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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Oxidative stress and immune aberrancies in attention-deficit/hyperactivity disorder (ADHD): a case–control comparison
Verlaet, Annelies A.J. ; Breynaert, Annelies ; Ceulemans, Berten ; Bruyne, Tess De; Fransen, Erik ; Pieters, Luc ; Savelkoul, Huub F.J. ; Hermans, Nina - \ 2019
European Child & Adolescent Psychiatry 28 (2019)5. - ISSN 1018-8827 - p. 719 - 729.
ADHD - Antioxidants - Diet - Immunity - Oxidative stress

The objective of this study is to compare oxidative stress and immune biomarkers between attention-deficit/hyperactivity disorder (ADHD) patients and controls without ADHD. A case–control comparison between 57 paediatric (6–12 years) untreated ADHD patients from the Antwerp University Hospital and 69 controls without ADHD from random schools in Flanders, Belgium, was conducted. Erythrocyte glutathione (GSH) and plasma lipid-soluble antioxidants (retinol, α-tocopherol, γ-tocopherol, retinyl palmitate, β-carotene, and co-enzyme Q10) were determined by HPLC with electrochemical detection, plasma malondialdehyde (MDA) by HPLC with fluorescence detection, plasma cytokines (interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor (TNF) and interferon (INF)-γ) and immunoglobulins (IgE, IgG and IgM) by flow cytometry and urinary 8-hydroxy-2′deoxyguanosine (8-OHdG) levels by ELISA assay. Dietary habits were determined by a food frequency questionnaire. Plasma MDA levels were on average 0.031 µM higher in patients than in controls (p < 0.05), and a trend for higher urinary 8-OHdG was observed. Erythrocyte GSH and plasma retinyl palmitate levels, as well as IgG and IgE levels, were higher in patients than in controls as well (on average 93.707 µg/ml, 0.006 µg/ml, 301.555 µg/ml and 125.004 µg/ml, resp., p < 0.05). Finally, a trend for lower plasma IL-5 levels was observed. After Bonferroni correction for multiple testing, the difference in GSH levels remained statistically significant (nominally significant for retinyl palmitate), while significance was lost for MDA, IgG and IgE levels. Dietary habits do not appear to cause the observed differences. These results point at the potential involvement of slight oxidative stress and immune disturbances in ADHD.

Ondervoeding bij ouderen staat nog te weinig op het netvlies
Groot, Lisette de - \ 2019
Are the G20 economies making enough progress to meet their NDC targets?
Elzen, Michel den; Kuramochi, Takeshi ; Höhne, Niklas ; Cantzler, Jasmin ; Esmeijer, Kendall ; Fekete, Hanna ; Fransen, Taryn ; Keramidas, Kimon ; Roelfsema, Mark ; Sha, Fu ; Soest, Heleen van; Vandyck, Toon - \ 2019
Energy Policy 126 (2019). - ISSN 0301-4215 - p. 238 - 250.
China - G20 economies - National climate and energy policies - NDCs - Paris Agreement

Under the Paris Agreement, countries committed to a variety of climate actions, including post-2020 greenhouse gas (GHG) emissions reduction targets. This study compares projected GHG emissions in the G20 economies under current climate policies to those under the GHG targets outlined in the nationally determined contributions (NDCs). It is based on an assessment of official governmental estimates and independent national and global studies. The study concludes that six G20 members (China, India, Indonesia, Japan, Russia and Turkey) are projected to meet their unconditional NDC targets with current policies. Eight members (Argentina, Australia, Canada, the European Union, Republic of Korea, South Africa and the United States) require further action to achieve their targets. Insufficient information is available for Saudi Arabia, and emission projections for Brazil and Mexico are subject to considerable uncertainty. The study also presents high-level decarbonisation indicators to better understand the current progress towards meeting the NDCs – Saudi Arabia and South Africa were found to continue increasing both emission intensity per unit GDP and emissions per capita under current policies by 2030 from 2015 levels.

Voluntary Sustainability Standards, Trade and Sustainable Development : 3rd Flagship Report of the United Nations Forum on Sustainability Standards (UNFSS)
Fernandez de Cordoba, Santiago ; Onguglo, Bonapas ; Hoekman, Bernard ; Schleifer, Philip ; Fiorini, Matteo ; Fransen, Luc ; Gjaltema, J.G. - \ 2018
- 74 p.
Aged mice display altered numbers and phenotype of basophils, and bone marrow-derived basophil activation, with a limited role for aging-associated microbiota
Beek, Adriaan A. Van; Fransen, Floris ; Meijer, Ben ; Vos, Paul de; Knol, Edward F. ; Savelkoul, Huub F.J. - \ 2018
Immunity and Ageing 15 (2018)1. - ISSN 1742-4933
Aging - Basophils - Bone marrow - Immunity - Microbiota - Spleen

Background: The influence of age on basophils is poorly understood, as well as the effect of aging-associated microbiota on basophils. Therefore, we studied the influence of aging and aging-associated microbiota on basophil frequency and phenotype, and differentiation from basophil precursors. Results: Basophils became more abundant in bone marrow (BM) and spleens of 19-month-old mice compared with 4-month-old mice. Aged basophils tended to express less CD200R3 and more CD123, both in BM and spleen. Differences in microbiota composition with aging were confirmed by 16S sequencing. Microbiota transfers from young and old mice to germ-free recipients revealed that CD11b tended to be lowered on splenic basophils by aging-associated microbiota. Furthermore, abundance of Alistipes, Oscillibacter, Bacteroidetes RC9 gut group, and S24-7 family positively correlated and CD123 expression, whereas Akkermansia abundance negatively correlated with basophils numbers. Subsequently, we purified FcϵRIα+CD11c-CD117- BM-derived basophils and found that those from aged mice expressed lower levels of CD11b upon stimulation. Higher frequencies of IL-4+ basophils were generated from basophil precursors of aged mice, which could be reproduced in basophils derived from germ-free recipients of aging-associated microbiota. Conclusions: Collectively, these results show the influence of aging on basophils. Furthermore, this study shows that aging-associated microbiota altered activation of BM-derived basophils in a similar fashion as observed in BM-derived basophils from aged mice.

Sex differences in lipid metabolism are affected by presence of the gut microbiota
Baars, Annemarie ; Oosting, Annemarie ; Lohuis, Mirjam ; Koehorst, Martijn ; Aidy, Sahar El; Hugenholtz, Floor ; Smidt, Hauke ; Mischke, Mona ; Boekschoten, Mark V. ; Verkade, Henkjan J. ; Garssen, Johan ; Beek, Eline M. van der; Knol, Jan ; Vos, Paul de; Bergenhenegouwen, Jeroen van; Fransen, Floris - \ 2018
Scientific Reports 8 (2018)1. - ISSN 2045-2322

Physiological processes are differentially regulated between men and women. Sex and gut microbiota have each been demonstrated to regulate host metabolism, but it is unclear whether both factors are interdependent. Here, we determined to what extent sex-specific differences in lipid metabolism are modulated via the gut microbiota. While male and female Conv mice showed predominantly differential expression in gene sets related to lipid metabolism, GF mice showed differences in gene sets linked to gut health and inflammatory responses. This suggests that presence of the gut microbiota is important in sex-specific regulation of lipid metabolism. Further, we explored the role of bile acids as mediators in the cross-talk between the microbiome and host lipid metabolism. Females showed higher total and primary serum bile acids levels, independent of presence of microbiota. However, in presence of microbiota we observed higher secondary serum bile acid levels in females compared to males. Analysis of microbiota composition displayed sex-specific differences in Conv mice. Therefore, our data suggests that bile acids possibly play a role in the crosstalk between the microbiome and sex-specific regulation of lipid metabolism. In conclusion, our data shows that presence of the gut microbiota contributes to sex differences in lipid metabolism.

On a collection of deep-water shrimp (Crustacea, Decapoda) from the Dutch Caribbean, with the description of a new species of Pseudocoutierea
Olthof, Gabriël ; Becking, Leontine E. ; Fransen, Charles H.J.M. - \ 2018
Zootaxa 4415 (2018)3. - ISSN 1175-5326 - p. 533 - 548.
Crustacea - Decapoda - Deep reef - Dutch Caribbean - New records - New species - Pseudocoutierea
A collection of shrimp from deep reefs in the Dutch Caribbean is described. Most material originates from the Bonaire deep reef expedition (2013) by Wageningen Marine Research of Wageningen University. Some additional material was available from dives on Curaçao (2014). A new species of Pseudocoutierea Holthuis was recognized in the material collected off Bonaire. The new species is described and illustrated and its position in the phylogeny of the genus Pseudocoutierea analyzed. A key to the species in the genus is presented.
De Fransen haten hen om hun pulsjes
Kraan, Marloes - \ 2018
β2→1-fructans modulate the immune system in vivo in a microbiota-dependent and -independent fashion
Fransen, Floris ; Sahasrabudhe, Neha M. ; Elderman, Marlies ; Bosveld, M. ; Aidy, Sahar El; Hugenholtz, F. ; Borghuis, Theo ; Kousemaker, Ben ; Winkel, Simon ; Gaast-de Jongh, Christa van der; Jonge, Marien I. de; Boekschoten, M.V. ; Smidt, H. ; Vos, Paul de - \ 2018
Mus musculus - GSE94516 - PRJNA371228
It has been shown in vitro that only specific dietary-fibers contribute to immunity but studies in vivo are not conclusive. Here we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLN), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in Peyer's patches, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b-CD103- DCs in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced Fut2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b-CD103- DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota-independent.
Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice
Fransen, Floris ; Beek, A.A. van; Borghuis, Theo ; Aidy, Sahar El; Hugenholtz, F. ; Gaast-de Jongh, Christa van der; Savelkoul, H.F.J. ; Jonge, Marien I. De; Boekschoten, M.V. ; Smidt, H. ; Faas, Marijke M. ; Vos, Paul de - \ 2018
Mus musculus - GSE104063 - PRJNA408136
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study gut microbiota from young or old conventional mice was transferred to young germ-free mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer’s patches, and mesenteric lymph nodes from conventionalized germ-free mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here we show by transferring aged microbiota to young germ-free mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the germ-free mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young germ-free mice.
Aged gut microbiota contributes to systemical inflammaging after transfer to germ-free mice
Fransen, Floris ; Beek, Adriaan A. van; Borghuis, Theo ; Aidy, Sahar El; Hugenholtz, Floor ; Gaast - de Jongh, Christa van der; Savelkoul, Huub F.J. ; Jonge, Marien I. de; Boekschoten, Mark V. ; Smidt, Hauke ; Faas, Marijke M. ; Vos, Paul de - \ 2017
Frontiers in Immunology 8 (2017). - ISSN 1664-3224
Aging - Germ-free mice - Gut microbiome - Immune system - Inflammaging
Advanced age is associated with chronic low-grade inflammation, which is usually referred to as inflammaging. Elderly are also known to have an altered gut microbiota composition. However, whether inflammaging is a cause or consequence of an altered gut microbiota composition is not clear. In this study, gut microbiota from young or old conventional mice was transferred to young germ-free (GF) mice. Four weeks after gut microbiota transfer immune cell populations in spleen, Peyer's patches, and mesenteric lymph nodes from conventionalized GF mice were analyzed by flow cytometry. In addition, whole-genome gene expression in the ileum was analyzed by microarray. Gut microbiota composition of donor and recipient mice was analyzed with 16S rDNA sequencing. Here, we show by transferring aged microbiota to young GF mice that certain bacterial species within the aged microbiota promote inflammaging. This effect was associated with lower levels of Akkermansia and higher levels of TM7 bacteria and Proteobacteria in the aged microbiota after transfer. The aged microbiota promoted inflammation in the small intestine in the GF mice and enhanced leakage of inflammatory bacterial components into the circulation was observed. Moreover, the aged microbiota promoted increased T cell activation in the systemic compartment. In conclusion, these data indicate that the gut microbiota from old mice contributes to inflammaging after transfer to young GF mice.
The impact of gut microbiota on gender-specific differences in immunity
Fransen, Floris ; Beek, Adriaan A. van; Borghuis, Theo ; Meijer, Ben ; Hugenholtz, Floor ; Gaast-de Jongh, Christa van der; Savelkoul, Huub F. ; Jonge, Marien I. de; Faas, Marijke M. ; Boekschoten, Mark V. ; Smidt, Hauke ; Aidy, Sahar El ; Vos, Paul de - \ 2017
Frontiers in Immunology 8 (2017). - ISSN 1664-3224 - 14 p.
Gender - Germ-free mice - Gut microbiota - Immunity - Inflammation

Males and females are known to have gender-specific differences in their immune system and gut microbiota composition. Whether these differences in gut microbiota composition are a cause or consequence of differences in the immune system is not known. To investigate this issue, gut microbiota from conventional males or females was transferred to germ-free (GF) animals of the same or opposing gender. We demonstrate that microbiota-independent gender differences in immunity are already present in GF mice. In particular, type I interferon signaling was enhanced in the intestine of GF females. Presumably, due to these immune differences bacterial groups, such as Alistipes, Rikenella, and Porphyromonadaceae, known to expand in the absence of innate immune defense mechanism were overrepresented in the male microbiota. The presence of these bacterial groups was associated with induction of weight loss, inflammation, and DNA damage upon transfer of the male microbiota to female GF recipients. In summary, our data suggest that microbiota-independent gender differences in the immune system select a gender-specific gut microbiota composition, which in turn further contributes to gender differences in the immune system.

Gezondheidsmakelaars verbeteren het Gezondheidsbevorderend Systeem van hun wijk of gemeente
Fransen, G.A.J. ; Riet, A. v.d.; Ham, L.T.J. v.d.; Wagemakers, Annemarie ; Molleman, G.R.M. - \ 2017
In: Nederlands Congres Volksgezondheid 2017 - De professional maakt het verschil. -
Achtergrond en doelstelling:
Sinds 2009 zijn er gezondheidsmakelaars werkzaam bij GGD Gelderland-Zuid, iedere gezondheidsmakelaar heeft zijn eigen wijken of gemeenten. Zij hebben als taak om het GezondheidsBevorderend Systeem (GBS) in hun gemeente/wijk te verbeteren, zoals beschreven in ons logisch model (gepresenteerd op NCVGZ 2015). Het doel van dit onderzoek is om een monitoringsinstrument te ontwikkelen voor het meten van het GBS en een eerste meting uit te voeren, zodat we inzicht krijgen in hoe “sterk” het GBS van iedere gemeente/wijk is.

Methode:
8 variabelen zijn benoemd om het GBS te operationaliseren: samenwerking; samenhang; duurzaamheid; integrale aanpak; draagvlak; aanpak gebaseerd op een gezondheidsprofiel; in staat zijn tussentijdse resultaten zichtbaar te maken; bereik einddoelgroep. Vanuit literatuurstudie is gezocht naar valide instrumenten om deze variabelen te meten en te kwantificeren en is een monitoringsinstrument ontwikkeld.
Per gemeente/wijk zijn 8 stakeholders uitgenodigd om de vragenlijst in te vullen: de gezondheidsmakelaar, ambtenaar volksgezondheid, huisarts, wijkverpleegkundige, welzijn, sportservice, fysiotherapeut en adviseur gezonde school. De meting vindt nu plaats in het hele werkgebied van GGD Gelderland-Zuid (16 gemeenten waaronder Nijmegen (8 wijken) en Wijchen (2 wijken)). Naast de vragenlijst vindt er documentanalyse plaats en gesprekken met gezondheidsmakelaar en evt andere stakeholders om de resultaten goed te kunnen duiden en in de context te beoordelen.

Resultaten:
Per gemeente/wijk zal een factsheet gemaakt worden met daarop de scores per variabele (gemiddelde van de 8 stakeholders). De resultaten verwachten wij in februari 2017.

Conclusie en aanbevelingen: Met dit monitoringsinstrument zijn we in staat om de sterke van het GBS te meten, waarmee de gezondheidsmakelaar beter kan bepalen waar het GBS van zijn/haar gemeente versterkt kan worden en hij/zij op zou kunnen inzetten. Daarnaast dragen deze metingen bij aan het zichtbaar maken van de resultaten van de gezondheidsmakelaars.
β2→1-fructans modulate the immune system in vivo in a microbiota-dependent and -independent fashion
Fransen, Floris ; Sahasrabudhe, Neha M. ; Elderman, Marlies ; Bosveld, Margaret ; Aidy, Sahar El; Hugenholtz, Floor ; Borghuis, Theo ; Kousemaker, Ben ; Winkel, Simon ; Gaast-de Jongh, Christa van der; Jonge, Marien I. de; Boekschoten, Mark V. ; Smidt, Hauke ; Schols, Henk A. ; Vos, Paul de - \ 2017
Frontiers in Immunology 8 (2017). - ISSN 1664-3224
Germ-free mice - Gut microbiota - Mucosal immunology - Prebiotics - β2→1-fructans
It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b-CD103- dendritic cells (DCs) in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced 2-alpha-l-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b-CD103- DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota independent.
Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes
Lachmandas, Ekta ; Boutens, Lily ; Ratter, Jacqueline M. ; Hijmans, Anneke ; Hooiveld, Guido J. ; Joosten, Leo A.B. ; Rodenburg, Richard J. ; Fransen, Jack A.M. ; Houtkooper, Riekelt H. ; Crevel, R. van; Netea, Mihai G. ; Stienstra, R. - \ 2016
Nature Microbiology 2 (2016). - ISSN 2058-5276

Microbial stimuli such as lipopolysaccharide (LPS) induce robust metabolic rewiring in immune cells known as the Warburg effect. It is unknown whether this increase in glycolysis and decrease in oxidative phosphorylation (OXPHOS) is a general characteristic of monocytes that have encountered a pathogen. Using CD14+ monocytes from healthy donors, we demonstrated that most microbial stimuli increased glycolysis, but that only stimulation of Toll-like receptor (TLR) 4 with LPS led to a decrease in OXPHOS. Instead, activation of other TLRs, such as TLR2 activation by Pam3CysSK4 (P3C), increased oxygen consumption and mitochondrial enzyme activity. Transcriptome and metabolome analysis of monocytes stimulated with P3C versus LPS confirmed the divergent metabolic responses between both stimuli, and revealed significant differences in the tricarboxylic acid cycle, OXPHOS and lipid metabolism pathways following stimulation of monocytes with P3C versus LPS. At a functional level, pharmacological inhibition of complex I of the mitochondrial electron transport chain diminished cytokine production and phagocytosis in P3C- but not LPS-stimulated monocytes. Thus, unlike LPS, complex microbial stimuli and the TLR2 ligand P3C induce a specific pattern of metabolic rewiring that involves upregulation of both glycolysis and OXPHOS, which enables activation of host defence mechanisms such as cytokine production and phagocytosis.

Paris Agreement climate proposals need a boost to keep warming well below 2 °c
Rogelj, Joeri ; Elzen, Michel Den; Höhne, Niklas ; Fransen, Taryn ; Fekete, Hanna ; Winkler, Harald ; Schaeffer, Roberto ; Sha, Fu ; Riahi, Keywan ; Meinshausen, Malte - \ 2016
Nature 534 (2016)7609. - ISSN 0028-0836 - p. 631 - 639.

The Paris climate agreement aims at holding global warming to well below 2 degrees Celsius and to "pursue efforts" to limit it to 1.5 degrees Celsius. To accomplish this, countries have submitted Intended Nationally Determined Contributions (INDCs) outlining their post-2020 climate action. Here we assess the effect of current INDCs on reducing aggregate greenhouse gas emissions, its implications for achieving the temperature objective of the Paris climate agreement, and potential options for overachievement. The INDCs collectively lower greenhouse gas emissions compared to where current policies stand, but still imply a median warming of 2.6-3.1 degrees Celsius by 2100. More can be achieved, because the agreement stipulates that targets for reducing greenhouse gas emissions are strengthened over time, both in ambition and scope. Substantial enhancement or over-delivery on current INDCs by additional national, sub-national and non-state actions is required to maintain a reasonable chance of meeting the target of keeping warming well below 2 degrees Celsius.

First Complete Genome Sequence of the Dutch Veterinary Coxiella burnetii Strain NL3262, Originating from the Largest Global Q Fever Outbreak, and Draft Genome Sequence of Its Epidemiologically Linked Chronic Human Isolate NLhu3345937
Kuley, R. ; Smith, H.E. ; Janse, I. ; Harders, F.L. ; Baas, F. ; Schijlen, E. ; Nabuurs-Fransen, M.H. ; Smits, M.A. ; Roest, H.I.J. ; Bossers, A. - \ 2016
Genome Announcements 4 (2016)2. - ISSN 2169-8287 - 2 p.
The largest global Q fever outbreak occurred in The Netherlands during 2007 to 2010. Goats and sheep were identified as the major sources of disease. Here, we report the first complete genome sequence of Coxiella burnetii goat outbreak strain NL3262 and that of an epidemiologically linked chronic human strain, both having the outbreak-related CbNL01 multilocus variable-number tandem-repeat analysis (MLVA) genotype
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
Adherence to dietary guidelines and cardiovascular disease risk in the EPIC-NL cohort
Struijk, E.A. ; May, A.M. ; Wezenbeek, N.L.W.J. ; Fransen, H. ; Soedamah-Muthu, S.S. ; Geelen, A. ; Boer, J. ; Schouw, Y.T. van der; Bueno de Mesquita, H.B. ; Beulens, J.W.J. - \ 2014
International Journal of Cardiology 176 (2014)2. - ISSN 0167-5273 - p. 354 - 359.
coronary-heart-disease - major chronic disease - systematic analysis - for-americans - global burden - style diet - 21 regions - women - men - questionnaire
Background Global and national dietary guidelines have been created to lower chronic disease risk. The aim of this study was to assess whether greater adherence to the WHO guidelines (Healthy Diet Indicator (HDI)); the Dutch guidelines for a healthy diet (Dutch Healthy Diet-index (DHD-index)); and the Dietary Approaches to Stop Hypertension (DASH) diet was associated with a lower risk of cardiovascular disease (CVD), coronary heart disease (CHD) or stroke. Methods A prospective cohort study was conducted among 33,671 healthy Dutch men and women aged 20–70 years recruited into the EPIC-NL study during 1993–1997. We used Cox regression adjusted for relevant confounders to estimate the hazard ratios per standard deviation increase in score and 95% confidence intervals (CI) of the associations between the dietary guidelines and CVD, CHD and stroke risk. Results After an average follow-up of 12.2 years, 2752 CVD cases were documented, including 1630 CHD cases and 527 stroke cases. We found no association between the HDI (0.98, 95% CI 0.94; 1.02) or DHD-index (0.96, 95% CI 0.92; 1.00) and CVD incidence. Similar results were found for these guidelines and CHD or stroke incidence. Higher adherence to the DASH diet was significantly associated with a lower CVD (0.92, 95% CI 0.89; 0.96), CHD (0.91, 95% CI 0.86; 0.95), and stroke (0.90, 95% CI 0.82; 0.99) risk. Conclusion The HDI and the DHD-index were not associated with CVD risk, while the DASH diet was significantly associated with a lower risk of developing CVD, CHD and stroke.
The emissions gap report 2013 - A UNEP Synthesis Report
Elzen, M.G.J. den; Fransen, T. ; Rogner, H.H. ; Luderer, G. ; Rogelj, J. ; Schaeffer, R. ; Neufeldt, H. ; Hoehne, N.E. ; Morgan, J. ; Olhoff, A. - \ 2013
Nairobi, Kenya : United Nations Environment Programme - ISBN 9789280733532 - 45
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