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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    Halotolerance mechanisms of the methanotroph Methylomicrobium alcaliphilum
    Bordel, Sergio ; Pérez, Rebeca ; Rodríguez, Elisa ; Cantera, Sara ; Fernández-González, Nuria ; Martínez, María A. ; Muñoz, Raúl - \ 2020
    Biotechnology and Bioengineering (2020). - ISSN 0006-3592
    ectoine - halotolerance - metabolism - metanotrophy - respiratory chains - RNA-seq

    Methylomicrobium alcaliphilum is an alkaliphilic and halotolerant methanotroph. The physiological responses of M. alcaliphilum to high NaCl concentrations, were studied using RNA sequencing and metabolic modeling. This study revealed that M. alcaliphilum possesses an unusual respiratory chain, in which complex I is replaced by a Na+ extruding NQR complex (highly upregulated under high salinity conditions) and a Na+ driven adenosine triphosphate (ATP) synthase coexists with a conventional H+ driven ATP synthase. A thermodynamic and metabolic model showing the interplay between these different components is presented. Ectoine is the main osmoprotector used by the cells. Ectoine synthesis is activated by the transcription of an ect operon that contains five genes, including the ectoine hydroxylase coding ectD gene. Enzymatic tests revealed that the product of ectD does not have catalytic activity. A new Genome Scale Metabolic Model for M. alcaliphilum revealed a higher flux in the oxidative branch of the pentose phosphate pathway leading to NADPH production and contributing to resistance to oxidative stress.

    Follicular fluid steroid profile in sows: Relationship to follicle size and oocyte quality
    Costermans, N.G.J. ; Soede, N.M. ; Tricht, F. Van; Blokland, M. ; Kemp, B. ; Keijer, J. ; Teerds, K.J. - \ 2020
    Biology of Reproduction 102 (2020)3. - ISSN 0006-3363 - p. 740 - 749.
    follicle - granulosa cells - insulin-like growth factor - metabolism - porcine - steroid hormones

    Identification of reliable characteristics of follicle quality and developmental competence has been pursued in numerous studies, but with inconsistent outcomes. Here, we aimed to identify these characteristics by analysis of the follicular fluid (FF) steroid profile in relation to cumulus-oocyte complex (COC) morphology and follicle size, followed by molecular substantiation. Multiparous sows at weaning were used to facilitate analysis at the start of the follicular phase of the oestrus cycle. Sows with a higher average follicle size (≥5 mm vs. < 5 mm) had a higher follicular fluid β-estradiol concentration, but did not differ in other measured steroids. Sows with high compared to low percentage high-quality COCs (<70% vs. ≥70% high-quality) had follicular fluid with a higher concentration of β-estradiol, 19-norandrostenedione, progesterone, and α-testosterone, while the concentration of cortisol was lower. Transcriptome analysis of granulosa cells of healthy follicles of sows with a high percentage high-quality COCs showed higher abundance of transcripts involved in ovarian steroidogenesis (e.g., CYP19A2 and 3, POR, VEGFA) and growth (IGF1) and differential abundance of transcripts involved in granulosa cell apoptosis (e.g., GADD45A, INHBB). Differences in aromatase transcript abundance (CYP19A1, 2 and 3) were confirmed at the protein level. In addition, sows with a high percentage high-quality COCs lost less weight during lactation and had higher plasma IGF1 concentration at weaning, which may have affected COC quality. To the best of our knowledge, this study is also the first to report the relation between FF steroid profile and COC quality.

    Limited mass-independent individual variation in resting metabolic rate in a wild population of snow voles (Chionomys nivalis)
    Hagmayer, Andres ; Camenisch, Glauco ; Canale, Cindy ; Postma, Erik ; Bonnet, Timothée - \ 2020
    Journal of Evolutionary Biology 33 (2020)5. - ISSN 1010-061X - p. 608 - 618.
    adaptation - constraints - measurement error - metabolism - mixed model - repeatability - rodent

    Resting metabolic rate (RMR) is a potentially important axis of physiological adaptation to the thermal environment. However, our understanding of the causes and consequences of individual variation in RMR in the wild is hampered by a lack of data, as well as analytical challenges. RMR measurements in the wild are generally characterized by large measurement errors and a strong dependency on mass. The latter is problematic when assessing the ability of RMR to evolve independently of mass. Mixed models provide a powerful and flexible tool to tackle these challenges, but they have rarely been used to estimate repeatability of mass-independent RMR from field data. We used respirometry to obtain repeated measurements of RMR in a long-term study population of snow voles (Chionomys nivalis) inhabiting an environment subject to large circadian and seasonal fluctuations in temperature. Using both uni- and bivariate mixed models, we quantify individual repeatability in RMR and decompose repeatability into mass-dependent and mass-independent components, while accounting for measurement error. RMR varies among individuals, that is, is repeatable (R =.46) and strongly co-varies with BM. Indeed, much of the repeatability of RMR is attributable to individual variation in BM, and the repeatability of mass-independent RMR is reduced by 41% to R =.27. These empirical results suggest that the evolutionary potential of RMR independent of mass may be severely constrained. This study illustrates how to leverage bivariate mixed models to model field data for metabolic traits, correct for measurement error and decompose the relative importance of mass-dependent and mass-independent physiological variation.

    “CATAStrophy,” a Genome-Informed Trophic Classification of Filamentous Plant Pathogens – How Many Different Types of Filamentous Plant Pathogens Are There?
    Hane, James K. ; Paxman, Jonathan ; Jones, Darcy A.B. ; Oliver, Richard P. ; Wit, Pierre de - \ 2020
    Frontiers in Microbiology 10 (2020). - ISSN 1664-302X
    biotroph - CAZymes - fungi - hemibiotroph - metabolism - necrotroph - plant pathogen

    The traditional classification of fungal and oomycete phytopathogens into three classes – biotrophs, hemibiotrophs, or necrotrophs – is unsustainable. This study highlights multiple phytopathogen species for which these labels have been inappropriately applied. We propose a novel and reproducible classification based solely on genome-derived analysis of carbohydrate-active enzyme (CAZyme) gene content called CAZyme-Assisted Training And Sorting of -trophy (CATAStrophy). CATAStrophy defines four major divisions for species associated with living plants. These are monomertrophs (Mo) (corresponding to biotrophs), polymertrophs (P) (corresponding to necrotrophs), mesotrophs (Me) (corresponding to hemibiotrophs), and vasculartrophs (including species commonly described as wilts, rots, or anthracnoses). The Mo class encompasses symbiont, haustorial, and non-haustorial species. Me are divided into the subclasses intracellular and extracellular Me, and the P into broad and narrow host sub-classes. This gives a total of seven discrete plant-pathogenic classes. The classification provides insight into the properties of these species and offers a facile route to develop control measures for newly recognized diseases. Software for CATAStrophy is available online at https://github.com/ccdmb/catastrophy. We present the CATAStrophy method for the prediction of trophic phenotypes based on CAZyme gene content, as a complementary method to the traditional tripartite “biotroph–hemibiotroph–necrotroph” classifications that may encourage renewed investigation and revision within the fungal biology community.

    Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) – MultiplexELISA data
    Stobernack, Tim ; Frankena, Klaas ; Rodrigues Pereira, Rob ; Schrama, Rosan P.H. ; Baarlen, Peter van; Kleerebezem, Michiel ; Pelsser, Lidy ; Hontelez, Saartje - \ 2020
    Wageningen University & Research
    ADHD - few-foods diet - biomarker - immunology - metabolism - hormones
    Multiplex ELISA data of immune, metabolism and hormone related molecules for 79 children included in the Biomarker Research in ADHD: the Impact of Nutrition (BRAIN) study, an open-label trial during which children with ADHD followed a few-foods diet (FFD). Sampling was done before the FFD (t1) and after 5 weeks of FFD (t2).
    Metabolic Model of the Phytophthora infestans-Tomato Interaction Reveals Metabolic Switches during Host Colonization
    Rodenburg, Sander Y.A. ; Seidl, Michael F. ; Judelson, Howard S. ; Vu, Andrea L. ; Govers, Francine ; Ridder, Dick de - \ 2019
    mBio 10 (2019)4. - ISSN 2150-7511
    metabolic modeling - metabolism - oomycetes - Phytophthora infestans - tomato

    The oomycete pathogen Phytophthora infestans causes potato and tomato late blight, a disease that is a serious threat to agriculture. P. infestans is a hemibiotrophic pathogen, and during infection, it scavenges nutrients from living host cells for its own proliferation. To date, the nutrient flux from host to pathogen during infection has hardly been studied, and the interlinked metabolisms of the pathogen and host remain poorly understood. Here, we reconstructed an integrated metabolic model of P. infestans and tomato (Solanum lycopersicum) by integrating two previously published models for both species. We used this integrated model to simulate metabolic fluxes from host to pathogen and explored the topology of the model to study the dependencies of the metabolism of P. infestans on that of tomato. This showed, for example, that P. infestans, a thiamine auxotroph, depends on certain metabolic reactions of the tomato thiamine biosynthesis. We also exploited dual-transcriptome data of a time course of a full late blight infection cycle on tomato leaves and integrated the expression of metabolic enzymes in the model. This revealed profound changes in pathogen-host metabolism during infection. As infection progresses, P. infestans performs less de novo synthesis of metabolites and scavenges more metabolites from tomato. This integrated metabolic model for the P. infestans-tomato interaction provides a framework to integrate data and generate hypotheses about in planta nutrition of P. infestans throughout its infection cycle.IMPORTANCE Late blight disease caused by the oomycete pathogen Phytophthora infestans leads to extensive yield losses in tomato and potato cultivation worldwide. To effectively control this pathogen, a thorough understanding of the mechanisms shaping the interaction with its hosts is paramount. While considerable work has focused on exploring host defense mechanisms and identifying P. infestans proteins contributing to virulence and pathogenicity, the nutritional strategies of the pathogen are mostly unresolved. Genome-scale metabolic models (GEMs) can be used to simulate metabolic fluxes and help in unravelling the complex nature of metabolism. We integrated a GEM of tomato with a GEM of P. infestans to simulate the metabolic fluxes that occur during infection. This yields insights into the nutrients that P. infestans obtains during different phases of the infection cycle and helps in generating hypotheses about nutrition in planta.

    Invited review: Nitrogen in ruminant nutrition: A review of measurement techniques
    Hristov, A.N. ; Bannink, A. ; Crompton, L.A. ; Huhtanen, P. ; Kreuzer, M. ; McGee, M. ; Nozière, P. ; Reynolds, C.K. ; Bayat, A.R. ; Yáñez-Ruiz, D.R. ; Dijkstra, J. ; Kebreab, E. ; Schwarm, A. ; Shingfield, K.J. ; Yu, Z. - \ 2019
    Journal of Dairy Science 102 (2019)7. - ISSN 0022-0302 - p. 5811 - 5852.
    environment - manure - metabolism - nitrogen - ruminant animal - technique

    Nitrogen is a component of essential nutrients critical for the productivity of ruminants. If excreted in excess, N is also an important environmental pollutant contributing to acid deposition, eutrophication, human respiratory problems, and climate change. The complex microbial metabolic activity in the rumen and the effect on subsequent processes in the intestines and body tissues make the study of N metabolism in ruminants challenging compared with nonruminants. Therefore, using accurate and precise measurement techniques is imperative for obtaining reliable experimental results on N utilization by ruminants and evaluating the environmental impacts of N emission mitigation techniques. Changeover design experiments are as suitable as continuous ones for studying protein metabolism in ruminant animals, except when changes in body weight or carryover effects due to treatment are expected. Adaptation following a dietary change should be allowed for at least 2 (preferably 3) wk, and extended adaptation periods may be required if body pools can temporarily supply the nutrients studied. Dietary protein degradability in the rumen and intestines are feed characteristics determining the primary AA available to the host animal. They can be estimated using in situ, in vitro, or in vivo techniques with each having inherent advantages and disadvantages. Accurate, precise, and inexpensive laboratory assays for feed protein availability are still needed. Techniques used for direct determination of rumen microbial protein synthesis are laborious and expensive, and data variability can be unacceptably large; indirect approaches have not shown the level of accuracy required for widespread adoption. Techniques for studying postruminal digestion and absorption of nitrogenous compounds, urea recycling, and mammary AA metabolism are also laborious, expensive (especially the methods that use isotopes), and results can be variable, especially the methods based on measurements of digesta or blood flow. Volatile loss of N from feces and particularly urine can be substantial during collection, processing, and analysis of excreta, compromising the accuracy of measurements of total-tract N digestion and body N balance. In studying ruminant N metabolism, nutritionists should consider the longer term fate of manure N as well. Various techniques used to determine the effects of animal nutrition on total N, ammonia- or nitrous oxide-emitting potentials, as well as plant fertilizer value, of manure are available. Overall, methods to study ruminant N metabolism have been developed over 150 yr of animal nutrition research, but many of them are laborious and impractical for application on a large number of animals. The increasing environmental concerns associated with livestock production systems necessitate more accurate and reliable methods to determine manure N emissions in the context of feed composition and ruminant N metabolism.

    Metaproteomic and 16S rRNA Gene Sequencing Analysis of the Infant Fecal Microbiome
    Cortes, Laetitia ; Wopereis, Harm ; Tartiere, Aude ; Piquenot, Julie ; Gouw, Joost W. ; Tims, Sebastian ; Knol, Jan ; Chelsky, Daniel - \ 2019
    International Journal of Molecular Sciences 20 (2019)6. - ISSN 1661-6596
    fecal - infants - intestinal - mass spectrometry - metabolism - metacluster - microbiome

    A metaproteomic analysis was conducted on the fecal microbiome of eight infants to characterize global protein and pathway expression. Although mass spectrometry-based proteomics is now a routine tool, analysis of the microbiome presents specific technical challenges, including the complexity and dynamic range of member taxa, the need for well-annotated metagenomic databases, and high inter-protein sequence redundancy and similarity. In this study, an approach was developed for assessment of biological phenotype and metabolic status, as a functional complement to DNA sequence analysis. Fecal samples were prepared and analysed by tandem mass spectrometry and a homology-based meta-clustering strategy was used to combine peptides from multiple species into representative proteins. In total, 15,250 unique peptides were sequenced and assigned to 2154 metaclusters, which were then assigned to pathways and functional groups. Differences were noted in several pathways, consistent with the dominant genera observed in different subjects. Although this study was not powered to draw conclusions from the comparisons, the results obtained demonstrate the applicability of this approach and provide the methods needed for performing semi-quantitative comparisons of human fecal microbiome composition, physiology and metabolism, as well as a more detailed assessment of microbial composition in comparison to 16S rRNA gene sequencing.

    How bacteria can keep your gut healthy: beneficial microbes
    Belzer, C. - \ 2019
    Wageningen : WURcast
    microorganisms - intestinal microorganisms - metabolism - pathogens
    Follicular development of sows at weaning in relation to estimated breeding value for within-litter variation in piglet birth weight
    Costermans, N.G.J. ; Teerds, K.J. ; Keijer, J. ; Knol, E.F. ; Koopmanschap, R.E. ; Kemp, B. ; Soede, N.M. - \ 2019
    Animal 13 (2019)3. - ISSN 1751-7311 - p. 554 - 563.
    lactation - litter uniformity - metabolism - reproduction - sows

    In this study we aimed to identify possible causes of within-litter variation in piglet birth weight (birth weight variation) by studying follicular development of sows at weaning in relation to their estimated breeding value (EBV) for birth weight variation. In total, 29 multiparous sows (parity 3 to 5) were selected on their EBV for birth weight variation (SD in grams; High-EBV: 15.8±1.6, N=14 and Low-EBV: −24.7±1.5, N=15). The two groups of sows had similar litter sizes (15.7 v. 16.9). Within 24 h after parturition, piglets were cross-fostered to ensure 13 suckling piglets per sow. Sows weaned 12.8±1.0 and 12.7±1.0 piglets, respectively, at days 26.1±0.2 of lactation. Blood and ovaries were collected within 2 h after weaning. The right ovary was immediately frozen to assess average follicle size and percentage healthy follicles of the 15 largest follicles. The left ovary was used to assess the percentage morphologically healthy cumulus-oocyte complexes (COCs) of the 15 largest follicles. To assess the metabolic state of the sows, body condition and the circulating metabolic markers insulin, IGF1, non-esterified fatty acid, creatinine, leptin, urea and fibroblast growth factor 21 were analysed at weaning. No significant differences were found in any of the measured follicular or metabolic parameters between High-EBV and Low-EBV. A higher weight loss during lactation was related to a lower percentage healthy COCs (β= −0.65, P=0.02). Serum creatinine, a marker for protein breakdown, was negatively related to average follicle size (β= −0.60, P=0.05). Backfat loss during lactation was related to a higher backfat thickness at parturition and to a higher average follicle size (β=0.36, P<0.001) at weaning. In conclusion, we hypothesise that modern hybrid sows with more backfat at the start of lactation are able to mobilise more energy from backfat during lactation and could thereby spare protein reserves to support follicular development.

    Hepatic Sel1L-Hrd1 ER-associated degradation (ERAD) manages FGF21 levels and systemic metabolism via CREBH
    Bhattacharya, Asmita ; Sun, Shengyi ; Wang, Heting ; Liu, Ming ; Long, Qiaoming ; Yin, Lei ; Kersten, Sander ; Zhang, Kezhong ; Qi, Ling - \ 2018
    The EMBO Journal 37 (2018)22. - ISSN 0261-4189
    ER quality control - FGF21 - gene transcription - metabolism - Sel1L-Hrd1 ERAD

    Fibroblast growth factor 21 (Fgf21) is a liver-derived, fasting-induced hormone with broad effects on growth, nutrient metabolism, and insulin sensitivity. Here, we report the discovery of a novel mechanism regulating Fgf21 expression under growth and fasting-feeding. The Sel1L-Hrd1 complex is the most conserved branch of mammalian endoplasmic reticulum (ER)-associated degradation (ERAD) machinery. Mice with liver-specific deletion of Sel1L exhibit growth retardation with markedly elevated circulating Fgf21, reaching levels close to those in Fgf21 transgenic mice or pharmacological models. Mechanistically, we show that the Sel1L-Hrd1 ERAD complex controls Fgf21 transcription by regulating the ubiquitination and turnover (and thus nuclear abundance) of ER-resident transcription factor Crebh, while having no effect on the other well-known Fgf21 transcription factor Pparα. Our data reveal a physiologically regulated, inverse correlation between Sel1L-Hrd1 ERAD and Crebh-Fgf21 levels under fasting-feeding and growth. This study not only establishes the importance of Sel1L-Hrd1 ERAD in the liver in the regulation of systemic energy metabolism, but also reveals a novel hepatic “ERAD-Crebh-Fgf21” axis directly linking ER protein turnover to gene transcription and systemic metabolic regulation.

    Tissue Metabolic Changes Drive Cytokine Responses to Mycobacterium tuberculosis
    Lachmandas, Ekta ; Rios-Miguel, Ana B. ; Koeken, Valerie A.C.M. ; Pasch, Eva van der; Kumar, Vinod ; Matzaraki, Vasiliki ; Li, Yang ; Oosting, Marije ; Joosten, Leo A.B. ; Notebaart, Richard A. ; Noursadeghi, Mahdad ; Netea, Mihai G. ; Crevel, Reinout van; Pollara, Gabriele - \ 2018
    The Journal of Infectious Diseases 218 (2018)1. - ISSN 0022-1899 - p. 165 - 170.
    cytokines - functional genomics - human challenge model - immune response - immunometabolism - metabolism - microarrays - transcriptomics - tuberculosis

    Cellular metabolism can influence host immune responses to Mycobacterium tuberculosis. Using a systems biology approach, differential expression of 292 metabolic genes involved in glycolysis, glutathione, pyrimidine, and inositol phosphate pathways was evident at the site of a human tuberculin skin test challenge in patients with active tuberculosis infection. For 28 metabolic genes, we identified single nucleotide polymorphisms that were trans-acting for in vitro cytokine responses to M. tuberculosis stimulation, including glutathione and pyrimidine metabolism genes that alter production of Th1 and Th17 cytokines. Our findings identify novel therapeutic targets in host metabolism that may shape protective immunity to tuberculosis.

    Food Design to Feed the Human Gut Microbiota
    Ercolini, Danilo ; Fogliano, Vincenzo - \ 2018
    Journal of Agricultural and Food Chemistry 66 (2018)15. - ISSN 0021-8561 - p. 3754 - 3758.
    food ingredients - food processing - Mediterranean diet - melanoidins - metabolism - phytochemicals
    The gut microbiome has an enormous impact on the life of the host, and the diet plays a fundamental role in shaping microbiome composition and function. The way food is processed is a key factor determining the amount and type of material reaching the gut bacteria and influencing their growth and the production of microbiota metabolites. In this perspective, the current possibilities to address food design toward a better feeding of gut microbiota are highlighted, together with a summary of the most interesting microbial metabolites that can be made from dietary precursors.
    No Adverse Programming by Post-Weaning Dietary Fructose of Body Weight, Adiposity, Glucose Tolerance, or Metabolic Flexibility
    Bouwman, Lianne M.S. ; Fernández-Calleja, José M.S. ; Swarts, Hans J.M. ; Stelt, Inge van der; Oosting, Annemarie ; Keijer, Jaap ; Schothorst, Evert M. van - \ 2018
    Molecular Nutrition & Food Research 62 (2018)2. - ISSN 1613-4125
    carbohydrates - indirect calorimetry - metabolic programming - metabolism - monosaccharides
    Scope: Metabolic programming can occur not only in the perinatal period, but also post-weaning. This study aims to assess whether fructose, in comparison to glucose, in the post-weaning diet programs body weight, adiposity, glucose tolerance, metabolic flexibility, and health at adult age. Methods and results: Three-week-old male and female C57BL6/JRccHsd mice are given an intervention diet with 32 energy percent (en%) glucose or fructose for only 3 weeks. Next, all animals are switched to the same 40 en% high fat diet for 9 weeks. Neither body weight nor adiposity differs significantly between the animals fed with glucose or fructose diets at any point during the study in both sexes. Glucose tolerance in adulthood is not affected by the post-weaning diet, nor are activity, energy expenditure, and metabolic flexibility, as measured by indirect calorimetry. At the end of the study, only in females fasting serum insulin levels and HOMA-IR index are lower in post-weaning fructose versus glucose diet (p = 0.02), without differences in pancreatic β-cell mass. Conclusions: Our present findings indicate no adverse programming of body weight, adiposity, glucose tolerance, and metabolic flexibility by dietary (solid) fructose in comparison to glucose in the post-weaning diet in mice.
    Age and Sex Effects on Plasma Metabolite Association Networks in Healthy Subjects
    Vignoli, Alessia ; Tenori, Leonardo ; Luchinat, Claudio ; Saccenti, Edoardo - \ 2018
    Journal of Proteome Research 17 (2018)1. - ISSN 1535-3893 - p. 97 - 107.
    differential network analysis - metabolism - metabolomics - network inference - NMR
    In the era of precision medicine, the analysis of simple information like sex and age can increase the potential to better diagnose and treat conditions that occur more frequently in one of the two sexes, present sex-specific symptoms and outcomes, or are characteristic of a specific age group. We present here a study of the association networks constructed from an array of 22 plasma metabolites measured on a cohort of 844 healthy blood donors. Through differential network analysis we show that specific association networks can be associated with sex and age: Different connectivity patterns were observed, suggesting sex-related variability in several metabolic pathways (branched-chain amino acids, ketone bodies, and propanoate metabolism). Reduction in metabolite hub connectivity was also found to be associated with age in both sex groups. Network analysis was complemented with standard univariate and multivariate statistical analysis that revealed age- and sex-specific metabolic signatures. Our results demonstrate that the characterization of metabolite-metabolite association networks is a promising and powerful tool to investigate the human phenotype at a molecular level.
    Metabolic status, lactation persistency, and udder health of dairy cows after different dry period lengths
    Hoeij, Renny van - \ 2017
    Wageningen University. Promotor(en): B. Kemp; T.J.G.M. Lam, co-promotor(en): A.T.M. Knegsel; J. Dijkstra. - Wageningen : Wageningen University - ISBN 9789463438070 - 285
    dairy cattle - animal health - animal behaviour - dry period - metabolism - energy balance - lactation - milk production - udders - cattle feeding - melkvee - diergezondheid - diergedrag - gustperiode - metabolisme - energiebalans - lactatie - melkproductie - uiers - rundveevoeding

    Cows traditionally have a 6 to 8 week non-lactating –‘dry period’- before calving and the start of the next lactation in order to maximize milk production in the subsequent lactation. An omitted, compared with a shortened, dry period reduces milk yield and improves energy availability in cows postpartum, but effects on udder health and persistency were unclear. Cows without a dry period fattened and spontaneously dried off due to the improved energy availability. Reducing the energy availability in the feed for cows without a dry period did not affect fattening or lactation persistency in late lactation. Cows with a short or without a dry period did not receive dry cow antibiotics in this study and this did not affect udder health across the dry period or in early lactation, but seemed to impair udder health in late lactation for cows without a dry period.

    Photosynthetic efficiency in microalgal lipid production
    Remmers, Ilse M. - \ 2017
    Wageningen University. Promotor(en): R.H. Wijffels, co-promotor(en): P.P. Lamers. - Wageningen : Wageningen University - ISBN 9789463434607 - 200
    algae - biofuels - light - triacylglycerols - lipids - metabolism - algae culture - cultural methods - algen - biobrandstoffen - licht - triacylglycerolen - lipiden - metabolisme - algenteelt - cultuurmethoden

    Microalgae can contain large amounts of lipids which make them a promising feedstock for sustainable production of food, feed, fuels and chemicals. Various studies, including pilot-scale, have been performed and the knowledge on microalgal processes has advanced quickly. Unfortunately, current production costs for cultivation are still too high for bulk lipid production from microalgae.

    One of the major causes for the high costs of bulk lipid production is the reduced solar-to-lipid conversion efficiency. Current research, however, does not provide sufficient insight to identify optimization targets. Therefore, in this thesis we have studied the lipid production in microalgae in depth.

    Different TAG-accumulation strategies were investigated from a process engineering and metabolic point of view. The combination of all findings were used in the general discussion to thoroughly evaluate the microalgal lipid accumulation strategies. Current phototrophic microalgal lipid yields are still 10 times lower than the theoretical maximum. There is, however, still an enormous potential for further improvements. Future research should focus on (genetically) improved strains and advanced cultivation strategies, including adaptation to fluctuating outdoor weather conditions.

    This thesis was performed within the EU FP7 FUEL4ME project under grand agreement No 308938. Objective of this program is to develop a sustainable and scalable process for biofuels from microalgae and to valorize the by-products.

    Metabolic modeling to understand and redesign microbial systems
    Heck, Ruben G.A. van - \ 2017
    Wageningen University. Promotor(en): V.A.P. Martins dos Santos, co-promotor(en): M. Suárez Diez. - Wageningen : Wageningen University - ISBN 9789463434553 - 239
    micro-organismen - modelleren - kooldioxide - biotechnologie - algen - metabolisme - pseudomonas - microorganisms - modeling - carbon dioxide - biotechnology - algae - metabolism - pseudomonas

    The goals of this thesis are to increase the understanding of microbial metabolism and to functionally (re-)design microbial systems using Genome- Scale Metabolic models (GSMs). GSMs are species-specific knowledge repositories that can be used to predict metabolic activities for wildtype and genetically modified organisms. Chapter 1 describes the assumptions associated with GSMs, the GSM generation process, common GSM analysis methods, and GSM-driven strain design methods. Thereby, chapter 1 provides a background for all other chapters. In this work, there is a focus on the metabolically versatile bacterium Pseudomonas putida (chapters 2,3,4,5,6), but also other model microbes and biotechnologically or societally relevant microbes are considered (chapters 3,4,6,7,8).

    GSMs are reflections of the genome annotation of the corresponding organism. For P. putida, the genome annotation that GSMs have been built on is more than ten years old. In chapter 2, this genome annotation was updated both on a structural and functional level using state-of-the-art annotation tools. A crucial part of the functional annotation relied on the most comprehensive P. putida GSM to date. This GSM was used to identify knowledge gaps in P. putida metabolism by determining the inconsistencies between its growth predictions and experimental measurements. Inconsistencies were found for 120 compounds that could be degraded by P. putida in vitro but not in silico. These compounds formed the basis for a targeted manual annotation process. Ultimately, suitable degradation pathways were identified for 86/120 as part of the functional reannotation of the P. putida genome.

    For P. putida there are 3 independently generated GSMs, which is not uncommon for model organisms. These GSMs differ in generation procedure and represent different and complementary subsets of the knowledge on the metabolism of the organism. However, the differing generation procedures also makes it extremely cumbersome to compare their contents, let alone to combine them into a single consensus GSM. Chapter 3 addresses this issue through the introduction of a computational tool for COnsensus Metabolic Model GENeration (COMMGEN). COMMGEN automatically identifies inconsistencies between independently generated GSMs and semi-automatically resolves them. Thereby, it greatly facilitates a detailed comparison of independently generated GSMs as well as the construction of consensus GSMs that more comprehensively describe the knowledge on the modeled organism.

    GSMs can predict whether or not the corresponding organism and derived mutants can grow in a large variety of different growth conditions. In comparison, experimental data is extremely limited. For example, BIOLOG data describes growth phenotypes for one strain in a few hundred different media, and genome-wide gene essentially data is typically limited to a single growth medium. In chapter 4 GSMs of multiple Pseudomonas species were used to predict growth phenotypes for all possible single-gene-deletion mutants in all possible minimal growth media to determine conditionally and unconditionally essential genes. This simulated data was integrated with genomic data on 432 sequenced Pseudomonas species, which revealed a clear link between the essentiality of a gene function and the persistence of the gene within the Pseudomonas genus.

    Chapters 5 and 6 describe the use of GSMs to (re-)design microbial systems. P. putida is, despite its acknowledged versatile metabolism, an obligate aerobe. As the oxygen-requirement limits the potential applications of P. putida, there have been several experimental attempts to enable it to grow anaerobically, which have so far not succeeded. Chapter 5 describes an in silico effort to determine why P. putida cannot grow anaerobically using a combination of GSM analyses and comparative genomics. These analyses resulted in a shortlist of several essential and oxygen-dependent processes in P. putida. The identification of these processes has enabled the design of P. putida strains that can grow anaerobically based on the current understanding of P. putida metabolism as represented in GSMs.

    Efficient microbial CO2 fixation is a requirement for the biobased community, but the natural CO2 fixation pathways are rather inefficient, while the synthetic CO2 fixation pathways have been designed without considering the metabolic context of a target organism. Chapter 6 introduces a computational tool, CO2FIX, that designs species-specific CO2 fixation pathways based on GSMs and biochemical reaction databases. The designed pathways are evaluated for their ATP efficiency, thermodynamic feasibility, and kinetic rates. CO2FIX is applied to eight different organisms, which has led to the identification of both species-specific and general CO2 fixation pathways that have promising features while requiring surprisingly few non-native reactions. Three of these pathways are described in detail.

    In all previous chapters GSMs of relatively well-understood microbes have been used to gain further insight into their metabolism and to functionally (re-)design them. For complex microbial systems, such as algae (chapter 7) and gut microbial communities (chapter 8), GSMs are similarly useful, but substantially more difficult to create and analyze. Algae are widely considered as potential centerpieces of a biobased economy. Chapter 7 reviews the current challenges in algal genome annotation, modeling and synthetic biology. The gut microbiota is an incredibly complex microbial system that is crucial to our well-being. Chapter 8 reviews the ongoing developments in the modeling of both single gut microbes and gut microbial communities, and discusses how these developments will enable the move from studying correlation to causation, and ultimately the rational steering of gut microbial activity.

    Chapter 9 discusses how the previous chapters contribute to the research goals of this thesis. In addition, it provides an extensive discussion on current GSM practices, the issues associated therewith, and how these issues can be tackled. In particular, the discussion focuses on issues related to: (i) The inability to distinguish between biological difference and GSM generation artifacts when using multiple GSMs, (ii) The lack of continuous GSM updates, (iii) The mismatch between what GSM predictions and experimental data represent, (iv) The need for standardization in GSM evaluation, and (v) The lack of experimental validation of GSM-driven strain design for metabolic engineering.

    FeedOmics, an approach to evaluate the functional properties of protein containing feed ingredients
    Kar, Soumya K. - \ 2017
    Wageningen University. Promotor(en): M.A. Smits; J.M. Wells, co-promotor(en): A.J.M. Jansman; D. Schokker. - Wageningen : Wageningen University - ISBN 9789463434461 - 254
    compound feeds - ingredients - protein sources - proteins - functional properties - metabolism - feed formulation - protein digestion - proteomics - digestive tract - nutrition physiology - animal nutrition - livestock feeding - mengvoer - ingrediënten - eiwitbronnen - eiwitten - functionele eigenschappen - metabolisme - voersamenstelling - eiwitvertering - eiwitexpressieanalyse - spijsverteringskanaal - voedingsfysiologie - diervoeding - veevoeding

    This thesis presents FeedOmics approach as a toolkit, to evaluate (novel) protein containing feed ingredients of different origin considering both their nutritional and functional value in terms of their capacity to support or modify nutrient supply, the animal’s physiology, tissue development and functioning. Such knowledge may contribute to introduce novel and/or alternative protein containing feed ingredients in the diet of livestock, thus creating a sustainable food supply for growing human population.

    First week nutrition for broiler chickens : effects on growth, metabolic status, organ development, and carcass composition
    Lamot, David - \ 2017
    Wageningen University. Promotor(en): Bas Kemp, co-promotor(en): Henry van den Brand; Peter Wijtten. - Wageningen : Wageningen University - ISBN 9789463430777 - 187
    broilers - animal nutrition - poultry feeding - feeds - growth - metabolism - carcass composition - nutrition physiology - vleeskuikens - diervoeding - pluimveevoeding - voer - groei - metabolisme - karkassamenstelling - voedingsfysiologie

    During the first week of life, broiler chickens undergo various developmental changes that are already initiated during incubation. Ongoing development of organs such as the gastro- intestinal tract and the immune system may affect the nutritional requirements during this age period. Despite the residual yolk that is available at hatch and that may provide nutritional support during the first days after hatch, the growth performance may be affected by the time in between hatch and first feed intake. Furthermore, it remains largely unknown to what extend nutritional composition of a pre-starter diet, as well as feed availability directly after hatch have an effect on physiological development directly after hatch, but also at later age. The aim of this thesis was to determine the impact of feed availability and feed composition provided during the first week of life on short-term physiological development, as well as potential long-term effects on growth performance of broiler chickens. Especially early hatched chickens were suggested to benefit more from direct feed access compared to midterm and late hatched chickens, as they tended to have a higher body weight gain during the first week after hatch. A delay in feed access for 48 h resulted in lowered body weight gain and feed intake when compared to direct feed access, but so did a short (13 to 26 h) delay in feed access after hatch. In the latter case, delayed feed access resulted in a lower weight to length ratio of the jejunum and ileum at 4 d of age compared with chickens with direct feed access. Although delayed feed access after hatch resulted in lower body weight gain during the first week after hatch and thereafter, it can be discussed whether this is truly an impairment of long-term growth or just a delayed onset of growth. With respect to feed composition, the inclusion of fish oil and medium chain fatty acids in a pre-starter diet had minor effects on humoral immune function. Inclusion of medium chain fatty acids did result in higher body weight gain and lowered feed efficiency during the first week of life, but only during the period it was provided. Feeding increased diet densities during the first week of life, obtained by formulating diets with different dietary fat levels, resulted in an increased gain to feed ratio, whereas body weight gain and feed intake decreased. Despite the shift in dietary energy supply from carbohydrates to fat and the perceived lower fat digestibility in young broiler chickens, nitrogen metabolizability and fat digestibility were not affected in the current study by feeding increased diet densities. The relative crop, liver and pancreas weights decreased when feeding increased diet densities, whereas the length of the entire intestinal tract increased. This suggests that broiler chickens repartition visceral organ development in response to feeding more concentrated diets during the first week of life. Interestingly, protein and fat accretion were not affected. Continued feeding of increased diet densities after 7 d of age resulted in increased BW gain, G:F ratio and metabolizable energy intake, but mainly during the periods that these diets were provided. In summary, even short durations of delayed feed access already impact intestinal development of young broiler chickens. However, a delayed feed access up to 48 h after hatch does not result in impaired growth, but only a delayed onset of growth. Even though digestibility of fats and oils may be suboptimal in young broiler chickens, feeding of these diets does not have to result in lowered performance per se. Young broiler chickens appear to adapt themselves towards high density diets with high fat inclusion levels in the first week of life, enabling them to digest and metabolize these diet types despite a suboptimal capacity for fat digestion. High density diets result in higher growth performance, but only for the period these diets are provided and thus carry-over effects at later age appear to be limited.

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