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.

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Nutrimetabolomics: An Integrative Action for Metabolomic Analyses in Human Nutritional Studies
Ulaszewska, Marynka M. ; Weinert, Christoph H. ; Trimigno, Alessia ; Portmann, Reto ; Andres Lacueva, Cristina ; Badertscher, René ; Brennan, Lorraine ; Brunius, Carl ; Bub, Achim ; Capozzi, Francesco ; Cialiè Rosso, Marta ; Cordero, Chiara E. ; Daniel, Hannelore ; Durand, Stéphanie ; Egert, Bjoern ; Ferrario, Paola G. ; Feskens, Edith J.M. ; Franceschi, Pietro ; Garcia-Aloy, Mar ; Giacomoni, Franck ; Giesbertz, Pieter ; González-Domínguez, Raúl ; Hanhineva, Kati ; Hemeryck, Lieselot Y. ; Kopka, Joachim ; Kulling, Sabine E. ; Llorach, Rafael ; Manach, Claudine ; Mattivi, Fulvio ; Migné, Carole ; Münger, Linda H. ; Ott, Beate ; Picone, Gianfranco ; Pimentel, Grégory ; Pujos-Guillot, Estelle ; Riccadonna, Samantha ; Rist, Manuela J. ; Rombouts, Caroline ; Rubert, Josep ; Skurk, Thomas ; Sri Harsha, Pedapati S.C. ; Meulebroek, Lieven Van; Vanhaecke, Lynn ; Vázquez-Fresno, Rosa ; Wishart, David ; Vergères, Guy - \ 2018
Molecular Nutrition & Food Research 63 (2018)1. - ISSN 1613-4125
GC–MS - LC–MS - metabolomics - NMR - nutrition
The life sciences are currently being transformed by an unprecedented wave of developments in molecular analysis, which include important advances in instrumental analysis as well as biocomputing. In light of the central role played by metabolism in nutrition, metabolomics is rapidly being established as a key analytical tool in human nutritional studies. Consequently, an increasing number of nutritionists integrate metabolomics into their study designs. Within this dynamic landscape, the potential of nutritional metabolomics (nutrimetabolomics) to be translated into a science, which can impact on health policies, still needs to be realized. A key element to reach this goal is the ability of the research community to join, to collectively make the best use of the potential offered by nutritional metabolomics. This article, therefore, provides a methodological description of nutritional metabolomics that reflects on the state-of-the-art techniques used in the laboratories of the Food Biomarker Alliance (funded by the European Joint Programming Initiative “A Healthy Diet for a Healthy Life” (JPI HDHL)) as well as points of reflections to harmonize this field. It is not intended to be exhaustive but rather to present a pragmatic guidance on metabolomic methodologies, providing readers with useful “tips and tricks” along the analytical workflow.
Characterization of SOC1’s central role in flowering by the identification of its upstream and downstream regulators
Immink, G.H. ; Posé, D. ; Ferrario, S.I.T. ; Ott, F. ; Kaufmann, K. ; Valentim, F.L. ; Folter, S. de; Wal, F. van der; Dijk, A.D.J. van; Schmid, M. ; Angenent, G.C. - \ 2016
Arabidopsis thaliana - GSE45846 - PRJNA196500
The transition from vegetative to reproductive development is one of the most important phase changes in the plant life cycle. This step is controlled by various environmental signals that are integrated at the molecular level by so-called floral integrators. One such floral integrator in Arabidopsis (Arabidopsis thaliana) is the MADS domain transcription factor SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). Despite extensive genetic studies, little is known about the transcriptional control of SOC1, and we are just starting to explore the network of genes under the direct control of SOC1 transcription factor complexes. Here, we show that several MADS domain proteins, including SOC1 heterodimers, are able to bind SOC1 regulatory sequences. Genome-wide target gene analysis by ChIP-seq confirmed the binding of SOC1 to its own locus and shows that it also binds to a plethora of flowering-time regulatory and floral homeotic genes. In turn, the encoded floral homeotic MADS domain proteins appear to bind SOC1 regulatory sequences. Subsequent in planta analyses revealed SOC1 repression by several floral homeotic MADS domain proteins, and we show that, mechanistically, this depends on the presence of the SOC1 protein. Together, our data show that SOC1 constitutes a major hub in the regulatory networks underlying floral timing and flower development and that these networks are composed of many positive and negative autoregulatory and feedback loops. The latter seems to be crucial for the generation of a robust flower-inducing signal, followed shortly after by repression of the SOC1 floral integrator.
Gut microbiota composition and Clostridium difficile infection in hospitalized elderly individuals : A metagenomic study
Milani, Christian ; Ticinesi, Andrea ; Gerritsen, Jacoline ; Nouvenne, Antonio ; Andrea Lugli, Gabriele ; Mancabelli, Leonardo ; Turroni, Francesca ; Duranti, Sabrina ; Mangifesta, Marta ; Viappiani, Alice ; Ferrario, Chiara ; Maggio, Marcello ; Lauretani, Fulvio ; Vos, Willem M. de; Sinderen, Douwe Van; Meschi, Tiziana ; Ventura, Marco - \ 2016
Scientific Reports 6 (2016). - ISSN 2045-2322

The gut microbiota composition of elderly hospitalized patients with Clostridium difficile infection (CDI) exposed to previous antibiotic treatment is still poorly investigated. The aim of this study was to compare the microbiota composition by means of 16S rRNA microbial profiling among three groups of hospitalized elderly patients (age ≥ 65) under standard diet including 25 CDI-positive (CDI group), 29 CDI-negative exposed to antibiotic treatment (AB+ group) and 30 CDI-negative subjects not on antibiotic treatment (ABâ group). The functional properties of the gut microbiomes of CDI-positive vs CDI-negative subjects were also assessed by shotgun metagenomics. A significantly lower microbial diversity was detected in CDI samples, whose microbiomes clustered separately from CDI-negative specimens. CDI was associated with a significant under-representation of gut commensals with putative protective functionalities, including Bacteroides, Alistipes, Lachnospira and Barnesiella, and over-representation of opportunistic pathogens. These findings were confirmed by functional shotgun metagenomics analyses, including an in-depth profiling of the Peptostreptococcaceae family. In CDI-negative patients, antibiotic treatment was associated with significant depletion of few commensals like Alistipes, but not with a reduction in species richness. A better understanding of the correlations between CDI and the microbiota in high-risk elderly subjects may contribute to identify therapeutic targets for CDI.

Characterization of SOC1’s Central Role in Flowering by the Identification of Its Upstream and Downstream Regulators1[C][W]
Immink, R.G.H. ; Posé, D. ; Ferrario, S.I.T. ; Ott, F. ; Kaufmann, K. ; Valentim, F.L. ; Folter, S. de; Wal, F. van der; Dijk, A.D.J. van; Schmid, M. ; Angenent, G.C. - \ 2012
Plant Physiology 160 (2012)1. - ISSN 0032-0889 - p. 433 - 449.
floral organ identity - mads domain proteins - time gene soc1 - arabidopsis-thaliana - transcription factor - homeotic gene - target genes - negative regulator - ectopic expression - meristem identity
The transition from vegetative to reproductive development is one of the most important phase changes in the plant life cycle. This step is controlled by various environmental signals that are integrated at the molecular level by so-called floral integrators. One such floral integrator in Arabidopsis (Arabidopsis thaliana) is the MADS domain transcription factor SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1 (SOC1). Despite extensive genetic studies, little is known about the transcriptional control of SOC1, and we are just starting to explore the network of genes under the direct control of SOC1 transcription factor complexes. Here, we show that several MADS domain proteins, including SOC1 heterodimers, are able to bind SOC1 regulatory sequences. Genome-wide target gene analysis by ChIP-seq confirmed the binding of SOC1 to its own locus and shows that it also binds to a plethora of flowering-time regulatory and floral homeotic genes. In turn, the encoded floral homeotic MADS domain proteins appear to bind SOC1 regulatory sequences. Subsequent in planta analyses revealed SOC1 repression by several floral homeotic MADS domain proteins, and we show that, mechanistically, this depends on the presence of the SOC1 protein. Together, our data show that SOC1 constitutes a major hub in the regulatory networks underlying floral timing and flower development and that these networks are composed of many positive and negative autoregulatory and feedback loops. The latter seems to be crucial for the generation of a robust flower-inducing signal, followed shortly after by repression of the SOC1 floral integrator.
Control of floral meristem determinancy in petunia by MADS box transcription factors
Ferrario, S.I.T. ; Shchennikova, A.V. ; Franken, J. ; Immink, R.G.H. ; Angenent, G.C. - \ 2006
Plant Physiology 140 (2006)3. - ISSN 0032-0889 - p. 890 - 898.
arabidopsis shoot meristem - stem-cell fate - ovule development - homeotic gene - identity - organ - wuschel - maintenance - deficiens - family
The shoot apical meristem (SAM), a small group of undifferentiated dividing cells, is responsible for the continuous growth of plants. Several genes have been identified that control the development and maintenance of the SAM. Among these, WUSCHEL (WUS) from Arabidopsis (Arabidopsis thaliana) is thought to be required for maintenance of a stem cell pool in the SAM. The MADS-box gene AGAMOUS, in combination with an unknown factor, has been proposed as a possible negative regulator of WUS, leading to the termination of meristematic activity within the floral meristem. Transgenic petunia (Petunia hybrida) plants were produced in which the E-type and D-type MADS-box genes FLORAL BINDING PROTEIN2 (FBP2) and FBP11, respectively, are simultaneously overexpressed. These plants show an early arrest in development at the cotyledon stage. Molecular analysis of these transgenic plants revealed a possible combined action of FBP2 and FBP11 in repressing the petunia WUS homolog, TERMINATOR. Furthermore, the ectopic up-regulation of the C-type and D-type homeotic genes FBP6 and FBP7, respectively, suggests that they may also participate in a complex, which causes the determinacy in transgenic plants. These data support the model that a transcription factor complex consisting of C-, D-, and E-type MADS-box proteins controls the stem cell population in the floral meristem
Functional characterization of MADS box transcription factors in Petunia hybrida
Ferrario, S.I.T. - \ 2004
Radboud University Nijmegen. Promotor(en): Gerco Angenent. - Radboud Universiteit Nijmegen : - ISBN 9064649154 - 190
petunia hybrida - transcriptiefactoren - moleculaire genetica - genen - plantenontwikkeling - bloemen - transcription factors - molecular genetics - genes - plant development - flowers
Ectopic expression of the Petunia MADS box gene UNSHAVEN accelerates flowering and confers leaf-like characteristics to floral organs in a dominant-negative manner
Ferrario, S.I.T. ; Busscher-Lange, J. ; Franken, J. ; Gerts, T. ; Vandenbussche, M. ; Angenent, G.C. ; Immink, R.G.H. - \ 2004
The Plant Cell 16 (2004). - ISSN 1040-4651 - p. 1490 - 1505.
serum response factor - transcription factor family - arabidopsis-thaliana - nuclear-localization - locus-c - molecular characterization - reproductive development - domain protein - sinapis-alba - vernalization
Several genes belonging to the MADS box transcription factor family have been shown to be involved in the transition from vegetative to reproductive growth. The Petunia hybrida MADS box gene UNSHAVEN (UNS) shares sequence similarity with the Arabidopsis thaliana flowering gene SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1, is expressed in vegetative tissues, and is downregulated upon floral initiation and the formation of floral meristems. To understand the role of UNS in the flowering process, knockout mutants were identified and UNS was expressed ectopically in petunia and Arabidopsis. No phenotype was observed in petunia plants in which UNS was disrupted by transposon insertion, indicating that its function is redundant. Constitutive expression of UNS leads to an acceleration of flowering and to the unshaven floral phenotype, which is characterized by ectopic trichome formation on floral organs and conversion of petals into organs with leaf-like features. The same floral phenotype, accompanied by a delay in flowering, was obtained when a truncated version of UNS, lacking the MADS box domain, was introduced. We demonstrated that the truncated protein is not translocated to the nucleus. Using the overexpression approach with both the full-length and the nonfunctional truncated UNS protein, we could distinguish between phenotypic alterations because of a dominant-negative action of the protein and because of its native function in promoting floral transition
The Petunia ortholog of Arabidopsis SUPERMAN plays a distinct role in floral morphogenesis
Nakagawa, H. ; Ferrario, S.I.T. ; Angenent, G.C. ; Kobayashi, A. ; Takatsuji, H. - \ 2004
The Plant Cell 16 (2004). - ISSN 1040-4651 - p. 920 - 932.
mads box - ectopic expression - homeotic genes - cell-proliferation - transgenic petunia - flower development - meristem - protein - identity - domain
Arabidopsis (Arabidopsis thaliana) SUPERMAN (SUP) plays a role in establishing a boundary between whorls 3 and 4 of flowers and in ovule development. We characterized a Petunia hybrida (petunia) homolog of SUP, designated PhSUP1, to compare with SUP. Genomic DNA of the PhSUP1 partially restored the stamen number and ovule development phenotypes of the Arabidopsis sup mutant. Two P. hybrida lines of transposon (dTph1) insertion mutants of PhSUP1 exhibited increased stamen number at the cost of normal carpel development, and ovule development was defective owing to aberrant growth of the integument. Unlike Arabidopsis sup mutants, phsup1 mutants also showed extra tissues connecting stamens, a petal tube and an ovary, and aberrancies in the development of anther and placenta. PhSUP1 transcripts occurred in the basal region of wild-type flowers around developing organ primordia in whorls 2 and 3 as well as in the funiculus of the ovule, concave regions of the placenta, and interthecal regions of developing anthers. Overexpression of PhSUP1 in P. hybrida resulted in size reduction of petals, leaves, and inflorescence stems. The shortening of inflorescence stems and petal tubes was primarily attributable to suppression of cell elongation, whereas a decrease in cell number was mainly responsible for the size reduction of petal limbs.
Conservation and diversity in flower land
Ferrario, S.I.T. ; Immink, R.G.H. ; Angenent, G.C. - \ 2004
Current Opinion in Plant Biology 7 (2004)1. - ISSN 1369-5266 - p. 84 - 91.
mads-box genes - floral organ identity - protein-protein interactions - transcription factor family - arabidopsis-thaliana - ovule development - homeotic proteins - draft sequence - class-b - petunia
During the past decade, enormous progress has been made in understanding the molecular regulation of flower development. In particular, homeotic genes that determine the identity of the floral organs have been characterised from different flowering plants, revealing considerable conservation among angiosperm species. On the other hand, evolutionary diversification has led to enormous variation in flower morphology. Increasing numbers of reports have described differences in the regulation, redundancy and function of homeotic genes from various species. These fundamentals of floral organ specification are therefore an ideal subject for comparative analyses of flower development, which will lead to a better understanding of plant evolution, plant development and the complexity of molecular mechanisms that control flower development and morphology.
Toward the analysis of the Petunia MADS box gene family by reverse and forward transposon insertion mutagenesis approaches: B, C, and D Floral organ identity functions require SEPALLATA-Like MADS box genes in Petunia
Vandenbussche, M. ; Zethof, J. ; Souer, E. ; Koes, R. ; Tornielli, G.B. ; Pezzotti, M. ; Ferrario, S.I.T. ; Angenent, G.C. ; Gerats, T. - \ 2003
The Plant Cell 15 (2003). - ISSN 1040-4651 - p. 2680 - 2693.
protein-protein interactions - transcription factor family - flower development - antirrhinum-majus - meristem identity - ovule development - seed development - homeotic genes - arabidopsis - plants
We have initiated a systematic functional analysis of the MADS box, intervening region, K domain, C domain-type MADS box gene family in petunia. The starting point for this has been a reverse-genetics approach, aiming to select for transposon insertions into any MADS box gene. We have developed and applied a family signature insertion screening protocol that is highly suited for this purpose, resulting in the isolation of 32 insertion mutants in 20 different MADS box genes. In addition, we identified three more MADS box gene insertion mutants using a candidate-gene approach. The defined insertion lines provide a sound foundation for a systematic functional analysis of the MADS box gene family in petunia. Here, we focus on the analysis of Floral Binding Protein2 (FBP2) and FBP5 genes that encode the E-function, which in Arabidopsis has been shown to be required for B and C floral organ identity functions. fbp2 mutants display sepaloid petals and ectopic inflorescences originating from the third floral whorl, whereas fbp5 mutants appear as wild type. In fbp2 fbp5 double mutants, reversion of floral organs to leaf-like organs is increased further. Strikingly, ovules are replaced by leaf-like structures in the carpel, indicating that in addition to the B- and C-functions, the D-function, which specifies ovule development, requires E-function activity. Finally, we compare our data with results obtained using cosuppression approaches and conclude that the latter might be less suited for assigning functions to individual members of the MADS box gene family
The MADS Box Gene FBP2 Is Required for SEPALLATA Function in Petunia
Ferrario, S.I.T. ; Immink, R.G.H. ; Shchennikova, A. ; Busscher-Lange, J. ; Angenent, G.C. - \ 2003
The Plant Cell 15 (2003). - ISSN 1040-4651 - p. 914 - 925.
floral-organ identity - controlling flower development - protein-protein interactions - homeotic gene - antirrhinum-majus - gerbera-hybrida - wild-type - arabidopsis - transcription - expression
The ABC model, which was accepted for almost a decade as a paradigm for flower development in angiosperms, has been subjected recently to a significant modification with the introduction of the new class of E-function genes. This function is required for the proper action of the B- and C-class homeotic proteins and is provided in Arabidopsis by the SEPALLATA1/2/3 MADS box transcription factors. A triple mutant in these partially redundant genes displays homeotic conversion of petals, stamens, and carpels into sepaloid organs and loss of determinacy in the center of the flower. A similar phenotype was obtained by cosuppression of the MADS box gene FBP2 in petunia. Here, we provide evidence that this phenotype is caused by the downregulation of both FBP2 and the paralog FBP5. Functional complementation of the sepallata mutant by FBP2 and our finding that the FBP2 protein forms multimeric complexes with other floral homeotic MADS box proteins indicate that FBP2 represents the same E function as SEP3 in Arabidopsis.
Analysis of the petunia MADS-box transcription factor family
Immink, R.G.H. ; Ferrario, S.I.T. ; Busscher-Lange, J. ; Kooiker, M. ; Busscher, M. ; Angenent, G.C. - \ 2003
Molecular Genetics and Genomics 268 (2003). - ISSN 1617-4615 - p. 598 - 606.
protein-protein interactions - floral organ identity - controlling flower development - ternary complex-formation - homeotic gene - antirrhinum-majus - reproductive development - ovule development - dna-binding - arabidopsis
Transcription factors are key regulators of plant development. One of the major groups of transcription factors is the MADS-box family, of which at least 80 members are encoded in the Arabidopsis genome. In this study, 23 members of the petunia MADS-box transcription factor family were investigated by Northern hybridisation, phylogenetic and yeast two-hybrid analyses. Many of the genes characterised appeared to have one or more close relatives that shared similar expression patterns. Comparison of the binding interactions of these proteins revealed that some show similar interaction patterns, and hence are likely to be functionally redundant. From an evolutionary point of view, their coding genes are probably derived from a recent duplication event. Furthermore, protein-protein interaction patterns, in combination with expression patterns and phylogenetic classification, appear to offer good criteria for the identification of functional homologues. Based on comparison of such data between petunia and Arabidopsis, functions can be predicted for several MADS-box transcription factors in both species.
Analysis of MADS box protein-protein interactions in living plant cells
Immink, R.G.H. ; Gadella, T.W.J. ; Ferrario, S.I.T. ; Busscher, M. ; Angenent, G.C. - \ 2002
Proceedings of the National Academy of Sciences of the United States of America 99 (2002). - ISSN 0027-8424 - p. 2416 - 2421.
Over the last decade, the yeast two-hybrid system has become the tool to use for the identification of protein-protein interactions and recently, even complete interactomes were elucidated by this method. Nevertheless, it is an artificial system that is sensitive to errors resulting in the identification of false-positive and false-negative interactions. In this study, plant MADS box transcription factor interactions identified by yeast two-hybrid systems where studied in living plant cells by a technique based on fluorescence resonance energy transfer (FRET). Petunia MADS box proteins were fused to either cyan fluorescent protein or yellow fluorescent protein and transiently expressed in protoplasts followed by FRET-spectral imaging microscopy and FRET-fluorescence lifetime imaging microscopy to detect FRET and hence protein-protein interactions. All petunia MADS box heterodimers identified in yeast were confirmed in protoplasts. However, in contrast to the yeast two-hybrid results, homodimerization was demonstrated in plant cells for three petunia MADS box proteins. Heterodimers were identified between the ovule-specific MADS box protein FLORAL BINDING PROTEIN 11 and members of the petunia FLORAL BINDING PROTEIN 2 subfamily, which are also expressed in ovules, suggesting that these dimers play a role in ovule development. Furthermore, the role of dimerization in translocation of MADS box protein dimers to the nucleus is demonstrated, and the nuclear localization signal of MADS box proteins has been mapped to the N-terminal region of the MADS domain by means of mutant analyses.
A petunia MADS box gene involved in the transition from vegetative to reproductive development
Immink, R.G.H. ; Hannapel, D.J. ; Ferrario, S. ; Busscher, M. ; Franken, J. ; Lookeren Campagne, M.M. ; Angenent, G.C. - \ 1999
Development 126 (1999)22. - ISSN 0950-1991 - p. 5117 - 5126.
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