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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    Predicting phase behavior of multi-component and polydisperse aqueous mixtures using a virial approach
    Sturtewagen, Luka - \ 2020
    Wageningen University. Promotor(en): E. van der Linden, co-promotor(en): H.G.J. van Mil. - Wageningen : Wageningen University - ISBN 9789463953771 - 210
    Curdlan, zymosan and a yeast-derived β-glucan reshape tumor-associated macrophages into producers of inflammatory chemo-attractants
    Graaff, Priscilla de; Berrevoets, Cor ; Rӧsch, Christiane ; Schols, Henk A. ; Verhoef, Kees ; Wichers, Harry J. ; Debets, Reno ; Govers, Coen - \ 2020
    Cancer Immunology, Immunotherapy (2020). - ISSN 0340-7004
    Beta-glucans - Chemo-attractants - Chemokines - Macrophages

    Anti-cancer T-cell responses are often halted due to the immune-suppressive micro-environment, in part related to tumor-associated macrophages. In the current study, we assessed indigestible β-glucans (oatβG, curdlan, grifolan, schizophyllan, lentinan, yeast whole glucan particles (yWGP), zymosan and two additional yeast-derived β-glucans a and b) for their physicochemical properties as well as their effects on the plasticity of human monocyte-derived macrophages that were polarized with IL-4 to immune-suppressive macrophages. Beta-glucans were LPS/LTA free, and tested for solubility, molecular masses, protein and monosaccharide contents. Curdlan, yeast-b and zymosan re-polarized M(IL-4) macrophages towards an M1-like phenotype, in particular showing enhanced gene expression of CCR7, ICAM1 and CD80, and secretion of TNF-α and IL-6. Notably, differential gene expression, pathway analysis as well as protein expressions demonstrated that M(IL-4) macrophages treated with curdlan, yeast-b or zymosan demonstrated enhanced production of chemo-attractants, such as CCL3, CCL4, and CXCL8, which contribute to recruitment of monocytes and neutrophils. The secretion of chemo-attractants was confirmed when using patient-derived melanoma-infiltrating immune cells. Taken together, the bacterial-derived curdlan as well as the yeast-derived β-glucans yeast-b and zymosan have the unique ability to preferentially skew macrophages towards a chemo-attractant-producing phenotype that may aid in anti-cancer immune responses.

    Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion
    Jansen, Jitske ; Jansen, Katja ; Neven, Ellen ; Poesen, Ruben ; Othman, Amr ; Mil, Alain van; Sluijter, Joost ; Torano, Javier Sastre ; Zaal, Esther A. ; Berkers, Celia R. ; Esser, Diederik ; Wichers, Harry J. ; Ede, Karin van; Duursen, Majorie van; Burtey, Stéphane ; Verhaar, Marianne C. ; Meijers, Björn ; Masereeuw, Rosalinde - \ 2019
    Proceedings of the National Academy of Sciences of the United States of America 116 (2019)32. - ISSN 0027-8424 - p. 16105 - 16110.
    Indoxyl sulfate - Kidney proximal tubule - Organic anion transporter 1 - Remote sensing and signaling

    Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.

    The positively-selected effector MiL648 of Meloidogyne incognita contributes to nematode virulence through its interactions with the 12-oxophytodienoate reductase OPR2 in tomato
    Verhoeven, Ava ; Tacken, Wannes ; Wesselink, Thomas ; Finkers-Tomczak, A.M. ; Prins, J.C.P. ; Raaij, D.R. van; Varossieau, K. ; Overmars, H.A. ; Slootweg, E.J. ; Goverse, A. ; Smant, G. - \ 2019
    The positively-selected effector MiL648 of Meloidogyne incognita contributes to nematode virulence through its interactions with the 12-oxophytodienoate reductase OPR2 in tomato
    Verhoeven, Ava - \ 2019
    Insight in the molecular basis of virulence can help to identify new and more durable sources of resistance to the root-knot nematode Meloidogyne incognita in tomato. In nematode genomes, evidence of positive, diversifying selection can point to loci involved in a molecular arms race with other organisms. We used evidence of positive selection as a first criterion to identify novel virulence genes in the genome of M. incognita, one of which encodes the effector MiL648. Bioassays with M. incognita on tomato plants overexpressing an RNAi construct matching the MiL648 sequence showed that this gene is required for nematode virulence. Likewise, tomato plants overexpressing MiL648 were more susceptible to M. incognita, demonstrating that it functions as a bona fide effector. We identified six likely host targets of MiL648 in a yeast two-hybrid screen of nematode-infected roots of tomato, including the 12-oxophytodienoate reductase SlOPR2. We confirmed the interaction between SlOPR2 and MiL648 in planta by transient expression and co-immunoprecipitation in leaves of Nicotiana benthamiana. We therefore concluded that the effector MiL648 enhances the virulence of M. incognita through its interactions with SlOPR2.
    MIL-53(Al) and NH2-MIL-53(Al) modified α-alumina membranes for efficient adsorption of dyes from organic solvents
    Amirilargani, Mohammad ; Merlet, Renaud B. ; Hedayati, Pegah ; Nijmeijer, Arian ; Winnubst, Louis ; Smet, Louis C.P.M. De; Sudhölter, Ernst J.R. - \ 2019
    Chemical Communications 55 (2019)28. - ISSN 1359-7345 - p. 4119 - 4122.

    To the best of our knowledge, for the first time MIL-53(Al) and NH 2 -MIL-53(Al) modified α-alumina membranes are investigated for the adsorption of organic dyes from organic solvents. These new, modified membranes show excellent adsorption of high concentrations of Rose Bengal dye in methanol and isopropanol solutions.

    The nematode effector MiL648 contributes to virulence through its interactions with the 12-oxophytodienoate reductase OPR2 in tomato
    Verhoeven, Ava ; Yang, Yixuan ; Raaij, D.R. van; Steenbrugge, Joris van; Goverse, A. ; Smant, G. - \ 2019
    Protein fermentation in the gut; implications for intestinal dysfunction in humans, pigs, and poultry
    Gilbert, Myrthe S. ; IJssennagger, Noortje ; Kies, Arie K. ; Mil, Saskia W.C. van - \ 2018
    American Journal of Physiology. Gastrointestinal and Liver Physiology 315 (2018)2. - ISSN 0193-1857 - p. G159 - G170.
    Broiler - Gut health - Human - Intestinal disease - Metabolomics - Pig - Protein fermentation

    The amount of dietary protein is associated with intestinal disease in different vertebrate species. In humans, this is exemplified by the association between high-protein intake and fermentation metabolite concentrations in patients with inflammatory bowel disease. In production animals, dietary protein intake is associated with postweaning diarrhea in piglets and with the occurrence of wet litter in poultry. The underlying mechanisms by which dietary protein contributes to intestinal problems remain largely unknown. Fermentation of undigested protein in the hindgut results in formation of fermentation products including short-chain fatty acids, branchedchain fatty acids, ammonia, phenolic and indolic compounds, biogenic amines, hydrogen sulfide, and nitric oxide. Here, we review the mechanisms by which these metabolites may cause intestinal disease. Studies addressing how different metabolites induce epithelial damage rely mainly on cell culture studies and occasionally on mice or rat models. Often, contrasting results were reported. The direct relevance of such studies for human, pig, and poultry gut health is therefore questionable and does not suffice for the development of interventions to improve gut health. We discuss a roadmap to improve our understanding of gut metabolites and microbial species associated with intestinal health in humans and production animals and to determine whether these metabolite/bacterial networks cause epithelial damage. The outcomes of these studies will dictate proof-of-principle studies to eliminate specific metabolites and or bacterial strains and will provide the basis for interventions aiming to improve gut health.

    The positively-selected effector MiL648 of the root-knot nematode Meloidogyne incognita plays a role in tomato infections
    Verhoeven, Ava ; Put, Sanne ; Slootweg, E.J. ; Raaij, D.R. van; Overmars, H.A. ; Goverse, A. ; Smant, G. - \ 2018
    Insight in the molecular basis of virulence can help us to identify new and more durable sources of resistance to the root-knot nematode Meloidogyne incognita in tomato. Recently, we identified the effector MiL648 by applying a genome-wide scan for positively selected secreted proteins. To acquire a better understanding of the function of MiL648, we are currently functionally characterising the protein in plants using host-induced gene silencing. Several in planta targets of the putative effector have now been found by a yeast-two-hybrid screening and interactions were checked using Co-IPs. To identify the role of the host targets in the infection process, homologs of the host targets were knocked out in Arabidopsis.
    Functional characterisation of the positively-selected effector MiL648 of the root-knot nematode Meloidogyne incognita
    Verhoeven, Ava ; Prins, J.C.P. ; Finkers-Tomczak, A.M. ; Slootweg, E.J. ; Varossieau, K. ; Raaij, D.R. van; Goverse, A. ; Smant, G. - \ 2018
    Functional characterization of the positively-selected effector MiL648 of the root-knot nematode Meloidogyne incognita
    Verhoeven, Ava - \ 2018
    PhenoLab: automatic recording of location, activity and proximity in group-housed laying hens
    Rodenburg, T.B. ; Eijk, J.A.J. van der; Pichova, Katarina ; Mil, B. van; Haas, E.N. de - \ 2017
    In: Proceedings of the ISAE Benelux conference 2017 International Society for Applied Ethology (ISAE) - p. 21 - 21.
    Phenolab: ultra-wide band tracking of individual group housed laying hens
    Haas, E.N. de; Eijk, J.A.J. van der; Nieuwe Weme, L.E. ; Mil, B. van; Rodenburg, T.B. - \ 2017
    In: Proceedings of the 7th International Conference on the Assessment of Animal Welfare at Farm and Group Level. - Wageningen : Wageningen Academic Publishers - ISBN 9789086863143 - p. 260 - 260.
    Farm animals are generally kept in groups of varying sizes. It is challenging to monitor thebehaviour of individual animals when they are housed in a group. To aid to this need, we havetested an innovative new automatic sensor technology which can track individuals in a group.With the use of this ultra-wide band tracking device and recording beacons, we were able totrack individual laying hens in an equipped arena (project PhenoLab). Hens had an activesending tag in a backpack. Every 30 s location of each tag was recorded. TrackLab softwareprovided distance moved and movement patterns based on location data. With this set-up,we tested if we could detect differences between birds who feather peck and victims of thebehaviour. We used a White Leghorn line selected on high feather pecking for 11 generations.Prior to tracking, home pen observations were made to record who was the feather peckerand who was the victim based on giving or receiving more than 2 severe FP per 0.5 h summedover observation times. FP data was obtained weekly from a 15 min video-recording from at28 and 29 weeks of age. Independent t-test was performed for comparison. At 37 weeks of agehens were tested inside a 8×7 m empty test-room with their pen-mates for 15 minutes. Featherpeckers tended to walk a greater distance (t15=1.89, P=0.07; 9,286±1,660 vs 5,251±1,361 cm)and had a higher average speed when moving (t15=2.62, P=0.02; 9.5±1 vs 5.5±1.1 m/s2) thanvictims. These results indicate that with automatic locomotor data differences in behaviouraltraits of individual birds can be detected, which affect welfare on a group level. Moreover, thesystem could be used to predict changes in activity patterns and detect individuals that haveor will perform damaging behaviour.
    Phenolab: ultra-wide band tracking shows feather pecking hens spent less time in close proximity compared to controls
    Haas, E.N. de; Eijk, J.A.J. van der; Mil, B. van; Rodenburg, T.B. - \ 2017
    In: Proceedings of the 51st Congress of the International Society for Applied Ethology (ISAE), 7-10 August 2017, Aarhus, Denmark. - Wageningen : Wageningen Academic Publishers - ISBN 9789086863112 - p. 176 - 176.
    animal welfare - animal behaviour

    Hens which feather peck can cause multiple victims in a group. As a result pen-mates could keep a greater distance from feather peckers. Our aim was to relate time spent in close proximity between birds selected divergently on feather pecking. Automatic ultra-wide band location data was obtained by using an active sending tag (UbisenseR) placed in a backpack on the birds. A group of birds was then placed for 15 minutes in a barren test-room equipped with four receiving beacons. We used 37-week old White Leghorn laying hen lines selected for high (HFP) or low feather pecking (LFP), and an unselected control (CON) line (n=76 in total, 5-7 hens per pen; 4 pens per line). Hens were habituated to the backpacks four weeks prior to observations, and were tested for 5-min to the test-room individually one week prior to group testing. Sample rate of tags was set to twice per second, detecting location of each tag separately and simultaneously. Location data was provided by TrackLab software (Noldus, Wageningen, The Netherlands) and compared between tags by Excel calculations. Percentage of time in close proximity was defined as being less than 25 cm apart from another tag, calculated for each bird and averaged per group. Behavioural sampling of feather pecking of 2×20 min at 28-29 wks of age was included on pen-level and used for identification of peckers (>2 bouts/20 min). Percentage of time in close proximity was correlated to feather pecking (pearson correlation), tested to differ between peckers and average of the group (t-test of groups with peckers) and tested to differ between lines (ANOVA including the number of animals per pen as covariate). Feather pecking on pen-level was not correlated to proximity measures (r=-0.28, P>0.10), but birds spent less time in close proximity of the feather pecker as opposed to time spent on average with other pen-mates (17.6・}1% vs 21.6・}1.2, t16=-1.18, P=0.04).



    Gas Phase Sensing of Alcohols by Metal Organic Framework-Polymer Composite Materials
    Sachdeva, Sumit ; Koper, Sander J.H. ; Sabetghadam, Anahid ; Soccol, Dimitri ; Gravesteijn, Dirk J. ; Kapteijn, Freek ; Sudhölter, Ernst J.R. ; Gascon, Jorge ; Smet, Louis C.P.M. De - \ 2017
    ACS Applied Materials and Interfaces 9 (2017)29. - ISSN 1944-8244 - p. 24926 - 24935.
    capacitive detection - composites - gas sensors - impedance spectroscopy - metal organic frameworks - mixed matrix membranes
    Affinity layers play a crucial role in chemical sensors for the selective and sensitive detection of analytes. Here, we report the use of composite affinity layers containing Metal Organic Frameworks (MOFs) in a polymeric matrix for sensing purposes. Nanoparticles of NH2-MIL-53(Al) were dispersed in a Matrimid polymer matrix with different weight ratios (0-100 wt %) and drop-casted on planar capacitive transducer devices. These coated devices were electrically analyzed using impedance spectroscopy and investigated for their sensing properties toward the detection of a series of alcohols and water in the gas phase. The measurements indicated a reversible and reproducible response in all devices. Sensor devices containing 40 wt % NH2-MIL-53(Al) in Matrimid showed a maximum response for methanol and water. The sensor response time slowed down with increasing MOF concentration until 40 wt %. The half time of saturation response (τ0.5) increased by ∼1.75 times for the 40 wt % composition compared to devices coated with Matrimid only. This is attributed to polymer rigidification near the MOF/polymer interface. Higher MOF loadings (≥50 wt %) resulted in brittle coatings with a response similar to the 100 wt % MOF coating. Cross-sensitivity studies showed the ability to kinetically distinguish between the different alcohols with a faster response for methanol and water compared to ethanol and 2-propanol. The observed higher affinity of the pure Matrimid polymer toward methanol compared to water allows also for a higher uptake of methanol in the composite matrices. Also, as indicated by the sensing studies with a mixture of water and methanol, the methanol uptake is independent of the presence of water up to 6000 ppm of water. The NH2-MIL-53(Al) MOFs dispersed in the Matrimid matrix show a sensitive and reversible capacitive response, even in the presence of water. By tuning the precise compositions, the affinity kinetics and overall affinity can be tuned, showing the promise of this type of chemical sensors.
    Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology.
    Lange, Katja ; IJssennagger, Noortje ; Bijsmans, Ingrid T. ; Mil, Saskia W.C. van; Jonker, Johan W. ; Hooiveld, Guido - \ 2017
    Wageningen University
    GSE82111 - Mus musculus - GSE82111 - Mus musculus - PRJNA324071
    Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets. Immortalized cell lines recapitulate NR biology very poorly and primary cultures are laborious and require a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology since technical uncertainty early in drug development is the cause of many preclinical drugs not reaching the clinic. Here, we studied whether organoids, mini-organs derived from the respective tissue’s stem cells, can serve as a novel (preclinical) model system to study NR biology and targeteability. We characterized mRNA expression profiles of the NR superfamily in mouse liver, ileum, and colon organoids. NR mRNA expression patterns were similar to the respective tissues, indicating their suitability for NR research. Metabolic NRs Fxrα, Lxrα, Lxrβ, Pparα, and Pparγ were responsive to ligands in an NR-dependent fashion, as demonstrated by regulation of expression and binding to endogenous target genes. Transcriptome analyses of wildtype colonic organoids stimulated with Rosiglitazone showed that lipid metabolism was the highest significant changed function, greatly mimicking the known function of PPARs and Rosiglitazone in vivo. In conclusion, our results demonstrate that organoids constitutes a versatile and promising in vitro system to study NR biology and targeteability.
    Functional characterization of the positively-selected effector MiL648 of the root-knot nematode Meloidogyne incognita
    Verhoeven, Ava ; Prins, J.C.P. ; Finkers-Tomczak, A.M. ; Slootweg, E.J. ; Varossieau, K. ; Raaij, D.R. van; Pomp, H. ; Goverse, A. ; Smant, G. - \ 2017
    Correlation of carotid artery reactivity with cardiovascular risk factors and coronary artery vasodilator responses in asymptomatic, healthy volunteers
    Mil, Anke C.C.M. Van; Hartman, Yvonne ; Oorschot, Frederieke Van; Heemels, Annemieke ; Bax, Nikki ; Dawson, Ellen A. ; Hopkins, Nicola ; Hopman, Maria T.E. ; Green, Daniel J. ; Oxborough, David L. ; Thijssen, Dick H.J. - \ 2017
    Journal of Hypertension 35 (2017)5. - ISSN 0263-6352 - p. 1026 - 1034.
    Cardiovascular risk - Carotid artery reactivity test - Cold pressor test - Coronary arteries - Endothelial function
    Objectives: Carotid artery reactivity (CAR%), involving carotid artery diameter responses to a cold pressor test (CPT), is a noninvasive measure of conduit artery function in humans. This study examined the impact of age and cardiovascular risk factors on the CAR% and the relationship between CAR% and coronary artery vasodilator responses to the CPT. Methods: Ultrasound was used to measure resting and peak carotid artery diameters during the CPT, with CAR% being calculated as the relative change from baseline (%). We compared CAR% between young (n=50, 24±3 years) and older participants (n=44, 61±8 years), and subsequently assessed relationships between CAR% and traditional cardiovascular risk factors in 50 participants (44±21 years). Subsequently, we compared left anterior descending (LAD) artery velocity (using transthoracic Doppler) with carotid artery diameter (i.e. CAR%) during the CPT (n=33, 37±17 years). Results: A significantly larger CAR% was found in young versus older healthy participants (4.1±3.7 versus 1.8±2.6, P<0.001). Participants without cardiovascular risk factors demonstrated a higher CAR% than those with at least two risk factors (2.9±2.9 versus 0.5±2.9, P=0.019). Carotid artery diameter and LAD velocity increased during CPT (P<0.001). Carotid diameter and change in velocity correlated with LAD velocity (r=0.486 and 0.402, P<0.004 and 0.02, respectively). Conclusion: Older age and cardiovascular risk factors are related to lower CAR%, while CAR% shows good correlation with coronary artery responses to the CPT. Therefore, CAR% may represent a valuable technique to assess cardiovascular risk, while CAR% seems to reflect coronary artery vasodilator function.
    Characterization of stem cell-derived liver and intestinal organoids as a model system to study nuclear receptor biology
    Bijsmans, Ingrid T.G.W. ; Milona, Alexandra ; Ijssennagger, Noortje ; Willemsen, Ellen C.L. ; Ramos Pittol, José M. ; Jonker, Johan W. ; Lange, Katja ; Hooiveld, Guido J.E.J. ; Mil, Saskia W.C. van - \ 2017
    Biochimica et Biophysica Acta. Molecular Basis of Disease 1863 (2017)3. - ISSN 0925-4439 - p. 687 - 700.
    Fxr - Ligands - Lxr - Nuclear receptors - Organoids - Ppar
    Nuclear receptors (NRs) are ligand-activated transcription factors regulating a large variety of processes involved in reproduction, development, and metabolism. NRs are ideal drug targets because they are activated by lipophilic ligands that easily pass cell membranes. Immortalized cell lines recapitulate NR biology poorly and generating primary cultures is laborious and requires a constant need for donor material. There is a clear need for development of novel preclinical model systems that better resemble human physiology. Uncertainty due to technical limitations early in drug development is often the cause of preclinical drugs not reaching the clinic. Here, we studied whether organoids, mini-organs derived from the respective mouse tissue's stem cells, can serve as a novel model system to study NR biology and targetability. We characterized mRNA expression profiles of the NR superfamily in mouse liver, ileum, and colon organoids. Tissue-specific expression patterns were largely maintained in the organoids, indicating their suitability for NR research. Metabolic NRs Fxrα, Lxrα, Lxrβ, Pparα, and Pparγ induced expression of and binding to endogenous target genes. Transcriptome analyses of wildtype colon organoids stimulated with Rosiglitazone showed that lipid metabolism was the highest significant changed function, greatly mimicking the PPARs and Rosiglitazone function in vivo. Finally, using organoids we identify Trpm6, Slc26a3, Ang1, and Rnase4, as novel Fxr target genes. Our results demonstrate that organoids represent a framework to study NR biology that can be further expanded to human organoids to improve preclinical testing of novel drugs that target this pharmacologically important class of ligand activated transcription factors.
    Polymer-metal organic framework composite films as affinity layer for capacitive sensor devices
    Sachdeva, Sumit ; Soccol, Dimitri ; Gravesteijn, Dirk J. ; Kapteijn, Freek ; Sudhölter, E.J.R. ; Gascon, Jorge ; Smet, L.C.P.M. de - \ 2016
    ACS Sensors 1 (2016). - ISSN 2379-3694 - p. 1188 - 1192.
    We report a simple method for sensor development using polymer-
    MOF composite films. Nanoparticles of NH2-MIL-53(Al) dispersed in a Matrimid
    polyimide were applied as a thin film on top of capacitive sensor devices with planar electrodes. These drop-cast films act as an affinity layer. Sensing studies carried out with methanol vapor using impedance spectroscopy demonstrate that the presence of MOF enhances the overall response and lowers the detection limit compared to MOF-free polymer films and bare devices. This can be understood by additional changes of the local polarity of the composite films due to higher adsorption of methanol by the porous MOF particles. We expect that this work will stimulate the design of composite polymeric affinity layers for a range of analytes by a proper choice of dispersed MOF particles.
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