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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Toward the improvement of total nitrogen deposition budgets in the United States
Walker, J.T. ; Beachley, G. ; Amos, H.M. ; Baron, J.S. ; Bash, J. ; Baumgardner, R. ; Bell, M.D. ; Benedict, K.B. ; Chen, X. ; Clow, D.W. ; Cole, A. ; Coughlin, J.G. ; Cruz, K. ; Daly, R.W. ; Decina, S.M. ; Elliott, E.M. ; Fenn, M.E. ; Ganzeveld, L. ; Gebhart, K. ; Isil, S.S. ; Kerschner, B.M. ; Larson, R.S. ; Lavery, T. ; Lear, G.G. ; Macy, T. ; Mast, M.A. ; Mishoe, K. ; Morris, K.H. ; Padgett, P.E. ; Pouyat, R.V. ; Puchalski, M. ; Pye, H.O.T. ; Rea, A.W. ; Rhodes, M.F. ; Rogers, C.M. ; Saylor, R. ; Scheffe, R. ; Schichtel, B.A. ; Schwede, D.B. ; Sexstone, G.A. ; Sive, B.C. ; Sosa, R. ; Templer, P.H. ; Thompson, T. ; Tong, D. ; Wetherbee, G.A. ; Whitlow, T.H. ; Wu, Z. ; Yu, Z. ; Zhang, L. - \ 2019
Science of the Total Environment 691 (2019). - ISSN 0048-9697 - p. 1328 - 1352.
Ammonia - Dry deposition - Organic nitrogen - Oxidized nitrogen - Reactive nitrogen - Wet deposition

Frameworks for limiting ecosystem exposure to excess nutrients and acidity require accurate and complete deposition budgets of reactive nitrogen (Nr). While much progress has been made in developing total Nr deposition budgets for the U.S., current budgets remain limited by key data and knowledge gaps. Analysis of National Atmospheric Deposition Program Total Deposition (NADP/TDep) data illustrates several aspects of current Nr deposition that motivate additional research. Averaged across the continental U.S., dry deposition contributes slightly more (55%) to total deposition than wet deposition and is the dominant process (>90%) over broad areas of the Southwest and other arid regions of the West. Lack of dry deposition measurements imposes a reliance on models, resulting in a much higher degree of uncertainty relative to wet deposition which is routinely measured. As nitrogen oxide (NOx) emissions continue to decline, reduced forms of inorganic nitrogen (NHx = NH3 + NH4 +) now contribute >50% of total Nr deposition over large areas of the U.S. Expanded monitoring and additional process-level research are needed to better understand NHx deposition, its contribution to total Nr deposition budgets, and the processes by which reduced N deposits to ecosystems. Urban and suburban areas are hotspots where routine monitoring of oxidized and reduced Nr deposition is needed. Finally, deposition budgets have incomplete information about the speciation of atmospheric nitrogen; monitoring networks do not capture important forms of Nr such as organic nitrogen. Building on these themes, we detail the state of the science of Nr deposition budgets in the U.S. and highlight research priorities to improve deposition budgets in terms of monitoring and flux measurements, leaf- to regional-scale modeling, source apportionment, and characterization of deposition trends and patterns.

Addendum: The FAIR Guiding Principles for scientific data management and stewardship
Wilkinson, Mark D. ; Dumontier, Michel ; Aalbersberg, Ijsbrand Jan ; Appleton, Gabrielle ; Axton, Myles ; Baak, Arie ; Blomberg, Niklas ; Boiten, Jan Willem ; Silva Santos, Luiz Bonino Da; Bourne, Philip E. ; Bouwman, Jildau ; Brookes, Anthony J. ; Clark, Tim ; Crosas, Mercè ; Dillo, Ingrid ; Dumon, Olivier ; Edmunds, Scott ; Evelo, Chris T. ; Finkers, Richard ; Gonzalez-Beltran, Alejandra ; Gray, Alasdair J.G. ; Groth, Paul ; Goble, Carole ; Grethe, Jeffrey S. ; Heringa, Jaap ; Hoen, Peter A.C. 't; Hooft, Rob ; Kuhn, Tobias ; Kok, Ruben ; Kok, Joost ; Lusher, Scott J. ; Martone, Maryann E. ; Mons, Albert ; Packer, Abel L. ; Persson, Bengt ; Rocca-Serra, Philippe ; Roos, Marco ; Schaik, Rene van; Sansone, Susanna Assunta ; Schultes, Erik ; Sengstag, Thierry ; Slater, Ted ; Strawn, George ; Swertz, Morris A. ; Thompson, Mark ; Lei, Johan van der; Mulligen, Erik van; Velterop, Jan ; Waagmeester, Andra ; Wittenburg, Peter ; Wolstencroft, Katherine ; Zhao, Jun ; Mons, Barend - \ 2019
Scientific Data 6 (2019). - ISSN 2052-4463

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.

One Health - Cycling of diverse microbial communities as a connecting force for soil, plant, animal, human and ecosystem health
Bruggen, A.H.C. van; Goss, E.M. ; Havelaar, A. ; Diepeningen, A.D. van; Finckh, Maria R. ; Morris, J.G. - \ 2019
Science of the Total Environment 664 (2019). - ISSN 0048-9697 - p. 927 - 937.
The One Health concept proposes that there is a connection between human, animal and environmental health. Plants and their health are not explicitly included. In this review, we broaden the One Health concept to include soil, plant, animal and ecosystemhealth.Weargue that the health conditions of all organisms in an ecosystemare interconnected through the cycling of subsets of microbial communities fromthe environment (in particular the soil) to plants, animals and humans, and back into the environment. After an introduction on health concepts,we present examples of community stability and resilience, diversity and interconnectedness as affected by pollutants, and integrity of nutrient cycles and energy flows. Next, we explain our concept of microbial cycling in relation to ecosystem health, and end with examples of plant and animal disease outbreaks in relation to microbial community composition and diversity.We conclude thatwe need a better understanding of the role of interconnected microbiomes in promoting plant and animal health and possible ways to stimulate a healthy, diverse microbiome throughout human-dominated ecosystems. We suggest that it is essential to maintain ecosystem and soil health through diversification of plant communities and oligotrophication of managed ecosystems.
What agricultural practices are most likely to deliver “sustainable intensification” in the UK?
Dicks, Lynn V. ; Rose, David C. ; Ang, Frederic ; Aston, Stephen ; Birch, A.N.E. ; Boatman, Nigel ; Bowles, Elizabeth L. ; Chadwick, David ; Dinsdale, Alex ; Durham, Sam ; Elliott, John ; Firbank, Les ; Humphreys, Stephen ; Jarvis, Phil ; Jones, Dewi ; Kindred, Daniel ; Knight, Stuart M. ; Lee, Michael R.F. ; Leifert, Carlo ; Lobley, Matt ; Matthews, Kim ; Midmer, Alice ; Moore, Mark ; Morris, Carol ; Mortimer, Simon ; Murray, T.C. ; Norman, Keith ; Ramsden, Stephen ; Roberts, Dave ; Smith, Laurence G. ; Soffe, Richard ; Stoate, Chris ; Taylor, Bryony ; Tinker, David ; Topliff, Mark ; Wallace, John ; Williams, Prysor ; Wilson, Paul ; Winter, Michael ; Sutherland, William J. - \ 2019
Food and Energy Security 8 (2019)1. - ISSN 2048-3694

Sustainable intensification is a process by which agricultural productivity is enhanced whilst also creating environmental and social benefits. We aimed to identify practices likely to deliver sustainable intensification, currently available for UK farms but not yet widely adopted. We compiled a list of 18 farm management practices with the greatest potential to deliver sustainable intensification in the UK, following a well-developed stepwise methodology for identifying priority solutions, using a group decision-making technique with key agricultural experts. The list of priority management practices can provide the focal point of efforts to achieve sustainable intensification of agriculture, as the UK develops post-Brexit agricultural policy, and pursues the second Sustainable Development Goal, which aims to end hunger and promote sustainable agriculture. The practices largely reflect a technological, production-focused view of sustainable intensification, including for example, precision farming and animal health diagnostics, with less emphasis on the social and environmental aspects of sustainability. However, they do reflect an integrated approach to farming, covering many different aspects, from business organization and planning, to soil and crop management, to landscape and nature conservation. For a subset of 10 of the priority practices, we gathered data on the level of existing uptake in English and Welsh farms through a stratified survey in seven focal regions. We find substantial existing uptake of most of the priority practices, indicating that UK farming is an innovative sector. The data identify two specific practices for which uptake is relatively low, but which some UK farmers find appealing and would consider adopting. These practices are: prediction of pest and disease outbreaks, especially for livestock farms; staff training on environmental issues, especially on arable farms.

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.

Update of the risk assessment on 3‐monochloropropane diol and its fatty acid esters
Knutsen, Helle Katrine ; Alexander, Jan ; Barregård, Lars ; Bignami, Margherita ; Brüschweiler, Beat ; Ceccatelli, Sandra ; Cottrill, Bruce ; Dinovi, Michael ; Edler, Lutz ; Grasl‐Kraupp, Bettina ; Hoogenboom, Laurentius ; Nebbia, Carlo Stefano ; Oswald, Isabelle P. ; Petersen, Annette ; Rose, Martin ; Roudot, Alain-Claude ; Schwerdtle, Tanja ; Vleminckx, Christiane ; Vollmer, Günter ; Wallace, Heather ; Lampen, Alfonso ; Morris, Ian ; Piersma, Aldert ; Schrenk, Dieter ; Binaglia, Marco ; Levorato, Sara ; Hogstrand, Christer - \ 2018
EFSA Journal 16 (2018)1. - ISSN 1831-4732
The CONTAM Panel updated the assessment of the risks for human health related to the presence of 3‐monochloropropane diol (3‐MCPD) and its fatty acid esters in food published in 2016 in view of the scientific divergence identified in the establishment of the tolerable daily intake (TDI) in the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (FAO/WHO) report published in 2017. In this update, dose–response analysis was performed following the recent EFSA Scientific Committee guidance on the use of benchmark dose (BMD) approach in risk assessment, and a review of available data on developmental and reproduction toxicity was included. The outcome of this review indicates that in rats short‐term exposure to 3‐MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity. Decreased sperm count and histopathological changes in the testis and epididymis were observed following longer treatment periods at higher doses. Regarding increased incidence kidney tubular hyperplasia, BMD analysis using model averaging resulted in a BMDL10 of 0.20 mg/kg bw per day in male rats, which was selected as the new Reference Point (RP) for renal effects. For the effects on male fertility, decreased sperm motility was selected as the most sensitive relevant endpoint and a BMDL05 of 0.44 mg/kg bw per day was calculated. The RP for renal effects was considered to derive an updated group TDI of 2 μg/kg bw per day for 3‐MCPD and its fatty acid esters and was considered protective also for effects on male fertility. The established TDI of 2 μg/kg bw per day is not exceeded in the adult population. A slight exceedance of the TDI was observed in the high consumers of the younger age groups and in particular for the scenarios on infants receiving formula only.
Modelling the Plant Microtubule Cytoskeleton
Deinum, Eva E. ; Mulder, Bela M. - \ 2018
In: Mathematical Modelling in Plant Biology / Morris, Richard J., Springer International Publishing - ISBN 9783319990699 - p. 53 - 67.
The physical shape and structure of plants are manifestations of the actions of gene products and their concerted responses to their environment. In this chapter we introduce the plant cortical microtubule array. This structure is both a nexus in the control of plant cell shape and function, and a fascinating out-of-equilibrium system for state-of-the-art physics research. We describe how analytical and computational approaches complement each other in the study of the array, and highlight some recent results and open research questions
Root branching toward water involves posttranslational modification of transcription factor ARF7
Orosa-Puente, Beatriz ; Leftley, Nicola ; Wangenheim, Daniel von; Banda, Jason ; Srivastava, Anjil K. ; Hill, Kristine ; Truskina, Jekaterina ; Bhosale, Rahul ; Morris, Emily ; Srivastava, Moumita ; Kümpers, Britta ; Goh, Tatsuaki ; Fukaki, Hidehiro ; Vermeer, Joop E.M. ; Vernoux, Teva ; Dinneny, José R. ; French, Andrew P. ; Bishopp, Anthony ; Sadanandom, Ari ; Bennett, Malcolm J. - \ 2018
Science 362 (2018)6421. - ISSN 0036-8075 - p. 1407 - 1410.

Plants adapt to heterogeneous soil conditions by altering their root architecture. For example, roots branch when in contact with water by using the hydropatterning response. We report that hydropatterning is dependent on auxin response factor ARF7. This transcription factor induces asymmetric expression of its target gene LBD16 in lateral root founder cells. This differential expression pattern is regulated by posttranslational modification of ARF7 with the small ubiquitin-like modifier (SUMO) protein. SUMOylation negatively regulates ARF7 DNA binding activity. ARF7 SUMOylation is required to recruit the Aux/IAA (indole-3-acetic acid) repressor protein IAA3. Blocking ARF7 SUMOylation disrupts IAA3 recruitment and hydropatterning. We conclude that SUMO-dependent regulation of auxin response controls root branching pattern in response to water availability.

SerpinA3N is a novel hypothalamic gene upregulated by a high-fat diet and leptin in mice
Sergi, Domenico ; Campbell, Fiona M. ; Grant, Christine ; Morris, Amanda C. ; Bachmair, Eva Maria ; Koch, Christiane ; McLean, Fiona H. ; Muller, Aifric ; Hoggard, Nigel ; Roos, Baukje de; Porteiro, Begona ; Boekschoten, Mark V. ; McGillicuddy, Fiona C. ; Kahn, Darcy ; Nicol, Phyllis ; Benzler, Jonas ; Mayer, Claus Dieter ; Drew, Janice E. ; Roche, Helen M. ; Muller, Michael ; Nogueiras, Ruben ; Dieguez, Carlos ; Tups, Alexander ; Williams, Lynda M. - \ 2018
Genes & Nutrition 13 (2018). - ISSN 1555-8932
High-fat diet - Hypothalamus - Leptin - SerpinA3N

Background: Energy homeostasis is regulated by the hypothalamus but fails when animals are fed a high-fat diet (HFD), and leptin insensitivity and obesity develops. To elucidate the possible mechanisms underlying these effects, a microarray-based transcriptomics approach was used to identify novel genes regulated by HFD and leptin in the mouse hypothalamus. Results: Mouse global array data identified serpinA3N as a novel gene highly upregulated by both a HFD and leptin challenge. In situ hybridisation showed serpinA3N expression upregulation by HFD and leptin in all major hypothalamic nuclei in agreement with transcriptomic gene expression data. Immunohistochemistry and studies in the hypothalamic clonal neuronal cell line, mHypoE-N42 (N42), confirmed that alpha 1-antichymotrypsin (α1AC), the protein encoded by serpinA3, is localised to neurons and revealed that it is secreted into the media. SerpinA3N expression in N42 neurons is upregulated by palmitic acid and by leptin, together with IL-6 and TNFα, and all three genes are downregulated by the anti-inflammatory monounsaturated fat, oleic acid. Additionally, palmitate upregulation of serpinA3 in N42 neurons is blocked by the NFκB inhibitor, BAY11, and the upregulation of serpinA3N expression in the hypothalamus by HFD is blunted in IL-1 receptor 1 knockout (IL-1R1 -/- ) mice. Conclusions: These data demonstrate that serpinA3 expression is implicated in nutritionally mediated hypothalamic inflammation.

DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood
Tobi, Elmar W. ; Slieker, Roderick C. ; Luijk, René ; Dekkers, Koen F. ; Stein, Aryeh D. ; Xu, Kate M. ; Slagboom, P.E. ; Zwet, Erik W. Van; Lumey, L.H. ; Heijmans, Bastiaan T. ; T'Hoen, Peter A. ; Pool, René ; Greevenbroek, Marleen M. Van; Stehouwer, Coen D. ; Kallen, Carla J. Van Der; Schalkwijk, Casper G. ; Wijmenga, Cisca ; Zhernakova, Sasha ; Tigchelaar, Ettje F. ; Beekman, Marian ; Deelen, Joris ; Heemst, Diana Van; Veldink, Jan H. ; Berg, Leonard H. Van Den; Duijn, Cornelia M. Van; Hofman, Albert ; Uitterlinden, André G. ; Jhamai, P.M. ; Verbiest, Michael ; Verkerk, Marijn ; Breggen, Ruud Van Der; Rooij, Jeroen Van; Lakenberg, Nico ; Mei, Hailiang ; Bot, Jan ; Zhernakova, Dasha V. ; Hof, Peter Van 't; Deelen, Patrick ; Nooren, Irene ; Moed, Matthijs ; Vermaat, Martijn ; Jan Bonder, Marc ; Dijk, Freerk Van; Arindrarto, Wibowo ; Kielbasa, Szymon M. ; Swertz, Morris A. ; Isaacs, Aaron ; Franke, Lude - \ 2018
Science Advances 4 (2018)1. - ISSN 2375-2548
Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342, 596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formalmediation analysis.DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing b cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-termmetabolic health. The specific mechanism awaits elucidation.
Erratum: Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
Zillikens, M.C. ; Demissie, Serkalem ; Hsu, Yi Hsiang ; Yerges-Armstrong, Laura M. ; Chou, Wen Chi ; Stolk, Lisette ; Livshits, Gregory ; Broer, Linda ; Johnson, Toby ; Koller, Daniel L. ; Kutalik, Zoltán ; Luan, J. ; Malkin, Ida ; Ried, Janina S. ; Smith, Albert V. ; Thorleifsson, Gudmar ; Vandenput, Liesbeth ; Hua Zhao, Jing ; Zhang, Weihua ; Aghdassi, Ali ; Åkesson, Kristina ; Amin, Najaf ; Baier, Leslie J. ; Barroso, Inês ; Bennett, David A. ; Bertram, Lars ; Biffar, Rainer ; Bochud, Murielle ; Boehnke, Michael ; Borecki, Ingrid B. ; Buchman, Aron S. ; Byberg, Liisa ; Campbell, Harry ; Campos Obanda, Natalia ; Cauley, Jane A. ; Cawthon, Peggy M. ; Cederberg, Henna ; Chen, Zhao ; Cho, Nam H. ; Jin Choi, Hyung ; Claussnitzer, Melina ; Collins, Francis ; Cummings, Steven R. ; Jager, Philip L. De; Demuth, Ilja ; Dhonukshe-Rutten, Rosalie A.M. ; Diatchenko, Luda ; Eiriksdottir, Gudny ; Enneman, Anke W. ; Erdos, Mike ; Eriksson, Johan G. ; Eriksson, Joel ; Estrada, Karol ; Evans, Daniel S. ; Feitosa, Mary F. ; Fu, Mao ; Garcia, Melissa ; Gieger, Christian ; Girke, Thomas ; Glazer, Nicole L. ; Grallert, Harald ; Grewal, Jagvir ; Han, Bok Ghee ; Hanson, Robert L. ; Hayward, Caroline ; Hofman, Albert ; Hoffman, Eric P. ; Homuth, Georg ; Hsueh, Wen Chi ; Hubal, Monica J. ; Hubbard, Alan ; Huffman, Kim M. ; Husted, Lise B. ; Illig, Thomas ; Ingelsson, Erik ; Ittermann, Till ; Jansson, John Olov ; Jordan, Joanne M. ; Jula, Antti ; Karlsson, Magnus ; Khaw, Kay Tee ; Kilpeläinen, Tuomas O. ; Klopp, Norman ; Kloth, Jacqueline S.L. ; Koistinen, Heikki A. ; Kraus, William E. ; Kritchevsky, Stephen ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Laakso, Markku ; Lahti, Jari ; Lang, Thomas ; Langdahl, Bente L. ; Launer, Lenore J. ; Lee, Jong Young ; Lerch, Markus M. ; Lewis, Joshua R. ; Lind, Lars ; Lindgren, Cecilia ; Liu, Yongmei ; Liu, Tian ; Liu, Youfang ; Ljunggren, Östen ; Lorentzon, Mattias ; Luben, Robert N. ; Maixner, William ; McGuigan, Fiona E. ; Medina-Gomez, Carolina ; Meitinger, Thomas ; Melhus, Håkan ; Mellström, Dan ; Melov, Simon ; Michaëlsson, Karl ; Mitchell, Braxton D. ; Morris, Andrew P. ; Mosekilde, Leif ; Newman, Anne ; Nielson, Carrie M. ; O'Connell, Jeffrey R. ; Oostra, Ben A. ; Orwoll, Eric S. ; Palotie, Aarno ; Parker, Stephen C.J. ; Peacock, Munro ; Perola, Markus ; Peters, Annette ; Polasek, Ozren ; Prince, Richard L. ; Räikkönen, Katri ; Ralston, Stuart H. ; Ripatti, Samuli ; Robbins, John A. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Satterfield, Suzanne ; Schadt, Eric E. ; Schipf, Sabine ; Scott, Laura ; Sehmi, Joban ; Shen, Jian ; Soo Shin, Chan ; Sigurdsson, Gunnar ; Smith, Shad ; Soranzo, Nicole ; Stančáková, Alena ; Steinhagen-Thiessen, Elisabeth ; Streeten, Elizabeth A. ; Styrkarsdottir, Unnur ; Swart, Karin M.A. ; Tan, Sian Tsung ; Tarnopolsky, Mark A. ; Thompson, Patricia ; Thomson, Cynthia A. ; Thorsteinsdottir, Unnur ; Tikkanen, Emmi ; Tranah, Gregory J. ; Tuomilehto, Jaakko ; Schoor, Natasja M. van; Verma, Arjun ; Vollenweider, Peter ; Völzke, Henry ; Wactawski-Wende, Jean ; Walker, Mark ; Weedon, Michael N. ; Welch, Ryan ; Wichmann, H.E. ; Widen, Elisabeth ; Williams, Frances M.K. ; Wilson, James F. ; Wright, Nicole C. ; Xie, Weijia ; Yu, Lei ; Zhou, Yanhua ; Chambers, John C. ; Döring, Angela ; Duijn, Cornelia M. van; Econs, Michael J. ; Gudnason, Vilmundur ; Kooner, Jaspal S. ; Psaty, Bruce M. ; Spector, Timothy D. ; Stefansson, Kari ; Rivadeneira, Fernando ; Uitterlinden, André G. ; Wareham, Nicholas J. ; Ossowski, Vicky ; Waterworth, Dawn ; Loos, Ruth J.F. ; Karasik, David ; Harris, Tamara B. ; Ohlsson, Claes ; Kiel, Douglas P. - \ 2017
Nature Communications 8 (2017)1. - ISSN 2041-1723 - 1 p.

A correction to this article has been published and is linked from the HTML version of this article.

Large-scale GWAS identifies multiple loci for hand grip strength providing biological insights into muscular fitness
Willems, Sara M. ; Wright, D.J. ; Day, Felix R. ; Trajanoska, Katerina ; Joshi, P.K. ; Morris, John A. ; Matteini, Amy M. ; Garton, Fleur C. ; Grarup, Niels ; Oskolkov, Nikolay ; Thalamuthu, Anbupalam ; Mangino, Massimo ; Liu, Jun ; Demirkan, Ayse ; Lek, Monkol ; Xu, Liwen ; Wang, Guan ; Oldmeadow, Christopher ; Gaulton, Kyle J. ; Lotta, Luca A. ; Miyamoto-Mikami, Eri ; Rivas, Manuel A. ; White, Tom ; Loh, Po Ru ; Aadahl, Mette ; Amin, Najaf ; Attia, John R. ; Austin, Krista ; Benyamin, Beben ; Brage, Søren ; Cheng, Yu Ching ; Ciȩszczyk, Paweł ; Derave, Wim ; Eriksson, Karl Fredrik ; Eynon, Nir ; Linneberg, Allan ; Lucia, Alejandro ; Massidda, Myosotis ; Mitchell, Braxton D. ; Miyachi, Motohiko ; Murakami, Haruka ; Padmanabhan, Sandosh ; Pandey, Ashutosh ; Papadimitriou, Ioannis ; Rajpal, Deepak K. ; Sale, Craig ; Schnurr, Theresia M. ; Sessa, Francesco ; Shrine, Nick ; Groot, Lisette C.P.G.M. De - \ 2017
Nature Communications 8 (2017). - ISSN 2041-1723
Hand grip strength is a widely used proxy of muscular fitness, a marker of frailty, and predictor of a range of morbidities and all-cause mortality. To investigate the genetic determinants of variation in grip strength, we perform a large-scale genetic discovery analysis in a combined sample of 195,180 individuals and identify 16 loci associated with grip strength (P<5 × 10-8) in combined analyses. A number of these loci contain genes implicated in structure and function of skeletal muscle fibres (ACTG1), neuronal maintenance and signal transduction (PEX14, TGFA, SYT1), or monogenic syndromes with involvement of psychomotor impairment (PEX14, LRPPRC and KANSL1). Mendelian randomization analyses are consistent with a causal effect of higher genetically predicted grip strength on lower fracture risk. In conclusion, our findings provide new biological insight into the mechanistic underpinnings of grip strength and the causal role of muscular strength in age-related morbidities and mortality.
Large meta-analysis of genome-wide association studies identifies five loci for lean body mass
Zillikens, M.C. ; Demissie, Serkalem ; Hsu, Yi Hsiang ; Yerges-Armstrong, Laura M. ; Chou, Wen Chi ; Stolk, Lisette ; Livshits, Gregory ; Broer, Linda ; Johnson, Toby ; Koller, Daniel L. ; Kutalik, Zoltán ; Luan, J.A. ; Malkin, Ida ; Ried, Janina S. ; Smith, Albert V. ; Thorleifsson, Gudmar ; Vandenput, Liesbeth ; Hua Zhao, Jing ; Zhang, Weihua ; Aghdassi, Ali ; Åkesson, Kristina ; Amin, Najaf ; Baier, Leslie J. ; Barroso, Inês ; Bennett, David A. ; Bertram, Lars ; Biffar, Rainer ; Bochud, Murielle ; Boehnke, Michael ; Borecki, Ingrid B. ; Buchman, Aron S. ; Byberg, Liisa ; Campbell, Harry ; Campos Obanda, Natalia ; Cauley, Jane A. ; Cawthon, Peggy M. ; Cederberg, Henna ; Chen, Zhao ; Cho, Nam H. ; Jin Choi, Hyung ; Claussnitzer, Melina ; Collins, Francis ; Cummings, Steven R. ; Jager, Philip L. De; Demuth, Ilja ; Dhonukshe-Rutten, Rosalie A.M. ; DIatchenko, Luda ; Eiriksdottir, Gudny ; Enneman, Anke W. ; Erdos, Mike ; Eriksson, Johan G. ; Eriksson, Joel ; Estrada, Karol ; Evans, Daniel S. ; Feitosa, Mary F. ; Fu, Mao ; Garcia, Melissa ; Gieger, Christian ; Girke, Thomas ; Glazer, Nicole L. ; Grallert, Harald ; Grewal, Jagvir ; Han, Bok Ghee ; Hanson, Robert L. ; Hayward, Caroline ; Hofman, Albert ; Hoffman, Eric P. ; Homuth, Georg ; Hsueh, Wen Chi ; Hubal, Monica J. ; Hubbard, Alan ; Huffman, Kim M. ; Husted, Lise B. ; Illig, Thomas ; Ingelsson, Erik ; Ittermann, Till ; Jansson, John Olov ; Jordan, Joanne M. ; Jula, Antti ; Karlsson, Magnus ; Khaw, Kay Tee ; Kilpelaïnen, Tuomas O. ; Klopp, Norman ; Kloth, Jacqueline S.L. ; Koistinen, Heikki A. ; Kraus, William E. ; Kritchevsky, Stephen ; Kuulasmaa, Teemu ; Kuusisto, Johanna ; Laakso, Markku ; Lahti, Jari ; Lang, Thomas ; Langdahl, Bente L. ; Launer, Lenore J. ; Lee, Jong Young ; Lerch, Markus M. ; Lewis, Joshua R. ; Lind, Lars ; Lindgren, Cecilia M. ; Liu, Yongmei ; Liu, Tian ; Liu, Youfang ; Ljunggren, Östen ; Lorentzon, Mattias ; Luben, Robert N. ; Maixner, William ; McGuigan, Fiona E. ; Medina-Gomez, Carolina ; Meitinger, Thomas ; Melhus, Håkan ; Mellström, Dan ; Melov, Simon ; Michaëlsson, Karl ; Mitchell, Braxton D. ; Morris, Andrew P. ; Mosekilde, Leif ; Newman, Anne ; Nielson, Carrie M. ; O'Connell, Jeffrey R. ; Oostra, Ben A. ; Orwoll, Eric S. ; Palotie, Aarno ; Parker, Stephan ; Peacock, Munro ; Perola, Markus ; Peters, Annette ; Polasek, Ozren ; Prince, Richard L. ; Raïkkönen, Katri ; Ralston, Stuart H. ; Ripatti, Samuli ; Robbins, John A. ; Rotter, Jerome I. ; Rudan, Igor ; Salomaa, Veikko ; Satterfield, Suzanne ; Schadt, Eric E. ; Schipf, Sabine ; Scott, Laura ; Sehmi, Joban ; Shen, Jian ; Soo Shin, Chan ; Sigurdsson, Gunnar ; Smith, Shad ; Soranzo, Nicole ; Stančáková, Alena ; Steinhagen-Thiessen, Elisabeth ; Streeten, Elizabeth A. ; Styrkarsdottir, Unnur ; Swart, Karin M.A. ; Tan, Sian Tsung ; Tarnopolsky, Mark A. ; Thompson, Patricia ; Thomson, Cynthia A. ; Thorsteinsdottir, Unnur ; Tikkanen, Emmi ; Tranah, Gregory J. ; Tuomilehto, Jaakko ; Schoor, Natasja M. van; Verma, Arjun ; Vollenweider, Peter ; Völzke, Henry ; Wactawski-Wende, Jean ; Walker, Mark ; Weedon, Michael N. ; Welch, Ryan ; Wichman, H.E. ; Widen, Elisabeth ; Williams, Frances M.K. ; Wilson, James F. ; Wright, Nicole C. ; Xie, Weijia ; Yu, Lei ; Zhou, Yanhua ; Chambers, John C. ; Döring, Angela ; Duijn, Cornelia M. Van; Econs, Michael J. ; Gudnason, Vilmundur ; Kooner, Jaspal S. ; Psaty, Bruce M. ; Spector, Timothy D. ; Stefansson, Kari ; Rivadeneira, Fernando ; Uitterlinden, André G. ; Wareham, Nicholas J. ; Ossowski, Vicky ; Waterworth, Dawn M. ; Loos, Ruth J.F. ; Karasik, David ; Harris, Tamara B. ; Ohlsson, Claes ; Kiel, Douglas P. - \ 2017
Nature Communications 8 (2017)1. - ISSN 2041-1723
Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p < 5 × 10-8) or suggestively genome wide (p < 2.3 × 10-6). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
The social and economic challenges for a bioeconomy
Smart, Richard D. ; Wesseler, J.H.H. - \ 2017
In: Creating Sustainable Bioeconomies / Virgin, Ivar, Morris, E. Jane, Routledge (Routledge Studies in Ecological Economics ) - ISBN 9781138818538 - p. 172 - 190.
Trees, forests and water : Cool insights for a hot world
Ellison, David ; Morris, Cindy E. ; Locatelli, Bruno ; Sheil, Douglas ; Cohen, Jane ; Murdiyarso, Daniel ; Gutierrez, Victoria ; Noordwijk, Meine van; Creed, Irena F. ; Pokorny, Jan ; Gaveau, David ; Spracklen, Dominick V. ; Tobella, Aida Bargués ; Ilstedt, Ulrik ; Teuling, Adriaan J. ; Gebrehiwot, Solomon Gebreyohannis ; Sands, David C. ; Muys, Bart ; Verbist, Bruno ; Springgay, Elaine ; Sugandi, Yulia ; Sullivan, Caroline A. - \ 2017
Global environmental change : human and policy dimensions 43 (2017). - ISSN 0959-3780 - p. 51 - 61.
Adaptation - Carbon - Climate - Energy - Forest - Mitigation - Reforestation - Sustainability - Water
Forest-driven water and energy cycles are poorly integrated into regional, national, continental and global decision-making on climate change adaptation, mitigation, land use and water management. This constrains humanity's ability to protect our planet's climate and life-sustaining functions. The substantial body of research we review reveals that forest, water and energy interactions provide the foundations for carbon storage, for cooling terrestrial surfaces and for distributing water resources. Forests and trees must be recognized as prime regulators within the water, energy and carbon cycles. If these functions are ignored, planners will be unable to assess, adapt to or mitigate the impacts of changing land cover and climate. Our call to action targets a reversal of paradigms, from a carbon-centric model to one that treats the hydrologic and climate-cooling effects of trees and forests as the first order of priority. For reasons of sustainability, carbon storage must remain a secondary, though valuable, by-product. The effects of tree cover on climate at local, regional and continental scales offer benefits that demand wider recognition. The forest- and tree-centered research insights we review and analyze provide a knowledge-base for improving plans, policies and actions. Our understanding of how trees and forests influence water, energy and carbon cycles has important implications, both for the structure of planning, management and governance institutions, as well as for how trees and forests might be used to improve sustainability, adaptation and mitigation efforts.
reGenotyper: Detecting mislabeled samples in genetic data
Zych, Konrad ; Snoek, Basten L. ; Elvin, Mark ; Rodriguez, Miriam ; Velde, K.J. Van Der; Arends, Danny ; Westra, Harm-Jan ; Swertz, Morris A. ; Poulin, Gino ; Kammenga, Jan E. ; Breitling, Rainer ; Jansen, Ritsert C. ; Li, Yang - \ 2017
PLoS ONE 12 (2017)2. - ISSN 1932-6203
In high-throughput molecular profiling studies, genotype labels can be wrongly assigned at various experimental steps; the resulting mislabeled samples seriously reduce the power to detect the genetic basis of phenotypic variation. We have developed an approach to detect potential mislabeling, recover the “ideal” genotype and identify “best-matched” labels for mislabeled samples. On average, we identified 4% of samples as mislabeled in eight published datasets, highlighting the necessity of applying a “data cleaning” step before standard data analysis.
Creating a Safe Operating Space for Wetlands in a Changing Climate
Green, A.J. ; Alcorlo, P. ; Peeters, E.T.H.M. ; Morris, E.P. ; Espinar, J.L. ; Bravo, M. ; Bustamante, J. ; Diaz-Delgado, R. ; Koelmans, A.A. ; Mateo, R. ; Mooij, W.M. ; Rodriguez-Rodriguez, M. ; Nes, E.H. van; Scheffer, M. - \ 2017
Frontiers in Ecology and the Environment 15 (2017)2. - ISSN 1540-9295 - p. 99 - 107.
Many of the world's wetlands may be profoundly affected by climate change over the coming decades. Although wetland managers may have little control over the causes of climate change, they can help to counteract its effects through local measures. This is because direct anthropogenic impacts, such as water extraction and nutrient loading, work in concert with climate change to damage wetlands. Control of these local stressors may therefore ameliorate undesired effects of climate change, such as a shift towards dominance by invasive floating plants, increasingly frequent cyanobacteria blooms, or extinction of key species. Using the iconic Doñana wetlands in Spain as a case study, we illustrate how the concept of creating a “safe operating space” may be implemented to better ensure that ecosystems do not surpass thresholds for collapse during an era of global change.
Engineers at the Patient’s Bedside: : The Case of Silence in Inter-institutional Educational Innovation
Verouden, Nick ; Sanden, M.C.A. van der; Aarts, M.N.C. - \ 2016
In: The Silences of Science / Mellor, Felicity, Webster, Stephen, London : Routledge - ISBN 9781472459978 - p. 89 - 112.
Innovation in science and technology is increasingly linked with interdisciplinarity. Encouraging this trend depends in part on cutting-edge educational programmes that revise, reinvent and redesign curricula as interdisciplinary vehicles, establishing and re-establishing relations between traditional fields and areas of expertise (Stone et al., 1999; Casey, 1994). Such programmes are valuable because they can overcome ‘silo’ mentalities and equip prospective students with the skills and knowledge necessary for understanding and solving complex societal problems (Stone et al.,1999; McFadden et al., 2010). Although these programmes are very promising, their development and

implementation also brings challenges. The literature on curriculum development shows that many programmes have struggled to achieve true integration (McFadden et al., 2010; Stone et al., 1999). Dam-Mieras et al. (2008), in their study of an international master’s programme in sustainable development and management developed collaboratively by nine universities, observed that universities have their own experts and own programmes and that the ‘not invented here’ argument influences how details about new programme are discussed. Focussing on innovative online instruction courses, Xu and Morris (2007) found that the absence of group cohesiveness between faculty and project coordinators can hinder the collaborative course development process and affect the quality of the end product. Stone et al. (1999) emphasize that faculty members and administrators work at cross-purposes and view each other’s initiatives with suspicion. Given the importance that scientists, academic institutions and policy makers ascribe to innovation, along with their assumption that such innovation is a sure result of interdisciplinarity, it is essential to gain a better understanding of how curriculum development in academic education actually works. For this chapter, we consider how processes of connecting and inter-

relating could add to our understanding of the problems and dilemmas that arise in developing and implementing such programmes. Scholars of innovation, in science and technology and beyond, have explained that innovation is not some abstract algorithm: it relies on interaction and collaboration between

multiple actors with different expertises, visions, priorities and investment (Van Bommel et al., 2011; Leeuwis and Aarts, 2011; Akrich et al., 2002; Fonseca, 2002). This process of interacting is very difficult, however, and creates many tensions. This is revealed by studies that show the lurking problems of connecting previously unconnected people around new ideas and technologies. These studies show how innovation processes become defined by competition for scarce resources, protracted negotiations over priorities and interests, and dynamics of inclusion and exclusion (Leeuwis andAarts, 2011; Pretty, 1995; Van Bommel et al., 2011). Fonseca (2002) hence explains that innovation always creates a paradoxical situation, in which organizations, in their search to accelerate change and adapt to and find solutions for external challenges and demands, unavoidably create new and unpredictable interactional patterns. Given that interacting is a complicated matter in innovation processes, a

key question within the management of innovation literature is how we can account for the way relevant actors connect, or fail to connect (Akrich et al., 2002). In this respect, verbal communication is often cited as an essential mechanism for effectively connecting important actors and social groups around innovative ideas, products, or technologies (Van Bommel et al., 2011). In turn, the markers of effective verbal communication as a frame for innovation are seen to be openness, dialogue, and the ability to cooperate and be reflective on one’s thoughts and actions (Stilgoe et al., 2013). Thorp and Goldstein (2010), writing about university innovation, describe conversations as the fertile ground from which innovation grows and urge us to make time and space for those conversations. Dialogue and openness are seen as indicators of the quality of interaction, and process transparency as a decisive component of academic innovation. By being open or transparent in discussing issues and problems, actors build confidence that negotiation is ‘real’ and not a cover-up for private backroom deals (de Bruijn and ten Heuvelhof, 2008). Although there is a wealth of research on communication for innovation,

most scholarly work focuses on what is exchanged verbally, on how actors collate all the relevant evidence, put it on the table and discuss it openly. As of yet, silence is absent from these studies of communication for innovation. Building on recent organizational and strategy scholarship, in which silence is approached as an intricate concept with powerful functions and meanings in social interaction (Van Assche and Costaglioli, 2012; Carter et al., 2008; Henriksen and Dayton, 2006; Panteli and Fineman, 2005; Tucker and Edmondson, 2003; Jaworski, 2005; Morrison and Milliken, 2000), we suggest that silence merits much more attention in analyses of academic innovation. This chapter therefore explores the role of moments of silence during interactions within networks developing and implementing educational innovation. The structure of this chapter is as follows. We start by looking at the litera-

ture on dynamic innovation networks and communication and complement these insights with scholarship on silence within organization studies. After briefly introducing our approach, we present the findings of a study of an inter-institutional and interdisciplinary joint bachelor’s programme that was

implemented at the interface of health and technology. The purpose of the study was to better understand the significance of moments of silence in developing and implementing this programme. We end with the implications of our findings for steering in the context of interdisciplinary innovation.
Genome-wide analysis identifies 12 loci influencing human reproductive behavior
Barban, Nicola ; Jansen, Rick ; Vlaming, Ronald de; Vaez, Ahmad ; Mandemakers, Jornt J. ; Tropf, Felix C. ; Shen, Xia ; Wilson, James F. ; Chasman, Daniel I. ; Nolte, Ilja M. ; Tragante, Vinicius ; Laan, Sander W. van der; Perry, John R.B. ; Kong, Augustine ; Ahluwalia, Tarunveer S. ; Albrecht, Eva ; Yerges-Armstrong, Laura ; Atzmon, Gil ; Auro, Kirsi ; Ayers, Kristin ; Bakshi, Andrew ; Ben-Avraham, Danny ; Berger, Klaus ; Bergman, Aviv ; Bertram, Lars ; Bielak, Lawrence F. ; Bjornsdottir, Gyda ; Bonder, Marc Jan ; Broer, Linda ; Bui, Minh ; Barbieri, Caterina ; Cavadino, Alana ; Chavarro, Jorge E. ; Turman, Constance ; Concas, Maria Pina ; Cordell, Heather J. ; Davies, Gail ; Eibich, Peter ; Eriksson, Nicholas ; Esko, Tõnu ; Eriksson, Joel ; Falahi, Fahimeh ; Felix, Janine F. ; Fontana, Mark Alan ; Franke, Lude ; Gandin, Ilaria ; Gaskins, Audrey J. ; Gieger, Christian ; Gunderson, Erica P. ; Guo, Xiuqing ; Hayward, Caroline ; He, Chunyan ; Hofer, Edith ; Huang, Hongyan ; Joshi, Peter K. ; Kanoni, Stavroula ; Karlsson, Robert ; Kiechl, Stefan ; Kifley, Annette ; Kluttig, Alexander ; Kraft, Peter ; Lagou, Vasiliki ; Lecoeur, Cecile ; Lahti, Jari ; Li-Gao, Ruifang ; Lind, Penelope A. ; Liu, Tian ; Makalic, Enes ; Mamasoula, Crysovalanto ; Matteson, Lindsay ; Mbarek, Hamdi ; McArdle, Patrick F. ; McMahon, George ; Meddens, S.F.W. ; Mihailov, Evelin ; Miller, Mike ; Missmer, Stacey A. ; Monnereau, Claire ; Most, Peter J. van der; Myhre, Ronny ; Nalls, Mike A. ; Nutile, Teresa ; Kalafati, Ioanna Panagiota ; Porcu, Eleonora ; Prokopenko, Inga ; Rajan, Kumar B. ; Rich-Edwards, Janet ; Rietveld, Cornelius A. ; Robino, Antonietta ; Rose, Lynda M. ; Rueedi, Rico ; Ryan, Kathleen A. ; Saba, Yasaman ; Schmidt, Daniel ; Smith, Jennifer A. ; Stolk, Lisette ; Streeten, Elizabeth ; Tönjes, Anke ; Thorleifsson, Gudmar ; Ulivi, Sheila ; Wedenoja, Juho ; Wellmann, Juergen ; Willeit, Peter ; Yao, Jie ; Yengo, Loic ; Zhao, Jing Hua ; Zhao, Wei ; Zhernakova, Daria V. ; Amin, Najaf ; Andrews, Howard ; Balkau, Beverley ; Barzilai, Nir ; Bergmann, Sven ; Biino, Ginevra ; Bisgaard, Hans ; Bønnelykke, Klaus ; Boomsma, Dorret I. ; Buring, Julie E. ; Campbell, Harry ; Cappellani, Stefania ; Ciullo, Marina ; Cox, Simon R. ; Cucca, Francesco ; Toniolo, Daniela ; Davey-Smith, George ; Deary, Ian J. ; Dedoussis, George ; Deloukas, Panos ; Duijn, Cornelia M. van; Geus, Eco J.C. de; Eriksson, Johan G. ; Evans, Denis A. ; Faul, Jessica D. ; Sala, Cinzia Felicita ; Froguel, Philippe ; Gasparini, Paolo ; Girotto, Giorgia ; Grabe, Hans-Jörgen ; Greiser, Karin Halina ; Groenen, Patrick J.F. ; Haan, Hugoline G. de; Haerting, Johannes ; Harris, Tamara B. ; Heath, Andrew C. ; Heikkilä, Kauko ; Hofman, Albert ; Homuth, Georg ; Holliday, Elizabeth G. ; Hopper, John ; Hyppönen, Elina ; Jacobsson, Bo ; Jaddoe, Vincent W.V. ; Johannesson, Magnus ; Jugessur, Astanand ; Kähönen, Mika ; Kajantie, Eero ; Kardia, Sharon L.R. ; Keavney, Bernard ; Kolcic, Ivana ; Koponen, Päivikki ; Kovacs, Peter ; Kronenberg, Florian ; Kutalik, Zoltan ; Bianca, Martina la; Lachance, Genevieve ; Iacono, William G. ; Lai, Sandra ; Lehtimäki, Terho ; Liewald, David C. ; Lindgren, Cecilia M. ; Liu, Yongmei ; Luben, Robert ; Lucht, Michael ; Luoto, Riitta ; Magnus, Per ; Magnusson, Patrik K.E. ; Martin, Nicholas G. ; McGue, Matt ; McQuillan, Ruth ; Medland, Sarah E. ; Meisinger, Christa ; Mellström, Dan ; Metspalu, Andres ; Traglia, Michela ; Milani, Lili ; Mitchell, Paul ; Montgomery, Grant W. ; Mook-Kanamori, Dennis ; Mutsert, Renée de; Nohr, Ellen A. ; Ohlsson, Claes ; Olsen, Jørn ; Ong, Ken K. ; Paternoster, Lavinia ; Pattie, Alison ; Penninx, Brenda W.J.H. ; Perola, Markus ; Peyser, Patricia A. ; Pirastu, Mario ; Polasek, Ozren ; Power, Chris ; Kaprio, Jaakko ; Raffel, Leslie J. ; Räikkönen, Katri ; Raitakari, Olli ; Ridker, Paul M. ; Ring, Susan M. ; Roll, Kathryn ; Rudan, Igor ; Ruggiero, Daniela ; Rujescu, Dan ; Salomaa, Veikko ; Schlessinger, David ; Schmidt, Helena ; Schmidt, Reinhold ; Schupf, Nicole ; Smit, Johannes ; Sorice, Rossella ; Spector, Tim D. ; Starr, John M. ; Stöckl, Doris ; Strauch, Konstantin ; Stumvoll, Michael ; Swertz, Morris A. ; Thorsteinsdottir, Unnur ; Thurik, A.R. ; Timpson, Nicholas J. ; Tung, Joyce Y. ; Uitterlinden, André G. ; Vaccargiu, Simona ; Viikari, Jorma ; Vitart, Veronique ; Völzke, Henry ; Vollenweider, Peter ; Vuckovic, Dragana ; Waage, Johannes ; Wagner, Gert G. ; Wang, Jie Jin ; Wareham, Nicholas J. ; Weir, David R. ; Willemsen, Gonneke ; Willeit, Johann ; Wright, Alan F. ; Zondervan, Krina T. ; Stefansson, Kari ; Krueger, Robert F. ; Lee, James J. ; Benjamin, Daniel J. ; Cesarini, David ; Koellinger, Philipp D. ; Hoed, Marcel den; Snieder, Harold ; Mills, Melinda C. - \ 2016
Nature Genetics 48 (2016)12. - ISSN 1061-4036 - p. 1462 - 1472.
The genetic architecture of human reproductive behavior—age at first birth (AFB) and number of children ever born (NEB)—has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.
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