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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    Pilot-scale hybrid constructed wetlands for the treatment of cooling tower water prior to its desalination and reuse
    Wagner, Thomas V. ; Wilde, Vinnie de; Willemsen, Bert ; Mutaqin, Muhamad ; Putri, Gita ; Opdam, Julia ; Parsons, John R. ; Rijnaarts, Huub H.M. ; Voogt, Pim de; Langenhoff, Alette A.M. - \ 2020
    Journal of Environmental Management 271 (2020). - ISSN 0301-4797
    Benzotriazole - Biocides - Nitrate - Phosphate - Removal mechanisms - Winter season

    Cooling towers are responsible for a large part of the industrial fresh water withdrawal, and the reuse of cooling tower water (CTW) effluents can strongly lower industrial fresh water footprints. CTW requires desalination prior to being reused, but various CTW components, such as total organic carbon (TOC), conditioning chemicals and total suspended solids (TSS) hamper physico-chemical desalination technologies and need to be removed from the CTW. A cost-efficient and robust pre-treatment is thus required, which can be provided by constructed wetlands (CWs). The present study is the first study that determined the CTW pre-treatment efficiency of hybrid-CWs and the impact of winter season and biocides in the CTW on the pre-treatment efficiency. The most efficient CW flow type and dominant removal mechanisms for CW components hampering physico-chemical desalination were determined. Subsurface flow CWs removed PO43−, TSS and TOC as a result of adsorption and filtration. Vertical subsurface flow CWs (VSSF-CW) excelled in the removal of benzotriazole as a result of aerobic biodegradation. Horizontal subsurface flow CWs (HSSF-CW) allowed the denitrification of NO3 due to their anaerobic conditions. Open water CWs (OW-CWs) did not contribute to the removal of components that hamper physico-chemical desalination technologies, but do provide water storage options and habitat. The biological removal processes in the different CW flow types were negatively impacted by the winter season, but were not impacted by concentrations of the biocides glutaraldehyde and DBNPA that are relevant in practice. For optimal pre-treatment, a hybrid-CW, consisting of an initial VSSF-CW followed by an OW-CW and HSSF-CW is recommended. Future research should focus on integrating the hybrid-CW with a desalination technology, e.g. reverse osmosis, electrodialysis or capacitive ionization, to produce water that meets the requirements for use as cooling water and allow the reuse of CTW in the cooling tower itself.

    Circulation of Shiga Toxin-Producing Escherichia coli Phylogenetic Group B1 Strains Between Calve Stable Manure and Pasture Land With Grazing Heifers
    Overbeek, L.S. van; Wichers, J.H. ; Amerongen, A. van; Roermund, H.J.W. van; Zouwen, P.S. van der; Willemsen, P.T.J. - \ 2020
    Frontiers in Microbiology 11 (2020). - ISSN 1664-302X - 14 p.
    Escherichia coli strains carrying Shiga toxins 1 and 2 (stx1 and stx2), intimin (eae), and hemolysin (ehxA) production genes were found in grass shoot, rhizosphere soil, and stable manure samples from a small-scale cattle farm located at the center of Netherlands, using cultivation-dependent and -independent microbiological detection techniques. Pasture land with grazing heifers in the first year of sampling in 2014 and without grazing cattle in 2015 was physically separated from the stable that housed rose calves during both years. Manure from the stable was applied to pasture via injection into soil once per year in early spring. Among a variety of 35 phylogenetic distinctly related E. coli strains, one large group consisting of 21 closely resembling E. coli O150:H2 (18), O98:H21 (2), and O84:H2 (1) strains, all belonging to phylogenetic group B1 and carrying all screened virulence traits, was found present on grass shoots (10), rhizosphere soil (3), and stable manure (8) in 2014, but not anymore in 2015 when grazing heifers were absent. Presence and absence of these strains, obtained via enrichments, were confirmed via molecular detection using PCR-NALFIA in all ecosystems in both years. We propose that this group of Shiga toxin-producing E. coli phylogenetic group B1 strains was originally introduced via stable manure injection into the pasture. Upon grazing, these potential pathogens proliferated in the intestinal track systems of the heifers resulting in defecation with higher loads of the STEC strain onto the grass cover. The STEC strain was further smeared over the field via the hooves of the heifers resulting in augmentation of the potential pathogen in the pasture in 2014, whereas in 2015, in the absence of heifers, no augmentation occurred and only a more diverse group of potentially mild virulent E. coli phylogenetic group A and B1 strains, indigenous to pasture plants, remained present. Via this model, it was postulated that human pathogens can circulate between plants and farm animals, using the plant as an alternative ecosystem. These data indicate that grazed pasture must be considered as a potential carrier of human pathogenic E. coli strains and possibly also of other pathogens.
    African Swine Fever Virus vaccine
    Willemsen, Petrus Theodorus Johannes ; Peeters, Bernardus Petrus Hubertus - \ 2020
    Octrooinummer: WO2020060403, gepubliceerd: 2020-03-26.

    The invention is directed to a recombinant nucleic acid molecule comprising an expression cassette encoding a polyepitope comprising T-cell antigens from proteins of African Swine Fever Virus. The invention further relates to a viral particle, comprising said recombinant nucleic acid molecule, and to a viral particle comprising B-cell antigens of African Swine Fever Virus. The invention further relates to methods of stimulating an immune response in a pig comprising administering the recombinant molecule of the invention, and/or the viral particle of the invention, to the pig in an amount effective to induce an immune response.

    A large-scaled field experiment on salt marsh construction
    Hendriks, M. ; Dankers, P. ; Cleveringa, J. ; Sittoni, L. ; Willemsen, P. ; Elschot, Kelly ; Puijenbroek, M.E.B. van; Baptist, M.J. - \ 2020
    In: NCK days 2020: Book of Abstracts. - NIOZ - p. 18 - 18.
    Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
    Hagenbeek, Fiona A. ; Pool, René ; Dongen, Jenny van; Draisma, H.M. ; Jan Hottenga, Jouke ; Willemsen, Gonneke ; Abdellaoui, Abdel ; Fedko, Iryna O. ; Braber, Anouk den; Visser, Pieter Jelle ; Geus, Eco J.C.N. de; Willems van Dijk, Ko ; Verhoeven, Aswin ; Suchiman, H.E. ; Beekman, Marian ; Slagboom, P.E. ; Duijn, Cornelia M. van; Barkey Wolf, J.J.H. ; Cats, D. ; Amin, N. ; Beulens, J.W. ; Bom, J.A. van der; Bomer, N. ; Demirkan, A. ; Hilten, J.A. van; Meessen, J.M.T.A. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; So-Osman, C. ; Flier, W.M. van der; Heijden, A.A.W.A. van der; Spek, A. van der; Asselbergs, F.W. ; Boersma, E. ; Elders, P.M. ; Geleijnse, J.M. ; Ikram, M.A. ; Kloppenburg, M. ; Meulenbelt, I. ; Mooijaart, S.P. ; Nelissen, R.G.H.H. ; Netea, M.G. ; Penninx, B.W.J.H. ; Stehouwer, C.D.A. ; Teunissen, C.E. ; Terwindt, G.M. ; Jukema, J.W. ; Reinders, M.J.T. - \ 2020
    Nature Communications 11 (2020)1. - ISSN 2041-1723

    The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. In addition, the original version of this Article contained an error in the author affiliations. An affiliation of Abdel Abdellaoui with Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

    Specific Polyunsaturated Fatty Acids Can Modulate in vitro Human moDC2s and Subsequent Th2 Cytokine Release
    Hoppenbrouwers, Tamara ; Fogliano, Vincenzo ; Garssen, Johan ; Pellegrini, Nicoletta ; Willemsen, Linette E.M. ; Wichers, Harry J. - \ 2020
    Frontiers in Immunology 11 (2020). - ISSN 1664-3224
    allergy - DC2 - DC2–T-cell model - docosahexaenoic acid - polyunsaturated fatty acid - Th2

    Allergy is becoming a rapidly increasing problem worldwide, and in vitro models are frequently used to study the mechanisms behind the different types of allergic response. The dendritic cell (DC)–T-cell model can be used to study sensitization. However, lipopolysaccharide (LPS) is often used to maturate the DCs, but it gives rise to a DC1 phenotype, whereas Th2-driven inflammatory diseases such as allergy are characterized by the involvement of the DC2 phenotype. Our aim was to create a DC2–T-cell human model (human moDC2s) to study in vitro sensitization and validate the model using polyunsaturated fatty acids (PUFAs) that were previously shown to have immunomodulatory properties. We found that the generated DC2s expressed OX40L and drove naive T-cells into IL-13 production of CD4+ effector T-cells. In line with in vivo findings, n−3 long-chain (LC)PUFA docosahexaenoic acid (DHA) effectively decreased the DC2's surface expression of OX40L, as well as the IL-12p40 and IL-23 cytokine production by DC2s and subsequently lowered IL-13 production by DC2-induced effector T-cells. Similar cytokine production effects were found with eicosapentaenoic acid (EPA) and arachidonic acid (AA), whereas linoleic acid (LA) increased OX40L surface expression and subsequent T-cell-derived IL-13/IFNγ ratios, suggesting an increased risk of allergy development. Altogether, these data show that human moDC2s are able to induce Th2-type IL-13 secretion by T-cell differentiated in the presence of these DC2s and that this model can be differentially modulated by PUFAs. These results are in line with previous in vivo studies using PUFAs, indicating that this model may be of use to predict in vivo outcomes.

    The effects of shift work and sleep duration on cancer incidence in Alberta`s Tomorrow Project cohort
    McNeil, Jessica ; Heer, Emily ; Willemsen, Romy F. ; Friedenreich, Christine M. ; Brenner, Darren R. - \ 2020
    Cancer Epidemiology 67 (2020). - ISSN 1877-7821
    Cancer risk - Cohort study - Shift work - Sleep duration

    Introduction: We investigated the main effects of shift work and sleep duration on cancer incidence, and effect modification of the shift work-cancer incidence association by sleep duration. Methods: Shift work and sleep duration were assessed among 21,804 participants from Alberta`s Tomorrow Project. Incident cases of breast, prostate, colorectal and lung cancers were identified through registry linkage. Results: Having worked ≥6 years of rotating shift work (HR = 1.59, 95 % CI = 1.07, 2.37; P = 0.02) and having ever worked night shifts were associated with an increased risk of lung cancer (HR=1.71, 95 % CI=1.18, 2.47; P = 0.01), whereas having ever worked night shifts was associated with a reduced risk of prostate cancer in the latency-adjusted model only (HR=0.70, 95 % CI=0.51, 0.98; P = 0.04). No associations were found between shift work or sleep duration on the risks of breast and colorectal cancers. Some evidence of effect modification by sleep duration for the rotating shift work-lung cancer incidence association was noted (P = 0.06), with stratified analyses revealing borderline increased risk of lung cancer in participants with ≥6 years of rotating shift work and <7 h of sleep/day (HR=2.27, 95 % CI=0.95, 5.41; P = 0.07), and an increased risk of lung cancer in participants with 0.1−5.9 years of rotating shift work and >9 h of sleep/day (HR=2.99, 95 % CI=1.12, 7.97; P = 0.03). No additional evidence of effect modification by sleep duration for shift work and cancer incidence was noted. Discussion: A consistent association between shift work employment and lung cancer risk was noted in this Canadian sample. Furthermore, some evidence of effect modification of the rotating shift work-lung cancer risk association by sleep duration was noted.

    A coherent feed-forward loop drives vascular regeneration in damaged aerial organs of plants growing in a normal developmental context
    Radhakrishnan, Dhanya ; Shanmukhan, Anju Pallipurath ; Kareem, Abdul ; Aiyaz, Mohammed ; Varapparambathu, Vijina ; Toms, Ashna ; Kerstens, Merijn ; Valsakumar, Devisree ; Landge, Amit N. ; Shaji, Anil ; Mathew, Mathew K. ; Sawchuk, Megan G. ; Scarpella, Enrico ; Krizek, Beth A. ; Efroni, Idan ; Mähönen, Ari Pekka ; Willemsen, Viola ; Scheres, Ben ; Prasad, Kalika - \ 2020
    Development 147 (2020)6. - ISSN 0950-1991
    Arabidopsis - Auxin - CUC2 - PIN1 - PLT - Vascular regeneration - Wound repair

    Aerial organs of plants, being highly prone to local injuries, require tissue restoration to ensure their survival. However, knowledge of the underlying mechanism is sparse. In this study, we mimicked natural injuries in growing leaves and stems to study the reunion between mechanically disconnected tissues. We show that PLETHORA (PLT) and AINTEGUMENTA (ANT) genes, which encode stem cell-promoting factors, are activated and contribute to vascular regeneration in response to these injuries. PLT proteins bind to and activate the CUC2 promoter. PLT proteins and CUC2 regulate the transcription of the local auxin biosynthesis gene YUC4 in a coherent feed-forward loop, and this process is necessary to drive vascular regeneration. In the absence of this PLT-mediated regeneration response, leaf ground tissue cells can neither acquire the early vascular identity marker ATHB8, nor properly polarise auxin transporters to specify new venation paths. The PLT-CUC2 module is required for vascular regeneration, but is dispensable for midvein formation in leaves. We reveal the mechanisms of vascular regeneration in plants and distinguish between the wound-repair ability of the tissue and its formation during normal development.

    From stained plant tissues to quantitative cell segmentation analysis with MorphoGraphX
    Kerstens, Merijn ; Strauss, Soeren ; Smith, Richard ; Willemsen, Viola - \ 2020
    In: Plant Embryogenesis / Bayer, M., New York : Humana Press Inc. (Methods in Molecular Biology ) - ISBN 9781071603413 - p. 63 - 83.
    3D imaging - 3D segmentation - Cell volume - Embryos - Lateral roots - MorphoGraphX - Roots - SCRI Renaissance

    Development and growth of plant organs is determined by a myriad of molecular processes that occur in each individual cell. As a direct consequence of these processes, cells alter in size and shape. They therefore serve as excellent parameters to thoroughly understand gene function. However, conventional single-plane analyses fail to accurately capture cell metrics. Here, we present a comprehensive illustrated guide that demonstrates how SCRI Renaissance 2200 staining of Arabidopsis thaliana embryos and roots can be combined with the open-source application MorphoGraphX to quantify cell parameters in 3D. We compare this staining method with other common staining techniques and provide examples of embryo and root tissue segmentation. With our novel approach, subtle single-cell phenotypes can be identified in their native context, providing new possibilities to dissect gene networks.

    Integration of epidemiologic, pharmacologic, genetic and gut microbiome data in a drug–metabolite atlas
    Liu, Jun ; Lahousse, Lies ; Nivard, Michel G. ; Bot, Mariska ; Chen, Lianmin ; Klinken, Jan Bert van; Thesing, Carisha S. ; Beekman, Marian ; Akker, Erik Ben van den; Slieker, Roderick C. ; Waterham, Eveline ; Kallen, Carla J.H. van der; Boer, Irene de; Li-Gao, Ruifang ; Vojinovic, Dina ; Amin, Najaf ; Radjabzadeh, Djawad ; Kraaij, Robert ; Alferink, Louise J.M. ; Murad, Sarwa Darwish ; Uitterlinden, André G. ; Willemsen, Gonneke ; Pool, Rene ; Milaneschi, Yuri ; Heemst, Diana van; Suchiman, H.E. ; Rutters, Femke ; Elders, Petra J.M. ; Beulens, Joline W.J. ; Heijden, Amber A.W.A. van der; Greevenbroek, Marleen M.J. van; Arts, Ilja C.W. ; Onderwater, Gerrit L.J. ; Maagdenberg, Arn M.J.M. van den; Mook-Kanamori, Dennis O. ; Hankemeier, Thomas ; Terwindt, Gisela M. ; Stehouwer, Coen D.A. ; Geleijnse, Johanna M. ; ‘t Hart, Leen M. ; Slagboom, Eline P. ; Dijk, Ko Willems van; Zhernakova, Alexandra ; Fu, Jingyuan ; Penninx, Brenda W.J.H. ; Boomsma, Dorret I. ; Demirkan, Ayşe ; Stricker, Bruno H.C. ; Duijn, Cornelia M. van - \ 2020
    Nature Medicine 26 (2020)1. - ISSN 1078-8956 - p. 110 - 117.

    Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug–metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug–metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (

    Heritability estimates for 361 blood metabolites across 40 genome-wide association studies
    Hagenbeek, Fiona A. ; Pool, René ; Dongen, Jenny van; Draisma, Harmen H.M. ; Hottenga, Jouke Jan ; Willemsen, Gonneke ; Abdellaoui, Abdel ; Fedko, Iryna O. ; Braber, Anouk den; Visser, Pieter Jelle ; Geus, Eco J.C.N. de; Willems van Dijk, Ko ; Verhoeven, Aswin ; Suchiman, H.E. ; Beekman, Marian ; Slagboom, Eline P. ; Duijn, Cornelia M. van; Barkey Wolf, J.J.H. ; Cats, D. ; Amin, N. ; Beulens, J.W. ; Bom, J.A. van der; Bomer, N. ; Demirkan, A. ; Hilten, J.A. van; Meessen, J.M.T.A. ; Moed, M.H. ; Fu, J. ; Onderwater, G.L.J. ; Rutters, F. ; So-Osman, C. ; Flier, W.M. van der; Heijden, A.A.W.A. van der; Spek, A. van der; Asselbergs, F.W. ; Boersma, E. ; Elders, P.M. ; Geleijnse, J.M. ; Ikram, M.A. ; Kloppenburg, M. ; Meulenbelt, I. ; Mooijaart, S.P. ; Nelissen, R.G.H.H. ; Netea, M.G. ; Penninx, B.W.J.H. ; Stehouwer, C.D.A. ; Teunissen, C.E. ; Terwindt, G.M. ; Jukema, J.W. ; Reinders, M.J.T. - \ 2020
    Nature Communications 11 (2020)1. - ISSN 2041-1723

    Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.

    The spatiotemporal control of cell divisions in Physcomitrella development
    Tang, Han - \ 2020
    Wageningen University. Promotor(en): B. Scheres; J.E.M. Vermeer, co-promotor(en): V. Willemsen; T. Ketelaar. - Wageningen : Wageningen University - ISBN 9789463952217 - 143

    Cell division is fundamental in the development of all living organisms. In plants, cells are caged in rigid cell walls, thus plant cell shape is solely determined by cell expansion and the orientation of the cell division plane. Additionally, a newly divided cell can acquire a different cell fate through an asymmetric cell division, which is essential for tissue innovations. During my PhD, I used Physcomitrella patens, a model moss system with powerful genetic toolkits and single-cell-layer tissues, to investigate cell division control in plant development. During cytokinesis, the last step of cell division when cells are physically separated, two antiparallel sets of microtubules overlap at the midline where cell plate formation takes place. I found that subunit Sec6 of the exocyst complex is positioned to the microtubule overlaps before membranous vesicles arrive, suggesting that Sec6 bridges the cytoskeletal network and membranous compartments in cytokinesis. During moss development, cells grow as branching filaments to form a 2D filamentous network. Filaments then start to generate initial cells with a new fate, becoming gametophore initial cells. These commence growth of a 3D leafy gametophore. I identified markers that can predict the fate of initial cells, providing a new tool to investigate the early stages of the 2D-to-3D growth transition. Next, I investigated the contribution of Rho-GTPase proteins, Rho-of-Plant (ROP), to gametophore formation. I demonstrated that deletion of ROP2 results in defects in filamentous cell type transition, gametophore initiation, and leaf development. Additive deletion of ROP’s effector, RIC, in rop2 mutants only rescued phenotypes in gametophore development, suggesting that the ROP2-RIC module is functional in a tissue-specific manner. Finally, I developed a controllable wounding system to study cell reprogramming in excised moss leaves as a start to elucidate the interplay of cell reprogramming and cell division control in the early land plant lineage.

    Geometric cues forecast the switch from two- to three-dimensional growth in Physcomitrella patens
    Tang, Han ; Duijts, Kilian ; Bezanilla, Magdalena ; Scheres, Ben ; Vermeer, Joop E.M. ; Willemsen, Viola - \ 2020
    New Phytologist 225 (2020)5. - ISSN 0028-646X - p. 1945 - 1955.
    2D-to-3D development - asymmetric cell division - cell fate switch - geometric cues - Physcomitrella patens

    During land colonization, plants acquired a range of body plan adaptations, of which the innovation of three-dimensional (3D) tissues increased organismal complexity and reproductivity. In the moss, Physcomitrella patens, a 3D leafy gametophore originates from filamentous cells that grow in a two-dimensional (2D) plane through a series of asymmetric cell divisions. Asymmetric cell divisions that coincide with different cell division planes and growth directions enable the developmental switch from 2D to 3D, but insights into the underlying mechanisms coordinating this switch are still incomplete. Using 2D and 3D imaging and image segmentation, we characterized two geometric cues, the width of the initial cell and the angle of the transition division plane, which sufficiently distinguished a gametophore initial cell from a branch initial cell. These identified cues were further confirmed in gametophore formation mutants. The identification of a fluorescent marker allowed us to successfully predict the gametophore initial cell with > 90% accuracy before morphological changes, supporting our hypothesis that, before the transition division, parental cells of the gametophore initials possess different properties from those of the branch initials. Our results suggest that the cell fate decision of the initial cell is determined in the parental cell, before the transition division.

    A large-scale field experiment on salt marsh construction in the Ems estuary, the Netherlands
    Baptist, M.J. ; Dankers, P. ; Cleveringa, J. ; Sittoni, L. ; Willemsen, P. ; Elschot, Kelly ; Puijenbroek, M.E.B. van; Hendriks, M. - \ 2019
    In: RCEM 2019 the 11th symposium on river, coastal and estuarine morphodynamics: book of abstracts. - - p. 95 - 95.
    No independent associations between preconception paternal dietary patterns and embryonic growth; the Predict Study
    Oostingh, Elsje C. ; Vos, Iris de; Ham, Annelies C. ; Brouwer-Brolsma, Elske M. ; Willemsen, Sten P. ; Eggink, Alex J. ; Steegers, Eric A.P. ; Steegers-Theunissen, Régine P.M. - \ 2019
    Clinical Nutrition 38 (2019)5. - ISSN 0261-5614 - p. 2333 - 2341.
    3D ultrasound - Crown-rump length - Embryonic volume - Nutrition - Periconception period - Virtual reality

    Background & aim: Several studies show the importance of periconceptional maternal dietary patterns on human embryonic growth. Healthy paternal nutrition has been associated with better semen quality and fecundability, however, evidence on the impact on pregnancy outcome is limited. Therefore, the aim of this study was to investigate the association between preconception paternal dietary patterns and first trimester embryonic growth using the parameters longitudinal crown-rump length (CRL) and embryonic volume (EV). Methods: A total of 638 couples were enrolled in the Rotterdam Periconceptional Cohort and received longitudinal three dimensional transvaginal ultrasound scans from 7+0 up to 12+0 weeks of gestation. Virtual reality software was used to perform offline measurements of the embryonic CRL and EV. Food frequency questionnaires (FFQ) were used to estimate habitual food intake in couples. Principal component analysis (PCA) was performed to identify paternal and maternal dietary patterns. Linear mixed models adjusted for potential confounders were applied to analyze associations between paternal and maternal dietary patterns and embryonic growth parameters. Results: The paternal dietary patterns retrieved were identified as “Whole wheat grains and Vegetables”, “Sauces and Snacks Refined Grains”, “Fish and Legumes” and explained 27.5% of the total variance of the dietary intake. No significant additional effects, independent of maternal dietary patters and other maternal and paternal potential confounders, were shown of these paternal dietary patterns on embryonic growth in spontaneous or IVF/ICSI pregnancies. Conclusion: No significant effects of paternal dietary patterns independent of maternal dietary patters and other parental potential confounders on embryonic growth parameters could be established in spontaneous or IVF/ICSI pregnancies. The biological importance of paternal nutrition on semen quality, however, supports the need of periconceptional tailored nutritional counselling of couples trying to conceive.

    Genome-wide association analysis in tetraploid potato reveals four QTLs for protein content
    Klaassen, Michiel T. ; Willemsen, Johan H. ; Vos, Peter G. ; Visser, Richard G.F. ; Eck, Herman J. van; Maliepaard, Chris ; Trindade, Luisa M. - \ 2019
    Molecular Breeding 39 (2019). - ISSN 1380-3743
    Valorisation of tuber protein is relevant for the potato starch industry to create added-value and reduce impact on the environment. Hence, protein content has emerged as a key quality trait for innovative potato breeders. In this study, we estimated trait heritability, explored the relationship between protein content and tuber under-water weight (UWW), inferred haplotypes underlying quantitative trait loci (QTLs) and pinpointed candidate genes. We used a panel of varieties (N = 277) that was genotyped using the SolSTW 20 K Infinium single-nucleotide polymorphism (SNP) marker array. Protein content data were collected from multiple environments and years. Our genome-wide association study (GWAS) identified QTLs on chromosomes 3, 5, 7 and 12. Alleles of StCDF1 (maturity) were associated with QTLs found on chromosome 5. The QTLs on chromosomes 7 and 12 are presented here for the first time, whereas those on chromosomes 3 and 5 co-localized with loci reported in earlier studies. The candidate genes underlying the QTLs proposed here are relevant for functional studies. This study provides resources for genomics-enabled breeding for protein content in potato.
    Gradient Expression of Transcription Factor Imposes a Boundary on Organ Regeneration Potential in Plants
    Durgaprasad, Kavya ; Roy, Merin V. ; Venugopal M., Anjali ; Kareem, Abdul ; Raj, Kiran ; Willemsen, Viola ; Mähönen, Ari Pekka ; Scheres, Ben ; Prasad, Kalika - \ 2019
    Cell Reports 29 (2019)2. - ISSN 2211-1247 - p. 453 - 463.
    Arabidopsis - autoregulation - dosage dependent - lateral root - multicellular organism - organ regeneration - organ size - PLETHORA gradient - root meristem - stem cells

    Durgaprasad et al. show that dosage of a gradient-expressed transcription factor orchestrates the regeneration competence in developing root tip. Interestingly, the regeneration potential of root meristem can be separated from its size.

    Long Chain Polyunsaturated Fatty Acids (LCPUFAs) in the Prevention of Food Allergy
    Hoppenbrouwers, Tamara ; Cvejić Hogervorst, Jelena H. ; Garssen, Johan ; Wichers, Harry J. ; Willemsen, Linette E.M. - \ 2019
    Frontiers in Immunology 10 (2019). - ISSN 1664-3224 - 1 p.
    anti-inflammatory - food allergy - immune response - LCPUFA - PUFA

    N-3 long chain polyunsaturated fatty acids (LCPUFAs) are considered to possess protective properties for human health by impacting on immunological reactions. An "inflammation-suppressive" effect appears to be the common denominator of the beneficial effects of most of these dietary components which may protect against the development of chronic immune disorders such as (food) allergy. LCPUFAs, especially n-3 LCPUFAs, have been shown to interact with both the sensitization as well as the effector phase in food allergy in pre-clinical models. In this review, we explore the anti-allergic properties of LCPUFAs by providing an overview of clinical, in vivo and in vitro studies. Furthermore, we discuss the susceptibility of LCPUFAs to lipid oxidation and possible strategies to support the efficacy of LCPUFAs in reducing the allergy risk by using additional components with anti-oxidative and anti-inflammatory capacities such as the flavonoid quercetin. Finally, we propose new strategies to prevent (food) allergy using combinations of LCPUFAs and additional nutrients in diets or supplements, and postulate to investigate the use of LCPUFAs in allergic symptom relief.

    Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
    Küpers, Leanne K. ; Monnereau, Claire ; Sharp, Gemma C. ; Yousefi, Paul ; Salas, Lucas A. ; Ghantous, Akram ; Page, Christian M. ; Reese, Sarah E. ; Wilcox, Allen J. ; Czamara, Darina ; Starling, Anne P. ; Novoloaca, Alexei ; Lent, Samantha ; Roy, Ritu ; Hoyo, Cathrine ; Breton, Carrie V. ; Allard, Catherine ; Just, Allan C. ; Bakulski, Kelly M. ; Holloway, John W. ; Everson, Todd M. ; Xu, Cheng Jian ; Huang, Rae Chi ; Plaat, Diana A. van der; Wielscher, Matthias ; Merid, Simon Kebede ; Ullemar, Vilhelmina ; Rezwan, Faisal I. ; Lahti, Jari ; Dongen, Jenny van; Langie, Sabine A.S. ; Richardson, Tom G. ; Magnus, Maria C. ; Nohr, Ellen A. ; Xu, Zongli ; Duijts, Liesbeth ; Zhao, Shanshan ; Zhang, Weiming ; Plusquin, Michelle ; DeMeo, Dawn L. ; Solomon, Olivia ; Heimovaara, Joosje H. ; Jima, Dereje D. ; Gao, Lu ; Bustamante, Mariona ; Perron, Patrice ; Wright, Robert O. ; Hertz-Picciotto, Irva ; Zhang, Hongmei ; Karagas, Margaret R. ; Gehring, Ulrike ; Marsit, Carmen J. ; Beilin, Lawrence J. ; Vonk, Judith M. ; Jarvelin, Marjo Riitta ; Bergström, Anna ; Örtqvist, Anne K. ; Ewart, Susan ; Villa, Pia M. ; Moore, Sophie E. ; Willemsen, Gonneke ; Standaert, Arnout R.L. ; Håberg, Siri E. ; Sørensen, Thorkild I.A. ; Taylor, Jack A. ; Räikkönen, Katri ; Yang, Ivana V. ; Kechris, Katerina ; Nawrot, Tim S. ; Silver, Matt J. ; Gong, Yun Yun ; Richiardi, Lorenzo ; Kogevinas, Manolis ; Litonjua, Augusto A. ; Eskenazi, Brenda ; Huen, Karen ; Mbarek, Hamdi ; Maguire, Rachel L. ; Dwyer, Terence ; Vrijheid, Martine ; Bouchard, Luigi ; Baccarelli, Andrea A. ; Croen, Lisa A. ; Karmaus, Wilfried ; Anderson, Denise ; Vries, Maaike de; Sebert, Sylvain ; Kere, Juha ; Karlsson, Robert ; Arshad, Syed Hasan ; Hämäläinen, Esa ; Routledge, Michael N. ; Boomsma, Dorret I. ; Feinberg, Andrew P. ; Newschaffer, Craig J. ; Govarts, Eva ; Moisse, Matthieu ; Fallin, M.D. ; Melén, Erik ; Prentice, Andrew M. ; Kajantie, Eero ; Almqvist, Catarina ; Oken, Emily ; Dabelea, Dana ; Boezen, H.M. ; Melton, Phillip E. ; Wright, Rosalind J. ; Koppelman, Gerard H. ; Trevisi, Letizia ; Hivert, Marie France ; Sunyer, Jordi ; Munthe-Kaas, Monica C. ; Murphy, Susan K. ; Corpeleijn, Eva ; Wiemels, Joseph ; Holland, Nina ; Herceg, Zdenko ; Binder, Elisabeth B. ; Davey Smith, George ; Jaddoe, Vincent W.V. ; Lie, Rolv T. ; Nystad, Wenche ; London, Stephanie J. ; Lawlor, Debbie A. ; Relton, Caroline L. ; Snieder, Harold ; Felix, Janine F. - \ 2019
    Nature Communications 10 (2019)1. - ISSN 2041-1723

    Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

    Discovery of Salmonella trehalose phospholipids reveals functional convergence with mycobacteria
    Reinink, Peter ; Buter, Jeffrey ; Mishra, Vivek K. ; Ishikawa, Eri ; Cheng, Tan Yun ; Willemsen, Peter T.J. ; Porwollik, Steffen ; Brennan, Patrick J. ; Heinz, Eva ; Mayfield, Jacob A. ; Dougan, Gordon ; Els, Cécile A. van; Cerundolo, Vincenzo ; Napolitani, Giorgio ; Yamasaki, Sho ; Minnaard, Adriaan J. ; McClelland, Michael ; Moody, D.B. ; Rhijn, Ildiko Van - \ 2019
    Journal of Experimental Medicine 216 (2019)4. - ISSN 0022-1007 - p. 757 - 771.

    Salmonella species are among the world's most prevalent pathogens. Because the cell wall interfaces with the host, we designed a lipidomics approach to reveal pathogen-specific cell wall compounds. Among the molecules differentially expressed between Salmonella Paratyphi and S. Typhi, we focused on lipids that are enriched in S. Typhi, because it causes typhoid fever. We discovered a previously unknown family of trehalose phospholipids, 6,6'-diphosphatidyltrehalose (diPT) and 6-phosphatidyltrehalose (PT). Cardiolipin synthase B (ClsB) is essential for PT and diPT but not for cardiolipin biosynthesis. Chemotyping outperformed clsB homology analysis in evaluating synthesis of diPT. DiPT is restricted to a subset of Gram-negative bacteria: large amounts are produced by S. Typhi, lower amounts by other pathogens, and variable amounts by Escherichia coli strains. DiPT activates Mincle, a macrophage activating receptor that also recognizes mycobacterial cord factor (6,6'-trehalose dimycolate). Thus, Gram-negative bacteria show convergent function with mycobacteria. Overall, we discovered a previously unknown immunostimulant that is selectively expressed among medically important bacterial species.

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