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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Workshop report : Experimental animal models for universal influenza vaccines
Alessio, Flavia D'; Koopman, Gerrit ; Houard, Sophie ; Remarque, Edmond J. ; Stockhofe, Norbert ; Engelhardt, Othmar G. - \ 2018
Vaccine 36 (2018)46. - ISSN 0264-410X - p. 6895 - 6901.
Animal models - Influenza - Workshop - “Universal” vaccine

A major challenge in influenza research is the selection of an appropriate animal model that accurately reflects the disease and the protective immune response observed in humans. A workshop organised by the EDUFLUVAC consortium, a European Union funded project coordinated by the European Vaccine Initiative, brought together experts from the influenza vaccine community with the aim to discuss the current knowledge and future perspectives for testing broadly reactive influenza vaccines in animal models. The programme included a diversity of models from well-established and publicly accepted models to cutting edge, newly developed animal models as well as ex-vivo approaches and human models. The audience concluded that different vaccine approaches may require evaluation in different animal models, depending on the type of immune response induced by the vaccine. Safety is the main concern for transition to clinical development and influenza vaccine associated enhanced disease was specifically emphasised. An efficient animal model to evaluate this aspect of safety still needs to be identified. Working with animal models requires ethical compliance and consideration of the 3R principles. Development of alternative approaches such as ex-vivo techniques is progressing but is still at an early stage and these methods are not yet suitable for broader application for vaccine evaluation. The human challenge is the ultimate model to assess influenza vaccines. However this model is expensive and not largely applicable. The currently used pre-clinical models are not yet specifically focused on studying unique aspects of a universal influenza vaccine. Further collaboration, communication and effective networking are needed for success in establishment of harmonised and standardised pre-clinical models for evaluation of new influenza vaccines. This report does not provide a complete review of the field but discusses the data presented by the speakers and discussion points raised during the meeting.

'Stel doelen en laat ondernemers hun eigen weg kiezen'
Wiskerke, Han - \ 2018
Risk of increased food insecurity under stringent global climate change mitigation policy
Hasegawa, Tomoko ; Fujimori, Shinichiro ; Havlík, Petr ; Valin, Hugo ; Bodirsky, Benjamin Leon ; Doelman, Jonathan C. ; Fellmann, Thomas ; Kyle, Page ; Koopman, Jason F.L. ; Lotze-Campen, Hermann ; Mason-D’Croz, Daniel ; Ochi, Yuki ; Pérez Domínguez, Ignacio ; Stehfest, Elke ; Sulser, Timothy B. ; Tabeau, Andrzej ; Takahashi, Kiyoshi ; Takakura, J. ; Meijl, Hans van; Zeist, Willem Jan van; Wiebe, Keith ; Witzke, Peter - \ 2018
Nature Climate Change 8 (2018)8. - ISSN 1758-678X - p. 699 - 703.

Food insecurity can be directly exacerbated by climate change due to crop-production-related impacts of warmer and drier conditions that are expected in important agricultural regions1–3. However, efforts to mitigate climate change through comprehensive, economy-wide GHG emissions reductions may also negatively affect food security, due to indirect impacts on prices and supplies of key agricultural commodities4–6. Here we conduct a multiple model assessment on the combined effects of climate change and climate mitigation efforts on agricultural commodity prices, dietary energy availability and the population at risk of hunger. A robust finding is that by 2050, stringent climate mitigation policy, if implemented evenly across all sectors and regions, would have a greater negative impact on global hunger and food consumption than the direct impacts of climate change. The negative impacts would be most prevalent in vulnerable, low-income regions such as sub-Saharan Africa and South Asia, where food security problems are already acute.

Comparing impacts of climate change and mitigation on global agriculture by 2050
Meijl, Hans Van; Havlik, Petr ; Lotze-Campen, Hermann ; Stehfest, Elke ; Witzke, Peter ; Domínguez, Ignacio P. ; Bodirsky, Benjamin L. ; Dijk, Michiel van; Doelman, Jonathan ; Fellmann, Thomas ; Humpenöder, Florian ; Koopman, Jason F.L. ; Müller, Christoph ; Popp, Alexander ; Tabeau, Andrzej ; Valin, Hugo ; Zeist, Willem J. van - \ 2018
Environmental Research Letters 13 (2018)6. - ISSN 1748-9318
adaptation - agriculture - climate change - economic models - mitigation - shared socioeconomic pathways

Systematic model inter-comparison helps to narrow discrepancies in the analysis of the future impact of climate change on agricultural production. This paper presents a set of alternative scenarios by five global climate and agro-economic models. Covering integrated assessment (IMAGE), partial equilibrium (CAPRI, GLOBIOM, MAgPIE) and computable general equilibrium (MAGNET) models ensures a good coverage of biophysical and economic agricultural features. These models are harmonized with respect to basic model drivers, to assess the range of potential impacts of climate change on the agricultural sector by 2050. Moreover, they quantify the economic consequences of stringent global emission mitigation efforts, such as non-CO2 emission taxes and land-based mitigation options, to stabilize global warming at 2 °C by the end of the century under different Shared Socioeconomic Pathways. A key contribution of the paper is a vis-à-vis comparison of climate change impacts relative to the impact of mitigation measures. In addition, our scenario design allows assessing the impact of the residual climate change on the mitigation challenge. From a global perspective, the impact of climate change on agricultural production by mid-century is negative but small. A larger negative effect on agricultural production, most pronounced for ruminant meat production, is observed when emission mitigation measures compliant with a 2 °C target are put in place. Our results indicate that a mitigation strategy that embeds residual climate change effects (RCP2.6) has a negative impact on global agricultural production relative to a no-mitigation strategy with stronger climate impacts (RCP6.0). However, this is partially due to the limited impact of the climate change scenarios by 2050. The magnitude of price changes is different amongst models due to methodological differences. Further research to achieve a better harmonization is needed, especially regarding endogenous food and feed demand, including substitution across individual commodities, and endogenous technological change.

Van koopman tot kopman : naar een nieuwe internationale positionering van de Nederlandse agrosector
Berkhout, Petra ; Berkum, Siemen van; Ruben, Ruerd - \ 2018
Den Haag : Wageningen Economic Research - 67
Managing LUC‐induced GHG emissions and price impacts from bioenergy under different scenarios
Levin-Koopman, Jason ; Meijl, J.C.M. van; Smeets, E.M.W. ; Tabeau, A.A. ; Faaij, A. ; Stehfest, Elke ; Vuuren, Detlef P. van; Daioglou, Vassilis ; Gerssen-Gondelach, S. ; Wicke, Birka - \ 2017
Challenges of Global Agriculture in a Climate Change Context by 2050 : AgCLIM50
Meijl, J.C.M. van; Havlík, Petr ; Lotze-Campen, H. ; Stehfest, E. ; Witzke, P. ; Pérez Domínguez, I. ; Bodirsky, B. ; Dijk, M. van; Doelman, J.C. ; Fellmann, T. ; Humpenoeder, F. ; Levin-Koopman, Jason ; Mueller, C. ; Popp, A. ; Tabeau, A.A. ; Valin, Hugo - \ 2017
JRC (JRC science for policy report ) - 70 p.
Van koopman naar kopman
Berkhout, P. - \ 2017
Wageningen University & Research
Finetunen op fosforbehoefte
Bovenhuis, Henk ; Dijkstra, Jan - \ 2017
Mitochondrial complex I inhibition triggers a mitophagy-dependent ROS increase leading to necroptosis and ferroptosis in melanoma cells
Basit, Farhan ; Oppen, Lisanne M.P.E. Van; Schöckel, Laura ; Bossenbroek, Hasse M. ; Emst-de Vries, Sjenet E. Van; Hermeling, Johannes C.W. ; Grefte, Sander ; Kopitz, Charlotte ; Heroult, Melanie ; Willems, Peter H.G.M. ; Koopman, W.J.H. - \ 2017
Cell Death & Disease 8 (2017)3. - ISSN 2041-4889
Inhibition of complex I (CI) of the mitochondrial respiratory chain by BAY 87-2243 (‘BAY’) triggers death of BRAFV600E melanoma cell lines and inhibits in vivo tumor growth. Here we studied the mechanism by which this inhibition induces melanoma cell death. BAY treatment depolarized the mitochondrial membrane potential (Δψ), increased cellular ROS levels, stimulated lipid peroxidation and reduced glutathione levels. These effects were paralleled by increased opening of the mitochondrial permeability transition pore (mPTP) and stimulation of autophagosome formation and mitophagy. BAY-induced cell death was not due to glucose shortage and inhibited by the antioxidant α-tocopherol and the mPTP inhibitor cyclosporin A. Tumor necrosis factor receptor-associated protein 1 (TRAP1) overexpression in BAY-treated cells lowered ROS levels and inhibited mPTP opening and cell death, whereas the latter was potentiated by TRAP1 knockdown. Knockdown of autophagy-related 5 (ATG5) inhibited the BAY-stimulated autophagosome formation, cellular ROS increase and cell death. Knockdown of phosphatase and tensin homolog-induced putative kinase 1 (PINK1) inhibited the BAY-induced Δψ depolarization, mitophagy stimulation, ROS increase and cell death. Dynamin-related protein 1 (Drp1) knockdown induced mitochondrial filamentation and inhibited BAY-induced cell death. The latter was insensitive to the pancaspase inhibitor z-VAD-FMK, but reduced by necroptosis inhibitors (necrostatin-1, necrostatin-1s)) and knockdown of key necroptosis proteins (receptor-interacting serine/threonine-protein kinase 1 (RIPK1) and mixed lineage kinase domain-like (MLKL)). BAY-induced cell death was also reduced by the ferroptosis inhibitor ferrostatin-1 and overexpression of the ferroptosis-inhibiting protein glutathione peroxidase 4 (GPX4). This overexpression also inhibited the BAY-induced ROS increase and lipid peroxidation. Conversely, GPX4 knockdown potentiated BAY-induced cell death. We propose a chain of events in which: (i) CI inhibition induces mPTP opening and Δψ depolarization, that (ii) stimulate autophagosome formation, mitophagy and an associated ROS increase, leading to (iii) activation of combined necroptotic/ferroptotic cell death.
Finetunen op fosforbehoefte
Bovenhuis, Henk ; Dijkstra, Jan - \ 2017

De fosfaatproductie van de Nederlandse melkveehouderij kan nog met miljoenen kilo’s naar beneden, stellen de Wageningse wetenschappers Henk Bovenhuis en Jan Dijkstra. Door het ontwikkelen van een methode om het fosforgehalte in melk routinematig te bepalen wordt het mogelijk om de gift beter af te stemmen op de behoefte.

Van dominee tot koopman? : Habitatbanking in Nederland
Gorissen, M.M.J. ; Heide, C.M. van der; Schaminée, J.H.J. ; Ruijs, A. - \ 2017
Wageningen : Wageningen Economic Research (Wageningen Economic Research rapport 2017-030) - ISBN 9789463431026 - 116
This report focuses on whether voluntary nature compensation has added value for biodiversity in the
Netherlands, and on whether habitat banking could be a supplement to the existing Dutch system of
mandatory nature compensation. In essence, habitat banking is the realisation of nature in exchange
for ‘rights’, which are subsequently traded and bought by parties who wish to compensate for their
detrimental effect on nature. The Netherlands does not have any practical experience with habitat
banking. It is recommended to facilitate room for learning and experimentation for habitat banking in
pilot areas. The required various instruments and frameworks are elaborated in this report.
GD-directeur Ynte Schukken reageert op suggesties: 'geen specifieke zorgen over diergezondheid op grote bedrijven' : groei vraagt meer aandacht voor infectieziekten
Schukken, Ynte - \ 2016
dairy cattle - dairy farming - animal health - farm size - infectious diseases - animal disease prevention

Theoretisch is goed te verklaren dat infectieziekten vaker voorkomen als melkveebedrij ven groeien. Maar GD-directeur Ynte Schukken wil daarmee niet gezegd hebben dat besmettingen op grote bedrij ven voor meer problemen zouden zorgen

Chromosomal copy number variation in Saccharomyces pastorianus is evidence for extensive genome dynamics in industrial lager brewing strains
Broek, M. van den; Bolat, I. ; Nijkamp, J.F. ; Ramos, E. ; Luttik, M.A.H. ; Koopman, F. ; Geertman, J.M. ; Ridder, D. de; Pronk, J.T. ; Daran, J.M. - \ 2015
Applied and Environmental Microbiology 81 (2015)18. - ISSN 0099-2240 - p. 6253 - 6267.

Lager brewing strains of Saccharomyces pastorianus are natural interspecific hybrids originating from the spontaneous hybridization of Saccharomyces cerevisiae and Saccharomyces eubayanus. Over the past 500 years, S. pastorianus has been domesticated to become one of the most important industrial microorganisms. Production of lager-type beers requires a set of essential phenotypes, including the ability to ferment maltose and maltotriose at low temperature, the production of flavors and aromas, and the ability to flocculate. Understanding of the molecular basis of complex brewing-related phenotypic traits is a prerequisite for rational strain improvement. While genome sequences have been reported, the variability and dynamics of S. pastorianus genomes have not been investigated in detail. Here, using deep sequencing and chromosome copy number analysis, we showed that S. pastorianus strain CBS1483 exhibited extensive aneuploidy. This was confirmed by quantitative PCR and by flow cytometry. As a direct consequence of this aneuploidy, a massive number of sequence variants was identified, leading to at least 1,800 additional protein variants in S. pastorianus CBS1483. Analysis of eight additional S. pastorianus strains revealed that the previously defined group I strains showed comparable karyotypes, while group II strains showed large interstrain karyotypic variability. Comparison of three strains with nearly identical genome sequences revealed substantial chromosome copy number variation, which may contribute to strain-specific phenotypic traits. The observed variability of lager yeast genomes demonstrates that systematic linking of genotype to phenotype requires a three-dimensional genome analysis encompassing physical chromosomal structures, the copy number of individual chromosomes or chromosomal regions, and the allelic variation of copies of individual genes.

Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism
Liemburg-Apers, D.C. ; Willems, P.H.G.M. ; Koopman, W.J.H. ; Grefte, Sander - \ 2015
Archives of Toxicology 89 (2015)8. - ISSN 0340-5761 - p. 1209 - 1226.
Glucose - GLUT1 - GLUT4 - Mitochondria - Oxidative stress - ROS

Mitochondrial reactive oxygen species (ROS) production and detoxification are tightly balanced. Shifting this balance enables ROS to activate intracellular signaling and/or induce cellular damage and cell death. Increased mitochondrial ROS production is observed in a number of pathological conditions characterized by mitochondrial dysfunction. One important hallmark of these diseases is enhanced glycolytic activity and low or impaired oxidative phosphorylation. This suggests that ROS is involved in glycolysis (dys)regulation and vice versa. Here we focus on the bidirectional link between ROS and the regulation of glucose metabolism. To this end, we provide a basic introduction into mitochondrial energy metabolism, ROS generation and redox homeostasis. Next, we discuss the interactions between cellular glucose metabolism and ROS. ROS-stimulated cellular glucose uptake can stimulate both ROS production and scavenging. When glucose-stimulated ROS production, leading to further glucose uptake, is not adequately counterbalanced by (glucose-stimulated) ROS scavenging systems, a toxic cycle is triggered, ultimately leading to cell death. Here we inventoried the various cellular regulatory mechanisms and negative feedback loops that prevent this cycle from occurring. It is concluded that more insight in these processes is required to understand why they are (un)able to prevent excessive ROS production during various pathological conditions in humans.

Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2
Grefte, Sander ; Wagenaars, J.A. ; Jansen, R. ; Willems, P.H. ; Koopman, W.J.H. - \ 2015
Biochimica et Biophysica Acta. C, Molecular Cell Research 1853 (2015)7. - ISSN 0167-4889 - p. 1606 - 1614.
Rotenone - murine myotube formation - Raf-1 - ROCK2
Rotenone (ROT) is a widely used inhibitor of complex I (CI), the first complex of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, particularly at high concentrations ROT was also described to display off-target effects. Here we studied how ROT affected in vitro primary murine myotube formation. We demonstrate that myotube formation is specifically inhibited by ROT (10–100 nM), but not by piericidin A (PA; 100 nM), another CI inhibitor. At 100 nM, both ROT and PA fully blocked myoblast oxygen consumption. Knock-down of Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and, to a lesser extent ROCK1, prevented the ROT-induced inhibition of myotube formation. Moreover, the latter was reversed by inhibiting Raf-1 activity. In contrast, ROT-induced inhibition of myotube formation was not prevented by knock-down of RhoA. Taken together, our results support a model in which ROT reduces primary myotube formation independent of its inhibitory effect on CI-driven mitochondrial ATP production, but via a mechanism primarily involving the Raf-1/ROCK2 pathway.
Live-cell assessment of mitochondrial reactive oxygen species using dihydroethidine
Forkink, M. ; Willems, P.H. ; Koopman, W.J.H. ; Grefte, Sander - \ 2015
In: Mitochondrial Medicine / Weissig, Volkmar, Edeas, Marvin, New York : Springer Science + Business Media (Methods in Molecular Biology ) - ISBN 9781493922567 - p. 161 - 169.
Live-cell assessment - mitochondrial reactive oxygen - dihydroethidine
Reactive oxygen species (ROS) play an important role in both physiology and pathology. Mitochondria are an important source of the primary ROS superoxide. However, accurate detection of mitochondrial superoxide especially in living cells remains a difficult task. Here, we describe a method and the pitfalls to detect superoxide in both mitochondria and the entire cell using dihydroethidium (HEt) and live-cell microscopy.
Mitochondrial dysfunction in primary human fibroblasts triggers an adaptive cell survival program that requires AMPK-alpha
Distelmaier, F. ; Valsecchi, F. ; Liemburg-Apers, D. ; Lebiedzinska, M. ; Rodenburg, R. ; Heil, S. ; Keijer, J. ; Fransen, J. ; Imamura, H. ; Danhauser, K. ; Seibt, A. ; Viollet, B. ; Gellerich, F. ; Smeitink, J. ; Wieckowski, M. ; Willems, P. ; Koopman, W.J.H. - \ 2015
Biochimica et Biophysica Acta. Molecular Basis of Disease 1852 (2015)3. - ISSN 0925-4439 - p. 529 - 540.
complex-i deficiency - ubiquinone oxidoreductase deficiency - activated protein-kinase - respiratory-chain dysfunction - human nadh - oxidative-phosphorylation - energy-metabolism - mammalian-cells - atp production - cancer-cells
Dysfunction of complex I (CI) of the mitochondrial electron transport chain (ETC) features prominently in human pathology. Cell models of ETC dysfunction display adaptive survival responses that still are poorly understood but of relevance for therapy development. Here we comprehensively examined how primary human skin fibroblasts adapt to chronic CI inhibition. CI inhibition triggered transient and sustained changes in metabolism, redox homeostasis and mitochondrial (ultra)structure but no cell senescence/death. CI-inhibited cells consumed no oxygen and displayed minor mitochondrial depolarization, reverse-mode action of complex V, a slower proliferation rate and futile mitochondrial biogenesis. Adaptation was neither prevented by antioxidants nor associated with increased PGC1-a/SIRT1/mTOR levels. Survival of CI-inhibited cells was strictly glucose-dependent and accompanied by increased AMPK-a phosphorylation, which occurred without changes in ATP or cytosolic calcium levels. Conversely, cells devoid of AMPK-a died upon CI inhibition. Chronic CI inhibition did not increase mitochondrial superoxide levels or cellular lipid peroxidation and was paralleled by a specific increase in SOD2/GR, whereas SOD1/CAT/Gpx1/Gpx2/Gpx5 levels remained unchanged. Upon hormone stimulation, fully adapted cells displayed aberrant cytosolic and ER calcium handling due to hampered ATP fueling of ER calcium pumps. It is concluded that CI dysfunction triggers an adaptive program that depends on extracellular glucose and AMPK-a. This response avoids cell death by suppressing energy crisis, oxidative stress induction and substantial mitochondrial depolarization
Polycistronic expression of a ß-carotene biosynthetic pathway in Saccharomyces cerevisiae coupled to ß-ionone production
Beekwilder, J. ; Rossum, H.M. ; Koopman, F. ; Sonntag, F. ; Buchhaupt, M. ; Schrader, J. ; Hall, R.D. ; Bosch, H.J. ; Pronk, J.T. ; Maris, A.J.A. van; Daran, J.M. - \ 2014
Journal of Biotechnology 192 (2014)partB. - ISSN 0168-1656 - p. 383 - 392.
cleavage dioxygenase - yeast - genes - sequences - transformation - translation - polyprotein - versatile - genome - strain
The flavour and fragrance compound ß-ionone, which naturally occurs in raspberry and many other fruits and flowers, is currently produced by synthetic chemistry. This study describes a synthetic biology approach for ß-ionone production from glucose by Saccharomyces cerevisiae that is partially based on polycistronic expression. Experiments with model proteins showed that the T2A sequence of the Thosea asigna virus mediated efficient production of individual proteins from a single transcript in S. cerevisiae. Subsequently, three ß-carotene biosynthesis genes from the carotenoid-producing ascomycete Xanthophyllomyces dendrorhous (crtI, crtE and crtYB) were expressed in S. cerevisiae from a single polycistronic construct. In this construct, the individual crt proteins were separated by T2A sequences. Production of the individual proteins from the polycistronic construct was confirmed by Western blot analysis and by measuring the production of ß-carotene. To enable ß-ionone production, a carotenoid-cleavage dioxygenase from raspberry (RiCCD1) was co-expressed in the ß-carotene producing strain. In glucose-grown cultures with a second phase of dodecane, ß-ionone and geranylacetone accumulated in the organic phase. Thus, by introducing a polycistronic construct encoding a fungal carotenoid pathway and an expression cassette encoding a plant dioxygenase, a novel microbial production system has been established for a fruit flavour compound.
The Development of an Aza-C-Glycoside Library Based on a Tandem Staudinger/Aza-Wittig/Ugi Three-Component Reaction
Wennekes, T. ; Bonger, K.M. ; Vogel, K. ; Berg, S.A. van den; Strijland, A. ; Donker-Koopman, W.E. ; Aerts, J. ; Marel, A. van der; Overkleeft, H.S. - \ 2012
European Journal of Organic Chemistry 2012 (2012)32. - ISSN 1434-193X - p. 6420 - 6454.
ugi 4-component condensation - gaucher-disease - multicomponent reactions - nonlysosomal glucosylceramidase - functionalized pyrrolidines - pharmacological chaperones - n-butyldeoxynojirimycin - combinatorial libraries - bicyclic scaffolds - storage disorders
We report the tandem Staudinger/aza-Wittig/Ugi three-component reaction mediated synthesis of a 64-member compound library of aza-C-glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4-azidopentanal and 5-azidohexanal derivatives as precursors for the Staudinger/aza-Wittig process. Further variation is achieved by using different isocyanides as well as protective- and functional-group manipulations on the fully protected Ugi-3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase
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