Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Can transcriptomics provide insight into the underlying chemopreventive mechanisms of complex mixtures of phytochemicals in humans?
Breda, S.G. van; Wilms, L.C. ; Gaj, S. ; Briedé, J.J. ; Helsper, J.P.F.G. ; Kleinjans, J.C. ; Kok, T.M. de - \ 2014
Antioxidants and redox signaling 20 (2014)14. - ISSN 1523-0864 - p. 2107 - 2113.
fruits
Blueberries contain relatively large amounts of different phytochemicals which are suggested to have chemopreventive properties, but little information is available on the underlying molecular modes of action. This study investigates whole genome gene expression changes in lymphocytes of 143 humans after a four-week blueberry-apple juice dietary intervention. Differentially expressed genes and genes correlating with the extent of antioxidant protection were identified in 4 subgroups. The magnitude of the preventive effect after the intervention differed between these four subgroups. Furthermore, subjects in two groups carried genetic polymorphisms that were previously found to influence the chemopreventive response. Pathway analysis of the identified genes showed strong but complex gene expression changes in pathways signaling for apoptosis, immune response, cell adhesion, and lipid metabolism. These pathways indicate increased apoptosis, upgraded growth control, induced immunity, reduced platelet aggregation and activation, blood glucose homeostasis, and regulation of fatty acid metabolism. Based on these observations, we hypothesize that combining transcriptomic data with phenotypic markers of oxidative stress may provide insight into the relevant cellular processes and genetic pathways which contribute to the antioxidant response of complex mixtures of phytochemicals, such as found in blueberry-apple juice
User-friendly solutions for microarray quality control and pre-processing on ArrayAnalysis.org
Eijssen, L.M. ; Jaillard, M. ; Adriaens, M.E. ; Gaj, S. ; Groot, P.J. de; Müller, M.R. ; Evelo, C.T. - \ 2013
Nucleic acids research 41 (2013)W1. - ISSN 0305-1048 - p. W71 - W76.
affymetrix-genechip data - expression analysis - probe level - bioconductor - interface - database - package - biology - biomart - update
Quality control (QC) is crucial for any scientific method producing data. Applying adequate QC introduces new challenges in the genomics field where large amounts of data are produced with complex technologies. For DNA microarrays, specific algorithms for QC and pre-processing including normalization have been developed by the scientific community, especially for expression chips of the Affymetrix platform. Many of these have been implemented in the statistical scripting language R and are available from the Bioconductor repository. However, application is hampered by lack of integrative tools that can be used by users of any experience level. To fill this gap, we developed a freely available tool for QC and pre-processing of Affymetrix gene expression results, extending, integrating and harmonizing functionality of Bioconductor packages. The tool can be easily accessed through a wizard-like web portal at http://www.arrayanalysis.org or downloaded for local use in R. The portal provides extensive documentation, including user guides, interpretation help with real output illustrations and detailed technical documentation. It assists newcomers to the field in performing state-of-the-art QC and pre-processing while offering data analysts an integral open-source package. Providing the scientific community with this easily accessible tool will allow improving data quality and reuse and adoption of standards.
'Omics analysis of low dose acetaminophen intake demonstrates novel response pathways in humans
Jetten, M.J.A. ; Gaj, S. ; Ruiz Aracama, A. ; Kok, T.M. de; Delft, J.H.M. van; Lommen, A. ; Someren, E.P. van; Jennen, D. ; Claessen, S.M. ; Peijnenburg, A.A.C.M. ; Stierum, R. ; Kleinjans, J.C.S. - \ 2012
Toxicology and Applied Pharmacology 259 (2012)3. - ISSN 0041-008X - p. 320 - 328.
induced liver-injury - gene-expression - induced hepatotoxicity - circulating micrornas - liquid-chromatography - potential biomarkers - toxicity - metabolomics - metabolites - paracetamol
Acetaminophen is the primary cause of acute liver toxicity in Europe/USA, which led the FDA to reconsider recommendations concerning safe acetaminophen dosage/use. Unfortunately, the current tests for liver toxicity are no ideal predictive markers for liver injury, i.e. they only measure acetaminophen exposure after profound liver toxicity has already occurred. Furthermore, these tests do not provide mechanistic information. Here, 'omics techniques (global analysis of metabolomic/gene-expression responses) may provide additional insight. To better understand acetaminophen-induced responses at low doses, we evaluated the effects of (sub-)therapeutic acetaminophen doses on metabolite formation and global gene-expression changes (including, for the first time, full-genome human miRNA expression changes) in blood/urine samples from healthy human volunteers. Many known and several new acetaminophen-metabolites were detected, in particular in relation to hepatotoxicity-linked, oxidative metabolism of acetaminophen. Transcriptomic changes indicated immune-modulating effects (2 g dose) and oxidative stress responses (4 g dose). For the first time, effects of acetaminophen on full-genome human miRNA expression have been considered and confirmed the findings on mRNA level. 'Omics techniques outperformed clinical chemistry tests and revealed novel response pathways to acetaminophen in humans. Although no definitive conclusion about potential immunotoxic effects of acetaminophen can be drawn from this study, there are clear indications that the immune system is triggered even after intake of low doses of acetaminophen. Also, oxidative stress-related gene responses, similar to those seen after high dose acetaminophen exposure, suggest the occurrence of possible pre-toxic effects of therapeutic acetaminophen doses. Possibly, these effects are related to dose-dependent increases in levels of hepatotoxicity-related metabolites.
Four selenoproteins, protein biosynthesis, and Wnt signalling are particularly sensitive to selenium intake in mice colon
Kipp, A. ; Banning, A. ; Schothorst, E.M. van; Meplan, C. ; Schomburg, L. ; Evelo, C. ; Coort, S.L. ; Gaj, S. ; Keijer, J. ; Hesketh, J. ; Brigelius, R. - \ 2009
Molecular Nutrition & Food Research 53 (2009)12. - ISSN 1613-4125 - p. 1561 - 1572.
messenger-rna stability - thioredoxin-like family - glutathione-peroxidase - gene-expression - microarray data - colorectal adenoma - cancer prevention - molecular targets - oxidative stress - selenocysteine
Selenium is an essential micronutrient. Its recommended daily allowance is not attained by a significant proportion of the population in many countries and its intake has been suggested to affect colorectal carcinogenesis. Therefore, microarrays were used to determine how both selenoprotein and global gene expression patterns in the mouse colon were affected by marginal selenium deficiency comparable to variations in human dietary intakes. Two groups of 12 mice each were fed a selenium-deficient (0.086 mg Se/kg) or a selenium-adequate (0.15 mg Se/kg) diet. After 6 wk, plasma selenium level, liver, and colon glutathione peroxidase (GPx) activity in the deficient group was 12, 34, and 50%, respectively, of that of the adequate group. Differential gene expression was analysed with mouse 44K whole genome microarrays. Pathway analysis by GenMAPP identified the protein biosynthesis pathway as most significantly affected, followed by inflammation, Delta-Notch and Wnt pathways. Selected gene expression changes were confirmed by quantitative real-time PCR. GPx1 and the selenoproteins W, H, and M, responded significantly to selenium intake making them candidates as biomarkers for selenium status. Thus, feeding a marginal selenium-deficient diet resulted in distinct changes in global gene expression in the mouse colon. Modulation of cancer-related pathways may contribute to the higher susceptibility to colon carcinogenesis in low selenium status
Reduction of colonic inflammation in HLA-B27 transgenic rats by feeding Marie Ménard apples, rich in polyphenols
Castagnini, C. ; Luceri, C. ; Toti, S. ; Bigagli, E. ; Caderni, G. ; Femia, A.P. ; Giovannelli, L. ; Lodovici, M. ; Pitozzi, V. ; Salvadori, M. ; Messerini, L. ; Martin, R. ; Zoetendal, E.G. ; Gaj, S. ; Eijssen, L. ; Evelo, C. ; Renard, C.M. ; Baron, A. ; Dolara, P. - \ 2009
The British journal of nutrition 102 (2009)11. - ISSN 0007-1145 - p. 1620 - 1628.
nf-kappa-b - gradient gel-electrophoresis - 16s ribosomal-rna - polymerase-chain-reaction - gene-expression profiles - bowel-disease - dna-damage - gastrointestinal-tract - bacteroides-vulgatus - ulcerative-colitis
Inflammatory bowel diseases (IBD) are immunomediated ailments affecting millions of individuals. Although diet is regarded as an important factor influencing IBD, there are no accepted dietary recommendations presently available. We administered 7.6 % lyophilised apples obtained from two cultivars (Golden Delicious and Marie Ménard, low and high in polyphenols, respectively) to HLA-B27 transgenic rats which develop spontaneous IBD. After 3 months feeding, rats fed Marie Ménard apples had reduced myeloperoxidase activity (3.6 (sem 0.3) v. 2.2 (sem 0.2) U/g tissue; P <0.05) and reduced cyclo-oxygenase-2 (P <0.05) and inducible NO synthase gene expression (P <0.01) in the colon mucosa and significantly less diarrhoea (P <0.05), compared with control rats. Cell proliferation in the colon mucosa was reduced significantly by feeding Golden Delicious apples, with a borderline effect of Marie Ménard apples. Gene expression profiling of the colon mucosa, analysed using the Whole Rat Genome 4 x 44 K Agilent Arrays, revealed a down-regulation of the pathways of PG synthesis, mitogen-activated protein kinase (MAPK) signalling and TNFalpha-NF-kappaB in Marie Ménard-fed rats. In the stools of the animals of this group we also measured a significant reduction of bacteria of the Bacteriodes fragilis group. In conclusion, the administration of Marie Ménard apples, rich in polyphenols and used at present only in the manufacturing of cider, ameliorates colon inflammation in transgenic rats developing spontaneous intestinal inflammation, suggesting the possible use of these and other apple varieties to control inflammation in IBD patients
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