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Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet

Derous, D. (author), Kelder, T. (author), van Schothorst, E.M. (author), van Erk, M. (author), Voigt, A. (author), Klaus, S. (author), Keijer, J. (author), Radonjic, M. (author)

Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing...

article 2015

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Differential modulation by Akkermansia muciniphila and faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids

Lukovac, S. (author), Belzer, C. (author), Pellis, L. (author), Keijser, B.J. (author), de Vos, W.M. (author), Montijn, R.C. (author), Roeselers, G. (author)

The gut microbiota is essential for numerous aspects of human health. However, the underlying mechanisms of many host-microbiota interactions remain unclear. The aim of this study was to characterize effects of the microbiota on host epithelium using a novel ex vivo model based on mouse ileal organoids. We have explored the transcriptional...

article 2014

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Aspergillus niger RhaR, a regulator involved in L-rhamnose release and catabolism

Gruben, B.S. (author), Zhou, M. (author), Wiebenga, A. (author), Ballering, J. (author), Overkamp, K.M. (author), Punt, P.J. (author), de Vries, R.P. (author)

The genome of the filamentous fungus Aspergillus niger is rich in genes encoding pectinases, a broad class of enzymes that have been extensively studied due to their use in industrial applications. The sequencing of the A. niger genome provided more knowledge concerning the individual pectinolytic genes, but little is known about the regulatory...

article 2014

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Generation of a catR deficient mutant of P. putida KT2440 that produces cis, cis-muconate from benzoate at high rate and yield

van Duuren, J.B.J.H. (author), Wijte, D. (author), Leprince, A. (author), Karge, B. (author), Puchalka, J. (author), Wery, J. (author), Dos Santos, V.A.P.M. (author), Eggink, G. (author), Mars, A.E. (author)

Pseudomonas putida KT2440-JD1 was derived from P. putida KT2440 after N-methyl-N'-nitro-N-nitrosoguanidine (NTG)-mutagenesis and exposure to 3-fluorobenzoate (3-FB). The mutant was no longer able to grow using benzoate as a sole carbon source, but co-metabolized benzoate to cis, cis-muconate during growth on glucose, which accumulated in the...

article 2011

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Time series analysis of benzo[a]pyrene-induced transcriptome changes suggests that a network of transcription factors regulates the effects on functional gene sets

van Delft, J.H.M. (author), Mathijs, K. (author), Staal, Y.C.M. (author), van Herwijnen, M.H.M. (author), Brauers, K.J.J. (author), Boorsma, A. (author), Kleinjans, J.C.S. (author), TNO Kwaliteit van Leven (author)

Chemical carcinogens may cause a multitude of effects inside cells, thereby affecting transcript levels of genes by direct activation of transcription factors (TF) or indirectly through the formation of DNA damage. As the temporal profiles of these responses may be profoundly different, examining time-dependent changes may provide new insights...

article 2010

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Metabolic flux analysis of a phenol producing mutant of Pseudomonas putida S12: Verification and complementation of hypotheses derived from transcriptomics

Wierckx, N. (author), Ruijssenaars, H.J. (author), de Winde, J.H. (author), Schmid, A. (author), Blank, L.M. (author), TNO Kwaliteit van Leven (author)

The physiological effects of genetic and transcriptional changes observed in a phenol producing mutant of the solvent-tolerant Pseudomonas putida S12 were assessed with metabolic flux analysis. The upregulation of a malate/lactate dehydrogenase encoding gene could be connected to a flux increase from malate to oxaloacetate. A mutation in the...

article 2009

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Mixed-species genomic microarray analysis of fecal samples reveals differential transcriptional responses of bifidobacteria in breast- And formula-fed infants

TNO Kwaliteit van Leven (author), Klaassens, E.S. (author), Boesten, R.J. (author), Haarman, M. (author), Knol, J. (author), Schuren, F.H. (author), Vaughan, E.E. (author), Vos, W.M.de (author)

Although their exact function remains enigmatic, bifidobacteria are among the first colonizers of the newborn infant gut and further develop into abundant communities, notably in response to diet. Therefore, the transcriptional responses of bifidobacteria in rapidly processed fecal samples from young infants that were fed either breast milk or a...

article 2009

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Aspergillus niger genome-wide analysis reveals a large number of novel alpha-glucan acting enzymes with unexpected expression profiles

Yuan, X.-L. (author), van der Kaaij, R.M. (author), van den Hondel, C.A.M.J.J. (author), Punt, P.J. (author), van der Maarel, M.J.E.C. (author), Dijkhuizen, L. (author), Ram, A.F.J. (author), TNO Kwaliteit van Leven (author)

The filamentous ascomycete Aspergillus niger is well known for its ability to produce a large variety of enzymes for the degradation of plant polysaccharide material. A major carbon and energy source for this soil fungus is starch, which can be degraded by the concerted action of α-amylase, glucoamylase and α-glucosidase enzymes, members of the...

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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Analysis of temporal gene expression during Bacillus subtilis spore germination and outgrowth

Keijser, B.J.F. (author), ter Beek, A. (author), Rauwerda, H. (author), Schuren, F. (author), Montijn, R. (author), van der Spek, H. (author), Brul, S. (author), TNO Kwaliteit van Leven (author)

Bacillus subtilis forms dormant spores upon nutrient depletion. Under favorable environmental conditions, the spore breaks its dormancy and resumes growth in a process called spore germination and outgrowth. To elucidate the physiological processes that occur during the transition of the dormant spore to an actively growing vegetative cell, we...

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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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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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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A hepatocyte nuclear factor-3 site in the fibrinogen beta promoter is important for interleukin 6-induced expression, and its activity is influenced by the adjacent -148C/T polymorphism

TNO Kwaliteit van Leven (author), Verschuur, M. (author), Jong, M.de (author), Felida, L. (author), Maat, M.P.M.de (author), Vos, H.L. (author)

An elevated plasma fibrinogen level is an independent risk factor for cardiovascular disease. Therefore, an understanding of the regulation of fibrinogen expression is important. Inflammation and genetic variation of the fibrinogen beta gene regulate plasma fibrinogen levels, and there are indications that inflammation and genetic variation...

article 2005

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Bromobenzene-induced hepatotoxicity at the transcriptome level

Heijne, W.H.M. (author), Slitt, A.L. (author), van Bladeren, P.J. (author), Groten, J.P. (author), Klaassen, C.D. (author), Stierum, R.H. (author), van Ommen, B. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)

Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while...

article 2004

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Endoplasmic reticulum stress leads to the selective transcriptional downregulation of the glucoamylase gene in Aspergillus niger

Al-Sheikh, H. (author), Watson, A.J. (author), Lacey, G.A. (author), Punt, P.J. (author), MacKenzie, D.A. (author), Jeenes, D.J. (author), Pakula, T. (author), Penttilä, M. (author), Alcocer, M.J.C. (author), Archer, D.B. (author), TNO Voeding (author)

We describe a new endoplasmic reticulum (ER)-associated stress response in the filamentous fungus Aspergillus niger. The inhibition of protein folding within the ER leads to cellular responses known collectively as the unfolded protein response (UPR) and we show that the selective transcriptional downregulation of the gene encoding glucoamylase,...

article 2004

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Global Suppression of IL-6-induced Acute Phase Response Gene Expression after Chronic in Vivo Treatment with the Peroxisome Proliferator-activated Receptor-alpha Activator Fenofibrate

TNO Preventie en Gezondheid (author), Gervois, P. (author), Kleemann, R. (author), Pilon, A. (author), Percevault, F. (author), Koenig, W. (author), Staels, B. (author), Kooistra, T. (author)

The peroxisome proliferator-activated receptor alpha (PPARalpha), which is highly expressed in liver, plays key roles in lipid metabolism and inflammation. Interleukin-6 (IL-6) is the principal inducer of acute phase response (APR) gene expression. In the present study, we demonstrate that chronic treatment with the PPARalpha agonist fenofibrate...

article 2004

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Development of an androgen reporter gene assay (AR-LUX) utilizing a human cell line with an endogenously regulated androgen receptor

Blankvoort, B.M.G. (author), de Groene, E.M. (author), van Meeteren-Kreikamp, A.P. (author), Witkamp, R.F. (author), Rodenburg, R.J.T. (author), Aarts, J.M.M.J.G. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

The aim of the work described in this report is to develop and characterize a cell-based androgen reporter assay. For this purpose, the androgen receptor (AR) expressing human breast cancer cell line T47D was stably transfected with a luciferase gene under transcriptional control of the PB-ARE-2 androgen response element. The application of this...

article 2001

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Regulation of expression of the Aspergillus niger benzoate para-hydroxylase cytochrome P450 system

van den Brink, J.M. (author), Punt, P.J. (author), van Gorcom, R.F.M. (author), van den Hondel, C.A.M.J.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Cytochrome P450 enzyme systems are found throughout nature and are involved in many different, often complex, bioconversions. In the endoplasmic reticulum of the filamentous fungus Aspergillus niger a cytochrome P450 enzyme system is present that is capable of the para-hydroxylation of benzoate. The expression of the two genes encoding the...

article 2000