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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    Antibiotics-induced monodominance of a novel gut bacterial order
    Hildebrand, Falk ; Moitinho-Silva, Lucas ; Blasche, Sonja ; Jahn, Martin Thomas Thomas ; Gossmann, Toni Ingolf ; Heuerta Cepas, Jaime ; Hercog, Rajna ; Luetge, Mechthild ; Bahram, Mohammad ; Pryszlak, Anna ; Alves, Renato J. ; Waszak, Sebastian M. ; Zhu, Ana ; Ye, Lumeng ; Costea, Paul Igor ; Aalvink, Steven ; Belzer, Clara ; Forslund, Sofia K. ; Sunagawa, Shinichi ; Hentschel, Ute ; Merten, Christoph ; Patil, Kiran Raosaheb ; Benes, Vladimir ; Bork, Peer - \ 2019
    Gut 68 (2019)10. - ISSN 0017-5749
    antibiotics - bacterial overgrowth - intestinal microbiology - molecular genetics

    Objective: The composition of the healthy human adult gut microbiome is relatively stable over prolonged periods, and representatives of the most highly abundant and prevalent species have been cultured and described. However, microbial abundances can change on perturbations, such as antibiotics intake, enabling the identification and characterisation of otherwise low abundant species. Design: Analysing gut microbial time-series data, we used shotgun metagenomics to create strain level taxonomic and functional profiles. Community dynamics were modelled postintervention with a focus on conditionally rare taxa and previously unknown bacteria. Results: In response to a commonly prescribed cephalosporin (ceftriaxone), we observe a strong compositional shift in one subject, in which a previously unknown species, UBorkfalki ceftriaxensis, was identified, blooming to 92% relative abundance. The genome assembly reveals that this species (1) belongs to a so far undescribed order of Firmicutes, (2) is ubiquitously present at low abundances in at least one third of adults, (3) is opportunistically growing, being ecologically similar to typical probiotic species and (4) is stably associated to healthy hosts as determined by single nucleotide variation analysis. It was the first coloniser after the antibiotic intervention that led to a long-lasting microbial community shift and likely permanent loss of nine commensals. Conclusion: The bloom of UB. ceftriaxensis and a subsequent one of Parabacteroides distasonis demonstrate the existence of monodominance community states in the gut. Our study points to an undiscovered wealth of low abundant but common taxa in the human gut and calls for more highly resolved longitudinal studies, in particular on ecosystem perturbations.

    Implementation of PROMETHEUS 4‐step approach for evidence use in EFSA scientific assessments: benefits, issues, needs and solutions
    Aiassa, Elisa ; Martino, Laura ; Barizzone, Fulvio ; Ciccolallo, Laura ; Garcia, Ana ; Georgiadis, Marios ; Guajardo, Irene Muñoz ; Tomcikova, Daniela ; Alexander, Jan ; Calistri, Paolo ; Gundert‐remy, Ursula ; Hart, Andrew David ; Hoogenboom, Ron Laurentius ; Messean, Antoine ; Naska, Androniki ; Navarro, Maria Navajas ; Noerrung, Birgit ; Ockleford, Colin ; Wallace, Robert John ; Younes, Maged ; Abuntori, Blaize ; Alvarez, Fernando ; Aryeetey, Monica ; Baldinelli, Francesca ; Barrucci, Federica ; Bau, Andrea ; Binaglia, Marco ; Broglia, Alessandro ; Castoldi, Anna Federica ; Christoph, Eugen ; Sesmaisons‐Lecarré, Agnes De; Georgiadis, Nikolaos ; Gervelmeyer, Andrea ; Istace, Frederique ; López‐Gálvez, Gloria ; Manini, Paola ; Maurici, Daniela ; Merten, Caroline ; Messens, Winy ; Mosbach‐Schulz, Olaf ; Putzu, Claudio ; Bordajandi, Luisa Ramos ; Smeraldi, Camilla ; Tiramani, Manuela ; Martínez, Silvia Valtueña ; Sybren, Vos ; Hardy, Anthony Richard ; Hugas, Marta ; Kleiner, Juliane ; Seze, Guilhem De - \ 2018
    EFSA Supporting Publications 15 (2018)4. - ISSN 2397-8325
    In 2014, the European Food Safety Authority (EFSA) started the PROMETHEUS (PROmoting METHods for Evidence Use in Scientific assessments) project to improve further and increase the consistency of the methods it uses in its scientific assessments. The project defined a set of principles for the scientific assessment process and a 4‐step approach (plan/carry out/verify/report) for their fulfilment, which was tested in ten case studies, one from each EFSA panel. The present report describes the benefits, issues, needs and solutions related to the implementation of the 4‐step approach in EFSA, identified in a dedicated workshop in October 2017. The key benefits of the approach, which was deemed applicable to all types of EFSA scientific assessment including assessments of regulated products, are: 1) increased ‘scientific value’ of EFSA outputs, i.e. the extent of impartiality, methodological rigour, transparency and engagement; 2) guarantee of fitness‐for‐purpose, as it implies tailoring the methods to the specificities of each assessment; 3) efficiency gain, since preparing a protocol for the assessment upfront helps more streamlined processes throughout the implementation phase; 4) innovation, as the approach promotes the pioneering practice of ‘planning before doing’ (well established in primary research) for broad scientific assessments in regulatory science; and 5) increased harmonisation and consistency of EFSA assessments. The 4‐step approach was also considered an effective system for detecting additional methodological and/or expertise needs and a useful basis for further defining a quality management system for EFSA's scientific processes. The identified issues and solutions related to the implementation of the approach are: a) lack of engagement and need for effective communication on benefits and added value; b) need for further advances especially in the field of problem formulation/protocol development, evidence appraisal and evidence integration; c) need for specialised expertise in the previous aspects; and specific needs for d) assessments of regulated products and e) outsourced projects.
    Origins of truncated supplementary capsid proteins in rAAV8 vectors produced with the baculovirus system
    Galibert, Lionel ; Savy, Adrien ; Dickx, Yohann ; Bonnin, Delphine ; Bertin, Bérangère ; Mushimiyimana, Isidore ; Oers, Monique M. van; Merten, Otto Wilhelm - \ 2018
    PLoS ONE 13 (2018)11. - ISSN 1932-6203

    The ability to produce large quantities of recombinant Adeno-Associated Virus (rAAV) vectors is an important factor for the development of gene therapy-based medicine. The baculovirus/insect cell expression system is one of the major systems for large scale rAAV production. So far, most technological developments concerned the optimization of the AAV rep and cap genes in order to be expressed correctly in a heterologous system. However, the effect of the baculovirus infection on the production of rAAV has not been examined in detail. In this study we show that the baculoviral cathepsin (v-CATH) protease is active on several (but not all) rAAV serotypes, leading to a partial degradation of VP1/VP2 proteins. Subsequently, we identified the principal v-CATH cleavage site in the rAAV8 capsid proteins and demonstrated that the cleavage is highly specific. The proteolytic degradation of VP1/ VP2 AAV capsid proteins reduces the infectivity of rAAV vectors but can be prevented by the use of a baculovirus vector with a deletion of the chiA/v-cath locus or by addition of the E64 protease inhibitor during production. Moreover, the codon optimization of AAV cap performed for several serotypes and originally aimed at the removal of potential alternative initiation codons, resulted in incorporation of additional forms of truncated VP1 into the rAAV capsids.

    Spot on: het landschap als vestigingsvoorwaarde
    Bootsma, Jeroen ; Henk, Baas ; Bos, Ernst ; Gerretsen, Paul ; Nefs, Merten ; Geuze, Adriaan ; Nijhuis, Steffen ; Veen, An van; Boeschoten, Harry - \ 2017
    Wageningen : Wageningen UR - ISBN 9789076630205 - 113
    Ringpark Utrecht : een ruimtelijk concept van de eenentwintigste eeuw voor 'healthy urban living'
    Roncken, P.A. ; Nefs, Merten ; Witte, Ymkje van de - \ 2017
    Ruimte+Wonen 1 (2017)03. - p. 30 - 41.
    park, regional design, governance, healthy urban living
    Blind spot : metropolitan landscape in the global battle for talent
    Nefs, Merten ; Geuze, A.H. ; Bos, E.J. - \ 2016
    Rotterdam : Deltametropolis Association - ISBN 9789076630182 - 132
    The essential baculovirus protein VP1054 is a hijacked cellular PURa, a nucleic-acid-binding protein specific for GGN repeats
    Marek, M. ; Romier, C. ; Galibert, L. ; Merten, O.W. ; Oers, M.M. van - \ 2014
    In: Proceedings of the 47th annual meeting of the society for invertebrate pathology and int. congress on invertebrate pathology and microbial control, August 3 - 7, 2014, Mainz, Germany. - Julius Kühn-Institut - p. 143 - 143.
    Baculovirus VP1054 Is an Acquired Cellular PURa, a Nucleic Acid-Binding Protein Specific for GGN Repeats
    Marek, M. ; Romier, C. ; Galibert, L. ; Merten, O.W. ; Oers, M.M. van - \ 2013
    Journal of Virology 87 (2013)15. - ISSN 0022-538X - p. 8465 - 8480.
    autographa-californica nucleopolyhedrovirus - multiple sequence alignment - occlusion-derived virus - stranded dna-binding - polyhedrosis-virus - hiv-1 tat - structural protein - escherichia-coli - glial-cells - f-actin
    Baculovirus VP1054 protein is a structural component of both of the virion types budded virus (BV) and occlusion-derived virus (ODV), but its exact role in virion morphogenesis is poorly defined. In this paper, we reveal sequence and functional similarity between the baculovirus protein VP1054 and the cellular purine-rich element binding protein PUR-alpha (PURa). The data strongly suggest that gene transfer has occurred from a host to an ancestral baculovirus. Deletion of the Autographa californica multiple nucleopolyhedrovirus (AcMNPV) vp1054 gene completely prevented viral cell-to-cell spread. Electron microscopy data showed that assembly of progeny nucleocapsids is dramatically reduced in the absence of VP1054. More precisely, VP1054 is required for proper viral DNA encapsidation, as deduced from the formation of numerous electron-lucent capsid-like tubules. Complementary searching identified the presence of genetic elements composed of repeated GGN trinucleotide motifs in baculovirus genomes, the target sequence for PURa proteins. Interestingly, these GGN-rich sequences are disproportionally distributed in baculoviral genomes and mostly occurred in proximity to the gene for the major occlusion body protein polyhedrin. We further demonstrate that the VP1054 protein specifically recognizes these GGN-rich islands, which at the same time encode crucial proline-rich domains in p78/83, an essential gene adjacent to the polyhedrin gene in the AcMNPV genome. While some viruses, like human immunodeficiency virus type 1 (HIV-1) and human JC virus (JCV), utilize host PURa protein, baculoviruses encode the PURa-like protein VP1054, which is crucial for viral progeny production.
    Proteins Required for Baculovirus Particle Formation: Relevance for the Development of a Baculovirion-Free Expression System
    Marek, M. ; Merten, O.W. ; Romier, C. ; Galibert, L. ; Vlak, J.M. ; Oers, M.M. van - \ 2013
    Improved baculovirus expression systems
    Galibert, L. ; Riviere, C. ; Oers, M.M. van; Merten, O.W. - \ 2013
    Octrooinummer: WO2013014294, gepubliceerd: 2013-01-31.
    The present invention relates to an optimized baculovirus construct useful for the production of virus ( like) particles or viral vectors in particular viral vectors for gene therapy.
    Development of a baculovirus-virion free expression system: Exploitation of the essential capsid protein VP80
    Marek, M. ; Merten, O.W. ; Vlak, J.M. ; Oers, M.M. van - \ 2012
    The development of a baculovirus-virion free expression system: Exploitation of the minor capsid protein VP80 and VP1054
    Marek, M. ; Merten, O.W. ; Vlak, J.M. ; Oers, M.M. van - \ 2012
    A single baculovirus for the production of rAAV8 vectors
    Galibert, L. ; Jacob, A. ; Lecomte, C. ; Bonnin, D. ; Langlet-Bertin, B. ; Boutin Fontaine, M. ; Rivière, C. ; Moullier, P. ; Oers, M.M. van; Merten, O.W. - \ 2012
    Essential C-Terminal region of the baculovirus minor capsid protein VP80 binds DNA
    Marek, M. ; Merten, O.W. ; Francis-Devaraj, F. ; Oers, M.M. van - \ 2012
    Journal of Virology 86 (2012). - ISSN 0022-538X - p. 1728 - 1738.
    nuclear polyhedrosis-virus - f-actin - bombyx-mori - nucleopolyhedrovirus - cytoskeleton - generation - localization - replication - genomics - sequence
    The essential Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) minor capsid protein VP80 has been recently shown to interact with the virus-triggered, nuclear F-actin cytoskeleton. A role for VP80 in virus morphogenesis has been proposed in the maturation of progeny nucleocapsids and in their egress from the virogenic stroma toward the nuclear periphery by a mechanism, which also includes F-actin filaments. We performed functional mapping of VP80 demonstrating that its highly conserved C-terminal region plays a crucial role in virion morphogenesis. Protein database mining identified a putative basic helix-loop-helix (bHLH) domain, a DNA-binding module typical for eukaryotic transcription factors, in the essential C-terminal region of VP80. Using a molecular modeling approach, we predicted the three-dimensional structure of this domain, revealing some unique properties. Biochemical assays proved that VP80 can form homodimers, a critical prerequisite of DNA-binding bHLH proteins. The ability of VP80 to bind DNA was subsequently confirmed by an electrophoretic mobility shift assay. We further show that AcMNPV DNA replication occurs in the absence of VP80. Immunolabeling of VP80 in baculovirus-infected cells rather points toward its involvement in nucleocapsid maturation. The competence of VP80 to interact with both F-actin and DNA provides novel insight into baculovirus morphogenesis.
    Baculovirus-based production of biopharmaceuticals free of contaminating baculoviral virions
    Oers, M.M. van; Marek, M. ; Merten, O.W. - \ 2011
    Octrooinummer: WO2011020710, gepubliceerd: 2011-02-24.
    The present invention relates to methods for the production of biopharmaceuticals implementing a baculovirus-based system. These methods advantageously allow the production of biopharmaceuticals with a reducednumber of orwithout contaminating baculoviral virions.
    Initiative to manufacture and characterize Baculovirus Reference Material
    Kamen, A. ; Aucoin, M. ; Merten, O.W. ; Alves, P.C.M. ; Hashimoto, Y. ; Airenne, K. ; Hu, Y.C. ; Mezzina, M. ; Oers, M.M. van - \ 2011
    Journal of Invertebrate Pathology 107 (2011)Suppl.. - ISSN 0022-2011 - p. S113 - S117.
    nuclear polyhedrosis-virus - real-time pcr - recombinant baculovirus - mammalian-cells - gene-therapy - insect cells - vectors - purification - titration - chromatography
    This letter to the editor brings to the attention of researchers an initiative to develop a baculovirus reference material repository. To be successful this initiative needs the support of a broad panel of researchers working with baculovirus vectors for recombinant protein production and gene delivery for either therapy or vaccination. First there is a need to reach a consensus on the nature of the reference material, the production protocols and the baculovirus characterization methods. It will also be important to define repository and distribution procedures so that the reference material is available to any researcher for calibrating experimental data and to compare experiments performed in the various laboratories. As more and more baculovirus-based products are licensed or in the final stages of development, the development of a repository of baculovirus reference material is timely. This letter describes the requirements for the reference material and for the project as a whole to be successful and calls for a partnership that would involve academic, industrial laboratories and governmental organizations to support this international initiative
    Baculovirus VP80 Protein and the F-Actin Cytoskeleton Interact and Connect the Viral Replication Factory with the Nuclear Periphery
    Marek, M. ; Merten, O.W. ; Galibert, L. ; Vlak, J.M. ; Oers, M.M. van - \ 2011
    Journal of Virology 85 (2011)11. - ISSN 0022-538X - p. 5350 - 5362.
    autographa-californica nucleopolyhedrovirus - multiple sequence alignment - occlusion-derived virus - polyhedrosis-virus - multicapsid nucleopolyhedrovirus - orgyia-pseudotsugata - efficient egress - mammalian-cells - dna-replication - new-generation
    Recently, we showed that the Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) VP80 protein is essential for the formation of both virion types, budded virus (BV) and occlusion-derived virus (ODV). Deletion of the vp80 gene did not affect assembly of nucleocapsids. However, these nucleocapsids were not able to migrate from the virogenic stroma to the nuclear periphery. In the current paper, we constructed a baculovirus recombinant with enhanced-green fluorescent protein (EGFP)-tagged VP80, allowing visualization of the VP80 distribution pattern during infection. In baculovirus-infected cells, the EGFP-VP80 protein is entirely localized in nuclei, adjacent to the virus-triggered F-actin scaffold that forms a highly organized three-dimensional network connecting the virogenic stroma physically with the nuclear envelope. Interaction between VP80 and host actin was confirmed by coimmunoprecipitation. We further showed that VP80 is associated with the nucleocapsid fraction of both BVs and ODVs, typically at one end of the nucleocapsids. In addition, the presence of sequence motifs with homology to invertebrate paramyosin proteins strongly supports a role for VP80 in the polar transport of nucleocapsids to the periphery of the nucleus on their way to the plasma membrane to form BVs and for assembly in the nuclear periphery to form ODVs for embedding in viral occlusion bodies
    Baculovirus virion formation requires the interaction between VP80 and the F-actin cytoskeleton to connect the viral replication factory with the nuclear periphery
    Marek, M. ; Devaraj, F.F. ; Galibert, L. ; Vlak, J.M. ; Merten, O.W. ; Oers, M.M. van - \ 2011
    In: Abstract Book of the 44th Annual Meeting of the Society for Invertebrate Pathology, 7-11 August 2011, Halifax, Nova Scotia, Canada. - Halifax : - p. 6 - 6.
    Engineering of Baculovirus Vectors for the Manufacture of Virion-Free Biopharmaceuticals
    Marek, M. ; Oers, M.M. van; Devaraj, F.F. ; Vlak, J.M. ; Merten, O.W. - \ 2011
    Biotechnology and Bioengineering 108 (2011)5. - ISSN 0006-3592 - p. 1056 - 1067.
    nuclear polyhedrosis-virus - occlusion-derived virus - classical swine-fever - mammalian-cells - insect cells - orgyia-pseudotsugata - escherichia-coli - immune-responses - envelope protein - foreign genes
    A novel baculovirus-based protein expression strategy was developed to produce recombinant proteins in insect cells without contaminating baculovirus virions. This novel strategy greatly simplifies the downstream processing of biopharmaceuticals produced in insect cells. The formation of these virions is prevented by deletion of a baculovirus gene essential for virion formation. The deletion is trans-complemented in a transgenic insect cell line in which the baculovirus seed stock is produced. The Autographa californica multicapsid nucleopolyhedrovirus vp80 gene was selected for this purpose, as absence of VP80 prevented the formation of budded virus as well as occlusion-derived virus, while foreign gene expression was not affected. Sf9 insect cells were engineered to functionally complement the vp80 deletion in the expression vector virus during seed stock production. The trans-complemented vp80-deletion baculovirus seed produced an amount of recombinant protein similar to that produced with conventional baculovirus vectors but without contaminating virions.
    Statistical modelling of usual intake. Scientific report submitted to EFSA
    Voet, H. van der; Klaveren, J.D. van; Arcella, D. ; Bakker, M. ; Boeing, H. ; Boon, P.E. ; Crépét, A. ; Dekkers, A. ; Boer, W. de; Dodd, K.W. ; Ferrari, P. ; Goedhart, P.W. ; Hart, A. ; Heijden, G.W.A.M. van der; Kennedy, M. ; Kipnis, V. ; Knüppel, S. ; Merten, C. ; Ocké, M. ; Slob, W. - \ 2010
    ETUI - 23 p.
    Within the EFSA Article 36 project “European Tool Usual Intake” (ETUI) a workshop was organised in May 2010 where the different available models to calculate usual intake were presented and discussed. This report integrates the workshop background document, the presentations given by experts, and the discussions during the workshop. The purpose of the workshop was to evaluate existing statistical methods for estimating usual intake with respect to a number of criteria, so that the performance of each method on each criterion will be well understood after the workshop. The outcome of the workshop allows choices to be made for a European Tool Usual Intake, to be implemented in the remainder of the project. A starting document was provided to the participants of the workshop with up-to-date information on methods, data and criteria, as a basis for discussion. It was apparent from the workshop that there is not one optimal model for all cases, rather a toolbox approach is suitable. The choice of the most appropriate model has to be fine-tuned case by case. Criteria to be considered are related to data availability and data pre-processing (e.g. compatibility of existing data formats, need to handle complicating factors like food code conversion, left-censored data, processing factors, brand loyalty, pooling over multiple datasets), the appropriateness of modelling assumptions for frequencies and amounts modelling (e.g. level of conservatism, additivity assumption and data transformations, the need to model intake as a function of covariates, correlations), the usefulness to combine survey and food frequency questionnaire data, the need to model single food intake or diet-aggregated intake, the need to evaluate uncertainties, and the usefulness of implementations. For the short term, case studies will be performed based on issues relevant for EFSA panels. Results from the workshop and possibilities of using models to calculate usual intake were recently discussed during the 5th meeting of the EFSA Expert group on food consumption data. Currently only few EU Member States use this kind of models but there is a lot of interest in gaining experience with the usual intake modelling. Several requests were received concerning the possibility of having more information about the ETUI project and even the organisation of a future training. In conclusion, this interim report is considered by EFSA to be a good review of the different models used and presents the main challenges related to the use of these techniques. Its publication could be useful to those who want to start using this kind of methodology
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