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.

    We have a manual that explains all the features 

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    Identification and in silico bioinformatics analysis of PR10 proteins in cashew nut
    Bastiaan-Net, Shanna ; Pina-Pérez, Maria C. ; Dekkers, Bas J.W. ; Westphal, Adrie H. ; America, Antoine H.P. ; Ariëns, Renata M.C. ; Jong, Nicolette W. de; Wichers, Harry J. ; Mes, Jurriaan J. - \ 2020
    Protein Science 29 (2020)7. - ISSN 0961-8368 - p. 1581 - 1595.
    Anacardium occidentale - Bet v 1-like - cashew nut - in silico allergenicity analysis - oral allergy syndrome (OAS) - PR10 - RNA-seq

    Proteins from cashew nut can elicit mild to severe allergic reactions. Three allergenic proteins have already been identified, and it is expected that additional allergens are present in cashew nut. pathogenesis-related protein 10 (PR10) allergens from pollen have been found to elicit similar allergic reactions as those from nuts and seeds. Therefore, we investigated the presence of PR10 genes in cashew nut. Using RNA-seq analysis, we were able to identify several PR10-like transcripts in cashew nut and clone six putative PR10 genes. In addition, PR10 protein expression in raw cashew nuts was confirmed by immunoblotting and liquid chromatography–mass spectrometry (LC–MS/MS) analyses. An in silico allergenicity assessment suggested that all identified cashew PR10 proteins are potentially allergenic and may represent three different isoallergens.

    Process history of calcium caseinate affects fibre formation
    Wang, Zhaojun ; Dekkers, Birgit L. ; Goot, Atze Jan van der - \ 2020
    Journal of Food Engineering 275 (2020). - ISSN 0260-8774
    Calcium caseinate - Drying - Fibre - Mechanical properties - Roller - Spray drying - Thermal history

    In this study, we compared the physical properties and structuring potential of spray-dried calcium caseinate (Scaca) and roller-dried calcium caseinate (Rcaca). Scaca formed more pronounced fibrous materials upon shearing compared with Rcaca. The rheological measurements revealed that the Scaca dispersion exhibited more solid-like behaviour. Besides, the particle size in excess water was larger for Rcaca (2–300 μm), while Scaca mainly contained small caseinate aggregates (<800 nm). Finally, Rcaca was less susceptible to enzymatic crosslinking with transglutaminase. The different physical properties and structuring potentials were explained by the intensive thermal treatment during roller drying for Rcaca. The application of a similar thermal process to Scaca resulted in similar properties as Rcaca. We concluded that the process history of calcium caseinate has major consequences for its fibre formation potential.

    GSE's 50th anniversary : Where do we go from now?
    Boichard, Didier ; Dekkers, Jack ; Hayes, Helene ; Werf, Julius van der; Bovenhuis, Henk ; Calus, Mario ; Groenen, Martien - \ 2019
    Genetics, Selection, Evolution 51 (2019). - ISSN 0999-193X
    Toasting as a tool to improve the functional properties of fababean protein concentrate
    Bühler, J. ; Dekkers, B.L. ; Bruins, M.E. ; Goot, A.J. van der - \ 2019
    Wageningen University & Research - 1 p.
    Toasting as a tool - protein concentration
    Protein Oxidation and in Vitro Gastric Digestion of Processed Soy-Based Matrices
    Duque-Estrada, Patrícia ; Berton-Carabin, Claire C. ; Nieuwkoop, Matthijs ; Dekkers, Birgit L. ; Janssen, Anja E.M. ; Goot, Atze Jan Van Der - \ 2019
    Journal of Agricultural and Food Chemistry 64 (2019)34. - ISSN 0021-8561 - p. 9591 - 9600.
    gastric digestion - meat analogues - processing - protein oxidation - soy proteins

    Process conditions that are applied to make structured soy-protein-based food commonly include high temperatures. Those conditions can induce protein oxidation, leading to a decrease in their susceptibility to proteolysis by digestive enzymes. We aimed to investigate the effects of thermomechanical processing on oxidation and in vitro gastric digestion of commercial soy protein ingredients. Samples were sheared at 100 to 140 °C and characterized for acid uptake, carbonyl content, electrophoresis, and surface hydrophobicity. The enzymatic hydrolysis was determined in simulated gastric conditions. Protein ingredients were already oxidized and showed higher surface hydrophobicity and hydrolysis rate compared with those of the processed matrices. However, no clear correlation between the level of carbonyls and the hydrolysis rate was found. Therefore, we conclude that gastric digestion is mostly driven by the matrix structure and composition and the available contact area between the substrate and proteolytic enzymes.

    DELAY OF GERMINATION 1-LIKE 4 acts as an inducer of seed reserve accumulation
    Sall, Khadidiatou ; Dekkers, Bas J.W. ; Nonogaki, Mariko ; Katsuragawa, Yoshihiko ; Koyari, Ryosuke ; Hendrix, David ; Willems, Leo A.J. ; Bentsink, Leónie ; Nonogaki, Hiroyuki - \ 2019
    The Plant Journal 100 (2019)1. - ISSN 0960-7412 - p. 7 - 19.
    abscisic acid - dormancy - hormone - seed development - seed maturation - storage proteins

    More than 70% of global food supply depends on seeds. The major seed reserves, such as proteins, lipids, and polysaccharides, are produced during seed maturation. Here, we report that DELAY OF GERMINATION 1-LIKE 4 (DOGL4) is a major inducer of reserve accumulation during seed maturation. The DOGL family proteins are plant-specific proteins of largely unknown biochemical function. DOGL4 shares only limited homology in amino acid sequence with DOG1, a major regulator of seed dormancy. DOGL4 was identified as one of the outstanding abscisic acid (ABA)-induced genes in our RNA sequencing analysis, whereas DOG1 was not induced by ABA. Induction of DOGL4 caused the expression of 70 seed maturation-specific genes, even in germinating seeds, including the major seed reserves ALBUMIN, CRUCIFERIN and OLEOSIN. Although DOG1 affects the expression of many seed maturation genes, the major seed reserve genes induced by DOGL4 are not altered by the dog1 mutation. Furthermore, the reduced dormancy and longevity phenotypes observed in the dog1 seeds were not observed in the dogl4 mutants, suggesting that these two genes have limited functional overlap. Taken together, these results suggest that DOGL4 is a central factor mediating reserve accumulation in seeds, and that the two DOG1 family proteins have diverged over the course of evolution into independent regulators of seed maturation, but retain some overlapping function.

    Mug en daas in Baronie worden aangepakt
    Verdonschot, Piet ; Dekkers, Dorine - \ 2019
    Met kennis de markt op
    Dekkers, B.L. ; Kortekaas, J.A. ; Meiling, Jan ; Houthoff, Iris ; Goot, A.J. van der; Berendse, Sebastiaan - \ 2019
    Marketing knowledge
    Kortekaas, J.A. ; Meiling, Jan ; Goot, A.J. van der; Dekkers, B.L. ; Houthoff, Iris ; Wijffels, R.H. ; Lindner, F. - \ 2019

    Researchers and students are increasingly being challenged to think about how they can market their knowledge. Various startups and spin-offs are already under development. ‘We no longer wait until an enterprising researcher wants to go into business.’

    Comparing structuring potential of pea and soy protein with gluten for meat analogue preparation
    Schreuders, Floor K.G. ; Dekkers, Birgit L. ; Bodnár, Igor ; Erni, Philipp ; Boom, Remko M. ; Goot, Atze Jan van der - \ 2019
    Journal of Food Engineering 261 (2019). - ISSN 0260-8774 - p. 32 - 39.
    Fibrous structures - Food processing - Plant protein - Shear cell processing - Shear-induced structuring

    Pea protein isolate can be combined with wheat gluten into materials with a fibrous morphology using shear induced structuring combined with heating. Results are partly in-line with soy protein isolate-wheat gluten blends, but the latter yields anisotropic materials in a much broader temperature range. Both blends also have the ability to include air. Air bubbles were aligned and deformed at process conditions that gave the most pronounce fibrous products. Mechanically, the pea protein-gluten materials processed at 140 °C had a similar strength as soy protein blends. At 110 and 120 °C, the pea protein blends had a strength that was comparable to a chicken meat reference (50–100 kPa) but weaker than their counterparts with soy (220–300 kPa). Blends of pea protein-gluten show potential for preparing structured plant protein materials, but the application area might be different compared with potential applications of soy protein-gluten blends.

    Maltodextrin promotes calcium caseinate fibre formation through air inclusion
    Wang, Zhaojun ; Dekkers, Birgit L. ; Boom, Remko ; Goot, Atze Jan van der - \ 2019
    Food Hydrocolloids 95 (2019). - ISSN 0268-005X - p. 143 - 151.
    Air bubble - Anisotropy - Calcium caseinate - Fibrous appearance - Maltodextrin

    Commercial calcium caseinate is available as spray-dried and roller-dried powder. Shearing a dense spray-dried calcium caseinate dispersion gives rise to a fibrous material, whereas shearing dense roller-dried calcium caseinate yields a layered material with only slight anisotropy in mechanical strength. The addition of a polysaccharide phase in a continuous protein phase may lead to formation of fibrous structures after shearing, which is hypothesized to be a result of the elongation and orientation of the dispersed polysaccharide domains. We report the effect of the addition of maltodextrin to roller-dried calcium caseinate on structure formation. The strength of the material increased with the addition of maltodextrin, which is partly caused by the withdrawal of water from the caseinate phase towards the maltodextrin phase, leading to a higher local caseinate concentration. The anisotropy of fracture stress and fracture strain were enhanced with up to 5 wt% maltodextrin. The effect of maltodextrin on the mechanical anisotropy and fibrous appearance could be ascribed to the greater air incorporation as a result of the presence of maltodextrin.

    Towards a sustainable banana supply chain in Colombia : Rainforest Alliance Certification and economic, social and environment conditions on small-scale banana plantations in Magdalena, Colombia
    Beekman, G. ; Dekkers, M. ; Koster, T. - \ 2019
    Wageningen : Wageningen Economic Research (Wageningen Economic Research report 2019-019) - ISBN 9789463435581 - 48
    Software Development for Deterministic Prediction of Selection Response in Livestock Breeding Programs Using Genomic Information
    Su, H. ; Bijma, P. ; Werf, Julius van der; Dekkers, J.C.M. - \ 2018
    Journal of Animal Science 96 (2018)Supplement 2. - ISSN 0021-8812 - p. 19 - 19.
    Theory to predict selection response in traditional livestock breeding programs has been well developed, validated and implemented in software in the past decades, for example in SelAction (Rutten et al. 2002), which has been successful as a tool to predict selection response in traditional livestock breeding programs for a wide range of population structures and selection strategies. This software used standard quantitative genetics theory and selection index theory to develop deterministic recursive equations, which model changes of trait means and variance-covariance structures to predict asymptotic response to multiple trait selection using best linear unbiased prediction (BLUP) estimated breeding values (EBV). Nowadays genetic improvement can further be enhanced by genomic predictions, which provide more accurate estimates of breeding values of animals in their earlier life and can improve the efficiency of breeding programs. While statistical methods to estimate genomic breeding values are now widely available, optimizing the use of genomics in practical livestock breeding programs is limited due to the lack of computer software that implements available theories. We're hereby to present a computer program that extends SelAction. Genomic information is included as the average phenotype of groups of individuals with both genotypic and phenotypic information following Wientjes et al. (2016). The heterogeneity of genomic information is considered in terms of the degree of relationship between selection candidates and the individuals that are both genotyped and phenotyped (van der Werf et al., 2015). This software can be used by breeders to reliably compare alternative breeding programs and for investment decisions for breeding programs that include genomic information.
    Plant-Based Meat Analogues
    Kyriakopoulou, K. ; Dekkers, B.L. ; Goot, A.J. van der - \ 2018
    In: Sustainable Meat Production and Processing / Galanakis, Charis, Academic Press - ISBN 9780128148747 - p. 103 - 126.
    As the world's population increases, the need for reliable protein sources is growing. Meat is considered a good source of high biological value protein, but meat is not sustainable. In Western countries, the shift toward a diet with reduced meat consumption demands healthy and tasteful meat-free food products. Following this trend, the market turned toward vegetable proteins, such as pulses, wheat gluten and soy protein, which are processed into meat-like products, also known as meat analogues. These products approximate certain aesthetic qualities, such as texture, flavor, and color, and nutritional characteristics of specific types of meat. The development of new, attractive food products is a challenge already, but this challenge becomes even greater considering that these products are meant as a substitute for meat. This chapter discusses the insights concerning plant-based meat analogues, their production and future developments.
    Harnessing longitudinal information to identify genetic variation in tolerance of pigs to Porcine Reproductive and Respiratory Syndrome virus infection
    Lough, Graham ; Hess, Andrew ; Hess, Melanie ; Rashidi, Hamed ; Matika, Oswald ; Lunney, Joan K. ; Rowland, Raymond R.R. ; Kyriazakis, Ilias ; Mulder, Han A. ; Dekkers, Jack C.M. ; Doeschl-Wilson, Andrea - \ 2018
    Genetics, Selection, Evolution 50 (2018). - ISSN 0999-193X

    Background: High resistance (the ability of the host to reduce pathogen load) and tolerance (the ability to maintain high performance at a given pathogen load) are two desirable host traits for producing animals that are resilient to infections. For Porcine Reproductive and Respiratory Syndrome (PRRS), one of the most devastating swine diseases worldwide, studies have identified substantial genetic variation in resistance of pigs, but evidence for genetic variation in tolerance has so far been inconclusive. Resistance and tolerance are usually considered as static traits. In this study, we used longitudinal viremia measurements of PRRS virus infected pigs to define discrete stages of infection based on viremia profile characteristics. These were used to investigate host genetic effects on viral load (VL) and growth at different stages of infection, to quantify genetic variation in tolerance at these stages and throughout the entire 42-day observation period, and to assess whether the single nucleotide polymorphism (SNP) WUR10000125 (WUR) with known large effects on resistance confers significant differences in tolerance. Results: Genetic correlations between resistance and growth changed considerably over time. Individuals that expressed high genetic resistance early in infection tended to grow slower during that time-period, but were more likely to experience lower VL and recovery in growth by the later stage. The WUR genotype was most strongly associated with VL at early- to mid-stages of infection, and with growth at mid- to late-stages of infection. Both, single-stage and repeated measurements random regression models identified significant genetic variation in tolerance. The WUR SNP was significantly associated only with the overall tolerance slope fitted through all stages of infection, with the genetically more resistant AB pigs for the WUR SNP being also more tolerant to PRRS. Conclusions: The results suggest that genetic selection for improved tolerance of pigs to PRRS is possible in principle, but may be feasible only with genomic selection, requiring intense recording schemes that involve repeated measurements to reliably estimate genetic effects. In the absence of such records, consideration of the WUR genotype in current selection schemes appears to be a promising strategy to improve simultaneously resistance and tolerance of growing pigs to PRRS.

    Structuring processes for meat analogues
    Dekkers, Birgit L. ; Boom, Remko M. ; Goot, Atze Jan van der - \ 2018
    Trends in Food Science and Technology 81 (2018). - ISSN 0924-2244 - p. 25 - 36.
    Anisotropy - Fibrous products - Meat analogues - Plant protein - Structuring

    Background: Animal-derived protein foods, such as meat, have a large impact on the environment. Meat analogues are products that replace meat in its functionality, i.e. have similar product properties and sensory attributes, which is achieved by the fibrous nature of those products. Scope and approach: The techniques used to make fibrous products that mimic muscle meats are outlined and categorized based on their approach. The bottom-up approach refers to assembly of structural elements that are combined. The top-down approach refers to structuring of biopolymer blends using an overall force field. The strengths and weaknesses of these approaches are discussed in terms of ingredient and equipment use, (achievable) product resemblance, robustness, scalability, and resource efficiency. To enlarge the theoretical framework, the techniques with the top-down strategy are further contextualized by relating to structure formation processes of materials with other applications, and the methods to analyse the fibrous structures are further outlined. Key findings and conclusions: Techniques that follow the bottom-up strategy have the potential to resemble the structure of meat most closely, by structuring the proteins hierarchically through assembly of individual structural components. The top-down strategy is better scalable, is more efficient in its use of resources, but can only create the desired structure on larger length scales. Significant progress has been made on the methods to analyse structured products from the last category. Most analysis methods focussed on the (micro)structural anisotropy of the fibrous products, however there is also a need for methods that allow in situ analysis of the evolution of the structure during processing.

    Creation of fibrous plant protein foods
    Dekkers, Birgit L. - \ 2018
    Wageningen University. Promotor(en): A.J. van der Goot; R.M. Boom. - Wageningen : Wageningen University - ISBN 9789463433198 - 204
    cum laude

    A transition from animal to plant-based protein is required to produce sufficient protein for the growing world population, while at the same time mitigates climate change. Especially the production of meat imposes a burden on the environment. Meat analogues, which are products that are similar to meat in its functionality, can help consumers to lower their meat consumption. The anisotropic, fibrous nature of meat is perhaps the most important characteristic of meat, which can be mimicked by structuring biopolymers, such as proteins and polysaccharides with the shear cell technology. The aim of this thesis is to obtain insight in the key mechanisms that play a role in the transformation of plant-based biopolymer blends into anisotropic/fibrous structures with shear cell technology. These two key mechanisms are the deformation of the two phases present in biopolymer blends, and the subsequent entrapment of this deformation during solidification. It was concluded that successful structure formation requires matching of the properties of the two phases. During structuring at elevated temperature, the two phases are deformed, while subsequent cooling ensures entrapment of the deformed dispersed phase(s) in the (continuous) phase. Ideally, the continuous and dispersed phase have different strength in the final product,.

    Chapter 2 presents a method to determine the water distribution in soy protein isolate (SPI) – wheat gluten (WG) blends. The concentration of water in each separate phase was directly determined with time-domain nuclear magnetic resonance relaxometry (TD-NMR), and oscillatory rheology was used to indirectly asses the water distribution by determining the viscoelastic properties of the separate phases and the blend. It was shown that water distributes unevenly in SPI-WG blends: more water was absorbed by the SPI as compared to the WG phase. This methodology was developed for SPI-WG blends at room temperature and subsequently also applied to heated and sheared samples in Chapter 3. First, water distribution in the blend after a heat and/or shear treatment was assessed with TD-NMR and the outcomes were then used to predict the viscoelastic properties of the SPI and WG phase in the blend. This yielded insight in the deformability of the two phases in the blend. The viscoelastic properties were measured under conditions that are relevant for structure formation, i.e. during and after heating and shearing. It was shown that the water distribution was hardly affected by a heat or shear treatment, whereas the viscoelastic properties of the two phases changed significantly. The viscoelastic properties of SPI and WG became more similar due to water redistribution in the blend, which allows deformation and alignment of the dispersed phase during structuring.

    Chapter 4 describes a study using a model blend that mimics soy protein concentrate (SPC). It consists of a relatively pure protein phase, soy protein isolate (SPI), and a soluble, more or less pure polysaccharide phase, pectin. This SPI-pectin blend formed fibrous materials at a similar heating temperature as SPC, being 140°C. Pectin formed the dispersed phase and was deformed when heated and sheared at optimal conditions. Chapter 5 extends the study on structure formation with SPI-pectin blends. Here, the deformation of the dispersed pectin phase and the influence of incorporated air were considered. The fibrous nature of these products appears upon tearing, and originates from detachment through or along the long side of the weak dispersed phase(s), being pectin and/or air. A model based on the rule of mixing was used to predict the mechanical anisotropy based on the volume fraction and the deformation of the weak, dispersed phase. The size and orientation of the dispersed phases, tailored by using different shear rates, were related to differences in fracture behavior when deforming the structures. Besides deformation, the strength and volume fraction of the weak phase(s) were important when composing a blend for fibrous structure formation. In Chapter 6, the behavior of the SPI and pectin phases in a blend was investigated by determining the viscoelastic properties while shearing and heating over time. A closed cavity rheometer (CCR) was used to determine these properties under similar conditions as used during fibrous structure formation. The addition of a small amount of pectin (2.2 wt.%) to a SPI dispersion (41.8 wt.%) resulted in viscoelastic behavior that changed in time during a shear treatment at elevated temperatures. Although one can clearly discern two distinct phases with SEM, the viscoelastic behavior of the SPI-pectin blend is more complex than that of a simple composite material.

    Chapter 7 demonstrates the importance of the fractionation process on the structuring potential of soy proteins. An enriched soy protein fraction was obtained through an aqueous fractionation process. Those fractions could be used to make fibrous structures when: i) the soy protein fractions were toasted, which is a dry heating step, and ii) when a concentrate (75% protein) was combined with full fat flour, in such a ratio that the protein content was similar to commercial SPC. Toasting results in decreased protein solubility, increased water holding capacity and increased viscosity of the fractions, and these changes turned out to be important for fibrous structure formation.

    Lastly, literature was reviewed to put all findings in perspective (Chapter 8). An overview is presented of all techniques that are commercially used and currently investigated to create meat-like structures. Structuring techniques are compared in their approach, being either bottom-up, which refers to assembly of structural elements that are then combined, or top-down, which refers to structuring of biopolymer blends using an overall force field. A bottom-up strategy has the potential to resemble the structure of meat most closely, by structuring the molecules including proteins into structural components (e.g. muscle cells) followed by assembly of individual structural components. A top-down strategy is more efficient in its use of resources and is better scalable, but can only create the desired structure on larger length scales. The techniques with a top-down strategy were further investigated by reviewing literature on similar processes outside this particular field of application, i.e. not meant to create fibrous structures. These insights were subsequently translated to the conditions as used in structure formation for meat analogues.

    Chapter 9 concludes with a general discussion of all results presented in this thesis. The different chapters are integrated in design rules for fibrous structure formation. Furthermore, the complexity encountered when studying material and conditions during fibrous structure formation are discussed. Then, the potential and the challenges for understanding and applying fibrous structure formation with simple shear flow are summarized.

    The overall societal goal of developing meat analogue food products is to help consumers in the transition from animal-based to a more plant-based diet. The scientific goal to obtain insight in fibrous structure formation with the shear technology as developed in this thesis is of importance, and can be the basis for developing the technology for the next generation meat analogues.

    Towards sustainable cocoa in Côte d'Ivoire : The impacts and contribution of UTZ certification combined with services provided by companies
    Ingram, V. ; Rijn, F. van; Waarts, Y. ; Dekkers, M. ; Vos, B. de; Koster, T. ; Tanoh, R. ; Galo, A. - \ 2018
    Wageningen : Wageningen Economic Research (Wageningen Economic Research rapport 2018-041) - ISBN 9789463437769 - 137
    Stekende insecten Griendtsveen 2017 : notitie
    Verdonschot, Piet F.M. ; Dekkers, T.B.M. - \ 2018
    Wageningen : Zoetwaterecosystemen, Wageningen Environmental Research - ISBN 9789463432924 - 58
    De inventarisatie van steekmuglarven leverde in 2016 4 kleinere gebiedsdelen op met hoge aantallen steekmuglarven (de zogenaamde ‘hotspots’). In april-mei 2017 is de larveninventarisatie herhaald. Hieruit bleek dat de larven van de moerassteekmug A. cinereus over het gehele gebied verspreid zijn met op de ‘hotspots’ opnieuw hoogste aantallen. In de periode daarna vielen de meeste locaties droog. Het jaar 2017 was een droog jaar waarbij al vroeg in het voorjaar, mogelijk zelfs in de winter, veel potentiële tijdelijke wateren al droog stonden. Het patroon van ontwikkeling van volwassen steekmuggen liet over 2017 een ‘klassiek’ beeld van een moerassteekmuggenpopulatie zien met hoge aantallen in het voorjaar die daarna snel uitdoven. Alleen in juni trad additioneel een kleine populatie van plantenboorsteekmuggen op. Dit beeld is een gevolg van het opdrogen van tijdelijke wateren in het gebied in het voorjaar. De in totaal lagere aantallen in het gehele gebied en de beperking van deze aantallen tot de maand mei hebben ertoe geleid dat in het dorp Griendtsveen in 2017 geen overlast is ervaren. De verdeling van de aantallen over de jaren 2015, 2016 en 2017 naar zone rondom en in het dorp laat zien dat er ieder jaar een afname van de aantallen optreedt richting de dorpskern. In de periode 2015-2017 is het aantallen verzamelde knutten toegenomen met een factor 3. Dit kan samenhangen met nattere weilanden aan de zuidzijde, in het dorp en aan de westzijde. De adviezen voor maatregelen om de ‘hotspots’ aan te pakken zijn in 2017 in gang gezet en ten dele uitgevoerd
    DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood
    Tobi, Elmar W. ; Slieker, Roderick C. ; Luijk, René ; Dekkers, Koen F. ; Stein, Aryeh D. ; Xu, Kate M. ; Slagboom, P.E. ; Zwet, Erik W. Van; Lumey, L.H. ; Heijmans, Bastiaan T. ; T'Hoen, Peter A. ; Pool, René ; Greevenbroek, Marleen M. Van; Stehouwer, Coen D. ; Kallen, Carla J. Van Der; Schalkwijk, Casper G. ; Wijmenga, Cisca ; Zhernakova, Sasha ; Tigchelaar, Ettje F. ; Beekman, Marian ; Deelen, Joris ; Heemst, Diana Van; Veldink, Jan H. ; Berg, Leonard H. Van Den; Duijn, Cornelia M. Van; Hofman, Albert ; Uitterlinden, André G. ; Jhamai, P.M. ; Verbiest, Michael ; Verkerk, Marijn ; Breggen, Ruud Van Der; Rooij, Jeroen Van; Lakenberg, Nico ; Mei, Hailiang ; Bot, Jan ; Zhernakova, Dasha V. ; Hof, Peter Van 't; Deelen, Patrick ; Nooren, Irene ; Moed, Matthijs ; Vermaat, Martijn ; Jan Bonder, Marc ; Dijk, Freerk Van; Arindrarto, Wibowo ; Kielbasa, Szymon M. ; Swertz, Morris A. ; Isaacs, Aaron ; Franke, Lude - \ 2018
    Science Advances 4 (2018)1. - ISSN 2375-2548
    Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342, 596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formalmediation analysis.DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing b cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-termmetabolic health. The specific mechanism awaits elucidation.
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