.M. (author), Quax, P.H.A. (author), Meijers, J.C.M. (author), Pannekoek, H. (author), Groen, A.K. (author), de Vries, C.J.M. (author), TNO Kwaliteit van Leven (author)

NR4A nuclear receptors are induced in the liver upon fasting and regulate hepatic gluconeogenesis. Here, we studied the role of nuclear receptor Nur77 (NR4A1) in hepatic lipid metabolism. We generated mice expressing hepatic Nur77 using adenoviral vectors, and demonstrate that these mice exhibit a modulation of the plasma lipid profile and a...

article 2008

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Transcriptional activity around bacterial cell death reveals molecular biomarkers for cell viability

TNO Kwaliteit van Leven (author), Kort, R. (author), Keijser, B.J. (author), Caspers, M.P.M. (author), Schuren, F.H. (author), Montijn, R. (author)

Background: In bacteriology, the ability to grow in selective media and to form colonies on nutrient agar plates is routinely used as a retrospective criterion for the detection of living bacteria. However, the utilization of indicators for bacterial viability-such as the presence of specific transcripts or membrane integrity-would overcome bias...

article 2008

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TGFbeta affects collagen cross-linking independent of chondrocyte phenotype but strongly depending on physical environment

TNO Kwaliteit van Leven (author), Bastiaansen-Jenniskens, Y.M. (author), Koevoet, W. (author), de Bart, A.C.W. (author), Zuurmond, A.M. (author), Bank, R.A. (author), Verhaar, J.A.N. (author), de Groot, J. (author), van Osch, G.J.V.M. (author)

Transforming growth factor beta (TGFbeta) is often used in cartilage tissue engineering to increase matrix formation by cells with various phenotypes. However, adverse effects of TGFbeta, such as extensive cross-linking in cultured fibroblasts, have also been reported. Our goal was to study effects of TGFbeta on collagen cross-linking and...

article 2008

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Human apolipoprotein C-I expression in mice impairs learning and memory functions

TNO Kwaliteit van Leven (author), Abildayeva, K. (author), Berbée, J.F.P. (author), Blokland, A. (author), Jansen, P.J. (author), Hoek, F.J. (author), Meijer, O. (author), Lütjohann, D. (author), Gautier, T. (author), Pillot, T. (author), Vente, J.de (author), Havekes, L.M. (author), Ramaekers, F.C.S. (author), Kuipers, F. (author), Rensen, P.C.N. (author), Mulder, M. (author)

The H2 allele of APOC1, giving rise to increased gene expression of apolipoprotein C-I (apoC-I), is in genetic disequilibrium with the APOE4 allele and may provide a major risk factor for Alzheimer's disease (AD). We found that apoC-I protein is present in astrocytes and endothelial cells within hippocampal regions in both human control and AD...

article 2008

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Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

TNO Kwaliteit van Leven (author), Joosten, M.M. (author), Beulens, J.W.J. (author), Kersten, S. (author), Hendriks, H.F.J. (author)

Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial conducted in the Netherlands, 36 apparently healthy...

article 2008

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Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction

TNO Kwaliteit van Leven (author), Timmers, L. (author), Sluijter, J.P.G. (author), van Keulen, J.K. (author), Hoefer, I.E. (author), Nederhoff, M.G.J. (author), Goumans, M.J. (author), Doevendans, P.A. (author), van Echteld, C.J.A. (author), Joles, J.A. (author), Quax, P.H. (author), Piek, J.J. (author), Pasterkamp, G. (author), de Kleijn, D.P.V. (author)

article 2008

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Testosterone 15β-hydroxylation by solvent tolerant Pseudomonas putida S12

Ruijssenaars, H.J. (author), Sperling, E.M.G.M. (author), Wiegerinck, P.H.G. (author), Brands, F.T.L. (author), Wery, J. (author), de Bont, J.A.M. (author), TNO Kwaliteit van Leven (author)

A steroid 15β-hydroxylating whole-cell solvent tolerant biocatalyst was constructed by expressing the Bacillus megaterium steroid hydroxylase CYP106A2 in the solvent tolerant Pseudomonas putida S12. Testosterone hydroxylation was improved by a factor 16 by co-expressing Fer, a putative Fe-S protein from Bacillus subtilis. In addition, the...

article 2007

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Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat

Hendriksen, P.J.M. (author), Freidig, A.P. (author), Jonker, D. (author), Thissen, U. (author), Bogaards, J.J.P. (author), Mumtaz, M.M. (author), Groten, J.P. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected based on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest...

article 2007

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Apolipoprotein CI aggravates atherosclerosis development in ApoE-knockout mice despite mediating cholesterol efflux from macrophages

Westerterp, M. (author), van Eck, M. (author), de Haan, W. (author), Offerman, E.H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on...

article 2007

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Dynamics of insulin signalling in liver during hyperinsulinemic euglycaemic clamp conditions in vivo and the effects of high-fat feeding in male mice

Korsheninnikova, E. (author), Voshol, P.J. (author), Baan, B. (author), van der Zon, G.C.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), Maassen, J.A. (author), Ouwens, D.M. (author), TNO Kwaliteit van Leven (author)

Insulin is an important regulator of hepatic carbohydrate, lipid, and protein metabolism, and the regulation of these processes by insulin is disturbed under conditions of insulin resistance and type 2 diabetes. Despite these alterations, the impact of insulin resistance on insulin signalling in the liver is not well defined. Variations in time...

article 2007

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Binary PAH mixtures cause additive or antagonistic effects on gene expression but synergistic effects on DNA adduct formation

Staal, Y.C.M. (author), Hebels, D.G.A.J. (author), van Herwijnen, M.H.M. (author), Gottschalk, R.W.H. (author), van Schooten, F.J. (author), van Delft, J.H.M. (author), TNO Kwaliteit van Leven (author)

Polycyclic aromatic hydrocarbons (PAHs) cover a wide range of structurally related compounds which differ greatly in their carcinogenic potency. PAH exposure usually occurs through mixtures rather than individual compounds. Therefore, we assessed whether the effects of binary PAH mixtures on gene expression, DNA adduct formation, apoptosis and...

article 2007

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Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation

van Bezooijen, R.L. (author), Svensson, J.P. (author), Eefting, D. (author), Visser, A. (author), van der Horst, G. (author), Karperien, M. (author), Quax, P.H.A. (author), Vrieling, H. (author), Papapoulos, S.E. (author), ten Dijke, P. (author), Löwik, W.G.M.C. (author), TNO Kwaliteit van Leven (author)

Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family...

article 2007

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Atherosclerosis and liver inflammation induced by increased dietary cholesterol intake: A combined transcriptomics and metabolomics analysis

Kleemann, R. (author), Verschuren, L. (author), van Erk, M.J. (author), Nikolsky, Y. (author), Cnubben, N.H.P. (author), Verheij, E.R. (author), Smilde, A.K. (author), Hendriks, H.F.J. (author), Zadelaar, A.S.M. (author), Smith, G.J. (author), Kaznacheev, V. (author), Nikolskaya, T. (author), Melnikov, A. (author), Hurt-Camejo, E. (author), van der Greef, J. (author), van Ommen, B. (author), Kooistra, T. (author), TNO Kwaliteit van Leven (author)

Background: Increased dietary cholesterol intake is associated with atherosclerosis. Atherosclerosis development requires a lipid and an inflammatory component. It is unclear where and how the inflammatory component develops. To assess the role of the liver in the evolution of inflammation, we treated ApoE* 3Leiden mice with cholesterol-free ...

article 2007

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Database mining and transcriptional analysis of genes encoding inulin-modifying enzymes of Aspergillus niger

Yuan, X.L. (author), Goosen, C. (author), Kools, H. (author), van der Maarel, M.J.E.C. (author), van den Hondel, C.A.M.J.J. (author), Dijkhuizen, L. (author), Ram, A.F.J. (author), TNO Kwaliteit van Leven (author)

As a soil fungus, Aspergillus niger can metabolize a wide variety of carbon sources, employing sets of enzymes able to degrade plant-derived polysaccharides. In this study the genome sequence of A. niger strain CBS 513.88 was surveyed, to analyse the gene/enzyme network involved in utilization of the plant storage polymer inulin, and of sucrose,...

article 2006

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High-protein and high-carbohydrate breakfasts differentially change the transcriptome of human blood cells

van Erk, M.J. (author), Blom, W.A.M. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)

Background: Application of transcriptomics technology in human nutrition intervention studies would allow for genome-wide screening of the effects of specific diets or nutrients and result in biomarker profiles. Objective: The aim was to evaluate the potential of gene expression profiling in blood cells collected in a human intervention study...

article 2006

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Human osteoblasts produce cathepsin K

Mandelin, J. (author), Hukkanen, M. (author), Li, T.F. (author), Korhonen, M. (author), Liljeström, M. (author), Sillat, T. (author), Hanemaaijer, R. (author), Salo, J. (author), Santavirta, S. (author), Konttinen, Y.T. (author), TNO Kwaliteit van Leven (author)

Healthy bone is a rigid yet living tissue that undergoes continuous remodeling. Osteoclasts resorb bone in the remodeling cycle. They secrete H+-ions and proteinases to dissolve bone mineral and degrade organic bone matrix, respectively. One of the main collagenolytic proteinase in osteoclasts is cathepsin K, a member of papain family cysteine...

article 2006