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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    Genetic Variation in Complex Traits in Transgenic α-Synuclein Strains of Caenorhabditis elegans
    Wang, Yiru ; Sluijs, L. van; Nie, Yu ; Sterken, M.G. ; Harvey, Simon C. ; Kammenga, J.E. - \ 2020
    Genes 11 (2020)7. - ISSN 2073-4425
    Different genetic backgrounds can modify the effect of mutated genes. Human α-synuclein (SNCA) gene encodes α-synuclein, and its oligomeric complexes accumulate with age and mediate the disruption of cellular homeostasis, resulting in the neuronal death that is characteristic of Parkinson’s Disease. Polymorphic variants modulate this complex pathologic mechanism. Previously, we constructed five transgenic introgression lines of a Caenorhabditis elegans model of α-synuclein using genetic backgrounds that are genetically diverse from the canonical wild-type Bristol N2. A gene expression analysis revealed that the α-synuclein transgene differentially affects genome-wide transcription due to background modifiers. To further investigate how complex traits are affected in these transgenic lines, we measured the α-synuclein transgene expression, the overall accumulation of the fusion protein of α-synuclein and yellow fluorescent protein (YFP), the lysosome-related organelles, and the body size. By using quantitative PCR (qPCR), we demonstrated stable and similar expression levels of the α-synuclein transgene in different genetic backgrounds. Strikingly, we observed that the levels of the a-synuclein:YFP fusion protein vary in different genetic backgrounds by using the COPAS™ biosorter. The quantification of the Nile Red staining assay demonstrates that α-synuclein also affects lysosome-related organelles and body size. Our results show that the same α-synuclein introgression in different C. elegans backgrounds can produces differing effects on complex traits due to background modifiers. View Full-Text
    Orsay virus infection reduces outcrossing behaviour of Caenorhabditis elegans males
    Sluijs, L. van; Liu, Jie ; Schrama, Mels ; Hamond, Sanne van; Vromans, Sophie ; Scholten, Marèl ; Žibrat, Nika ; Riksen, J.A.G. ; Sterken, M.G. ; Pijlman, G.P. ; Kammenga, J.E. - \ 2020
    Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain
    Vissers, Linda E.T. ; Soedamah-Muthu, Sabita S. ; Schouw, Yvonne T. van der; Zuithoff, Nicolaas P.A. ; Geleijnse, Johanna M. ; Sluijs, Ivonne - \ 2020
    Nutrition, Metabolism & Cardiovascular Diseases 30 (2020)5. - ISSN 0939-4753 - p. 804 - 809.
    Circulating fatty acids - Dairy products - Margaric acid - Myristic acid - Pentadecanoic acid - Randomized cross-over trial

    Background and aims: A higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA). Methods and results: In a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m2 received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (β; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10−5, and β: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10−2, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (β: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10−5), but not when compared to the grain diet. 17:0 did not differ between diets. Conclusion: The plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat. Clinical trial registration: ClinicalTrials.gov, NCT01314040.

    Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort
    Harbers, Marjolein C. ; Kroon, Marleen A. de; Boer, Jolanda M.A. ; Asselbergs, Folkert W. ; Geleijnse, Johanna M. ; Verschuren, Monique W. ; Schouw, Yvonne T. van der; Sluijs, Ivonne - \ 2020
    European Journal of Nutrition (2020). - ISSN 1436-6207
    Dietary patterns - Dutch dietary guidelines - Dutch Healthy Diet 2015 Index - Heart failure

    Purpose: A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF. Methods: We studied 37,468 participants aged 20–70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993–1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics. Results: The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1–16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HRQ4vsQ1 0.73; 95% CI 0.58–0.93; Ptrend 0.001). Conclusion: In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.

    Sex-specific viral susceptibility of Caenorhabditis elegans
    Sluijs, Lisa van; Liu, Jie ; Hamond, Sanne van; Vromans, Sophie ; Scholten, Marèl ; Riksen, Joost ; Pijlman, Gorben ; Kammenga, Jan - \ 2019
    Addiction systems antagonize bacterial adaptive immunity
    Sluijs, Lisa van; Houte, Stineke van; Oost, John van der; Brouns, Stan J.J. ; Buckling, Angus ; Westra, Edze R. - \ 2019
    FEMS Microbiology Letters 366 (2019)5. - ISSN 0378-1097
    adaptive immunity - bacteria - CRISPR - plasmid - TA - toxin

    CRISPR-Cas systems provide adaptive immunity against mobile genetic elements, but employment of this resistance mechanism is often reported with a fitness cost for the host. Whether or not CRISPR-Cas systems are important barriers for the horizontal spread of conjugative plasmids, which play a crucial role in the spread of antibiotic resistance, will depend on the fitness costs of employing CRISPR-based defences and the benefits of resisting conjugative plasmids. To estimate these costs and benefits we measured bacterial fitness associated with plasmid immunity using Escherichia coli and the conjugative plasmid pOX38-Cm. We find that CRISPR-mediated immunity fails to confer a fitness benefit in the absence of antibiotics, despite the large fitness cost associated with carrying the plasmid in this context. Similar to many other conjugative plasmids, pOX38-Cm carries a CcdAB toxin-anti-toxin (TA) addiction system. These addiction systems encode long-lived toxins and short-lived anti-toxins, resulting in toxic effects following the loss of the TA genes from the bacterial host. Our data suggest that the lack of a fitness benefit associated with CRISPR-mediated defence is due to expression of the TA system before plasmid detection and degradation. As most antibiotic resistance plasmids encode TA systems this could have important consequences for the role of CRISPR-Cas systems in limiting the spread of antibiotic resistance.

    Sex-specific viral susceptibility of Caenorhabditis elegans nematodes
    Sluijs, L. van; Liu, Jie ; Schrama, M. ; Hamond, Sanne van; Vromans, S. ; Pijlman, G.P. ; Kammenga, J.E. - \ 2019
    The sex of an organism affects a variety of phenotypes including pathogen susceptibility. Hermaphrodites of the androdioecious model organism Caenorhabditis elegans can be infected by an intestinal virus: the Orsay virus. The viral susceptibility of C. elegans males has not been studied, but it is known that males are more resistant to a pathogenic fungus than hermaphrodites. We investigated the viral susceptibility of C. elegans males and found that male populations are less often successfully infected by the Orsay virus than hermaphrodite populations. Infection in hermaphrodites causes upregulation of genes of the Intracellular Pathogen Response (IPR) which counteracts infection. We have found that several genes in this pathway are constitutively higher expressed in males and that their expression increases even further after infection. Additionally, we infected a strain with a natural mutation in the RNA interference pathway which makes the hermaphrodites highly susceptible. We found that males of this strain are as susceptible as the hermaphrodites. Deep-sequencing of small RNAs from infected populations supports that RNAi processing of the virus differs between the sexes. Therefore, both the RNAi and IPR pathway may determine sex-specific susceptibility. In nature C. elegans males are rarely found among populations, but male frequencies can increase upon experiencing unfavourable conditions which facilitates adaptation in the lab. Preliminary data suggests that males are less attracted to the lysate of infected hermaphrodites than that of uninfected hermaphrodites. The presence of relatively resistant males with a preference for healthy hermaphrodites within a population could facilitate longer-term survival of the species. This may be one of the answers to why males occur in a species that could also exist without them.
    Circulating Phylloquinone Concentrations and Risk of Type 2 Diabetes: a Mendelian Randomization Study
    Zwakenberg, Sabine ; Remmelzwaal, S. ; Beulens, J.W.J. ; Booth, S.L. ; Burgess, Stephen ; Dashti, Hassan ; Imamura, Fumiaki ; Feskens, E.J.M. ; Schouw, Y.T. van der; Sluijs, Ivonne - \ 2019
    Diabetes 68 (2019)1. - ISSN 0012-1797 - p. 220 - 225.
    This study aims to investigate the causal relation between circulating phylloquinone (vitamin K1) concentrations and type 2 diabetes using a Mendelian Randomization (MR) approach. We used data from thee cohorts: the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study, Diabetes Genetics Replication and Meta-analysis (DIAGRAM) and the UK Biobank, resulting in 69,647 type 2 diabetes cases. We calculated a weighted genetic risk score including four genetic variants previously found to be associated with circulating phylloquinone concentrations. Inverse-variance weighted analysis was used to obtain a risk ratio (RR) for the causal relation between circulating phylloquinone concentrations and risk of type 2 diabetes. Presence of pleiotropy and the robustness of the results were assessed using MR-Egger and weighted-median analyses. Genetically-predicted concentrations of circulating phylloquinone was associated with lower risk of type 2 diabetes with a RR of 0.93 (95% confidence interval: 0.89;0.97) per every ln-nmol/L unit increase in circulating phylloquinone. The MR-Egger and weighted median analyses showed RRs of 0.94 (0.86;1.02) and 0.93 (0.88;0.98), respectively, indicating no pleiotropy. In conclusion, our study supports that higher circulating phylloquinone may be causally related with lower risk of type 2 diabetes, highlighting the importance of sufficient phylloquinone in the human diet.
    Caenorhabditis elegans males and hermaphrodites differ in susceptibility upon Orsay virus infection
    Sluijs, L. van; Liu, Jie ; Schrama, Mels ; Hamond, Sanne van; Pijlman, G.P. ; Kammenga, J.E. - \ 2018
    Individuals differ in their susceptibility upon viral infection as a result of a complex interplay between the individuals genetic background and the environment. The genetic background determines the sex of an organism and affects a large range of traits. Here we show that the sex of Caenorhabdtis elegans affects the susceptibility upon infection with the intestinal pathogen the Orsay virus. We noticed that outbred, mixed male and hermaphrodite populations showed a lower viral load than inbred, hermaphrodite populations. This result suggested that either the method of breeding or the sex of the nematodes in the population affected the viral load. Therefore, males and hermaphrodites were separately infected. Populations of infected males showed a larger number of failed infections than hermaphrodites that originated from the same plate. Moreover, preliminary results suggest that the mechanism may be genotype-dependent. As Orsay virus infects nematodes after ingestion the difference in viral susceptibility may be determined by a different food intake by males and hermaphrodites. Yet, the food intake as measured by grinder movements is similar in males and hermaphrodites. Currently we are also quantifying the volume of food taken in by the male and hermaphrodite nematodes in liquid to get a better estimation of food intake during the viral infection. Besides, we are investigating if differences in molecular networks between both sexes can alter the viral susceptibility by measuring the transcriptional response upon infection. In nature C. elegans males may benefit from a higher resistance towards viruses and possibly other intestinal pathogens that are counteracted by similar mechanisms. An ecological advantage like increased pathogen resistance might be important for males in a species that suffers from outbreeding depression.
    Genetic variation causes differential viral susceptibilities in the model organism Caenorhabditis elegans
    Sluijs, Lisa van - \ 2018
    Predicting individual differences in viral susceptibility caused by natural genetic variation within species
    Sluijs, L. van; Sterken, M.G. ; Wang, Yiru A. ; Ritmahan, Wannisa ; Gultom, Mitra ; Pankok, Frederik ; Blokhina, T. ; Riksen, J.A.G. ; Volkers, J.M. ; Snoek, L.B. ; Pijlman, G.P. ; Kammenga, J.E. - \ 2018
    Natural genetic variation within species can underlie different individual susceptibilities upon viral infection. The molecular mechanisms by which genetic variation affects the viral susceptibility are currently poorly understood. Here we use Caenorhabditis elegans as a model organism to identify which polymorphisms alter the viral susceptibility. Moreover, we predict how the molecular mechanisms behind altered susceptibilities may work. The viral susceptibility towards Orsay virus of the commonly used lab strain, N2, is higher than that of the Hawaiian isolate CB4856. The phenotype of N2xCB4856 recombinant inbred strains was obtained by measuring the viral load upon infection and these viral loads were correlated to the genotypes by quantitative trait locus (QTL) mapping. A region on chromosome IV was found to correlate with changes in the viral susceptibility. This QTL region, containing hundreds of candidate polymorphisms, was fine mapped using two introgression line panels. The first introgression line panel contained an introgression of N2 into the genome of CB4856, whereas the second panel contained an introgression of CB4856 into the genome of N2. Using these two panels the QTL region was fine mapped to a region containing about 30 polymorphisms. Using known protein structures we predicted possible effects of candidate polymorphisms. An example is a single nucleotide polymorphism in a conserved region of the known antiviral defence gene cul-6. This polymorphism may be responsible for an altered stability of the SCF complex that targets viral particles for degradation. A causal relationship could be experimentally verified by exchanging the polymorphism of the resistant and susceptible strain, an approach we are currently taking.
    Genetic variation causes differential viral susceptibilities in the model organism Caenorhabditis elegans
    Sluijs, L. van; Sterken, M.G. ; Wang, Yiru A. ; Ritmahan, Wannisa ; Gultom, Mitra ; Pankok, Frederik ; Blokhina, T. ; Riksen, J.A.G. ; Volkers, J.M. ; Snoek, L.B. ; Pijlman, G.P. ; Kammenga, J.E. - \ 2018
    Individual genetic variation in the same species can cause different susceptibilities upon viral infection. Causal polymorphisms that underlie susceptibility differences can be identified by mapping the susceptibility of individuals to the genetic variants the individuals carry. Genetic mapping usually indicates a locus containing multiple candidate polymorphisms that may be the causal one. Here, we used three independent mapping populations of the nematode Caenorhabditis elegans to find a small group of candidate polymorphisms that determine the susceptibility to infection by a natural virus. Homozygous mapping populations of C. elegans were previously obtained by crossing two strains with a different viral susceptibility: the susceptible strain N2 and the more resistant strain CB4856. A recombinant inbred panel was used for quantitative trait locus (QTL) mapping to identify a region containing hundreds of candidate genes. Two introgression line panels experimentally confirmed the causal region and fine mapped the candidate region to about 30 potentially causal polymorphisms. One of these polymorphisms, the known antiviral defence gene cul-6, contains a single nucleotide polymorphism in a conserved region. We hypothesise that this polymorphism may be responsible for the difference in viral susceptibility and we are currently trying to exchange polymorphisms between the susceptible and resistant strain using CRISPR/Cas9. In the end, finding how polymorphisms in viral response pathways alter the molecular mechanisms upon viral infection can contribute to a better understanding of the close interactions between host and virus.

    Ranavirus genotypes in Netherlands and their potential association with virulence in water frogs (Pelophylax spp.)
    Saucedo, Bernardo ; Hughes, Joseph ; Spitzen-Van Der Sluijs, Annemarieke ; Kruithof, Natasja ; Schills, Marc ; Rijks, Jolianne M. ; Jacinto-Maldonado, Mónica ; Suarez, Nicolás ; Haenen, Olga L.M. ; Voorbergen-Laarman, Michal ; Broek, Jan Van Den; Gilbert, Maarten ; Gröne, Andrea ; Beurden, Steven J. van; Verheije, M.H. - \ 2018
    Emerging Microbes and Infections 7 (2018)1. - ISSN 2222-1751
    Ranaviruses are pathogenic viruses for poikilothermic vertebrates worldwide. The identification of a common midwife toad virus (CMTV) associated with massive die-offs in water frogs (Pelophylax spp.) in Netherlands has increased awareness for emerging viruses in amphibians in the country. Complete genome sequencing of 13 ranavirus isolates collected from ten different sites in the period 2011-2016 revealed three CMTV groups present in distinct geographical areas in Netherlands. Phylogenetic analysis showed that emerging viruses from the northern part of Netherlands belonged to CMTV-NL group I. Group II and III viruses were derived from the animals located in the center-east and south of the country, and shared a more recent common ancestor to CMTV-amphibian associated ranaviruses reported in China, Italy, Denmark, and Switzerland. Field monitoring revealed differences in water frog host abundance at sites where distinct ranavirus groups occur; with ranavirus-associated deaths, host counts decreasing progressively, and few juveniles found in the north where CMTV-NL group I occurs but not in the south with CMTV-NL group III. Investigation of tandem repeats of coding genes gave no conclusive information about phylo-geographical clustering, while genetic analysis of the genomes revealed truncations in 17 genes across CMTV-NL groups II and III compared to group I. Further studies are needed to elucidate the contribution of these genes as well as environmental variables to explain the observed differences in host abundance.
    Intake of dietary saturated fatty acids and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition-Netherlands cohort : associations by types, sources of fatty acids and substitution by macronutrients
    Liu, Shengxin ; Schouw, Yvonne T. van der; Soedamah-Muthu, Sabita S. ; Spijkerman, Annemieke M.W. ; Sluijs, Ivonne - \ 2018
    European Journal of Nutrition 58 (2018). - ISSN 1436-6207 - p. 1125 - 1136.
    Cohort study - Epidemiology - Nutrition - Saturated fatty acids - Type 2 diabetes
    Purpose: The association between dietary saturated fatty acids (SFA) intake and type 2 diabetes (T2D) remains unclear. This study aimed at investigating the association between SFA intake and T2D risk based on (1) individual SFA (differing in carbon chain length), (2) food sources of SFA and (3) the substituting macronutrients. Methods: 37,421 participants from the European Prospective Investigation into Cancer and Nutrition-Netherlands (EPIC-NL) cohort were included in this study. Baseline dietary intake was assessed by a validated food frequency questionnaire. T2D risks were estimated by Cox regression models adjusted for non-dietary and dietary covariates. Results: 893 incident T2D cases were documented during 10.1-year follow-up. We observed no association between total SFA and T2D risk. Marginally inverse associations were found for lauric acid (HR per 1 SD of energy%, 95% CI 0.92, 0.85–0.99), myristic acid (0.89, 0.79–0.99), margaric acid (0.84, 0.73–0.97), odd-chain SFA (pentadecylic plus margaric acids; 0.88, 0.79–0.99), and cheese derived SFA (0.90, 0.83–0.98). Soft and liquid fats derived SFA was found related to higher T2D risk (1.08, 1.01–1.17). When substituting SFA by proteins, carbohydrates and polyunsaturated fatty acids, significantly higher risks of T2D were observed (HRs per 1 energy% ranging from 1.05 to 1.15). Conclusion: In this Dutch population, total SFA does not relate to T2D risk. Rather, the association may depend on the types and food sources of SFA. Cheese-derived SFA and individual SFA that are commonly found in cheese, were significantly related to lower T2D risks. We cannot exclude the higher T2D risks found for soft and liquid fats derived SFA and for substituting SFA with other macronutrients are influenced by residual confounding by trans fatty acids or limited intake variation in polyunsaturated fatty acids and vegetable protein.
    Using the model organism C. elegans to determine why individuals differ in their viral susceptibility
    Sluijs, Lisa van - \ 2018
    Designing synthetic networks in silico : A generalised evolutionary algorithm approach
    Smith, Robert W. ; Sluijs, Bob van; Fleck, Christian - \ 2017
    BMC Systems Biology 11 (2017)1. - ISSN 1752-0509
    Evolutionary algorithm - Network design - Synthetic biology
    Background: Evolution has led to the development of biological networks that are shaped by environmental signals. Elucidating, understanding and then reconstructing important network motifs is one of the principal aims of Systems & Synthetic Biology. Consequently, previous research has focused on finding optimal network structures and reaction rates that respond to pulses or produce stable oscillations. In this work we present a generalised in silico evolutionary algorithm that simultaneously finds network structures and reaction rates (genotypes) that can satisfy multiple defined objectives (phenotypes). Results: The key step to our approach is to translate a schema/binary-based description of biological networks into systems of ordinary differential equations (ODEs). The ODEs can then be solved numerically to provide dynamic information about an evolved networks functionality. Initially we benchmark algorithm performance by finding optimal networks that can recapitulate concentration time-series data and perform parameter optimisation on oscillatory dynamics of the Repressilator. We go on to show the utility of our algorithm by finding new designs for robust synthetic oscillators, and by performing multi-objective optimisation to find a set of oscillators and feed-forward loops that are optimal at balancing different system properties. In sum, our results not only confirm and build on previous observations but we also provide new designs of synthetic oscillators for experimental construction. Conclusions: In this work we have presented and tested an evolutionary algorithm that can design a biological network to produce desired output. Given that previous designs of synthetic networks have been limited to subregions of network- and parameter-space, the use of our evolutionary optimisation algorithm will enable Synthetic Biologists to construct new systems with the potential to display a wider range of complex responses.
    The viral susceptibility of individuals is affected by their genetic make-up
    Sluijs, Lisa van - \ 2017
    Viral susceptibility differs between individuals due to genetic and environmental differences. Currently, the molecular mechanisms underlying differences in individual susceptibility are poorly understood. Here, we use the model organism Caenorhabditis elegans to unravel molecular pathways affected by genetic polymorphisms that lead to differences in susceptibility of an individual. Two distinct genotypes, N2 and CB4856, differ in viral susceptibility to infection by Orsay virus. Here, we used quantitative trait loci (QTL) mapping in N2xCB4856 recombinant inbred lines (RILs) in order to identify loci affecting susceptibility. We found two genomic loci correlated with viral susceptibility. Introgression lines (ILs) containing single genetic fragments of one parental strain in the genetic background of the other strain were used to finemap the genetic loci. After infection of a panel of ILs, the QTL region could be narrowed down to a region containing about 30 polymorphic genes. We selected genes using literature data and databases that predict the structure and function of proteins. The selected candidate polymorphisms found by the analysis will be targeted by CRISPR-Cas9 to exchange specific alleles between the parental strains. In the end, this approach can help to unravel how genetic polymorphisms can determine the viral susceptibility of an individual.
    Association between plasma phospholipid saturated fatty acids and metabolic markers of lipid, hepatic, inflammation and glycaemic pathways in eight European countries: a cross-sectional analysis in the EPIC-InterAct study
    Zheng, Ju-Sheng ; Sharp, Stephen J. ; Imamura, Fumiaki ; Koulman, Albert ; Schulze, Matthias B. ; Ye, Zheng ; Griffin, Jules ; Guevara, Marcela ; Huerta, José María ; Kröger, Janine ; Sluijs, Ivonne ; Agudo, Antonio ; Barricarte, Aurelio ; Boeing, Heiner ; Colorado-Yohar, Sandra ; Dow, Courtney ; Dorronsoro, Miren ; Dinesen, Pia T. ; Fagherazzi, Guy ; Franks, Paul W. ; Feskens, Edith J.M. ; Kühn, Tilman ; Katzke, Verena Andrea ; Key, Timothy J. ; Khaw, Kay-Tee ; Magistris, Maria Santucci De; Mancini, Francesca Romana ; Molina-Portillo, Elena ; Nilsson, Peter M. ; Olsen, Anja ; Overvad, Kim ; Palli, Domenico ; Quirós, Jose Ramón ; Rolandsson, Olov ; Ricceri, Fulvio ; Spijkerman, Annemieke M.W. ; Slimani, Nadia ; Tagliabue, Giovanna ; Tjonneland, Anne ; Tumino, Rosario ; Schouw, Yvonne T. Van Der; Langenberg, Claudia ; Riboli, Elio ; Forouhi, Nita G. ; Wareham, Nicholas J. - \ 2017
    BMC Medicine 15 (2017)1. - ISSN 1741-7015
    Background
    Accumulating evidence suggests that individual circulating saturated fatty acids (SFAs) are heterogeneous in their associations with cardio-metabolic diseases, but evidence about associations of SFAs with metabolic markers of different pathogenic pathways is limited. We aimed to examine the associations between plasma phospholipid SFAs and the metabolic markers of lipid, hepatic, glycaemic and inflammation pathways.
    Methods
    We measured nine individual plasma phospholipid SFAs and derived three SFA groups (odd-chain: C15:0 + C17:0, even-chain: C14:0 + C16:0 + C18:0, and very-long-chain: C20:0 + C22:0 + C23:0 + C24:0) in individuals from the subcohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct case-cohort study across eight European countries. Using linear regression in 15,919 subcohort members, adjusted for potential confounders and corrected for multiple testing, we examined cross-sectional associations of SFAs with 13 metabolic markers. Multiplicative interactions of the three SFA groups with pre-specified factors, including body mass index (BMI) and alcohol consumption, were tested.
    Results
    Higher levels of odd-chain SFA group were associated with lower levels of major lipids (total cholesterol (TC), triglycerides, apolipoprotein A-1 (ApoA1), apolipoprotein B (ApoB)) and hepatic markers (alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transferase (GGT)). Higher even-chain SFA group levels were associated with higher levels of low-density lipoprotein cholesterol (LDL-C), TC/high-density lipoprotein cholesterol (HDL-C) ratio, triglycerides, ApoB, ApoB/A1 ratio, ALT, AST, GGT and CRP, and lower levels of HDL-C and ApoA1. Very-long-chain SFA group levels showed inverse associations with triglycerides, ApoA1 and GGT, and positive associations with TC, LDL-C, TC/HDL-C, ApoB and ApoB/A1. Associations were generally stronger at higher levels of BMI or alcohol consumption.
    Conclusions
    Subtypes of SFAs are associated in a differential way with metabolic markers of lipid metabolism, liver function and chronic inflammation, suggesting that odd-chain SFAs are associated with lower metabolic risk and even-chain SFAs with adverse metabolic risk, whereas mixed findings were obtained for very-long-chain SFAs. The clinical and biochemical implications of these findings may vary by adiposity and alcohol intake.
    Why do Individuals Differ in Viral Susceptibility? : A Story Told by Model Organisms
    Sluijs, L. van; Pijlman, G.P. ; Kammenga, J.E. - \ 2017
    Viruses 9 (2017)10. - ISSN 1999-4915
    Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for well-studied viruses the genetic basis of individual susceptibility differences remains elusive. Investigating the effect of causal polymorphisms in humans is complicated, because genetic methods to detect rare or small-effect polymorphisms are limited and genetic manipulation is not possible in human populations. Model organisms have proven a powerful experimental platform to identify and characterize polymorphisms that underlie natural variations in viral susceptibility using quantitative genetic tools. We summarize and compare the genetic tools available in three main model organisms, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, and illustrate how these tools can be applied to detect polymorphisms that determine the viral susceptibility. Finally, we analyse how candidate polymorphisms from model organisms can be used to shed light on the underlying mechanism of individual variation. Insights in causal polymorphisms and mechanisms underlying individual differences in viral susceptibility in model organisms likely provide a better understanding in humans.
    Plant-mediated changes in soil communities affect aboveground plant-insect Interactions, COST ACTION FA 1405 “Plant-mediated communication between above and belowground foodwebs"
    Heinen, R. ; Huberty, M. ; Sluijs, M. van der; Zhu, F. ; Bezemer, T.M. - \ 2016
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