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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Fluctuations in milk yield are heritable and can be used as a resilience indicator to breed healthy cows
Elgersma, G.G. ; Jong, G. de; Linde, R. van der; Mulder, H.A. - \ 2018
Journal of Dairy Science 101 (2018)2. - ISSN 0022-0302 - p. 1240 - 1250.
Big data - Fluctuation - Health - Resilience - Variance
Automatic milking systems record an enormous amount of data on milk yield and the cow itself. These type of big data are expected to contain indicators for health and resilience of cows. In this study, the aim was to define and estimate heritabilities for traits related with fluctuations in daily milk yield and to estimate genetic correlations with existing functional traits, such as udder health, fertility, claw health, ketosis, and longevity. We used daily milk yield records from automatic milking systems of 67,025 lactations in the first parity from 498 herds in the Netherlands. We defined 3 traits related to the number of drops in milk yield using Student t-tests based on either a rolling average (drop rolling average) or a regression (drop regression) and the natural logarithm of the within-cow variance of milk yield (LnVar). Average milk yield was added to investigate the relationships between milk yield and these new traits. ASReml was used to estimate heritabilities, breeding values (EBV), and genetic correlations among these new traits and average milk yield. Approximate genetic correlations were calculated using correlations between EBV of the new traits and existing EBV for health and functional traits correcting for nonunity reliabilities using the Calo method. Partial genetic correlations controlling for persistency and average milk yield and relative contributions to reliability were calculated to investigate whether the new traits add new information to predict fertility, health, and longevity. Heritabilities were 0.08 for drop rolling average, 0.06 for drop regression, and 0.10 for LnVar. Approximate genetic correlations between the new traits and the existing health traits differed quite a bit, with the strongest correlations (-0.29 to -0.52) between LnVar and udder health, ketosis, persistency, and longevity. This study shows that fluctuations in daily milk yield are heritable and that the variance of milk production is best among the 3 fluctuations traits tested to predict udder health, ketosis, and longevity. Using the residual variance of milk production instead of the raw variance is expected to further improve the trait to breed healthy, resilient, and long-lasting dairy cows.
Weed suppression greatly increased by plant diversity in intensively managed grasslands: a continental-scale experiment
Connolly, J. ; Sebastià, M.T. ; Kirwan, L. ; Finn, John A. ; Llurba, Rosa ; Suter, M. ; Collins, Rosemary P. ; Porqueddu, C. ; Helgadóttir, A. ; Baadshaug, Ole H. ; Bélanger, Gilles ; Black, A. ; Brophy, C. ; Čop, Jure ; Dalmannsdóttir, S. ; Delgado, I. ; Elgersma, A. ; Fothergill, M. ; Frankow-Lindberg, Bodil E. ; Ghesquiere, A. ; Golinski, P. ; Grieu, P. ; Gustavsson, A.M. ; Höglind, M. ; Huguenin-Elie, O. ; Jørgensen, M. ; Kadziuliene, Z. ; Lunnan, T. ; Nykanen-Kurki, P. ; Ribas, A. ; Taube, F. ; Thumm, U. ; Vliegher, A. de; Lüscher, A. - \ 2018
Journal of Applied Ecology 55 (2018)2. - ISSN 0021-8901 - p. 852 - 862.
1.Grassland diversity can support sustainable intensification of grassland production through increased yields, reduced inputs and limited weed invasion. We report the effects of diversity on weed suppression from three years of a 31-site continental-scale field experiment.

2.At each site, fifteen grassland communities comprising four monocultures and 11 4-species mixtures based on a wide range of species’ proportions were sown at two densities and managed by cutting. Forage species were selected according to two crossed functional traits, ‘method-of-nitrogen-acquisition’ and ‘pattern-of-temporal- development’.

3.Across sites, years, and sown densities, annual weed biomass in mixtures and monocultures was 0.5 and 2.0 t DM ha−1 (7% and 33% of total biomass respectively). Over 95% of mixtures had weed biomass lower than the average of monocultures, and, in two thirds of cases, lower than in the most suppressive monoculture (transgressive suppression). Suppression was significantly transgressive for 58% of site-years. Transgressive suppression by mixtures was maintained across years, independent of site productivity.

4.Based on models, average weed biomass in mixture over the whole experiment was 52% less (95% confidence interval 30% to 75%) than in the most suppressive monoculture. Transgressive suppression of weed biomass was significant at each year across all mixtures and for each mixture.

5.Weed biomass was consistently low across all mixtures and years and was in some cases significantly but not largely different from that in the equiproportional mixture. The average variability (standard deviation) of annual weed biomass within a site was much lower for mixtures (0.42) than for monocultures (1.77).

6.Synthesis and applications. Weed invasion can be diminished through a combination of forage species selected for complementarity and persistence traits in systems designed to reduce reliance on fertilizer nitrogen. In this study, effects of diversity on weed suppression were consistently strong across mixtures varying widely in species proportions and over time. The level of weed biomass did not vary greatly across mixtures varying widely in proportions of sown species. These diversity benefits in intensively managed grasslands are relevant for the sustainable intensification of agriculture and, importantly, are achievable through practical farm-scale actions.
The variance of daily milk production as predictor for health and resilience in dairy cattle
Mulder, H.A. ; Elgersma, G.G. ; Linde, R. van de; Jong, G. de - \ 2017
In: Book of Abstracts of the 68th Annual Meeting of the European Federation of Animal Science. - Wageningen : Wageningen Academic Publishers (Book of abstracts 23) - ISBN 9789086863129 - p. 462 - 462.
Automatic milking systems (AMS) record an enormous amount of data on milk production and the cow itself. This type of big data is expected to contain indicators for health and resilience of cows. In this study, the aim was to define and estimate heritabilities for traits related with fluctuations in daily milk production and to estimate genetic correlations with existing functional traits such as udder health, fertility, claw health, ketosis and longevity. We used daily milk production records of AMS of 212,433 lactations in parities 1, 2 and 3 from 498 herds in the Netherlands. We defined several traits related to the number of drops in milk production using Student t-tests (DROP) as well as the natural logarithm of the within-cow variance of milk yield (LNvar). ASReml was used to estimate heritabilities and breeding values (EBV) for the new traits. Genetic correlations were estimated using correlations between EBV of the new traits and existing EBV for health and functional traits correcting for non-unity reliabilities using the Calo-method. Heritabilities for the DROP traits and LNvar were around 0.1, similar to heritabilities for health and functional traits. Genetic correlations between the new traits and the existing health traits differed a lot, the strongest correlations (0.4-0.6) were between LNvar and udder health, ketosis, persistency and longevity. LNvar was in this study the best trait, based on the combination of the heritability and the genetic correlations with health traits. Selection of the 20 bulls with the lowest EBV for LNvar, i.e. less fluctuations in milk production, showed that the daughters of these bulls have better udder health i.e. less mastitis, less ketosis, better fertility and stay 150 days longer in the farm than average. This study shows that the variance in daily milk production is heritable and can be used to breed healthy and resilient cows.
Major shifts in species’ relative abundance in grassland mixtures alongside positive effects of species diversity in yield: a continental-scale experiment
Brophy, Caroline ; Finn, John A. ; Lüscher, Andreas ; Suter, Matthias ; Kirwan, Laura ; Sebastià, Maria Teresa ; Helgadóttir, Áslaug ; Baadshaug, Ole H. ; Bélanger, Gilles ; Black, Alistair ; Collins, Rosemary P. ; Čop, Jure ; Dalmannsdottir, Sigridur ; Delgado, Ignacio ; Elgersma, Anjo ; Fothergill, Michael ; Frankow-Lindberg, Bodil E. ; Ghesquiere, A. ; Golinska, Barbara ; Golinski, Piotr ; Grieu, Philippe ; Gustavsson, Anne Maj ; Höglind, Mats ; Huguenin-Elie, Olivier ; Jørgensen, Marit ; Kadziuliene, Zydre ; Kurki, Päivi ; Llurba, Rosa ; Lunnan, Tor ; Porqueddu, Claudio ; Thumm, Ulrich ; Connolly, John - \ 2017
Journal of Ecology 105 (2017)5. - ISSN 0022-0477 - p. 1210 - 1222.
Increased species diversity promotes ecosystem function; however, the dynamics of multi-species grassland systems over time and their role in sustaining higher yields generated by increased diversity are still poorly understood. We investigated the development of species’ relative abundances in grassland mixtures over 3 years to identify drivers of diversity change and their links to yield diversity effects.
A continental-scale field experiment was conducted at 31 sites using 11 different four-species mixtures each sown at two seed abundances. The four species consisted of two grasses and two legumes, of which one was fast establishing and the other temporally persistent. We modelled the dynamics of the four-species mixtures, and tested associations with diversity effects on yield.
We found that species’ dynamics were primarily driven by differences in the relative growth rates (RGRs) of competing species, and secondarily by density dependence and climate. The temporally persistent grass species typically had the highest RGRs and hence became dominant over time. Density dependence sometimes induced stabilising processes on the dominant species and inhibited shifts to monoculture. Legumes persisted at most sites at low or medium abundances and persistence was improved at sites with higher annual minimum temperature.
Significant diversity effects were present at the majority of sites in all years and the strength of diversity effects was improved with higher legume abundance in the previous year. Observed diversity effects, when legumes had declined, may be due to (i) important effects of legumes even at low abundance, (ii) interaction between the two grass species or (iii) a store of N because of previous presence of legumes.
Synthesis. Alongside major compositional changes driven by RGR differences, diversity effects were observed at most sites, albeit at reduced strength as legumes declined. This evidence strongly supports the sowing of multi-species mixtures that include legumes over the long-standing practice of sowing grass monocultures. Careful and strategic selection of the identity of the species used in mixtures is suggested to facilitate the maintenance of species diversity and especially persistence of legumes over time, and to preserve the strength of yield increases associated with diversity.
Quantifying the environmental performance of individual dairy farms - the Annual Nutrient Cycling Assessment (ANCA)
Aarts, H.F.M. ; Haan, M.H.A. de; Schroder, J.J. ; Holster, H.C. ; Boer, J.A. de; Reijs, Joan ; Oenema, J. ; Hilhorst, G.J. ; Sebek, L.B. ; Verhoeven, F.P.M. ; Meerkerk, B. - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Wageningen Academic Publishers (Grassland Science in Europe ) - ISBN 9789090289618 - p. 377 - 380.
ANCA, nutrient cycling assessment, dairy farming, sustainability standards
Dairy farming is characterised by extensive fluxes of nitrogen (N) and phosphorus (P): large amounts of these elements cycle via feed, manure, soils and crops. Losses and exports in the form of milk, meat and manure are compensated for by purchased feeds and fertilisers. At this moment, farmers lack accurate insight into the impact of their management on the functioning of these cycles. We therefore developed the model ANCA, based on the results of the pilot farm network ‘Cows & Opportunities’ and the experimental farm ‘De Marke’. The ANCA model quantifies the main performance indicator related to the nutrient cycles. The ANCA model is based on verifiable input data that can be collected with little effort, as the model is to be used by commercial farmers whilst being fraud resistant. The model outcomes help dairy farmers to demonstrate towards authorities and the dairy industry that they have produced their milk in accordance with sustainability standards. From 2015 onwards, ANCA will serve as a licence to produce for any dairy farm in The Netherlands with a manure surplus (about 70% of the number of farms).
Economic impact of grazing dairy cows on farms equipped with an automatic milking system
Oudshoorn, Frank W. ; Brocard, V. ; Pol, A. van den - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Wageningen Academic Publishers (Grassland science in Europe ) - ISBN 9789090289618 - p. 469 - 471.
Automatic milking Systems (AMS) have been practised for a number of years in Denmark, France and the Netherlands. During these years, combining automatic milking (AM) and pasture access for feeding has remained problematic. Grazing has, however, many benefits, both for farmers, animals, landscape, biodiversity, and for the overall image of dairy farming. In this study we compared the conomic results of dairy farms with AMS (AMS farms) which practice grazing with those of AMS farms without grazing. The economic impact of grazing dairy cows on AMS farms was analysed using accounting data of commercial dairy farms in Denmark, France and the Netherlands. In the Netherlands grazing was economically beneficial but this effect declined with increasing farm size. In France, income tended to be higher on farms that practised grazing, and in Denmark no economic difference of farmer incomes were found. A complicating factor of the analysis was that the actual feed uptake during grazing was not
recorded in the database in any of the three countries. A key recommendation from this study is that the level of grazing and intake from grazing as a proportion of the total diet is recorded in the future.
Possibilities and constraints for grazing in high output dairy systems
Hennessy, D. ; Delaby, L. ; Pol, A. van den; Shalloo, L. - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Wageningen Academic Publishers (Grassland Science in Europe ) - ISBN 9789090289618 - p. 151 - 162.
In temperate and oceanic regions, grazed grass is the lowest cost feed available for milk production. In other regions, grazed grass is less important but can contribute to the diet of livestock. Within high output systems the interaction between the animal and sward is challenging for a host of reasons, including
intake and milk production potential, substitution, grass allowance, quality, etc., which often means that grass utilisation and quality are compromised. Adaptation of grazing management and implementation of a range of grazing strategies can provide possibilities to increase the proportion of grazed grass in the diet of dairy cows in high output systems. As Europe transitions to a non-milk quota situation, increasing scale, or herd size, will probably lead to a trend towards a reduction in grazing, and may lead to a loss of the benefits of grazing. Therefore, strategies are required to increase the level of grazed grass in the diet of dairy cows on high output farms through the integration of grassland measurement and budgeting within everyday grassland management practices. There is a growing body of literature describing the benefits of grazing from an economic, environmental, animal welfare and overall social dimension. However,
there are fewer reviews highlighting the constraints and difficulties to maintaining a high level of grass utilisation and good grazing performance in high output systems. The objective of this review is to present a balanced overview of the possibilities and the constraints for grazing in dairy systems in the future.
Grassland and forages in high output dairy farming systems
Pol, A. van den; Aarts, H.F.M. ; Vliegher, Alex De; Elgersma, A. ; Reheul, D.D. ; Reijneveld, J.A. ; Verloop, J. ; Hopkins, A. - \ 2015
EGF (Grassland Science in Europe ) - ISBN 9789090289618 - 529 p.
The dairy sector within the EU is currently confronted with many challenges as a consequence of political, economic and societal demands. These include price fluctuations, increasing competition in terms of farm inputs and products in the EU and on world markets, and increasing public demands for food product quality and safety, optimal animal welfare and biodiversity. The end of the milk quota system in 2015 represents an additional major change for the European dairy sector. Many countries are already responding to this change by exploring the possibilities and constraints of scaling up and intensification. The 18th Symposium of the European Grassland Federation therefore focuses on grassland and forages in high output dairy farming systems. The issue of food security is asking for high output from agricultural systems. A major question is the extent to which societal demands, such as animal welfare and grazing, can be met in intensified production systems. Will further optimization of grassland management enhance profitability and reduce the environmental pressure of farming systems? The symposium focuses on high output at farm level (milk
production per ha). Keynote speakers from a number of different regions have been invited to address their regional high output dairy farming systems in their specific context, the problems encountered within those farming systems and, if possible, the solutions found. Secondly, optimal use of grassland and
fodder crops in high output systems is discussed. Finally, sustainable intensification in profitable animal production systems is examined focusing on high output and high (eco)efficiency at the farm level.
Grassland and forages in high output dairy farming systems in Flanders and the Netherlands
Pol, A. van den; Aarts, H. ; Caesteker, E. De; Vliegher, A. de; Elgersma, A. ; Reheul, D. ; Reijneveld, J.A. ; Vaes, R. - \ 2015
In: Grassland and forages in high output dairy farming systems. - EGF (Grassland Science in Europe ) - ISBN 9789090289618 - p. 3 - 11.
The dairy sector in the EU faces many challenges as a consequence of political, economic and societal developments. Many countries are responding to these changes by exploring the possibilities and constraints of scaling up and intensification. This also holds for Flanders and the Netherlands, where
dairy farming systems are already intensive. This paper describes high output dairy farming systems in the Netherlands and Flanders and discusses their problems, solutions and perspectives associated with grassland and forages. The dairy farming systems are generally characterised by high fluxes of nitrogen
and phosphorus through the systems. Research has led to a strong decrease in mineral losses to the environment in practice. The decrease in grazing is another concern of high output systems. Many activities have been initiated with the aim of stabilisation of the number of dairy cows grazing. Further scaling up of farms and intensification is thought to be possible in the Netherlands and Flanders because of high soil fertility, favourable weather conditions, a good infrastructure and well-educated farmers.
Sward quality and yields of grassland in a dairy farm with reduced fertilizer N rates
Verloop, J. ; Oenema, J. ; Geerts, R.H.E.M. - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Wageningen Academic Publishers (Grassland Science in Europe ) - ISBN 9789090289618 - p. 337 - 339.
The objective of this study was to explore under farming conditions the effect of reduced fertilizer N application rates on the dynamics of botanical composition and yields of grass-clover-swards. In both temporary and permanent grassland the percentage of highly productive grasses (good grasses) declined at a constant rate of 3.0 to 6.3% points y‑1 during the aging of the sward. Good grasses were replaced by less-productive grasses and herbs. The percentage of clover did not show a significant trend. Reduced N fertilization did not significantly change these dynamics. The percentage of white clover and, in some cases, high-yielding grasses in the sward, enhanced the yields of nitrogen and herbage dry matter, while the percentage of herbs reduced yields.
Reduced tillage for silage maize on sand and clay soils: effect on yield and soil organic matter
Deru, J.G.C. ; Schooten, H.A. van; Huiting, H.F. ; Weide, R.Y. van der - \ 2015
In: Grassland and forages in high output dairy farming systems. - European Grassland Federation EGF (Grassland Science in Europe ) - ISBN 9789090289618 - p. 398 - 400.
Maize (Zea mays) cultivation for silage has negative impacts on soil and water quality: reduced soil organic matter, nitrate leaching, soil-biota decline, etc. These problems can be caused partly by intensive soil tillage, like ploughing. The suitability of less-intensive tillage alternatives for farmers, in terms of
effects on yield and soil quality, is unknown. On three field experiments, two on sandy soils and one on marine clay soil, we compared ‘full-field inversion tillage’ with two reduced tillage systems: ‘full-field non-inversion tillage’ and ‘strip-cutter’. Reducing tillage intensity in silage maize cropping influenced both yields and soil quality: at two locations yields tended to be reduced, and at two locations soil organic matter content was lower in inversion tillage compared to reduced tillage. The possible implications of reduced soil organic matter mineralisation for nitrogen dynamics are discussed
Species-rich grasslands for a higher biodiversity on highly productive dairy farms
Korevaar, H. ; Geerts, R.H.E.M. - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Nederlandse Vereniging voor Weide- en Voederbouw - ISBN 9789090289618 - p. 443 - 445.
During the past decade trials have shown the value of species-rich grasslands for farmland biodiversity. On four highly productive dairy farms, where farming was combined with management of species-rich grasslands and habitat creation for meadow birds, we analysed the value of these species-diverse swards with respect to grass production and quality, farm management and biodiversity. Compared with grass, herbs and legumes generally contained higher levels of minerals and their herbage offered more structure in the cattle diet. Speeding up the creation of species-diverse swards is possible by reseeding with speciesrich mixtures. On these farms a species richness of 17-30 species per 100 m-2 was obtained. Previous research showed that replacement of 25-30% Lolium perenne silage by silage from comparable speciesrich swards is possible without a decline in milk production. When highly productive dairy farms create species-diverse swards on part of their acreage, it will be possible to produce healthy forage while also providing a good habitat for meadow birds.
Developing mixed farming systems at regional level: examples from intensive dairy farming
Hanegraaf, M.C. ; Vertes, F. ; Corson, M.S. ; Boer, D.J. den; Moraine, M. ; Korevaar, H. - \ 2015
In: Grassland and forages in high output dairy farming systems. - Wageningen : Nederlandse Vereniging voor Weide- en Voederbouw - ISBN 9789090289618 - p. 96 - 98.
Regional animal feed centra as an intermediary between fodder farming and milk production
Galama, P. ; Walsum, P.E.V. van; Hack-ten Broeke, M.J.D. ; Cormont, A. ; Roelsma, J. - \ 2015
In: Proceedings of the 18th Symposium of the European Grassland Federation. - - p. 413 - 415.
Economic and environmental viability of regionally growing feed concentrate replacers
Hack-ten Broeke, M.J.D. ; Cormont, A. ; Roelsma, J. ; Galama, P. ; Walsum, P.E.V. van - \ 2015
In: Proceedings of the 18th Symposium of the European Grassland Federation. - - p. 428 - 430.
The agrodiversity experiment : three years of data from a multisite study in intensively managed grasslands
Kirwan, L. ; Connolly, J. ; Brophy, C. ; Elgersma, A. - \ 2014
grasslands
Intensively managed grasslands are globally prominent ecosystems. We investigated whether experimental increases in plant diversity in intensively managed grassland communities can increase their resource use efficiency. This work consisted of a coordinated, continental-scale 33-site experiment. The core design was 30 plots, representing 15 grassland communities at two seeding densities. The 15 communities were comprised of four monocultures (two grasses and two legumes) and 11 four-species mixtures that varied in the relative abundance of the four species at sowing. There were 1028 plots in the core experiment, with another 572 plots sown for additional treatments. Sites agreed a protocol and employed the same experimental methods with certain plot management factors, such as seeding rates and number of cuts, determined by local practice. The four species used at a site depended on geographical location, but the species were chosen according to four functional traits: a fast-establishing grass, a slow-establishing persistent grass, a fast-establishing legume, and a slow-establishing persistent legume. As the objective was to maximize yield for intensive grassland production, the species chosen were all high-yielding agronomic species. The data set contains species-specific biomass measurements (yield per species and of weeds) for all harvests for up to four years at 33 sites. Samples of harvested vegetation were also analyzed for forage quality at 26 sites. Analyses showed that the yield of the mixtures exceeded that of the average monoculture in >97% of comparisons. Mixture biomass also exceeded that of the best monoculture (transgressive overyielding) at about 60% of sites. There was also a positive relationship between the diversity of the communities and aboveground biomass that was consistent across sites and persisted for three years. Weed invasion in mixtures was very much less than that in monocultures. These data should be of interest to ecologists studying relationships between diversity and ecosystem function and to agronomists interested in sustainable intensification. The large spatial scale of the sites provides opportunity for analyses across spatial (and temporal) scales. The database can also complement existing databases and meta-analyses on biodiversity–ecosystem function relationships in natural communities by focusing on those same relationships within intensively managed agricultural grasslands.
The agrodiversity experiment : three years of data from a multisite study in intensively managed grasslands
Kirwan, L. ; Connolly, J. ; Brophy, C. ; Elgersma, A. - \ 2014
Ecology 95 (2014)9. - ISSN 0012-9658 - p. 2680 - 2680.
Intensively managed grasslands are globally prominent ecosystems. We investigated whether experimental increases in plant diversity in intensively managed grassland communities can increase their resource use efficiency. This work consisted of a coordinated, continental-scale 33-site experiment. The core design was 30 plots, representing 15 grassland communities at two seeding densities. The 15 communities comprised four monocultures (two grasses and two legumes) and 11 four-species mixtures that varied in the relative abundance of the four species at sowing. There were 1028 plots in the core experiment, with another 572 plots sown for additional treatments. Sites followed a protocol and employed the same experimental methods with certain plot management factors, such as seeding rates and number of cuts, determined by local practice. The four species used at a site depended on geographical location, but the species were chosen according to four functional traits: a fast-establishing grass, a slow-establishing persistent grass, a fast-establishing legume, and a slow-establishing persistent legume. As the objective was to maximize yield for intensive grassland production, the species chosen were all highyielding agronomic species. The data set contains species-specific biomass measurements (yield per species and of weeds) for all harvests for up to four years at 33 sites. Samples of harvested vegetation were also analyzed for forage quality at 26 sites. These data should be of interest to ecologists studying relationships between diversity and ecosystem function and to agronomists interested in sustainable intensification. The large spatial scale of the sites provides opportunity for analyses across spatial (and temporal) scales. The database can also complement existing databases and meta-analyses on biodiversity– ecosystem function relationships in natural communities by focusing on those same relationships within intensively managed agricultural grasslands.
Preclinical Profile of the HER2-Targeting ADC SYD983/SYD985: Introduction of a New Duocarmycin-Based Linker-Drug Platform
Dokter, W. ; Ubink, R. ; Lee, M. van der; Vleuten, M. van der; Achterberg, T. van; Jacobs, D. ; Loosveld, E. ; Dobbelsteen, D. van den; Egging, D. ; Mattaar, E. ; Groothuis, P. ; Beusker, P. ; Coumans, R. ; Elgersma, R. ; Menge, W. ; Joosten, J. ; Spijker, H. ; Huijbregts, T. ; Groot, V. de; Eppink, M.H.M. ; Roo, G. de; Verheijden, G. ; Timmers, M. - \ 2014
Molecular Cancer Therapeutics 13 (2014). - ISSN 1535-7163 - p. 2618 - 2629.
metastatic breast-cancer - growth-factor receptor - phase-ii - trastuzumab emtansine - brentuximab vedotin - cathepsin-b - human pharmacokinetics - monoclonal-antibody - malignant-melanoma - antitumor-activity
A linker-drug platform was built on the basis of a cleavable linker-duocarmycin payload for the development of new-generation antibody–drug conjugates (ADC). A leading ADC originating from that platform is SYD983, a HER2-targeting ADC based on trastuzumab. HER2-binding, antibody-dependent cell-mediated cytotoxicity and HER2-mediated internalization are similar for SYD983 as compared with trastuzumab. HER2- expressing cells in vitro are very potently killed by SYD983, but SYD983 is inactive in cells that do not express HER2. SYD983 dose dependently reduces tumor growth in a BT-474 mouse xenograft in vivo. TheADCis stable in human and cynomolgus monkey plasma in vitro but shows relatively poor stability in mouse plasma due to mouse-specific carboxylesterase. SYD983 could be dosed up to 30 mg/kg in cynomolgus monkeys with high exposure, excellent stability in blood, and without severe toxic effects. The monkey safety study showed no SYD983-induced thrombocytopenia and no induction of peripheral sensory neuropathy, both commonly observed in trials and studies with ADCs based on tubulin inhibitors. Finally, to improve homogeneity, SYD983 was further purified by hydrophobic interaction chromatography resulting in an ADC (designated SYD985) predominantly containing DAR2 and DAR4 species. SYD985 showed high antitumor activity in two patient-derived xenograft models of HER2-positive metastatic breast cancers. In conclusion, the data obtained indicate great potential for this new HER2-targeting ADC to become an effective drug for patients with HER2- positive cancers with a favorable safety profile. More generally, this new-generation duocarmycin-based linker-drug technology could be used with other mAbs to serve more indications in oncology.
Is phytanic acid a suitable marker for authentification of milk and dairy products from grass-fed cows or organic farming systems?
Capuano, E. ; Elgersma, A. ; Tres, A. ; Ruth, S.M. van - \ 2014
In: EGF at 50: The Future of European Grasslands. - Aberystwyth : European Grassland Federation EGF (Grassland science in Europe ) - ISBN 9780992694012 - p. 672 - 674.
Cow milk samples were collected from herds of 30 Dutch farms and analysed by gas chromatography-mass spectrometry for phytanic acid (PHY) and its diastereomers SRR and RRR to test the hypothesis that PHY could be a suitable marker for authentification of milk from grass-fed cows. The samples differed in the proportion of fresh grass in the cows’ daily dry matter intake (0 to 94%). Grass was either fed indoors or grazed (during daytime, or day and night). Of the latter category, three farms had an organic and three a biodynamic farming system. PHY concentrations were not significantly higher in organic/biodynamic milk compared with conventional milk, nor were they correlated with the proportion or amount of fresh grass in the diet. The proportion of RRR in total PHY was positively correlated with the proportion of fresh grass in the diet. These results indicate that, in contrast to our hypothesis, PHY content is not a suitable indicators of pasture grazing or organic/biodynamic farming, while the proportion of diastereomers of PHY may be useful as such.
Verification of fresh grass feeding, pasture grazing and organic farming by cows farm milk fatty acid profile
Capuano, E. ; Veer, G. van der; Boerrigter-Eenling, G.R. ; Elgersma, A. ; Rademaker, J. ; Sterian, A. ; Ruth, S.M. van - \ 2014
Food Chemistry 164 (2014). - ISSN 0308-8146 - p. 234 - 241.
near-infrared spectroscopy - stable-isotope - linoleic-acid - cutting date - diet - authentication - transition - systems - origin
The present study investigated the use of fatty acid (FA) profiling in combination with chemometric modelling to verify claims for cow milk in terms of fresh grass feeding, pasture grazing and organic/biodynamic farming. The FA profile was determined for 113 tank milk samples collected in the Netherlands from 30 farms over four different months, and used to develop classification models based on the PLS-DA algorithm. Milk from cows with daily rations of fresh grass could be successfully distinguished from milk from cows with no fresh grass in their diet. Milk from cows at pasture could easily be distinguished from milk from stabled cows without fresh grass in the diet, but the correct prediction of milk from stabled cows fed fresh grass indoors proved difficult. The FA profile of organic/biodynamic milk was different compared to conventional milk but an unequivocal discrimination was not possible either in summer or in winter.
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