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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Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats
Stedman, Anna ; Wright, Daniel ; Wichgers Schreur, Paul J. ; Clark, Madeleine H.A. ; Hill, Adrian V.S. ; Gilbert, Sarah C. ; Francis, Michael J. ; Keulen, Lucien van; Kortekaas, Jeroen ; Charleston, Bryan ; Warimwe, George M. - \ 2019
Vaccines 4 (2019)1. - ISSN 2076-393X

Rift Valley fever virus (RVFV) is a zoonotic mosquito-borne virus that was first discovered in Kenya in 1930 and has since spread to become endemic in much of Africa and the Arabian Peninsula. Rift Valley fever (RVF) causes recurrent outbreaks of febrile illness associated with high levels of mortality and poor outcomes during pregnancy—including foetal malformations, spontaneous abortion and stillbirths—in livestock, and associated with miscarriage in humans. No vaccines are available for human use and those licensed for veterinary use have potential drawbacks, including residual virulence that may contraindicate their use in pregnancy. To address this gap, we previously developed a simian adenovirus vectored vaccine, ChAdOx1 RVF, that encodes RVFV envelope glycoproteins. ChAdOx1 RVF is fully protective against RVF in non-pregnant livestock and is also under development for human use. Here, we now demonstrate that when administered to pregnant sheep and goats, ChAdOx1 RVF is safe, elicits high titre RVFV neutralizing antibody, and provides protection against viraemia and foetal loss, although this protection is not as robust for the goats. In addition, we provide a description of RVFV challenge in pregnant goats and contrast this to the pathology observed in pregnant sheep. Together, our data further support the ongoing development of ChAdOx1 RVF vaccine for use in livestock and humans.

The ecology of lianas and trees in tropical forest canopies
Medina Vega, José A. - \ 2019
Wageningen University. Promotor(en): F.J. Sterck; F.J.J.M. Bongers, co-promotor(en): S.J. Wright; S.A. Schnitzer. - Wageningen : Wageningen University - ISBN 9789463951050 - 198
Rift Valley fever: biology and epidemiology
Wright, Daniel ; Kortekaas, Jeroen ; Bowden, Thomas A. ; Warimwe, George M. - \ 2019
Journal of General Virology 100 (2019)8. - ISSN 0022-1317 - p. 1187 - 1199.
epidemiology - one health - pathogenesis - Rift Valley fever - transmission - vaccine

Rift Valley fever (RVF) is a mosquito-borne viral zoonosis that was first discovered in Kenya in 1930 and is now endemic throughout multiple African countries and the Arabian Peninsula. RVF virus primarily infects domestic livestock (sheep, goats, cattle) causing high rates of neonatal mortality and abortion, with human infection resulting in a wide variety of clinical outcomes, ranging from self-limiting febrile illness to life-threatening haemorrhagic diatheses, and miscarriage in pregnant women. Since its discovery, RVF has caused many outbreaks in Africa and the Arabian Peninsula with major impacts on human and animal health. However, options for the control of RVF outbreaks are limited by the lack of licensed human vaccines or therapeutics. For this reason, RVF is prioritized by the World Health Organization for urgent research and development of countermeasures for the prevention and control of future outbreaks. In this review, we highlight the current understanding of RVF, including its epidemiology, pathogenesis, clinical manifestations and status of vaccine development.

Leaf economics and plant hydraulics drive leaf: wood area ratios
Mencuccini, Maurizio ; Rosas, Teresa ; Rowland, Lucy ; Choat, Brendan ; Cornelissen, Hans ; Jansen, Steven ; Kramer, Koen ; Lapenis, Andrei ; Manzoni, Stefano ; Niinemets, Ülo ; Reich, Peter ; Schrodt, Franziska ; Soudzilovskaia, Nadia ; Wright, Ian J. ; Martínez-Vilalta, Jordi - \ 2019
New Phytologist (2019). - ISSN 0028-646X
biomechanics - Corner's rules - Huber value - leaf economics spectrum - leaf size - trait trade-off - wood density - xylem hydraulics

Biomass and area ratios between leaves, stems and roots regulate many physiological and ecological processes. The Huber value Hv (sapwood area/leaf area ratio) is central to plant water balance and drought responses. However, its coordination with key plant functional traits is poorly understood, and prevents developing trait-based prediction models. Based on theoretical arguments, we hypothesise that global patterns in Hv of terminal woody branches can be predicted from variables related to plant trait spectra, that is plant hydraulics and size and leaf economics. Using a global compilation of 1135 species-averaged Hv, we show that Hv varies over three orders of magnitude. Higher Hv are seen in short small-leaved low-specific leaf area (SLA) shrubs with low Ks in arid relative to tall large-leaved high-SLA trees with high Ks in moist environments. All traits depend on climate but climatic correlations are stronger for explanatory traits than Hv. Negative isometry is found between Hv and Ks, suggesting a compensation to maintain hydraulic supply to leaves across species. This work identifies the major global drivers of branch sapwood/leaf area ratios. Our approach based on widely available traits facilitates the development of accurate models of above-ground biomass allocation and helps predict vegetation responses to drought.

A sound approach: Exploring a rapid and non-destructive ultrasonic pulse echo system for vegetable oils characterization
Yan, Jing ; Wright, William M.D. ; O'Mahony, James A. ; Roos, Yrjö ; Cuijpers, Eric ; Ruth, Saskia M. van - \ 2019
Food Research International 125 (2019). - ISSN 0963-9969
Density - Fatty acids - Rheology - Ultrasonic velocity

A rapid and non-destructive ultrasonic pulse echo system was developed for vegetable oils characterization. To understand the differences in the ultrasonic properties of the oils, physical traits, such as their viscosity and density, were related to the ultrasonic data. In turn, these physical traits were correlated with the fatty acid compositions of the oils. Eighty oil samples, including 30 extra virgin olive oil (EVOO), 15 refined olive oil, 15 pomace olive oil, 10 rapeseed oil, 5 sunflower oil and 5 peanut oil samples, were analysed for their sound properties, viscosities, densities and fatty acid compositions. It was observed that the ultrasonic velocity of EVOO decreased linearly with increase in temperature, the temperature coefficient of ultrasonic velocity in EVOO was −2.92 m·s−1·°C−1. The ultrasonic velocity of EVOO (1453 ± 2 m/s) differed significantly from those of pomace olive oil and the oils of other botanical origin, but not from the velocity of refined olive oil. Ultrasonic velocity was positively correlated with the density and negatively correlated with the viscosity of the oils. The higher density and lower viscosity of the oils were in turn related to a higher unsaturation degree of the oils. Hence, oils with a higher proportion of unsaturated fat present higher densities and lower viscosities, which resulted in higher ultrasonic velocity values. Ultrasonic measurements allow rapid, non-destructive analysis, and this first application for characterization of these oils is promising.

Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts
Santos, S. ; Voerman, E. ; Amiano, P. ; Barros, H. ; Beilin, L.J. ; Bergström, A. ; Charles, M.A. ; Chatzi, L. ; Chevrier, C. ; Chrousos, G.P. ; Corpeleijn, E. ; Costa, O. ; Costet, N. ; Crozier, S. ; Devereux, G. ; Doyon, M. ; Eggesbø, M. ; Fantini, M.P. ; Farchi, S. ; Forastiere, F. ; Georgiu, V. ; Godfrey, K.M. ; Gori, D. ; Grote, V. ; Hanke, W. ; Hertz-Picciotto, I. ; Heude, B. ; Hivert, M.F. ; Hryhorczuk, D. ; Huang, R.C. ; Inskip, H. ; Karvonen, A.M. ; Kenny, L.C. ; Koletzko, B. ; Küpers, L.K. ; Lagström, H. ; Lehmann, I. ; Magnus, P. ; Majewska, R. ; Mäkelä, J. ; Manios, Y. ; McAuliffe, F.M. ; McDonald, S.W. ; Mehegan, J. ; Melén, E. ; Mommers, M. ; Morgen, C.S. ; Moschonis, G. ; Murray, D. ; Ní Chaoimh, C. ; Nohr, E.A. ; Nybo Andersen, A.M. ; Oken, E. ; Oostvogels, A.J.J.M. ; Pac, A. ; Papadopoulou, E. ; Pekkanen, J. ; Pizzi, C. ; Polanska, K. ; Porta, D. ; Richiardi, L. ; Rifas-Shiman, S.L. ; Roeleveld, N. ; Ronfani, L. ; Santos, A.C. ; Standl, M. ; Stigum, H. ; Stoltenberg, C. ; Thiering, E. ; Thijs, C. ; Torrent, M. ; Tough, S.C. ; Trnovec, T. ; Turner, S. ; Gelder, M.M.H.J. van; Rossem, L. van; Berg, A. von; Vrijheid, M. ; Vrijkotte, T.G.M. ; West, J. ; Wijga, A.H. ; Wright, J. ; Zvinchuk, O. ; Sørensen, T.I.A. ; Lawlor, D.A. ; Gaillard, R. ; Jaddoe, V.W.V. - \ 2019
BJOG : an international journal of obstetrics and gynaecology 126 (2019)8. - ISSN 1470-0328 - p. 984 - 995.
Birthweight - body mass index - pregnancy complications - preterm birth - weight gain

Objective: To assess the separate and combined associations of maternal pre-pregnancy body mass index (BMI) and gestational weight gain with the risks of pregnancy complications and their population impact. Design: Individual participant data meta-analysis of 39 cohorts. Setting: Europe, North America, and Oceania. Population: 265 270 births. Methods: Information on maternal pre-pregnancy BMI, gestational weight gain, and pregnancy complications was obtained. Multilevel binary logistic regression models were used. Main outcome measures: Gestational hypertension, pre-eclampsia, gestational diabetes, preterm birth, small and large for gestational age at birth. Results: Higher maternal pre-pregnancy BMI and gestational weight gain were, across their full ranges, associated with higher risks of gestational hypertensive disorders, gestational diabetes, and large for gestational age at birth. Preterm birth risk was higher at lower and higher BMI and weight gain. Compared with normal weight mothers with medium gestational weight gain, obese mothers with high gestational weight gain had the highest risk of any pregnancy complication (odds ratio 2.51, 95% CI 2.31– 2.74). We estimated that 23.9% of any pregnancy complication was attributable to maternal overweight/obesity and 31.6% of large for gestational age infants was attributable to excessive gestational weight gain. Conclusions: Maternal pre-pregnancy BMI and gestational weight gain are, across their full ranges, associated with risks of pregnancy complications. Obese mothers with high gestational weight gain are at the highest risk of pregnancy complications. Promoting a healthy pre-pregnancy BMI and gestational weight gain may reduce the burden of pregnancy complications and ultimately the risk of maternal and neonatal morbidity. Tweetable abstract: Promoting a healthy body mass index and gestational weight gain might reduce the population burden of pregnancy complications.

Mutation dynamics of CpG dinucleotides during a recent event of vertebrate diversification
Pértille, Fábio ; Silva, Vinicius H. Da; Johansson, Anna M. ; Lindström, Tom ; Wright, Dominic ; Coutinho, Luiz L. ; Jensen, Per ; Guerrero-Bosagna, Carlos - \ 2019
Epigenetics 14 (2019)7. - ISSN 1559-2294 - p. 685 - 707.
copy number variations - CpG - DNA methylation - Gallus gallus - genetic variation - germ line - single nucleotide polymorphisms

DNA methylation in CpGs dinucleotides is associated with high mutability and disappearance of CpG sites during evolution. Although the high mutability of CpGs is thought to be relevant for vertebrate evolution, very little is known on the role of CpG-related mutations in the genomic diversification of vertebrates. Our study analysed genetic differences in chickens, between Red Junglefowl (RJF; the living closest relative to the ancestor of domesticated chickens) and domesticated breeds, to identify genomic dynamics that have occurred during the process of their domestication, focusing particularly on CpG-related mutations. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) between RJF and these domesticated breeds were assessed in a reduced fraction of their genome. Additionally, DNA methylation in the same fraction of the genome was measured in the sperm of RJF individuals to identify possible correlations with the mutations found between RJF and the domesticated breeds. Our study shows that although the vast majority of CpG-related mutations found relate to CNVs, CpGs disproportionally associate to SNPs in comparison to CNVs, where they are indeed substantially under-represented. Moreover, CpGs seem to be hotspots of mutations related to speciation. We suggest that, on the one hand, CpG-related mutations in CNV regions would promote genomic ‘flexibility’ in evolution, i.e., the ability of the genome to expand its functional possibilities; on the other hand, CpG-related mutations in SNPs would relate to genomic ‘specificity’ in evolution, thus, representing mutations that would associate with phenotypic traits relevant for speciation.

Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
Küpers, Leanne K. ; Monnereau, Claire ; Sharp, Gemma C. ; Yousefi, Paul ; Salas, Lucas A. ; Ghantous, Akram ; Page, Christian M. ; Reese, Sarah E. ; Wilcox, Allen J. ; Czamara, Darina ; Starling, Anne P. ; Novoloaca, Alexei ; Lent, Samantha ; Roy, Ritu ; Hoyo, Cathrine ; Breton, Carrie V. ; Allard, Catherine ; Just, Allan C. ; Bakulski, Kelly M. ; Holloway, John W. ; Everson, Todd M. ; Xu, Cheng Jian ; Huang, Rae Chi ; Plaat, Diana A. van der; Wielscher, Matthias ; Merid, Simon Kebede ; Ullemar, Vilhelmina ; Rezwan, Faisal I. ; Lahti, Jari ; Dongen, Jenny van; Langie, Sabine A.S. ; Richardson, Tom G. ; Magnus, Maria C. ; Nohr, Ellen A. ; Xu, Zongli ; Duijts, Liesbeth ; Zhao, Shanshan ; Zhang, Weiming ; Plusquin, Michelle ; DeMeo, Dawn L. ; Solomon, Olivia ; Heimovaara, Joosje H. ; Jima, Dereje D. ; Gao, Lu ; Bustamante, Mariona ; Perron, Patrice ; Wright, Robert O. ; Hertz-Picciotto, Irva ; Zhang, Hongmei ; Karagas, Margaret R. ; Gehring, Ulrike ; Marsit, Carmen J. ; Beilin, Lawrence J. ; Vonk, Judith M. ; Jarvelin, Marjo Riitta ; Bergström, Anna ; Örtqvist, Anne K. ; Ewart, Susan ; Villa, Pia M. ; Moore, Sophie E. ; Willemsen, Gonneke ; Standaert, Arnout R.L. ; Håberg, Siri E. ; Sørensen, Thorkild I.A. ; Taylor, Jack A. ; Räikkönen, Katri ; Yang, Ivana V. ; Kechris, Katerina ; Nawrot, Tim S. ; Silver, Matt J. ; Gong, Yun Yun ; Richiardi, Lorenzo ; Kogevinas, Manolis ; Litonjua, Augusto A. ; Eskenazi, Brenda ; Huen, Karen ; Mbarek, Hamdi ; Maguire, Rachel L. ; Dwyer, Terence ; Vrijheid, Martine ; Bouchard, Luigi ; Baccarelli, Andrea A. ; Croen, Lisa A. ; Karmaus, Wilfried ; Anderson, Denise ; Vries, Maaike de; Sebert, Sylvain ; Kere, Juha ; Karlsson, Robert ; Arshad, Syed Hasan ; Hämäläinen, Esa ; Routledge, Michael N. ; Boomsma, Dorret I. ; Feinberg, Andrew P. ; Newschaffer, Craig J. ; Govarts, Eva ; Moisse, Matthieu ; Fallin, M.D. ; Melén, Erik ; Prentice, Andrew M. ; Kajantie, Eero ; Almqvist, Catarina ; Oken, Emily ; Dabelea, Dana ; Boezen, H.M. ; Melton, Phillip E. ; Wright, Rosalind J. ; Koppelman, Gerard H. ; Trevisi, Letizia ; Hivert, Marie France ; Sunyer, Jordi ; Munthe-Kaas, Monica C. ; Murphy, Susan K. ; Corpeleijn, Eva ; Wiemels, Joseph ; Holland, Nina ; Herceg, Zdenko ; Binder, Elisabeth B. ; Davey Smith, George ; Jaddoe, Vincent W.V. ; Lie, Rolv T. ; Nystad, Wenche ; London, Stephanie J. ; Lawlor, Debbie A. ; Relton, Caroline L. ; Snieder, Harold ; Felix, Janine F. - \ 2019
Nature Communications 10 (2019)1. - ISSN 2041-1723

Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (P Bonferroni < 1.06 x 10 −7 ). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10 −74 ) and BMI in pregnancy (3/914, p = 1.13x10 −3 ), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.

Wet and dry tropical forests show opposite successional pathways in wood density but converge over time
Poorter, Lourens ; Rozendaal, Danaë M.A. ; Bongers, Frans ; Almeida-Cortez, Jarcilene S. de; Almeyda Zambrano, Angélica María ; Álvarez, Francisco S. ; Andrade, José Luís ; Villa, Luis Felipe Arreola ; Balvanera, Patricia ; Becknell, Justin M. ; Bentos, Tony V. ; Bhaskar, Radika ; Boukili, Vanessa ; Brancalion, Pedro H.S. ; Broadbent, Eben N. ; César, Ricardo G. ; Chave, Jerome ; Chazdon, Robin L. ; Colletta, Gabriel Dalla ; Craven, Dylan ; Jong, Ben H.J. de; Denslow, Julie S. ; Dent, Daisy H. ; DeWalt, Saara J. ; García, Elisa Díaz ; Dupuy, Juan Manuel ; Durán, Sandra M. ; Espírito Santo, Mário M. ; Fandiño, María C. ; Fernandes, Geraldo Wilson ; Finegan, Bryan ; Moser, Vanessa Granda ; Hall, Jefferson S. ; Hernández-Stefanoni, José Luis ; Jakovac, Catarina C. ; Junqueira, André B. ; Kennard, Deborah ; Lebrija-Trejos, Edwin ; Letcher, Susan G. ; Lohbeck, Madelon ; Lopez, Omar R. ; Marín-Spiotta, Erika ; Martínez-Ramos, Miguel ; Martins, Sebastião V. ; Massoca, Paulo E.S. ; Meave, Jorge A. ; Mesquita, Rita ; Mora, Francisco ; Souza Moreno, Vanessa de; Müller, Sandra C. ; Muñoz, Rodrigo ; Muscarella, Robert ; Oliveira Neto, Silvio Nolasco de; Nunes, Yule R.F. ; Ochoa-Gaona, Susana ; Paz, Horacio ; Peña-Claros, Marielos ; Piotto, Daniel ; Ruíz, Jorge ; Sanaphre-Villanueva, Lucía ; Sanchez-Azofeifa, Arturo ; Schwartz, Naomi B. ; Steininger, Marc K. ; Thomas, William Wayt ; Toledo, Marisol ; Uriarte, Maria ; Utrera, Luis P. ; Breugel, Michiel van; Sande, Masha T. van der; Wal, Hans van der; Veloso, Maria D.M. ; Vester, Hans F.M. ; Vieira, Ima C.G. ; Villa, Pedro Manuel ; Williamson, G.B. ; Wright, S.J. ; Zanini, Kátia J. ; Zimmerman, Jess K. ; Westoby, Mark - \ 2019
Nature Ecology & Evolution 3 (2019). - ISSN 2397-334X - p. 928 - 934.

Tropical forests are converted at an alarming rate for agricultural use and pastureland, but also regrow naturally through secondary succession. For successful forest restoration, it is essential to understand the mechanisms of secondary succession. These mechanisms may vary across forest types, but analyses across broad spatial scales are lacking. Here, we analyse forest recovery using 1,403 plots that differ in age since agricultural abandonment from 50 sites across the Neotropics. We analyse changes in community composition using species-specific stem wood density (WD), which is a key trait for plant growth, survival and forest carbon storage. In wet forest, succession proceeds from low towards high community WD (acquisitive towards conservative trait values), in line with standard successional theory. However, in dry forest, succession proceeds from high towards low community WD (conservative towards acquisitive trait values), probably because high WD reflects drought tolerance in harsh early successional environments. Dry season intensity drives WD recovery by influencing the start and trajectory of succession, resulting in convergence of the community WD over time as vegetation cover builds up. These ecological insights can be used to improve species selection for reforestation. Reforestation species selected to establish a first protective canopy layer should, among other criteria, ideally have a similar WD to the early successional communities that dominate under the prevailing macroclimatic conditions.

Disentangling the genetics of lean mass
Karasik, David ; Zillikens, M.C. ; Hsu, Yi Hsiang ; Aghdassi, Ali ; Akesson, Kristina ; Amin, Najaf ; Barroso, Inês ; Bennett, David A. ; Bertram, Lars ; Bochud, Murielle ; Borecki, Ingrid B. ; Broer, Linda ; Buchman, Aron S. ; Byberg, Liisa ; Campbell, Harry ; Campos-Obando, Natalia ; Cauley, Jane A. ; Cawthon, Peggy M. ; Chambers, John C. ; Chen, Zhao ; Cho, Nam H. ; Choi, Hyung Jin ; Chou, Wen Chi ; Cummings, Steven R. ; Groot, Lisette C.P.G.M. De; Jager, Phillip L. De; Demuth, Ilja ; Diatchenko, Luda ; Econs, Michael J. ; Eiriksdottir, Gudny ; Enneman, Anke W. ; Eriksson, Joel ; Eriksson, Johan G. ; Estrada, Karol ; Evans, Daniel S. ; Feitosa, Mary F. ; Fu, Mao ; Gieger, Christian ; Grallert, Harald ; Gudnason, Vilmundur ; Lenore, Launer J. ; Hayward, Caroline ; Hofman, Albert ; Homuth, Georg ; Huffman, Kim M. ; Husted, Lise B. ; Illig, Thomas ; Ingelsson, Erik ; Ittermann, Till ; Jansson, John Olov ; Johnson, Toby ; Biffar, Reiner ; Jordan, Joanne M. ; Jula, Antti ; Karlsson, Magnus ; Khaw, Kay Tee ; Kilpeläinen, Tuomas O. ; Klopp, Norman ; Kloth, Jacqueline S.L. ; Koller, Daniel L. ; Kooner, Jaspal S. ; Kraus, William E. ; Kritchevsky, Stephen ; Kutalik, Zoltán ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Laakso, Markku ; Lahti, Jari ; Lang, Thomas ; Langdahl, Bente L. ; Lerch, Markus M. ; Lewis, Joshua R. ; Lill, Christina ; Lind, Lars ; Lindgren, Cecilia ; Liu, Yongmei ; Livshits, Gregory ; Ljunggren, Östen ; Loos, Ruth J.F. ; Lorentzon, Mattias ; Luan, Jian An ; Luben, Robert N. ; Malkin, Ida ; McGuigan, Fiona E. ; Medina-Gomez, Carolina ; Meitinger, Thomas ; Melhus, Håkan ; Mellström, Dan ; Michaëlsson, Karl ; Mitchell, Braxton D. ; Morris, Andrew P. ; Mosekilde, Leif ; Nethander, Maria ; Newman, Anne B. ; Oconnell, Jeffery R. ; Oostra, Ben A. ; Orwoll, Eric S. ; Palotie, Aarno ; Peacock, Munro ; Perola, Markus ; Peters, Annette ; Prince, Richard L. ; Psaty, Bruce M. ; Räikkönen, Katri ; Ralston, Stuart H. ; Ripatti, Samuli ; Rivadeneira, Fernando ; Robbins, John A. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Satterfield, Suzanne ; Schipf, Sabine ; Shin, Chan Soo ; Smith, Albert V. ; Smith, Shad B. ; Soranzo, Nicole ; Spector, Timothy D. ; StanÄ Áková, Alena ; Stefansson, Kari ; Steinhagen-Thiessen, Elisabeth ; Stolk, Lisette ; Streeten, Elizabeth A. ; Styrkarsdottir, Unnur ; Swart, Karin M.A. ; Thompson, Patricia ; Thomson, Cynthia A. ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Tikkanen, Emmi ; Tranah, Gregory J. ; Uitterlinden, André G. ; Duijn, Cornelia M. Van; Schoor, Natasja M. Van; Vandenput, Liesbeth ; Vollenweider, Peter ; Völzke, Henry ; Wactawski-Wende, Jean ; Walker, Mark ; J Wareham, Nicholas ; Waterworth, Dawn ; Weedon, Michael N. ; Wichmann, H.E. ; Widen, Elisabeth ; Williams, Frances M.K. ; Wilson, James F. ; Wright, Nicole C. ; Yerges-Armstrong, Laura M. ; Yu, Lei ; Zhang, Weihua ; Zhao, Jing Hua ; Zhou, Yanhua ; Nielson, Carrie M. ; Harris, Tamara B. ; Demissie, Serkalem ; Kiel, Douglas P. ; Ohlsson, Claes - \ 2019
American Journal of Clinical Nutrition 109 (2019)2. - ISSN 0002-9165 - p. 276 - 278.
body composition - body fat - meta-Analysis of genome-wide association studies - metabolic profile - skeletal muscle

Background Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age 2, and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based on the strengths of the associations in Model 1 vs Model 3, we divided the LM loci into those with an effect on both lean mass and fat mass in the same direction and refer to those as "sumo wrestler" loci (FTO and MC4R). In contrast, loci with an impact specifically on LM were termed "body builder" loci (VCAN and ADAMTSL3). Using existing available genome-wide association study databases, LM increasing alleles of SNPs in sumo wrestler loci were associated with an adverse metabolic profile, whereas LM increasing alleles of SNPs in "body builder" loci were associated with metabolic protection. Conclusions In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

The plastidial metabolite 2-C-methyl-D-erythritol-2,4-cyclodiphosphate modulates defence responses against aphids
Onkokesung, Nawaporn ; Reichelt, Michael ; Wright, Louwrance P. ; Phillips, Michael A. ; Gershenzon, Jonathan ; Dicke, Marcel - \ 2019
Plant, Cell & Environment 42 (2019)7. - ISSN 0140-7791 - p. 2309 - 2323.
aphid resistance - Arabidopsis - indole glucosinolates - phloem-sucking herbivores - phytohormone signalling - retrograde signalling - secondary metabolites

Feeding by insect herbivores such as caterpillars and aphids induces plant resistance mechanisms that are mediated by the phytohormones jasmonic acid (JA) and salicylic acid (SA). These phytohormonal pathways often crosstalk. Besides phytohormones, methyl-D-erythriol-2,4-cyclodiphosphate (MEcPP), the penultimate metabolite in the methyl-D-erythritol-4-phosphate pathway, has been speculated to regulate transcription of nuclear genes in response to biotic stressors such as aphids. Here, we show that MEcPP uniquely enhances the SA pathway without attenuating the JA pathway. Arabidopsis mutant plants that accumulate high levels of MEcPP (hds3) are highly resistant to the cabbage aphid (Brevicoryne brassicae), whereas resistance to the large cabbage white caterpillar (Pieris brassicae) remains unaltered. Thus, MEcPP is a distinct signalling molecule that acts beyond phytohormonal crosstalk to induce resistance against the cabbage aphid in Arabidopsis. We dissect the molecular mechanisms of MEcPP mediating plant resistance against the aphid B. brassicae. This shows that MEcPP induces the expression of genes encoding enzymes involved in the biosynthesis of several primary and secondary metabolic pathways contributing to enhanced resistance against this aphid species. A unique ability to regulate multifaceted molecular mechanisms makes MEcPP an attractive target for metabolic engineering in Brassica crop plants to increase resistance to cabbage aphids.

CRISPR-Cas Systems Reduced to a Minimum
Almendros, Cristóbal ; Kieper, Sebastian N. ; Brouns, Stan J.J. - \ 2019
Molecular Cell 73 (2019)4. - ISSN 1097-2765 - p. 641 - 642.

In two recent studies in Molecular Cell, Wright et al. (2019) report complete spacer integration by a Cas1 mini-integrase and Edraki et al. (2019) describe accurate genome editing by a small Cas9 ortholog with less stringent PAM requirements.

Maternal body mass index, gestational weight gain, and the risk of overweight and obesity across childhood : An individual participant data meta-analysis
Voerman, Ellis ; Santos, Susana ; Patro Golab, Bernadeta ; Amiano, Pilar ; Ballester, Ferran ; Barros, Henrique ; Bergström, Anna ; Charles, Marie Aline ; Chatzi, Leda ; Chevrier, Cécile ; Chrousos, George P. ; Corpeleijn, Eva ; Costet, Nathalie ; Crozier, Sarah ; Devereux, Graham ; Eggesbø, Merete ; Ekström, Sandra ; Fantini, Maria Pia ; Farchi, Sara ; Forastiere, Francesco ; Georgiu, Vagelis ; Godfrey, Keith M. ; Gori, Davide ; Grote, Veit ; Hanke, Wojciech ; Hertz-Picciotto, Irva ; Heude, Barbara ; Hryhorczuk, Daniel ; Huang, Rae Chi ; Inskip, Hazel ; Iszatt, Nina ; Karvonen, Anne M. ; Kenny, Louise C. ; Koletzko, Berthold ; Küpers, Leanne K. ; Lagström, Hanna ; Lehmann, Irina ; Magnus, Per ; Majewska, Renata ; Mäkelä, Johanna ; Manios, Yannis ; McAuliffe, Fionnuala M. ; McDonald, Sheila W. ; Mehegan, John ; Mommers, Monique ; Morgen, Camilla S. ; Mori, Trevor A. ; Moschonis, George ; Murray, Deirdre ; Chaoimh, Carol Ní ; Nohr, Ellen A. ; Nybo Andersen, Anne Marie ; Oken, Emily ; Oostvogels, Adriëtte J.J.M. ; Pac, Agnieszka ; Papadopoulou, Eleni ; Pekkanen, Juha ; Pizzi, Costanza ; Polanska, Kinga ; Porta, Daniela ; Richiardi, Lorenzo ; Rifas-Shiman, Sheryl L. ; Ronfani, Luca ; Santos, Ana C. ; Standl, Marie ; Stoltenberg, Camilla ; Thiering, Elisabeth ; Thijs, Carel ; Torrent, Maties ; Tough, Suzanne C. ; Trnovec, Tomas ; Turner, Steve ; Rossem, Lenie van; Berg, Andrea von; Vrijheid, Martine ; Vrijkotte, Tanja G.M. ; West, Jane ; Wijga, Alet ; Wright, John ; Zvinchuk, Oleksandr ; Sørensen, Thorkild I.A. ; Lawlor, Debbie A. ; Gaillard, Romy ; Jaddoe, Vincent W.V. - \ 2019
PLOS Medicine 16 (2019)2. - ISSN 1549-1676 - p. e1002744 - e1002744.

BACKGROUND: Maternal obesity and excessive gestational weight gain may have persistent effects on offspring fat development. However, it remains unclear whether these effects differ by severity of obesity, and whether these effects are restricted to the extremes of maternal body mass index (BMI) and gestational weight gain. We aimed to assess the separate and combined associations of maternal BMI and gestational weight gain with the risk of overweight/obesity throughout childhood, and their population impact. METHODS AND FINDINGS: We conducted an individual participant data meta-analysis of data from 162,129 mothers and their children from 37 pregnancy and birth cohort studies from Europe, North America, and Australia. We assessed the individual and combined associations of maternal pre-pregnancy BMI and gestational weight gain, both in clinical categories and across their full ranges, with the risks of overweight/obesity in early (2.0-5.0 years), mid (5.0-10.0 years) and late childhood (10.0-18.0 years), using multilevel binary logistic regression models with a random intercept at cohort level adjusted for maternal sociodemographic and lifestyle-related characteristics. We observed that higher maternal pre-pregnancy BMI and gestational weight gain both in clinical categories and across their full ranges were associated with higher risks of childhood overweight/obesity, with the strongest effects in late childhood (odds ratios [ORs] for overweight/obesity in early, mid, and late childhood, respectively: OR 1.66 [95% CI: 1.56, 1.78], OR 1.91 [95% CI: 1.85, 1.98], and OR 2.28 [95% CI: 2.08, 2.50] for maternal overweight; OR 2.43 [95% CI: 2.24, 2.64], OR 3.12 [95% CI: 2.98, 3.27], and OR 4.47 [95% CI: 3.99, 5.23] for maternal obesity; and OR 1.39 [95% CI: 1.30, 1.49], OR 1.55 [95% CI: 1.49, 1.60], and OR 1.72 [95% CI: 1.56, 1.91] for excessive gestational weight gain). The proportions of childhood overweight/obesity prevalence attributable to maternal overweight, maternal obesity, and excessive gestational weight gain ranged from 10.2% to 21.6%. Relative to the effect of maternal BMI, excessive gestational weight gain only slightly increased the risk of childhood overweight/obesity within each clinical BMI category (p-values for interactions of maternal BMI with gestational weight gain: p = 0.038, p < 0.001, and p = 0.637 in early, mid, and late childhood, respectively). Limitations of this study include the self-report of maternal BMI and gestational weight gain for some of the cohorts, and the potential of residual confounding. Also, as this study only included participants from Europe, North America, and Australia, results need to be interpreted with caution with respect to other populations. CONCLUSIONS: In this study, higher maternal pre-pregnancy BMI and gestational weight gain were associated with an increased risk of childhood overweight/obesity, with the strongest effects at later ages. The additional effect of gestational weight gain in women who are overweight or obese before pregnancy is small. Given the large population impact, future intervention trials aiming to reduce the prevalence of childhood overweight and obesity should focus on maternal weight status before pregnancy, in addition to weight gain during pregnancy.

Homoeostatic maintenance of nonstructural carbohydrates during the 2015–2016 El Niño drought across a tropical forest precipitation gradient
Dickman, Lee Turin ; McDowell, Nate G. ; Grossiord, Charlotte ; Collins, Adam D. ; Wolfe, Brett T. ; Detto, Matteo ; Wright, S.J. ; Medina-Vega, José A. ; Goodsman, Devin ; Rogers, Alistair ; Serbin, Shawn P. ; Wu, Jin ; Ely, Kim S. ; Michaletz, Sean T. ; Xu, Chonggang ; Kueppers, Lara ; Chambers, Jeffrey Q. - \ 2019
Plant, Cell & Environment 42 (2019)5. - ISSN 0140-7791 - p. 1705 - 1714.
climate - ENSO - NSC - Panama - storage - sugars - tropics - vegetation

Nonstructural carbohydrates (NSCs) are essential for maintenance of plant metabolism and may be sensitive to short- and long-term climatic variation. NSC variation in moist tropical forests has rarely been studied, so regulation of NSCs in these systems is poorly understood. We measured foliar and branch NSC content in 23 tree species at three sites located across a large precipitation gradient in Panama during the 2015–2016 El Niño to examine how short- and long-term climatic variation impact carbohydrate dynamics. There was no significant difference in total NSCs as the drought progressed (leaf P = 0.32, branch P = 0.30) nor across the rainfall gradient (leaf P = 0.91, branch P = 0.96). Foliar soluble sugars decreased while starch increased over the duration of the dry period, suggesting greater partitioning of NSCs to storage than metabolism or transport as drought progressed. There was a large variation across species at all sites, but total foliar NSCs were positively correlated with leaf mass per area, whereas branch sugars were positively related to leaf temperature and negatively correlated with daily photosynthesis and wood density. The NSC homoeostasis across a wide range of conditions suggests that NSCs are an allocation priority in moist tropical forests.

The Future of Complementarity : Disentangling Causes from Consequences
Barry, Kathryn E. ; Mommer, Liesje ; Ruijven, Jasper van; Wirth, Christian ; Wright, Alexandra J. ; Bai, Yongfei ; Connolly, John ; Deyn, Gerlinde B. De; Kroon, Hans de; Isbell, Forest ; Milcu, Alexandru ; Roscher, Christiane ; Scherer-Lorenzen, Michael ; Schmid, Bernhard ; Weigelt, Alexandra - \ 2019
Trends in Ecology and Evolution 34 (2019)2. - ISSN 0169-5347 - p. 167 - 180.
Abiotic facilitation - Biodiversity - Biotic feedbacks - Complementarity - Complementarity effect - Ecosystem functioning - Plant-soil feedback - Resource partitioning - Resource tracers - Stress amelioration

Evidence suggests that biodiversity supports ecosystem functioning. Yet, the mechanisms driving this relationship remain unclear. Complementarity is one common explanation for these positive biodiversity–ecosystem functioning relationships. Yet, complementarity is often indirectly quantified as overperformance in mixture relative to monoculture (e.g., ‘complementarity effect’). This overperformance is then attributed to the intuitive idea of complementarity or, more specifically, to species resource partitioning. Locally, however, several unassociated causes may drive this overperformance. Here, we differentiate complementarity into three types of species differences that may cause enhanced ecosystem functioning in more diverse ecosystems: (i) resource partitioning, (ii) abiotic facilitation, and (iii) biotic feedbacks. We argue that disentangling these three causes is crucial for predicting the response of ecosystems to future biodiversity loss.

6S rRNA sequence of rumen microbes in dairy cattle
Difford, Gareth ; Plichta, Damian Rafal ; Løvendahl, Peter ; Lassen, Jan ; Noel, Samantha Joan ; Højberg, Ole ; Wright, André Denis G. ; Zhu, Zhigang ; Kristensen, Lise ; Nielsen, Henrik Bjørn ; Guldbrandtsen, Bernt ; Sahana, Goutam - \ 2018
Aarhus University
PRJEB28065 - ERP110230
The 16S rRNA sequence data was generated in the project entitled "Reduction of methane emissions from dairy cows and concurrent improvement of feed efficiency obtained through host genetics and next generation sequencing of rumen microbiome" using Illumina sequencing technology.
Assessment of the genetic and clinical determinants of fracture risk : Genome wide association and mendelian randomisation study
Trajanoska, Katerina ; Morris, John A. ; Oei, Ling ; Zheng, Hou Feng ; Evans, David M. ; Kiel, Douglas P. ; Ohlsson, Claes ; Richards, J.B. ; Rivadeneira, Fernando ; Forgett, V. ; Leong, A. ; Ahmad, O.S. ; Laurin, C. ; Mokry, L.E. ; Ross, S. ; Elks, C.E. ; Bowden, J. ; Warrington, N.M. ; Kleinman, A. ; Willems, S.M. ; Wright, D. ; Day, F.R. ; Murray, A. ; Ruth, K.S. ; Tsilidis, K.K. ; Ackert-Bicknell, C.L. ; Bassett, J.H.D. ; Eerden, B.C.J. van der; Gautvik, K. ; Reppe, S. ; Williams, G.R. ; Medina-Gómez, C. ; Estrada, K. ; Amin, N. ; Enneman, A.W. ; Li, G. ; Liu, C.T. ; Liu, Y. ; Xiao, S.M. ; Lee, S.H. ; Koh, J.M. ; Tang, N.L.S. ; Cummings, S.R. ; Brown, M. ; Groot, L. de; Jukema, J.W. ; Lips, P. ; Meurs, J.B.J. van; Smith, A.V. ; Tian, S. - \ 2018
BMJ: British Medical Journal 362 (2018). - ISSN 0959-8146

Objectives To identify the genetic determinants of fracture risk and assess the role of 15 clinical risk factors on osteoporotic fracture risk. Design Meta-analysis of genome wide association studies (GWAS) and a two-sample mendelian randomisation approach. Setting 25 cohorts from Europe, United States, east Asia, and Australia with genome wide genotyping and fracture data. Participants A discovery set of 37 857 fracture cases and 227 116 controls; with replication in up to 147 200 fracture cases and 150 085 controls. Fracture cases were defined as individuals (>18 years old) who had fractures at any skeletal site confirmed by medical, radiological, or questionnaire reports. Instrumental variable analyses were performed to estimate effects of 15 selected clinical risk factors for fracture in a two-sample mendelian randomisation framework, using the largest previously published GWAS meta-analysis of each risk factor. Results Of 15 fracture associated loci identified, all were also associated with bone mineral density and mapped to genes clustering in pathways known to be critical to bone biology (eg, SOST, WNT16, and ESR1) or novel pathways (FAM210A, GRB10, and ETS2). Mendelian randomisation analyses showed a clear effect of bone mineral density on fracture risk. One standard deviation decrease in genetically determined bone mineral density of the femoral neck was associated with a 55% increase in fracture risk (odds ratio 1.55 (95% confidence interval 1.48 to 1.63; P=1.5×10'68). Hand grip strength was inversely associated with fracture risk, but this result was not significant after multiple testing correction. The remaining clinical risk factors (including vitamin D levels) showed no evidence for an effect on fracture. Conclusions This large scale GWAS meta-analysis for fracture identified 15 genetic determinants of fracture, all of which also influenced bone mineral density. Among the clinical risk factors for fracture assessed, only bone mineral density showed a major causal effect on fracture. Genetic predisposition to lower levels of vitamin D and estimated calcium intake from dairy sources were not associated with fracture risk.

Study highlights novel approach to dry cows
Knegsel, Ariette van - \ 2018
EFSA Scientific Colloquium 24 – 'omics in risk assessment: state of the art and next steps
Aguilera, Jaime ; Aguilera‐gomez, Margarita ; Barrucci, Federica ; Cocconcelli, Pier Sandro ; Davies, Howard ; Denslow, Nancy ; Lou Dorne, Jean ; Grohmann, Lutz ; Herman, Lieve ; Hogstrand, Christer ; Kass, George E.N. ; Kille, Peter ; Kleter, Gijs ; Nogué, Fabien ; Plant, Nick J. ; Ramon, Matthew ; Schoonjans, Reinhilde ; Waigmann, Elisabeth ; Wright, Matthew C. - \ 2018
EFSA Supporting Publications 15 (2018)11. - ISSN 2397-8325
In recent years, the development of innovative tools in genomics, transcriptomics, proteomics and metabolomics (designated collectively as 'omics technologies) has opened up new possibilities for applications in scientific research and led to the availability of vast amounts of analytical data. The interpretation and integration of 'omics data can provide valuable information on the functional status of an organism and on the effect of external factors such as stressors. The European Food Safety Authority's (EFSA) 24th Scientific Colloquium on 'omics in risk assessment: state of the art and next steps explored the opportunities for integration of datasets produced via specific 'omics tools within the remit of EFSA's risk assessment approaches and tried to build further towards concrete paths of implementation. Discussions focused on genomics in microbial strain characterisation, metabolomics for the comparative assessment of GM plants and the use of 'omics for toxicological and environmental risk assessment. From the Colloquium it became clear that 'omics technologies are a valuable addition in some aspects of risk assessment of food and feed products and the environment, especially now that this technology is almost mature and stable. However, a consistent reporting framework for data collection, processing, interpretation, storage and curation should be further drawn up together with national and international organisations before 'omics technologies can be routinely used in risk assessment. For 'omics datasets in chemical and environmental risk assessments, the use of 'omics technologies alongside current toxicological or environmental risk assessment approaches is needed to re‐inforce confidence and expertise before implementation of these datasets as a standalone tool in risk assessment. Test cases could be worked out to enhance confidence in the use of 'omics datasets in risk assessment.
Host genetics and the rumen microbiome jointly associate with methane emissions in dairy cows
Difford, Gareth Frank ; Plichta, Damian Rafal ; Løvendahl, Peter ; Lassen, Jan ; Noel, Samantha Joan ; Højberg, Ole ; Wright, André Denis G. ; Zhu, Zhigang ; Kristensen, Lise ; Nielsen, Henrik Bjørn ; Guldbrandtsen, Bernt ; Sahana, Goutam - \ 2018
Plos Genetics 14 (2018)10. - ISSN 1553-7404

Cattle and other ruminants produce large quantities of methane (~110 million metric tonnes per annum), which is a potent greenhouse gas affecting global climate change. Methane (CH4) is a natural by-product of gastro-enteric microbial fermentation of feedstuffs in the rumen and contributes to 6% of total CH4 emissions from anthropogenic-related sources. The extent to which the host genome and rumen microbiome influence CH4 emission is not yet well known. This study confirms individual variation in CH4 production was influenced by individual host (cow) genotype, as well as the host's rumen microbiome composition. Abundance of a small proportion of bacteria and archaea taxa were influenced to a limited extent by the host's genotype and certain taxa were associated with CH4 emissions. However, the cumulative effect of all bacteria and archaea on CH4 production was 13%, the host genetics (heritability) was 21% and the two are largely independent. This study demonstrates variation in CH4 emission is likely not modulated through cow genetic effects on the rumen microbiome. Therefore, the rumen microbiome and cow genome could be targeted independently, by breeding low methane-emitting cows and in parallel, by investigating possible strategies that target changes in the rumen microbiome to reduce CH4 emissions in the cattle industry.

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