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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    Estimating the impact of clinical mastitis in dairy cows on greenhouse gas emissions using a dynamic stochastic simulation model: A case study
    Mostert, P.F. ; Bokkers, E.A.M. ; Boer, I.J.M. De; Middelaar, C.E. Van - \ 2019
    Animal 13 (2019)12. - ISSN 1751-7311 - p. 2913 - 2921.
    carbon footprint - disease - environmental impact - health - modeling

    The increasing attention for global warming is likely to contribute to the introduction of policies or other incentives to reduce greenhouse gas (GHG) emissions related to livestock production, including dairy. The dairy sector is an important contributor to GHG emissions. Clinical mastitis (CM), an intramammary infection, results in reduced milk production and fertility, increases culling and mortality of cows and, therefore, has a negative impact on the efficiency (output/input) of milk production. This may increase GHG emissions per unit of product. Our objective was to estimate the impact of CM in dairy cows on GHG emissions of milk production for the Dutch situation. A dynamic stochastic simulation model was developed to simulate the dynamics and losses of CM for individual lactations. Cows receive a parity (1 to 5+), a milk production and a calving interval (CI). Based on the parity, cows have a risk of CM, with a maximum of three cases in a lactation. Pathogens causing CM were classified as gram-positive bacteria, gram-negative bacteria, or other. Based on the parity and pathogen combinations, cows had a reduced milk production, discarded milk, prolonged CI and a risk of removal (culling and mortality) that reduce productivity of dairy cows and therefore increase GHG emissions per unit of product. Using life cycle assessment, emissions of GHGs were estimated from cradle to farm gate for processes along the milk production chain that are affected by CM. Processes included were feed production, enteric fermentation, and manure management. Emissions of GHGs were expressed as kg CO2 equivalents per ton of fat-and-protein-corrected milk (kg CO2e/t FPCM). Emissions of cows with CM increased on average by 57.5 (6.2%) kg CO2e/t FPCM compared with cows without CM. This increase was caused by removal (39%), discarded milk (38%), reduced milk production (17%) and prolonged CI (6%). The GHG emissions increased by 48 kg CO2e/t FPCM for cows with one case of CM, by 69 kg CO2e/t FPCM for cows with two cases of CM and by 92 kg CO2e/t FPCM for cows with three cases of CM compared with cows without CM. Preventing CM can be an effective strategy for farmers to reduce GHG emissions and can contribute to sustainable development of the dairy sector, because this also can improve the income of farmers and the welfare of cows. The impact of CM on GHG emissions, however, will vary between farms due to environmental conditions and management practices.

    Estimating the economic impact of subclinical ketosis in dairy cattle using a dynamic stochastic simulation model
    Mostert, P.F. ; Bokkers, E.A.M. ; Middelaar, C.E. van; Hogeveen, H. ; Boer, I.J.M. de - \ 2018
    Animal 12 (2018)1. - ISSN 1751-7311 - p. 145 - 154.
    cost - dairy cow - disease - modelling - parity

    The objective of this study was to estimate the economic impact of subclinical ketosis (SCK) in dairy cows. This metabolic disorder occurs in the period around calving and is associated with an increased risk of other diseases. Therefore, SCK affects farm productivity and profitability. Estimating the economic impact of SCK may make farmers more aware of this problem, and can improve their decision-making regarding interventions to reduce SCK. We developed a dynamic stochastic simulation model that enables estimating the economic impact of SCK and related diseases (i.e. mastitis, metritis, displaced abomasum, lameness and clinical ketosis) occurring during the first 30 days after calving. This model, which was applied to a typical Dutch dairy herd, groups cows according to their parity (1 to 5+), and simulates the dynamics of SCK and related diseases, and milk production per cow during one lactation. The economic impact of SCK and related diseases resulted from a reduced milk production, discarded milk, treatment costs, costs from a prolonged calving interval and removal (culling or dying) of cows. The total costs of SCK were €130 per case per year, with a range between €39 and €348 (5 to 95 percentiles). The total costs of SCK per case per year, moreover, increased from €83 per year in parity 1 to €175 in parity 3. Most cows with SCK, however, had SCK only (61%), and costs were €58 per case per year. Total costs of SCK per case per year resulted for 36% from a prolonged calving interval, 24% from reduced milk production, 19% from treatment, 14% from discarded milk and 6% from removal. Results of the sensitivity analysis showed that the disease incidence, removal risk, relations of SCK with other diseases and prices of milk resulted in a high variation of costs of SCK. The costs of SCK, therefore, might differ per farm because of farm-specific circumstances. Improving data collection on the incidence of SCK and related diseases, and on consequences of diseases can further improve economic estimations.

    Olfaction: An Overlooked Sensory Modality in Applied Ethology and Animal Welfare
    Nielsen, B.L. ; Jezierski, T. ; Bolhuis, J.E. ; Amo, L. ; Rosell, F. ; Oostindjer, M. ; Christensen, J.W. ; Mckeegan, D. ; Wells, D.L. ; Hepper, P. - \ 2015
    Frontiers in Veterinary Science 2 (2015)69. - ISSN 2297-1769
    odors - chemoreception - behavior - feeding - stress - housing - reproduction - disease
    Allostasis and Resilience of the Human Individual Metabolic Phenotype
    Ghini, V. ; Saccenti, E. ; Tenori, L. ; Assfalg, M. ; Luchinat, C. - \ 2015
    Journal of Proteome Research 14 (2015)7. - ISSN 1535-3893 - p. 2951 - 2962.
    nmr metabolomics - gut microbiota - health - stress - biomarkers - nutrition - disease - urine - load - discovery
    The urine metabotype of 12 individuals was followed over a period of 8-10 years, which provided the longest longitudinal study of metabolic phenotypes to date. More than 2000 NMR metabolic profiles were analyzed. The majority of subjects have a stable metabotype. Subjects who were exposed to important pathophysiological stressful conditions had a significant metabotype drift. When the stress conditions ceased, the original metabotypes were regained, while an irreversible stressful condition resulted in a permanent metabotype change. These results suggest that each individual occupies a well-defined region in the broad metabolic space, within which a limited degree of allostasis is permitted. The insurgence of significant stressful conditions causes a shift of the metabotype to another distinct region. The spontaneous return to the original metabolic region when the stressful conditions are removed suggests that the original metabotype has some degree of resilience. In this picture, precision medicine should aim at reinforcing the patient's metabolic resilience, that is, his or her ability to revert to his or her specific metabotype rather than to a generic healthy one
    Network-based integration of molecular and physiological data elucidates regulatory mechanisms underlying adaptation to high-fat diet
    Derous, D. ; Kelder, T. ; Schothorst, E.M. van; Erk, M. van; Voigt, A. ; Klaus, S. ; Keijer, J. ; Radonjic, M. - \ 2015
    Genes & Nutrition 10 (2015)4. - ISSN 1555-8932
    obesity - disease - expression - receptor
    Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing different aspects of health. Previously, we have reported physiological and gene expression changes associated with adaptation of murine epididymal white adipose tissue (eWAT) to 5 days and 12 weeks of high-fat diet (HFD) and low-fat diet feeding (Voigt et al. in Mol Nutr Food Res 57:1423–1434, 2013. doi:10.1002/mnfr.201200671). In the current study, we apply network analysis on this dataset to comprehensively characterize mechanisms driving the short- and long-term adaptation of eWAT to HFD across multiple levels of complexity. We built a three-layered interaction network comprising enriched biological processes, their transcriptional regulators and associated changes in physiological parameters. The multi-layered network model reveals that early eWAT adaptation to HFD feeding involves major changes at a molecular level, including activation of TGF-ß signalling pathway, immune and stress response and downregulation of mitochondrial functioning. Upon prolonged HFD intake, initial transcriptional response tails off, mitochondrial functioning is even further diminished, and in turn the relation between eWAT gene expression and physiological changes becomes more prominent. In particular, eWAT weight and total energy intake negatively correlate with cellular respiration process, revealing mitochondrial dysfunction as a hallmark of late eWAT adaptation to HFD. Apart from global understanding of the time-resolved adaptation to HFD, the multi-layered network model allows several novel mechanistic hypotheses to emerge: (1) early activation of TGF-ß signalling as a trigger for structural and morphological changes in mitochondrial organization in eWAT, (2) modulation of cellular respiration as an intervention strategy to effectively deal with excess dietary fat and (3) discovery of putative intervention targets, such those in pathways related to appetite control. In conclusion, the generated network model comprehensively characterizes eWAT adaptation to high-fat diet, spanning from global aspects to mechanistic details. Being open to further exploration by the research community, it provides a resource of health-relevant interactions ready to be used in a broad range of research applications.
    West Nile Virus: High Transmission Rate in North-Western European Mosquitoes Indicates Its Epidemic Potential and Warrants Increased Surveillance
    Fros, J.J. ; Geertsema, C. ; Vogels, C.B.F. ; Roosjen, P.P.J. ; Failloux, A.B. ; Vlak, J.M. ; Koenraadt, C.J.M. ; Takken, W. ; Pijlman, G.P. - \ 2015
    PLoS Neglected Tropical Diseases 9 (2015)7. - ISSN 1935-2727
    united-states - differential virulence - experimental-infection - vector competence - lineage 1 - outbreak - circulation - strains - disease - encephalitis
    West Nile virus (WNV) is on the rise in Europe, with increasing numbers of human cases of neurological disease and death since 2010. However, it is currently unknown whether or not WNV will continue to spread to north-western Europe (NWE), in a fashion similar to the WNV epidemic sweep in the United States (1999–2004). The presence of competent mosquitoes is a strict requirement for WNV transmission, but no laboratory studies have been conducted with the new European lineage 2 WNV outbreak strain. Our study is the first to investigate transmissibility in NWE Culex pipiens for lineage 2 WNV in a systematic, direct comparison with North American Culex pipiens and with the lineage 1 WNV strain. We demonstrate that European mosquitoes are highly competent for both WNV lineages, which underscores the epidemic potential ofWNV in Europe. However, the transmission rate for lineage 2 WNV was significantly lower in North American mosquitoes, which indicates different risk levels between both continents for lineage 2 but not lineage 1 WNV. Based on our result, we propose that WNV surveillance in mosquitoes and birds must be intensified in Europe to allow early detection, timely intervention strategies and prevent outbreaks of WNV neurological disease.
    Genetic and Non-Genetic Inheritance of Natural Antibodies Binding Keyhole Limpet Hemocyanin in a Purebred Layer Chicken Line
    Berghof, T.V.L. ; Klein, S.A.S. van der; Arts, J.A.J. ; Parmentier, H.K. ; Poel, J.J. van der; Bovenhuis, H. - \ 2015
    PLoS ONE 10 (2015)6. - ISSN 1932-6203 - 13 p.
    laying hens - immune-responses - parameters - iga - survival - isotypes - associations - sensitivity - disease - cells
    Natural antibodies (NAb) are defined as antibodies present in individuals without known antigenic challenge. Levels of NAb binding keyhole limpet hemocyanin (KLH) in chickens were earlier shown to be heritable, and to be associated with survival. Selective breeding may thus provide a strategy to improve natural disease resistance. We phenotyped 3,689 white purebred laying chickens for KLH binding NAb of different isotypes around 16 weeks of age. Heritabilities of 0.12 for the titers of total antibodies (IgT), 0.14 for IgM, 0.10 for IgA, and 0.07 for IgG were estimated. We also estimated high, positive genetic, and moderate to high, positive phenotypic correlations of IgT, IgM, IgA, and IgG, suggesting that selective breeding for NAb can be done on all antibody isotypes simultaneously. In addition, a relatively substantial non-genetic maternal environmental effect of 0.06 was detected for IgM, which may reflect a transgenerational effect. This suggests that not only the genes of the mother, but also the maternal environment affects the immune system of the offspring. Breaking strength and early eggshell whiteness of the mother’s eggs were predictive for IgM levels in the offspring, and partly explained the observed maternal environmental effects. The present results confirm that NAb are heritable, however maternal effects should be taken into account.
    High urinary homoarginine excretion is associated with low rates of all-cause mortality and graft failure in renal transplant recipients
    Tsikas, D. ; Frenay, A.S. ; Kayacelebi, A.A. ; Beckmann, B. ; Soedamah-Muthu, S.S. ; Borst, M.H. de; Berg, E. van den; Bakker, S.J.L. - \ 2015
    Amino Acids 47 (2015)9. - ISSN 0939-4451 - p. 1827 - 1836.
    glomerular-filtration-rate - nitric-oxide synthase - cardiovascular risk - heart-failure - substrate-specificity - blood-pressure - l-arginine - disease - serum - dysfunction
    Renal transplant recipients (RTR) have an increased cardiovascular risk profile. Low levels of circulating homoarginine (hArg) are a novel risk factor for mortality and the progression of atherosclerosis. The kidney is known as a major source of hArg, suggesting that urinary excretion of hArg (UhArg) might be associated with mortality and graft failure in RTR. hArg was quantified by mass spectrometry in 24-h urine samples of 704 RTR (functioning graft =1 year) and 103 healthy subjects. UhArg determinants were identified with multivariable linear regression models. Associations of UhArg with all-cause mortality and graft failure were assessed using multivariable Cox regression analyses. UhArg excretion was significantly lower in RTR compared to healthy controls [1.62 (1.09–2.61) vs. 2.46 (1.65–4.06) µmol/24 h, P <0.001]. In multivariable linear regression models, body surface area, diastolic blood pressure, eGFR, pre-emptive transplantation, serum albumin, albuminuria, urinary excretion of urea and uric acid and use of sirolimus were positively associated with UhArg, while donor age and serum phosphate were inversely associated (model R 2 = 0.43). During follow-up for 3.1 (2.7–3.9) years, 83 (12 %) patients died and 45 (7 %) developed graft failure. UhArg was inversely associated with all-cause mortality [hazard risk (HR) 0.52 (95 % CI 0.40–0.66), P <0.001] and graft failure [HR 0.58 (0.42–0.81), P = 0.001]. These associations remained independent of potential confounders. High UhArg levels are associated with reduced all-cause mortality and graft failure in RTR. Kidney-derived hArg is likely to be of particular importance for proper maintenance of cardiovascular and renal systems.
    Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study
    Gichohi-Wainaina, W.N. ; Boonstra, A. ; Feskens, E.J.M. ; Demir, A.Y. ; Veenemans, J. ; Verhoef, H. - \ 2015
    Malaria Journal 14 (2015). - ISSN 1475-2875 - 11 p.
    plasmodium-falciparum malaria - tnf-alpha promoter - cerebral malaria - linkage disequilibrium - rheumatoid-arthritis - diabetes-mellitus - polymorphisms - gene - disease - hla
    Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. Methods Data from a placebo-controlled trial in which 612 Tanzanian children aged 6–60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature =37.5°C or whole blood C-reactive protein concentration =8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. Results Genotyping of 94.9% (581/612) children for TNF-1031 (TNF-1031 T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF-308 G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF-1031 CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01¿1.97] and 1.31 [0.97¿1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF-308 AA genotype (corresponding HR: 0.13 [0.02¿0.63] and 0.16 [0.04¿0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF-1031 and TNF-308 affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed.
    The perceived impact of the National Health Service on personalised nutrition service delivery among the UK public
    Fallaize, R. ; Macready, A.L. ; Butler, L.T. ; Ellis, J.A. ; Berezowska, A. ; Fischer, A.R.H. ; Walsh, M.C. ; Gallagher, C. ; Stewart-Knox, B.J. ; Kuznesof, S. ; Frewer, L.J. ; Gibney, M.J. ; Lovegrove, J.A. - \ 2015
    The British journal of nutrition 113 (2015)8. - ISSN 0007-1145 - p. 1271 - 1279.
    nutrigenomics - communication - disease - information - consumer - medicine - intervention - acceptance - knowledge - attitudes
    Personalised nutrition (PN) has the potential to reduce disease risk and optimise health and performance. Although previous research has shown good acceptance of the concept of PN in the UK, preferences regarding the delivery of a PN service (e.g. online v. face-to-face) are not fully understood. It is anticipated that the presence of a free at point of delivery healthcare system, the National Health Service (NHS), in the UK may have an impact on end-user preferences for deliverances. To determine this, supplementary analysis of qualitative data obtained from focus group discussions on PN service delivery, collected as part of the Food4Me project in the UK and Ireland, was undertaken. Irish data provided comparative analysis of a healthcare system that is not provided free of charge at the point of delivery to the entire population. Analyses were conducted using the ‘framework approach’ described by Rabiee (Focus-group interview and data analysis. Proc Nutr Soc 63, 655-660). There was a preference for services to be led by the government and delivered face-to-face, which was perceived to increase trust and transparency, and add value. Both countries associated paying for nutritional advice with increased commitment and motivation to follow guidelines. Contrary to Ireland, however, and despite the perceived benefit of paying, UK discussants still expected PN services to be delivered free of charge by the NHS. Consideration of this unique challenge of free healthcare that is embedded in the NHS culture will be crucial when introducing PN to the UK.
    Ten-Year Blood Pressure Trajectories, Cardiovascular Mortality, and Life Years Lost in 2 Extinction Cohorts: the Minnesota Business and Professional Men Study and the Zutphen Study
    Tielemans, S.M.A.J. ; Geleijnse, J.M. ; Menotti, A. ; Boshuizen, H.C. ; Soedamah-Muthu, S.S. ; Jacobs, D.R. ; Blackburn, H. ; Kromhout, D. - \ 2015
    Journal of the American Heart Association 4 (2015). - ISSN 2047-9980 - 12 p.
    follow-up - disease - risk - age - adulthood
    Background Blood pressure (BP) trajectories derived from measurements repeated over years have low measurement error and may improve cardiovascular disease prediction compared to single, average, and usual BP (single BP adjusted for regression dilution). We characterized 10-year BP trajectories and examined their association with cardiovascular mortality, all-cause mortality, and life years lost. Methods and Results Data from 2 prospective and nearly extinct cohorts of middle-aged men—the Minnesota Business and Professional Men Study (n=261) and the Zutphen Study (n=632)—were used. BP was measured annually during 1947–1957 in Minnesota and 1960–1970 in Zutphen. BP trajectories were identified by latent mixture modeling. Cox proportional hazards and linear regression models examined BP trajectories with cardiovascular mortality, all-cause mortality, and life years lost. Associations were adjusted for age, serum cholesterol, smoking, and diabetes mellitus. Mean initial age was about 50 years in both cohorts. After 10 years of BP measurements, men were followed until death on average 20 years later. All Minnesota men and 98% of Zutphen men died. Four BP trajectories were identified, in which mean systolic BP increased by 5 to 49 mm Hg in Minnesota and 5 to 20 mm Hg in Zutphen between age 50 and 60. The third systolic BP trajectories were associated with 2 to 4 times higher cardiovascular mortality risk, 2 times higher all-cause mortality risk, and 4 to 8 life years lost, compared to the first trajectory. Conclusions Ten-year BP trajectories were the strongest predictors, among different BP measures, of cardiovascular mortality, all-cause mortality, and life years lost in Minnesota. However, average BP was the strongest predictor in Zutphen.
    Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium
    Mons, U. ; Müezzinler, A. ; Gellert, C. ; Schöttker, B. ; Abnet, C.C. ; Bobak, M. ; Groot, C.P.G.M. de; Freedman, N.D. ; Jansen, E. ; Kee, F. ; Kromhout, D. ; Kuulasmaa, K. ; Laatikainen, T. - \ 2015
    BMJ: British Medical Journal 350 (2015). - ISSN 0959-8138 - 12 p.
    rate advancement periods - myocardial-infarction - cigarette-smoking - united-states - risk-factors - health - disease - population - stroke - women
    Objective - To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures. Design - Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis. Results - Overall, 503¿905 participants aged 60 and older were included in this study, of whom 37¿952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar. Conclusions - Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.
    Long-lasting effects of Early-life Antibiotic Treatment and routine Animal Handling on Gut Microbiota Composition and Immune System in Pigs
    Schokker, D. ; Zhang, J. ; Vastenhouw, S.A. ; Heilig, G.H.J. ; Smidt, H. ; Rebel, J.M.J. ; Smits, M.A. - \ 2015
    PLoS ONE 10 (2015)2. - ISSN 1932-6203
    large gene lists - intestinal microbiota - bacterial - extraction - expression - disease - health - asthma - young - diet
    Background In intensive pig husbandry systems, antibiotics are frequently administrated during early life stages to prevent respiratory and gastro-intestinal tract infections, often in combination with stressful handlings. The immediate effects of these treatments on microbial colonization and immune development have been described recently. Here we studied whether the early life administration of antibiotics has long-lasting effects on the pig’s intestinal microbial community and on gut functionality. Methodology/Principal Findings To investigate the long-lasting effect of early-life treatment, piglets were divided into three different groups receiving the following treatments: 1) no antibiotics and no stress, 2) antibiotics and no stress, and 3) antibiotics and stress. All treatments were applied at day four after birth. Sampling of jejunal content for community scale microbiota analysis, and jejunal and ileal tissue for genome-wide transcription profiling, was performed at day 55 (~8 weeks) and day 176 (~25 weeks) after birth. Antibiotic treatment in combination with or without exposure to stress was found to have long-lasting effects on host intestinal gene expression involved in a multitude of processes, including immune related processes. Conclusions/Significance The results obtained in this study indicate that early life (day 4 after birth) perturbations have long-lasting effects on the gut system, both in gene expression (day 55) as well as on microbiota composition (day 176). At day 55 high variance was observed in the microbiota data, but no significant differences between treatment groups, which is most probably due to the newly acquired microbiota during and right after weaning (day 28). Based on the observed difference in gene expression at day 55, it is hypothesized that due to the difference in immune programming during early life, the systems respond differently to the post-weaning newly acquired microbiota. As a consequence, the gut systems of the treatment groups develop into different homeostasis.
    Common variants and haplotypes in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in a female black South African population
    Gichohi-Wainaina, W.N. ; Boonstra, A. ; Swinkels, D.W. ; Zimmermann, M.B. ; Feskens, E.J.M. ; Towers, G.W. - \ 2015
    The Journal of Nutrition 145 (2015)5. - ISSN 0022-3166 - p. 945 - 953.
    tumor-necrosis-factor - transferrin g277s mutation - deficiency anemia - serum hepcidin - women - risk - disease - hfe - polymorphisms - saturation
    Background: It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population. Objectives: We aimed to investigate associations of reported SNPs with iron markers in a South African cohort. Methods: Blood concentrations of hemoglobin, serum ferritin (SF), serum soluble transferrin receptor (sTfR), and body iron (BI) stores were determined from women (n = 686; range, 32–86 y) who were part of the Prospective Urban and Rural Epidemiology study. Thirty-two SNPs in 12 genes were selected based on existing genome-wide association study data. Results: In the transferrin (TF) gene, SF and BI were significantly lower in the heterozygote genotype (AG) of reference SNP (rs) 1799852 (P = 0.01 and 0.03, respectively) and sTfR concentrations were significantly higher (P = 0.004) than the homozygote minor allele genotype (AA), whereas transferrin receptor and BI concentrations were significantly lower in the heterozygote genotype (AG) of rs3811647 (both P = 0.03) than the homozygote wild-type (AA) and minor allele groups (GG). The chromosome 6 allele combination (AAA) consisting of rs1799964 and rs1800629 both in tumor necrosis factor-a (TNF-a) and rs2071592 in nuclear factor ¿B inhibitor–like protein 1 (NFKBIL1) was associated with higher odds for low SF concentrations (SF <15 µg/L; OR: 1.86; 95% CI: 1.23, 2.79) than the allele combinations AGA, GGT, and AGT. The chromosome 22 allele combination (GG) consisting of rs228918 and rs228921 in the transmembrane protease serine 6 (TMPRSS6) gene was associated with lower odds for increased sTfR concentrations (sTfR > 8.3mg/L; OR: 0.79; 95% CI: 0.63, 0.98) than the allele combination AA. Conclusions: Various SNPs and allele combinations in the TF, TNF-a, and TMPRSS6 genes are associated with iron status in black South African women; however, these association patterns are different compared with European ancestry populations. This stresses the need for population-specific genomic data.
    Hypothesis: the sound of the individual metabolic phenotype? Acoustic detection of NMR experiments
    Cacciatore, S. ; Saccenti, E. ; Piccioli, M. - \ 2015
    OMICS - A Journal of Integrative Biology 19 (2015)3. - ISSN 1536-2310 - p. 147 - 156.
    breast-cancer - personalized medicine - disease - profiles - models - health - time - classification - identification - metabonomics
    We present here an innovative hypothesis and report preliminary evidence that the sound of NMR signals could provide an alternative to the current representation of the individual metabolic fingerprint and supply equally significant information. The NMR spectra of the urine samples provided by four healthy donors were converted into audio signals that were analyzed in two audio experiments by listeners with both musical and non-musical training. The listeners were first asked to cluster the audio signals of two donors on the basis of perceived similarity and then to classify unknown samples after having listened to a set of reference signals. In the clustering experiment, the probability of obtaining the same results by pure chance was 7.04% and 0.05% for non-musicians and musicians, respectively. In the classification experiment, musicians scored 84% accuracy which compared favorably with the 100% accuracy attained by sophisticated pattern recognition methods. The results were further validated and confirmed by analyzing the NMR metabolic profiles belonging to two other different donors. These findings support our hypothesis that the uniqueness of the metabolic phenotype is preserved even when reproduced as audio signal and warrants further consideration and testing in larger study samples
    Induced lung inflammation and dietary protein supply affect nitrogen retention and amino acid metabolism in growing pigs
    Kampman-van de Hoek, E. ; Sakkas, P. ; Gerrits, W.J.J. ; Borne, J.J.G.C. van den; Peet-Schwering, C.M.C. van der; Jansman, A.J.M. - \ 2015
    The British journal of nutrition 113 (2015)3. - ISSN 0007-1145 - p. 414 - 425.
    immune-system activation - acute-phase proteins - body protein - tryptophan - plasma - growth - piglets - disease - sepsis - rats
    It is hypothesised that during immune system activation, there is a competition for amino acids (AA) between body protein deposition and immune system functioning. The aim of the present study was to quantify the effect of immune system activation on N retention and AA metabolism in growing pigs, depending on dietary protein supply. A total of sixteen barrows received an adequate (Ad) or restricted (Res) amount of dietary protein, and were challenged at day 0 with intravenous complete Freund's adjuvant (CFA). At days - 5, 3 and 8, an irreversible loss rate (ILR) of eight AA was determined. CFA successfully activated the immune system, as indicated by a 2- to 4-fold increase in serum concentrations of acute-phase proteins (APP). Pre-challenge C-reactive protein concentrations were lower (P<0·05) and pre- and post-challenge albumin tended to be lower in Res-pigs. These findings indicate that a restricted protein supply can limit the acute-phase response. CFA increased urinary N losses (P= 0·04) and tended to reduce N retention in Ad-pigs, but not in Res-pigs (P= 0·07). The ILR for Val was lower (P= 0·05) at day 8 than at day 3 in the post-challenge period. The ILR of most AA, except for Trp, were strongly affected by dietary protein supply and positively correlated with N retention. The correlations between the ILR and APP indices were absent or negative, indicating that changes in AA utilisation for APP synthesis were either not substantial or more likely outweighed by a decrease in muscle protein synthesis during immune system activation in growing pigs.
    Bright fluorescent Streptococcus pneumoniae for live cell imaging of host-pathogen interactions
    Kjos, M. ; Aprianto, R. ; Fernandes, V.E. ; Andrew, P.W. ; Strijp, J.A.G. van; Nijland, R. ; Veening, J.W. - \ 2015
    Journal of Bacteriology 197 (2015)5. - ISSN 0021-9193 - p. 807 - 818.
    epithelial-cells - gene-expression - pneumococcal virulence - bacillus-subtilis - in-vivo - protein - capsule - colonization - disease - invasion
    Streptococcus pneumoniae is a common nasopharyngeal resident in healthy people, but at the same time one of the major causes of infectious diseases such as pneumonia, meningitis and sepsis. The shift from commensal to pathogen and its interaction with host cells is poorly understood. One of the major limitations for research on pneumococcal-host interactions is the lack of suitable tools for live cell imaging. To address this issue, we developed a generally applicable strategy to create genetically stable, highly fluorescent bacteria. Our strategy relies on fusing superfolder green fluorescent protein (GFP) or a far-red fluorescent protein (RFP) to the abundant histone-like protein HlpA. Due to efficient translation and limited cellular diffusion of these fusions, the cells are 25-fold brighter than the currently best available imaging S. pneumoniae strain. These novel bright pneumococcal strains are fully virulent and the GFP-reporter can be used for in situ imaging in mouse tissue. We used our reporter strains to study the effect of the polysaccharide capsule, a major pneumococcal virulence factor, on different stages of infection. By dual-color live cell imaging experiments, we show that unencapsulated pneumococci adhere significantly better to human lung epithelial cells compared to encapsulated strains, in line with previous data obtained by classical approaches. We also confirm with live cell imaging that the capsule protects pneumococci from neutrophil phagocytosis, demonstrating the versatility and usability of our reporters. The described imaging tools will pave the way for live cell imaging of pneumococcal infection and help understand the mechanisms of pneumococcal pathogenesis.
    Quantitative economic impact assessment of invasive plant pests: What does it require and when is it worth the effort?
    Soliman, T.A.A. ; Mourits, M.C.M. ; Oude Lansink, A.G.J.M. ; Werf, W. van der - \ 2015
    Crop Protection 69 (2015). - ISSN 0261-2194 - p. 9 - 17.
    maps - ecology - disease - system - growth
    According to the International Plant Protection Convention and theWorld Trade Organization Agreement on the Application of Sanitary and Phytosanitary measures, any measure against the introduction and spread of new pests must be justified by a science-based pest risk analysis. Economic impact assessments are usually carried out using a qualitative approach, based on classifying the size of impact into five categories, from “minimal” to “massive”. Whilst the qualitative approach may be adequate in many instances, it lacks transparency and demonstrable objectivity. A quantitative approach for economic impact assessment may improve transparency and strengthen the justification for measures, if taken, but requires additional work, and it requires specific data and models. This paper, first, compares the strengths and weaknesses of qualitative and quantitative approaches. Second, it clarifies the data and models needed to conduct a quantitative economic impact assessment to support a decision on the pest quarantine status or justify management measures. Third, it identifies the criteria for choosing the appropriate level of complexity, regarding the resolution, economic technique and time frame of the quantitative approach. The greater transparency and objectivity of the quantitative vis-a-vis qualitative economic impact assessment may enhance plant health policy and decision making at national and international regulatory bodies. However, uncertainties that are inherent to this approach may weaken this position. Hence, PRAs require a mixture of quantitative and qualitative approaches for assessing impacts and the exact balance of the two has to be case-specific.
    A weekly alternating diet between caloric restriction and medium-fat protects the liver from fatty liver development in middle-aged C57BL/6J mice
    Rusli, F. ; Boekschoten, M.V. ; Zubia, A.A. ; Lute, C. ; Müller, M.R. ; Steegenga, W.T. - \ 2015
    Molecular Nutrition & Food Research 59 (2015)3. - ISSN 1613-4125 - p. 533 - 543.
    metabolic syndrome - insulin-resistance - small-intestine - induced obesity - adipose-tissue - life-span - disease - prevalence - population - expression
    Scope : We aimed to investigate whether a novel dietary intervention consisting of an every-other-week calorie restricted diet could prevent non-alcoholic fatty liver disease (NAFLD) development induced by a medium-fat diet. Methods and results : Nine week-old male C57BL/6J mice received either a 1) control (C), 2) 30E% calorie restricted (CR), 3) medium-fat (MF; 25E% fat) or 4) intermittent (INT) diet, a diet alternating weekly between 40E% CR and an ad libitum MF diet until sacrifice at the age of 12 months. The metabolic, morphological, and molecular features of NAFLD were examined. The INT diet resulted in healthy metabolic and morphological features as displayed by the continuous CR diet: glucose tolerant, low hepatic triglyceride content, low plasma alanine aminotransferase. In contrast, the C- and MF-exposed mice with high body weight developed signs of NAFLD. However, the gene expression profiles of INT-exposed mice differed to those of CR-exposed mice and showed to be more similar with those of C- and MF-exposed mice with a comparable body weight. Conclusions : Our study reveals that the INT diet maintains metabolic health and reverses the adverse effects of the MF diet, thus effectively prevent the development of NAFLD in 12-month-old male C57BL/6J mice.
    Liver DNA methylation analysis in adult female C57BL/6JxFVB mice following perinatal exposure to bisphenol A
    Esterik, J.C. van; Vitins, A.P. ; Hodemaekers, H.M. ; Kamstra, J.H. ; Legler, J. ; Pennings, J.L.A. ; Steegenga, W.T. ; Lute, C. ; Jelinek, J. ; Issa, J.P. ; Dollé, M.E.T. ; Ven, L.T.M. van der - \ 2015
    Toxicology Letters 232 (2015)1. - ISSN 0378-4274 - p. 293 - 300.
    endocrine disruptors - disease - bpa - xenoestrogens - association - epigenetics - expression - nutrition - evolution - chemicals
    Bisphenol A (BPA) is a compound released from plastics and other consumer products used in everyday life. BPA exposure early in fetal development is proposed to contribute to programming of chronic diseases like obesity and diabetes, by affecting DNA methylation levels. Previously, we showed that in utero and lactational exposure of C57BL/6JxFVB hybrid mice via maternal feed using a dose range of 0–3000 µg/kg body weight/day resulted in a sex-dependent altered metabolic phenotype in offspring at 23 weeks of age. The most univocal effects were observed in females, with reduced body weights and related metabolic effects associated with perinatal BPA exposure. To identify whether the effects of BPA in females are associated with changes in DNA methylation, this was analyzed in liver, which is important in energy homeostasis. Measurement of global DNA methylation did not show any changes. Genome-wide DNA methylation analysis at specific CpG sites in control and 3000 µg/kg body weight/day females with the digital restriction enzyme analysis of methylation (DREAM) assay revealed potential differences, that could, however, not be confirmed by bisulfite pyrosequencing. Overall, we demonstrated that the observed altered metabolic phenotype in female offspring after maternal exposure to BPA was not detectably associated with liver DNA methylation changes. Still, other tissues may be more informative.
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